Evidence for extensive intercellular mRNA transfer in vertebrates

Evidence for extensive intercellular mRNA transfer in vertebrates | 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 Biological Sciences - Article Evidence for extensive intercellular mRNA transfer in vertebrates Xionglei He, Huimin Xiang, Shanjun Deng, Tianqi Cao, Di Zhang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6751746/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 It is generally believed that a cell’s mRNAs are transcribed from the cell’s own DNA. This view has, however, not been rigorously tested in multicellular organisms. We here designed an assay to quantify genome-wide intercellular mRNA transfer in vivo using chimeric zebrafish. By fusing early embryonic cells of two genetically distinct zebrafish lines (TU and TL), we created chimeric organisms in which the origin of mRNAs could be traced using divergent genomic sites between the TU and TL lines. Single-cell RNA sequencing the TL cells obtained from the chimeric organisms revealed an average of 5.8% (up to 15.7%) of the transcripts originating from TU cells, indicating widespread intercellular mRNA transfer. This transfer occurred in various cell types, exhibiting a bias toward highly expressed genes. Subsequent analyses showed that the transferred transcripts retained intact structure, and with normal biological functionality according to a Cre recombinase reporter system. Further, similar observations were made in chimeric mice, demonstrating evolutionary conservation of this phenomenon in both vertebrates. The results thus reveal unexpectedly strong intercellular mRNA transfer in vertebrates under normal physiological conditions, challenging current models of cellular autonomy in gene expression and suggesting novel biology in multicellular organisms for achieving cell-cell communication. Biological sciences/Genetics/Gene expression Biological sciences/Molecular biology/Transcriptomics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryFigs.pdf Supplementary Figures 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-6751746","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":470494048,"identity":"82df492b-be0a-4bd1-949b-6f78cfe2441e","order_by":0,"name":"Xionglei 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