“潘氏细胞”(Paneth cells,即小肠上皮中的专门化细胞)已知通过生成杀菌化合物来保护干细胞。现在,研究人员又报告了它们的另一关键功能:它们为小肠中表达Lgr5的干细胞提供必要的生境信号(EGF/TGFα, Notch and Wnt)。表达Lgr5的多能干细胞产生全部的小肠上皮细胞类型,包括“潘氏细胞”在内,干细胞生境经常被看作是干细胞可向其迁移的预先存在的地点。这项工作表明,小肠干细胞从它们自己的后代获得生境支持。(生物谷Bioon.com)
生物谷推荐原文出处:
Nature doi:10.1038/nature09637
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Toshiro Sato,Johan H. van Es,Hugo J. Snippert,Daniel E. Stange,Robert G. Vries,Maaike van den Born,Nick Barker,Noah F. Shroyer,Marc van de Wetering& Hans Clevers
Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms1, 2. Lgr5 stem cells are interspersed between terminally differentiated Paneth cells that are known to produce bactericidal products such as lysozyme and cryptdins/defensins3. Single Lgr5-expressing stem cells can be cultured to form long-lived, self-organizing crypt–villus organoids in the absence of non-epithelial niche cells4. Here we find a close physical association of Lgr5 stem cells with Paneth cells in mice, both in vivo and in vitro. CD24+ Paneth cells express EGF, TGF-α, Wnt3 and the Notch ligand Dll4, all essential signals for stem-cell maintenance in culture. Co-culturing of sorted stem cells with Paneth cells markedly 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.