ハットリ フミユキ
HATTORI FUMIYUKI 服部 文幸 所属 関西医科大学 iPS・幹細胞再生医学講座 職種 研究教授 |
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論文種別 | 原著(症例報告除く) |
言語種別 | 英語 |
査読の有無 | その他(不明) |
表題 | Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells |
掲載誌名 | 正式名:Cell metabolism 略 称:Cell Metab ISSNコード:1932742015504131 |
巻・号・頁 | 23(4),pp.663-674 |
著者・共著者 | Tohyama Shugo, Fujita Jun, Hishiki Takako, Matsuura Tomomi, Hattori Fumiyuki, Ohno Rei, Kanazawa Hideaki, Seki Tomohisa, Nakajima Kazuaki, Kishino Yoshikazu, Okada Marina, Hirano Akinori, Kuroda Takuya, Yasuda Satoshi, Sato Yoji, Yuasa Shinsuke, Sano Motoaki, Suematsu Makoto, Fukuda Keiichi |
発行年月 | 2016/04 |
概要 | 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. |
DOI | 10.1016/j.cmet.2016.03.001 |
PMID | 27050306 |