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

被引:5797
作者
Sato, Toshiro [1 ,2 ]
Vries, Robert G. [1 ,2 ]
Snippert, Hugo J. [1 ,2 ]
van de Wetering, Marc [1 ,2 ]
Barker, Nick [1 ,2 ]
Stange, Daniel E. [1 ,2 ]
van Es, Johan H. [1 ,2 ]
Abo, Arie [3 ]
Kujala, Pekka [4 ]
Peters, Peter J. [4 ]
Clevers, Hans [1 ,2 ]
机构
[1] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands
[3] Nuvelo Inc, San Carlos, CA 94070 USA
[4] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands
关键词
SMALL-INTESTINE; EPITHELIAL-CELLS; EXPRESSION; DIFFERENTIATION; PROLIFERATION; INHIBITION; CULTURES; GROWTH; COLON; MICE;
D O I
10.1038/nature07935
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr(5+) stem cells at the bottoms of small-intestinal crypts(1). 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 Lgr(5+) stem cells can also initiate these crypt-villus organoids. Tracing experiments indicate that the Lgr(5+) 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.
引用
收藏
页码:262 / U147
页数:5
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