{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T21:09:57Z","timestamp":1780607397168,"version":"3.54.1"},"reference-count":38,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":37,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/T001631\/1"],"award-info":[{"award-number":["MR\/T001631\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,22]]},"abstract":"<jats:p>Fibroblasts are central to pathogenesis of systemic sclerosis (SSc). However, studies of conventional explant fibroblast cultures incompletely reflect disease biology and treatment response. We isolated a second nonmigratory \u201cresident\u201d population of fibroblasts from skin biopsies after outgrowth of explant \u201cmigratory\u201d cells. These nonmotile resident fibroblasts were compared with migratory cells from the same biopsy, using functional studies, bulk and single-cell RNA-seq, and localized in situ by multichannel immunofluorescence. Migratory and resident fibroblast populations in SSc showed distinct profibrotic characteristics and gene expression for pathogenic pathways differing by stage and autoantibody subgroup. TGF-\u03b2 signaling was highly active in migratory fibroblasts in early-stage diffuse cutaneous SSc (dcSSc). Conversely, resident fibroblasts had less upregulated TGF-\u03b2 signaling, especially in late-stage dcSSc. Increased chemokine expression was a hallmark of resident fibroblasts at all stages. In vitro studies confirmed differential response to TGF-\u03b21 and CCL2 between migratory and resident cells. We suggest that migratory fibroblasts are especially important in early skin disease, whereas nonmigratory fibroblasts may have a regulatory role and contribute more to fibrosis in later-stage disease. Thus, we have identified a pathogenic fibroblast population in SSc, not isolated by conventional explant culture, that could play an important role in fibrosis and be targeted therapeutically.<\/jats:p>","DOI":"10.1172\/jci.insight.185618","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T12:00:21Z","timestamp":1744718421000},"source":"Crossref","is-referenced-by-count":5,"title":["Characterization of a pathogenic nonmigratory fibroblast population in systemic sclerosis skin"],"prefix":"10.1172","volume":"10","author":[{"given":"Kristina E.N.","family":"Clark","sequence":"first","affiliation":[{"name":"Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom."},{"name":"Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwen","family":"Xu","sequence":"additional","affiliation":[{"name":"Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moustafa","family":"Attar","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Voon H.","family":"Ong","sequence":"additional","affiliation":[{"name":"Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Buckley","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3975-8938","authenticated-orcid":true,"given":"Christopher P.","family":"Denton","sequence":"additional","affiliation":[{"name":"Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22721"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224184"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220402"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/art.42510"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159566"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00232-4"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30318-0"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213031"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1076700"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02824.x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2017.11.001"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.12.021"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1263-7"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.029"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.008"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-223862"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab580"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/art.21725"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.09.288"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200955"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.09.045"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.03.011"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02191"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24607-6"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24110-y"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/art.42536"},{"key":"B27","doi-asserted-by":"crossref","unstructured":"Abel TR, et al. 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