Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts

被引：1875

作者：

Sato, Toshiro ^{[1
,2
]}

van Es, Johan H. ^{[1
,2
]}

Snippert, Hugo J. ^{[1
,2
]}

Stange, Daniel E. ^{[1
,2
]}

Vries, Robert G. ^{[1
,2
]}

van den Born, Maaike ^{[1
,2
]}

Barker, Nick ^{[1
,2
]}

Shroyer, Noah F. ^{[3
]}

van de Wetering, Marc ^{[1
,2
]}

Clevers, Hans ^{[1
,2
]}

机构：

[1] KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[3] Cincinnati Childrens Hosp, Div Gastroenterol, Med Ctr, MLC 2010, Cincinnati, OH 45229 USA

来源：

NATURE | 2011年 / 469卷 / 7330期

关键词：

BETA-CATENIN; ADULT-MOUSE; EPITHELIUM; DIFFERENTIATION; GENE; EXPRESSION; CANCER; MATH1; COLON; SOX9;

D O I：

10.1038/nature09637

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：

07 ; 0710 ; 09 ;

摘要：

Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms(1,2). Lgr5 stem cells are interspersed between terminally differentiated Paneth cells that are known to produce bactericidal products such as lysozyme and cryptdins/defensins(3). 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(4). 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-alpha, 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.

引用

页码：415 / +

页数：5

共 29 条

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