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Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche
Reina Aoki1, Michal Shoshkes-Carmel1, Nan Gao1
1Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cellular and Molecular Gastroenterology and Hepatology
|March 8, 2016
Summary
Mesenchymal cells expressing Foxl1 are essential for intestinal stem cell niche function. Ablating these cells halts stem and progenitor cell proliferation by disrupting Wnt signaling.
Area of Science:
- Gastroenterology
- Stem Cell Biology
- Developmental Biology
Background:
- Intestinal epithelial stem cells (Lgr5+, Bmi1+) continuously self-renew.
- Paneth cells were previously thought to regulate stem cell behavior but their ablation had no effect.
- A subset of mesenchymal cells expressing Foxl1 is identified as a critical component of the stem cell niche.
Purpose of the Study:
- To definitively identify the cellular components of the intestinal stem cell niche.
- To investigate the role of Foxl1-expressing mesenchymal cells in maintaining intestinal stem cells.
Main Methods:
- Genetically ablated Foxl1-expressing mesenchymal cells in adult mice.
- Utilized two models with diphtheria toxin receptor (DTR) under Foxl1 promoter control.
- Administered diphtheria toxin to induce cell ablation.
Main Results:
- Diphtheria toxin administration led to rapid cessation of proliferation in both stem and transit-amplifying progenitor cells.
- Ablation of Foxl1+ cells resulted in a loss of active Wnt signaling to the intestinal epithelium.
Conclusions:
- Foxl1-expressing mesenchymal cells are the fundamental niche for intestinal stem cells.
- These mesenchymal cells are crucial for maintaining intestinal stem cell proliferation and Wnt signaling.
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