Metabolic Quadrivalency in RSeT Human Embryonic Stem Cells

Metabolic Quadrivalency in RSeT Human Embryonic 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 Metabolic Quadrivalency in RSeT Human Embryonic Stem Cells Kevin Chen, Kyeyoon Park, Dragan Maric, Kory Johnson, Pamela Robey, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4005405/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 One of the most important properties of human embryonic stem cells (hESCs) is related to their pluripotent states. In our recent study, we identified a previously unrecognized pluripotent state induced by RSeT medium. This state makes primed hESCs resistant to conversion to naïve pluripotent state. In this study, we have further characterized the metabolic features in these RSeT hESCs, including metabolic gene expression, metabolomic analysis, and various functional assays. The commonly reported metabolic modes include glycolysis or both glycolysis and oxidative phosphorylation (i.e., metabolic bivalency) in pluripotent stem cells. However, besides the presence of metabolic bivalency, RSeT hESCs exhibited a unique metabolome with additional fatty acid oxidation and imbalanced nucleotide metabolism. This metabolic quadrivalency is linked to hESC growth independent of oxygen tension and restricted capacity for naïve reprogramming in these cells. Thus, this study provides new insights into pluripotent state transitions and metabolic stress-associated hPSC growth in vitro. Biological sciences/Biochemistry/Metabolomics Biological sciences/Stem cells/Embryonic stem cells human pluripotent stem cells pluripotency RSeT medium metabolism Metabolomics hypoxia cell proliferation Figures Figure 1 Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplFig1ComprehensiveMetabolonpwys.tif Supplementary Dataset 1 SupplFig2primedvsRSeTnucleotide.tif Supplementary Dataset 2 SupplTable1Geneexpressionsignatures.pdf Supplementary Dataset 3 SupplTable2Metabolicgeneontology.xlsx Supplementary Dataset 4 SupplTable3Metabolonnormalizeddataset.xlsx Supplementary Dataset 5 SupplTable4Metabolicpathwayenrichment.xlsx Supplementary Dataset 6 Figure1to11.pdf 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-4005405","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":284395959,"identity":"f93059e2-2252-4a28-8dd5-1f90d3c94c92","order_by":0,"name":"Kevin 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