p57<SUP>Kip2</SUP> imposes the reserve stem cell state of gastric chief cells

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Ji-Hyun Lee - , Austrian Academy of Sciences (Author)
  • Somi Kim - , Pohang University of Science and Technology, Daegu Gyeongbuk Institute of Science and Technology (Author)
  • Seungmin Han - , University of Cambridge, Wellcome Sanger Institute (Author)
  • Jimin Min - , Vanderbilt University (Author)
  • Brianna Caldwell - , Vanderbilt University (Author)
  • Aileen-Diane Bamford - , Austrian Academy of Sciences (Author)
  • Andreia Sofia Batista Rocha - , Austrian Academy of Sciences (Author)
  • JinYoung Park - , Austrian Academy of Sciences (Author)
  • Sieun Lee - , Austrian Academy of Sciences (Author)
  • Szu-Hsien Sam Wu - , Austrian Academy of Sciences (Author)
  • Heetak Lee - , Austrian Academy of Sciences (Author)
  • Juergen Fink - , University of Cambridge (Author)
  • Sandra Pilat-Carotta - , Austrian Academy of Sciences (Author)
  • Jihoon Kim - , Austrian Academy of Sciences, Catholic University of Korea (Author)
  • Manon Josserand - , University of Cambridge (Author)
  • Reka Szep-Bakonyi - , Austrian Academy of Sciences (Author)
  • Yohan An - , Korea Advanced Institute of Science & Technology (KAIST) (Author)
  • Young Seok Ju - , Korea Advanced Institute of Science & Technology (KAIST) (Author)
  • Anna Philpott - , University of Cambridge (Author)
  • Benjamin D. Simons - , University of Cambridge, Wellcome Sanger Institute (Author)
  • Daniel E. Stange - , Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden (Author)
  • Eunyoung Choi - , Vanderbilt University (Author)
  • Bon-Kyoung Koo - , Austrian Academy of Sciences, Institute for Basic Science - Korea (IBS) (Author)
  • Jong Kyoung Kim - , Pohang University of Science and Technology, Daegu Gyeongbuk Institute of Science and Technology (Author)

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 p57(Kip2) (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.

Details

Original languageEnglish
Pages (from-to)826-+
Number of pages24
JournalCell Stem Cell
Volume29
Issue number5
Early online dateMay 2022
Publication statusPublished - 5 May 2022
Peer-reviewedYes

External IDs

PubMed 35523142
Scopus 85129641032

Keywords

Keywords

  • Rna-seq, Progenitor cells, Expression, Quiescence, Metaplasia, Regeneration, Signature, Lineages, Stomach, Atrophy