Transcription Factor Achaete Scute-Like 2 Controls Intestinal Stem Cell Fate

Laurens G. van der Flier, Marielle E. van Gijn, Pantelis Hatzis, Pekka Kujala, Andrea Haegebarth, Daniel E. Stange, Harry Begthel, Maaike van den Born, Victor Guryev, Irma Oving, Johan H. van Es, Nick Barker, Peter J. Peters, Marc van de Wetering, Hans Clevers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

580 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)903-912
Aantal pagina's10
TijdschriftCell
Volume136
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 6 mrt. 2009
Extern gepubliceerdJa

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