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p57Kip2 imposes the reserve stem cell state of gastric chief cells

Published version
Peer-reviewed

Type

Article

Change log

Authors

Simons, Ben 

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 mouse. 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 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.

Description

Keywords

Gif, Lgr5, Troy, base stem cells, gastric chief cells, p57, reserve stem cells, scRNA-seq, stem cell quiescence, stomach, Animals, Cell Lineage, Chief Cells, Gastric, Cyclin-Dependent Kinase Inhibitor p57, Mice, Organoids, Stem Cells, Stomach

Journal Title

Cell Stem Cell

Conference Name

Journal ISSN

1934-5909
1875-9777

Volume Title

Publisher

Elsevier
Sponsorship
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (098357/Z/12/Z)
European Research Council (639050)
Cancer Research UK (A25636)
Wellcome Trust (212253/Z/18/Z)
Medical Research Council (MC_PC_17230)
Wellcome Trust (219478/Z/19/Z)
Cancer Research UK (25636)