Mitochondrial pyruvate dehydrogenase phosphatase 1 regulates the early differentiation of cardiomyocytes from mouse embryonic stem cells.
- Author:
Hye Jin HEO
1
;
Hyoung Kyu KIM
;
Jae Boum YOUM
;
Sung Woo CHO
;
In Sung SONG
;
Sun Young LEE
;
Tae Hee KO
;
Nari KIM
;
Kyung Soo KO
;
Byoung Doo RHEE
;
Jin HAN
Author Information
- Publication Type:Original Article
- MeSH: 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
- From:Experimental & Molecular Medicine 2016;48(8):e254-
- CountryRepublic of Korea
- Language:English
- 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 Ca²⁺. 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.
