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We performed single-cell RNA sequencing (scRNA-Seq) of fibrotic and nonfibrotic ileal tissues from patients with CD with intestinal obstruction. Analysis revealed mesenchymal stromal cells (MSCs) as the major producers of ECM and the increased infiltration of its subset FAP\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts in fibrotic sites, which was confirmed by immunofluorescence and flow cytometry. Single-cell transcriptomic profiling of chronic dextran sulfate sodium salt murine colitis model revealed that CD81\n                    <jats:sup>+<\/jats:sup>\n                    Pi16\n                    <jats:sup>\u2013<\/jats:sup>\n                    fibroblasts exhibited transcriptomic and functional similarities to human FAP\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts. Consistently, FAP\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts were identified as the key subtype with the highest level of ECM production in fibrotic intestines. Furthermore, specific knockout or pharmacological inhibition of TWIST1, which was highly expressed by FAP\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts, could significantly ameliorate fibrosis in mice. In addition, TWIST1 expression was induced by CXCL9\n                    <jats:sup>+<\/jats:sup>\n                    macrophages enriched in fibrotic tissues via IL-1\u03b2 and TGF-\u03b2 signal. These findings suggest the inhibition of TWIST1 as a promising strategy for CD fibrosis treatment.\n                  <\/jats:p>","DOI":"10.1172\/jci179472","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T12:01:28Z","timestamp":1721304088000},"source":"Crossref","is-referenced-by-count":78,"title":["TWIST1+FAP+ fibroblasts in the pathogenesis of intestinal fibrosis in Crohn\u2019s disease"],"prefix":"10.1172","volume":"134","author":[{"given":"Yao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Center for Immune-Related Diseases, Ruijin Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Center for Immune-Related Diseases, Ruijin 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