TY - JOUR
T1 - Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro
AU - Barker, Nick
AU - Huch, Meritxell
AU - Kujala, Pekka
AU - van de Wetering, Marc
AU - Snippert, Hugo J.
AU - van Es, Johan H.
AU - Sato, Toshiro
AU - Stange, Daniel E.
AU - Begthel, Harry
AU - van den Born, Maaike
AU - Danenberg, Esther
AU - van den Brink, Stieneke
AU - Korving, Jeroen
AU - Abo, Arie
AU - Peters, Peter J.
AU - Wright, Nick
AU - Poulsom, Richard
AU - Clevers, Hans
N1 - Funding Information:
N.B. and H.C. are supported by KWF program grant # PF-HUBR-2007-3956. M.H. is supported by an Intra-European Fellowship from Marie Curie Actions-European commission. We thank Rob Vries for help with the BrdU injections and Nico Ong for help with EM imaging and Ramesh Shivdasani for providing reagents.
PY - 2010/1/8
Y1 - 2010/1/8
N2 - The study of gastric epithelial homeostasis and cancer has been hampered by the lack of stem cell markers and in vitro culture methods. The Wnt 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.
AB - The study of gastric epithelial homeostasis and cancer has been hampered by the lack of stem cell markers and in vitro culture methods. The Wnt 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.
KW - STEMCELL
UR - http://www.scopus.com/inward/record.url?scp=73049116186&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73049116186&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2009.11.013
DO - 10.1016/j.stem.2009.11.013
M3 - Article
C2 - 20085740
AN - SCOPUS:73049116186
SN - 1934-5909
VL - 6
SP - 25
EP - 36
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 1
ER -
