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

T Sato, RG Vries, HJ Snippert, M Van De Wetering… - Nature, 2009 - nature.com
T Sato, RG Vries, HJ Snippert, M Van De Wetering, N Barker, DE Stange, JH Van Es, A Abo…
Nature, 2009nature.com
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 …
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.
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