Multimodal gene expression and chromatin accessibility profiles at the single-cell level of synovial tissue from individuals with arthritis

In this study, we sought to understand the cell states in which autoimmune disease heritability is enriched. To do so, we performed single-nucleus multimodal sequencing of cells in the inflamed synovial tissue of individuals with arthritis (11 with rheumatoid arthritis and 1 with osteoarthritis). We measured both gene expression levels and chromatin peak accessibility levels. We found that dynamically accessible chromatin peaks were disproportionately enriched for the heritability of 14 autoimmune and allergic conditions and pointed to specific RNA-defined cell states where this signal was prevalent. Synovial tissue samples from 11 RA patients and 1 OA patient were collected from Brigham and Women’s Hospital (BWH) and the Hospital for Special Surgery (HSS) for use in the multimodal single-nucleus RNA + ATAC experiments. Histologic sections of RA synovial tissue were examined, and samples with inflammatory features were selected in both cases. ***Raw sequencing data are available through dbGaP (controlled access) due to patient privacy concerns. Accession number: phs003417.v1***