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

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)663-674
Number of pages12
JournalCell Metabolism
Volume23
Issue number4
DOIs
Publication statusPublished - 2016 Apr 12

    Fingerprint

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

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