Exp Mol Med.
2016 Aug;48(8):e254. 10.1038/emm.2016.70.
Mitochondrial pyruvate dehydrogenase phosphatase 1 regulates the early differentiation of cardiomyocytes from mouse embryonic stem cells
- Affiliations
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- 1National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea. phyhanj@inje.ac.kr
- 2Laboratory of Vascular Biology and Stem Cell, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
- KMID: 2361541
- DOI: http://doi.org/10.1038/emm.2016.70
Abstract
- Mitochondria are crucial for maintaining the properties of embryonic stem cells (ESCs) and for regulating their subsequent differentiation into diverse cell lineages, including cardiomyocytes. However, mitochondrial regulators that manage the rate of differentiation or cell fate have been rarely identified. This study aimed to determine the potential mitochondrial factor that controls the differentiation of ESCs into cardiac myocytes. We induced cardiomyocyte differentiation from mouse ESCs (mESCs) and performed microarray assays to assess messenger RNA (mRNA) expression changes at differentiation day 8 (D8) compared with undifferentiated mESCs (D0). Among the differentially expressed genes, Pdp1 expression was significantly decreased (27-fold) on D8 compared to D0, which was accompanied by suppressed mitochondrial indices, including ATP levels, membrane potential, ROS and mitochondrial Ca²âº. Notably, Pdp1 overexpression significantly enhanced the mitochondrial indices and pyruvate dehydrogenase activity and reduced the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate compared to a mock control. In confirmation of this, a knockdown of the Pdp1 gene promoted the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate. In conclusion, our results suggest that mitochondrial PDP1 is a potential regulator that controls cardiac differentiation at an early differentiation stage in ESCs.
MeSH Terms
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Adenosine Triphosphate
Animals
Cell Lineage
Embryonic Stem Cells
Membrane Potentials
Mice*
Mitochondria
Mouse Embryonic Stem Cells*
Myocytes, Cardiac*
Oxidoreductases
Pyruvate Dehydrogenase (Lipoamide)-Phosphatase*
Pyruvic Acid*
RNA, Messenger
Adenosine Triphosphate
Oxidoreductases
Pyruvate Dehydrogenase (Lipoamide)-Phosphatase
Pyruvic Acid
RNA, Messenger
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