MEGF10 Accelerates a Developing Niche to Improve Engrafted Progenitor Cell Retention in Dystrophic and Regenerating Skeletal Muscle

MEGF10 Accelerates a Developing Niche to Improve Engrafted Progenitor Cell Retention in Dystrophic and Regenerating Skeletal Muscle | 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 MEGF10 Accelerates a Developing Niche to Improve Engrafted Progenitor Cell Retention in Dystrophic and Regenerating Skeletal Muscle Michael Hicks, Benjamin Clock, Sebastien Colobong, Nikitha Pavar, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9408825/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Skeletal muscle cell therapies are limited by poor long-term engraftment, particularly in diseased muscle, where retention of a PAX7+ stem cell pool depends on formation of a supportive niche. Here, we used spatial transcriptomics to map niche development across engraftment time, healthy versus dystrophic microenvironments, and secondary injury. Engrafted myogenic cells underwent rapid early transcriptional remodeling and marked donor-cell loss, whereas regenerating myofibers acquired niche-associated programs that stabilized surviving PAX7+ cells. Dystrophic microenvironments impaired niche maturation, altered donor-cell state, and blunted regenerative adaptation after reinjury. MEGF10 emerged as an early niche-associated regulator that was transiently expressed during healthy regeneration but persisted in dystrophic muscle. Using CRISPR-engineered hPSC models, we found that MEGF10 induction during the first 10 days after transplantation more than doubled PAX7+ cell retention and donor-derived myofiber output, whereas MEGF10 loss of function, which models a severe early onset myopathy, failed to maintain engrafted PAX7+ cells. Spatial profiling of Tet-On engraftments identified a MEGF10-responsive regenerative myofiber program linked to early niche support. These findings define an early therapeutic window for improving muscle cell transplantation. Biological sciences/Stem cells/Regeneration Biological sciences/Stem cells/Muscle stem cells Biological sciences/Biological techniques/Genetic engineering Biological sciences/Developmental biology/Stem-cell niche Full Text Additional Declarations There is NO Competing Interest. Supplementary Files EXTENDEDMETHODS.pdf Extended Methods TableS1.xlsx Table S1 TableS2.xlsx Table S2 TableS3.xlsx Table S3 TableS4.xlsx Table S4 Cite Share Download PDF Status: Under Review 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-9408825","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":624022033,"identity":"72e7bda6-207a-419c-8a0e-7f81f5c421fb","order_by":0,"name":"Michael 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