@article{8de658bbfd6d4aef84d33d7a7b083ccf,
title = "Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells",
abstract = "Summary 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.",
author = "Shugo Tohyama and Jun Fujita and Takako Hishiki and Tomomi Matsuura and Fumiyuki Hattori and Rei Ohno and Hideaki Kanazawa and Tomohisa Seki and Kazuaki Nakajima and Yoshikazu Kishino and Marina Okada and Akinori Hirano and Takuya Kuroda and Satoshi Yasuda and Yoji Sato and Shinsuke Yuasa and Motoaki Sano and Makoto Suematsu and Keiichi Fukuda",
note = "Funding Information: The authors thank Yoshiko Nagahata-Naito and Noriyo Hayakawa for technical assistance with metabolome analysis (Department of Biochemistry, Keio University), Drs. Satoru Okamoto and Yusuke Natsume for producing the modified DMEM (Ajinomoto), and Yoshiko Miyake, Sayaka Kanaami, Chihana Fujita, and Miho Yamaguchi for technical assistance with cell preparation (Department of Cardiology, Keio University). The authors also thank the Center for iPSC Research and Application, Kyoto University, for the 253G4 and 201B7 cell line, and the Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, for the hESC line (KhES2). The present work was mainly supported by the Highway Program for Realization of Regenerative Medicine from Japan Science and Technology Agency (to K.F.) and the Support Program to break the bottlenecks at R&D Systems for accelerating the practical use of Health Research Outcome (to K.F.) and partly supported by Biobank Japan Project by MEXT (to T.H. and T.M.), JSPS KAKENHI grant 25505004 (to J.F.), the Takeda Science Foundation (to J.F.), and JSPS KAKENHI grant 25-30005 (to S.T.) Funding Information: The authors thank Yoshiko Nagahata-Naito and Noriyo Hayakawa for technical assistance with metabolome analysis (Department of Biochemistry, Keio University), Drs. Satoru Okamoto and Yusuke Natsume for producing the modified DMEM (Ajinomoto), and Yoshiko Miyake, Sayaka Kanaami, Chihana Fujita, and Miho Yamaguchi for technical assistance with cell preparation (Department of Cardiology, Keio University). The authors also thank the Center for iPSC Research and Application, Kyoto University, for the 253G4 and 201B7 cell line, and the Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, for the hESC line (KhES2). The present work was mainly supported by the Highway Program for Realization of Regenerative Medicine from Japan Science and Technology Agency (to K.F.) and the Support Program to break the bottlenecks at R&D Systems for accelerating the practical use of Health Research Outcome (to K.F.) and partly supported by Biobank Japan Project by MEXT (to T.H. and T.M.), JSPS KAKENHI grant 25505004 (to J.F.), the Takeda Science Foundation (to J.F.), and JSPS KAKENHI grant 25-30005 (to S.T.) Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = apr,
day = "12",
doi = "10.1016/j.cmet.2016.03.001",
language = "English",
volume = "23",
pages = "663--674",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",
}