Transcription factor achaete scute-like 2 controls intestinal stem cell fate.
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.
van der Flier
Laurens G
LG
Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalaan, The Netherlands.
van Gijn
Marielle E
ME
Hatzis
Pantelis
P
Kujala
Pekka
P
Haegebarth
Andrea
A
Stange
Daniel E
DE
Begthel
Harry
H
van den Born
Maaike
M
Guryev
Victor
V
Oving
Irma
I
van Es
Johan H
JH
Barker
Nick
N
Peters
Peter J
PJ
van de Wetering
Marc
M
Clevers
Hans
H
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
D051792:Basic Helix-Loop-Helix Proteins; C489311:Ascl2 protein, mouse