PT - JOURNAL ARTICLE AU - Zhang, Fan AU - Wei, Kevin AU - Slowikowski, Kamil AU - Fonseka, Chamith Y. AU - Rao, Deepak A. AU - Kelly, Stephen AU - Goodman, Susan M. AU - Tabechian, Darren AU - Hughes, Laura B. AU - Salomon-Escoto, Karen AU - Watts, Gerald F. M. AU - Apruzzese, William AU - Lieb, David J. AU - Boyle, David L. AU - Mandelin, Arthur M. AU - , AU - Boyce, Brendan F. AU - DiCarlo, Edward AU - Gravallese, Ellen M. AU - Gregersen, Peter K. AU - Moreland, Larry AU - Firestein, Gary S. AU - Hacohen, Nir AU - Nusbaum, Chad AU - Lederer, James A. AU - Perlman, Harris AU - Pitzalis, Costantino AU - Filer, Andrew AU - Holers, V. Michael AU - Bykerk, Vivian P. AU - Donlin, Laura T. AU - Anolik, Jennifer H. AU - Brenner, Michael B. AU - Raychaudhuri, Soumya TI - Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry AID - 10.1101/351130 DP - 2018 Jan 01 TA - bioRxiv PG - 351130 4099 - http://biorxiv.org/content/early/2018/06/20/351130.short 4100 - http://biorxiv.org/content/early/2018/06/20/351130.full AB - To define the cell populations in rheumatoid arthritis (RA) driving joint inflammation, we applied single-cell RNA-seq (scRNA-seq), mass cytometry, bulk RNA-seq, and flow cytometry to sorted T cells, B cells, monocytes, and fibroblasts from 51 synovial tissue RA and osteoarthritis (OA) patient samples. Utilizing an integrated computational strategy based on canonical correlation analysis to 5,452 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics together revealed cell states expanded in RA synovia: THY1+HLAhigh sublining fibroblasts (OR=33.8), IL1B+ pro-inflammatory monocytes (OR=7.8), CD11c+T-bet+ autoimmune-associated B cells (OR=5.7), and PD-1+Tph/Tfh (OR=3.0). We also defined CD8+ T cell subsets characterized by GZMK+, GZMB+, and GNLY+ expression. Using bulk and single-cell data, we mapped inflammatory mediators to source cell populations, for example attributing IL6 production to THY1+HLAhigh fibroblasts and naïve B cells, and IL1B to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.