Comprehensive Epigenetic Landscape of Rheumatoid Arthritis FLS
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PROVIDER: PRJNA474569 | ENA |
REPOSITORIES: ENA
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Project description:Comprehensive Epigenetic Landscape of Rheumatoid Arthritis FLS
| PRJNA474568 | ENA
Project description:<p>We characterized the epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes (FLS) compared with osteoarthritis FLS. Multiple technologies were used, including ChIP-seq to assay H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3, ATAC-seq for chromatin accessibility, the transcriptome by RNA-seq and whole genomic bisulfite sequencing for DNA methylation. Integrative analysis was performed using a novel unbiased method to identify regions of the genome that have similar epigenetic marks. The regions that distinguished RA and osteoarthritis cells were primarily located in active enhancers and promoters. The regions and genes identified included immunological pathways. In addition, some unexpected pathways, most notably "Huntington's Disease Signaling", were discovered. The Huntington's Disease pathway was biologically validated for Huntingtin-interacting protein-1, which regulated invasive behavior of FLS. For a complete description, see R. Ai <i>et al.</i>, Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes. <i>Nat Commun</i> 9, 1921 (2018).</p> <p>Sequencing data of study participants are available through dbGaP's Authorized Access portal, while analyses of the sequencing data may be obtained through NCBI's GEO portal under <a href="https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112658">GSE112658.</a></p>
| phs001615 | dbGaP
Project description:Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes
| PRJNA448630 | ENA
Project description:Epigenetics is important in the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first complete epigenomic characterization of RA fibroblast-like synoviocytes (FLS) by profiling histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, H3K9me3), open chromatin, RNA expression and whole genome DNA methylation. To address the complex multidimensional relationship and reveal the epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells are particularly associated with active enhancers and promoters as well as specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with “Huntington's Disease Signaling” identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
2018-04-30 | GSE112657 | GEO
Project description:Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease involving primarily the synovial membranes and articular structures of multiple joints. A hallmark of RA is the pseudo-tumoral expansion of fibroblast-like synoviocytes (FLS), as these cells invade and finally destroy the joint structure. RA FLS have been therefore proposed as a therapeutic target. > TNF-related apoptosis-inducing ligand (TRAIL) has been described as a pro-apoptotic factor on malignant cells. The fact that fibroblasts-like-synoviocytes (FLS) in rheumatoid arthritis RA patients exhibit tumor like features led us to investigate the effect of TRAIL on ex-vivo RA FLS. We have previously described that TRAIL induces apoptosis only in a subset of RA FLS, but an induction of proliferation in the surviving cells. This observation corresponds to the pleiotropic effects of TRAIL observed on primary human tumor cells. We also observed that sensitivity to TRAIL-induced apoptosis varied in RA FLS from one patient to another, and was correlated with disease severity. We therefore screened for genes that were differentially expressed in RA FLS sensitive and resistant to TRAIL induced apoptosis in order to understand molecular factors making cells resistant or sensitive to TRAIL induced apoptosis.
2018-02-12 | GSE65908 | GEO
Project description:Epigenetics is important in the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first complete epigenomic characterization of RA fibroblast-like synoviocytes (FLS) by profiling histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, H3K9me3), open chromatin, RNA expression and whole genome DNA methylation. To address the complex multidimensional relationship and reveal the epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells are particularly associated with active enhancers and promoters as well as specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with “Huntington's Disease Signaling” identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
2018-04-30 | GSE112656 | GEO
Project description:Epigenetics is important in the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first complete epigenomic characterization of RA fibroblast-like synoviocytes (FLS) by profiling histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, H3K9me3), open chromatin, RNA expression and whole genome DNA methylation. To address the complex multidimensional relationship and reveal the epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells are particularly associated with active enhancers and promoters as well as specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with “Huntington's Disease Signaling” identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
2018-04-30 | GSE112654 | GEO
Project description:Epigenetics is important in the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first complete epigenomic characterization of RA fibroblast-like synoviocytes (FLS) by profiling histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, H3K9me3), open chromatin, RNA expression and whole genome DNA methylation. To address the complex multidimensional relationship and reveal the epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells are particularly associated with active enhancers and promoters as well as specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with “Huntington's Disease Signaling” identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.
2018-04-30 | GSE112655 | GEO
Project description:Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes [WGBS]
| PRJNA448633 | ENA
Project description:We report the effects of Hfol on TNF induction of inflammatory genes in wild type cells versus cells depleted of GCN2 RNA-seq analysis of primary rheumatoid arthritis fibroblast like synoviocytes (RA-FLS) treated with TNFa in the presence or absence of Halofuginone (HF).
2020-03-22 | GSE145204 | GEO