Title |
Secreted Phospholipases A2 Are Intestinal Stem Cell Niche Factors with Distinct Roles in Homeostasis, Inflammation, and Cancer
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Published in |
Cell Stem Cell, June 2016
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DOI | 10.1016/j.stem.2016.05.023 |
Pubmed ID | |
Authors |
Matthias Schewe, Patrick F. Franken, Andrea Sacchetti, Mark Schmitt, Rosalie Joosten, René Böttcher, Martin E. van Royen, Louise Jeammet, Christine Payré, Patricia M. Scott, Nancy R. Webb, Michael Gelb, Robert T. Cormier, Gérard Lambeau, Riccardo Fodde |
Abstract |
The intestinal stem cell niche provides cues that actively maintain gut homeostasis. Dysregulation of these cues may compromise intestinal regeneration upon tissue insult and/or promote tumor growth. Here, we identify secreted phospholipases A2 (sPLA2s) as stem cell niche factors with context-dependent functions in the digestive tract. We show that group IIA sPLA2, a known genetic modifier of mouse intestinal tumorigenesis, is expressed by Paneth cells in the small intestine, while group X sPLA2 is expressed by Paneth/goblet-like cells in the colon. During homeostasis, group IIA/X sPLA2s inhibit Wnt signaling through intracellular activation of Yap1. However, upon inflammation they are secreted into the intestinal lumen, where they promote prostaglandin synthesis and Wnt signaling. Genetic ablation of both sPLA2s improves recovery from inflammation but increases colon cancer susceptibility due to release of their homeostatic Wnt-inhibitory role. This "trade-off" effect suggests sPLA2s have important functions as genetic modifiers of inflammation and colon cancer. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 20% |
Netherlands | 3 | 15% |
France | 2 | 10% |
United Kingdom | 1 | 5% |
Germany | 1 | 5% |
Unknown | 9 | 45% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 11 | 55% |
Science communicators (journalists, bloggers, editors) | 5 | 25% |
Scientists | 4 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Iran, Islamic Republic of | 1 | <1% |
Netherlands | 1 | <1% |
China | 1 | <1% |
Unknown | 158 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 32 | 20% |
Student > Ph. D. Student | 29 | 18% |
Student > Bachelor | 17 | 11% |
Student > Master | 16 | 10% |
Other | 12 | 7% |
Other | 24 | 15% |
Unknown | 31 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 53 | 33% |
Agricultural and Biological Sciences | 30 | 19% |
Immunology and Microbiology | 14 | 9% |
Medicine and Dentistry | 12 | 7% |
Nursing and Health Professions | 4 | 2% |
Other | 9 | 6% |
Unknown | 39 | 24% |