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mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
Open accessAbstract
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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“DR increases intestinal and muscle stem functions through cell-extrinsic mechanisms”
From The Hallmarks of Aging (2013) · cites this paper as Yilmaz et al., 2012
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“mTORC1 inhibition with rapamycin, which can postpone aging by improving proteostasis (see section on Loss of Proteostasis) and by affecting energy sensing (see section on Deregulated Nutrient-sensing), may also improve stem cell function in the epidermis, in the hematopoietic system, and in the intestine”
From The Hallmarks of Aging (2013) · cites this paper as Yilmaz et al., 2012
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“Rapamycin also increases the self-renewal capacity of mouse intestinal stem cells, via a non-cell autonomous mechanism mediated by inhibition of mTORC1 in the adjacent Paneth cells 96.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [96]
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“mTOR, a potent activator of protein translation and inhibitor of autophagy, has been shown to regulate the self-renewal and differentiation of HSCs and intestinal stem cells79,80.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [79]
In the citing paper
“CR can also enhance or maintain stem cell function during aging by increasing the expression of brain-derived neurotrophic factor in the brain and reducing the mTOR complex 1 (mTORC1) pathway in intestine79,112.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [79]
In the citing paper
“CR can also enhance or maintain stem cell function during aging by increasing the expression of brain-derived neurotrophic factor in the brain and reducing the mTOR complex 1 (mTORC1) pathway in intestine79,112.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [79]
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“Paneth cells, found in close association with intestinal stem cells in humans and mice, are an important source of niche factors, including epidermal growth factor, Wnt3A and Notch ligand79,156, although the effect of aging on their activity is yet to be elucidated.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [79]
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Cites
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M., & Clevers, H. (2011) · Nature · doi:10.1038/nature09637 · Cited by 2,510
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365
Self-citationSnippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951
Bmi1 is expressed in vivo in intestinal stem cells
Sangiorgi, E., & Capecchi, M. R. (2008) · Nature Genetics · doi:10.1038/ng.165 · Cited by 1,245
Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells
Yilmaz, Ö. H., Valdez, R., Theisen, B. K., Guo, W., Ferguson, D. O., Wu, H., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature04703 · Cited by 1,113
Self-citationTranscription Factor Achaete Scute-Like 2 Controls Intestinal Stem Cell Fate
van der Flier, L. G., van Gijn, M. E., Hatzis, P., Kujala, P., Haegebarth, A., Stange, D. E., Begthel, H., van den Born, M., Guryev, V., Oving, I. M., et al. (2009) · Cell · doi:10.1016/j.cell.2009.01.031 · Cited by 752
Interconversion Between Intestinal Stem Cell Populations in Distinct Niches
Takeda, N., Jain, R., LeBoeuf, M. R., Wang, Q., Lu, M. M., & Epstein, J. A. (2011) · Science · doi:10.1126/science.1213214 · Cited by 742
Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation
Zhu, L., Gibson, P., Currle, D. S., Tong, Y., Richardson, R. J., Bayazitov, I. T., Poppleton, H., Zakharenko, S. S., Ellison, D. W., & Gilbertson, R. J. (2008) · Nature · doi:10.1038/nature07589 · Cited by 690
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Yue, R., Zhou, B. O., Shimada, I. S., Zhao, Z., & Morrison, S. J. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.02.015 · Cited by 495
Cheng, C., Adams, G. B., Perin, L., Wei, M., Zhou, X., Lam, B. S., Sacco, S. D., Mirisola, M. G., Quinn, D. I., Dorff, T. B., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.04.014 · Cited by 491
Wyant, G. A., Abu-Remaileh, M., Wolfson, R. L., Chen, W. W., Freinkman, E., Danai, L. V., Heiden, M. G. V., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.09.046 · Cited by 494
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Vitale, I., Manic, G., De Maria, R., Kroemer, G., & Galluzzi, L. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.04.006 · Cited by 361
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Wang, F., Scoville, D., He, X., Mahé, M. M., Box, A., Perry, J. M., Smith, N. R., Lei, N., Davies, P. S., Fuller, M. K., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.04.050 · Cited by 222
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High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity
Mana, M., Hussey, A. M., Tzouanas, C. N., Imada, S., Millan, Y. B., Bahceci, D. H., Saiz, D. R., Webb, A., Lewis, C. A., Carmeliet, P., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109212 · Cited by 209
Self-citationKhaloian, S., Rath, E., Hammoudi, N., Urbauer, E., Blutke, A., Giesbertz, P., Berger, E., Metwaly, A., Waldschmitt, N., Allez, M., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-319514 · Cited by 209
Cell plasticity in epithelial homeostasis and tumorigenesis
Varga, J., & Greten, F. R. (2017) · Nature Cell Biology · doi:10.1038/ncb3611 · Cited by 209
Organoids for Drug Discovery and Personalized Medicine
Takahashi, T. (2018) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010818-021108 · Cited by 210
Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer
Xie, Y., Zhao, Y., Shi, L., Li, W., Chen, K., Li, M., Chen, X., Zhang, H., Li, T., Matsuzawa, Y., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133264 · Cited by 202
Inhibition of the Mechanistic Target of Rapamycin (mTOR)–Rapamycin and BeyondPreprint
Lamming, D. W. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025924 · Cited by 205
Self-citationGut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway
He, D. N., Wu, H., Xiang, J., Ruan, X., Peng, P., Ruan, Y., Chen, Y., Wang, Y., Yu, Q., Zhang, H., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13911-x · Cited by 198
mTOR signaling in stem and progenitor cells
Meng, D., Frank, A. R., & Jewell, J. L. (2018) · Development · doi:10.1242/dev.152595 · Cited by 201
NAD + metabolism: A therapeutic target for age-related metabolic disease
Mouchiroud, L., Houtkooper, R. H., & Auwerx, J. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.789479 · Cited by 193
“It is interesting to note, however, that a recent study demonstrated a role for CD157 in the response of intestinal Paneth cells to caloric restriction (CR) (Yilmaz et al., 2012).”
BackgroundDiet, microbiota and autoimmune diseases
Vieira, S., Pagovich, O., & Kriegel, M. A. (2014) · Lupus · doi:10.1177/0961203313501401 · Cited by 197
Gut microbiota mediates the anti-obesity effect of calorie restriction in mice
Wang, S., Huang, M., You, X., Zhao, J., Chen, L., Wang, L., Luo, Y., & Chen, Y. (2018) · Scientific Reports · doi:10.1038/s41598-018-31353-1 · Cited by 189
mTOR pathway in colorectal cancer: an update
Francipane, M. G., & Lagasse, E. (2013) · Oncotarget · doi:10.18632/oncotarget.1548 · Cited by 186
Energy metabolism and energy-sensing pathways in mammalian embryonic and adult stem cell fate
Rafalski, V. A., Mancini, E., & Brunet, A. (2012) · Journal of Cell Science · doi:10.1242/jcs.114827 · Cited by 181
Cellular Plasticity in Intestinal Homeostasis and Disease
Melo, F. D. S. E., & de Sauvage, F. J. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.11.019 · Cited by 184
Aging-Induced Stem Cell Mutations as Drivers for Disease and Cancer
Adams, P. D., Jasper, H., & Rudolph, K. L. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.05.002 · Cited by 182
Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation
He, G.-W., Lin, L., DeMartino, J., Zheng, X., Staliarova, N., Dayton, T., Begthel, H., van de Wetering, W. J., Bodewes, E., van Zon, J., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.08.002 · Cited by 178
Intestinal Stem Cell Aging: Origins and Interventions
Jasper, H. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021119-034359 · Cited by 183
Stem Cells Marked by the R-Spondin Receptor LGR5
Koo, B., & Clevers, H. C. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.05.007 · Cited by 174
Stretching the limits: from homeostasis to stem cell plasticity in wound healing and cancer
Ge, Y., & Fuchs, E. V. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2018.9 · Cited by 172
Ageing, metabolism and the intestine
Funk, M. C., Zhou, J., & Boutros, M. (2020) · EMBO Reports · doi:10.15252/embr.202050047 · Cited by 174
Urfer, S. R., Kaeberlein, T. L., Mailheau, S., Bergman, P. J., Creevy, K. E., Promislow, D. E. L., & Kaeberlein, M. (2017) · GeroScience · doi:10.1007/s11357-017-9972-z · Cited by 158
The central moTOR of metabolism
Simcox, J., & Lamming, D. W. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.02.024 · Cited by 174
Self-citationHypoxia and HIF-1 as key regulators of gut microbiota and host interactions
Pral, L. P., Fachi, J. L., Corrêa, R. O., Colonna, M., & Vinolo, M. A. R. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.05.004 · Cited by 174
Lgr5+ telocytes are a signaling source at the intestinal villus tip
Halpern, K. B., Massalha, H., Zwick, R. K., Moor, A. E., Castillo‐Azofeifa, D., Rozenberg, M., Farack, L., Egozi, A., Miller, D. R., Averbukh, I., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15714-x · Cited by 158
Dietary and Metabolic Control of Stem Cell Function in Physiology and Cancer
Mihaylova, M. M., Sabatini, D. M., & Yilmaz, Ö. H. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.008 · Cited by 158
Self-citation
Metadata
- Authors
- Yilmaz, Ö. H., Katajisto, P., Lamming, D. W., Gültekin, Y., Bauer-Rowe, K. E., Sengupta, S., Birsoy, K., Dursun, A., Yilmaz, V. O., Selig, M., Nielsen, G. P., Mino-Kenudson, M., Zukerberg, L. R., Bhan, A. K., Deshpande, V., & Sabatini, D. M.
- Affiliations
- Harvard University (US)
- Broad Institute (US)
- Corresponding author
- Sabatini, David M.
- ORCID
- Venue
- Nature
- Published
- 2012-05-20
- Volume
- 486
- Issue
- 7404
- Pages
- 490-495
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3387287
- OpenAlex
- W2113486346
- Cited by
- 753
- References
- 33
- Citations by year
- 2026: 38 · 2025: 45 · 2024: 44 · 2023: 58 · 2022: 53 · 2021: 75 · 2020: 69 · 2019: 54 · 2018: 63 · 2017: 56 · 2016: 39 · 2015: 39 · 2014: 52 · 2013: 47 · 2012: 19
- FWCI
- 20.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (F32AG032833)
- National Cancer Institute (T32CA09216, CA129105, CA103866, R01CA103866, R01CA129105, T32CA009216)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mTORC1, Paneth cells, intestinal stem cells, intestinal stem cell niche, caloric restriction, BST1, cyclic ADP-ribose, paracrine signaling, stem cell self-renewal, intestinal regeneration, nutritional status, rapamycin, lifespan
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Energy Intake, Cell Count, Cell Division, Female, Intestines, Longevity, Male, Proteins, Regeneration, Stem Cells, Signal Transduction, Antigens, CD, Paneth Cells, Paracrine Communication, Sirolimus, Caloric Restriction, ADP-ribosyl Cyclase, Cyclic ADP-Ribose, Multiprotein Complexes, Mice, Stem Cell Niche, TOR Serine-Threonine Kinases, GPI-Linked Proteins
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