{"paper_id":"adc700f6-40fa-4d64-b3ee-93cec6e4e774","body_text":"Omental Adipocyte-to-Myeloid Reprogramming Drives Effective Skin Flap Regeneration | 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 Omental Adipocyte-to-Myeloid Reprogramming Drives Effective Skin Flap Regeneration Hongwei Liu, Chen Zhao, jiaxian Zhang, Jianxin Yan, Hengyu Du, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9399262/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract The greater omentum possesses exceptional regenerative capacity, widely utilized for reconstructing complex tissue defects; yet, the cellular mechanisms underlying this efficacy remain obscure. Here, we show that omental adipocyte reprogramming is a pivotal mechanism driving angiogenesis and tissue repair, underscoring its indispensable role in orchestrating effective tissue regeneration. Integrating genetic lineage tracing with single-nucleus RNA sequencing (snRNA-seq) identifies that transplanted omental adipocytes undergo extensive dedifferentiation and functionally integrate into the wound bed. Strikingly, these cells shed their adipogenic identity and are reprogrammed into a pro-angiogenic myeloid phenotype to orchestrate tissue remodeling. Mechanistically, Pparγ downregulation acts as a prerequisite for dedifferentiation, while Cebpβ drives transdifferentiation toward a myeloid fate. Importantly, inhibiting this plasticity by sustaining Pparγ activity impairs regenerative outcomes. These findings reveal that depot-specific omental adipocytes serve as a non-canonical macrophage source that orchestrates vascular assembly via lineage plasticity, highlighting a therapeutic avenue for enhancing tissue repair. Biological sciences/Developmental biology/Transdifferentiation Biological sciences/Stem cells/Reprogramming greater omentum adipocyte plasticity angiogenesis tissue repair Full Text Additional Declarations (Not answered) Supplementary Files KeyResourcesTable.docx Key Resources Table Originalwesternblots1.png Original western blots 1 Originalwesternblots2.png Original western blots 2 ajchecklist.pdf checklist SupplementalMaterial.docx Supplemental Figure AnimalWelfareandEthics.pdf Animal Welfare and Ethics Cite Share Download PDF Status: Under Review Version 1 posted Review # 1 received at journal 06 May, 2026 Reviewer # 2 agreed at journal 29 Apr, 2026 Reviewer # 1 agreed at journal 29 Apr, 2026 Reviewers invited by journal 28 Apr, 2026 Submission checks completed at journal 13 Apr, 2026 Editor assigned by journal 13 Apr, 2026 First submitted to journal 13 Apr, 2026 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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