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Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry.
Zhang, Fan; Wei, Kevin; Slowikowski, Kamil; Fonseka, Chamith Y; Rao, Deepak A; Kelly, Stephen; Goodman, Susan M; Tabechian, Darren; Hughes, Laura B; Salomon-Escoto, Karen; Watts, Gerald F M; Jonsson, A Helena; Rangel-Moreno, Javier; Meednu, Nida; Rozo, Cristina; Apruzzese, William; Eisenhaure, Thomas M; Lieb, David J; Boyle, David L; Mandelin, Arthur M; Boyce, Brendan F; DiCarlo, Edward; Gravallese, Ellen M; Gregersen, Peter K; Moreland, Larry; Firestein, Gary S; Hacohen, Nir; Nusbaum, Chad; Lederer, James A; Perlman, Harris; Pitzalis, Costantino; Filer, Andrew; Holers, V Michael; Bykerk, Vivian P; Donlin, Laura T; Anolik, Jennifer H; Brenner, Michael B; Raychaudhuri, Soumya.
Afiliação
  • Zhang F; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
  • Wei K; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Slowikowski K; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • Fonseka CY; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Rao DA; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Kelly S; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Goodman SM; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
  • Tabechian D; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Hughes LB; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • Salomon-Escoto K; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Watts GFM; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Jonsson AH; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
  • Rangel-Moreno J; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Meednu N; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • Rozo C; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Apruzzese W; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Eisenhaure TM; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Lieb DJ; Department of Rheumatology, Barts Health NHS Trust, London, UK.
  • Boyle DL; Division of Rheumatology, Hospital for Special Surgery, New York, NY, USA.
  • Mandelin AM; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Boyce BF; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • DiCarlo E; Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
  • Gravallese EM; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Gregersen PK; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Moreland L; Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
  • Firestein GS; Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
  • Hacohen N; Arthritis and Tissue Degeneration, Hospital for Special Surgery, New York, NY, USA.
  • Nusbaum C; Division of Rheumatology, Immunology, Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Lederer JA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Perlman H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pitzalis C; Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA.
  • Filer A; Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Bykerk VP; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
  • Donlin LT; Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY, USA.
  • Anolik JH; Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
  • Brenner MB; Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, NY, USA.
  • Raychaudhuri S; Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Nat Immunol ; 20(7): 928-942, 2019 07.
Article em En | MEDLINE | ID: mdl-31061532
ABSTRACT
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-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Membrana Sinovial / Perfilação da Expressão Gênica / Transcriptoma Tipo de estudo: Clinical_trials / Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Membrana Sinovial / Perfilação da Expressão Gênica / Transcriptoma Tipo de estudo: Clinical_trials / Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article