Cep192 insufficiency underlies haploid instability in human cells

Cep192 insufficiency underlies haploid instability in human 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 Cep192 insufficiency underlies haploid instability in human cells Ryota Uehara, Koya Yoshizawa, Hemang Raj Singh, Kathirvel Paramasivam, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9217489/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 Mammalian somatic haploid cells offer advantages for genome engineering, yet rapid diploidization limits their utility. Here, we reveal that a haploidy-specific attenuation of mitotic spindle bipolarization, independent of previously characterized centrosome loss, underlies haploid instability in human cells. Comparative imaging and structure-function analyses demonstrate that the halved absolute dosage of the pericentriolar scaffolding protein Cep192 prevents its centrosomal accumulation to the threshold required for Aurora A–Eg5 axis. Consequently, haploids exhibit innate fragility in centrosome separation and spindle maintenance. Supplementing Cep192 restored spindle bipolarization to diploid levels and, when combined with genetic enhancement of the acentrosomal spindle pathway, profoundly stabilized the haploid state. Moreover, a genome-wide CRISPR-activation screen leveraging the above principle identified novel haploid-stabilizing genes, including the glutamate transporter SLC1A2. Our findings uncover an absolute-dosage scaling limit of mitotic scaffolding in haploids and establish genetic enhancement of spindle fidelity as an effective strategy for engineering stable animal haploid bioresources. Biological sciences/Cell biology/Cell division/Mitotic spindle Biological sciences/Cell biology/Cytoskeleton/Centrosome Biological sciences/Molecular biology/Cell division/Chromosome segregation Full Text Additional Declarations There is NO Competing Interest. Supplementary Files YHS2026DatasetS5.xlsx Dataset S5 SupplementalMaterialS1.zip Supplementary Material S1 YHS2026DatasetS4.xlsx Dataset S4 YHS2026DatasetS1.xlsx Dataset S1 YHS2026DatasetS2.xlsx Dataset S2 YHS2026DatasetS3.xlsx Dataset S3 SIYoshizawa2603252KYZ.docx Supplementary Information YHS2026DatasetS6.xlsx Dataset S6 SIYoshizawa2603252KYZ.pdf Supplementary Information (PDF version) 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-9217489","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":630077041,"identity":"7b05db47-e289-457f-b5ad-76fe02b80ba3","order_by":0,"name":"Ryota 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