mTORC1 in the Paneth Cell Niche Couples Intestinal Stem Cell Function to Calorie Intake

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mTORC1 in the Paneth Cell Niche Couples Intestinal Stem Cell Function to Calorie Intake

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Title: mTORC1 in the Paneth Cell Niche Couples Intestinal Stem Cell Function to Calorie Intake
Author: Katajisto, Pekka; Lamming, Dudley W.; Gültekin, Yetis; Bauer-Rowe, Khristian E.; Sengupta, Shomit; Birsoy, Kivanc; Dursun, Abdulmetin; Yilmaz, V. Onur; Selig, Martin; Nielson, G. Petur; Sabatini, David M.; Yilmaz, Omer Hidir; Mino-Kenudson, Mari; Zukerberg, Lawrence R.; Bhan, Atul Kumar; Deshpande, Vikram

Note: Order does not necessarily reflect citation order of authors.

Citation: Yilmaz, Omer Hidir, Pekka Katajisto, Dudley W. Lamming, Yetis Gültekin, Khristian E. Bauer-Rowe, Shomit Sengupta, Kivanc Birsoy, et al. 2012. mTORC1 in the Paneth cell niche couples intestinal stem cell function to calorie intake. Nature 486(7404): 490-495.
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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.
Published Version: doi:10.1038/nature11163
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387287/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10610369
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