Single-Cell Transcriptomic Insights into Conserved and Divergent Oligodendrocyte Lineage Programs Across Species

Single-Cell Transcriptomic Insights into Conserved and Divergent Oligodendrocyte Lineage Programs Across Species | 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 Single-Cell Transcriptomic Insights into Conserved and Divergent Oligodendrocyte Lineage Programs Across Species Fucheng Luo, Xi Han, Lingyan Zuo, Zhen Zhang, Yuanyi Yu, Qian Long, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7827530/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 Oligodendrocyte lineage cells (OLLCs) are essential for myelination and neural support, yet how their transcriptional programs are conserved or diverge across species remains unclear. We analyzed around one million hippocampal single-cell and single-nucleus transcriptomes from humans, cynomolgus macaques, rhesus macaques, and mice. OLLCs exhibited high transcriptional conservation, with precursor subtypes preserved but oligodendrocytes showing species-specific diversity. We identified primate-specific regulators such as CNDP1 and temporally shifted ETV1 expression, which were validated by immunofluorescence staining and qRT-PCR. Disease module analysis showed OLLCs provide a conserved substrate for brain aging and neurological disorders, with rhesus macaques displaying greater concordance with humans than cynomolgus macaques or mice. Analysis of OLLC aging trajectories identified primate-specific activation of Wnt pathways in oligodendrocyte precursor cell, contrasting with ribosomal enrichment in mice. These findings define conserved and divergent OLLC programs and underscore nonhuman primates—particularly rhesus macaques—as highly relevant translational models for human myelin biology. Biological sciences/Neuroscience/Glial biology/Oligodendrocyte Biological sciences/Neuroscience/Diseases of the nervous system oligodendrocyte myelin hippocampus nonhuman primate models single-cell transcriptomics rhesus macaques aging Full Text Additional Declarations There is NO Competing Interest. 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. 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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-7827530","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":540173971,"identity":"8918e924-2951-40a0-a8f2-a2d712c4fe89","order_by":0,"name":"Fucheng 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