van der Flier Laurens G, van Gijn Marielle E, Hatzis Pantelis, Kujala Pekka, Haegebarth Andrea, Stange Daniel E, Begthel Harry, van den Born Maaike, Guryev Victor, Oving Irma, van Es Johan H, Barker Nick, Peters Peter J, van de Wetering Marc, Clevers Hans
Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalaan, The Netherlands.
Cell. 2009 Mar 6;136(5):903-12. doi: 10.1016/j.cell.2009.01.031.
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.
小肠上皮是哺乳动物中自我更新最迅速的组织。增殖细胞局限于隐窝，而分化的细胞类型主要占据绒毛。我们最近证明了存在一个由Lgr5表达定义的长寿循环干细胞池，它们与有丝分裂后的潘氏细胞在隐窝底部混合存在。我们现在已经确定了这些Lgr5干细胞的基因特征。这个干细胞特征中的一个基因是Wnt靶标类无翅型-M相关转录因子2（Ascl2）。Ascl2转录因子在整个肠道上皮中的转基因表达会诱导隐窝增生和绒毛上的异位隐窝。在成年小肠中诱导删除Ascl2基因会导致Lgr5干细胞在数天内消失。这些功能获得和功能丧失实验的综合结果表明，Ascl2控制肠道干细胞的命运。
