Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
<p>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 f...
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| フォーマット: | Journal article |
| 出版事項: |
Nature Research
2019
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| _version_ | 1826298324825669632 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zhang, F |
| collection | OXFORD |
| description | <p>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: <em>THY1(CD90)</em><em><sup>+</sup></em><em>HLA-DRA</em><sup>hi</sup> sublining fibroblasts, <em>IL1B</em><sup>+</sup> pro-inflammatory monocytes, <em>ITGAX</em><sup>+</sup><em>TBX21</em><sup>+</sup> autoimmune-associated B cells and <em>PDCD1</em><sup>+</sup> peripheral helper T (T<sub>PH</sub>) cells and follicular helper T (T<sub>FH</sub>) cells. We defined distinct subsets of CD8<sup>+</sup> T cells characterized by <em>GZMK</em><sup>+</sup>, <em>GZMB</em><sup>+</sup>, and <em>GNLY</em><sup>+</sup> phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed <em>IL6</em> expression to <em>THY1</em><sup>+</sup><em>HLA-DRA</em><sup>hi</sup> fibroblasts and <em>IL1B</em> production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.</p> |
| first_indexed | 2024-03-07T04:45:06Z |
| format | Journal article |
| id | oxford-uuid:d2f8e218-c5dd-4f33-a3d4-de61cc5a1e9d |
| institution | University of Oxford |
| last_indexed | 2024-03-07T04:45:06Z |
| publishDate | 2019 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:d2f8e218-c5dd-4f33-a3d4-de61cc5a1e9d2022-03-27T08:08:13ZDefining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometryJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d2f8e218-c5dd-4f33-a3d4-de61cc5a1e9dSymplectic Elements at OxfordNature Research2019Zhang, FWei, KSlowikowski, KFonseka, CYRao, DAKelly, SGoodman, SMTabechian, DHughes, LBSalomon-Escoto, KWatts, GFMJonsson, AHRangel-Moreno, JMeednu, NRozo, CApruzzese, WEisenhaure, TMLieb, DJBoyle, DLMandelin, AMAlbrecht, JBridges, SLBuckley, CDBuckner, JHDolan, JGuthridge, JMGutierrez-Arcelus, MIvashkiv, LBJames, EAJames, JAKeegan, JLee, YCMcGeachy, MJMcNamara, MAMears, JRMizoguchi, FNguyen, JPNoma, AOrange, DERohani-Pichavant, MRitchlin, CRobinson, WHSeshadri, ASutherby, DSeifert, JTurner, JDUtz, PJBoyce, BFDicarlo, EGravallese, EMGregersen, PKMoreland, LFirestein, GSHacohen, NNusbaum, CLederer, JAPerlman, HPitzalis, CFiler, AHolers, VMBykerk, VPDonlin, LTAnolik, JHBrenner, MBRaychaudhuri, S<p>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: <em>THY1(CD90)</em><em><sup>+</sup></em><em>HLA-DRA</em><sup>hi</sup> sublining fibroblasts, <em>IL1B</em><sup>+</sup> pro-inflammatory monocytes, <em>ITGAX</em><sup>+</sup><em>TBX21</em><sup>+</sup> autoimmune-associated B cells and <em>PDCD1</em><sup>+</sup> peripheral helper T (T<sub>PH</sub>) cells and follicular helper T (T<sub>FH</sub>) cells. We defined distinct subsets of CD8<sup>+</sup> T cells characterized by <em>GZMK</em><sup>+</sup>, <em>GZMB</em><sup>+</sup>, and <em>GNLY</em><sup>+</sup> phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed <em>IL6</em> expression to <em>THY1</em><sup>+</sup><em>HLA-DRA</em><sup>hi</sup> fibroblasts and <em>IL1B</em> production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.</p> |
| spellingShingle | 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 Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry |
| title | Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry |
| title_full | Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry |
| title_fullStr | Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry |
| title_full_unstemmed | Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry |
| title_short | Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry |
| title_sort | defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single cell transcriptomics and mass cytometry |
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