Pro-fibrotic Fcer1g-expressing mesenchymal cells induced by macrophages during wound healing

Pro-fibrotic Fcer1g-expressing mesenchymal cells induced by macrophages during wound healing | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Pro-fibrotic Fcer1g-expressing mesenchymal cells induced by macrophages during wound healing Benjamin Alman, Xinyi Ma, Ergang Wang, Vijitha Puviindran, Xiaoxi Liu, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6373202/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Feb, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Fibrosis commonly occurs during adult skin wound healing, characterized by excessive extracellular matrix (ECM), leading to scarring. Mesenchymal cells, the primary ECM-producing population, are heterogeneous with varying fibrotic propensity during wound healing. While pro-fibrotic embryonically derived mesenchymal lineages have been identified, adult mesenchymal cells responsible for fibrosis are not yet fully characterized. In adult mice with conditional macrophage depletion during the early phase of wound healing, wounds exhibited attenuated fibrosis and a reduction in mesenchymal cell numbers. Single-cell RNA sequencing revealed a Fcer1g-expressing mesenchymal subpopulation that was significantly decreased following macrophage depletion. Targeted ablation of this cell population did not delay wound closure but resulted in diminished cutaneous scarring. During wound healing, these Fcer1g-expressing mesenchymal cells localized at the wound bed and exhibited a high proliferation rate. Fibronectin is secreted by macrophages and known to modulate fibrosis during wound healing. Wounds from EDA fibronectin-deficient mice contained significantly fewer Fcer1g-expressing mesenchymal cells. Our findings reveal a macrophage-induced adult mesenchymal subpopulation responsible for fibrosis. Biological sciences/Immunology/Innate immune cells/Monocytes and macrophages Biological sciences/Developmental biology/Stem cells/Regeneration Biological sciences/Cell biology Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementaryinformation.pdf Supplementary Figures and Tables SupplementaryTable2uniqueness.factor.csv Supplementary Dataset 1 Cite Share Download PDF Status: Published Journal Publication published 12 Feb, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6373202","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":438450610,"identity":"a4688873-5be1-4abe-bb55-4b05fc0bb1f2","order_by":0,"name":"Benjamin 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Mesenchymal cells, the primary ECM-producing population, are heterogeneous with varying fibrotic propensity during wound healing. While pro-fibrotic embryonically derived mesenchymal lineages have been identified, adult mesenchymal cells responsible for fibrosis are not yet fully characterized. In adult mice with conditional macrophage depletion during the early phase of wound healing, wounds exhibited attenuated fibrosis and a reduction in mesenchymal cell numbers. Single-cell RNA sequencing revealed a Fcer1g-expressing mesenchymal subpopulation that was significantly decreased following macrophage depletion. Targeted ablation of this cell population did not delay wound closure but resulted in diminished cutaneous scarring. During wound healing, these Fcer1g-expressing mesenchymal cells localized at the wound bed and exhibited a high proliferation rate. Fibronectin is secreted by macrophages and known to modulate fibrosis during wound healing. 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