dc.contributor.author | Saadatpour, Assieh | |
dc.contributor.author | Hong, Sue-Jean | |
dc.contributor.author | Pinello, Luca | |
dc.contributor.author | Katz, Yarden | |
dc.contributor.author | Lamming, Dudley W. | |
dc.contributor.author | Guo, Guoji | |
dc.contributor.author | Bell, George W. | |
dc.contributor.author | Selig, Martin | |
dc.contributor.author | Nielsen, G. Petur | |
dc.contributor.author | Gupta, Nitin | |
dc.contributor.author | Ferrone, Cristina R. | |
dc.contributor.author | Deshpande, Vikram | |
dc.contributor.author | Yuan, Guo-Cheng | |
dc.contributor.author | Orkin, Stuart H. | |
dc.contributor.author | Beyaz, Semir | |
dc.contributor.author | Mana, Miyeko | |
dc.contributor.author | Roper, Jatin | |
dc.contributor.author | Kedrin, Dmitriy | |
dc.contributor.author | Bauer-Rowe, Khristian E. | |
dc.contributor.author | Xifaras, Michael | |
dc.contributor.author | Akkad, Adam | |
dc.contributor.author | Arias, Erika | |
dc.contributor.author | Shinagare, Shweta | |
dc.contributor.author | Abu-Remaileh, Monther | |
dc.contributor.author | Dogum, Rizkullah | |
dc.contributor.author | Sabatini, David | |
dc.contributor.author | Yilmaz, Omer | |
dc.contributor.author | Mihaylova, Maria M. | |
dc.date.accessioned | 2017-01-24T15:44:16Z | |
dc.date.available | 2017-01-24T15:44:16Z | |
dc.date.issued | 2016-03 | |
dc.date.submitted | 2015-03 | |
dc.identifier.issn | 0028-0836 | |
dc.identifier.issn | 1476-4687 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/106594 | |
dc.description.abstract | Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5[superscript +] intestinal stem-cells (ISCs) of the mammalian intestine. Mechanistically, HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-d) signature in intestinal stem and (nonISC) progenitor cells, and pharmacologic activation of PPAR-d recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-d dependent manner. Interestingly, HFD- and agonist-activated PPAR-d signaling endow organoidinitiating capacity to progenitors, and enforced PPAR-d signaling permits these progenitors to form in vivo tumors upon loss of the tumor suppressor Apc. These findings highlight how dietmodulated PPAR-d activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumors. | en_US |
dc.description.sponsorship | Howard Hughes Medical Institute | en_US |
dc.description.sponsorship | Ellison Medical Foundation (Aging Grant) | en_US |
dc.description.sponsorship | United States. Department of Defense (PRCRP Career Development Award CA120198) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grants R01 CA103866, AI47389, K08 CA198002, R00 AG045144, R00 AG041765, and DK043351) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Cancer Center Support Core Grant P30-CA14051) | en_US |
dc.description.sponsorship | Kathy and Curt Marble Cancer Research Fund | en_US |
dc.description.sponsorship | American Federation for Aging Research | en_US |
dc.description.sponsorship | V Foundation for Cancer Research (Scholar Grant) | en_US |
dc.description.sponsorship | Massachusetts Institute of Technology. Ludwig Center for Molecular Oncology (Post-doctoral Fellowship) | en_US |
dc.description.sponsorship | Massachusetts General Hospital (Fellowship T32DK007191) | en_US |
dc.description.sponsorship | Damon Runyon Cancer Research Foundation (Robert Black Fellowship) | en_US |
dc.language.iso | en_US | |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/nature17173 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | High-fat diet enhances stemness and tumorigenicity of intestinal progenitors | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Beyaz, Semir et al. “High-Fat Diet Enhances Stemness and Tumorigenicity of Intestinal Progenitors.” Nature 531.7592 (2016): 53–58. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Beyaz, Semir | |
dc.contributor.mitauthor | Mana, Miyeko | |
dc.contributor.mitauthor | Roper, Jatin | |
dc.contributor.mitauthor | Kedrin, Dmitriy | |
dc.contributor.mitauthor | Bauer-Rowe, Khristian E. | |
dc.contributor.mitauthor | Xifaras, Michael | |
dc.contributor.mitauthor | Akkad, Adam | |
dc.contributor.mitauthor | Arias, Erika | |
dc.contributor.mitauthor | Shinagare, Shweta | |
dc.contributor.mitauthor | Abu-Remaileh, Monther | |
dc.contributor.mitauthor | Dogum, Rizkullah | |
dc.contributor.mitauthor | Sabatini, David | |
dc.contributor.mitauthor | Yilmaz, Omer | |
dc.contributor.mitauthor | Mihaylova, Maria M. | |
dc.relation.journal | Nature | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Beyaz, Semir; Mana, Miyeko D.; Roper, Jatin; Kedrin, Dmitriy; Saadatpour, Assieh; Hong, Sue-Jean; Bauer-Rowe, Khristian E.; Xifaras, Michael E.; Akkad, Adam; Arias, Erika; Pinello, Luca; Katz, Yarden; Shinagare, Shweta; Abu-Remaileh, Monther; Mihaylova, Maria M.; Lamming, Dudley W.; Dogum, Rizkullah; Guo, Guoji; Bell, George W.; Selig, Martin; Nielsen, G. Petur; Gupta, Nitin; Ferrone, Cristina R.; Deshpande, Vikram; Yuan, Guo-Cheng; Orkin, Stuart H.; Sabatini, David M.; Yilmaz, Ömer H. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-5516-4008 | |
dc.identifier.orcid | https://orcid.org/0000-0001-6093-7282 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1446-7256 | |
dc.identifier.orcid | https://orcid.org/0000-0002-7577-4612 | |
mit.license | OPEN_ACCESS_POLICY | en_US |