{"database": "metadata", "table": "run_metadata", "is_view": false, "human_description_en": "where devstage_curation = \"Adult\" and experiment.platform = \"DNBSEQ\"", "rows": [[44, "DRR668250", "DRX648352", "DRS458865", "DRP012880", "PRJDB18466", "Comparison of spinal cord regeneration capacity in zebrafish and medaka", "PRJDB18466", "Other", "Unlike mammals zebrafish have the remarkable ability to regenerate many tissues including the spinal cord. Medaka another model fish species has a low regenerative ability in the spinal cord. Therefore comparisons with them advantageous to revealing regeneration specific mechanisms in the spinal cord. The comparison of the spinal cord regeneration abilities of zebrafish and medaka could be a promising research field to elucidate new factors that determine spinal cord regeneration ability.", null, "pubmed:40278963", "Zebrafish 2 weeks post spinal cord injury replicate 3", "Zebrafish 2wpi 3", "SAMD00799623", null, "sample name:Zebrafish 2wpi 3|biological replicate:3|biomaterial provider:Center of Medical Innovation and Translational Research Osaka University|collection date:2023 04 25|dev stage:Adult|geo loc name:Japan|sex:not determined|strain:AB Zebrafish|tissue:Spinal cord", null, null, null, null, null, null, null, null, "DNBSEQ G400 paired end sequencing of SAMD00799623", "DRX648352", "RNA seq of spinal cord in zebrafish at 2wpi injured 3", "1", "Total RNA was extracted using RNeasy Micro Kit Qiagen 74104 with DNase treatment RNase Free DNase Set Qiagen 79254. Libraries were constructed from the amplified total RNA.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "DRP012880", "DNBSEQ G400 paired end sequencing of SAMD00799623", null, null, null, 14782516800.0, 73912584.0, "DRR668250", "0:100 1:100", "A:4058090278;C:3335994894;G:3323563782;T:4062467903;N:2399943", 100, 100, null, null, 4058090278, 3335994894, 3323563782, 4062467903, 2399943, "DRX648352", "DRS458865", "DRA020617", "Osaka University", "Osaka University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2025-05-12", "Adult", "Adult", "Spinal Cord", "Nervous System"], [45, "DRR668249", "DRX648351", "DRS458864", "DRP012880", "PRJDB18466", "Comparison of spinal cord regeneration capacity in zebrafish and medaka", "PRJDB18466", "Other", "Unlike mammals zebrafish have the remarkable ability to regenerate many tissues including the spinal cord. Medaka another model fish species has a low regenerative ability in the spinal cord. Therefore comparisons with them advantageous to revealing regeneration specific mechanisms in the spinal cord. The comparison of the spinal cord regeneration abilities of zebrafish and medaka could be a promising research field to elucidate new factors that determine spinal cord regeneration ability.", null, "pubmed:40278963", "Zebrafish 2 weeks post spinal cord injury replicate 2", "Zebrafish 2wpi 2", "SAMD00799622", null, "sample name:Zebrafish 2wpi 2|biological replicate:2|biomaterial provider:Center of Medical Innovation and Translational Research Osaka University|collection date:2023 04 14|dev stage:Adult|geo loc name:Japan|sex:not determined|strain:AB Zebrafish|tissue:Spinal cord", null, null, null, null, null, null, null, null, "DNBSEQ G400 paired end sequencing of SAMD00799622", "DRX648351", "RNA seq of spinal cord in zebrafish at 2wpi injured 2", "1", "Total RNA was extracted using RNeasy Micro Kit Qiagen 74104 with DNase treatment RNase Free DNase Set Qiagen 79254. Libraries were constructed from the amplified total RNA.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "DRP012880", "DNBSEQ G400 paired end sequencing of SAMD00799622", null, null, null, 13687641800.0, 68438209.0, "DRR668249", "0:100 1:100", "A:3759784620;C:3087398782;G:3083881581;T:3754378915;N:2197902", 100, 100, null, null, 3759784620, 3087398782, 3083881581, 3754378915, 2197902, "DRX648351", "DRS458864", "DRA020617", "Osaka University", "Osaka University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2025-05-12", "Adult", "Adult", "Spinal Cord", "Nervous System"], [46, "DRR668248", "DRX648350", "DRS458863", "DRP012880", "PRJDB18466", "Comparison of spinal cord regeneration capacity in zebrafish and medaka", "PRJDB18466", "Other", "Unlike mammals zebrafish have the remarkable ability to regenerate many tissues including the spinal cord. Medaka another model fish species has a low regenerative ability in the spinal cord. Therefore comparisons with them advantageous to revealing regeneration specific mechanisms in the spinal cord. The comparison of the spinal cord regeneration abilities of zebrafish and medaka could be a promising research field to elucidate new factors that determine spinal cord regeneration ability.", null, "pubmed:40278963", "Zebrafish 2 weeks post spinal cord injury replicate 1", "Zebrafish 2wpi 1", "SAMD00799621", null, "sample name:Zebrafish 2wpi 1|biological replicate:1|biomaterial provider:Center of Medical Innovation and Translational Research Osaka University|collection date:2023 04 14|dev stage:Adult|geo loc name:Japan|sex:not determined|strain:AB Zebrafish|tissue:Spinal cord", null, null, null, null, null, null, null, null, "DNBSEQ G400 paired end sequencing of SAMD00799621", "DRX648350", "RNA seq of spinal cord in zebrafish at 2wpi injured 1", "1", "Total RNA was extracted using RNeasy Micro Kit Qiagen 74104 with DNase treatment RNase Free DNase Set Qiagen 79254. Libraries were constructed from the amplified total RNA.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "DRP012880", "DNBSEQ G400 paired end sequencing of SAMD00799621", null, null, null, 16376197200.0, 81880986.0, "DRR668248", "0:100 1:100", "A:4485868844;C:3700974430;G:3710833937;T:4475827800;N:2692189", 100, 100, null, null, 4485868844, 3700974430, 3710833937, 4475827800, 2692189, "DRX648350", "DRS458863", "DRA020617", "Osaka University", "Osaka University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2025-05-12", "Adult", "Adult", "Spinal Cord", "Nervous System"], [47, "DRR668247", "DRX648349", "DRS458862", "DRP012880", "PRJDB18466", "Comparison of spinal cord regeneration capacity in zebrafish and medaka", "PRJDB18466", "Other", "Unlike mammals zebrafish have the remarkable ability to regenerate many tissues including the spinal cord. Medaka another model fish species has a low regenerative ability in the spinal cord. Therefore comparisons with them advantageous to revealing regeneration specific mechanisms in the spinal cord. The comparison of the spinal cord regeneration abilities of zebrafish and medaka could be a promising research field to elucidate new factors that determine spinal cord regeneration ability.", null, "pubmed:40278963", "Zebrafish Intact biological replicate 3", "Zebrafish Control 3", "SAMD00799620", null, "sample name:Zebrafish Control 3|biological replicate:3|biomaterial provider:Center of Medical Innovation and Translational Research Osaka University|collection date:2023 04 21|dev stage:Adult|geo loc name:Japan|sex:not determined|strain:AB Zebrafish|tissue:Spinal cord", null, null, null, null, null, null, null, null, "DNBSEQ G400 paired end sequencing of SAMD00799620", "DRX648349", "RNA seq of spinal cord in zebrafish at 0wpi control 3", "1", "Total RNA was extracted using RNeasy Micro Kit Qiagen 74104 with DNase treatment RNase Free DNase Set Qiagen 79254. Libraries were constructed from the amplified total RNA.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "DRP012880", "DNBSEQ G400 paired end sequencing of SAMD00799620", null, null, null, 13377538600.0, 66887693.0, "DRR668247", "0:100 1:100", "A:3725064764;C:2973653932;G:2980883214;T:3695767890;N:2168800", 100, 100, null, null, 3725064764, 2973653932, 2980883214, 3695767890, 2168800, "DRX648349", "DRS458862", "DRA020617", "Osaka University", "Osaka University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2025-05-12", "Adult", "Adult", "Spinal Cord", "Nervous System"], [48, "DRR668246", "DRX648348", "DRS458861", "DRP012880", "PRJDB18466", "Comparison of spinal cord regeneration capacity in zebrafish and medaka", "PRJDB18466", "Other", "Unlike mammals zebrafish have the remarkable ability to regenerate many tissues including the spinal cord. Medaka another model fish species has a low regenerative ability in the spinal cord. Therefore comparisons with them advantageous to revealing regeneration specific mechanisms in the spinal cord. The comparison of the spinal cord regeneration abilities of zebrafish and medaka could be a promising research field to elucidate new factors that determine spinal cord regeneration ability.", null, "pubmed:40278963", "Zebrafish Intact biological replicate 2", "Zebrafish Control 2", "SAMD00799619", null, "sample name:Zebrafish Control 2|biological replicate:2|biomaterial provider:Center of Medical Innovation and Translational Research Osaka University|collection date:2023 04 21|dev stage:Adult|geo loc name:Japan|sex:not determined|strain:AB Zebrafish|tissue:Spinal cord", null, null, null, null, null, null, null, null, "DNBSEQ G400 paired end sequencing of SAMD00799619", "DRX648348", "RNA seq of spinal cord in zebrafish at 0wpi control 2", "1", "Total RNA was extracted using RNeasy Micro Kit Qiagen 74104 with DNase treatment RNase Free DNase Set Qiagen 79254. Libraries were constructed from the amplified total RNA.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "DRP012880", "DNBSEQ G400 paired end sequencing of SAMD00799619", null, null, null, 14971411400.0, 74857057.0, "DRR668246", "0:100 1:100", "A:4160326445;C:3329083037;G:3329123314;T:4150453700;N:2424904", 100, 100, null, null, 4160326445, 3329083037, 3329123314, 4150453700, 2424904, "DRX648348", "DRS458861", "DRA020617", "Osaka University", "Osaka University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2025-05-12", "Adult", "Adult", "Spinal Cord", "Nervous System"], [49, "DRR668245", "DRX648347", "DRS458860", "DRP012880", "PRJDB18466", "Comparison of spinal cord regeneration capacity in zebrafish and medaka", "PRJDB18466", "Other", "Unlike mammals zebrafish have the remarkable ability to regenerate many tissues including the spinal cord. Medaka another model fish species has a low regenerative ability in the spinal cord. Therefore comparisons with them advantageous to revealing regeneration specific mechanisms in the spinal cord. The comparison of the spinal cord regeneration abilities of zebrafish and medaka could be a promising research field to elucidate new factors that determine spinal cord regeneration ability.", null, "pubmed:40278963", "Zebrafish Intact biological replicate 1", "Zebrafish Control 1", "SAMD00799618", null, "sample name:Zebrafish Control 1|biological replicate:1|biomaterial provider:Center of Medical Innovation and Translational Research Osaka University|collection date:2024 05 04|dev stage:Adult|geo loc name:Japan|sex:not determined|strain:AB Zebrafish|tissue:Spinal cord", null, null, null, null, null, null, null, null, "DNBSEQ G400 paired end sequencing of SAMD00799618", "DRX648347", "RNA seq of spinal cord in zebrafish at 0wpi control 1", "1", "Total RNA was extracted using RNeasy Micro Kit Qiagen 74104 with DNase treatment RNase Free DNase Set Qiagen 79254. Libraries were constructed from the amplified total RNA.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "DRP012880", "DNBSEQ G400 paired end sequencing of SAMD00799618", null, null, null, 13912523800.0, 69562619.0, "DRR668245", "0:100 1:100", "A:3888902049;C:3079617959;G:3075111814;T:3866655202;N:2236776", 100, 100, null, null, 3888902049, 3079617959, 3075111814, 3866655202, 2236776, "DRX648347", "DRS458860", "DRA020617", "Osaka University", "Osaka University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2025-05-12", "Adult", "Adult", "Spinal Cord", "Nervous System"], [25297, "SRR25764099", "SRX21486772", "SRS18719072", "SRP457109", "PRJNA1009810", "Live tracking of basal stem cells of the epidermis during growth homeostasis and injury response in zebrafish", "GSE241757", "Transcriptome Analysis", "Basal stem cells of the epidermis continuously differentiate into keratinocytes and replenish themselves via self renewal to maintain skin homeostasis. Numerous studies have attempted to reveal how basal cells undergo differentiation or self renewal; however this has been hampered by a lack of robust basal cell markers and analytical platforms that allow single cell tracking. Here we report integrin b4 itgb4 is a useful marker for basal cell labelling irrespective of the body region stage and regenerative status. We employed Cre loxP recombination in combination with live cell tracking of single basal clones in the caudal fin and investigated the embryonic origin and behaviour of basal cells during fish growth and homeostasis. Although most basal cells including those in fins became quiescent in the adult stage genetic cell ablation showed that basal cells were reactivated to either self renew or differentiate depending on the injured cell type. Our findings provide a platform for quantitative in vivo imaging of basal stem cells applicable at wider stages and under various conditions and reveal unanticipated basal cell dynamism in response to distinct wound signals. Overall design: To investigate whether itgb4+ epidermal basal precursors already possess a basal cell like identity immediately post fate segregation at 1 dpf dpf we isolated itgb4+ basal precursors krt4+ periderm cells from zebrafish embryos at 1 dpf and adult itgb4+ basal cells from zebrafish caudal fin by fluorescence activated cell sorting. We then performed gene expression profiling analysis using data obtained from RNA seq of 3 different cells at 2 time points. Comparative gene expression profiling analysis of RNA seq data for embryonic basal cell precursors embryonic periderm and adult basal cells.", null, "pubmed:38265193", null, "Adult itgb4+ basal cells", "GSM7734879", null, "tissue:epidermal cells|cell type:adult fin epidermal basal cells|genotype:Tgitgb4:mcherry|geo loc name:missing|collection date:missing", "Adult itgb4+ basal cells", "High quality reads were mapped using hisat2 ver. 2.2.1 Trimmed sequence reads were mapped to GRCz11 using hisat2. Read count extraxction and normalization were performed using featureCounts ver. 2.0.3 Assembly: GRCz11 Supplementary files format and content: tab delimited text file includes basic gene information gene id length Genebank id RNA type gene name product raw count RPKM and TPM values.", "epidermal cells", "Different types of cells were sorted by the fluorescence activated cell sorter SH800S SONY.", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer\u2019s protocol.", "Fish were maintained in a recirculating water system in a 14 h day/10 h night photoperiod at 28.5 \u00b0C. The wild type zebrafish Danio rerio strain used in this study was originally derived from the Tubingen strain and has been maintained in our facility for more than 10 years by inbreeding.", "cell type:adult fin epidermal basal cells|genotype:Tgitgb4:mcherry", "GSM7734879", "GSM7734879: Adult itgb4+ basal cells; Danio rerio; RNA Seq", "GSM7734879 r1", "GSM7734879", "1", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer's protocol.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP457109", null, null, "Adult_itgb4mcherry_S230_R1_001.fastq.gz Adult_itgb4mcherry_S230_R2_001.fastq.gz", "fastq fastq", 5035430000.0, 12588575.0, "GSM7734879 r1", "0:200 1:200", "A:1339392170;C:1117195164;G:1254708952;T:1323174485;N:959229", 200, 200, null, null, 1339392170, 1117195164, 1254708952, 1323174485, 959229, "SRX21486772", "SRS18719072", "SRA1700438", "Kawakami Lab, School of Life Science and Technology, Tokyo Institute of Technology", "Kawakami Lab, School of Life Science and Technology, Tokyo Institute of Technology", 2, 0.01543, 0.02468, 0.00098, 0.00102, 0.99318, 0.99387, 0.47878, 0.31718, 200, 200, "T", "T", "mates < 9% mapping rate", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2023-08-28", "Adult", "Adult", "Skin", "Surface Structure"], [28397, "SRR26216293", "SRX21926780", "SRS19011110", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep11 [22 01885 S45]", "GSM7813348", null, "source name:brain|tissue:brain|home tank:P1 lay1.2|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain BC WT rep11 [22 01885 S45]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P1 lay1.2|genotype:WT|Sex:female", "GSM7813348", "GSM7813348: Brain BC WT rep11 [22 01885 S45]; Danio rerio; RNA Seq", "GSM7813348 r1", "GSM7813348", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01885_S45_R2_001.merged.fastq.gz 22-01885_S45_R1_001.merged.fastq.gz", "fastq fastq", 20434168356.0, 104255961.0, "GSM7813348 r1", "0:98 1:98", "A:5389036438;C:4758919928;G:4775862064;T:5506840669;N:3509257", 98, 98, null, null, 5389036438, 4758919928, 4775862064, 5506840669, 3509257, "SRX21926780", "SRS19011110", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.94374, 0.9373, 0.09831, 0.09986, 0.70051, 0.7012, 0.49691, 0.49749, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28398, "SRR26216294", "SRX21926779", "SRS19011109", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep10 [22 01884 S44]", "GSM7813347", null, "source name:brain|tissue:brain|home tank:P1 lay1.2|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain BC WT rep10 [22 01884 S44]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P1 lay1.2|genotype:WT|Sex:female", "GSM7813347", "GSM7813347: Brain BC WT rep10 [22 01884 S44]; Danio rerio; RNA Seq", "GSM7813347 r1", "GSM7813347", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01884_S44_R2_001.merged.fastq.gz 22-01884_S44_R1_001.merged.fastq.gz", "fastq fastq", 18009760272.0, 91886532.0, "GSM7813347 r1", "0:98 1:98", "A:4720233526;C:4238307986;G:4233288270;T:4814852918;N:3077572", 98, 98, null, null, 4720233526, 4238307986, 4233288270, 4814852918, 3077572, "SRX21926779", "SRS19011109", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.94296, 0.93818, 0.09822, 0.10014, 0.69674, 0.69808, 0.50095, 0.49564, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28399, "SRR26216295", "SRX21926778", "SRS19011108", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIB rep8 [22 01883 S43]", "GSM7813346", null, "source name:brain|tissue:brain|home tank:P1 lay1.2|genotype:MPSIIIB|Sex:female|geo loc name:missing|collection date:missing", "Brain BC MPSIIIB rep8 [22 01883 S43]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P1 lay1.2|genotype:MPSIIIB|Sex:female", "GSM7813346", "GSM7813346: Brain BC MPSIIIB rep8 [22 01883 S43]; Danio rerio; RNA Seq", "GSM7813346 r1", "GSM7813346", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01883_S43_R1_001.merged.fastq.gz 22-01883_S43_R2_001.merged.fastq.gz", "fastq fastq", 17370595648.0, 88625488.0, "GSM7813346 r1", "0:98 1:98", "A:4566434950;C:4075041360;G:4075273162;T:4650852579;N:2993597", 98, 98, null, null, 4566434950, 4075041360, 4075273162, 4650852579, 2993597, "SRX21926778", "SRS19011108", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.94109, 0.93655, 0.09902, 0.10131, 0.69785, 0.69921, 0.49509, 0.49323, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28400, "SRR26216296", "SRX21926777", "SRS19011106", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIB rep7 [22 01882 S42]", "GSM7813345", null, "source name:brain|tissue:brain|home tank:P1 lay1.1|genotype:MPSIIIB|Sex:male|geo loc name:missing|collection date:missing", "Brain BC MPSIIIB rep7 [22 01882 S42]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P1 lay1.1|genotype:MPSIIIB|Sex:male", "GSM7813345", "GSM7813345: Brain BC MPSIIIB rep7 [22 01882 S42]; Danio rerio; RNA Seq", "GSM7813345 r1", "GSM7813345", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01882_S42_R2_001.merged.fastq.gz 22-01882_S42_R1_001.merged.fastq.gz", "fastq fastq", 22556257808.0, 115082948.0, "GSM7813345 r1", "0:98 1:98", "A:5932142973;C:5277274711;G:5294964347;T:6047997396;N:3878381", 98, 98, null, null, 5932142973, 5277274711, 5294964347, 6047997396, 3878381, "SRX21926777", "SRS19011106", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.93651, 0.93565, 0.10798, 0.10948, 0.70337, 0.70388, 0.48941, 0.49034, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28401, "SRR26216297", "SRX21926776", "SRS19011107", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIB rep6 [22 01881 S41]", "GSM7813344", null, "source name:brain|tissue:brain|home tank:P1 lay1.1|genotype:MPSIIIB|Sex:male|geo loc name:missing|collection date:missing", "Brain BC MPSIIIB rep6 [22 01881 S41]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P1 lay1.1|genotype:MPSIIIB|Sex:male", "GSM7813344", "GSM7813344: Brain BC MPSIIIB rep6 [22 01881 S41]; Danio rerio; RNA Seq", "GSM7813344 r1", "GSM7813344", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01881_S41_R2_001.merged.fastq.gz 22-01881_S41_R1_001.merged.fastq.gz", "fastq fastq", 13544867140.0, 69106465.0, "GSM7813344 r1", "0:98 1:98", "A:3593957976;C:3143252317;G:3143192820;T:3662150851;N:2313176", 98, 98, null, null, 3593957976, 3143252317, 3143192820, 3662150851, 2313176, "SRX21926776", "SRS19011107", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.94189, 0.93615, 0.09975, 0.10129, 0.70195, 0.70307, 0.5056, 0.505, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28402, "SRR26216298", "SRX21926775", "SRS19011105", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIB rep3 [22 01862 S24]", "GSM7813327", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank2.1|genotype:MPSIIIB|Sex:male|geo loc name:missing|collection date:missing", "Brain BC MPSIIIB rep3 [22 01862 S24]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank2.1|genotype:MPSIIIB|Sex:male", "GSM7813327", "GSM7813327: Brain BC MPSIIIB rep3 [22 01862 S24]; Danio rerio; RNA Seq", "GSM7813327 r1", "GSM7813327", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01862_S24_R1_001.merged.fastq.gz 22-01862_S24_R2_001.merged.fastq.gz", "fastq fastq", 16452824668.0, 83942983.0, "GSM7813327 r1", "0:98 1:98", "A:4477559720;C:3648309090;G:3661532584;T:4662575737;N:2847537", 98, 98, null, null, 4477559720, 3648309090, 3661532584, 4662575737, 2847537, "SRX21926775", "SRS19011105", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91104, 0.91207, 0.18247, 0.18984, 0.70463, 0.70309, 0.48379, 0.4869, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28403, "SRR26216299", "SRX21926774", "SRS19011104", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIC rep1 [22 01861 S23]", "GSM7813326", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank2.1|genotype:MPSIIIC|Sex:male|geo loc name:missing|collection date:missing", "Brain BC MPSIIIC rep1 [22 01861 S23]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank2.1|genotype:MPSIIIC|Sex:male", "GSM7813326", "GSM7813326: Brain BC MPSIIIC rep1 [22 01861 S23]; Danio rerio; RNA Seq", "GSM7813326 r1", "GSM7813326", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01861_S23_R1_001.merged.fastq.gz 22-01861_S23_R2_001.merged.fastq.gz", "fastq fastq", 15049678112.0, 76784072.0, "GSM7813326 r1", "0:98 1:98", "A:4184698968;C:3230678326;G:3246295686;T:4385460926;N:2544206", 98, 98, null, null, 4184698968, 3230678326, 3246295686, 4385460926, 2544206, "SRX21926774", "SRS19011104", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.8935, 0.9026, 0.2241, 0.23699, 0.70707, 0.70311, 0.48218, 0.48558, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28404, "SRR26216300", "SRX21926773", "SRS19011103", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIB rep2 [22 01860 S22]", "GSM7813325", null, "source name:brain|tissue:brain|home tank:P2 lay1 tank1|genotype:MPSIIIB|Sex:male|geo loc name:missing|collection date:missing", "Brain BC MPSIIIB rep2 [22 01860 S22]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay1 tank1|genotype:MPSIIIB|Sex:male", "GSM7813325", "GSM7813325: Brain BC MPSIIIB rep2 [22 01860 S22]; Danio rerio; RNA Seq", "GSM7813325 r1", "GSM7813325", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01860_S22_R2_001.merged.fastq.gz 22-01860_S22_R1_001.merged.fastq.gz", "fastq fastq", 12822405456.0, 65420436.0, "GSM7813325 r1", "0:98 1:98", "A:3468590749;C:2881037791;G:2902765490;T:3567850437;N:2160989", 98, 98, null, null, 3468590749, 2881037791, 2902765490, 3567850437, 2160989, "SRX21926773", "SRS19011103", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.90916, 0.92042, 0.1609, 0.17347, 0.70561, 0.70313, 0.48953, 0.48767, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28405, "SRR26216301", "SRX21926772", "SRS19011102", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIB rep1 [22 01859 S21]", "GSM7813324", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank1|genotype:MPSIIIB|Sex:female|geo loc name:missing|collection date:missing", "Brain BC MPSIIIB rep1 [22 01859 S21]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank1|genotype:MPSIIIB|Sex:female", "GSM7813324", "GSM7813324: Brain BC MPSIIIB rep1 [22 01859 S21]; Danio rerio; RNA Seq", "GSM7813324 r1", "GSM7813324", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01859_S21_R1_001.merged.fastq.gz 22-01859_S21_R2_001.merged.fastq.gz", "fastq fastq", 13719489420.0, 69997395.0, "GSM7813324 r1", "0:98 1:98", "A:3755751512;C:3014995385;G:3035398792;T:3910996480;N:2347251", 98, 98, null, null, 3755751512, 3014995385, 3035398792, 3910996480, 2347251, "SRX21926772", "SRS19011102", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.90744, 0.9116, 0.20528, 0.21455, 0.70364, 0.70153, 0.49418, 0.49312, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28406, "SRR26216302", "SRX21926771", "SRS19011101", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIC rep6 [22 01858 S20]", "GSM7813323", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank5|genotype:MPSIIIC|Sex:male|geo loc name:missing|collection date:missing", "Brain AC MPSIIIC rep6 [22 01858 S20]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank5|genotype:MPSIIIC|Sex:male", "GSM7813323", "GSM7813323: Brain AC MPSIIIC rep6 [22 01858 S20]; Danio rerio; RNA Seq", "GSM7813323 r1", "GSM7813323", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01858_S20_R2_001.merged.fastq.gz 22-01858_S20_R1_001.merged.fastq.gz", "fastq fastq", 15310607816.0, 78115346.0, "GSM7813323 r1", "0:98 1:98", "A:4165340199;C:3454649027;G:3451450322;T:4236592701;N:2575567", 98, 98, null, null, 4165340199, 3454649027, 3451450322, 4236592701, 2575567, "SRX21926771", "SRS19011101", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92444, 0.92137, 0.18296, 0.18603, 0.70017, 0.70061, 0.48135, 0.4834, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28407, "SRR26216303", "SRX21926770", "SRS19011100", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIC rep5 [22 01857 S19]", "GSM7813322", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank5|genotype:MPSIIIC|Sex:male|geo loc name:missing|collection date:missing", "Brain AC MPSIIIC rep5 [22 01857 S19]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank5|genotype:MPSIIIC|Sex:male", "GSM7813322", "GSM7813322: Brain AC MPSIIIC rep5 [22 01857 S19]; Danio rerio; RNA Seq", "GSM7813322 r1", "GSM7813322", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01857_S19_R1_001.merged.fastq.gz 22-01857_S19_R2_001.merged.fastq.gz", "fastq fastq", 13226432604.0, 67481799.0, "GSM7813322 r1", "0:98 1:98", "A:3542509388;C:3031510779;G:3045645724;T:3604459613;N:2307100", 98, 98, null, null, 3542509388, 3031510779, 3045645724, 3604459613, 2307100, "SRX21926770", "SRS19011100", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.93408, 0.92841, 0.13142, 0.13298, 0.70816, 0.70826, 0.49404, 0.49271, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28408, "SRR26216304", "SRX21926769", "SRS19011099", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC WT rep7 [22 01856 S18]", "GSM7813321", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank5|genotype:WT|Sex:male|geo loc name:missing|collection date:missing", "Brain AC WT rep7 [22 01856 S18]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank5|genotype:WT|Sex:male", "GSM7813321", "GSM7813321: Brain AC WT rep7 [22 01856 S18]; Danio rerio; RNA Seq", "GSM7813321 r1", "GSM7813321", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01856_S18_R1_001.merged.fastq.gz 22-01856_S18_R2_001.merged.fastq.gz", "fastq fastq", 20503339304.0, 104608874.0, "GSM7813321 r1", "0:98 1:98", "A:5528898139;C:4659501597;G:4659355396;T:5652075850;N:3508322", 98, 98, null, null, 5528898139, 4659501597, 4659355396, 5652075850, 3508322, "SRX21926769", "SRS19011099", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92682, 0.92364, 0.16389, 0.16778, 0.70096, 0.70112, 0.4854, 0.48333, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28409, "SRR26216305", "SRX21926768", "SRS19011098", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIA rep7 [22 01855 S17]", "GSM7813320", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank5|genotype:MPSIIIA|Sex:male|geo loc name:missing|collection date:missing", "Brain AC MPSIIIA rep7 [22 01855 S17]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank5|genotype:MPSIIIA|Sex:male", "GSM7813320", "GSM7813320: Brain AC MPSIIIA rep7 [22 01855 S17]; Danio rerio; RNA Seq", "GSM7813320 r1", "GSM7813320", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01855_S17_R1_001.merged.fastq.gz 22-01855_S17_R2_001.merged.fastq.gz", "fastq fastq", 19394559856.0, 98951836.0, "GSM7813320 r1", "0:98 1:98", "A:5289871689;C:4352372013;G:4340663511;T:5408322812;N:3329831", 98, 98, null, null, 5289871689, 4352372013, 4340663511, 5408322812, 3329831, "SRX21926768", "SRS19011098", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92046, 0.92135, 0.17988, 0.18544, 0.70157, 0.7011, 0.49298, 0.48867, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28410, "SRR26216306", "SRX21926767", "SRS19011097", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC WT rep6 [22 01854 S16]", "GSM7813319", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank4|genotype:WT|Sex:male|geo loc name:missing|collection date:missing", "Brain AC WT rep6 [22 01854 S16]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank4|genotype:WT|Sex:male", "GSM7813319", "GSM7813319: Brain AC WT rep6 [22 01854 S16]; Danio rerio; RNA Seq", "GSM7813319 r1", "GSM7813319", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01854_S16_R1_001.merged.fastq.gz 22-01854_S16_R2_001.merged.fastq.gz", "fastq fastq", 16294765956.0, 83136561.0, "GSM7813319 r1", "0:98 1:98", "A:4363489648;C:3732286771;G:3728959754;T:4467240758;N:2789025", 98, 98, null, null, 4363489648, 3732286771, 3728959754, 4467240758, 2789025, "SRX21926767", "SRS19011097", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.93124, 0.92636, 0.14699, 0.14912, 0.6999, 0.69964, 0.48136, 0.47855, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28411, "SRR26216307", "SRX21926766", "SRS19011096", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC WT rep5 [22 01853 S15]", "GSM7813318", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank4|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain AC WT rep5 [22 01853 S15]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank4|genotype:WT|Sex:female", "GSM7813318", "GSM7813318: Brain AC WT rep5 [22 01853 S15]; Danio rerio; RNA Seq", "GSM7813318 r1", "GSM7813318", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01853_S15_R2_001.merged.fastq.gz 22-01853_S15_R1_001.merged.fastq.gz", "fastq fastq", 20409440996.0, 104129801.0, "GSM7813318 r1", "0:98 1:98", "A:5486026796;C:4642485802;G:4659975719;T:5617468124;N:3484555", 98, 98, null, null, 5486026796, 4642485802, 4659975719, 5617468124, 3484555, "SRX21926766", "SRS19011096", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.9275, 0.92451, 0.15776, 0.16157, 0.70682, 0.7065, 0.48261, 0.48684, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28412, "SRR26216308", "SRX21926765", "SRS19011095", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIA rep6 [22 01852 S14]", "GSM7813317", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank4|genotype:MPSIIIA|Sex:male|geo loc name:missing|collection date:missing", "Brain AC MPSIIIA rep6 [22 01852 S14]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank4|genotype:MPSIIIA|Sex:male", "GSM7813317", "GSM7813317: Brain AC MPSIIIA rep6 [22 01852 S14]; Danio rerio; RNA Seq", "GSM7813317 r1", "GSM7813317", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01852_S14_R1_001.merged.fastq.gz 22-01852_S14_R2_001.merged.fastq.gz", "fastq fastq", 17445291444.0, 89006589.0, "GSM7813317 r1", "0:98 1:98", "A:4748102103;C:3888877889;G:3908613563;T:4896710898;N:2986991", 98, 98, null, null, 4748102103, 3888877889, 3908613563, 4896710898, 2986991, "SRX21926765", "SRS19011095", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91763, 0.9177, 0.18209, 0.18808, 0.70278, 0.70147, 0.48372, 0.48072, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28413, "SRR26216309", "SRX21926764", "SRS19011094", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIA rep5 [22 01851 S13]", "GSM7813316", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank3|genotype:MPSIIIA|Sex:male|geo loc name:missing|collection date:missing", "Brain AC MPSIIIA rep5 [22 01851 S13]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank3|genotype:MPSIIIA|Sex:male", "GSM7813316", "GSM7813316: Brain AC MPSIIIA rep5 [22 01851 S13]; Danio rerio; RNA Seq", "GSM7813316 r1", "GSM7813316", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01851_S13_R1_001.merged.fastq.gz 22-01851_S13_R2_001.merged.fastq.gz", "fastq fastq", 21121699116.0, 107763771.0, "GSM7813316 r1", "0:98 1:98", "A:5723207150;C:4754780028;G:4777942447;T:5862189785;N:3579706", 98, 98, null, null, 5723207150, 4754780028, 4777942447, 5862189785, 3579706, "SRX21926764", "SRS19011094", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92295, 0.92126, 0.1654, 0.17001, 0.7037, 0.70335, 0.49469, 0.49631, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28414, "SRR26216310", "SRX21926763", "SRS19011093", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC WT rep4 [22 01850 S12]", "GSM7813315", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank3|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain AC WT rep4 [22 01850 S12]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank3|genotype:WT|Sex:female", "GSM7813315", "GSM7813315: Brain AC WT rep4 [22 01850 S12]; Danio rerio; RNA Seq", "GSM7813315 r1", "GSM7813315", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01850_S12_R1_001.merged.fastq.gz 22-01850_S12_R2_001.merged.fastq.gz", "fastq fastq", 14970865532.0, 76381967.0, "GSM7813315 r1", "0:98 1:98", "A:4034135351;C:3397406994;G:3405648099;T:4131112485;N:2562603", 98, 98, null, null, 4034135351, 3397406994, 3405648099, 4131112485, 2562603, "SRX21926763", "SRS19011093", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92279, 0.92064, 0.16643, 0.17092, 0.70402, 0.70418, 0.48212, 0.48221, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28415, "SRR26216311", "SRX21926762", "SRS19011092", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC WT rep3 [22 01849 S11]", "GSM7813314", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank3|genotype:WT|Sex:male|geo loc name:missing|collection date:missing", "Brain AC WT rep3 [22 01849 S11]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank3|genotype:WT|Sex:male", "GSM7813314", "GSM7813314: Brain AC WT rep3 [22 01849 S11]; Danio rerio; RNA Seq", "GSM7813314 r1", "GSM7813314", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01849_S11_R1_001.merged.fastq.gz 22-01849_S11_R2_001.merged.fastq.gz", "fastq fastq", 13483949164.0, 68795659.0, "GSM7813314 r1", "0:98 1:98", "A:3631909201;C:3062376139;G:3075381714;T:3711984954;N:2297156", 98, 98, null, null, 3631909201, 3062376139, 3075381714, 3711984954, 2297156, "SRX21926762", "SRS19011092", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92694, 0.92533, 0.16165, 0.16577, 0.70688, 0.70745, 0.48712, 0.48231, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28416, "SRR26216312", "SRX21926761", "SRS19011091", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIC rep4 [22 01848 S10]", "GSM7813313", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank3|genotype:MPSIIIC|Sex:male|geo loc name:missing|collection date:missing", "Brain AC MPSIIIC rep4 [22 01848 S10]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank3|genotype:MPSIIIC|Sex:male", "GSM7813313", "GSM7813313: Brain AC MPSIIIC rep4 [22 01848 S10]; Danio rerio; RNA Seq", "GSM7813313 r1", "GSM7813313", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01848_S10_R1_001.merged.fastq.gz 22-01848_S10_R2_001.merged.fastq.gz", "fastq fastq", 11196327520.0, 57124120.0, "GSM7813313 r1", "0:98 1:98", "A:3039336227;C:2518474505;G:2535218436;T:3101406136;N:1892216", 98, 98, null, null, 3039336227, 2518474505, 2535218436, 3101406136, 1892216, "SRX21926761", "SRS19011091", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92351, 0.9222, 0.15807, 0.16264, 0.70924, 0.70916, 0.48542, 0.49384, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28417, "SRR26216313", "SRX21926760", "SRS19011090", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIC rep3 [22 01847 S9]", "GSM7813312", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank6|genotype:MPSIIIC|Sex:female|geo loc name:missing|collection date:missing", "Brain AC MPSIIIC rep3 [22 01847 S9]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank6|genotype:MPSIIIC|Sex:female", "GSM7813312", "GSM7813312: Brain AC MPSIIIC rep3 [22 01847 S9]; Danio rerio; RNA Seq", "GSM7813312 r1", "GSM7813312", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01847_S9_R1_001.merged.fastq.gz 22-01847_S9_R2_001.merged.fastq.gz", "fastq fastq", 18631162788.0, 95056953.0, "GSM7813312 r1", "0:98 1:98", "A:5031487220;C:4206022334;G:4219973839;T:5170494547;N:3184848", 98, 98, null, null, 5031487220, 4206022334, 4219973839, 5170494547, 3184848, "SRX21926760", "SRS19011090", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92274, 0.92264, 0.16323, 0.16972, 0.70538, 0.70449, 0.48765, 0.48719, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28418, "SRR26216314", "SRX21926759", "SRS19011089", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB WT rep4 [22 00160 S16]", "GSM7813303", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank3|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain AB WT rep4 [22 00160 S16]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank3|genotype:WT|Sex:female", "GSM7813303", "GSM7813303: Brain AB WT rep4 [22 00160 S16]; Danio rerio; RNA Seq", "GSM7813303 r1", "GSM7813303", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00160_S16_R1_001.merged.fastq.gz 22-00160_S16_R2_001.merged.fastq.gz", "fastq fastq", 19648243636.0, 100246141.0, "GSM7813303 r1", "0:98 1:98", "A:5325999167;C:4367508008;G:4409495594;T:5538729015;N:6511852", 98, 98, null, null, 5325999167, 4367508008, 4409495594, 5538729015, 6511852, "SRX21926759", "SRS19011089", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91143, 0.91395, 0.18214, 0.20284, 0.70175, 0.69901, 0.4973, 0.49726, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28419, "SRR26216315", "SRX21926758", "SRS19011088", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB MPSIIIB rep4 [22 00159 S15]", "GSM7813302", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIB|Sex:female|geo loc name:missing|collection date:missing", "Brain AB MPSIIIB rep4 [22 00159 S15]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIB|Sex:female", "GSM7813302", "GSM7813302: Brain AB MPSIIIB rep4 [22 00159 S15]; Danio rerio; RNA Seq", "GSM7813302 r1", "GSM7813302", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00159_S15_R1_001.merged.fastq.gz 22-00159_S15_R2_001.merged.fastq.gz", "fastq fastq", 21499917376.0, 109693456.0, "GSM7813302 r1", "0:98 1:98", "A:5745647949;C:4893192375;G:4930514968;T:5923547766;N:7014318", 98, 98, null, null, 5745647949, 4893192375, 4930514968, 5923547766, 7014318, "SRX21926758", "SRS19011088", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92648, 0.92654, 0.15109, 0.16305, 0.70059, 0.70037, 0.49317, 0.48848, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28420, "SRR26216316", "SRX21926757", "SRS19011087", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB sgsh het rep4 [22 00158 S14]", "GSM7813301", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank3|genotype:sgsh het|Sex:female|geo loc name:missing|collection date:missing", "Brain AB sgsh het rep4 [22 00158 S14]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank3|genotype:sgsh het|Sex:female", "GSM7813301", "GSM7813301: Brain AB sgsh het rep4 [22 00158 S14]; Danio rerio; RNA Seq", "GSM7813301 r1", "GSM7813301", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00158_S14_R1_001.merged.fastq.gz 22-00158_S14_R2_001.merged.fastq.gz", "fastq fastq", 22230319412.0, 113419997.0, "GSM7813301 r1", "0:98 1:98", "A:6130721912;C:4821098792;G:4876843039;T:6394368688;N:7286981", 98, 98, null, null, 6130721912, 4821098792, 4876843039, 6394368688, 7286981, "SRX21926757", "SRS19011087", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.90557, 0.91073, 0.20914, 0.23456, 0.71155, 0.70723, 0.49955, 0.4974, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28421, "SRR26216317", "SRX21926756", "SRS19011086", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB MPSIIIA rep4 [22 00157 S13]", "GSM7813300", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIA|Sex:female|geo loc name:missing|collection date:missing", "Brain AB MPSIIIA rep4 [22 00157 S13]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIA|Sex:female", "GSM7813300", "GSM7813300: Brain AB MPSIIIA rep4 [22 00157 S13]; Danio rerio; RNA Seq", "GSM7813300 r1", "GSM7813300", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00157_S13_R2_001.merged.fastq.gz 22-00157_S13_R1_001.merged.fastq.gz", "fastq fastq", 22546811588.0, 115034753.0, "GSM7813300 r1", "0:98 1:98", "A:6142967085;C:4991190165;G:5035361097;T:6369886796;N:7406445", 98, 98, null, null, 6142967085, 4991190165, 5035361097, 6369886796, 7406445, "SRX21926756", "SRS19011086", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91532, 0.91952, 0.18459, 0.20386, 0.70707, 0.70666, 0.49308, 0.49332, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28422, "SRR26216318", "SRX21926755", "SRS19011085", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB MPSIIIA rep3 [22 00156 S12]", "GSM7813299", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIA|Sex:female|geo loc name:missing|collection date:missing", "Brain AB MPSIIIA rep3 [22 00156 S12]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIA|Sex:female", "GSM7813299", "GSM7813299: Brain AB MPSIIIA rep3 [22 00156 S12]; Danio rerio; RNA Seq", "GSM7813299 r1", "GSM7813299", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00156_S12_R2_001.merged.fastq.gz 22-00156_S12_R1_001.merged.fastq.gz", "fastq fastq", 21659471372.0, 110507507.0, "GSM7813299 r1", "0:98 1:98", "A:5967042457;C:4685520941;G:4732611066;T:6267172239;N:7124669", 98, 98, null, null, 5967042457, 4685520941, 4732611066, 6267172239, 7124669, "SRX21926755", "SRS19011085", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.90281, 0.90971, 0.22168, 0.25011, 0.7027, 0.6994, 0.48627, 0.48623, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28423, "SRR26216319", "SRX21926754", "SRS19011084", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB MPSIIIB rep3 [22 00155 S11]", "GSM7813298", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIB|Sex:female|geo loc name:missing|collection date:missing", "Brain AB MPSIIIB rep3 [22 00155 S11]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIB|Sex:female", "GSM7813298", "GSM7813298: Brain AB MPSIIIB rep3 [22 00155 S11]; Danio rerio; RNA Seq", "GSM7813298 r1", "GSM7813298", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00155_S11_R2_001.merged.fastq.gz 22-00155_S11_R1_001.merged.fastq.gz", "fastq fastq", 22973518092.0, 117211827.0, "GSM7813298 r1", "0:98 1:98", "A:6205640622;C:5145809555;G:5198001598;T:6416628989;N:7437328", 98, 98, null, null, 6205640622, 5145809555, 5198001598, 6416628989, 7437328, "SRX21926754", "SRS19011084", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91842, 0.92237, 0.17436, 0.19254, 0.69883, 0.69834, 0.49394, 0.49304, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28424, "SRR26216320", "SRX21926753", "SRS19011083", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB sgsh het rep3 [22 00154 S10]", "GSM7813297", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank3|genotype:sgsh het|Sex:female|geo loc name:missing|collection date:missing", "Brain AB sgsh het rep3 [22 00154 S10]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank3|genotype:sgsh het|Sex:female", "GSM7813297", "GSM7813297: Brain AB sgsh het rep3 [22 00154 S10]; Danio rerio; RNA Seq", "GSM7813297 r1", "GSM7813297", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00154_S10_R1_001.merged.fastq.gz 22-00154_S10_R2_001.merged.fastq.gz", "fastq fastq", 21605437896.0, 110231826.0, "GSM7813297 r1", "0:98 1:98", "A:5873646278;C:4818397053;G:4875408993;T:6030978522;N:7007050", 98, 98, null, null, 5873646278, 4818397053, 4875408993, 6030978522, 7007050, "SRX21926753", "SRS19011083", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91754, 0.9191, 0.1734, 0.18936, 0.70863, 0.70853, 0.49545, 0.49342, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28425, "SRR26216321", "SRX21926752", "SRS19011082", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB MPSIIIB rep2 [22 00153 S9]", "GSM7813296", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank2|genotype:MPSIIIB|Sex:female|geo loc name:missing|collection date:missing", "Brain AB MPSIIIB rep2 [22 00153 S9]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank2|genotype:MPSIIIB|Sex:female", "GSM7813296", "GSM7813296: Brain AB MPSIIIB rep2 [22 00153 S9]; Danio rerio; RNA Seq", "GSM7813296 r1", "GSM7813296", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00153_S9_R1_001.merged.fastq.gz 22-00153_S9_R2_001.merged.fastq.gz", "fastq fastq", 20290379816.0, 103522346.0, "GSM7813296 r1", "0:98 1:98", "A:5512611544;C:4506159259;G:4545779658;T:5719122488;N:6706867", 98, 98, null, null, 5512611544, 4506159259, 4545779658, 5719122488, 6706867, "SRX21926752", "SRS19011082", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91537, 0.92019, 0.18133, 0.20302, 0.70205, 0.69929, 0.49316, 0.49323, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28426, "SRR26216322", "SRX21926751", "SRS19011081", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep9 [22 01879 S40]", "GSM7813343", null, "source name:brain|tissue:brain|home tank:P1 lay1.1|genotype:WT|Sex:male|geo loc name:missing|collection date:missing", "Brain BC WT rep9 [22 01879 S40]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P1 lay1.1|genotype:WT|Sex:male", "GSM7813343", "GSM7813343: Brain BC WT rep9 [22 01879 S40]; Danio rerio; RNA Seq", "GSM7813343 r1", "GSM7813343", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01879_S40_R1_001.merged.fastq.gz 22-01879_S40_R2_001.merged.fastq.gz", "fastq fastq", 20379409680.0, 103976580.0, "GSM7813343 r1", "0:98 1:98", "A:5369707205;C:4764694596;G:4769087059;T:5472372608;N:3548212", 98, 98, null, null, 5369707205, 4764694596, 4769087059, 5472372608, 3548212, "SRX21926751", "SRS19011081", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.93829, 0.93274, 0.1147, 0.11712, 0.70485, 0.70737, 0.48791, 0.48911, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28427, "SRR26216323", "SRX21926750", "SRS19011080", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep8 [22 01877 S39]", "GSM7813342", null, "source name:brain|tissue:brain|home tank:P1 lay1.1|genotype:WT|Sex:male|geo loc name:missing|collection date:missing", "Brain BC WT rep8 [22 01877 S39]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P1 lay1.1|genotype:WT|Sex:male", "GSM7813342", "GSM7813342: Brain BC WT rep8 [22 01877 S39]; Danio rerio; RNA Seq", "GSM7813342 r1", "GSM7813342", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01877_S39_R1_001.merged.fastq.gz 22-01877_S39_R2_001.merged.fastq.gz", "fastq fastq", 20300298984.0, 103572954.0, "GSM7813342 r1", "0:98 1:98", "A:5322006867;C:4768036193;G:4786472382;T:5420285698;N:3497844", 98, 98, null, null, 5322006867, 4768036193, 4786472382, 5420285698, 3497844, "SRX21926750", "SRS19011080", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.93935, 0.93555, 0.10951, 0.11139, 0.70879, 0.7094, 0.48625, 0.4844, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28428, "SRR26216324", "SRX21926749", "SRS19011079", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIB rep5 [22 01876 S38]", "GSM7813341", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank1|genotype:MPSIIIB|Sex:female|geo loc name:missing|collection date:missing", "Brain BC MPSIIIB rep5 [22 01876 S38]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank1|genotype:MPSIIIB|Sex:female", "GSM7813341", "GSM7813341: Brain BC MPSIIIB rep5 [22 01876 S38]; Danio rerio; RNA Seq", "GSM7813341 r1", "GSM7813341", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01876_S38_R1_001.merged.fastq.gz 22-01876_S38_R2_001.merged.fastq.gz", "fastq fastq", 20658198904.0, 105398974.0, "GSM7813341 r1", "0:98 1:98", "A:5601204040;C:4656310461;G:4653067969;T:5744065008;N:3551426", 98, 98, null, null, 5601204040, 4656310461, 4653067969, 5744065008, 3551426, "SRX21926749", "SRS19011079", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92156, 0.92055, 0.16792, 0.17216, 0.69739, 0.6955, 0.4896, 0.49082, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28429, "SRR26216325", "SRX21926748", "SRS19011078", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep7 [22 01875 S37]", "GSM7813340", null, "source name:brain|tissue:brain|home tank:P2 lay1 tank1|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain BC WT rep7 [22 01875 S37]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay1 tank1|genotype:WT|Sex:female", "GSM7813340", "GSM7813340: Brain BC WT rep7 [22 01875 S37]; Danio rerio; RNA Seq", "GSM7813340 r1", "GSM7813340", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01875_S37_R1_001.merged.fastq.gz 22-01875_S37_R2_001.merged.fastq.gz", "fastq fastq", 19187850220.0, 97897195.0, "GSM7813340 r1", "0:98 1:98", "A:5098960652;C:4434084345;G:4444522551;T:5206970324;N:3312348", 98, 98, null, null, 5098960652, 4434084345, 4444522551, 5206970324, 3312348, "SRX21926748", "SRS19011078", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.93549, 0.93041, 0.12194, 0.1247, 0.70059, 0.70145, 0.49104, 0.4936, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28430, "SRR26216326", "SRX21926747", "SRS19011077", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep6 [22 01874 S36]", "GSM7813339", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank1|genotype:WT|Sex:male|geo loc name:missing|collection date:missing", "Brain BC WT rep6 [22 01874 S36]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank1|genotype:WT|Sex:male", "GSM7813339", "GSM7813339: Brain BC WT rep6 [22 01874 S36]; Danio rerio; RNA Seq", "GSM7813339 r1", "GSM7813339", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01874_S36_R1_001.merged.fastq.gz 22-01874_S36_R2_001.merged.fastq.gz", "fastq fastq", 22842365672.0, 116542682.0, "GSM7813339 r1", "0:98 1:98", "A:6130106950;C:5210131371;G:5219905571;T:6278234629;N:3987151", 98, 98, null, null, 6130106950, 5210131371, 5219905571, 6278234629, 3987151, "SRX21926747", "SRS19011077", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92799, 0.92418, 0.13514, 0.13864, 0.7035, 0.70201, 0.50044, 0.50326, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28431, "SRR26216327", "SRX21926746", "SRS19011076", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIC rep6 [22 01873 S35]", "GSM7813338", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank1|genotype:MPSIIIC|Sex:male|geo loc name:missing|collection date:missing", "Brain BC MPSIIIC rep6 [22 01873 S35]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank1|genotype:MPSIIIC|Sex:male", "GSM7813338", "GSM7813338: Brain BC MPSIIIC rep6 [22 01873 S35]; Danio rerio; RNA Seq", "GSM7813338 r1", "GSM7813338", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01873_S35_R2_001.merged.fastq.gz 22-01873_S35_R1_001.merged.fastq.gz", "fastq fastq", 16529710176.0, 84335256.0, "GSM7813338 r1", "0:98 1:98", "A:4451252334;C:3754181517;G:3773431912;T:4547979245;N:2865168", 98, 98, null, null, 4451252334, 3754181517, 3773431912, 4547979245, 2865168, "SRX21926746", "SRS19011076", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92964, 0.92525, 0.13434, 0.13809, 0.70698, 0.70794, 0.50154, 0.49876, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28432, "SRR26216328", "SRX21926745", "SRS19011075", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIC rep5 [22 01872 S34]", "GSM7813337", null, "source name:brain|tissue:brain|home tank:P2 lay1 tank2|genotype:MPSIIIC|Sex:male|geo loc name:missing|collection date:missing", "Brain BC MPSIIIC rep5 [22 01872 S34]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay1 tank2|genotype:MPSIIIC|Sex:male", "GSM7813337", "GSM7813337: Brain BC MPSIIIC rep5 [22 01872 S34]; Danio rerio; RNA Seq", "GSM7813337 r1", "GSM7813337", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01872_S34_R1_001.merged.fastq.gz 22-01872_S34_R2_001.merged.fastq.gz", "fastq fastq", 17967699064.0, 91671934.0, "GSM7813337 r1", "0:98 1:98", "A:4842209289;C:4058928742;G:4066249511;T:4997263523;N:3047999", 98, 98, null, null, 4842209289, 4058928742, 4066249511, 4997263523, 3047999, "SRX21926745", "SRS19011075", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91823, 0.9197, 0.16266, 0.16861, 0.6999, 0.69761, 0.48703, 0.48793, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28433, "SRR26216329", "SRX21926744", "SRS19011074", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIC rep4 [22 01871 S33]", "GSM7813336", null, "source name:brain|tissue:brain|home tank:P2 lay1 tank1|genotype:MPSIIIC|Sex:female|geo loc name:missing|collection date:missing", "Brain BC MPSIIIC rep4 [22 01871 S33]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay1 tank1|genotype:MPSIIIC|Sex:female", "GSM7813336", "GSM7813336: Brain BC MPSIIIC rep4 [22 01871 S33]; Danio rerio; RNA Seq", "GSM7813336 r1", "GSM7813336", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01871_S33_R2_001.merged.fastq.gz 22-01871_S33_R1_001.merged.fastq.gz", "fastq fastq", 17684828532.0, 90228717.0, "GSM7813336 r1", "0:98 1:98", "A:4726611575;C:4048652163;G:4054748200;T:4851839555;N:2977039", 98, 98, null, null, 4726611575, 4048652163, 4054748200, 4851839555, 2977039, "SRX21926744", "SRS19011074", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92694, 0.92539, 0.1433, 0.14788, 0.70059, 0.70039, 0.48117, 0.47985, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28434, "SRR26216330", "SRX21926743", "SRS19011073", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep5 [22 01870 S32]", "GSM7813335", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank2.1|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain BC WT rep5 [22 01870 S32]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank2.1|genotype:WT|Sex:female", "GSM7813335", "GSM7813335: Brain BC WT rep5 [22 01870 S32]; Danio rerio; RNA Seq", "GSM7813335 r1", "GSM7813335", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01870_S32_R1_001.merged.fastq.gz 22-01870_S32_R2_001.merged.fastq.gz", "fastq fastq", 16763673808.0, 85528948.0, "GSM7813335 r1", "0:98 1:98", "A:4509188057;C:3795157983;G:3802083269;T:4654341788;N:2902711", 98, 98, null, null, 4509188057, 3795157983, 3802083269, 4654341788, 2902711, "SRX21926743", "SRS19011073", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92254, 0.92353, 0.14925, 0.15514, 0.7025, 0.70114, 0.49102, 0.48977, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28435, "SRR26216331", "SRX21926742", "SRS19011072", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep4 [22 01869 S31]", "GSM7813334", null, "source name:brain|tissue:brain|home tank:P2 lay1 tank1|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain BC WT rep4 [22 01869 S31]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay1 tank1|genotype:WT|Sex:female", "GSM7813334", "GSM7813334: Brain BC WT rep4 [22 01869 S31]; Danio rerio; RNA Seq", "GSM7813334 r1", "GSM7813334", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01869_S31_R2_001.merged.fastq.gz 22-01869_S31_R1_001.merged.fastq.gz", "fastq fastq", 16021352032.0, 81741592.0, "GSM7813334 r1", null, null, null, null, null, null, null, null, null, null, null, "SRX21926742", "SRS19011072", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92208, 0.92219, 0.15664, 0.16229, 0.70025, 0.69879, 0.49147, 0.49026, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28436, "SRR26216332", "SRX21926741", "SRS19011071", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep3 [22 01868 S30]", "GSM7813333", null, "source name:brain|tissue:brain|home tank:P2 lay1 tank2|genotype:WT|Sex:male|geo loc name:missing|collection date:missing", "Brain BC WT rep3 [22 01868 S30]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay1 tank2|genotype:WT|Sex:male", "GSM7813333", "GSM7813333: Brain BC WT rep3 [22 01868 S30]; Danio rerio; RNA Seq", "GSM7813333 r1", "GSM7813333", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01868_S30_R1_001.merged.fastq.gz 22-01868_S30_R2_001.merged.fastq.gz", "fastq fastq", 15332432220.0, 78226695.0, "GSM7813333 r1", "0:98 1:98", "A:4159395326;C:3427681764;G:3442087841;T:4300635995;N:2631294", 98, 98, null, null, 4159395326, 3427681764, 3442087841, 4300635995, 2631294, "SRX21926741", "SRS19011071", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91474, 0.91611, 0.16784, 0.1749, 0.70573, 0.70404, 0.48815, 0.48389, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28437, "SRR26216333", "SRX21926740", "SRS19011070", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep2 [22 01867 S29]", "GSM7813332", null, "source name:brain|tissue:brain|home tank:P2 lay1 tank2|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain BC WT rep2 [22 01867 S29]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay1 tank2|genotype:WT|Sex:female", "GSM7813332", "GSM7813332: Brain BC WT rep2 [22 01867 S29]; Danio rerio; RNA Seq", "GSM7813332 r1", "GSM7813332", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01867_S29_R1_001.merged.fastq.gz 22-01867_S29_R2_001.merged.fastq.gz", "fastq fastq", 14123797632.0, 72060192.0, "GSM7813332 r1", "0:98 1:98", "A:3794161474;C:3207083345;G:3218143109;T:3901992007;N:2417697", 98, 98, null, null, 3794161474, 3207083345, 3218143109, 3901992007, 2417697, "SRX21926740", "SRS19011070", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92409, 0.91991, 0.15688, 0.16104, 0.70155, 0.70027, 0.49045, 0.4913, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28438, "SRR26216334", "SRX21926739", "SRS19011069", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIC rep3 [22 01866 S28]", "GSM7813331", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank2.2|genotype:MPSIIIC|Sex:female|geo loc name:missing|collection date:missing", "Brain BC MPSIIIC rep3 [22 01866 S28]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank2.2|genotype:MPSIIIC|Sex:female", "GSM7813331", "GSM7813331: Brain BC MPSIIIC rep3 [22 01866 S28]; Danio rerio; RNA Seq", "GSM7813331 r1", "GSM7813331", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01866_S28_R1_001.merged.fastq.gz 22-01866_S28_R2_001.merged.fastq.gz", "fastq fastq", 15245076196.0, 77781001.0, "GSM7813331 r1", "0:98 1:98", "A:4135875559;C:3414058363;G:3428678892;T:4263872270;N:2591112", 98, 98, null, null, 4135875559, 3414058363, 3428678892, 4263872270, 2591112, "SRX21926739", "SRS19011069", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91726, 0.91853, 0.17756, 0.18357, 0.70494, 0.70347, 0.48952, 0.49391, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28439, "SRR26216335", "SRX21926738", "SRS19011068", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIC rep2 [22 01865 S27]", "GSM7813330", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank2.2|genotype:MPSIIIC|Sex:male|geo loc name:missing|collection date:missing", "Brain BC MPSIIIC rep2 [22 01865 S27]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank2.2|genotype:MPSIIIC|Sex:male", "GSM7813330", "GSM7813330: Brain BC MPSIIIC rep2 [22 01865 S27]; Danio rerio; RNA Seq", "GSM7813330 r1", "GSM7813330", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01865_S27_R1_001.merged.fastq.gz 22-01865_S27_R2_001.merged.fastq.gz", "fastq fastq", 15038751504.0, 76728324.0, "GSM7813330 r1", "0:98 1:98", "A:4106772665;C:3342615146;G:3356678074;T:4230068148;N:2617471", 98, 98, null, null, 4106772665, 3342615146, 3356678074, 4230068148, 2617471, "SRX21926738", "SRS19011068", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91431, 0.91483, 0.17286, 0.17947, 0.70512, 0.70508, 0.49867, 0.49437, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28440, "SRR26216336", "SRX21926737", "SRS19011067", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC WT rep1 [22 01864 S26]", "GSM7813329", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank2.2|genotype:WT|Sex:male|geo loc name:missing|collection date:missing", "Brain BC WT rep1 [22 01864 S26]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank2.2|genotype:WT|Sex:male", "GSM7813329", "GSM7813329: Brain BC WT rep1 [22 01864 S26]; Danio rerio; RNA Seq", "GSM7813329 r1", "GSM7813329", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01864_S26_R1_001.merged.fastq.gz 22-01864_S26_R2_001.merged.fastq.gz", "fastq fastq", 14585845288.0, 74417578.0, "GSM7813329 r1", "0:98 1:98", "A:4018411963;C:3192874484;G:3205170768;T:4166868705;N:2519368", 98, 98, null, null, 4018411963, 3192874484, 3205170768, 4166868705, 2519368, "SRX21926737", "SRS19011067", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.90578, 0.90969, 0.19878, 0.20733, 0.70656, 0.70327, 0.49101, 0.49381, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28441, "SRR26216337", "SRX21926736", "SRS19011066", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain BC MPSIIIB rep4 [22 01863 S25]", "GSM7813328", null, "source name:brain|tissue:brain|home tank:P2 lay3 tank2.1|genotype:MPSIIIB|Sex:female|geo loc name:missing|collection date:missing", "Brain BC MPSIIIB rep4 [22 01863 S25]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:P2 lay3 tank2.1|genotype:MPSIIIB|Sex:female", "GSM7813328", "GSM7813328: Brain BC MPSIIIB rep4 [22 01863 S25]; Danio rerio; RNA Seq", "GSM7813328 r1", "GSM7813328", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01863_S25_R1_001.merged.fastq.gz 22-01863_S25_R2_001.merged.fastq.gz", "fastq fastq", 12236162792.0, 62429402.0, "GSM7813328 r1", "0:98 1:98", "A:3402237481;C:2636320054;G:2656738248;T:3538765917;N:2101092", 98, 98, null, null, 3402237481, 2636320054, 2656738248, 3538765917, 2101092, "SRX21926736", "SRS19011066", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.89964, 0.9044, 0.22191, 0.23254, 0.70871, 0.70682, 0.49884, 0.49572, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28442, "SRR26216338", "SRX21926735", "SRS19011065", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIA rep4 [22 01846 S8]", "GSM7813311", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank6|genotype:MPSIIIA|Sex:male|geo loc name:missing|collection date:missing", "Brain AC MPSIIIA rep4 [22 01846 S8]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank6|genotype:MPSIIIA|Sex:male", "GSM7813311", "GSM7813311: Brain AC MPSIIIA rep4 [22 01846 S8]; Danio rerio; RNA Seq", "GSM7813311 r1", "GSM7813311", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01846_S8_R1_001.merged.fastq.gz 22-01846_S8_R2_001.merged.fastq.gz", "fastq fastq", 16127355104.0, 82282424.0, "GSM7813311 r1", "0:98 1:98", "A:4403612584;C:3561549756;G:3579590782;T:4579822708;N:2779274", 98, 98, null, null, 4403612584, 3561549756, 3579590782, 4579822708, 2779274, "SRX21926735", "SRS19011065", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91173, 0.91641, 0.18072, 0.18991, 0.70565, 0.70378, 0.48485, 0.4827, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28443, "SRR26216339", "SRX21926734", "SRS19011064", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIC rep2 [22 01845 S7]", "GSM7813310", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank2|genotype:MPSIIIC|Sex:female|geo loc name:missing|collection date:missing", "Brain AC MPSIIIC rep2 [22 01845 S7]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank2|genotype:MPSIIIC|Sex:female", "GSM7813310", "GSM7813310: Brain AC MPSIIIC rep2 [22 01845 S7]; Danio rerio; RNA Seq", "GSM7813310 r1", "GSM7813310", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01845_S7_R1_001.merged.fastq.gz 22-01845_S7_R2_001.merged.fastq.gz", "fastq fastq", 15508712072.0, 79126082.0, "GSM7813310 r1", "0:98 1:98", "A:4188137687;C:3513986940;G:3515000413;T:4288950665;N:2636367", 98, 98, null, null, 4188137687, 3513986940, 3515000413, 4288950665, 2636367, "SRX21926734", "SRS19011064", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92402, 0.9236, 0.17078, 0.17482, 0.70226, 0.70197, 0.49018, 0.48817, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28444, "SRR26216340", "SRX21926733", "SRS19011063", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC WT rep2 [22 01844 S6]", "GSM7813309", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank2|genotype:WT|Sex:male|geo loc name:missing|collection date:missing", "Brain AC WT rep2 [22 01844 S6]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank2|genotype:WT|Sex:male", "GSM7813309", "GSM7813309: Brain AC WT rep2 [22 01844 S6]; Danio rerio; RNA Seq", "GSM7813309 r1", "GSM7813309", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01844_S6_R1_001.merged.fastq.gz 22-01844_S6_R2_001.merged.fastq.gz", "fastq fastq", 16409825796.0, 83723601.0, "GSM7813309 r1", "0:98 1:98", "A:4471700709;C:3680179991;G:3683157895;T:4571927688;N:2859513", 98, 98, null, null, 4471700709, 3680179991, 3683157895, 4571927688, 2859513, "SRX21926733", "SRS19011063", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.9212, 0.92021, 0.16733, 0.17218, 0.70782, 0.70733, 0.48416, 0.48241, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28445, "SRR26216341", "SRX21926732", "SRS19011062", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIA rep3 [22 01843 S5]", "GSM7813308", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank2|genotype:MPSIIIA|Sex:female|geo loc name:missing|collection date:missing", "Brain AC MPSIIIA rep3 [22 01843 S5]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank2|genotype:MPSIIIA|Sex:female", "GSM7813308", "GSM7813308: Brain AC MPSIIIA rep3 [22 01843 S5]; Danio rerio; RNA Seq", "GSM7813308 r1", "GSM7813308", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01843_S5_R2_001.merged.fastq.gz 22-01843_S5_R1_001.merged.fastq.gz", "fastq fastq", 12529597920.0, 63926520.0, "GSM7813308 r1", "0:98 1:98", "A:3444508631;C:2752865530;G:2766555023;T:3563525948;N:2142788", 98, 98, null, null, 3444508631, 2752865530, 2766555023, 3563525948, 2142788, "SRX21926732", "SRS19011062", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.90998, 0.91217, 0.19948, 0.20656, 0.70043, 0.6985, 0.49474, 0.49331, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28446, "SRR26216342", "SRX21926731", "SRS19011061", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIA rep2 [22 01842 S4]", "GSM7813307", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank1|genotype:MPSIIIA|Sex:female|geo loc name:missing|collection date:missing", "Brain AC MPSIIIA rep2 [22 01842 S4]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank1|genotype:MPSIIIA|Sex:female", "GSM7813307", "GSM7813307: Brain AC MPSIIIA rep2 [22 01842 S4]; Danio rerio; RNA Seq", "GSM7813307 r1", "GSM7813307", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01842_S4_R1_001.merged.fastq.gz 22-01842_S4_R2_001.merged.fastq.gz", "fastq fastq", 16506577276.0, 84217231.0, "GSM7813307 r1", "0:98 1:98", "A:4457603132;C:3737370134;G:3742179917;T:4566576027;N:2848066", 98, 98, null, null, 4457603132, 3737370134, 3742179917, 4566576027, 2848066, "SRX21926731", "SRS19011061", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.926, 0.92349, 0.16775, 0.17157, 0.70161, 0.70134, 0.49085, 0.49135, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28447, "SRR26216343", "SRX21926730", "SRS19011060", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC WT rep1 [22 01841 S3]", "GSM7813306", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank1|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain AC WT rep1 [22 01841 S3]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank1|genotype:WT|Sex:female", "GSM7813306", "GSM7813306: Brain AC WT rep1 [22 01841 S3]; Danio rerio; RNA Seq", "GSM7813306 r1", "GSM7813306", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01841_S3_R1_001.merged.fastq.gz 22-01841_S3_R2_001.merged.fastq.gz", "fastq fastq", 12185306672.0, 62169932.0, "GSM7813306 r1", "0:98 1:98", "A:3327952186;C:2717345655;G:2719684390;T:3418239630;N:2084811", 98, 98, null, null, 3327952186, 2717345655, 2719684390, 3418239630, 2084811, "SRX21926730", "SRS19011060", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91958, 0.91716, 0.17632, 0.18035, 0.70264, 0.70145, 0.48946, 0.49372, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28448, "SRR26216344", "SRX21926729", "SRS19011059", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIC rep1 [22 01840 S2]", "GSM7813305", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank1|genotype:MPSIIIC|Sex:male|geo loc name:missing|collection date:missing", "Brain AC MPSIIIC rep1 [22 01840 S2]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank1|genotype:MPSIIIC|Sex:male", "GSM7813305", "GSM7813305: Brain AC MPSIIIC rep1 [22 01840 S2]; Danio rerio; RNA Seq", "GSM7813305 r1", "GSM7813305", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01840_S2_R1_001.merged.fastq.gz 22-01840_S2_R2_001.merged.fastq.gz", "fastq fastq", 15366595608.0, 78400998.0, "GSM7813305 r1", "0:98 1:98", "A:4176085395;C:3454640713;G:3462167295;T:4271061985;N:2640220", 98, 98, null, null, 4176085395, 3454640713, 3462167295, 4271061985, 2640220, "SRX21926729", "SRS19011059", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.9238, 0.92066, 0.16449, 0.1677, 0.70662, 0.70577, 0.49188, 0.49263, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28449, "SRR26216345", "SRX21926728", "SRS19011058", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AC MPSIIIA rep1 [22 01839 S1]", "GSM7813304", null, "source name:brain|tissue:brain|home tank:AC P2 lay1 tank1|genotype:MPSIIIA|Sex:female|geo loc name:missing|collection date:missing", "Brain AC MPSIIIA rep1 [22 01839 S1]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AC P2 lay1 tank1|genotype:MPSIIIA|Sex:female", "GSM7813304", "GSM7813304: Brain AC MPSIIIA rep1 [22 01839 S1]; Danio rerio; RNA Seq", "GSM7813304 r1", "GSM7813304", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-01839_S1_R1_001.merged.fastq.gz 22-01839_S1_R2_001.merged.fastq.gz", "fastq fastq", 12347212668.0, 62995983.0, "GSM7813304 r1", "0:98 1:98", "A:3347171972;C:2787017638;G:2791908611;T:3418993066;N:2121381", 98, 98, null, null, 3347171972, 2787017638, 2791908611, 3418993066, 2121381, "SRX21926728", "SRS19011058", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92786, 0.92297, 0.15927, 0.1621, 0.70404, 0.70431, 0.49153, 0.49029, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28450, "SRR26216346", "SRX21926727", "SRS19011057", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB sgsh het rep2 [22 00152 S8]", "GSM7813295", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank2|genotype:sgsh het|Sex:male|geo loc name:missing|collection date:missing", "Brain AB sgsh het rep2 [22 00152 S8]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank2|genotype:sgsh het|Sex:male", "GSM7813295", "GSM7813295: Brain AB sgsh het rep2 [22 00152 S8]; Danio rerio; RNA Seq", "GSM7813295 r1", "GSM7813295", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00152_S8_R2_001.merged.fastq.gz 22-00152_S8_R1_001.merged.fastq.gz", "fastq fastq", 25966816372.0, 132483757.0, "GSM7813295 r1", "0:98 1:98", "A:6973183255;C:5877834155;G:5930243960;T:7177178083;N:8376919", 98, 98, null, null, 6973183255, 5877834155, 5930243960, 7177178083, 8376919, "SRX21926727", "SRS19011057", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92369, 0.92575, 0.15407, 0.16762, 0.70224, 0.70244, 0.49045, 0.48532, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28451, "SRR26216347", "SRX21926726", "SRS19011056", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB WT rep3 [22 00151 S7]", "GSM7813294", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank2|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain AB WT rep3 [22 00151 S7]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank2|genotype:WT|Sex:female", "GSM7813294", "GSM7813294: Brain AB WT rep3 [22 00151 S7]; Danio rerio; RNA Seq", "GSM7813294 r1", "GSM7813294", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00151_S7_R1_001.merged.fastq.gz 22-00151_S7_R2_001.merged.fastq.gz", "fastq fastq", 20429512180.0, 104232205.0, "GSM7813294 r1", "0:98 1:98", "A:5524943642;C:4569903416;G:4618023597;T:5709981807;N:6659718", 98, 98, null, null, 5524943642, 4569903416, 4618023597, 5709981807, 6659718, "SRX21926726", "SRS19011056", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91753, 0.92093, 0.17609, 0.1946, 0.70705, 0.70498, 0.49526, 0.49595, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28452, "SRR26216348", "SRX21926725", "SRS19011055", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB WT rep2 [22 00150 S6]", "GSM7813293", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank2|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain AB WT rep2 [22 00150 S6]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank2|genotype:WT|Sex:female", "GSM7813293", "GSM7813293: Brain AB WT rep2 [22 00150 S6]; Danio rerio; RNA Seq", "GSM7813293 r1", "GSM7813293", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00150_S6_R1_001.merged.fastq.gz 22-00150_S6_R2_001.merged.fastq.gz", "fastq fastq", 20872419064.0, 106491934.0, "GSM7813293 r1", "0:98 1:98", "A:5631355778;C:4682808382;G:4724172615;T:5827274589;N:6807700", 98, 98, null, null, 5631355778, 4682808382, 4724172615, 5827274589, 6807700, "SRX21926725", "SRS19011055", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91815, 0.9219, 0.1737, 0.19345, 0.70329, 0.70299, 0.4931, 0.48343, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28453, "SRR26216349", "SRX21926724", "SRS19011054", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB sgsh het rep1 [22 00148 S5]", "GSM7813292", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank2|genotype:sgsh het|Sex:female|geo loc name:missing|collection date:missing", "Brain AB sgsh het rep1 [22 00148 S5]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank2|genotype:sgsh het|Sex:female", "GSM7813292", "GSM7813292: Brain AB sgsh het rep1 [22 00148 S5]; Danio rerio; RNA Seq", "GSM7813292 r1", "GSM7813292", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00148_S5_R2_001.merged.fastq.gz 22-00148_S5_R1_001.merged.fastq.gz", "fastq fastq", 22105679288.0, 112784078.0, "GSM7813292 r1", "0:98 1:98", "A:5823448386;C:5145130246;G:5179195236;T:5950683795;N:7221625", 98, 98, null, null, 5823448386, 5145130246, 5179195236, 5950683795, 7221625, "SRX21926724", "SRS19011054", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.93457, 0.93377, 0.12761, 0.13206, 0.70569, 0.70867, 0.48476, 0.48428, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28454, "SRR26216350", "SRX21926723", "SRS19011053", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB MPSIIIA rep2 [22 00147 S4]", "GSM7813291", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank2|genotype:MPSIIIA|Sex:male|geo loc name:missing|collection date:missing", "Brain AB MPSIIIA rep2 [22 00147 S4]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank2|genotype:MPSIIIA|Sex:male", "GSM7813291", "GSM7813291: Brain AB MPSIIIA rep2 [22 00147 S4]; Danio rerio; RNA Seq", "GSM7813291 r1", "GSM7813291", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00147_S4_R1_001.merged.fastq.gz 22-00147_S4_R2_001.merged.fastq.gz", "fastq fastq", 24994383540.0, 127522365.0, "GSM7813291 r1", "0:98 1:98", "A:6713459564;C:5636288152;G:5694678404;T:6941948817;N:8008603", 98, 98, null, null, 6713459564, 5636288152, 5694678404, 6941948817, 8008603, "SRX21926723", "SRS19011053", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91898, 0.92159, 0.17146, 0.18718, 0.70201, 0.70161, 0.48479, 0.48311, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28455, "SRR26216351", "SRX21926722", "SRS19011052", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB WT rep1 [22 00145 S3]", "GSM7813290", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank4|genotype:WT|Sex:female|geo loc name:missing|collection date:missing", "Brain AB WT rep1 [22 00145 S3]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank4|genotype:WT|Sex:female", "GSM7813290", "GSM7813290: Brain AB WT rep1 [22 00145 S3]; Danio rerio; RNA Seq", "GSM7813290 r1", "GSM7813290", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00145_S3_R1_001.merged.fastq.gz 22-00145_S3_R2_001.merged.fastq.gz", "fastq fastq", 21971383420.0, 112098895.0, "GSM7813290 r1", "0:98 1:98", "A:5817485267;C:5059820956;G:5101690277;T:5985434835;N:6952085", 98, 98, null, null, 5817485267, 5059820956, 5101690277, 5985434835, 6952085, "SRX21926722", "SRS19011052", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.92434, 0.9301, 0.13339, 0.14984, 0.70181, 0.70013, 0.48702, 0.48827, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28456, "SRR26216352", "SRX21926721", "SRS19011051", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB MPSIIIA rep1 [22 00138 S2]", "GSM7813289", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIA|Sex:female|geo loc name:missing|collection date:missing", "Brain AB MPSIIIA rep1 [22 00138 S2]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank3|genotype:MPSIIIA|Sex:female", "GSM7813289", "GSM7813289: Brain AB MPSIIIA rep1 [22 00138 S2]; Danio rerio; RNA Seq", "GSM7813289 r1", "GSM7813289", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00138_S2_R1_001.merged.fastq.gz 22-00138_S2_R2_001.merged.fastq.gz", "fastq fastq", 20393895648.0, 104050488.0, "GSM7813289 r1", "0:98 1:98", "A:5535222513;C:4521860121;G:4564229476;T:5765827363;N:6756175", 98, 98, null, null, 5535222513, 4521860121, 4564229476, 5765827363, 6756175, "SRX21926721", "SRS19011051", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.91058, 0.91708, 0.19504, 0.22041, 0.69741, 0.69392, 0.4866, 0.4891, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [28457, "SRR26216353", "SRX21926720", "SRS19011050", "SRP463830", "PRJNA1022392", "Zebrafish models of Mucopolysaccharidosis types IIIA B & C show hyperactivity and changes in oligodendrocyte state", "GSE244310", "Transcriptome Analysis", "Sanfilippo syndrome childhood dementia also known as mucopolysaccharidosis type III MPS III is a rare inherited lysosomal storage disorder. Subtypes of MPS III are caused by deficiencies in one of four enzymes required for degradation of the glycosaminoglycan heparan sulfate HS. An inability to degrade HS leads to progressive neurodegeneration and death in the second or third decades of life. Knowledge of MPS III pathogenesis is incomplete and no effective therapies exist. We generated the hypomorphic mutations sgshS387Lfs nagluA603Efs and hgsnatG577Sfsin the endogenous zebrafish genes orthologous to human SGSH NAGLU and HGSNAT that are loci for mutations causing MPS III subtypes MPS IIIA B and C respectively. Our models display the primary MPS III disease signature of significant brain accumulation of HS while behavioural analyses support hyperactivity phenotypes. Brain transcriptome analysis revealed changes related to lysosomal glycosaminoglycan immune system and iron homeostasis biology in all three models but also distinct differences in brain transcriptome state between models. The transcriptome analysis also indicated marked disturbance of the oligodendrocyte cell state in the brains of MPS IIIA B and C zebrafish supporting that effects on this cell type are an early and consistent characteristic of MPS III. Overall our zebrafish models recapture key characteristics of the human disease and phenotypes seen in mouse models. Our models will allow exploitation of the zebrafish's extreme fecundity and accessible anatomy to dissect the pathological mechanisms both common and divergent between the MPS IIIA B and C subtypes. Overall design: To compare brain transcriptomes in our three MPS III zebrafish lines we generated families of 2nd Filial generation zebrafish originating from G0 in crosses of parental zebrafish heterozygous for two of the MPS III mutations. We initially aimed to analyse n = 6 fish per genotype from single families of progeny from in crosses of doubly heterozygous mutant fish. We chose n = 6 as according to a previous power calculation this would allow approximately 70% power to detect differentially expressed genes in zebrafish models of Alzheimer's disease. However due to smaller than expected clutch sizes and questionable purified RNA quality we were forced to use multiple families of siblings or n<6 in some analyses. For the A and B AB arm of the experiment we analysed n = 4 fish per genotype which also included 4 sgsh S387Lfs/+ fish to explore cellular processes affected in the brains of presumably unaffected carriers of MPS III mutations. For the A and C AC arm we sequenced all homozygous sgsh S387Lfs zebrafish in the family n = 7 to account for the lower number of fish with this genotype in the AB arm. For the B and C BC arm we could not obtain a large enough family in a single breeding event within our timeframe to be able to compare with the other families. Therefore we analysed fish spawned by two pairs of parents P1 and P2 both doubly heterozygous for the nagluA603fs and hgsnatG577fs mutations in a total of 3 spawning events.", null, null, null, "Brain AB MPSIIIB rep1 [22 00136 S1]", "GSM7813288", null, "source name:brain|tissue:brain|home tank:AB P1 lay1 tank2|genotype:MPSIIIB|Sex:male|geo loc name:missing|collection date:missing", "Brain AB MPSIIIB rep1 [22 00136 S1]", "Pre processing was performed using a custom pipeline implemented in snakemake. Briefly the raw fastq files were subjected to initial quality checks using fastQC version 0.11.9. Then adaptors were trimmed and low quality reads removed using fastp version 0.23.1. The remaining reads were aligned to the zebrafish genomes e GRCz11 Ensembl release 101 using the splice aware alignment software STAR version 2.7.0d. Aligned reads associated with the same unique molecular identifier UMI correspond to PCR duplicates generated using library preparation. These were deduplicated using the dedup function of umi tools v1.0.1. A gene level counts matrix was then generated using featureCounts version 2.0.1. Assembly: GRCz11 Ensembl release 101 Supplementary files format and content: Both processed data files counts AB.out & counts AC BC.out consist of count data in TSV format output by featureCounts software as described in the data processing section.", "brain", null, "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer\u2019s protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", "Each fish was raised until 3 month of age in a shared water circulation system. Fish were fed twice a day with dry food in the morning and live food Artermia salina in the postnoon.", "tissue:brain|home tank:AB P1 lay1 tank2|genotype:MPSIIIB|Sex:male", "GSM7813288", "GSM7813288: Brain AB MPSIIIB rep1 [22 00136 S1]; Danio rerio; RNA Seq", "GSM7813288 r1", "GSM7813288", "1", "Each family of fish was raised until 3 month of age at which time the entire family was humanely euthanised in an ice slurry. Entire heads were excised at the level of the gills and were each incubated in 600 \u00b5l of RNAlater\u2122 Stabilization Solution Invitrogen Thermo Fisher Scientific Waltham USA overnight at 4\u00b0C before storage at 80\u00b0C until use. The tail of each fish was also removed for genomic DNA extraction and genotype determination by PCR. Total RNAs were isolated from RNAlater preserved brains using the mirVana\u2122 miRNA Isolation Kit Ambion Life Technologies Thermo Fisher Scientific Waltham USA following the manufacturer's protocol. To remove any carried over genomic DNA during RNA purification we treated the total RNA samples with DNaseI using the DNA free\u2122 DNA Removal Kit Invitrogen Thermo Fisher Scientific Waltham USA following the manufacturers protocol for routine DNase treatment. 500 ng of high quality total RNA with RINe generally \u2265 8 was delivered on dry ice to the South Australian Genomics Centre SAGC Adelaide Australia for preparation of stranded polyA+ libraries using Nugen Universal Plus mRNA seq NuGEN Ltd. UK. Cluster generation was performed using the Illumina to MGI Library Conversion MGIEasy Universal Library Conversion Kit Part No. MGI1000004155. Then 2 x 98bp paired end sequencing was performed including 8 bp unique molecular identifiers UMIs using MGI DNBSEQ G400 chemistry MGI Tech Shenzhen China. Each of the libraries was sequenced over multiple lanes and the data from each library subsequently combined.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP463830", null, null, "22-00136_S1_R1_001.merged.fastq.gz 22-00136_S1_R2_001.merged.fastq.gz", "fastq fastq", 22736679532.0, 116003467.0, "GSM7813288 r1", "0:98 1:98", "A:6160987473;C:5083325909;G:5143258939;T:6341622029;N:7485182", 98, 98, null, null, 6160987473, 5083325909, 5143258939, 6341622029, 7485182, "SRX21926720", "SRS19011050", "SRA1723608", "The University of Adelaide", "The University of Adelaide", 2, 0.918, 0.92042, 0.18082, 0.19533, 0.70301, 0.70195, 0.49, 0.48891, 98, 98, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Australia", "2023-09-29", "Adult", "Adult", "Brain", "Nervous System"], [29191, "SRR27308233", "SRX22985581", "SRS19950789", "SRP479308", "PRJNA1055256", "Independent mesenchymal progenitor pools respectively produce and maintain osteogenic and chondrogenic cells in zebrafish", "GSE251757", "Transcriptome Analysis", "Skeletal tissues including cartilage and bones are characteristic features of vertebrates that are crucial for supporting body morphology and locomotion. Studies mainly in mice have shown that osteoblasts and chondroblasts are supplied from several progenitors in development growth and homeostasis. However developmental origins of osteoblasts and chondroblasts lineage relationship progenitor cells and their differentiation potentials throughout animal life are not seamlessly understood. In this study we used clonal cell tracking in zebrafish and found that sox9a+ cells are committed to either chondrogenic or osteogenic fates during embryonic stages and that respective progenies are independently maintained as mesenchymal progenitor pools. Once committed they never change their lineage identities throughout their lives even through regeneration. We further showed that osteogenic mesenchymal cells replenish the osteoblast progenitor cells OPCs which are the reserved stem cells for osteoblast production during regeneration and homeostasis. Independent mesenchymal progenitors dedicated to produce either chondroblasts or osteoblasts would be important targets for skeletal tissue regeneration. Overall design: To investigate the lineage relationship between mesenchymal cells and osteoblasts in the zebrafish caudal fin we isolated sp7 mesenchymal cells and sp7+ osteoblasts derived from sox9a+ somite cells from 14 dy post amputation dpa caudal fin by fluorescence activated cell sorting. We then performed gene expression profiling analysis using data obtained from RNA seq of 3 different cells. Comparative gene expression profiling analysis of RNA seq data for osteogenic mesenchymal progenitors OMPs chondrogenic mesenchymal progenitors CMPs and osteoblasts.", null, "pubmed:38193362", null, "EGFP /sp7+ Osteoblast rep2", "GSM7987448", null, "source name:14 dpa adult caudal fin|tissue:14 dpa adult caudal fin|cell type:Osteoblasts|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry|geo loc name:missing|collection date:missing", "EGFP /sp7+ Osteoblast rep2", "High quality reads were mapped using hisat2 ver. 2.2.1. Trimmed sequence reads were mapped to GRCz11 using hisat2. Read count extraction and normalization were performed using featureCounts ver. 2.0.3. Assembly: GRCz11 Supplementary files format and content: Tab delimited text file includes basic gene information gene id length Genbank id RNA type gene name product raw count RPKM and TPM values.", "14 dpa adult caudal fin", "Different types of cells were sorted by the fluorescence activated cell sorter SH800S SONY.", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer\u2019s protocol.", "Fish were maintained in a recirculating water system in a 14 h day/10 h night photoperiod at 28.5 \u00b0C. The wild type zebrafish Danio rerio strain used in this study was originally derived from the Tubingen strain and has been maintained in our facility for more than 10 years by inbreeding.", "tissue:14 dpa adult caudal fin|cell type:Osteoblasts|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry", "GSM7987448", "GSM7987448: EGFP /sp7+ Osteoblast rep2; Danio rerio; RNA Seq", "GSM7987448 r1", "GSM7987448", "1", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer's protocol.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP479308", null, null, "Ob-GR2_S6_R2_001.fastq.gz Ob-GR2_S6_R1_001.fastq.gz", "fastq fastq", 6044999600.0, 15112499.0, "GSM7987448 r1", "0:200 1:200", "A:1547731745;C:1388120378;G:1581574912;T:1523597213;N:3975352", 200, 200, null, null, 1547731745, 1388120378, 1581574912, 1523597213, 3975352, "SRX22985581", "SRS19950789", "SRA1773396", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", 2, 0.36888, 0.02272, 0.01109, 0.00038, 0.86914, 0.99328, 0.46943, 0.4982, 200, 200, "B", "T", "mate2 technical by mapping diff", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2023-12-20", "Adult", "Adult", "Fin", "Surface Structure"], [29192, "SRR27308234", "SRX22985580", "SRS19950790", "SRP479308", "PRJNA1055256", "Independent mesenchymal progenitor pools respectively produce and maintain osteogenic and chondrogenic cells in zebrafish", "GSE251757", "Transcriptome Analysis", "Skeletal tissues including cartilage and bones are characteristic features of vertebrates that are crucial for supporting body morphology and locomotion. Studies mainly in mice have shown that osteoblasts and chondroblasts are supplied from several progenitors in development growth and homeostasis. However developmental origins of osteoblasts and chondroblasts lineage relationship progenitor cells and their differentiation potentials throughout animal life are not seamlessly understood. In this study we used clonal cell tracking in zebrafish and found that sox9a+ cells are committed to either chondrogenic or osteogenic fates during embryonic stages and that respective progenies are independently maintained as mesenchymal progenitor pools. Once committed they never change their lineage identities throughout their lives even through regeneration. We further showed that osteogenic mesenchymal cells replenish the osteoblast progenitor cells OPCs which are the reserved stem cells for osteoblast production during regeneration and homeostasis. Independent mesenchymal progenitors dedicated to produce either chondroblasts or osteoblasts would be important targets for skeletal tissue regeneration. Overall design: To investigate the lineage relationship between mesenchymal cells and osteoblasts in the zebrafish caudal fin we isolated sp7 mesenchymal cells and sp7+ osteoblasts derived from sox9a+ somite cells from 14 dy post amputation dpa caudal fin by fluorescence activated cell sorting. We then performed gene expression profiling analysis using data obtained from RNA seq of 3 different cells. Comparative gene expression profiling analysis of RNA seq data for osteogenic mesenchymal progenitors OMPs chondrogenic mesenchymal progenitors CMPs and osteoblasts.", null, "pubmed:38193362", null, "EGFP /sp7+ Osteoblast rep1", "GSM7987447", null, "source name:14 dpa adult caudal fin|tissue:14 dpa adult caudal fin|cell type:Osteoblasts|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry|geo loc name:missing|collection date:missing", "EGFP /sp7+ Osteoblast rep1", "High quality reads were mapped using hisat2 ver. 2.2.1. Trimmed sequence reads were mapped to GRCz11 using hisat2. Read count extraction and normalization were performed using featureCounts ver. 2.0.3. Assembly: GRCz11 Supplementary files format and content: Tab delimited text file includes basic gene information gene id length Genbank id RNA type gene name product raw count RPKM and TPM values.", "14 dpa adult caudal fin", "Different types of cells were sorted by the fluorescence activated cell sorter SH800S SONY.", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer\u2019s protocol.", "Fish were maintained in a recirculating water system in a 14 h day/10 h night photoperiod at 28.5 \u00b0C. The wild type zebrafish Danio rerio strain used in this study was originally derived from the Tubingen strain and has been maintained in our facility for more than 10 years by inbreeding.", "tissue:14 dpa adult caudal fin|cell type:Osteoblasts|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry", "GSM7987447", "GSM7987447: EGFP /sp7+ Osteoblast rep1; Danio rerio; RNA Seq", "GSM7987447 r1", "GSM7987447", "1", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer's protocol.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP479308", null, null, "Ob-GR_S77_R1_001.fastq.gz Ob-GR_S77_R2_001.fastq.gz", "fastq fastq", 4847773600.0, 12119434.0, "GSM7987447 r1", "0:200 1:200", "A:1242312480;C:1120397684;G:1256425065;T:1226991694;N:1646677", 200, 200, null, null, 1242312480, 1120397684, 1256425065, 1226991694, 1646677, "SRX22985580", "SRS19950790", "SRA1773396", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", 2, 0.0146, 0.02559, 0.00038, 0.00052, 0.99397, 0.99405, 0.50471, 0.47146, 200, 200, "T", "T", "mates < 9% mapping rate", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2023-12-20", "Adult", "Adult", "Fin", "Surface Structure"], [29193, "SRR27308235", "SRX22985579", "SRS19950788", "SRP479308", "PRJNA1055256", "Independent mesenchymal progenitor pools respectively produce and maintain osteogenic and chondrogenic cells in zebrafish", "GSE251757", "Transcriptome Analysis", "Skeletal tissues including cartilage and bones are characteristic features of vertebrates that are crucial for supporting body morphology and locomotion. Studies mainly in mice have shown that osteoblasts and chondroblasts are supplied from several progenitors in development growth and homeostasis. However developmental origins of osteoblasts and chondroblasts lineage relationship progenitor cells and their differentiation potentials throughout animal life are not seamlessly understood. In this study we used clonal cell tracking in zebrafish and found that sox9a+ cells are committed to either chondrogenic or osteogenic fates during embryonic stages and that respective progenies are independently maintained as mesenchymal progenitor pools. Once committed they never change their lineage identities throughout their lives even through regeneration. We further showed that osteogenic mesenchymal cells replenish the osteoblast progenitor cells OPCs which are the reserved stem cells for osteoblast production during regeneration and homeostasis. Independent mesenchymal progenitors dedicated to produce either chondroblasts or osteoblasts would be important targets for skeletal tissue regeneration. Overall design: To investigate the lineage relationship between mesenchymal cells and osteoblasts in the zebrafish caudal fin we isolated sp7 mesenchymal cells and sp7+ osteoblasts derived from sox9a+ somite cells from 14 dy post amputation dpa caudal fin by fluorescence activated cell sorting. We then performed gene expression profiling analysis using data obtained from RNA seq of 3 different cells. Comparative gene expression profiling analysis of RNA seq data for osteogenic mesenchymal progenitors OMPs chondrogenic mesenchymal progenitors CMPs and osteoblasts.", null, "pubmed:38193362", null, "EGFP+/sp7+ OMP rep2", "GSM7987446", null, "source name:14 dpa adult caudal fin|tissue:14 dpa adult caudal fin|cell type:Osteogenic mesenchymal progenitors|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry|geo loc name:missing|collection date:missing", "EGFP+/sp7+ OMP rep2", "High quality reads were mapped using hisat2 ver. 2.2.1. Trimmed sequence reads were mapped to GRCz11 using hisat2. Read count extraction and normalization were performed using featureCounts ver. 2.0.3. Assembly: GRCz11 Supplementary files format and content: Tab delimited text file includes basic gene information gene id length Genbank id RNA type gene name product raw count RPKM and TPM values.", "14 dpa adult caudal fin", "Different types of cells were sorted by the fluorescence activated cell sorter SH800S SONY.", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer\u2019s protocol.", "Fish were maintained in a recirculating water system in a 14 h day/10 h night photoperiod at 28.5 \u00b0C. The wild type zebrafish Danio rerio strain used in this study was originally derived from the Tubingen strain and has been maintained in our facility for more than 10 years by inbreeding.", "tissue:14 dpa adult caudal fin|cell type:Osteogenic mesenchymal progenitors|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry", "GSM7987446", "GSM7987446: EGFP+/sp7+ OMP rep2; Danio rerio; RNA Seq", "GSM7987446 r1", "GSM7987446", "1", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer's protocol.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP479308", null, null, "Ob-G2_S5_R2_001.fastq.gz Ob-G2_S5_R1_001.fastq.gz", "fastq fastq", 6253558800.0, 15633897.0, "GSM7987446 r1", "0:200 1:200", "A:1638931864;C:1404420075;G:1600115132;T:1605939571;N:4152158", 200, 200, null, null, 1638931864, 1404420075, 1600115132, 1605939571, 4152158, "SRX22985579", "SRS19950788", "SRA1773396", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", 2, 0.41021, 0.02334, 0.01523, 0.00074, 0.83989, 0.99099, 0.52255, 0.52173, 200, 200, "B", "T", "mate2 technical by mapping diff", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2023-12-20", "Adult", "Adult", "Fin", "Surface Structure"], [29194, "SRR27308236", "SRX22985578", "SRS19950791", "SRP479308", "PRJNA1055256", "Independent mesenchymal progenitor pools respectively produce and maintain osteogenic and chondrogenic cells in zebrafish", "GSE251757", "Transcriptome Analysis", "Skeletal tissues including cartilage and bones are characteristic features of vertebrates that are crucial for supporting body morphology and locomotion. Studies mainly in mice have shown that osteoblasts and chondroblasts are supplied from several progenitors in development growth and homeostasis. However developmental origins of osteoblasts and chondroblasts lineage relationship progenitor cells and their differentiation potentials throughout animal life are not seamlessly understood. In this study we used clonal cell tracking in zebrafish and found that sox9a+ cells are committed to either chondrogenic or osteogenic fates during embryonic stages and that respective progenies are independently maintained as mesenchymal progenitor pools. Once committed they never change their lineage identities throughout their lives even through regeneration. We further showed that osteogenic mesenchymal cells replenish the osteoblast progenitor cells OPCs which are the reserved stem cells for osteoblast production during regeneration and homeostasis. Independent mesenchymal progenitors dedicated to produce either chondroblasts or osteoblasts would be important targets for skeletal tissue regeneration. Overall design: To investigate the lineage relationship between mesenchymal cells and osteoblasts in the zebrafish caudal fin we isolated sp7 mesenchymal cells and sp7+ osteoblasts derived from sox9a+ somite cells from 14 dy post amputation dpa caudal fin by fluorescence activated cell sorting. We then performed gene expression profiling analysis using data obtained from RNA seq of 3 different cells. Comparative gene expression profiling analysis of RNA seq data for osteogenic mesenchymal progenitors OMPs chondrogenic mesenchymal progenitors CMPs and osteoblasts.", null, "pubmed:38193362", null, "EGFP+/sp7+ OMP rep1", "GSM7987445", null, "source name:14 dpa adult caudal fin|tissue:14 dpa adult caudal fin|cell type:Osteogenic mesenchymal progenitors|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry|geo loc name:missing|collection date:missing", "EGFP+/sp7+ OMP rep1", "High quality reads were mapped using hisat2 ver. 2.2.1. Trimmed sequence reads were mapped to GRCz11 using hisat2. Read count extraction and normalization were performed using featureCounts ver. 2.0.3. Assembly: GRCz11 Supplementary files format and content: Tab delimited text file includes basic gene information gene id length Genbank id RNA type gene name product raw count RPKM and TPM values.", "14 dpa adult caudal fin", "Different types of cells were sorted by the fluorescence activated cell sorter SH800S SONY.", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer\u2019s protocol.", "Fish were maintained in a recirculating water system in a 14 h day/10 h night photoperiod at 28.5 \u00b0C. The wild type zebrafish Danio rerio strain used in this study was originally derived from the Tubingen strain and has been maintained in our facility for more than 10 years by inbreeding.", "tissue:14 dpa adult caudal fin|cell type:Osteogenic mesenchymal progenitors|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry", "GSM7987445", "GSM7987445: EGFP+/sp7+ OMP rep1; Danio rerio; RNA Seq", "GSM7987445 r1", "GSM7987445", "1", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer's protocol.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP479308", null, null, "Ob-G_S28_R2_001.fastq.gz Ob-G_S28_R1_001.fastq.gz", "fastq fastq", 4832320400.0, 12080801.0, "GSM7987445 r1", "0:200 1:200", "A:1252095509;C:1107971153;G:1236349772;T:1233319775;N:2584191", 200, 200, null, null, 1252095509, 1107971153, 1236349772, 1233319775, 2584191, "SRX22985578", "SRS19950791", "SRA1773396", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", 2, 0.01133, 0.02895, 0.00033, 0.00043, 0.99439, 0.99297, 0.50298, 0.45574, 200, 200, "T", "T", "mates < 9% mapping rate", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2023-12-20", "Adult", "Adult", "Fin", "Surface Structure"], [29195, "SRR27308237", "SRX22985577", "SRS19950787", "SRP479308", "PRJNA1055256", "Independent mesenchymal progenitor pools respectively produce and maintain osteogenic and chondrogenic cells in zebrafish", "GSE251757", "Transcriptome Analysis", "Skeletal tissues including cartilage and bones are characteristic features of vertebrates that are crucial for supporting body morphology and locomotion. Studies mainly in mice have shown that osteoblasts and chondroblasts are supplied from several progenitors in development growth and homeostasis. However developmental origins of osteoblasts and chondroblasts lineage relationship progenitor cells and their differentiation potentials throughout animal life are not seamlessly understood. In this study we used clonal cell tracking in zebrafish and found that sox9a+ cells are committed to either chondrogenic or osteogenic fates during embryonic stages and that respective progenies are independently maintained as mesenchymal progenitor pools. Once committed they never change their lineage identities throughout their lives even through regeneration. We further showed that osteogenic mesenchymal cells replenish the osteoblast progenitor cells OPCs which are the reserved stem cells for osteoblast production during regeneration and homeostasis. Independent mesenchymal progenitors dedicated to produce either chondroblasts or osteoblasts would be important targets for skeletal tissue regeneration. Overall design: To investigate the lineage relationship between mesenchymal cells and osteoblasts in the zebrafish caudal fin we isolated sp7 mesenchymal cells and sp7+ osteoblasts derived from sox9a+ somite cells from 14 dy post amputation dpa caudal fin by fluorescence activated cell sorting. We then performed gene expression profiling analysis using data obtained from RNA seq of 3 different cells. Comparative gene expression profiling analysis of RNA seq data for osteogenic mesenchymal progenitors OMPs chondrogenic mesenchymal progenitors CMPs and osteoblasts.", null, "pubmed:38193362", null, "EGFP+/sp7 CMP rep2", "GSM7987444", null, "source name:14 dpa adult caudal fin|tissue:14 dpa adult caudal fin|cell type:Chondrogenic mesenchymal progenitors|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry|geo loc name:missing|collection date:missing", "EGFP+/sp7 CMP rep2", "High quality reads were mapped using hisat2 ver. 2.2.1. Trimmed sequence reads were mapped to GRCz11 using hisat2. Read count extraction and normalization were performed using featureCounts ver. 2.0.3. Assembly: GRCz11 Supplementary files format and content: Tab delimited text file includes basic gene information gene id length Genbank id RNA type gene name product raw count RPKM and TPM values.", "14 dpa adult caudal fin", "Different types of cells were sorted by the fluorescence activated cell sorter SH800S SONY.", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer\u2019s protocol.", "Fish were maintained in a recirculating water system in a 14 h day/10 h night photoperiod at 28.5 \u00b0C. The wild type zebrafish Danio rerio strain used in this study was originally derived from the Tubingen strain and has been maintained in our facility for more than 10 years by inbreeding.", "tissue:14 dpa adult caudal fin|cell type:Chondrogenic mesenchymal progenitors|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry", "GSM7987444", "GSM7987444: EGFP+/sp7 CMP rep2; Danio rerio; RNA Seq", "GSM7987444 r1", "GSM7987444", "1", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer's protocol.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP479308", null, null, "Mes-G2_S4_R1_001.fastq.gz Mes-G2_S4_R2_001.fastq.gz", "fastq fastq", 5812163600.0, 14530409.0, "GSM7987444 r1", "0:200 1:200", "A:1538664561;C:1291748975;G:1473028809;T:1504905134;N:3816121", 200, 200, null, null, 1538664561, 1291748975, 1473028809, 1504905134, 3816121, "SRX22985577", "SRS19950787", "SRA1773396", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", 2, 0.40138, 0.02482, 0.0176, 0.00091, 0.83918, 0.99099, 0.47875, 0.43124, 200, 200, "B", "T", "mate2 technical by mapping diff", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2023-12-20", "Adult", "Adult", "Fin", "Surface Structure"], [29196, "SRR27308238", "SRX22985576", "SRS19950786", "SRP479308", "PRJNA1055256", "Independent mesenchymal progenitor pools respectively produce and maintain osteogenic and chondrogenic cells in zebrafish", "GSE251757", "Transcriptome Analysis", "Skeletal tissues including cartilage and bones are characteristic features of vertebrates that are crucial for supporting body morphology and locomotion. Studies mainly in mice have shown that osteoblasts and chondroblasts are supplied from several progenitors in development growth and homeostasis. However developmental origins of osteoblasts and chondroblasts lineage relationship progenitor cells and their differentiation potentials throughout animal life are not seamlessly understood. In this study we used clonal cell tracking in zebrafish and found that sox9a+ cells are committed to either chondrogenic or osteogenic fates during embryonic stages and that respective progenies are independently maintained as mesenchymal progenitor pools. Once committed they never change their lineage identities throughout their lives even through regeneration. We further showed that osteogenic mesenchymal cells replenish the osteoblast progenitor cells OPCs which are the reserved stem cells for osteoblast production during regeneration and homeostasis. Independent mesenchymal progenitors dedicated to produce either chondroblasts or osteoblasts would be important targets for skeletal tissue regeneration. Overall design: To investigate the lineage relationship between mesenchymal cells and osteoblasts in the zebrafish caudal fin we isolated sp7 mesenchymal cells and sp7+ osteoblasts derived from sox9a+ somite cells from 14 dy post amputation dpa caudal fin by fluorescence activated cell sorting. We then performed gene expression profiling analysis using data obtained from RNA seq of 3 different cells. Comparative gene expression profiling analysis of RNA seq data for osteogenic mesenchymal progenitors OMPs chondrogenic mesenchymal progenitors CMPs and osteoblasts.", null, "pubmed:38193362", null, "EGFP+/sp7 CMP rep1", "GSM7987443", null, "source name:14 dpa adult caudal fin|tissue:14 dpa adult caudal fin|cell type:Chondrogenic mesenchymal progenitors|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry|geo loc name:missing|collection date:missing", "EGFP+/sp7 CMP rep1", "High quality reads were mapped using hisat2 ver. 2.2.1. Trimmed sequence reads were mapped to GRCz11 using hisat2. Read count extraction and normalization were performed using featureCounts ver. 2.0.3. Assembly: GRCz11 Supplementary files format and content: Tab delimited text file includes basic gene information gene id length Genbank id RNA type gene name product raw count RPKM and TPM values.", "14 dpa adult caudal fin", "Different types of cells were sorted by the fluorescence activated cell sorter SH800S SONY.", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer\u2019s protocol.", "Fish were maintained in a recirculating water system in a 14 h day/10 h night photoperiod at 28.5 \u00b0C. The wild type zebrafish Danio rerio strain used in this study was originally derived from the Tubingen strain and has been maintained in our facility for more than 10 years by inbreeding.", "tissue:14 dpa adult caudal fin|cell type:Chondrogenic mesenchymal progenitors|genotype:Tgcryaa:EGFP sox9a:Cre ERt2; Ola.Actb:loxp TagBFP loxp EGFP; Ola.Sp7:mCherry", "GSM7987443", "GSM7987443: EGFP+/sp7 CMP rep1; Danio rerio; RNA Seq", "GSM7987443 r1", "GSM7987443", "1", "The sorted cells were directly collected in a lysis buffer and used for RNA extraction using the RNeasy Plus Micro Kit Qiagen. RNA libraries were prepared by MGIEasy\u2122 WES rapid library preparation kit according to the manufacturer's protocol.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP479308", null, null, "Mes-G_S15_R1_001.fastq.gz Mes-G_S15_R2_001.fastq.gz", "fastq fastq", 5321588000.0, 13303970.0, "GSM7987443 r1", "0:200 1:200", "A:1405233304;C:1195662643;G:1342003810;T:1376732727;N:1955516", 200, 200, null, null, 1405233304, 1195662643, 1342003810, 1376732727, 1955516, "SRX22985576", "SRS19950786", "SRA1773396", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", "Kawakami lab, School of Life Science and Technology, Tokyo Institute of Technology", 2, 0.00961, 0.02419, 0.00032, 0.00052, 0.9945, 0.99324, 0.51073, 0.48429, 200, 200, "T", "T", "mates < 9% mapping rate", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Japan", "2023-12-20", "Adult", "Adult", "Fin", "Surface Structure"], [31980, "SRR28892728", "SRX24451189", "SRS21204958", "SRP505641", "PRJNA1107713", "Tea polyphenols induce hepatotoxicity by interfering with adult zebrafish lipid metabolism and gut microbiota through the gut liver axis", "PRJNA1107713", "Other", "High dose tea polyphenols may promote fatty acid absorption by hepatocytes by up regulating FABP CD36 and SRB1 genes inhibiting fatty acid efflux by down regulating ABCA1 genes and inhibiting fatty acid beta oxidation by down regulating CPT1 and ACAA2 genes resulting in fat accumulation in hepatocytes upregulation of inflammatory pathways and increased expression of pro inflammatory factors TNF a and IL1 b.", null, null, null, null, "TP3", null, "strain:not applicable|isolate:not applicable|breed:not collected|cultivar:not applicable|ecotype:AB ecotype|age:5 month|collection date:2022 11 24|geo loc name:China|sex:male|tissue:liver|replicate:replicate=biological replicate 6|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "Adult zebrafish liver", "TP3", "TP3", "mRNAseq of zebrafish liver replication 3 of TP", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "PolyA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP505641", null, null, "TP3_1.fq.gz TP3_2.fq.gz", "fastq fastq", 6657069900.0, 22190233.0, "TP3 1.fq.gz", "0:150 1:150", "A:1808410149;C:1512668682;G:1536153888;T:1799837181;N:0", 150, 150, null, null, 1808410149, 1512668682, 1536153888, 1799837181, 0, "SRX24451189", "SRS21204958", "SRA1858747", "Beibu Gulf University|college of Food Engineering", "Beibu Gulf University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "China", "2024-05-04", "Adult", "Adult", "Liver", "Liver and Biliary System"], [31981, "SRR28892729", "SRX24451188", "SRS21204959", "SRP505641", "PRJNA1107713", "Tea polyphenols induce hepatotoxicity by interfering with adult zebrafish lipid metabolism and gut microbiota through the gut liver axis", "PRJNA1107713", "Other", "High dose tea polyphenols may promote fatty acid absorption by hepatocytes by up regulating FABP CD36 and SRB1 genes inhibiting fatty acid efflux by down regulating ABCA1 genes and inhibiting fatty acid beta oxidation by down regulating CPT1 and ACAA2 genes resulting in fat accumulation in hepatocytes upregulation of inflammatory pathways and increased expression of pro inflammatory factors TNF a and IL1 b.", null, null, null, null, "TP2", null, "strain:not applicable|isolate:not applicable|breed:not collected|cultivar:not applicable|ecotype:AB ecotype|age:5 month|collection date:2022 11 24|geo loc name:China|sex:male|tissue:liver|replicate:replicate=biological replicate 5|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "Adult zebrafish liver", "TP2", "TP2", "mRNAseq of zebrafish liver replication 2 of TP", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "PolyA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP505641", null, null, "TP2_1.fq.gz TP2_2.fq.gz", "fastq fastq", 6617368500.0, 22057895.0, "TP2 1.fq.gz", "0:150 1:150", "A:1799646726;C:1503407966;G:1523443584;T:1790870224;N:0", 150, 150, null, null, 1799646726, 1503407966, 1523443584, 1790870224, 0, "SRX24451188", "SRS21204959", "SRA1858747", "Beibu Gulf University|college of Food Engineering", "Beibu Gulf University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "China", "2024-05-04", "Adult", "Adult", "Liver", "Liver and Biliary System"], [31982, "SRR28892730", "SRX24451187", "SRS21204956", "SRP505641", "PRJNA1107713", "Tea polyphenols induce hepatotoxicity by interfering with adult zebrafish lipid metabolism and gut microbiota through the gut liver axis", "PRJNA1107713", "Other", "High dose tea polyphenols may promote fatty acid absorption by hepatocytes by up regulating FABP CD36 and SRB1 genes inhibiting fatty acid efflux by down regulating ABCA1 genes and inhibiting fatty acid beta oxidation by down regulating CPT1 and ACAA2 genes resulting in fat accumulation in hepatocytes upregulation of inflammatory pathways and increased expression of pro inflammatory factors TNF a and IL1 b.", null, null, null, null, "TP1", null, "strain:not applicable|isolate:not applicable|breed:not collected|cultivar:not applicable|ecotype:AB ecotype|age:5 month|collection date:2022 11 24|geo loc name:China|sex:male|tissue:liver|replicate:replicate=biological replicate 4|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "Adult zebrafish liver", "TP1", "TP1", "mRNAseq of zebrafish liver replication 1 of TP", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "PolyA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP505641", null, null, "TP1_1.fq.gz TP1_2.fq.gz", "fastq fastq", 6432586800.0, 21441956.0, "TP1 1.fq.gz", "0:150 1:150", "A:1743341515;C:1465440262;G:1488109144;T:1735695879;N:0", 150, 150, null, null, 1743341515, 1465440262, 1488109144, 1735695879, 0, "SRX24451187", "SRS21204956", "SRA1858747", "Beibu Gulf University|college of Food Engineering", "Beibu Gulf University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "China", "2024-05-04", "Adult", "Adult", "Liver", "Liver and Biliary System"], [31983, "SRR28892731", "SRX24451186", "SRS21204957", "SRP505641", "PRJNA1107713", "Tea polyphenols induce hepatotoxicity by interfering with adult zebrafish lipid metabolism and gut microbiota through the gut liver axis", "PRJNA1107713", "Other", "High dose tea polyphenols may promote fatty acid absorption by hepatocytes by up regulating FABP CD36 and SRB1 genes inhibiting fatty acid efflux by down regulating ABCA1 genes and inhibiting fatty acid beta oxidation by down regulating CPT1 and ACAA2 genes resulting in fat accumulation in hepatocytes upregulation of inflammatory pathways and increased expression of pro inflammatory factors TNF a and IL1 b.", null, null, null, null, "CONT3", null, "strain:not applicable|isolate:not applicable|breed:not collected|cultivar:not applicable|ecotype:AB ecotype|age:5 month|collection date:2022 11 24|geo loc name:China|sex:male|tissue:liver|replicate:replicate=biological replicate 3|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "Adult zebrafish liver", "CON3", "CON3", "mRNAseq of zebrafish liver replication 3 of CONT", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "PolyA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP505641", null, null, "CONT3_1.fq.gz CONT3_2.fq.gz", "fastq fastq", 6595768200.0, 21985894.0, "CONT3 1.fq.gz", "0:150 1:150", "A:1762107185;C:1525175684;G:1547321856;T:1761163475;N:0", 150, 150, null, null, 1762107185, 1525175684, 1547321856, 1761163475, 0, "SRX24451186", "SRS21204957", "SRA1858747", "Beibu Gulf University|college of Food Engineering", "Beibu Gulf University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "China", "2024-05-04", "Adult", "Adult", "Liver", "Liver and Biliary System"], [31984, "SRR28892732", "SRX24451185", "SRS21204954", "SRP505641", "PRJNA1107713", "Tea polyphenols induce hepatotoxicity by interfering with adult zebrafish lipid metabolism and gut microbiota through the gut liver axis", "PRJNA1107713", "Other", "High dose tea polyphenols may promote fatty acid absorption by hepatocytes by up regulating FABP CD36 and SRB1 genes inhibiting fatty acid efflux by down regulating ABCA1 genes and inhibiting fatty acid beta oxidation by down regulating CPT1 and ACAA2 genes resulting in fat accumulation in hepatocytes upregulation of inflammatory pathways and increased expression of pro inflammatory factors TNF a and IL1 b.", null, null, null, null, "CONT2", null, "strain:not applicable|isolate:not applicable|breed:not collected|cultivar:not applicable|ecotype:AB ecotype|age:5 month|collection date:2022 11 24|geo loc name:China|sex:male|tissue:liver|replicate:replicate=biological replicate 2|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "Adult zebrafish liver", "CON2", "CON2", "mRNAseq of zebrafish liver replication 2 of CONT", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "PolyA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP505641", null, null, "CONT2_1.fq.gz CONT2_2.fq.gz", "fastq fastq", 6175346400.0, 20584488.0, "CONT2 1.fq.gz", "0:150 1:150", "A:1656546719;C:1421990443;G:1442409824;T:1654399414;N:0", 150, 150, null, null, 1656546719, 1421990443, 1442409824, 1654399414, 0, "SRX24451185", "SRS21204954", "SRA1858747", "Beibu Gulf University|college of Food Engineering", "Beibu Gulf University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "China", "2024-05-04", "Adult", "Adult", "Liver", "Liver and Biliary System"], [31985, "SRR28892733", "SRX24451184", "SRS21204955", "SRP505641", "PRJNA1107713", "Tea polyphenols induce hepatotoxicity by interfering with adult zebrafish lipid metabolism and gut microbiota through the gut liver axis", "PRJNA1107713", "Other", "High dose tea polyphenols may promote fatty acid absorption by hepatocytes by up regulating FABP CD36 and SRB1 genes inhibiting fatty acid efflux by down regulating ABCA1 genes and inhibiting fatty acid beta oxidation by down regulating CPT1 and ACAA2 genes resulting in fat accumulation in hepatocytes upregulation of inflammatory pathways and increased expression of pro inflammatory factors TNF a and IL1 b.", null, null, null, null, "CONT1", null, "strain:not applicable|isolate:not applicable|breed:not collected|cultivar:not applicable|ecotype:AB ecotype|age:5 month|collection date:2022 11 24|geo loc name:China|sex:male|tissue:liver|replicate:replicate=biological replicate 1|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "Adult zebrafish liver", "CON1", "CON1", "mRNAseq of zebrafish liver replication 1 of CONT", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "PolyA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP505641", null, null, "CONT1_1.fq.gz CONT1_2.fq.gz", "fastq fastq", 6342828300.0, 21142761.0, "CONT1 1.fq.gz", "0:150 1:150", "A:1698306803;C:1464261565;G:1482929449;T:1697330483;N:0", 150, 150, null, null, 1698306803, 1464261565, 1482929449, 1697330483, 0, "SRX24451184", "SRS21204955", "SRA1858747", "Beibu Gulf University|college of Food Engineering", "Beibu Gulf University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "China", "2024-05-04", "Adult", "Adult", "Liver", "Liver and Biliary System"], [34508, "SRR32041235", "SRX27390499", "SRS23823272", "SRP558202", "PRJNA1212333", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212333", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating brain hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr[VI]+VC 3 group", "Cr+VC 3", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 14|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:brain|death date:2023 8 14|health state:health|sample type:tissue|lep:Cr+VC 3|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "EHK0300476", "EHK0300476", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558202", null, null, "Cr+VC-3.R1.raw.fastq.gz Cr+VC-3.R2.raw.fastq.gz", "fastq fastq", 6579236402.0, 21785551.0, "Cr+VC 3.R1.raw.fastq.gz", "0:151 1:151", "A:1950296368;C:1342383640;G:1373591474;T:1912893257;N:71663", 151, 151, null, null, 1950296368, 1342383640, 1373591474, 1912893257, 71663, "SRX27390499", "SRS23823272", "SRA2054545", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-18", "Adult", "Adult", "Brain", "Nervous System"], [34509, "SRR32041236", "SRX27390498", "SRS23823271", "SRP558202", "PRJNA1212333", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212333", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating brain hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr[VI]+VC 2 group", "Cr+VC 2", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 14|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:brain|death date:2023 8 14|health state:health|sample type:tissue|lep:Cr+VC 2|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "EHK0300475", "EHK0300475", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558202", null, null, "Cr+VC-2.R1.raw.fastq.gz Cr+VC-2.R2.raw.fastq.gz", "fastq fastq", 7431192898.0, 24606599.0, "Cr+VC 2.R1.raw.fastq.gz", "0:151 1:151", "A:2185434880;C:1533450452;G:1567401090;T:2144825061;N:81415", 151, 151, null, null, 2185434880, 1533450452, 1567401090, 2144825061, 81415, "SRX27390498", "SRS23823271", "SRA2054545", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-18", "Adult", "Adult", "Brain", "Nervous System"], [34510, "SRR32041237", "SRX27390497", "SRS23823270", "SRP558202", "PRJNA1212333", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212333", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating brain hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr[VI]+VC 1 group", "Cr+VC 1", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 14|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:brain|death date:2023 8 14|health state:health|sample type:tissue|lep:Cr+VC 1|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "EHK0300474", "EHK0300474", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558202", null, null, "Cr+VC-1.R1.raw.fastq.gz Cr+VC-1.R2.raw.fastq.gz", "fastq fastq", 6385666180.0, 21144590.0, "Cr+VC 1.R1.raw.fastq.gz", "0:151 1:151", "A:1864936934;C:1329491594;G:1363211111;T:1827956599;N:69942", 151, 151, null, null, 1864936934, 1329491594, 1363211111, 1827956599, 69942, "SRX27390497", "SRS23823270", "SRA2054545", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-18", "Adult", "Adult", "Brain", "Nervous System"], [34511, "SRR32041238", "SRX27390496", "SRS23823269", "SRP558202", "PRJNA1212333", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212333", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating brain hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr[VI] 3 group", "Cr 3", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 13|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:brain|death date:2023 8 13|health state:health|sample type:tissue|lep:Cr 3|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "EHK0300473", "EHK0300473", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558202", null, null, "Cr-3.R1.raw.fastq.gz Cr-3.R2.raw.fastq.gz", "fastq fastq", 6339933716.0, 20993158.0, "Cr 3.R1.raw.fastq.gz", "0:151 1:151", "A:1873178321;C:1296125569;G:1333622723;T:1836939106;N:67997", 151, 151, null, null, 1873178321, 1296125569, 1333622723, 1836939106, 67997, "SRX27390496", "SRS23823269", "SRA2054545", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-18", "Adult", "Adult", "Brain", "Nervous System"], [34512, "SRR32041239", "SRX27390495", "SRS23823268", "SRP558202", "PRJNA1212333", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212333", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating brain hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr[VI] 2 group", "Cr 2", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 13|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:brain|death date:2023 8 13|health state:health|sample type:tissue|lep:Cr 2|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "EHK0300472", "EHK0300472", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558202", null, null, "Cr-2.R1.raw.fastq.gz Cr-2.R2.raw.fastq.gz", "fastq fastq", 6461518010.0, 21395755.0, "Cr 2.R1.raw.fastq.gz", "0:151 1:151", "A:1878799067;C:1352321588;G:1386809443;T:1843520259;N:67653", 151, 151, null, null, 1878799067, 1352321588, 1386809443, 1843520259, 67653, "SRX27390495", "SRS23823268", "SRA2054545", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-18", "Adult", "Adult", "Brain", "Nervous System"], [34513, "SRR32041240", "SRX27390494", "SRS23823267", "SRP558202", "PRJNA1212333", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212333", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating brain hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr[VI] 1 group", "Cr 1", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 13|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:brain|death date:2023 8 13|health state:health|sample type:tissue|lep:Cr 1|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "EHK0300471", "EHK0300471", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558202", null, null, "Cr-1.R1.raw.fastq.gz Cr-1.R2.raw.fastq.gz", "fastq fastq", 7143701582.0, 23654641.0, "Cr 1.R1.raw.fastq.gz", "0:151 1:151", "A:1955056767;C:1615392059;G:1650478323;T:1922695182;N:79251", 151, 151, null, null, 1955056767, 1615392059, 1650478323, 1922695182, 79251, "SRX27390494", "SRS23823267", "SRA2054545", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-18", "Adult", "Adult", "Brain", "Nervous System"], [34514, "SRR32041241", "SRX27390493", "SRS23823266", "SRP558202", "PRJNA1212333", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212333", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating brain hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "control 3 group", "Con 3", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 12|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:brain|death date:2023 8 12|health state:health|sample type:tissue|lep:Con 3|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "EHK0300470", "EHK0300470", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558202", null, null, "Con-3.R1.raw.fastq.gz Con-3.R2.raw.fastq.gz", "fastq fastq", 6474159730.0, 21437615.0, "Con 3.R1.raw.fastq.gz", "0:151 1:151", "A:1937289968;C:1298659806;G:1337603954;T:1900535989;N:70013", 151, 151, null, null, 1937289968, 1298659806, 1337603954, 1900535989, 70013, "SRX27390493", "SRS23823266", "SRA2054545", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-18", "Adult", "Adult", "Brain", "Nervous System"], [34515, "SRR32041242", "SRX27390492", "SRS23823265", "SRP558202", "PRJNA1212333", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212333", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating brain hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "control 2 group", "Con 2", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 12|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:brain|death date:2023 8 12|health state:health|sample type:tissue|lep:Con 2|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "EHK0300469", "EHK0300469", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558202", null, null, "Con-2.R1.raw.fastq.gz Con-2.R2.raw.fastq.gz", "fastq fastq", 8372440828.0, 27723314.0, "Con 2.R1.raw.fastq.gz", "0:151 1:151", "A:2235968446;C:1933538809;G:1977416201;T:2225425413;N:91959", 151, 151, null, null, 2235968446, 1933538809, 1977416201, 2225425413, 91959, "SRX27390492", "SRS23823265", "SRA2054545", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-18", "Adult", "Adult", "Brain", "Nervous System"], [34516, "SRR32041243", "SRX27390491", "SRS23823264", "SRP558202", "PRJNA1212333", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212333", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating brain hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "control 1 group", "Con 1", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 12|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:brain|death date:2023 8 12|health state:health|sample type:tissue|lep:Con 1|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "EHK0300468", "EHK0300468", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558202", null, null, "Con-1.R1.raw.fastq.gz Con-1.R2.raw.fastq.gz", "fastq fastq", 6527063486.0, 21612793.0, "Con 1.R1.raw.fastq.gz", "0:151 1:151", "A:1939230604;C:1326702799;G:1357063348;T:1903995450;N:71285", 151, 151, null, null, 1939230604, 1326702799, 1357063348, 1903995450, 71285, "SRX27390491", "SRS23823264", "SRA2054545", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-18", "Adult", "Adult", "Brain", "Nervous System"], [34517, "SRR32044795", "SRX27393953", "SRS23824014", "SRP558295", "PRJNA1212482", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212482", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating gut hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr+VC 3", "I", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 14|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:gut|death date:2023 8 14|health state:health|sample type:tissue|replication:Cr+VC 3|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "Cr+VC 3", "Cr+VC 3", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558295", null, null, "Cr+VC-3.R1.raw.fastq.gz Cr+VC-3.R2.raw.fastq.gz", "fastq fastq", 6773536558.0, 22428929.0, "Cr+VC 3.R1.raw.fastq.gz", "0:151 1:151", "A:1792253952;C:1581454013;G:1629330621;T:1770470694;N:27278", 151, 151, null, null, 1792253952, 1581454013, 1629330621, 1770470694, 27278, "SRX27393953", "SRS23824014", "SRA2054568", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-19", "Adult", "Adult", "Gut", "Digestive System"], [34518, "SRR32044796", "SRX27393952", "SRS23824013", "SRP558295", "PRJNA1212482", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212482", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating gut hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr+VC 2", "H", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 14|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:gut|death date:2023 8 14|health state:health|sample type:tissue|replication:Cr+VC 2|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "Cr+VC 2", "Cr+VC 2", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558295", null, null, "Cr+VC-2.R1.raw.fastq.gz Cr+VC-2.R2.raw.fastq.gz", "fastq fastq", 7449518862.0, 24667281.0, "Cr+VC 2.R1.raw.fastq.gz", "0:151 1:151", "A:1969693675;C:1748150730;G:1771267240;T:1960378098;N:29119", 151, 151, null, null, 1969693675, 1748150730, 1771267240, 1960378098, 29119, "SRX27393952", "SRS23824013", "SRA2054568", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-19", "Adult", "Adult", "Gut", "Digestive System"], [34519, "SRR32044797", "SRX27393951", "SRS23824012", "SRP558295", "PRJNA1212482", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212482", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating gut hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr+VC 1", "G", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 14|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:gut|death date:2023 8 14|health state:health|sample type:tissue|replication:Cr+VC 1|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "Cr+VC 1", "Cr+VC 1", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558295", null, "loader:fastq load.py|options: doNotUseSharq", "Cr+VC-1.R1.raw.fastq Cr+VC-1.R2.raw.fastq", "fastq fastq", 6865491179.0, 45466829.0, "Cr+VC 1.R1.raw.fastq.gz", "0:151", "A:1830069736;C:1600281531;G:1626303427;T:1808809011;N:27474", 151, null, null, null, 1830069736, 1600281531, 1626303427, 1808809011, 27474, "SRX27393951", "SRS23824012", "SRA2054568", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", null, "usable mapping rate", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-19", "Adult", "Adult", "Gut", "Digestive System"], [34520, "SRR32044798", "SRX27393950", "SRS23824011", "SRP558295", "PRJNA1212482", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212482", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating gut hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr 3", "F", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 13|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:gut|death date:2023 8 13|health state:health|sample type:tissue|replication:Cr 3|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "Cr 3", "Cr 3", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558295", null, null, "Cr-3.R1.raw.fastq.gz Cr-3.R2.raw.fastq.gz", "fastq fastq", 6069804078.0, 20098689.0, "Cr 3.R1.raw.fastq.gz", "0:151 1:151", "A:1603886661;C:1431213970;G:1440806224;T:1593873144;N:24079", 151, 151, null, null, 1603886661, 1431213970, 1440806224, 1593873144, 24079, "SRX27393950", "SRS23824011", "SRA2054568", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-19", "Adult", "Adult", "Gut", "Digestive System"], [34521, "SRR32044799", "SRX27393949", "SRS23824010", "SRP558295", "PRJNA1212482", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212482", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating gut hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr 2", "E", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 13|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:gut|death date:2023 8 13|health state:health|sample type:tissue|replication:Cr 2|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "Cr 2", "Cr 2", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558295", null, "loader:fastq load.py|options: doNotUseSharq", "Cr-2.R1.raw.fastq Cr-2.R2.raw.fastq", "fastq fastq", 8327156985.0, 55146735.0, "Cr 2.R1.raw.fastq.gz", "0:151", "A:2181317777;C:1974793526;G:2003240106;T:2167771431;N:34145", 151, null, null, null, 2181317777, 1974793526, 2003240106, 2167771431, 34145, "SRX27393949", "SRS23824010", "SRA2054568", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", null, "usable mapping rate", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-19", "Adult", "Adult", "Gut", "Digestive System"], [34522, "SRR32044800", "SRX27393948", "SRS23824009", "SRP558295", "PRJNA1212482", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212482", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating gut hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Cr 1", "D", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 13|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:gut|death date:2023 8 13|health state:health|sample type:tissue|replication:Cr 1|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "Cr 1", "Cr 1", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558295", null, null, "Cr-1.R1.raw.fastq.gz Cr-1.R2.raw.fastq.gz", "fastq fastq", 7322067614.0, 24245257.0, "Cr 1.R1.raw.fastq.gz", "0:151 1:151", "A:1927213281;C:1727973559;G:1748866497;T:1917985720;N:28557", 151, 151, null, null, 1927213281, 1727973559, 1748866497, 1917985720, 28557, "SRX27393948", "SRS23824009", "SRA2054568", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-19", "Adult", "Adult", "Gut", "Digestive System"], [34523, "SRR32044801", "SRX27393947", "SRS23824008", "SRP558295", "PRJNA1212482", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212482", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating gut hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Con 3", "C", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 12|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:gut|death date:2023 8 12|health state:health|sample type:tissue|replication:Con 3|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "Con 3", "Con 3", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558295", null, null, "Con-3.R1.raw.fastq.gz Con-3.R2.raw.fastq.gz", "fastq fastq", 10329187314.0, 34202607.0, "Con 3.R1.raw.fastq.gz", "0:151 1:151", "A:2805764955;C:2343400161;G:2421657823;T:2758323021;N:41354", 151, 151, null, null, 2805764955, 2343400161, 2421657823, 2758323021, 41354, "SRX27393947", "SRS23824008", "SRA2054568", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-19", "Adult", "Adult", "Gut", "Digestive System"], [34524, "SRR32044802", "SRX27393946", "SRS23824007", "SRP558295", "PRJNA1212482", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212482", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating gut hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Con 2", "B", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 12|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:gut|death date:2023 8 12|health state:health|sample type:tissue|replication:Con 2|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "Con 2", "Con 2", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558295", null, null, "Con-2.R1.raw.fastq.gz Con-2.R2.raw.fastq.gz", "fastq fastq", 10789961398.0, 35728349.0, "Con 2.R1.raw.fastq.gz", "0:151 1:151", "A:2983305704;C:2396592872;G:2488165589;T:2921853880;N:43353", 151, 151, null, null, 2983305704, 2396592872, 2488165589, 2921853880, 43353, "SRX27393946", "SRS23824007", "SRA2054568", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-19", "Adult", "Adult", "Gut", "Digestive System"], [34525, "SRR32044803", "SRX27393945", "SRS23824006", "SRP558295", "PRJNA1212482", "vitamin C mitigated hexavalent chromium toxicity by microbiota gut brain axis in zebrafish", "PRJNA1212482", "Other", "Zebrafish is characterized by small size rapid development high fertility short life cycle easy and economical rearing; it has now become one of the model organisms for drug screening disease research and ecological environment evaluation. Therefore this project takes zebrafish as a model organism as the research object and intends to study the role of vitamins in alleviating gut hexavalent chromium toxicity from the perspective of oxidative damage through the application of toxicology transcriptome molecular biology and other techniques.", null, null, null, "Con 1", "A", null, "ecotype:wild type zebrafish|age:6 month|dev stage:adult|collection date:2023 08 12|geo loc name:China: Haikou Hainan Province|sex:pooled male and female|tissue:gut|death date:2023 8 12|health state:health|sample type:tissue|replication:Con 1|BioSampleModel:Model organism or animal", null, null, null, null, null, null, null, null, "RNA Seq of brian:Adult female and male zebrafish", "Con 1", "Con 1", "normal", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP558295", null, null, "Con-1.R1.raw.fastq.gz Con-1.R2.raw.fastq.gz", "fastq fastq", 7118179260.0, 23570130.0, "Con 1.R1.raw.fastq.gz", "0:151 1:151", "A:1874284939;C:1673861890;G:1718740497;T:1851263659;N:28275", 151, 151, null, null, 1874284939, 1673861890, 1718740497, 1851263659, 28275, "SRX27393945", "SRS23824006", "SRA2054568", "Hainan University|School of Life and Health Sciences", "Hainan University", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_droplet", "10x", null, "China", "2025-01-19", "Adult", "Adult", "Gut", "Digestive System"], [64538, "SRR14915030", "SRX11229465", "SRS9283357", "SRP324000", "PRJNA737474", "Construction the larval and adult zebrafish cell atlas at single cell resolution", "GSE178150", "Transcriptome Analysis", "Single cell mRNA sequencing scRNA seq technologies are reshaping the current cell type classification system. In previous studies we built the mouse cell atlas MCA and human cell landscape HCL to catalog all cell types by collecting scRNA seq data. However systematically study for zebrafish Danio rerio and fruit fly Drosophila melanogaster are still lacking. Here we construct the zebrafish and Drosophila cell atlas with Microwell seq protocols which provides valuable resources for characterization of diverse cell populations of zebrafish and Drosophila and studying difference between vertebrates and Invertebrates at single cell level. Overall design: Over 550 000 cells derived from zebrafish whole body single cell dissociation and profiling at the larval stage 72 hpf 3 replicates 10 fish for each replicate and adult 90 day 6 replicates 1 fish for each replicate.", "parent bioproject:PRJNA737471", "pubmed:36229673", null, "Microwell seq datasets of Zebrafish 3m COL64", "GSM5400025", null, "source name:Zebrafish 3m sample3|strain:AB|age:3 month 90 day|tissue:whole organism", "Microwell seq datasets of Zebrafish 3m COL64", "Base call files were performed with Illumina bcl2fastq. Sequenced reads were trimmed for adaptor sequences. Then reads in bam files were tagged with the cell and molecular UMI barcode sequences using Drop seq tools 1.12. The reads quality under 10 were removed. For raw file 1 5 in each COL cellbarcode: in read1 the bases 1 6 22 27 43 48 are merged 18bp; UMI: in read1 the bases 49 54 6bp. For raw file 6 in each COL cellbarcode: in read1 the bases 1 6 7 12 13 18 are merged 18bp; UMI: in read1 the bases 19 24 6bp. scRNA seq reads were aligned to the Danio rerio GRCz11 genome assembly using STAR version 2.5.2a with default configurations. Next merge the STAR alignment tagged bam SAM to recover cell/molecular barcodes and the reads are annotated with exon tags. Last we demultiplexed all cell barcodes taken into consideration for the analysis from the exon tagged bam files to get a digital expression matrix DGE based on UMI counts. The cell barcode is tagged with XC the UMI is tagged with XM and the gene is tagged with GE. Genome build: Danio rerio GRCz11 Supplementary files format and content: Tab delimited text files of digital expression matrix DGE based on raw UMI counts with genes as rows and cells as columns.", "Zebrafish 3m sample3", null, "Whole body single cell dissociation and lysate Library preparations were performed with the Microwell seq protocol", null, "strain:AB|age:3 month 90 day|tissue:whole organism", "GSM5400025", "GSM5400025: Microwell seq datasets of Zebrafish 3m COL64; Danio rerio; RNA Seq", "GSM5400025", null, "1", "Whole body single cell dissociation and lysate Library preparations were performed with the Microwell seq protocol", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP324000", null, null, "Zebrafish_3m_COL64_1_1.fq.gz Zebrafish_3m_COL64_1_2.fq.gz", "fastq fastq", 3509355300.0, 23395702.0, "GSM5400025 r1", "0:150 1:150", "A:1033838372;C:621125453;G:637527732;T:1213662404;N:3201339", 150, 150, null, null, 1033838372, 621125453, 637527732, 1213662404, 3201339, "SRX11229465", "SRS9283357", "SRA1244752", "GEO", "Zhejiang University School of Medicine, Center for Stem Cell and Regenerative Medicine", 1, 0.36321, null, 0.02305, null, 0.82554, null, 0.50827, null, 150, null, "B", null, "usable mapping rate", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_plate", "microwellseq", null, "China", "2021-06-25", "Adult", "Adult", "Whole Organism", "All anatomical structures"], [64539, "SRR14915031", "SRX11229465", "SRS9283357", "SRP324000", "PRJNA737474", "Construction the larval and adult zebrafish cell atlas at single cell resolution", "GSE178150", "Transcriptome Analysis", "Single cell mRNA sequencing scRNA seq technologies are reshaping the current cell type classification system. In previous studies we built the mouse cell atlas MCA and human cell landscape HCL to catalog all cell types by collecting scRNA seq data. However systematically study for zebrafish Danio rerio and fruit fly Drosophila melanogaster are still lacking. Here we construct the zebrafish and Drosophila cell atlas with Microwell seq protocols which provides valuable resources for characterization of diverse cell populations of zebrafish and Drosophila and studying difference between vertebrates and Invertebrates at single cell level. Overall design: Over 550 000 cells derived from zebrafish whole body single cell dissociation and profiling at the larval stage 72 hpf 3 replicates 10 fish for each replicate and adult 90 day 6 replicates 1 fish for each replicate.", "parent bioproject:PRJNA737471", "pubmed:36229673", null, "Microwell seq datasets of Zebrafish 3m COL64", "GSM5400025", null, "source name:Zebrafish 3m sample3|strain:AB|age:3 month 90 day|tissue:whole organism", "Microwell seq datasets of Zebrafish 3m COL64", "Base call files were performed with Illumina bcl2fastq. Sequenced reads were trimmed for adaptor sequences. Then reads in bam files were tagged with the cell and molecular UMI barcode sequences using Drop seq tools 1.12. The reads quality under 10 were removed. For raw file 1 5 in each COL cellbarcode: in read1 the bases 1 6 22 27 43 48 are merged 18bp; UMI: in read1 the bases 49 54 6bp. For raw file 6 in each COL cellbarcode: in read1 the bases 1 6 7 12 13 18 are merged 18bp; UMI: in read1 the bases 19 24 6bp. scRNA seq reads were aligned to the Danio rerio GRCz11 genome assembly using STAR version 2.5.2a with default configurations. Next merge the STAR alignment tagged bam SAM to recover cell/molecular barcodes and the reads are annotated with exon tags. Last we demultiplexed all cell barcodes taken into consideration for the analysis from the exon tagged bam files to get a digital expression matrix DGE based on UMI counts. The cell barcode is tagged with XC the UMI is tagged with XM and the gene is tagged with GE. Genome build: Danio rerio GRCz11 Supplementary files format and content: Tab delimited text files of digital expression matrix DGE based on raw UMI counts with genes as rows and cells as columns.", "Zebrafish 3m sample3", null, "Whole body single cell dissociation and lysate Library preparations were performed with the Microwell seq protocol", null, "strain:AB|age:3 month 90 day|tissue:whole organism", "GSM5400025", "GSM5400025: Microwell seq datasets of Zebrafish 3m COL64; Danio rerio; RNA Seq", "GSM5400025", null, "1", "Whole body single cell dissociation and lysate Library preparations were performed with the Microwell seq protocol", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-T7", null, "SRP324000", null, null, "Zebrafish_3m_COL64_2_1.fq.gz Zebrafish_3m_COL64_2_2.fq.gz", "fastq fastq", 1665060900.0, 11100406.0, "GSM5400025 r2", "0:150 1:150", "A:462369470;C:317060096;G:327014453;T:557786784;N:830097", 150, 150, null, null, 462369470, 317060096, 327014453, 557786784, 830097, "SRX11229465", "SRS9283357", "SRA1244752", "GEO", "Zhejiang University School of Medicine, Center for Stem Cell and Regenerative Medicine", 1, 0.13839, null, 0.00808, null, 0.91569, null, 0.53255, null, 150, null, "B", null, "usable mapping rate", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "sc", "single_cell_plate", "microwellseq", null, "China", "2021-06-25", "Adult", "Adult", "Whole Organism", "All anatomical structures"]], "truncated": false, "filtered_table_rows_count": 852, "expanded_columns": [], "expandable_columns": [], "columns": ["rowid", "run.accession", "experiment.accession", "sample.accession", "study.accession", "bioproject", "study.title", "study.alias", "study.type", "study.abstract", "study.attributes", "study.PMIDs", "sample.description", "sample.title", "sample.alias", "sample.centername", "sample.attributes", "GEOsample.title", "GEOsample.dataprocessing", "GEOsample.source", "GEOsample.treatmentprotocol", "GEOsample.extractprotocol", "GEOsample.growthprotocol", "GEOsample.characteristics", "GEOsample.accession", "experiment.title", "experiment.alias", "experiment.library_name", "experiment.design_description", "experiment.library_construction_protocol", "experiment.attributes", "experiment.library_strategy", "experiment.library_source", "experiment.library_selection", "experiment.library_layout", "experiment.platform", "experiment.instrument_model", "experiment.spot_descriptor", "experiment.study_ref", "run.title", "run.attributes", "run.filename", "run.semantic_name", "run.total_bases", "run.total_spots", "run.alias", "run.read_lengths", "run.base_counts", "run.r1_length", "run.r2_length", "run.r3_length", "run.r4_length", "run.Acount", "run.Ccount", "run.Gcount", "run.Tcount", "run.Ncount", "run.experiment", "run.pool_member", "submission.accession", "submission.srasource", "submission.bioprojectsource", "seqdetective.n_mates", "seqdetective.mapping_rate.mate1", "seqdetective.mapping_rate.mate2", "seqdetective.nofeature_rate.mate1", "seqdetective.nofeature_rate.mate2", "seqdetective.sparsity.mate1", "seqdetective.sparsity.mate2", "seqdetective.pos_strand_rate.mate1", "seqdetective.pos_strand_rate.mate2", "seqdetective.readlen.mate1", "seqdetective.readlen.mate2", "seqdetective.judgement.mate1", "seqdetective.judgement.mate2", "seqdetective.judgement.reason", "platform_family", "instrument_generation", "read_bias", "selection_class", "prep_kit", "sc_or_bulk", "tech_class", "technology", "tech_variant", "submission.bioprojectsource.country", "earliest_date", "devstage_curation", "devstage_curation_coarse", "tissue_curation", "tissue_curation_coarse"], "primary_keys": [], "units": {}, "query": {"sql": "select rowid, [run.accession], [experiment.accession], [sample.accession], [study.accession], bioproject, [study.title], [study.alias], [study.type], [study.abstract], [study.attributes], [study.PMIDs], [sample.description], [sample.title], [sample.alias], [sample.centername], [sample.attributes], [GEOsample.title], [GEOsample.dataprocessing], [GEOsample.source], [GEOsample.treatmentprotocol], [GEOsample.extractprotocol], [GEOsample.growthprotocol], [GEOsample.characteristics], [GEOsample.accession], [experiment.title], [experiment.alias], [experiment.library_name], [experiment.design_description], [experiment.library_construction_protocol], [experiment.attributes], [experiment.library_strategy], [experiment.library_source], [experiment.library_selection], [experiment.library_layout], [experiment.platform], [experiment.instrument_model], [experiment.spot_descriptor], [experiment.study_ref], [run.title], [run.attributes], [run.filename], [run.semantic_name], [run.total_bases], [run.total_spots], [run.alias], [run.read_lengths], [run.base_counts], [run.r1_length], [run.r2_length], [run.r3_length], [run.r4_length], [run.Acount], [run.Ccount], [run.Gcount], [run.Tcount], [run.Ncount], [run.experiment], [run.pool_member], [submission.accession], [submission.srasource], [submission.bioprojectsource], [seqdetective.n_mates], [seqdetective.mapping_rate.mate1], [seqdetective.mapping_rate.mate2], [seqdetective.nofeature_rate.mate1], [seqdetective.nofeature_rate.mate2], [seqdetective.sparsity.mate1], [seqdetective.sparsity.mate2], [seqdetective.pos_strand_rate.mate1], [seqdetective.pos_strand_rate.mate2], [seqdetective.readlen.mate1], [seqdetective.readlen.mate2], [seqdetective.judgement.mate1], [seqdetective.judgement.mate2], [seqdetective.judgement.reason], platform_family, instrument_generation, read_bias, selection_class, prep_kit, sc_or_bulk, tech_class, technology, tech_variant, [submission.bioprojectsource.country], earliest_date, devstage_curation, devstage_curation_coarse, tissue_curation, tissue_curation_coarse from run_metadata where \"devstage_curation\" = :p0 and \"experiment.platform\" = :p1 order by rowid limit 101", "params": {"p0": "Adult", "p1": "DNBSEQ"}}, "facet_results": {"experiment.library_strategy": {"name": "experiment.library_strategy", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "RNA-Seq", "label": "RNA-Seq", "count": 849, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&experiment.library_strategy=RNA-Seq", "selected": false}, {"value": "OTHER", "label": "OTHER", "count": 3, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&experiment.library_strategy=OTHER", "selected": false}], "truncated": false}, "experiment.library_source": {"name": "experiment.library_source", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "TRANSCRIPTOMIC", "label": "TRANSCRIPTOMIC", "count": 848, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&experiment.library_source=TRANSCRIPTOMIC", "selected": false}, {"value": "TRANSCRIPTOMIC SINGLE CELL", "label": "TRANSCRIPTOMIC SINGLE CELL", "count": 4, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&experiment.library_source=TRANSCRIPTOMIC+SINGLE+CELL", "selected": false}], "truncated": false}, "experiment.library_selection": {"name": "experiment.library_selection", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "cDNA", "label": "cDNA", "count": 843, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&experiment.library_selection=cDNA", "selected": false}, {"value": "PolyA", "label": "PolyA", "count": 6, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&experiment.library_selection=PolyA", "selected": false}, {"value": "other", "label": "other", "count": 3, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&experiment.library_selection=other", "selected": false}], "truncated": false}, "experiment.library_layout": {"name": "experiment.library_layout", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "PAIRED", "label": "PAIRED", "count": 565, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&experiment.library_layout=PAIRED", "selected": false}, {"value": "SINGLE", "label": "SINGLE", "count": 287, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&experiment.library_layout=SINGLE", "selected": false}], "truncated": false}, "experiment.platform": {"name": "experiment.platform", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "DNBSEQ", "label": "DNBSEQ", "count": 852, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult", "selected": true}], "truncated": false}, "devstage_curation_coarse": {"name": "devstage_curation_coarse", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "Adult", "label": "Adult", "count": 852, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&devstage_curation_coarse=Adult", "selected": false}], "truncated": false}, "devstage_curation": {"name": "devstage_curation", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "Adult", "label": "Adult", "count": 852, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?experiment.platform=DNBSEQ", "selected": true}], "truncated": false}, "tissue_curation_coarse": {"name": "tissue_curation_coarse", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "All anatomical structures", "label": "All anatomical structures", "count": 711, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation_coarse=All+anatomical+structures", "selected": false}, {"value": "Nervous System", "label": "Nervous System", "count": 80, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation_coarse=Nervous+System", "selected": false}, {"value": "Surface Structure", "label": "Surface Structure", "count": 43, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation_coarse=Surface+Structure", "selected": false}, {"value": "Digestive System", "label": "Digestive System", "count": 9, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation_coarse=Digestive+System", "selected": false}, {"value": "Liver and Biliary System", "label": "Liver and Biliary System", "count": 6, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation_coarse=Liver+and+Biliary+System", "selected": false}, {"value": "Renal System", "label": "Renal System", "count": 3, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation_coarse=Renal+System", "selected": false}], "truncated": false}, "tissue_curation": {"name": "tissue_curation", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "Whole Organism", "label": "Whole Organism", "count": 711, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation=Whole+Organism", "selected": false}, {"value": "Brain", "label": "Brain", "count": 70, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation=Brain", "selected": false}, {"value": "Fin", "label": "Fin", "count": 42, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation=Fin", "selected": false}, {"value": "Spinal Cord", "label": "Spinal Cord", "count": 10, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation=Spinal+Cord", "selected": false}, {"value": "Gut", "label": "Gut", "count": 9, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation=Gut", "selected": false}, {"value": "Liver", "label": "Liver", "count": 6, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation=Liver", "selected": false}, {"value": "Kidney", "label": "Kidney", "count": 3, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation=Kidney", "selected": false}, {"value": "Skin", "label": "Skin", "count": 1, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&tissue_curation=Skin", "selected": false}], "truncated": false}, "technology": {"name": "technology", "type": "column", "hideable": false, "toggle_url": "/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ", "results": [{"value": "microwellseq", "label": "microwellseq", "count": 711, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&technology=microwellseq", "selected": false}, {"value": "unknown", "label": "unknown", "count": 80, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&technology=unknown", "selected": false}, {"value": "bulk", "label": "bulk", "count": 36, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&technology=bulk", "selected": false}, {"value": "10x", "label": "10x", "count": 25, "toggle_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&technology=10x", "selected": false}], "truncated": false}}, "suggested_facets": [], "next": "64539", "next_url": "http://metadata.rnaquarium.org/metadata/run_metadata.json?devstage_curation=Adult&experiment.platform=DNBSEQ&_next=64539", "private": false, "allow_execute_sql": true, "query_ms": 130.69317800545832}