Author:
Gupta Anika,Weinand Kathryn,Nathan Aparna,Sakaue Saori,Donlin Laura,Wei Kevin,Price Alkes L.,Amariuta Tiffany,Raychaudhuri Soumya,
Abstract
In autoimmune diseases such as rheumatoid arthritis (RA), the immune system attacks host tissues1-3. Developing a precise understanding of the fine-grained cell states that mediate the genetics of autoimmunity is critical to uncover causal disease mechanisms and develop potentially curative therapies. We leveraged multimodal single-nucleus (sn) RNA-seq and ATAC-seq data across 28,674 cells from the inflamed synovium of 12 donors with arthritis to identify accessible regions of chromatin associated with gene expression patterns that reflect cell states. For 12 autoimmune diseases, we discovered that cell-state-dependent (“dynamic”) peaks in immune cell types disproportionately captured heritability, compared to cell-state-invariant (“cs-invariant”) peaks. These dynamic peaks marked regulatory elements associated with T peripheral helper, regulatory T, dendritic, and STAT1+CXCL10+myeloid cell states. We argue that dynamic regulatory elements can help identify precise cell states enriched for disease-critical genetic variation.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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