title: Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium.
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."
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, 3584 CT Utrecht, the Netherlands; Department of General, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, University of Dresden, 01307 Dresden, Germany.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Stange
authors.forename: Bon-Kyoung
authors.initials: BK
authors.lastname: Koo
authors.forename: Meritxell
authors.initials: M
authors.lastname: Huch
authors.forename: Greg
authors.initials: G
authors.lastname: Sibbel
authors.forename: Onur
authors.initials: O
authors.lastname: Basak
authors.forename: Anna
authors.initials: A
authors.lastname: Lyubimova
authors.forename: Pekka
authors.initials: P
authors.lastname: Kujala
authors.forename: Sina
authors.initials: S
authors.lastname: Bartfeld
authors.forename: Jan
authors.initials: J
authors.lastname: Koster
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Geahlen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Peters
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Es
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.forename: Jason C
authors.initials: JC
authors.lastname: Mills
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000818:Animals; D019070:Cell Lineage; D019872:Chief Cells, Gastric / Q000737:chemistry / Q000166:cytology*; D005753:Gastric Mucosa / Q000166:cytology; D051379:Mice; D009940:Organoids / Q000166:cytology; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D013234:Stem Cells / Q000166:cytology*; D013270:Stomach / Q000166:cytology*; D060449:Wnt Signaling Pathway
chemical_list: D018124:Receptors, Tumor Necrosis Factor; C409471:Tnfrsf19 protein, mouse