Prospective identification of a multilineage progenitor in murine stomach epithelium.
OBJECTIVE
Epithelial stem cells in the stomach are responsible for constant renewal of the epithelium through generation of multiple gastric cell lineages that populate the gastric glands. However, gastric stem or progenitor cells have not been well-characterized because of the lack of specific markers that permit their prospective recognition. We identified an intestinal promoter that is active in a rare subpopulation of gastric epithelial cells and investigated whether these cells possess multilineage potential.


METHODS
A marked allele of the endogenous mouse villin locus was used to visualize single beta-galactosidase-positive cells located in the lower third of antral glands. A 12.4-kb villin promoter/enhancer fragment drives several transgenes (EGFP, beta-galactosidase, and Cre recombinase) in these cells in a pattern similar to that of the marked villin allele. Reporter gene activity was used to track these cells during development and to examine cell number in the context of inflammatory challenge while Cre activity allowed lineage tracing in vivo.


RESULTS
We show that these rare epithelial cells are normally quiescent, but multiply in response to interferon gamma. Lineage tracing studies confirm that these cells give rise to all gastric lineages of the antral glands. In the embryo, these cells are located basally in the stomach epithelium before completion of gastric gland morphogenesis.


CONCLUSIONS
We have identified a rare subpopulation of gastric progenitors with multilineage potential. The ability to prospectively identify and manipulate such progenitors in situ represents a major step forward in gastric stem cell biology and has potential implications for gastric cancer.
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
Xiaotan T
XT
Qiao
Joshua W
JW
Ziel
Wendy
W
McKimpson
Blair B
BB
Madison
Andrea
A
Todisco
Juanita L
JL
Merchant
Linda C
LC
Samuelson
Deborah L
DL
Gumucio
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology*; D005753:Gastric Mucosa / Q000166:cytology*; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics; D023421:Models, Animal; D013234:Stem Cells / Q000166:cytology*
D008840:Microfilament Proteins; C026615:villin; D007371:Interferon-gamma