{
  "abstract": "Given its 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, namely, 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-positive esophageal stem cells compared to Krt15-negative 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 tricarboxylic acid cycle and biosynthetic pathways. In conclusion, these results showed that Msh2 is implicated in the homeostasis of esophageal organoids, potentially through metabolic rewiring.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1E 4K8, Canada",
    "Centre de Recherche du Centre Hospitalier de l'Université de Sherbrooke (CRCHUS), Sherbrooke, J1H 5N4, Canada",
    "Institut de Recherche sur le Cancer de l'Université de Sherbrooke (IRCUS), Sherbrooke, J1E 4K8, Canada",
    "Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, G1V 0A6, Canada",
    "Endocrinology – Nephrology Axis, CHU de Québec-Université Laval Research Center, Québec, G1V 4G2, Canada"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Marjorie Rolland"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Dominique Jean"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Maude Hamilton"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Molly Sedeuil"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Alexis Gonneaud"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Line Berthiaume"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Étienne Audet-Walsh"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Véronique Giroux",
      "orcid": "0000-0002-3722-6447"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3td6aqdwgjtvg.bib",
  "cited_by": 0,
  "doi": "10.1242/jcs.264470",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723390/",
  "id": "3td6aqdwgjtvg",
  "issns": [
    "0021-9533",
    "1477-9137"
  ],
  "landing_url": "https://doi.org/10.1242/jcs.264470",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2730|Cancer Cells and Metastasis"
    ]
  ],
  "openalex": "W7171708888",
  "pdf_url": null,
  "pmcid": "PMC13723390",
  "pmid": "42522328",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3td6aqdwgjtvg.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:02Z",
      "native_id": "PMC13723390",
      "source": "pmc",
      "url": "https://doi.org/10.1242/jcs.264470"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Cells and Metastasis",
      "subfield": "oncology"
    }
  ],
  "title": "Msh2 depletion impairs cell differentiation, proliferation and metabolism in esophageal organoids",
  "title_text": "Msh2 depletion impairs cell differentiation, proliferation and metabolism in esophageal organoids",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:13Z",
  "url": "https://research.draconitic.com/paper/3td6aqdwgjtvg",
  "venue": "Journal of Cell Science",
  "versions": []
}