Journal
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Volume 2, Issue 2, Pages 175-188Publisher
ELSEVIER INC
DOI: 10.1016/j.jcmgh.2015.12.004
Keywords
Intestinal Stem Cell Niche; Wnt; Mesenchyme
Categories
Funding
- National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R37-DK053839, 5U01-DK089570, 5U01-DK072473]
- Transgenic Mouse and Molecular Pathology and Imaging Cores of the Center for Molecular Studies in Digestive and Liver Diseases (National Institutes of Health) [P30 DK050306]
Ask authors/readers for more resources
BACKGROUND & AIMS: Intestinal epithelial stem cells that express leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) and/or B cell specific Moloney murine leukemia virus integration site 1 (Bmi1) continuously replicate and generate differentiated cells throughout life. Previously, Paneth cells were suggested to constitute an epithelium-intrinsic niche that regulates the behavior of these stem cells. However, ablating Paneth cells has no effect on the maintenance of functional stem cells. Here, we show definitively that a small subset of mesenchymal subepithelial cells expressing the winged-helix transcription factor forkhead box l1 (Foxl1) are a critical component of the intestinal stem cell niche. METHODS: We genetically ablated Foxl1+ mesenchymal cells in adult mice using 2 separate models by expressing either the human or simian diphtheria toxin receptor under Foxl1 promoter control. CONCLUSIONS: Killing Foxl1+ cells by diphtheria toxin administration led to an abrupt cessation of proliferation of both epithelial stem- and transit-amplifying progenitor cell populations that was associated with a loss of active Wnt signaling to the intestinal epithelium. Therefore, Foxl1-expressing mesenchymal cells constitute the fundamental niche for intestinal stem cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available