单个Lgr5干细胞在体外无需间充质微环境即可构建隐窝-绒毛结构。
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.
作者信息
Sato Toshiro, Vries Robert G, Snippert Hugo J, van de Wetering Marc, Barker Nick, Stange Daniel E, van Es Johan H, Abo Arie, Kujala Pekka, Peters Peter J, Clevers Hans
机构信息
Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
出版信息
Nature. 2009 May 14;459(7244):262-5. doi: 10.1038/nature07935. Epub 2009 Mar 29.
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.
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,在小肠隐窝底部存在约六个循环的Lgr5(+)干细胞。在此,我们描述了长期培养条件的建立,在此条件下,单个隐窝经历多次隐窝分裂事件,同时产生包含所有分化细胞类型的绒毛样上皮结构域。单个分选的Lgr5(+)干细胞也可以启动这些隐窝-绒毛类器官。追踪实验表明,类器官中Lgr5(+)干细胞层级得以维持。我们得出结论,肠隐窝-绒毛单元是自组织结构,在没有非上皮细胞微环境的情况下,可以由单个干细胞构建而成。