run_metadata: 71607
This data as json
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| 71607 | SRR21782745 | SRX17777231 | SRS15303485 | SRP400712 | PRJNA886442 | Tulp1 deficiency causes early onset retinal degeneration through affecting ciliogenesis and activating ferroptosis in zebrafish | GSE214642 | Transcriptome Analysis | Mutations in TUB like protein 1 TULP1 are associated with severe early onset retinal degeneration in humans. However the pathogenesis remains largely unknown. There are two homologous genes of TULP1 in zebrafish namely tulp1a and tulp1b. Here we generated the single knockout tulp1a / and tulp1b / and double knockout tulp1 dKO models in zebrafish. Knockout of tulp1a results in the mislocalization of UV cone opsins and the degeneration of UV cones specifically while knockout of tulp1b results in mislocalization of rod opsins and rod cone degeneration. In the tulp1 dKO zebrafish mislocalization of opsins was present in all types of photoreceptors and severe degeneration was observed at a very early age mimicking the clinical manifestations of TULP1 patients. Photoreceptor cilium length was significantly reduced in the tulp1 dKO retinas. RNA seq analysis showed that the expression of tektin2 tekt2 a ciliary and flagellar microtubule structural component was downregulated in the tulp1 dKO zebrafish. Dual luciferase reporter assay suggested that Tulp1a and Tulp1b transcriptionally activate the promoter of tekt2. Additionally ferroptosis might be activated in the tulp1 dKO zebrafish as suggested by the up regulation of genes related to the ferroptosis pathway the shrinkage of mitochondria reduction or disappearance of mitochondria cristae and the iron and lipid droplet deposition in the retina of tulp1 dKO zebrafish. In conclusion our study establishes an appropriate zebrafish model for TULP1 associated retinal degeneration and proposes that loss of TULP1 causes defects in cilia structure and opsin trafficking through the downregulation of tekt2 which further increases the death of photoreceptors via ferroptosis. These findings offer insight into the pathogenesis and clinical treatment of early onset retinal degeneration. Overall design: Comparative gene expression profiling analysis of RNA seq data for wt and tulp1a&tulp1b zebrafish. | pubmed:36396940 | WT1 | GSM6613552 | source name:head|tissue:head|strain:AB|genotype:wild type|developmental stage:4 dpf | WT1 | Illumina Novaseq 6000 software used for basecalling. Raw data raw reads of fastq format were firstly processed through in house perl scripts. In this step clean data clean reads were obtained by removing reads containing adapter reads containing poly N and low quality reads from raw data. At the same time Q20 Q30 and GC content the clean data were calculated. All the downstream analyses were based on the clean data with high quality. Index of the reference genome was built using Hisat2 and paired end clean reads were aligned to the reference genome using Hisat2. TPM conversion was performed to obtain the standardized gene/transcript expression level. Assembly: GRCz11 Supplementary files format and content: * TPM.csv: Comma separated text files include TPM values. | head | The heads of zebrafish larvae were dissected for RNA extraction. Total RNA was extracted with the RNA isolater Total RNA Extraction Reagent. RNA libraries were prepared for sequencing using standard Illumina protocols. | tissue:head|strain:AB|genotype:wild type|developmental stage:4 dpf | GSM6613552 | GSM6613552: WT1; Danio rerio; RNA Seq | GSM6613552 r1 | GSM6613552 | 1 | The heads of zebrafish larvae were dissected for RNA extraction. Total RNA was extracted with the RNA isolater Total RNA Extraction Reagent. RNA libraries were prepared for sequencing using standard Illumina protocols. | RNA-Seq | TRANSCRIPTOMIC | cDNA | PAIRED | ILLUMINA | Illumina NovaSeq 6000 | SRP400712 | L1EFA141669_WT1.R1.raw.fastq.gz L1EFA141669_WT1.R2.raw.fastq.gz | fastq fastq | 7238862688.0 | 23969744.0 | GSM6613552 r1 | 0:151 1:151 | A:1972024445;C:1640211955;G:1685856317;T:1940696938;N:73033 | 151 | 151 | 1972024445 | 1640211955 | 1685856317 | 1940696938 | 73033 | SRX17777231 | SRS15303485 | SRA1511428 | Huazhong University of Science and Technology | Huazhong University of Science and Technology | 2 | 0.9253 | 0.92638 | 0.11986 | 0.11995 | 0.6521 | 0.6519 | 0.47312 | 0.47348 | 151 | 151 | B | B | biological fallback assumption | illumina | novaseq_era | unknown | cdna_unspecified | unknown | bulk | bulk | bulk | China | 2022-10-02 | Larval | Larval | Head | Nervous System |