{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:59:28Z","timestamp":1785311968870,"version":"3.55.0"},"reference-count":0,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","award":["178171"],"award-info":[{"award-number":["178171"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"crossref","award":["06185"],"award-info":[{"award-number":["06185"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Due to a rapid cell turnover, the esophageal stratified squamous epithelium must maintain homeostasis. This process is ensured by a long-lived subpopulation of basal stem cells that express Keratin 15 (Krt15). However, the mechanisms that specifically control their characteristics, i.e. self-renewal, multipotency and regeneration, remain unknown. Interestingly, MutS Homolog 2 (Msh2), implicated in the DNA mismatch repair pathway, is the most upregulated gene in Krt15+ esophageal stem cells compared to Krt15- cells. Accentuated DNA repair capacity is often observed in stem cells to maintain their genomic integrity and avoid the acquisition of mutations. Hence, this study aimed to evaluate the effects of Msh2 loss on stem cell functions, including differentiation, clonogenicity, and proliferation, in murine esophageal organoids. Msh2-depleted organoids were generated by CRISPR\/Cas9. They displayed morphogenic alterations and significant homeostasis perturbations. Cell differentiation was decreased while clonogenicity and proliferation were increased. Loss of Msh2 also caused lower expression of stem cell markers and changes in response to chemotherapy drugs. Proteomic analysis confirmed variations in epithelial cell differentiation and showed major changes in proteins associated with metabolic processes. In line with these results, metabolomic analysis confirmed an altered abundance of various metabolites of the TCA cycle and biosynthetic pathways. In conclusion, these results showed that Msh2 is implicated in the homeostasis of esophageal organoids, potentially through metabolic rewiring.<\/jats:p>","DOI":"10.1242\/jcs.264470","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:01:31Z","timestamp":1785308491000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Msh2<\/i>\n                    depletion impairs cell differentiation, proliferation and metabolism in esophageal organoids"],"prefix":"10.1242","author":[{"given":"Marjorie","family":"Rolland","sequence":"first","affiliation":[{"name":"1 Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Canada"},{"name":"2 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Sherbrooke (CRCHUS), Sherbrooke, Canada"},{"name":"3 Institut de Recherche sur le Cancer de l'Universit\u00e9 de Sherbrooke (IRCUS), Sherbrooke, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Jean","sequence":"additional","affiliation":[{"name":"1 Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Canada"},{"name":"2 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Sherbrooke (CRCHUS), Sherbrooke, Canada"},{"name":"3 Institut de Recherche sur le Cancer de l'Universit\u00e9 de Sherbrooke (IRCUS), Sherbrooke, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maude","family":"Hamilton","sequence":"additional","affiliation":[{"name":"1 Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Canada"},{"name":"2 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Sherbrooke (CRCHUS), Sherbrooke, Canada"},{"name":"3 Institut de Recherche sur le Cancer de l'Universit\u00e9 de Sherbrooke (IRCUS), Sherbrooke, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Sedeuil","sequence":"additional","affiliation":[{"name":"1 Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Canada"},{"name":"2 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Sherbrooke (CRCHUS), Sherbrooke, Canada"},{"name":"3 Institut de Recherche sur le Cancer de l'Universit\u00e9 de Sherbrooke (IRCUS), Sherbrooke, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Gonneaud","sequence":"additional","affiliation":[{"name":"1 Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Canada"},{"name":"2 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Sherbrooke (CRCHUS), Sherbrooke, Canada"},{"name":"3 Institut de Recherche sur le Cancer de l'Universit\u00e9 de Sherbrooke (IRCUS), Sherbrooke, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Berthiaume","sequence":"additional","affiliation":[{"name":"4 Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, Canada"},{"name":"5 Endocrinology \u2013 Nephrology Axis, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9tienne","family":"Audet-Walsh","sequence":"additional","affiliation":[{"name":"4 Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, Canada"},{"name":"5 Endocrinology \u2013 Nephrology Axis, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3722-6447","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Giroux","sequence":"additional","affiliation":[{"name":"1 Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Canada"},{"name":"2 Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Sherbrooke (CRCHUS), Sherbrooke, Canada"},{"name":"3 Institut de Recherche sur le Cancer de l'Universit\u00e9 de Sherbrooke (IRCUS), Sherbrooke, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,7,29]]},"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.264470\/3710670\/jcs264470.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.264470\/3710670\/jcs264470.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:01:32Z","timestamp":1785308492000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/doi\/10.1242\/jcs.264470\/372421\/Msh2-depletion-impairs-cell-differentiation"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1242\/jcs.264470","relation":{},"ISSN":["0021-9533","1477-9137"],"issn-type":[{"value":"0021-9533","type":"print"},{"value":"1477-9137","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"article-number":"jcs.264470"}}