{"database": "metadata", "table": "run_metadata", "rows": [[30621, "SRR27907609", "SRX23567385", "SRS20412877", "SRP488782", "PRJNA1074407", "Ctla 4 deficiency induces an inflammatory bowel disease like phenotype in a zebrafish model [bulkRNA seq]", "GSE255304", "Transcriptome Analysis", "Inflammatory bowel disease IBD is a chronic and relapsing immune mediated disorder characterized by intestinal inflammation and epithelial injury. The underlying causes of IBD are not fully understood  but genetic factors have implicated in genome wide association studies  including CTLA 4  an essential negative regulator of T cell activation. However  establishing a direct link between CTLA 4 and IBD has been challenging due to the early lethality of CTLA 4 knockout mice. In this study  we identified zebrafish Ctla 4 ortholog and investigated its role in maintaining intestinal immune homeostasis by generating a Ctla 4 deficient ctla 4 /  zebrafish line. These mutant zebrafish exhibit reduced weight  along with impaired epithelial barrier integrity and lymphocytic infiltration in their intestines. Transcriptomics analysis revealed upregulation of inflammation related genes  disturbing immune system homeostasis. Moreover  single cell RNA sequencing analysis indicated increased Th2 cells and interleukin 13 expression  along with decreased innate lymphoid cells and upregulated proinflammatory cytokines. Additionally  Ctla 4 deficient zebrafish exhibited reduced diversity and an altered composition of the intestinal microbiota. All these phenotypes closely resemble those found in mammalian IBD. Lastly  supplementation with Ctla 4 Ig successfully alleviated intestinal inflammation in these mutants. Altogether  these findings offer substantial evidence linking CTLA 4 to IBD and establish a new model for investigating pathogenesis and potential treatments. Overall design: Total RNAs were isolated from wild type or ctla 4 /  intestines three biological replicates using TRIzol reagent following the manufacturer's instructions Takara. cDNA libraries were constructed using NEB Next Ultra Directional RNA Library Prep Kit NEB  and sequencing was performed according to the Illumina Hiseq2500 standard protocol at LC Bio Hangzhou  China.", null, "pubmed:40392591", null, "KO11  Ctla 4 knockout", "GSM8068838", null, "source name:intestine|tissue:intestine|cell type:leukocyte|genotype:Ctla 4 KO|geo loc name:missing|collection date:missing", "KO11  Ctla 4 knockout", "The differentially expressed genes DEGs were identified with absolute Log2 fold change > 1 and adjusted p value < 0.05 by R package DESeq2. Gene Ontology GO enrichment and Kyoto encyclopedia of genes and genomes KEGG enrichment analyses were performed by the OmicStudio http://www.omicstudio.cn/tool tools. Gene set enrichment analysis was performed using software GSEA v4.1.0  https://www.gsea msigdb.org/gsea/index.jsp  and the heatmap was generated using the R package ggplot2. For the protein protein interaction PPI networks  the DEGs were retrieved in STRING version 11.5  https://string db.org/ database combined score > 0.4  and the PPI network was visualized by Cytoscape software version 3.9.16. The betweenness centrality BC was calculated using the CytoNCA plugin in Cytoscape software. Assembly: GRCz11 Supplementary files format and content: Tab separated values files and matrix files", "intestine", null, "Total RNAs were isolated from wild type or ctla 4 /  intestines three biological replicates using TRIzol reagent following the manufacturer's instructions Takara. cDNA libraries were constructed using NEB Next Ultra Directional RNA Library Prep Kit NEB  and sequencing was performed according to the Illumina Hiseq2500 standard protocol at LC Bio Hangzhou  China.", null, "tissue:intestine|cell type:leukocyte|genotype:Ctla 4 KO", "GSM8068838", "GSM8068838: KO11  Ctla 4 knockout; Danio rerio; RNA Seq", "GSM8068838 r1", "GSM8068838", "1", "Total RNAs were isolated from wild type or ctla 4 /  intestines three biological replicates using TRIzol reagent following the manufacturer's instructions Takara. cDNA libraries were constructed using NEB Next Ultra Directional RNA Library Prep Kit NEB  and sequencing was performed according to the Illumina Hiseq2500 standard protocol at LC Bio Hangzhou  China.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "ILLUMINA", "Illumina HiSeq 2500", null, "SRP488782", null, "loader:fastq load.py", "KO11_Clean_Data2.fq.gz KO11_Clean_Data1.fq.gz", "fastq fastq", 5443694370.0, 18290488.0, "GSM8068838 r1", "0:148.81 1:148.81", "A:1480267395;C:1230300897;G:1247791644;T:1485302181;N:32253", 148, 148, null, null, 1480267395, 1230300897, 1247791644, 1485302181, 32253, "SRX23567385", "SRS20412877", "SRA1799527", "zhejiang university", "zhejiang university", 2, 0.86445, 0.86409, 0.07094, 0.06652, 0.74738, 0.74897, 0.51339, 0.51762, 149, 149, "B", "B", "biological fallback assumption", "illumina", "hiseq_era", "unknown", "cdna_unspecified", "nebnext", "sc_generic", "single_cell_generic", "generic-scrnaseq-only", null, "China", "2024-02-07", "Undetermined", "Undetermined", "Gut", "Digestive 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": ["30621"], "units": {}, "query_ms": 7.111850994988345}