run_metadata: 33629

This data as json

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
33629	SRR30310497	SRX25770922	SRS22407025	SRP527479	PRJNA1150074	Epileptic phenotypes in slc13a5 loss of function zebrafish are rescued by blocking NMDA receptor signaling	GSE275235	Transcriptome Analysis	SLC13A5 encodes a citrate transporter highly expressed in the brain important for regulating intra and extracellular citrate levels. Mutations in this gene cause a rare infantile epilepsy characterized by lifelong seizures developmental delays behavioral deficits poor motor progression and language impairments. SLC13A5 individuals respond poorly to treatment options; yet drug discovery programs are limited due to a paucity of animal models that phenocopy human symptoms. Here we used CRISPR/Cas9 to create loss of function mutations in slc13a5a and slc13a5b the zebrafish paralogs to human SLC13A5. slc13a5 mutant larvae showed cognitive dysfunction and sleep disturbances consistent with SLC13A5 individuals. These mutants also exhibited fewer neurons and a concomitant increase in apoptosis across the optic tectum a region important for sensory processing. slc13a5 mutants displayed hallmark features of epilepsy including an imbalance in glutamatergic and GABAergic excitatory inhibitory gene expression disrupted neurometabolism and neuronal hyperexcitation as measured in vivo by extracellular field recordings and live calcium imaging. Mechanistically we tested the involvement of NMDA signaling in slc13a5 mutant epilepsy like phenotypes. Slc13a5 protein co localizes with excitatory NMDA receptors in wild type zebrafish and blocking NMDA receptors in slc13a5 mutant larvae rescued bioenergetics hyperexcitable calcium events and behavioral defects. These data provide empirical evidence in support of the hypothesis that excess extracellular citrate over chelates the ions needed to regulate NMDA receptor function leading to sustained channel opening and an exaggerated excitatory response that manifests as seizures. These data show the utility of slc13a5 mutant zebrafish for studying SLC13A5 epilepsy and open new avenues for drug discovery. Overall design: 5 dpf zebrafish heads were pooled to generate three biological replicates of each group. Four groups of samples were generated: WT controls 5a mutants 5b mutants and 5a/5b double mutants		pubmed:40208862		WT biol rep 2	GSM8473249		source name:heads\|tissue:heads\|genotype:WT\|treatment:untreated\|geo loc name:missing\|collection date:missing	WT biol rep 2	Fastq files were aligned using STAR and gene counts obtained from STAR were given as input to DESeq2 for differential gene analysis and obtained normalised counts. Genes with zero values in more than 4 samples were exlcuded from the analysis Assembly: GRCz11 Supplementary files format and content: tab delimited text file include raw counts for each sample Supplementary files format and content: tab delimited text file include log normalised counts for each sample	heads	untreated	Trizol based RNA extraction and column purification purified RNA with RIN>7 were sent for sequencing NextSeq2000 P2 100 cycle	Adult zebrafish TL and AB strains were maintained at 28°C in a 14 hour light/10 hour dark cycle under standard aquaculture conditions and fertilized eggs were collected via natural spawning.	tissue:heads\|genotype:WT\|treatment:untreated	GSM8473249	GSM8473249: WT biol rep 2; Danio rerio; RNA Seq	GSM8473249 r1	GSM8473249	1	Trizol based RNA extraction and column purification purified RNA with RIN>7 were sent for sequencing NextSeq2000 P2 100 cycle		RNA-Seq	TRANSCRIPTOMIC	cDNA	PAIRED	ILLUMINA	NextSeq 2000		SRP527479			Li47810-WT2_S2_R2_001.fastq.gz Li47810-WT2_S2_R1_001.fastq.gz	fastq fastq	4788359140.0	39599012.0	GSM8473249 r1	0:60.48 1:60.44	A:1237189996;C:1129331953;G:1143753687;T:1268980159;N:9103345	60	60			1237189996	1129331953	1143753687	1268980159	9103345	SRX25770922	SRS22407025	SRA1951631	Kurrasch Lab, Department of Medical Genetics, University of Calgary	Kurrasch Lab, Department of Medical Genetics, University of Calgary	2	0.94746	0.95043	0.1121	0.11092	0.64411	0.64342	0.46922	0.47301	59	61	B	B	biological fallback assumption	illumina	nextseq_v2	unknown	cdna_unspecified	unknown	bulk	unknown	unknown		Canada	2024-08-20	Adult	Adult	Head	Nervous System