BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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.
Authors: Jeanmarie Houghton; Calin Stoicov; Sachiyo Nomura; Arlin B Rogers; Jane Carlson; Hanchen Li; Xun Cai; James G Fox; James R Goldenring; Timothy C Wang Journal: Science Date: 2004-11-26 Impact factor: 47.728
Authors: Wensheng Lin; April Kemper; Ken D McCarthy; Peter Pytel; Jian-Ping Wang; Iain L Campbell; Manuel F Utset; Brian Popko Journal: J Neurosci Date: 2004-11-10 Impact factor: 6.167
Authors: Rupesh Chaturvedi; Mohammad Asim; Judith Romero-Gallo; Daniel P Barry; Svea Hoge; Thibaut de Sablet; Alberto G Delgado; Lydia E Wroblewski; M Blanca Piazuelo; Fang Yan; Dawn A Israel; Robert A Casero; Pelayo Correa; Alain P Gobert; D Brent Polk; Richard M Peek; Keith T Wilson Journal: Gastroenterology Date: 2011-08-10 Impact factor: 22.682
Authors: Elise S Demitrack; Gail B Gifford; Theresa M Keeley; Alexis J Carulli; Kelli L VanDussen; Dafydd Thomas; Thomas J Giordano; Zhenyi Liu; Raphael Kopan; Linda C Samuelson Journal: EMBO J Date: 2015-08-12 Impact factor: 11.598