mTORC1 in the Paneth cell niche couples intestinal stem cell function to calorie intake
Name
Yilmaz Nature 2012.pdf
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2.61 MB
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Adobe PDF
Checksum (MD5)
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Author(s)
Katajisto, Pekka
Lamming, Dudley W.
Gultekin, Yetis
Bauer-Rowe, Khristian E.
Sengupta, Shomit
Birsoy, Kivanc
Dursun, Abdulmetin
Yilmaz, V. Onur
Selig, Martin
Nielson, G. Petur
Date Issued
May 2012
Journal
Nature
Publisher
Nature Publishing Group
Citation
Yilmaz, Ömer H. et al. “mTORC1 in the Paneth Cell Niche Couples Intestinal Stem-cell Function to Calorie Intake.” Nature (2012): Web.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nature11163
