Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro

被引：1269

作者：

Barker, Nick ^{[1
,2
]}

Huch, Meritxell ^{[1
,2
]}

Kujala, Pekka ^{[3
]}

van de Wetering, Marc ^{[1
,2
]}

Snippert, Hugo J. ^{[1
,2
]}

van Es, Johan H. ^{[1
,2
]}

Sato, Toshiro ^{[1
,2
]}

Stange, Daniel E. ^{[1
,2
]}

Begthel, Harry ^{[1
,2
]}

van den Born, Maaike ^{[1
,2
]}

Danenberg, Esther ^{[1
,2
]}

van den Brink, Stieneke ^{[1
,2
]}

Korving, Jeroen ^{[1
,2
]}

Abo, Arie ^{[4
]}

Peters, Peter J. ^{[3
,5
]}

Wright, Nick ^{[6
]}

Poulsom, Richard ^{[7
]}

Clevers, Hans ^{[1
,2
]}

机构：

[1] Hubrecht Inst Dev Biol & Stem Cell Res, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Utrecht, Netherlands

[3] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands

[4] Nuvelo Inc, San Carlos, CA 94070 USA

[5] Delft Univ Technol, Kavli Inst Nanosci, NL-2628 CJ Delft, Netherlands

[6] Barts & London Queen Marys Sch Med & Dent, London E1 2AD, England

[7] Canc Res UK London Res Inst, London WC2A 3PX, England

来源：

CELL STEM CELL | 2010年 / 6卷 / 01期

关键词：

EPITHELIAL-CELLS; MOUSE STOMACH; BETA-CATENIN; SMALL-INTESTINE; DYNAMICS; CANCER; CORPUS; IDENTIFICATION; ACTIVATION; MIGRATION;

D O I：

10.1016/j.stem.2009.11.013

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The study of gastric epithelial homeostasis and cancer has been hampered by the lack of stem cell markers and in vitro culture methods. The Writ target gene Lgr5 marks stem cells in the small intestine, colon, and hair follicle. Here, we investigated Lgr5 expression in the stomach and assessed the stem cell potential of the Lgr5(+ve) cells by using in vivo lineage tracing. In neonatal stomach, Lgr5 was expressed at the base of prospective corpus and pyloric glands, whereas expression in the adult was predominantly restricted to the base of mature pyloric glands. Lineage tracing revealed these Lgr5(+ve) cells to be self-renewing, multipotent stem cells responsible for the long-term renewal of the gastric epithelium. With an in vitro culture system, single Lgr5(+ve) cells efficiently generated long-lived organoids resembling mature pyloric epithelium. The Lgr5 stem cell marker and culture method described here will be invaluable tools for accelerating research into gastric epithelial renewal, inflammation/infection, and cancer.

引用

页码：25 / 36

页数：12

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