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Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells.


ABSTRACT: Lifelong self-renewal of the adult intestinal epithelium requires the activity of stem cells located in mucosal crypts. Lgr5 and Bmi1 are two molecular markers of crypt-cell populations that replenish all lineages over time and hence function as stem cells. Intestinal stem cells require Wnt signaling, but the understanding of their cellular niche is incomplete. Lgr5-expressing crypt base columnar cells (CBCs) reside deep in the crypt, mingled among mature Paneth cells that are well positioned for short-range signaling. Partial lineage ablation previously had implied that Paneth cells are nonessential constituents of the stem-cell niche, but recently their absence was reported to interfere with Lgr5(+) CBCs, resurrecting an appealing idea. However, previous mouse models failed to remove Paneth cells completely or permanently; defining the intestinal stem-cell niche requires clarity with respect to the Paneth cell role. We find that Lgr5(+) cells with stem-cell activity cluster in future crypts early in life, before Paneth cells develop. We also crossed conditional Atoh1(-/-) mice, which lack Paneth cells entirely, with Lgr5(GFP) mice to visualize Lgr5(+) CBCs and to track their stem-cell function. In the sustained absence of Paneth cells, Lgr5(+) CBCs occupied the full crypt base, proliferated briskly, and generated differentiated progeny over many months. Gene expression in fluorescence-sorted Lgr5(+) CBCs reflected intact Wnt signaling despite the loss of Paneth cells. Thus, Paneth cells are dispensable for survival, proliferation, and stem-cell activity of CBCs, and direct contact with Lgr5-nonexpressing cells is not essential for CBC function.

SUBMITTER: Kim TH 

PROVIDER: S-EPMC3309789 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells.

Kim Tae-Hee TH   Escudero Silvia S   Shivdasani Ramesh A RA  

Proceedings of the National Academy of Sciences of the United States of America 20120221 10


Lifelong self-renewal of the adult intestinal epithelium requires the activity of stem cells located in mucosal crypts. Lgr5 and Bmi1 are two molecular markers of crypt-cell populations that replenish all lineages over time and hence function as stem cells. Intestinal stem cells require Wnt signaling, but the understanding of their cellular niche is incomplete. Lgr5-expressing crypt base columnar cells (CBCs) reside deep in the crypt, mingled among mature Paneth cells that are well positioned fo  ...[more]

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