| Literature DB >> 27050306 |
Shugo Tohyama1, Jun Fujita2, Takako Hishiki3, Tomomi Matsuura4, Fumiyuki Hattori5, Rei Ohno6, Hideaki Kanazawa6, Tomohisa Seki6, Kazuaki Nakajima6, Yoshikazu Kishino6, Marina Okada6, Akinori Hirano7, Takuya Kuroda8, Satoshi Yasuda8, Yoji Sato8, Shinsuke Yuasa6, Motoaki Sano6, Makoto Suematsu4, Keiichi Fukuda9.
Abstract
Human pluripotent stem cells (hPSCs) are uniquely dependent on aerobic glycolysis to generate ATP. However, the importance of oxidative phosphorylation (OXPHOS) has not been elucidated. Detailed amino acid profiling has revealed that glutamine is indispensable for the survival of hPSCs. Under glucose- and glutamine-depleted conditions, hPSCs quickly died due to the loss of ATP. Metabolome analyses showed that hPSCs oxidized pyruvate poorly and that glutamine was the main energy source for OXPHOS. hPSCs were unable to utilize pyruvate-derived citrate due to negligible expression of aconitase 2 (ACO2) and isocitrate dehydrogenase 2/3 (IDH2/3) and high expression of ATP-citrate lyase. Cardiomyocytes with mature mitochondria were not able to survive without glucose and glutamine, although they were able to use lactate to synthesize pyruvate and glutamate. This distinguishing feature of hPSC metabolism allows preparation of clinical-grade cell sources free of undifferentiated hPSCs, which prevents tumor formation during stem cell therapy.Entities:
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Year: 2016 PMID： 27050306 DOI： 10.1016/j.cmet.2016.03.001
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287