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dc.contributor.authorPhilpott, Anna
dc.contributor.authorSimons, Ben
dc.date.accessioned2022-06-24T23:30:12Z
dc.date.available2022-06-24T23:30:12Z
dc.date.issued2022-05-05
dc.identifier.issn1934-5909
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338349
dc.description.abstractAdult 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.
dc.publisherElsevier
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titlep57Kip2 imposes the reserve stem cell state of gastric chief cells
dc.typeArticle
dc.publisher.departmentoffice of The School of The Biological Sciences
dc.date.updated2022-04-21T14:03:41Z
prism.publicationNameCell Stem Cell
dc.identifier.doi10.17863/CAM.85758
dcterms.dateAccepted2022-04-01
rioxxterms.versionofrecord10.1016/j.stem.2022.04.001
rioxxterms.versionVoR
dc.contributor.orcidPhilpott, Anna [0000-0003-3789-2463]
dc.identifier.eissn1875-9777
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
pubs.funder-project-idWellcome Trust (098357/Z/12/Z)
pubs.funder-project-idEuropean Research Council (639050)
pubs.funder-project-idCancer Research UK (A25636)
pubs.funder-project-idWellcome Trust (212253/Z/18/Z)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
pubs.funder-project-idWellcome Trust (219478/Z/19/Z)
cam.issuedOnline2022-05-05
cam.depositDate2022-04-21
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International