Mitochondrial pyruvate dehydrogenase phosphatase 1 regulates the early differentiation of cardiomyocytes from mouse embryonic stem cells
Experimental & Molecular Medicine
;
: e254-2016.
Artículo
en Inglés
| WPRIM
| ID: wpr-78634
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.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Oxidorreductasas
/
ARN Mensajero
/
Adenosina Trifosfato
/
Piruvato Deshidrogenasa (Lipoamida)-Fosfatasa
/
Linaje de la Célula
/
Ácido Pirúvico
/
Miocitos Cardíacos
/
Células Madre Embrionarias
/
Células Madre Embrionarias de Ratones
/
Potenciales de la Membrana
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2016
Tipo del documento:
Artículo
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