Fibroblast Dynamics and NR2F2 Pathway in the Development of Mouse Radiation Induced Skin Fibrosis

Fibroblast Dynamics and NR2F2 Pathway in the Development of Mouse Radiation Induced Skin Fibrosis | 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 Fibroblast Dynamics and NR2F2 Pathway in the Development of Mouse Radiation Induced Skin Fibrosis Derrick Wan, Darren Abbas, Michelle Griffin, Jason Guo, Charlotte Berry, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3874650/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Radiation induced skin fibrosis (RIF) is a debilitating sequela of radiation therapy. Fat grafting represents a primary therapeutic option, but its mechanism remains unknown. We aimed to delineate the cellular contributions to RIF and their part in the evolution of this disease. Furthermore, as fat grafting represents a therapeutic option employed clinically, we explored how this strategy may impact prevalence of various cellular subpopulations and pathways involved. C57BL/6J and Actin Cre / ROSA26 VT2/GK3 mice underwent radiation wounding and mice were euthanized at weeks 0, 2, 4, and 8 following radiation. Fibrosis had a temporal response from week 0 to 8 with progressive increases in dermal thickness and collagen density along with changes to extracellular matrix organization and loss of vascularity. Tissue-resident cells expanded clonally in response to radiation injury. With single cell RNA sequencing, five transcriptionally distinct fibroblast subpopulations were identified, creating the first murine atlas for RIF. Dynamic alterations in subpopulation prevalence were appreciated in fat grafted mice, and downregulation of the NR2F2 pathway was associated with improvement of RIF. Health sciences/Medical research/Translational research Health sciences/Diseases/Cancer/Cancer therapy/Radiotherapy Fibrosis radiation fibrosis skin fat grafting Nr2f2 pathway Full Text Additional Declarations (Not answered) Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: revise 05 Mar, 2024 Review # 3 received at journal 28 Feb, 2024 Review # 2 received at journal 20 Feb, 2024 Reviewer # 3 agreed at journal 16 Feb, 2024 Review # 1 received at journal 15 Feb, 2024 Reviewer # 2 agreed at journal 14 Feb, 2024 Reviewer # 1 agreed at journal 04 Feb, 2024 Reviewers invited by journal 04 Feb, 2024 Editor assigned by journal 18 Jan, 2024 Submission checks completed at journal 18 Jan, 2024 First submitted to journal 17 Jan, 2024 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-3874650","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":271023051,"identity":"abde284d-d24b-4a2e-908b-9d9f23bf4185","order_by":0,"name":"Derrick 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