mTORC1 in the Paneth cell niche couples intestinal stem cell function to calorie intake
| Autor: | Kıvanç Birsoy, Vikram Deshpande, Ömer H. Yilmaz, Pekka Katajisto, Yetis Gultekin, Atul K. Bhan, G. Petur Nielsen, David M. Sabatini, Dudley W. Lamming, Khristian E. Bauer-Rowe, Martin K. Selig, Shomit Sengupta, Lawrence R. Zukerberg, Abdulmetin Dursun, V. Onur Yilmaz, Mari Mino-Kenudson |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Paneth Cells Stromal cell Calorie restriction Longevity Paracrine Communication Cell Count mTORC1 Biology Mechanistic Target of Rapamycin Complex 1 GPI-Linked Proteins digestive system Article 03 medical and health sciences Paracrine signalling Mice 0302 clinical medicine Antigens CD medicine Animals Regeneration Stem Cell Niche ADP-ribosyl Cyclase 030304 developmental biology Caloric Restriction Sirolimus 0303 health sciences Cyclic ADP-Ribose Multidisciplinary Stem Cells TOR Serine-Threonine Kinases LGR5 Proteins Cell biology Intestines medicine.anatomical_structure Multiprotein Complexes Paneth cell Female Stem cell Energy Intake 030217 neurology & neurosurgery Cell Division Signal Transduction |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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