{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:41:46Z","timestamp":1792172506521,"version":"4.4.0"},"reference-count":27,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T00:00:00Z","timestamp":1641340800000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2021,12,1]]},"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To integrate published single-cell RNA sequencing (scRNA-seq) data and assess the contribution of synovial fibroblast (SF) subsets to synovial pathotypes and respective clinical characteristics in treatment-na\u00efve early arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this in silico study, we integrated scRNA-seq data from published studies with additional unpublished in-house data. Standard Seurat, Harmony and Liger workflow was performed for integration and differential gene expression analysis. We estimated single cell type proportions in bulk RNA-seq data (deconvolution) from synovial tissue from 87 treatment-na\u00efve early arthritis patients in the Pathobiology of Early Arthritis Cohort using MuSiC. SF proportions across synovial pathotypes (fibroid, lymphoid and myeloid) and relationship of disease activity measurements across different synovial pathotypes were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified four SF clusters with respective marker genes:\n                      <jats:italic>\n                        PRG4\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF (\n                      <jats:italic>\n                        CD55, MMP3, PRG4, THY1\n                        <jats:sup>neg<\/jats:sup>\n                      <\/jats:italic>\n                      );\n                      <jats:italic>CXCL12<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      SF (\n                      <jats:italic>\n                        CXCL12, CCL2, ADAMTS1, THY1\n                        <jats:sup>low<\/jats:sup>\n                      <\/jats:italic>\n                      );\n                      <jats:italic>\n                        POSTN\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF (\n                      <jats:italic>POSTN, collagen genes, THY1<\/jats:italic>\n                      );\n                      <jats:italic>\n                        CXCL14\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF (\n                      <jats:italic>CXCL14, C3, CD34, ASPN, THY1<\/jats:italic>\n                      ) that correspond to lining (\n                      <jats:italic>\n                        PRG4\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF) and sublining (\n                      <jats:italic>\n                        CXCL12\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF,\n                      <jats:italic>\n                        POSTN\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      + and\n                      <jats:italic>\n                        CXCL14\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF) SF subsets.\n                      <jats:italic>\n                        CXCL12\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF and\n                      <jats:italic>\n                        POSTN\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      + were most prominent in the fibroid while\n                      <jats:italic>\n                        PRG4\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF appeared highest in the myeloid pathotype. Corresponding, lining assessed by histology (assessed by Krenn-Score) was thicker in the myeloid, but also in the lymphoid pathotype + the fibroid pathotype.\n                      <jats:italic>\n                        PRG4\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF correlated positively with disease severity parameters in the fibroid,\n                      <jats:italic>\n                        POSTN\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF in the lymphoid pathotype whereas\n                      <jats:italic>\n                        CXCL14\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      SF showed negative association with disease severity in all pathotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study shows a so far unexplored association between distinct synovial pathologies and SF subtypes defined by scRNA-seq. The knowledge of the diverse interplay of SF with immune cells will advance opportunities for tailored targeted treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2021-001949","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T11:45:19Z","timestamp":1641383119000},"page":"e001949","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["Role of synovial fibroblast subsets across synovial pathotypes in rheumatoid arthritis: a deconvolution analysis"],"prefix":"10.1136","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8918-7304","authenticated-orcid":false,"given":"Raphael","family":"Micheroli","sequence":"first","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Elhai","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Edalat","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojca","family":"Frank-Bertoncelj","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"B\u00fcrki","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-7132","authenticated-orcid":false,"given":"Adrian","family":"Ciurea","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Research Into Inflammatory Arthritis Centre Versus Arthritis (RACE), Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Kurowska-Stolarska","sequence":"additional","affiliation":[{"name":"Research Into Inflammatory Arthritis Centre Versus Arthritis (RACE), Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles J","family":"Lewis","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katriona","family":"Goldmann","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cankut","family":"Cubuk","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadeja","family":"Kuret","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Medical Center Ljubljana, Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Distler","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costantino","family":"Pitzalis","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9151-4650","authenticated-orcid":false,"given":"Caroline","family":"Ospelt","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Zurich, 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regulate inflammation and remission in rheumatoid arthritis","volume":"26","author":"Alivernini","year":"2020","journal-title":"Nat Med"},{"key":"2025090313414563000_8.1.e001949.8","doi-asserted-by":"publisher","DOI":"10.1186\/ar4555"},{"key":"2025090313414563000_8.1.e001949.9","doi-asserted-by":"publisher","DOI":"10.1002\/art.20811"},{"key":"2025090313414563000_8.1.e001949.10","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.138461"},{"key":"2025090313414563000_8.1.e001949.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"2025090313414563000_8.1.e001949.12","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2019.05.006"},{"key":"2025090313414563000_8.1.e001949.13","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat 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Available: http:\/\/cole-trapnell-lab.github.io\/monocle-release\/"},{"key":"2025090313414563000_8.1.e001949.17","unstructured":"Array Express . E-MTAB-6141 - Comprehensive transcriptome analysis of synovium and peripheral blood reveals major disease heterogeneity early in the RA disease process prior to therapeutic intervention. Available: https:\/\/www.ebi.ac.uk\/arrayexpress\/experiments\/E-MTAB-6141\/samples\/"},{"key":"2025090313414563000_8.1.e001949.18","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2025090313414563000_8.1.e001949.19","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2025090313414563000_8.1.e001949.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08023-x"},{"key":"2025090313414563000_8.1.e001949.21","unstructured":"GitHub . xuranw \/ MuSiC. 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