XDifferentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium

Daniel E. Stange, Bon Kyoung Koo, Meritxell Huch, Greg Sibbel, Onur Basak, Anna Lyubimova, Pekka Kujala, Sina Bartfeld, Jan Koster, Jessica H. Geahlen, Peter J. Peters, Johan H. Van Es, Marc Van De Wetering, Jason C. Mills, Hans Clevers

Research output: Contribution to journalArticlepeer-review

339 Scopus citations

Abstract

Proliferation of the self-renewing epithelium of the gastric corpus occurs almost exclusively in the isthmus of the glands, from where cells migrate bidirectionally toward pit and base. The isthmus is therefore generally viewed as the stem cell zone. We find that the stem cell marker Troy is expressed at the gland base by a small subpopulation of fully differentiated chief cells. By lineage tracing with a Troy-eGFP-ires-CreERT2 allele, single marked chief cells are shown to generate entirely labeled gastric units over periods of months. This phenomenon accelerates upon tissue damage. Troy+ chief cells can be cultured to generate long-lived gastric organoids. Troy marks a specific subset of chief cells that display plasticity in that they are capable of replenishing entire gastric units, essentially serving as quiescent "reserve" stem cells. These observations challenge the notion that stem cell hierarchies represent a "one-way street."

Original languageEnglish
Pages (from-to)357
Number of pages1
JournalCell
Volume155
Issue number2
DOIs
StatePublished - Oct 10 2013

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