Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche

Toshiro Sato, Robert G. Vries, Hugo J. Snippert, Marc Van De Wetering, Nick Barker, Daniel E. Stange, Johan H. Van Es, Arie Abo, Pekka Kujala, Peter J. Peters, Hans Clevers

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Abstract

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr5 + stem cells at the bottoms of small-intestinal crypts. Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while simultanously generating villus-like epithelial domains in which all differentiated cell types are present. Single sorted Lgr5 + stem cells can also initiate these crypt-villus organoids. Tracing experiments indicate that the Lgr5 + stem-cell hierarchy is maintained in organoids. We conclude that intestinal crypt-villus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.

Original languageEnglish
Pages (from-to)262-265
Number of pages4
JournalNature
Volume459
Issue number7244
DOIs
Publication statusPublished - 2009 May 14
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Sato, T., Vries, R. G., Snippert, H. J., Van De Wetering, M., Barker, N., Stange, D. E., Van Es, J. H., Abo, A., Kujala, P., Peters, P. J., & Clevers, H. (2009). Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 459(7244), 262-265. https://doi.org/10.1038/nature07935