PMID- 19269367 OWN - NLM STAT- MEDLINE DCOM- 20090327 LR - 20220316 IS - 1097-4172 (Electronic) IS - 0092-8674 (Linking) VI - 136 IP - 5 DP - 2009 Mar 6 TI - Transcription factor achaete scute-like 2 controls intestinal stem cell fate. PG - 903-12 LID - 10.1016/j.cell.2009.01.031 [doi] AB - 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. FAU - van der Flier, Laurens G AU - van der Flier LG AD - Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalaan, The Netherlands. FAU - van Gijn, Marielle E AU - van Gijn ME FAU - Hatzis, Pantelis AU - Hatzis P FAU - Kujala, Pekka AU - Kujala P FAU - Haegebarth, Andrea AU - Haegebarth A FAU - Stange, Daniel E AU - Stange DE FAU - Begthel, Harry AU - Begthel H FAU - van den Born, Maaike AU - van den Born M FAU - Guryev, Victor AU - Guryev V FAU - Oving, Irma AU - Oving I FAU - van Es, Johan H AU - van Es JH FAU - Barker, Nick AU - Barker N FAU - Peters, Peter J AU - Peters PJ FAU - van de Wetering, Marc AU - van de Wetering M FAU - Clevers, Hans AU - Clevers H LA - eng SI - GEO/GSE14201 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Ascl2 protein, mouse) RN - 0 (Basic Helix-Loop-Helix Transcription Factors) SB - IM MH - Adult Stem Cells/*metabolism MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/*metabolism MH - Cell Separation MH - Gene Deletion MH - Gene Expression Profiling MH - Intestine, Small/*cytology MH - Mice MH - Mice, Transgenic EDAT- 2009/03/10 09:00 MHDA- 2009/03/28 09:00 CRDT- 2009/03/10 09:00 PHST- 2008/07/29 00:00 [received] PHST- 2008/11/07 00:00 [revised] PHST- 2009/01/07 00:00 [accepted] PHST- 2009/03/10 09:00 [entrez] PHST- 2009/03/10 09:00 [pubmed] PHST- 2009/03/28 09:00 [medline] AID - S0092-8674(09)00079-8 [pii] AID - 10.1016/j.cell.2009.01.031 [doi] PST - ppublish SO - Cell. 2009 Mar 6;136(5):903-12. doi: 10.1016/j.cell.2009.01.031.