Wnt-β-catenin signalling plays a pivotal role in the homeostasis of the intestinal epithelium by promoting stem cell renewal1,2. In the small intestine, epithelial Paneth cells secrete Wnt ligands and thus adopt the function of the stem cell niche to maintain epithelial homeostasis3,4. 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.

Functional Genomics Center Zurich ETH University of Zurich Zurich Switzerland

Institute of Molecular Genetics of the ASCR Prague Czech Republic

Institute of Molecular Life Sciences University of Zurich Zurich Switzerland

Comment In

Nature. 2018 Jun;558(7710):380-381. doi: 10.1038/d41586-018-05281-z. PubMed

References provided by Crossref.org

Tcf4 regulates secretory cell fate decisions in the small intestine and colon tumors: insights from transcriptomic, histological, and microbiome analyses

Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members

Wnt signaling from Gli1-expressing apical stem/progenitor cells is essential for the coordination of tooth root development

Epithelial Wnt secretion drives the progression of inflammation-induced colon carcinoma in murine model

Distinct populations of crypt-associated fibroblasts act as signaling hubs to control colon homeostasis