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Transcription factor achaete scute-like 2 controls intestinal stem cell fate.

Flier van der, L.G. and Gijn van, M.E. and Hatzis, P. and Kujala, P. and Haegebarth, A. and Stange, D.E. and Begthel, H.L. and Born van den, M.M.W. and Guryev, V. and Oving, I.M. and Es van, J.H. and Barker, N. and Peters, P.J. and Wetering van de, M.L. and Clevers, H. (2009) Transcription factor achaete scute-like 2 controls intestinal stem cell fate. Cell, 136, 903-12. ISSN 0092-8674.

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The small intestinal epithelium is the most rapidly self-renewing tissue of mammals. Proliferative cells are confined to crypts, while differentiated cell types predominantly occupy the villi. We recently demonstrated the existence of a long-lived pool of cycling stem cells defined by Lgr5 expression and intermingled with post-mitotic Paneth cells at crypt bottoms. We have now determined a gene signature for these Lgr5 stem cells. One of the genes within this stem cell signature is the Wnt target Achaete scute-like 2 (Ascl2). Transgenic expression of the Ascl2 transcription factor throughout the intestinal epithelium induces crypt hyperplasia and ectopic crypts on villi. Induced deletion of the Ascl2 gene in adult small intestine leads to disappearance of the Lgr5 stem cells within days. The combined results from these gain- and loss-of-function experiments imply that Ascl2 controls intestinal stem cell fate.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:6938
Deposited On:15 Dec 2009 01:00
Last Modified:10 Aug 2011 14:57

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