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p57Kip2 imposes the reserve stem cell state of gastric chief cells

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Title
p57Kip2 imposes the reserve stem cell state of gastric chief cells
Author(s)
Lee, Ji-Hyun; Kim, Somi; Han, Seungmin; Min, Jimin; Caldwell, Brianna; Bamford, Aileen-Diane; Rocha, Andreia Sofia Batista; Park, JinYoung; Lee, Sieun; Wu, Szu-Hsien Sam; Lee, Heetak; Fink, Juergen; Pilat-Carotta, Sandra; Kim, Jihoon; Josserand, Manon; Szep-Bakonyi, Réka; An, Yohan; Ju, Young Seok; Philpott, Anna; Simons, Benjamin D.; Stange, Daniel E.; Choi, Eunyoung; Bon-kyoung Koo; Kim, Jong Kyoung
Publication Date
2022-05
Journal
Cell Stem Cell, v.29, no.5, pp.826 - 839.e9
Publisher
Cell Press
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.
URI
https://pr.ibs.re.kr/handle/8788114/12301
DOI
10.1016/j.stem.2022.04.001
ISSN
1934-5909
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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