ZMAT3 alleviates cell death of Fanconi Anemia deficient cells by modulating sphingolipid metabolism and ferroptosis.

ZMAT3 alleviates cell death of Fanconi Anemia deficient cells by modulating sphingolipid metabolism and ferroptosis. | 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 ZMAT3 alleviates cell death of Fanconi Anemia deficient cells by modulating sphingolipid metabolism and ferroptosis. Dominique BLUTEAU, Maeva LOOCK, Emmanuelle LATOUR, Carele FEDRONIE, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4668683/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 Fanconi Anemia (FA) is a genetic disorder marked by bone marrow failure and cancer risk. FA features continuous activation of the p53 pathway, leading to an exacerbated cellular response to stress and DNA damage and significantly altering cellular metabolism. Here, we pointed out for the first time the overexpression of ZMAT3, an RNA-binding protein, in murine FA-deficient hematopoietic cells. To elucidate the functions of ZMAT3 in the context of FA, we employed a two-pronged experimental approach. Initially, hematopoietic stem cells from FA knockout (FA-KO) mice with targeted downregulation of ZMAT3 and a human fibroblast cell line derived from an FA patient. Combining functional and Omics approaches, our study uncovers the critical involvement of ZMAT3 in enhancing the survival of FA-deficient cells by modulating sphingolipid metabolism and ferroptosis. ZMAT3 emerges as a pivotal factor in mitigating hematopoietic stem cell exhaustion during the initial stages of FA. Biological sciences/Cell biology/Mechanisms of disease Health sciences/Diseases/Haematological diseases/Anaemia Full Text Additional Declarations There is NO Competing Interest. 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. 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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-4668683","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":331286011,"identity":"d9d6b6d1-f1a7-4ceb-9338-ab8e550152bd","order_by":0,"name":"Dominique BLUTEAU","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-6530-2363","institution":"EPHE, Ecole Pratique des Hautes Etudes, PSL university","correspondingAuthor":true,"prefix":"","firstName":"Dominique","middleName":"","lastName":"BLUTEAU","suffix":""},{"id":331286012,"identity":"0fe22e56-4cd3-4655-aad2-c3adb861d90f","order_by":1,"name":"Maeva LOOCK","email":"","orcid":"","institution":"UMR9019 CNRS, Gustave Roussy cancer campus, Villejuif.","correspondingAuthor":false,"prefix":"","firstName":"Maeva","middleName":"","lastName":"LOOCK","suffix":""},{"id":331286014,"identity":"c5819e43-176d-436c-9e99-d2e859c219c1","order_by":2,"name":"Emmanuelle LATOUR","email":"","orcid":"","institution":"U944/UMR7212 INSERM/CNRS, Saint-Louis Hospital.","correspondingAuthor":false,"prefix":"","firstName":"Emmanuelle","middleName":"","lastName":"LATOUR","suffix":""},{"id":331286016,"identity":"e56f0b7e-669b-4a86-b2cd-50e1f96e7e94","order_by":3,"name":"Carele FEDRONIE","email":"","orcid":"","institution":"U944/UMR7212 INSERM/CNRS, Saint-Louis Hospital.","correspondingAuthor":false,"prefix":"","firstName":"Carele","middleName":"","lastName":"FEDRONIE","suffix":""},{"id":331286017,"identity":"b9164bbe-8592-448f-aebe-cfa531a1c1a9","order_by":4,"name":"Margot TISSANDIER","email":"","orcid":"","institution":"UMR9019 CNRS, Gustave Roussy cancer campus, Villejuif.","correspondingAuthor":false,"prefix":"","firstName":"Margot","middleName":"","lastName":"TISSANDIER","suffix":""},{"id":331286018,"identity":"e876eb42-75eb-4d04-9daa-c2e3a32c3552","order_by":5,"name":"Lucie HERNANDEZ","email":"","orcid":"","institution":"U944/UMR7212 INSERM/CNRS, Saint-Louis Hospital.","correspondingAuthor":false,"prefix":"","firstName":"Lucie","middleName":"","lastName":"HERNANDEZ","suffix":""},{"id":331286020,"identity":"73c7a392-7500-4862-9709-f51f70cf5c5b","order_by":6,"name":"Marie LHOMME","email":"","orcid":"","institution":"IHU-ICAN, Foundation for Innovation in Cardiometabolism and Nutrition","correspondingAuthor":false,"prefix":"","firstName":"Marie","middleName":"","lastName":"LHOMME","suffix":""},{"id":331286021,"identity":"1bb50b48-a591-49bf-9355-338e1ece556f","order_by":7,"name":"Maharajah PONNAIAH","email":"","orcid":"https://orcid.org/0000-0001-7761-4228","institution":"IHU-ICAN, Foundation for Innovation in Cardiometabolism and Nutrition","correspondingAuthor":false,"prefix":"","firstName":"Maharajah","middleName":"","lastName":"PONNAIAH","suffix":""},{"id":331286022,"identity":"b2702125-1eda-482b-8bd9-a1df0fbfb6db","order_by":8,"name":"Julie LEFRANCOIS","email":"","orcid":"","institution":"U944/UMR7212 INSERM/CNRS, Saint-Louis Hospital.","correspondingAuthor":false,"prefix":"","firstName":"Julie","middleName":"","lastName":"LEFRANCOIS","suffix":""},{"id":331286023,"identity":"a6440dca-475f-4c70-91b3-7262857368a5","order_by":9,"name":"Loïc Maillard","email":"","orcid":"","institution":"INSERM U1131","correspondingAuthor":false,"prefix":"","firstName":"Loïc","middleName":"","lastName":"Maillard","suffix":""},{"id":331286024,"identity":"c24a0615-4557-445d-8937-8e5eff1ad99a","order_by":10,"name":"Samuel Quentin","email":"","orcid":"","institution":"AP-HP - inserm - cnrs","correspondingAuthor":false,"prefix":"","firstName":"Samuel","middleName":"","lastName":"Quentin","suffix":""},{"id":331286025,"identity":"fc801aaf-2f19-434d-bb0e-6ec6b20cf40d","order_by":11,"name":"veronique parietti","email":"","orcid":"","institution":"Département d’Expérimentation Animale, Institut Universitaire d’Hématologie, Paris, France ; 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