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Nutritional perception in stem-cell fate decision and tissue regeneration
Adaptation to dietary changes profoundly influenced human evolution and continues to impact our modern lives in health and diseases. After embryonic development, tissue-resident adult stem and progenitor cells remain the capacity to adjust their regenerative activity in response to diets and nutritional states to maintain tissue homeostasis. Such adaptation must rely on the systemic mediators integrating the inter-organ crosstalk to coordinate whole-body metabolism and the intracellular signaling machinery converting the nutritional messages into the transcriptional regulatory actions to determine the stem cell fate.
Our research focuses on the interface of nutritional and transcriptional regulatory networks. We study how adult stem and progenitor cells perceive the nutritional states and fine-tune their lineage decisions in tissue regeneration and disease development processes. Our goal is to illustrate the conversion from the nutritional perception to cell fate decisions at the single-cell level, in the hope of inspiring new therapeutic strategies. Towards this end, we use genetic mouse models, organoid systems, and transplantation experiments to identify and characterize the endocrinal and metabolic cell-fate determinants in the contexts of tissue homeostasis and adaptation to diet. Current projects investigate the therapeutic potential of signaling metabolites in treating cancer, diabetes, and age-related degenerative diseases.
Calibasi-Kocal G, Mashinchian O, Basbinar Y, Ellidokuz E, Cheng CW* and Yilmaz O*. (*co-corresponding author) Nutritional Control of Intestinal Stem Cells in Homeostasis and Tumorigenesis. (2020). Trends Endocrinol Metab. In press
Cheng CW, Yilmaz OH, Mihaylova MM. Strategies for Measuring Induction of Fatty Acid Oxidation in Intestinal Stem and Progenitor Cells. (2020). Methods Mol Biol. p53-64. doi: 10.1007/978-1-0716-0747-3_4. PMID: 32705635
Cheng CW, Biton M, Haber A, Rickelt S, Butty V, Whary MT, Levine SS, Mino-Kenudson M, Deshpande V, Hynes RO, Fox JG, Regev A and Yilmaz ÖH. Ketone Body Signaling Mediates Intestinal Stem Cell Homeostasis and Adaptation to Diet. (2019).Cell. PMID:31442404.
Mihaylova MM*, Cheng CW*, Cao AQ, Tripathi S, Mana MD, Bauer-Rowe KE, Abu-Remaileh M, Clavain L, Erdemir A, Lewis C, Freinkman E, Huang Y, Bell G, Deshpande V, Carmeliet P, Katajisto P, Sabatini DM and Yilmaz ÖH. (*co-first author) Fasting-Activated Fatty Acid Oxidation Enhances Intestinal Stem Cell Function. (2018). Cell Stem Cell. PMID:29727683
Cheng CW and Yilmaz ÖH. FAOund the Link: Phospholipid Remodeling and Intestinal Stem Cell Growth and Tumorigenesis. (2018). Cell Stem Cell. PMID:29395049
Cheng CW and Yilmaz ÖH. Starving leukemia to induce differentiation. (2017). Nature Medicine. PMID:28060803
Cheng CW, Villani V, Buono R, Wei M, Kumar S, Yilmaz OH, Cohen P, Sneddon J, Perin L, and Longo V. Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes. (2017).Cell. PMID:28235195
Cheng CW and Yilmaz ÖH. IGFBP3 and T1D: Systemic Factors in Colonic Stem Cell Function and Diabetic Enteropathy. (2015). Cell Stem Cell. PMID:26431180.
Cheng CW, Gregor B. Adams, Laura Perin, Min Wei, Xiaoying Zhou, Ben S. Lam, Stefano Da Sacco, Mario Mirisola, David Quinn, Tanya Dorff, John J. Kopchick and Valter D. Longo. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. (2014). Cell Stem Cell. PMID: 24905167