The Chromatin Landscape of Pathogenic Transcriptional Cell States in Rheumatoid Arthritis

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 (AMP) 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 (CD4⁺CD127^-CD25^hi Tregs, CD4⁺CD127^-CD25^int Tregs, CD4⁺CD25^-PD1⁺CXCR5^- 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 Synapse.

The presence of pooled subjects inflates the automatically-generated subject count; the actual consented subject count for this data is 34.

• Type: Case Set
• Archiver: The database of Genotypes and Phenotypes (dbGaP)