Human CD24+ dental papilla cells are highly competent seed cells for dentin-pulp regeneration via BMP2/SIRT1 metabolic axis

Human CD24+ dental papilla cells are highly competent seed cells for dentin-pulp regeneration via BMP2/SIRT1 metabolic axis | 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 Human CD24 + dental papilla cells are highly competent seed cells for dentin-pulp regeneration via BMP2/SIRT1 metabolic axis Tian Chen, Cheng Liang, Zhi Liu, Jie Li, Cong Han, Yu Gao, Bohuai Zhou, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7598595/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 Regeneration of the dentin-pulp complex is essential for the lifelong structural integrity and biological function of damaged teeth. However, the inherent heterogeneity of dental stem cells limits our understanding of lineage-specific subsets critical for efficient odontogenesis and regenerative outcomes. Here, we identify a distinct subpopulation of human dental papilla cells (hDPCs) marked by CD24 expression. CD24+ hDPCs exhibit robust odontogenic differentiation capacity, preferential localization in odontoblast-generating regions during tooth development, and accumulation beneath reparative dentin in carious teeth. Functionally, CD24+ hDPCs drive coordinated regeneration of well-vascularized pulp and structurally integrated dentin tissues in both ectopic murine and preclinical in situ minipig models, significantly outperforming conventional dental pulp stem cells. Mechanistically, we delineate a BMP2-driven metabolic axis where elevated BMP signaling sustains SIRT1 expression and promotes mitochondrial metabolism. Inhibition of BMP signaling disrupts this axis, resulting in WNT signaling activation, reduced SIRT1 expression, compromised antioxidant and autophagic responses, and consequently diminished odontogenic capacity. Furthermore, BMP signaling in CD24+ hDPCs induces VEGF expression, which enhances endothelial cell recruitment and neovascularization via paracrine effects. CD24 is also a downstream marker of odontogenic BMP signaling, reflecting BMP pathway activation and correlating with odontogenic potential, though it does not directly mediate differentiation. Together, our findings characterize CD24+ hDPCs as a regeneration-competent subpopulation that integrates mitochondrial metabolism and signaling crosstalk to enable coordinated dentin and pulp regeneration, representing a translationally relevant cell source for dental tissue engineering. Biological sciences/Stem cells/Regeneration Biological sciences/Stem cells/Embryonic stem cells Biological sciences/Cell biology Biological sciences/Stem cells/Stem-cell differentiation Full Text Additional Declarations There is NO Competing Interest. Supplementary Files NCSI.pdf Supplementary info 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7598595","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":515371072,"identity":"46050240-20cf-4adc-acf7-4926f04bc5db","order_by":0,"name":"Tian 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However, the inherent heterogeneity of dental stem cells limits our understanding of lineage-specific subsets critical for efficient odontogenesis and regenerative outcomes. Here, we identify a distinct subpopulation of human dental papilla cells (hDPCs) marked by CD24 expression. CD24+ hDPCs exhibit robust odontogenic differentiation capacity, preferential localization in odontoblast-generating regions during tooth development, and accumulation beneath reparative dentin in carious teeth. Functionally, CD24+ hDPCs drive coordinated regeneration of well-vascularized pulp and structurally integrated dentin tissues in both ectopic murine and preclinical in situ minipig models, significantly outperforming conventional dental pulp stem cells. Mechanistically, we delineate a BMP2-driven metabolic axis where elevated BMP signaling sustains SIRT1 expression and promotes mitochondrial metabolism. 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