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

Nick Barker, Meritxell Huch, Pekka Kujala, Marc van de Wetering, Hugo J. Snippert, Johan H. van Es, Toshiro Sato, Daniel E. Stange, Harry Begthel, Maaike van den Born, Esther Danenberg, Stieneke van den Brink, Jeroen Korving, Arie Abo, Peter J. Peters, Nick Wright, Richard Poulsom, Hans Clevers

Research output: Contribution to journalArticle

843 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)25-36
Number of pages12
JournalCell stem cell
Volume6
Issue number1
DOIs
Publication statusPublished - 2010 Jan 8
Externally publishedYes

Keywords

  • STEMCELL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H. J., van Es, J. H., Sato, T., Stange, D. E., Begthel, H., van den Born, M., Danenberg, E., van den Brink, S., Korving, J., Abo, A., Peters, P. J., Wright, N., Poulsom, R., & Clevers, H. (2010). Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro. Cell stem cell, 6(1), 25-36. https://doi.org/10.1016/j.stem.2009.11.013