Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro.
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.
Barker
Nick
N
Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht & University Medical Centre Utrecht, Netherlands.
Huch
Meritxell
M
Kujala
Pekka
P
van de Wetering
Marc
M
Snippert
Hugo J
HJ
van Es
Johan H
JH
Sato
Toshiro
T
Stange
Daniel E
DE
Begthel
Harry
H
van den Born
Maaike
M
Danenberg
Esther
E
van den Brink
Stieneke
S
Korving
Jeroen
J
Abo
Arie
A
Peters
Peter J
PJ
Wright
Nick
N
Poulsom
Richard
R
Clevers
Hans
H
D000375:Aging; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D005753:Gastric Mucosa / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D013270:Stomach / Q000737:chemistry / Q000166:cytology*
D015415:Biomarkers; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled