Header

UZH-Logo

Maintenance Infos

GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells


Degirmenci, Bahar; Valenta, Tomas; Dimitrieva, Slavica; Hausmann, George; Basler, Konrad (2018). GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells. Nature, 558(7710):449-453.

Abstract

Wnt-β-catenin signalling plays a pivotal role in the homeostasis of the intestinal epithelium by promoting stem cell renewal. In the small intestine, epithelial Paneth cells secrete Wnt ligands and thus adopt the function of the stem cell niche to maintain epithelial homeostasis. It is unclear which cells comprise the stem cell niche in the colon. Here we show that subepithelial mesenchymal GLI1-expressing cells form this essential niche. Blocking Wnt secretion from GLI1-expressing cells prevents colonic stem cell renewal in mice: the stem cells are lost and, as a consequence, the integrity of the colonic epithelium is corrupted, leading to death. GLI1-expressing cells also play an important role in the maintenance of the small intestine, where they serve as a reserve Wnt source that becomes critical when Wnt secretion from epithelial cells is prevented. Our data suggest a mechanism by which the stem cell niche is adjusted to meet the needs of the intestine via adaptive changes in the number of mesenchymal GLI1-expressing cells.

Abstract

Wnt-β-catenin signalling plays a pivotal role in the homeostasis of the intestinal epithelium by promoting stem cell renewal. In the small intestine, epithelial Paneth cells secrete Wnt ligands and thus adopt the function of the stem cell niche to maintain epithelial homeostasis. It is unclear which cells comprise the stem cell niche in the colon. Here we show that subepithelial mesenchymal GLI1-expressing cells form this essential niche. Blocking Wnt secretion from GLI1-expressing cells prevents colonic stem cell renewal in mice: the stem cells are lost and, as a consequence, the integrity of the colonic epithelium is corrupted, leading to death. GLI1-expressing cells also play an important role in the maintenance of the small intestine, where they serve as a reserve Wnt source that becomes critical when Wnt secretion from epithelial cells is prevented. Our data suggest a mechanism by which the stem cell niche is adjusted to meet the needs of the intestine via adaptive changes in the number of mesenchymal GLI1-expressing cells.

Statistics

Citations

Dimensions.ai Metrics
17 citations in Web of Science®
9 citations in Scopus®
1 citation in Microsoft Academic
Google Scholar™

Altmetrics

Downloads

4 downloads since deposited on 28 Jun 2018
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:Multidisciplinary
Language:English
Date:6 June 2018
Deposited On:28 Jun 2018 08:44
Last Modified:19 Aug 2018 16:03
Publisher:Nature Publishing Group
ISSN:0028-0836
OA Status:Closed
Publisher DOI:https://doi.org/10.1038/s41586-018-0190-3
PubMed ID:29875413

Download