{"database": "metadata", "table": "run_metadata", "rows": [[33938, "SRR30947098", "SRX26349626", "SRS22874782", "SRP537826", "PRJNA1171482", "TAK1 operates at the primary cilium in non canonical TGFB/BMP signaling to control heart development", "GSE279246", "Transcriptome Analysis", "Transforming Growth Factor Beta Activated Kinase 1 TAK1/MAP3K7  along with its upstream regulators TAK1 Binding Protein 2 TAB2 and the catalytic alpha subunit of Protein Kinase A PKA Ca/PRKACA  has been identified as a pivotal player in regulation of developmental processes. Haploinsufficiency of TAB2 causes Congenital Heart Disease CHD and rare variants in PKA Ca and TAK1 cause cardioacrofacial dysplasia CAFD  and Frontometaphyseal Dysplasia FMD and cardiospondylocarpofacial syndrome CSCFS  respectively  rare multisystem syndromes  where CHD may appear in the clinical spectrum. We hypothesized that TAK1 plays a significant role in heart development and CHD and addressed this by genetic analysis in CHD patient cohorts and experiments in cell and animal models. Exome sequencing data from 1 471 CHD patients with extracardiac anomalies syndromic CHD  sCHD  2 405 patients with nonsyndromic CHD nsCHD and 45 082 controls showed increased burden of rare TAB2 and TAK1 variants in sCHD  but not in nsCHD. Detailed characterization of tak1 /  and tab2 /  zebrafish mutants revealed cardiac defects dilated atrium  trabeculation defects  tachycardia and reduced contractility as well as  extracardiac developmental anomalies. RNA sequencing of tak1 /  mutant hearts showed downregulation of genes encoding core cardiac transcription factors  sarcomeric proteins and extracellular matrix proteins. Experiments with cell cultures and analysis of zebrafish larvae and gastruloids indicated that TAK1 via TAB2 and PKA Ca is activated at the primary cilium during cardiomyogenesis and that TAK1 activation at this site is enhanced by cardiomyogenic signaling molecules  including ligands of the TGFB/BMP superfamily. Consistent with these findings  CRISPR/Cas9 mediated editing of TAK1 or administration of small molecule inhibitors targeting TAK1 inhibited ciliary signaling and cardiomyocyte differentiation in vitro  while FMD causing mutations in TAK1 reduced its ciliary localization. In conclusion  our data establishes a central role for TAK1 and its upstream regulators in cardiac development and syndromic CHD  coordinated via the primary cilium. Overall design: To investigate the function of tak1 in heart development  we created a zebrafish mutant using CRISPR cas9. Three groups of hearts from 3 dpf tak1 /  and tak1+/+ zebrafish larvae 15 hearts of each genotype respectively were extracted as previously described PMID 25651299 and RNAseq was used to compare the transcription profile between mutant and wild type.", null, null, null, "whole heart  tak1 /  mutant  replicate #2", "GSM8565201", null, "source name:Whole heart  3 dpf|tissue:Whole heart  3 dpf|genotype:tak1 / |geo loc name:missing|collection date:missing", "whole heart  tak1 /  mutant  replicate #2", "post quality filtering  reads were aligned to reference sequence GCF 000002035.6 GRCz11 using HISAT and Bowtie 2. Average mapping ratio with reference genome was 88.50%  average mapping ratio with genes was 74.56%. In total 23966 genes were identified. Assembly: GCF 000002035.6 GRCz11 Supplementary files format and content: Matrix txt file. Columns: gene id  NCBI; gene symbol; tpm mut 1; tpm mut 2; tpm mut 3; tpm WT 1; tpm WT 2; tpm WT 3. Data is shown as transcripts per million TPM.", "Whole heart  3 dpf", null, "RNA isolation using Qiagen Rneasy micro kit Bulk RNAseq was performed as a service by BGI  China. Samples were paired end sequenced using the DNBSEQ platform.", null, "tissue:Whole heart  3 dpf|genotype:tak1 / ", "GSM8565201", "GSM8565201: whole heart  tak1 /  mutant  replicate #2; Danio rerio; RNA Seq", "GSM8565201 r1", "GSM8565201", "1", "RNA isolation using Qiagen Rneasy micro kit Bulk RNAseq was performed as a service by BGI  China. Samples were paired end sequenced using the DNBSEQ platform.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "DNBSEQ", "DNBSEQ-G400", null, "SRP537826", null, null, "mut_2_1.fq.gz mut_2_2.fq.gz", "fastq fastq", 4534495200.0, 22672476.0, "GSM8565201 r1", null, null, null, null, null, null, null, null, null, null, null, "SRX26349626", "SRS22874782", "SRA1990217", "Department of Cellular and Molecular Medicine, University of Copenhagen", "Department of Cellular and Molecular Medicine, University of Copenhagen", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "cdna_unspecified", "unknown", "bulk", "bulk", "bulk", null, "Denmark", "2024-10-10", "Larval", "Larval", "Heart", "Cardiovascular System"]], "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": ["rowid"], "primary_key_values": ["33938"], "units": {}, "query_ms": 9.66319399594795}