| Literature DB >> 35523142 |
Ji-Hyun Lee1, Somi Kim2, Seungmin Han3, Jimin Min4, Brianna Caldwell4, Aileen-Diane Bamford1, Andreia Sofia Batista Rocha1, JinYoung Park1, Sieun Lee1, Szu-Hsien Sam Wu1, Heetak Lee1, Juergen Fink5, Sandra Pilat-Carotta1, Jihoon Kim6, Manon Josserand5, Réka Szep-Bakonyi1, Yohan An7, Young Seok Ju7, Anna Philpott8, Benjamin D Simons9, Daniel E Stange10, Eunyoung Choi11, Bon-Kyoung Koo12, Jong Kyoung Kim13.
Abstract
Adult stem cells constantly react to local changes to ensure tissue homeostasis. In the main body of the stomach, chief cells produce digestive enzymes; however, upon injury, they undergo rapid proliferation for prompt tissue regeneration. Here, we identified p57Kip2 (p57) as a molecular switch for the reserve stem cell state of chief cells in mice. During homeostasis, p57 is constantly expressed in chief cells but rapidly diminishes after injury, followed by robust proliferation. Both single-cell RNA sequencing and dox-induced lineage tracing confirmed the sequential loss of p57 and activation of proliferation within the chief cell lineage. In corpus organoids, p57 overexpression induced a long-term reserve stem cell state, accompanied by altered niche requirements and a mature chief cell/secretory phenotype. Following the constitutive expression of p57 in vivo, chief cells showed an impaired injury response. Thus, p57 is a gatekeeper that imposes the reserve stem cell state of chief cells in homeostasis.Entities:
Keywords: Gif; Lgr5; Troy; base stem cells; gastric chief cells; p57; reserve stem cells; scRNA-seq; stem cell quiescence; stomach
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Year: 2022 PMID： 35523142 PMCID： PMC9097776 DOI： 10.1016/j.stem.2022.04.001
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 25.269