The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Mitochondrial energy metabolic transcriptome profiles during cardiac differentiation from mouse and human pluripotent stem cells

  • Cho, Sung Woo (Division of Cardiology, Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Cardiac & Vascular Center) ;
  • Kim, Hyoung Kyu (Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutics Center, Inje University College of Medicine) ;
  • Sung, Ji Hee (Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutics Center, Inje University College of Medicine) ;
  • Kim, Yeseul (Department of Physiology, School of Medicine, Pusan National University) ;
  • Kim, Jae Ho (Department of Physiology, School of Medicine, Pusan National University) ;
  • Han, Jin (Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutics Center, Inje University College of Medicine)
  • Received : 2022.05.02
  • Accepted : 2022.07.21
  • Published : 2022.09.01
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Abstract

Simultaneous myofibril and mitochondrial development is crucial for the cardiac differentiation of pluripotent stem cells (PSCs). Specifically, mitochondrial energy metabolism (MEM) development in cardiomyocytes is essential for the beating function. Although previous studies have reported that MEM is correlated with cardiac differentiation, the process and timing of MEM regulation for cardiac differentiation remain poorly understood. Here, we performed transcriptome analysis of cells at specific stages of cardiac differentiation from mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs). We selected MEM genes strongly upregulated at cardiac lineage commitment and in a time-dependent manner during cardiac maturation and identified the protein-protein interaction networks. Notably, MEM proteins were found to interact closely with cardiac maturation-related proteins rather than with cardiac lineage commitment-related proteins. Furthermore, MEM proteins were found to primarily interact with cardiac muscle contractile proteins rather than with cardiac transcription factors. We identified several candidate MEM regulatory genes involved in cardiac lineage commitment (Cck, Bdnf, Fabp4, Cebpα, and Cdkn2a in mESC-derived cells, and CCK and NOS3 in hiPSC-derived cells) and cardiac maturation (Ppargc1α, Pgam2, Cox6a2, and Fabp3 in mESC-derived cells, and PGAM2 and SLC25A4 in hiPSC-derived cells). Therefore, our findings show the importance of MEM in cardiac maturation.

Keywords

Acknowledgement

This research was funded by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2017R1D1A3B03034465), the NRF of Korea funded by the Ministry of Science and ICT (MSIT) (2020R1C1C1015104), and the Basic Research Lab Program through the NRF of Korea funded by the MSIT (2020R1A4A1018943).

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