Ex Vivo Expansion of Human Serial Transplantable Haematopoietic Stem Cells

Ex Vivo Expansion of Human Serial Transplantable Haematopoietic Stem Cells | 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 Ex Vivo Expansion of Human Serial Transplantable Haematopoietic Stem Cells Linheng Li, Xinjian Mao, Ning Zhang, Xi He, Ruochen Dong, Zhe Yang, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6149433/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The scarcity of haematopoietic stem cells (HSCs) limits clinical HSC transplantation, a curative therapy for various blood disorders. Although substantial advances have been made in the ex vivo expansion of HSCs, the expansion of long-term (LT-) HSCs capable of sustaining serial and multilineage engraftment remains an unmet challenge. Here, we present a culture system that couples intrinsic HSC programming with extrinsic bone marrow (BM) niche factors to sustain human umbilical cord blood (UCB) and BM-derived LT-HSCs ex vivo. This platform, in combination with pyrimidoindole derivative UM729, synergistically expands LT-HSCs while preserving balanced multilineage potential, as validated against fresh UCB controls. Single-cell multiome sequencing revealed that this system preserves HSC identity at transcriptional and epigenetic levels. Furthermore, we identified correlations between transcriptional and epigenetic signatures in HSCs and their transplantation outcomes, suggesting their potential for prospectively assessing HSC functionality and heterogeneity. This platform and framework advance HSC biology with clinical implications. Biological sciences/Stem cells/Haematopoietic stem cells Biological sciences/Biotechnology/Stem-cell biotechnology Full Text Additional Declarations Yes there is potential Competing Interest. A patent application on the HSPC expansion has been filed by the Stowers Institute. C.H. is a scientific founder, a member of the scientific advisory board and equity holder of Aferna Bio and Ellis Bio, a scientific cofounder and equity holder of Accent Therapeutics and a member of the scientific advisory board of Rona Therapeutics and Element Biosciences. IACUC All mice used in this study were housed in the AAALAC-accredited animal facility at the Stowers Institute for Medical Research (SIMR) and handled according to SIMR and National Institutes of Health (NIH) guidelines. All procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of SIMR. IRB Since we used commercial provided umbilical cord blood and deidentified bone marrow cells vis KUMC tissue bank. There is a need of IRB. Cite Share Download PDF Status: Posted 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-6149433","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":427330093,"identity":"dda7aa8b-9fbc-4f14-ad49-b199e76ff3f0","order_by":0,"name":"Linheng 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