mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
- PMID: 22722868
- PMCID: PMC3387287
- DOI: 10.1038/nature11163
mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
Abstract
How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mTORC1 in Paneth cells, but not ISCs, and forced activation of mTORC1 in Paneth cells during calorie restriction abolishes the ISC-augmenting effects of the niche. Finally, increased expression of bone stromal antigen 1 (Bst1) in Paneth cells—an ectoenzyme that produces the paracrine factor cyclic ADP ribose—mediates the effects of calorie restriction and rapamycin on ISC function. Our findings establish that mTORC1 non-cell-autonomously regulates stem-cell self-renewal, and highlight a significant role of the mammalian intestinal niche in coupling stem-cell function to organismal physiology.
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Comment in
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Metabolism: WeightWatching for stem cells.Nat Rev Mol Cell Biol. 2012 Jun 8;13(7):406. doi: 10.1038/nrm3374. Nat Rev Mol Cell Biol. 2012. PMID: 22678485 No abstract available.
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Ageing: A healthy diet for stem cells.Nature. 2012 Jun 27;486(7404):477-8. doi: 10.1038/486477a. Nature. 2012. PMID: 22739309 No abstract available.
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Caloric restriction in mTORC1 control of intestinal homeostasis.Cell Metab. 2012 Jul 3;16(1):6-8. doi: 10.1016/j.cmet.2012.06.010. Cell Metab. 2012. PMID: 22768834
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