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2. Longitudinal multi-omics analysis of host microbiome architecture and immune responses during short-term spaceflight

Author

Tierney, Braden T., Kim, JangKeun, Overbey, Eliah G., Ryon, Krista A., Foox, Jonathan, Sierra, Maria A., Bhattacharya, Chandrima, Damle, Namita, Najjar, Deena, Park, Jiwoon, Garcia Medina, J. Sebastian, Houerbi, Nadia, Meydan, Cem, Wain Hirschberg, Jeremy, Qiu, Jake, Kleinman, Ashley S., Al-Ghalith, Gabriel A., MacKay, Matthew, Afshin, Evan E., Dhir, Raja, Borg, Joseph, Gatt, Christine, Brereton, Nicholas, Readhead, Benjamin P., Beyaz, Semir, Venkateswaran, Kasthuri J., Wiseman, Kelly, Moreno, Juan, Boddicker, Andrew M., Zhao, Junhua, Lajoie, Bryan R., Scott, Ryan T., Altomare, Andrew, Kruglyak, Semyon, Levy, Shawn, Church, George M., and Mason, Christopher E.

Published
2024
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4. Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation

Author

Rogava, Meri, Aprati, Tyler J., Chi, Wei-Yu, Melms, Johannes C., Hug, Clemens, Davis, Stephanie H., Earlie, Ethan M., Chung, Charlie, Deshmukh, Sachin K., Wu, Sharon, Sledge, George, Tang, Stephen, Ho, Patricia, Amin, Amit Dipak, Caprio, Lindsay, Gurjao, Carino, Tagore, Somnath, Ngo, Bryan, Lee, Michael J., Zanetti, Giorgia, Wang, Yiping, Chen, Sean, Ge, William, Melo, Luiza Martins Nascentes, Allies, Gabriele, Rösler, Jonas, Gibney, Goeffrey T., Schmitz, Oliver J., Sykes, Megan, Creusot, Rémi J., Tüting, Thomas, Schadendorf, Dirk, Röcken, Martin, Eigentler, Thomas K., Molotkov, Andrei, Mintz, Akiva, Bakhoum, Samuel F., Beyaz, Semir, Cantley, Lewis C., Sorger, Peter K., Meckelmann, Sven W., Tasdogan, Alpaslan, Liu, David, Laughney, Ashley M., and Izar, Benjamin

Published
2024
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5. Neurotensin neurons in the extended amygdala control dietary choice and energy homeostasis.

Author

Beyaz, Semir, Janowitz, Tobias, Shea, Stephen, Li, Bo, Furlan, Alessandro, Corona, Alberto, Boyle, Sara, Sharma, Radhashree, Rubino, Rachel, Habel, Jill, Gablenz, Eva, and Giovanniello, Jacqueline

Subjects
Mice, Animals, Neurotensin, Neurons, Central Amygdaloid Nucleus, Energy Metabolism, Homeostasis, Obesity
Abstract

Obesity is a global pandemic that is causally linked to many life-threatening diseases. Apart from some rare genetic conditions, the biological drivers of overeating and reduced activity are unclear. Here, we show that neurotensin-expressing neurons in the mouse interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a nucleus of the central extended amygdala, encode dietary preference for unhealthy energy-dense foods. Optogenetic activation of IPACNts neurons promotes obesogenic behaviors, such as hedonic eating, and modulates food preference. Conversely, acute inhibition of IPACNts neurons reduces feeding and decreases hedonic eating. Chronic inactivation of IPACNts neurons recapitulates these effects, reduces preference for sweet, non-caloric tastants and, furthermore, enhances locomotion and energy expenditure; as a result, mice display long-term weight loss and improved metabolic health and are protected from obesity. Thus, the activity of a single neuronal population bidirectionally regulates energy homeostasis. Our findings could lead to new therapeutic strategies to prevent and treat obesity.

Published
2022

6. A Roadmap for the Human Gut Cell Atlas

Author

Zilbauer, Matthias, James, Kylie R., Kaur, Mandeep, Pott, Sebastian, Li, Zhixin, Burger, Albert, Thiagarajah, Jay R., Burclaff, Joseph, Jahnsen, Frode L., Perrone, Francesca, Ross, Alexander D., Matteoli, Gianluca, Stakenborg, Nathalie, Sujino, Tomohisa, Moor, Andreas, Bartolome-Casado, Raquel, Bækkevold, Espen S., Zhou, Ran, Xie, Bingqing, Lau, Ken S., Din, Shahida, Magness, Scott T., Yao, Qiuming, Beyaz, Semir, Arends, Mark, Denadai-Souza, Alexandre, Coburn, Lori A., Gaublomme, Jellert T., Baldock, Richard, Papatheodorou, Irene, Ordovas-Montanes, Jose, Boeckxstaens, Guy, Hupalowska, Anna, Teichmann, Sarah A., Regev, Aviv, Xavier, Ramnik J., Simmons, Alison, Snyder, Michael P., and Wilson, Keith T.

Published
2023
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8. Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis

Author

Beyaz, Semir, Chung, Charlie, Mou, Haiwei, Bauer-Rowe, Khristian E, Xifaras, Michael E, Ergin, Ilgin, Dohnalova, Lenka, Biton, Moshe, Shekhar, Karthik, Eskiocak, Onur, Papciak, Katherine, Ozler, Kadir, Almeqdadi, Mohammad, Yueh, Brian, Fein, Miriam, Annamalai, Damodaran, Valle-Encinas, Eider, Erdemir, Aysegul, Dogum, Karoline, Shah, Vyom, Alici-Garipcan, Aybuke, Meyer, Hannah V, Özata, Deniz M, Elinav, Eran, Kucukural, Alper, Kumar, Pawan, McAleer, Jeremy P, Fox, James G, Thaiss, Christoph A, Regev, Aviv, Roper, Jatin, Orkin, Stuart H, and Yilmaz, Ömer H

Subjects
Genetics, Digestive Diseases, Cancer, Stem Cell Research, Human Genome, Stem Cell Research - Nonembryonic - Non-Human, Nutrition, 2.1 Biological and endogenous factors, Aetiology, 1.1 Normal biological development and functioning, Underpinning research, Inflammatory and immune system, Carcinogenesis, Diet, High-Fat, Epithelial Cells, Histocompatibility Antigens Class II, Humans, Intestines, MHC-II, antigen presentation, cancer, diet, high-fat diet, intestinal stem cells, microbiome, obesity, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Little is known about how interactions of diet, intestinal stem cells (ISCs), and immune cells affect early-stage intestinal tumorigenesis. We show that a high-fat diet (HFD) reduces the expression of the major histocompatibility complex class II (MHC class II) genes in intestinal epithelial cells, including ISCs. This decline in epithelial MHC class II expression in a HFD correlates with reduced intestinal microbiome diversity. Microbial community transfer experiments suggest that epithelial MHC class II expression is regulated by intestinal flora. Mechanistically, pattern recognition receptor (PRR) and interferon-gamma (IFNγ) signaling regulates epithelial MHC class II expression. MHC class II-negative (MHC-II-) ISCs exhibit greater tumor-initiating capacity than their MHC class II-positive (MHC-II+) counterparts upon loss of the tumor suppressor Apc coupled with a HFD, suggesting a role for epithelial MHC class II-mediated immune surveillance in suppressing tumorigenesis. ISC-specific genetic ablation of MHC class II increases tumor burden cell autonomously. Thus, HFD perturbs a microbiome-stem cell-immune cell interaction that contributes to tumor initiation in the intestine.

Published
2021

10. Excess Dietary Sugar Alters Colonocyte Metabolism and Impairs the Proliferative Response to Damage

Author

Burr, Ansen H.P., Ji, Junyi, Ozler, Kadir, Mentrup, Heather L., Eskiocak, Onur, Yueh, Brian, Cumberland, Rachel, Menk, Ashley V., Rittenhouse, Natalie, Marshall, Chris W., Chiaranunt, Pailin, Zhang, Xiaoyi, Mullinax, Lauren, Overacre-Delgoffe, Abigail, Cooper, Vaughn S., Poholek, Amanda C., Delgoffe, Greg M., Mollen, Kevin P., Beyaz, Semir, and Hand, Timothy W.

Published
2023
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11. β-Hydroxybutyrate suppresses colorectal cancer

Author

Dmitrieva-Posocco, Oxana, Wong, Andrea C., Lundgren, Patrick, Golos, Aleksandra M., Descamps, Hélène C., Dohnalová, Lenka, Cramer, Zvi, Tian, Yuhua, Yueh, Brian, Eskiocak, Onur, Egervari, Gabor, Lan, Yemin, Liu, Jinping, Fan, Jiaxin, Kim, Jihee, Madhu, Bhoomi, Schneider, Kai Markus, Khoziainova, Svetlana, Andreeva, Natalia, Wang, Qiaohong, Li, Ning, Furth, Emma E., Bailis, Will, Kelsen, Judith R., Hamilton, Kathryn E., Kaestner, Klaus H., Berger, Shelley L., Epstein, Jonathan A., Jain, Rajan, Li, Mingyao, Beyaz, Semir, Lengner, Christopher J., Katona, Bryson W., Grivennikov, Sergei I., Thaiss, Christoph A., and Levy, Maayan

Published
2022
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12. T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation.

Author

Chen, Zuojia, Wu, Chuan, Ordovas-Montanes, Jose, Alvarez, David, Herbst, Rebecca, Biton, Moshe, Haber, Adam, Rogel, Noga, Burgin, Grace, Beyaz, Semir, Schnell, Alexandra, Ashenberg, Orr, Su, Chien-Wen, Smillie, Christopher, Zhang, Mei, Tirosh, Itay, Dionne, Danielle, Nguyen, Lan, Xifaras, Michael, Shalek, Alex, von Andrian, Ulrich, Graham, Daniel, Rozenblatt-Rosen, Orit, Shi, Hai, Kuchroo, Vijay, Yilmaz, Omer, Regev, Aviv, Xavier, Ramnik, and Shekhar, Karthik

Subjects
ISCs, MHC class II, MHCII, T helper, T regulatory, T(reg), Th, epithelial differentiation, gut biology, intestinal stem cells, mucosal immunity, scRNA-seq, single cell RNA-seq, stem cell renewal, tuft cells, Animals, Cell Differentiation, Cell Self Renewal, Cytokines, Epithelial Cells, Female, Histocompatibility Antigens Class II, Immune System, Interleukin-10, Intestines, Male, Mice, Mice, Inbred C57BL, Organoids, Receptors, G-Protein-Coupled, Salmonella enterica, Stem Cells, T-Lymphocytes, Helper-Inducer
Abstract

In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear, however, if and how immune cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting cells in co-cultures with CD4+ T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr5+ ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.

Published
2018

13. T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation

Author

Biton, Moshe, Haber, Adam L, Rogel, Noga, Burgin, Grace, Beyaz, Semir, Schnell, Alexandra, Ashenberg, Orr, Su, Chien-Wen, Smillie, Christopher, Shekhar, Karthik, Chen, Zuojia, Wu, Chuan, Ordovas-Montanes, Jose, Alvarez, David, Herbst, Rebecca H, Zhang, Mei, Tirosh, Itay, Dionne, Danielle, Nguyen, Lan T, Xifaras, Michael E, Shalek, Alex K, von Andrian, Ulrich H, Graham, Daniel B, Rozenblatt-Rosen, Orit, Shi, Hai Ning, Kuchroo, Vijay, Yilmaz, Omer H, Regev, Aviv, and Xavier, Ramnik J

Subjects
Biodefense, Digestive Diseases, Regenerative Medicine, Stem Cell Research, Prevention, Vaccine Related, Stem Cell Research - Nonembryonic - Non-Human, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Animals, Cell Differentiation, Cell Self Renewal, Cytokines, Epithelial Cells, Female, Histocompatibility Antigens Class II, Immune System, Interleukin-10, Intestines, Male, Mice, Mice, Inbred C57BL, Organoids, Receptors, G-Protein-Coupled, Salmonella enterica, Stem Cells, T-Lymphocytes, Helper-Inducer, ISCs, MHC class II, MHCII, T helper, T regulatory, T(reg), Th, epithelial differentiation, gut biology, intestinal stem cells, mucosal immunity, scRNA-seq, single cell RNA-seq, stem cell renewal, tuft cells, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear, however, if and how immune cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting cells in co-cultures with CD4+ T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr5+ ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.

Published
2018

17. A single-cell survey of the small intestinal epithelium

Author

Haber, Adam L, Biton, Moshe, Rogel, Noga, Herbst, Rebecca H, Shekhar, Karthik, Smillie, Christopher, Burgin, Grace, Delorey, Toni M, Howitt, Michael R, Katz, Yarden, Tirosh, Itay, Beyaz, Semir, Dionne, Danielle, Zhang, Mei, Raychowdhury, Raktima, Garrett, Wendy S, Rozenblatt-Rosen, Orit, Shi, Hai Ning, Yilmaz, Omer, Xavier, Ramnik J, and Regev, Aviv

Subjects
Emerging Infectious Diseases, Digestive Diseases, Infectious Diseases, Vaccine Related, Aetiology, 2.1 Biological and endogenous factors, Animals, Cell Differentiation, Cytokines, Enterocytes, Epithelial Cells, Epithelium, Female, Gene Expression Profiling, Homeostasis, Intestine, Small, Leukocyte Common Antigens, Male, Mice, Organoids, Paneth Cells, Single-Cell Analysis, Transcription, Genetic, Thymic Stromal Lymphopoietin, General Science & Technology
Abstract

Intestinal epithelial cells absorb nutrients, respond to microbes, function as a barrier and help to coordinate immune responses. Here we report profiling of 53,193 individual epithelial cells from the small intestine and organoids of mice, which enabled the identification and characterization of previously unknown subtypes of intestinal epithelial cell and their gene signatures. We found unexpected diversity in hormone-secreting enteroendocrine cells and constructed the taxonomy of newly identified subtypes, and distinguished between two subtypes of tuft cell, one of which expresses the epithelial cytokine Tslp and the pan-immune marker CD45, which was not previously associated with non-haematopoietic cells. We also characterized the ways in which cell-intrinsic states and the proportions of different cell types respond to bacterial and helminth infections: Salmonella infection caused an increase in the abundance of Paneth cells and enterocytes, and broad activation of an antimicrobial program; Heligmosomoides polygyrus caused an increase in the abundance of goblet and tuft cells. Our survey highlights previously unidentified markers and programs, associates sensory molecules with cell types, and uncovers principles of gut homeostasis and response to pathogens.

Published
2017

18. IL-22 receptor signaling in Paneth cells is critical for their maturation, microbiota colonization, Th17-related immune responses, and anti-Salmonella immunity

Author

Gaudino, Stephen J., Beaupre, Michael, Lin, Xun, Joshi, Preet, Rathi, Sonika, McLaughlin, Patrick A., Kempen, Cody, Mehta, Neil, Eskiocak, Onur, Yueh, Brian, Blumberg, Richard S., van der Velden, Adrianus W. M., Shroyer, Kenneth R., Bialkowska, Agnieszka B., Beyaz, Semir, and Kumar, Pawan

Published
2021
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19. p17/C18-ceramide–mediated mitophagy is an endogenous neuroprotective response in preclinical and clinical brain injury

Author

Karakaya, Eda, primary, Oleinik, Natalia, additional, Edwards, Jazlyn, additional, Tomberlin, Jensen, additional, Barker, Randy Bent, additional, Berber, Burak, additional, Ericsson, Maria, additional, Alsudani, Habeeb, additional, Ergul, Adviye, additional, Beyaz, Semir, additional, Lemasters, John J, additional, Ogretmen, Besim, additional, and Albayram, Onder, additional

Published
2024
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22. Viral activation and ecological restructuring characterize a microbiome axis of spaceflight-associated immune activation

Author

Mason, Christopher, primary, Tierney, Braden, additional, Kim, JangKeun, additional, Overbey, Eliah, additional, Ryon, Krista, additional, Foox, Jonathan, additional, Sierra, Maria, additional, Bhattacharya, Chandrima, additional, Damle, Namita, additional, Najjar, Deena, additional, Park, Jiwoon, additional, Medina, J. Sebastian Garcia, additional, Houerbi, Nadia, additional, Meydan, Cem, additional, Hirschberg, Jeremy, additional, Qiu, Jake, additional, Kleinman, Ashley, additional, Al-Ghalith, Gabriel, additional, MacKay, Matthew, additional, Afshin, Evan, additional, Dhir, Raja, additional, Borg, Joseph, additional, Gatt, Christine, additional, Brereton, Nicholas, additional, Readhead, Ben, additional, Beyaz, Semir, additional, Venkateswaran, Kasthuri, additional, Blease, Kelly, additional, Moreno, Juan, additional, Boddicker, Andrew, additional, Zhao, Junhua, additional, Lajoie, Bryan, additional, Scott, Ryan, additional, Altomare, Andrew, additional, Kruglyak, Semyon, additional, Levy, Shawn, additional, and Church, George, additional

Published
2023
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26. Abstract 1298: Single cell analysis of breast cancer progression and metastasis to lymph nodes reveals cancer cell plasticity and MHC class II-mediated immune regulation

Author

Lei, Pin-Ji, primary, Pereira, Ethel, additional, Andersson, Patrik, additional, Amoozgar, Zohreh, additional, Van Wijnbergen, Jan Willem, additional, O'Melia, Meghan J., additional, Zhou, Hengbo, additional, Chatterjee, Sampurna, additional, Ho, William Wee, additional, Posada, Jessica M., additional, Kumar, Ashwin Srinivasan, additional, Morita, Satoru, additional, Chuang, Charlie, additional, Ergin, Ilgin, additional, Jones, Dennis, additional, Huang, Peigen, additional, Beyaz, Semir, additional, and Padera, Timothy P., additional

Published
2023
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29. Immunometabolism at the crossroads of obesity and cancer—a Keystone Symposia report

Author

Cable, Jennifer, primary, Rathmell, Jeffrey C., additional, Pearce, Erika L., additional, Ho, Ping‐Chih, additional, Haigis, Marcia C., additional, Mamedov, Murad R., additional, Wu, Meng‐Ju, additional, Kaech, Susan M., additional, Lynch, Lydia, additional, Febbraio, Mark A., additional, Bapat, Sagar P., additional, Hong, Hanna S., additional, Zou, Weiping, additional, Belkaid, Yasmine, additional, Sullivan, Zuri A., additional, Keller, Andrea, additional, Wculek, Stefanie K., additional, Green, Douglas R., additional, Postic, Catherine, additional, Amit, Ido, additional, Benitah, Salvador Aznar, additional, Jones, Russell G., additional, Reina‐Campos, Miguel, additional, Torres, Santiago Valle, additional, Beyaz, Semir, additional, Brennan, Donal, additional, O'Neill, Luke A. J., additional, Perry, Rachel J., additional, and Brenner, Dirk, additional

Published
2023
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30. CRISPR ‐induced exon skipping of β‐catenin reveals tumorigenic mutants driving distinct subtypes of liver cancer

Author

Mou, Haiwei, primary, Eskiocak, Onur, additional, Özler, Kadir A., additional, Gorman, Megan, additional, Yue, Junjiayu, additional, Jin, Ying, additional, Wang, Zhikai, additional, Gao, Ya, additional, Janowitz, Tobias, additional, Meyer, Hannah V., additional, Yu, Tianxiong, additional, Wilkinson, John E, additional, Kucukural, Alper, additional, Ozata, Deniz M., additional, and Beyaz, Semir, additional

Published
2023
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31. EXCESS DIETARY SUGAR ALTERS COLONOCYTE METABOLISM AND IMPAIRS THE EARLY PROLIFERATIVE RESPONSE TO DAMAGE

Author

Burr, Ansen, primary, Ji, Junyi, additional, Ozler, Kadir, additional, Mentrup, Heather, additional, Eskiocak, Onur, additional, Cumberland, Rachel, additional, Menk, Ashley, additional, Zhang, Xiaoyi, additional, Overacre-Delgoffe, Abigail, additional, Rittenhouse, Natalie, additional, Marshall, Chris, additional, Cooper, Vaughn, additional, Poholek, Amanda, additional, Delgoffe, Greg, additional, Beyaz, Semir, additional, and Hand, Timothy, additional

Published
2023
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32. In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis

Author

Roper, Jatin, Tammela, Tuomas, Cetinbas, Naniye Malli, Akkad, Adam, Roghanian, Ali, Rickelt, Steffen, Almeqdadi, Mohammad, Wu, Katherine, Oberli, Matthias A, Sánchez-Rivera, Francisco J, Park, Yoona K, Liang, Xu, Eng, George, Taylor, Martin S, Azimi, Roxana, Kedrin, Dmitriy, Neupane, Rachit, Beyaz, Semir, Sicinska, Ewa T, Suarez, Yvelisse, Yoo, James, Chen, Lillian, Zukerberg, Lawrence, Katajisto, Pekka, Deshpande, Vikram, Bass, Adam J, Tsichlis, Philip N, Lees, Jacqueline, Langer, Robert, Hynes, Richard O, Chen, Jianzhu, Bhutkar, Arjun, Jacks, Tyler, and Yilmaz, Ömer H

Published
2017
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33. Breast cancer progression and metastasis to lymph nodes reveals cancer cell plasticity and MHC class II-mediated immune regulation

Author

Lei, Pin-Ji, primary, Pereira, Ethel R., additional, Andersson, Patrik, additional, Amoozgar, Zohreh, additional, Van Wijnbergen, Jan Willem, additional, O’Melia, Meghan, additional, Zhou, Hengbo, additional, Chatterjee, Sampurna, additional, Ho, William W., additional, Posada, Jessica M., additional, Kumar, Ashwin Srinivasan, additional, Morita, Satoru, additional, Chung, Charlie, additional, Ergin, Ilgin, additional, Jones, Dennis, additional, Huang, Peigen, additional, Beyaz, Semir, additional, and Padera, Timothy P., additional

Published
2022
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34. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors

Author

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., and Yilmaz, mer H.

Subjects
High fat diet -- Health aspects, Cancer research, Carcinogenesis -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5[sup.+] intestinal stem cells of the mammalian intestine. Mechanistically, a HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR- 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--dependent manner. Notably, HFD- and agonist-activated PPAR- signalling endow organoid-initiating capacity to progenitors, and enforced PPAR- signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressor Apc. These findings highlight how diet-modulated PPAR- activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours., Author(s): Semir Beyaz [1, 2]; Miyeko D. Mana [1]; Jatin Roper [1, 3]; Dmitriy Kedrin [1, 4]; Assieh Saadatpour [5]; Sue-Jean Hong [6]; Khristian E. Bauer-Rowe [1]; Michael E. Xifaras [...]

Published
2016
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35. Correction: γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans

Author

Chu, Timothy H., primary, Khairallah, Camille, additional, Shieh, Jason, additional, Cho, Rhea, additional, Qiu, Zhijuan, additional, Zhang, Yue, additional, Eskiocak, Onur, additional, Thanassi, David G., additional, Kaplan, Mark H., additional, Beyaz, Semir, additional, Yang, Vincent W., additional, Bliska, James B., additional, and Sheridan, Brian S., additional

Published
2022
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40. IL-17RA-signaling in Lgr5+ intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment

Author

Lin, Xun, primary, Gaudino, Stephen J., additional, Jang, Kyung Ku, additional, Bahadur, Tej, additional, Singh, Ankita, additional, Banerjee, Anirban, additional, Beaupre, Michael, additional, Chu, Timothy, additional, Wong, Hoi Tong, additional, Kim, Chang-Kyung, additional, Kempen, Cody, additional, Axelrad, Jordan, additional, Huang, Huakang, additional, Khalid, Saba, additional, Shah, Vyom, additional, Eskiocak, Onur, additional, Parks, Olivia B., additional, Berisha, Artan, additional, McAleer, Jeremy P., additional, Good, Misty, additional, Hoshino, Miko, additional, Blumberg, Richard, additional, Bialkowska, Agnieszka B., additional, Gaffen, Sarah L., additional, Kolls, Jay K., additional, Yang, Vincent W., additional, Beyaz, Semir, additional, Cadwell, Ken, additional, and Kumar, Pawan, additional

Published
2022
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41. γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans

Author

Chu, Timothy H., primary, Khairallah, Camille, additional, Shieh, Jason, additional, Cho, Rhea, additional, Qiu, Zhijuan, additional, Zhang, Yue, additional, Eskiocak, Onur, additional, Thanassi, David G., additional, Kaplan, Mark H., additional, Beyaz, Semir, additional, Yang, Vincent W., additional, Bliska, James B., additional, and Sheridan, Brian S., additional

Published
2021
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42. Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis

Author

Hanasoge Somasundara, Amritha Varshini, primary, Moss, Matthew A., additional, Feigman, Mary J., additional, Chen, Chen, additional, Cyrill, Samantha L., additional, Ciccone, Michael F., additional, Trousdell, Marygrace C., additional, Vollbrecht, Macy, additional, Li, Siran, additional, Kendall, Jude, additional, Beyaz, Semir, additional, Wilkinson, John E., additional, and dos Santos, Camila O., additional

Published
2021
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44. Author Correction: High-fat diet enhances stemness and tumorigenicity of intestinal progenitors

Author

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., and Yilmaz, Ömer H.

Published
2018
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45. Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis

Author

Hanasoge Somasundara, Amritha V., primary, Moss, Matthew A., additional, Feigman, Mary J., additional, Chen, Chen, additional, Cyrill, Samantha L., additional, Ciccone, Michael F., additional, Trousdell, Marygrace C., additional, Vollbrecht, Macy, additional, Li, Siran, additional, Kendall, Jude, additional, Beyaz, Semir, additional, Wilkinson, John E., additional, and dos Santos, Camila O., additional

Published
2021
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46. Excess dietary sugar impairs colonic epithelial regeneration in response to damage

Author

Burr, Ansen H.P., primary, Ji, Junyi, additional, Ozler, Kadir, additional, Eskiocak, Onur, additional, Yueh, Brian, additional, Menk, Ashley V., additional, Costa, Ana S.H., additional, Rittenhouse, Natalie, additional, Marshall, Chris W., additional, Chiaranunt, Pailin, additional, Mullinax, Lauren, additional, Overacre-Delgoffe, Abigail, additional, Cooper, Vaughn S., additional, Poholek, Amanda C., additional, Delgoffe, Greg M., additional, Beyaz, Semir, additional, and Hand, Timothy W., additional

Published
2021
Full Text
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47. Neurotensin neurons in the central extended amygdala control energy balance

Author

Furlan, Alessandro, primary, Corona, Alberto, additional, Boyle, Sara, additional, Sharma, Radhashree, additional, Rubino, Rachel, additional, Habel, Jill, additional, Gablenz, Eva Carlotta, additional, Giovanniello, Jacqueline, additional, Beyaz, Semir, additional, Janowitz, Tobias, additional, Shea, Stephen D., additional, and Li, Bo, additional

Published
2021
Full Text
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