Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts.
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts.
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DOI：
10.1038/nature09637
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发表时间：
2011-01-20
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;van Es, Johan H.;Snippert, Hugo J.;Stange, Daniel E.;Vries, Robert G.;van den Born, Maaike;Barker, Nick;Shroyer, Noah F.;van de Wetering, Marc;Clevers, Hans
自我更新的小肠隐窝的稳态是由位于隐窝底部的Lgr 5干细胞（小循环细胞）之间的中性竞争引起的。Lgr 5干细胞散布在终末分化的潘氏细胞之间，已知潘氏细胞产生杀菌产物，如溶菌酶和cryptdins/防御素。单个Lgr 5表达干细胞可以在不存在非上皮小生境细胞的情况下培养以形成长寿命的自组织隐窝-绒毛类器官。在这里，我们注意到Lgr 5干细胞与潘氏细胞在体内和体外的密切物理联系。CD 24 + Paneth细胞表达EGF、TGFα、Wnt 3和Notch配体Dll 4，所有这些都是培养物中干细胞维持的必要信号。分选的干细胞与潘氏细胞的共培养显著改善了类器官形成。这种潘氏细胞的需求可以由外源性Wnt的脉冲替代。体内Paneth细胞的遗传去除导致Lgr 5干细胞的伴随损失。在结肠隐窝中，位于Lgr 5干细胞之间的CD 24+细胞可能代表潘氏细胞等同物。我们得出结论，LGR 5干细胞竞争的一个专门的子细胞，潘氏细胞提供的必要的利基信号。
Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, small cycling cells located at crypt bottoms. Lgr5 stem cells are interspersed between terminally differentiated Paneth cells, that are known to produce bactericidal products such as lysozyme and cryptdins/defensins. Single Lgr5-expressing stem cells can be cultured to form long-lived, self-organizing crypt-villus organoids in the absence of non-epithelial niche cells. Here, we note a close physical association of Lgr5 stem cells with Paneth cells in vivo and in vitro. CD24+ Paneth cells express EGF, TGFα, Wnt3 and the Notch-ligand Dll4, all essential signals for stem cell maintenance in culture. Co-culturing of sorted stem cells with Paneth cells dramatically improves organoid formation. This Paneth cell requirement can be substituted by a pulse of exogenous Wnt. Genetic removal of Paneth cells in vivo results in the concomitant loss of Lgr5 stem cells. In colon crypts, CD24+ cells residing between Lgr5 stem cells may represent the Paneth cell equivalents. We conclude that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell.
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