Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts (Nature, 2011, 469:415-417)

報告日期: 2011/04/19
報告時間: 17:10/18:00
報告學生: 簡郡緯 (英文報告)
講評老師: 辛致煒
附件下載:

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0419-3.pdf

Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
 
Nature. 2011, 469: 415-419
 
Speaker: Chun-Wei Chien
Commentator: Jyh-Wei Shin Ph.D.
Date: 2011. 04.19
 
Abstract
The intestinal epithelium is the most self-renewing tissue in adult mammals. Lgr5 were identified by it is Wnt signaling target gene. In the previous study, the authors already proved that single Lgr5 stem cell can build crypt-villus structures in vitro without a mesenchymal niche. Lgr5 stem cells locate at the bottom of crypt with Paneth cells. Thus, the authors hypothesized that Paneth cells can provide the niche for Lgr5 stem cells. Confocal cross-section of crypt bottoms of Lgr5-EGFP-ires-creERT2 mice revealed an almost geometrical distribution of Paneth cells and Lgr5 stem cells that maximized heterotypic contact area. Next, the Lgr5 stem cells were sorted from Lgr5-EGFP-ires-creERT2 mice and were recombined with wild-type Paneth cells. Notably, Paneth cells reside between Lgr5 stem cells and the organoids formed. Thus, Lgr5 stem cells and Paneth cells appeared to require physical contact. Next, the authors performed comparative gene expression profiling on Lgr5 stem cells and Paneth cells. The genes associated in crypt development are highly enriched in Paneth cells, such as Wnt3, Wnt11, Egf, Dll4. It is suggested that Paneth cells provide essential signals for stem-cell support. Reduced Paneth cells in vivo result in the concomitant loss of Lgr5 stem cells. According to these data, the authors conclude that Lgr5 stem cells compete for essential niche signals provided by its daughter cells, the Paneth cells.
 
Reference
1.     Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007, 449: 1003-1008.
2.    Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009, 459: 262-266