title: Transcription factor achaete scute-like 2 controls intestinal stem cell fate.
abstract: 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.
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalaan, The Netherlands.
authors.forename: Laurens G
authors.initials: LG
authors.lastname: van der Flier
authors.forename: Marielle E
authors.initials: ME
authors.lastname: van Gijn
authors.forename: Pantelis
authors.initials: P
authors.lastname: Hatzis
authors.forename: Pekka
authors.initials: P
authors.lastname: Kujala
authors.forename: Andrea
authors.initials: A
authors.lastname: Haegebarth
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Stange
authors.forename: Harry
authors.initials: H
authors.lastname: Begthel
authors.forename: Maaike
authors.initials: M
authors.lastname: van den Born
authors.forename: Victor
authors.initials: V
authors.lastname: Guryev
authors.forename: Irma
authors.initials: I
authors.lastname: Oving
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Es
authors.forename: Nick
authors.initials: N
authors.lastname: Barker
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Peters
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002469:Cell Separation; D017353:Gene Deletion; D020869:Gene Expression Profiling; D007421:Intestine, Small / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C489311:Ascl2 protein, mouse