p57Kip2 imposes the reserve stem cell state of gastric chief cells.

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. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Ji-Hyun Lee, Somi Kim, Seungmin Han, Jimin Min, Brianna Caldwell, Aileen-Diane Bamford, Andreia Sofia Batista Rocha, JinYoung Park, Sieun Lee, Szu-Hsien Sam Wu, Heetak Lee, Juergen Fink, Sandra Pilat-Carotta, Jihoon Kim, Manon Josserand, Réka Szep-Bakonyi, Yohan An, Young Seok Ju, Anna Philpott, Benjamin D Simons, Daniel E Stange, Eunyoung Choi, Bon-Kyoung Koo, Jong Kyoung Kim. p57Kip2 imposes the reserve stem cell state of gastric chief cells. Cell stem cell. 2022 May 05;29(5):826-839.e9

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PMID: 35523142

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