Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
| العنوان: | Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry |
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| المؤلفون: | Zhang, F, Wei, K, Slowikowski, K, Fonseka, CY, Rao, DA, Kelly, S, Goodman, SM, Tabechian, D, Hughes, LB, Salomon-Escoto, K, Watts, GFM, Jonsson, AH, Rangel-Moreno, J, Meednu, N, Rozo, C, Apruzzese, W, Eisenhaure, TM, Lieb, DJ, Boyle, DL, Mandelin, AM, Albrecht, J, Bridges, SL, Buckley, CD, Buckner, JH, Dolan, J, Guthridge, JM, Gutierrez-Arcelus, M, Ivashkiv, LB, James, EA, James, JA, Keegan, J, Lee, YC, McGeachy, MJ, McNamara, MA, Mears, JR, Mizoguchi, F, Nguyen, JP, Noma, A, Orange, DE, Rohani-Pichavant, M, Ritchlin, C, Robinson, WH, Seshadri, A, Sutherby, D, Seifert, J, Turner, JD, Utz, PJ, Boyce, BF, Dicarlo, E, Gravallese, EM, Gregersen, PK, Moreland, L, Firestein, GS, Hacohen, N, Nusbaum, C, Lederer, JA, Perlman, H, Pitzalis, C, Filer, A, Holers, VM, Bykerk, VP, Donlin, LT, Anolik, JH, Brenner, MB, Raychaudhuri, S |
| المصدر: | Nature immunology |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Immunology, Cell, Arthritis, Gene Expression, Autoimmunity, Monocytes, Article, Flow cytometry, GZMB, Workflow, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, GNLY, T-Lymphocyte Subsets, medicine, Leukocytes, Immunology and Allergy, Humans, CD90, Mass cytometry, medicine.diagnostic_test, Chemistry, Gene Expression Profiling, Synovial Membrane, Histocompatibility Antigens Class II, Computational Biology, High-Throughput Nucleotide Sequencing, Fibroblasts, medicine.disease, Flow Cytometry, Molecular biology, 030104 developmental biology, medicine.anatomical_structure, Cross-Sectional Studies, Cytokines, Single-Cell Analysis, Transcriptome, CD8, Biomarkers, 030215 immunology, Signal Transduction |
| الوصف: | To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia:THY1(CD90)+HLA-DRAhisublining fibroblasts,IL1B+pro-inflammatory monocytes,ITGAX+TBX21+autoimmune-associated B cells andPDCD1+peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+T cells characterized byGZMK+,GZMB+, andGNLY+phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributedIL6expression toTHY1+HLA-DRAhifibroblasts andIL1Bproduction to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis. |
| تدمد: | 1529-2916 1529-2908 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::01ee50dc3727ea777143a03dc057cc2eTest http://ora.ox.ac.uk/objects/uuidTest: |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....01ee50dc3727ea777143a03dc057cc2e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292916 15292908 |
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