Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells

Shugo Tohyama; Jun Fujita; Takako Hishiki; Tomomi Matsuura; Fumiyuki Hattori; Rei Ohno; Hideaki Kanazawa; Tomohisa Seki; Kazuaki Nakajima; Yoshikazu Kishino; Marina Okada; Akinori Hirano; Takuya Kuroda; Satoshi Yasuda; Yoji Sato; Shinsuke Yuasa; Motoaki Sano; Makoto Suematsu; Keiichi Fukuda

doi:10.1016/j.cmet.2016.03.001

Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells

Shugo Tohyama, Jun Fujita, Takako Hishiki, Tomomi Matsuura, Fumiyuki Hattori, Rei Ohno, Hideaki Kanazawa, Tomohisa Seki, Kazuaki Nakajima, Yoshikazu Kishino, Marina Okada, Akinori Hirano, Takuya Kuroda, Satoshi Yasuda, Yoji Sato, Shinsuke Yuasa, Motoaki Sano, Makoto Suematsu, Keiichi Fukuda

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

192 被引用数 (Scopus)

抄録

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.

本文言語	英語
ページ（範囲）	663-674
ページ数	12
ジャーナル	Cell Metabolism
巻	23
号	4
DOI	https://doi.org/10.1016/j.cmet.2016.03.001
出版ステータス	出版済み - 12-04-2016
外部発表	はい

All Science Journal Classification (ASJC) codes

生理学
分子生物学
細胞生物学

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10.1016/j.cmet.2016.03.001

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Tohyama, S., Fujita, J., Hishiki, T., Matsuura, T., Hattori, F., Ohno, R., Kanazawa, H., Seki, T., Nakajima, K., Kishino, Y., Okada, M., Hirano, A., Kuroda, T., Yasuda, S., Sato, Y., Yuasa, S., Sano, M., Suematsu, M., & Fukuda, K. (2016). Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells. Cell Metabolism, 23(4), 663-674. https://doi.org/10.1016/j.cmet.2016.03.001

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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",

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doi = "10.1016/j.cmet.2016.03.001",

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Tohyama, S, Fujita, J, Hishiki, T, Matsuura, T, Hattori, F, Ohno, R, Kanazawa, H, Seki, T, Nakajima, K, Kishino, Y, Okada, M, Hirano, A, Kuroda, T, Yasuda, S, Sato, Y, Yuasa, S, Sano, M, Suematsu, M & Fukuda, K 2016, 'Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells', Cell Metabolism, vol. 23, no. 4, pp. 663-674. https://doi.org/10.1016/j.cmet.2016.03.001

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T1 - Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells

AU - Tohyama, Shugo

AU - Fujita, Jun

AU - Hishiki, Takako

AU - Matsuura, Tomomi

AU - Hattori, Fumiyuki

AU - Ohno, Rei

AU - Kanazawa, Hideaki

AU - Seki, Tomohisa

AU - Nakajima, Kazuaki

AU - Kishino, Yoshikazu

AU - Okada, Marina

AU - Hirano, Akinori

AU - Kuroda, Takuya

AU - Yasuda, Satoshi

AU - Sato, Yoji

AU - Yuasa, Shinsuke

AU - Sano, Motoaki

AU - Suematsu, Makoto

AU - Fukuda, Keiichi

PY - 2016/4/12

Y1 - 2016/4/12

N2 - 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.

AB - 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.

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Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells

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