Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
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DOI：
10.1038/nature07935
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发表时间：
2009-05-14
期刊：
影响因子：
64.8
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
Sato, Toshiro;Vries, Robert G.;Clevers, Hans
肠上皮是成年哺乳动物中自我更新最快的组织。我们最近证明了在小肠隐窝底部存在约6个循环Lgr（5+）干细胞（1）。在这里，我们描述了建立长期的培养条件下，单隐窝经历多个隐窝分裂事件，同时错误地产生绒毛样上皮结构域中的所有分化的细胞类型存在。单个分选的Lgr（5+）干细胞也可以启动这些隐窝-绒毛类器官。示踪实验表明，Lgr（5+）干细胞层次结构在类器官中得以维持。我们的结论是，肠隐窝绒毛单位是自组织结构，它可以建立从一个单一的干细胞在没有一个非上皮细胞龛。
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.