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

T. Sato; R.G.J. Vries; H.J.G. Snippert; M.L. van de Wetering; N. Barker; D.E. Stange; J.H. van Es; A. Abo; P. Kujala; P.J. Peters; H. Clevers

doi:10.1038/nature07935

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

T. Sato, R.G.J. Vries, H.J.G. Snippert, M.L. van de Wetering, N. Barker, D.E. Stange, J.H. van Es, A. Abo, P. Kujala, P.J. Peters, H. Clevers

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

5286 Citations (Scopus)

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 cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.

Original language	English
Pages (from-to)	262-265
Journal	Nature
Volume	459
Issue number	7244
DOIs	https://doi.org/10.1038/nature07935
Publication status	Published - 2009

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title = "Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.",

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 cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.",

author = "T. Sato and R.G.J. Vries and H.J.G. Snippert and {van de Wetering}, M.L. and N. Barker and D.E. Stange and {van Es}, J.H. and A. Abo and P. Kujala and P.J. Peters and H. Clevers",

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year = "2009",

doi = "10.1038/nature07935",

language = "English",

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journal = "Nature",

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TY - JOUR

T1 - Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.

AU - Sato, T.

AU - Vries, R.G.J.

AU - Snippert, H.J.G.

AU - van de Wetering, M.L.

AU - Barker, N.

AU - Stange, D.E.

AU - van Es, J.H.

AU - Abo, A.

AU - Kujala, P.

AU - Peters, P.J.

AU - Clevers, H.

N1 - Reporting year: 2009

PY - 2009

Y1 - 2009

N2 - 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 cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.

AB - 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 cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.

U2 - 10.1038/nature07935

DO - 10.1038/nature07935

M3 - Article

SN - 0028-0836

VL - 459

SP - 262

EP - 265

JO - Nature

JF - Nature

IS - 7244

ER -

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

Abstract

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