Journal
CELL METABOLISM
Volume 23, Issue 4, Pages 663-674Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2016.03.001
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Funding
- Highway Program for Realization of Regenerative Medicine from Japan Science and Technology Agency
- Support Program to break the bottlenecks at R&D Systems for accelerating the practical use of Health Research Outcome
- Biobank Japan Project by MEXT
- JSPS [25505004]
- Takeda Science Foundation
- JSPS KAKENHI grant [25-30005]
- Grants-in-Aid for Scientific Research [25505004] Funding Source: KAKEN
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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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