In this study, we characterized 24 rheumatoid arthritis (RA) synovial tissue chromatin classes (i.e., cell states defined by chromatin accessibility) across 5 cell types (T, B/plasma, myeloid, stromal, and endothelial). We also investigated the transcription factors that may regulate these chromatin classes, their connections to transcriptional cell states in a proposed superstate model, and their interplay with RA pathology through associations with histological parameters and risk variants.As part of the Accelerating Medicines Partnership (<a href="https://www.nih.gov/research-training/accelerating-medicines-partnership-amp/autoimmune-diseases-rheumatoid-arthritis-lupus">AMP</a>) network, we obtained 18 synovial tissue samples from 14 RA and 4 osteoarthritis (OA) patients for this study. Samples were collected from 7 clinical sites. We performed a 10x single cell ATAC-seq experiment on each sample.We further collected synovial tissue samples from 11 RA patients and 1 OA patient from 2 clinical sites; each sample was used for a 10x single cell multimodal ATAC and Gene Expression experiment.For additional support of the proposed superstate model, we also collected peripheral blood mononuclear cells (PBMCs) from 4 RA patients, sorted for 4 populations (<a href="https://www.ncbi.nlm.nih.gov/gene/920">CD4</a>+<a href="https://www.ncbi.nlm.nih.gov/gene/3575">CD127</a>-<a href="https://www.ncbi.nlm.nih.gov/gene/3559">CD25</a>hi Tregs, CD4+CD127-CD25int Tregs, CD4+CD25-<a href="https://www.ncbi.nlm.nih.gov/gene/5133">PD1</a>+<a href="https://www.ncbi.nlm.nih.gov/gene/643">CXCR5</a>- TPH, CD4+CD25-PD1+CXCR5+ TFH), tagged each population with a hashing antibody, and pooled populations for one multimodal sequencing run.The FASTQ files are available for controlled access via dbGaP. Additional data can be found on <a href="https://doi.org/10.7303/syn53650034">Synapse</a>.The presence of pooled subjects inflates the automatically-generated subject count; the actual consented subject count for this data is 34.

The Chromatin Landscape of Pathogenic Transcriptional Cell States in Rheumatoid Arthritis

Tissue-specific enhancer–gene maps from multimodal single-cell data identify causal disease alleles

The Chromatin Landscape of Pathogenic Transcriptional Cell States in Rheumatoid Arthritis

Dynamic regulatory elements in single-cell multimodal data implicate key immune cell states enriched for autoimmune disease heritability