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  - , 
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 naive B cells, and ILB to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.