EXPERIMENT_TITLE: GSM4981513: 424_TNF: Hi-C, Primary FLS, TNF stimulated; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Cultured human FLS from RA patients were treated with 10 ng/ml TNF for 24 h or were left untreated. Cells (1e7 to 3e7 per condition), were scratched in 10ml DMEM, spun down, suspended in 35ml DMEM and fixed (2% formaldehyde in DMEM, 10min, RT, with mixing on a rocker). The reaction was quenched with cold 0.125M glycine. Cells were incubated at RT for 5 min, followed by 15 min incubation on ice and centrifugation (1500 rpm, 10 min, 4 ⁰C). Pellets were suspended and washed in cold PBS (1500 rpm, 10 min, 4 ⁰C). Washed pellets were snap frozen and stored at -80 ⁰C. Hi-C libraries from RA FLS samples, were generated as previously described in Lieberman-Aiden, E. et al.
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Genome-wide association studies have reported more than 100 risk loci for rheumatoid arthritis, and there loci have been shown to be enriched in immune cell-specific enhancers, we add Synovial fibroblasts (FLS), the local stromal cells of joints to this analysis.  We integrated ChIP-seq, Hi-C, Capture Hi-C, ATAC-seq and RNA-seq datasets from FLS , with genetic fine-mapping of RA loci. From this we identified putative casual variants, enhancers and genes for 30-60% of RA loci and demonstrated that FLS regulatory elements accounts for up to 24% of RA heritability.  We also examined the effects of TNF stimulation on the chromatin landscape of FLS, and we found there are significant alterations in the organization of topologically associated domains, chromatin interactions and the expression of several putative causal genes. Overall design: Examine the enrichment of RA signals in FLS functional elements, assign putative gene targets for these RA signals in FLS, and quantify the effects of TNF stimulation on FLS.
SAMPLE_TITLE: 424_TNF: Hi-C, Primary FLS, TNF stimulated
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "Primary FLS"}, {"TAG": "sample id", "VALUE": "424_TNF"}, {"TAG": "stimulation", "VALUE": "10 ng/ml TNF for 24 hours"}, {"TAG": "joint", "VALUE": "MCP"}, {"TAG": "disease state", "VALUE": "Rheumatoid Arthritis"}]
Pool_Member_@attributes_sample_title: 424_TNF: Hi-C, Primary FLS, TNF stimulated
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