Mitochondrial energy metabolic transcriptome profiles during cardiac differentiation from mouse and human pluripotent stem cells

• Published in: The Korean journal of physiology & pharmacology Vol. 26; no. 5; pp. 357 - 365
• Main Author: 조성우(Sung Woo Cho), 김형규(Hyoung Kyu Kim), 성지희(Ji Hee Sung), 김예슬(Yeseul Kim), 김재호(Jae Ho Kim), 한진(Jin Han)
• Format: Journal Article
• Language: Korean
• Published: 대한생리학회-대한약리학회 30.09.2022; The Korean Journal of Physiology & Pharmacology Editorial Office
• Subjects: Pluripotent stem cell; Cardiac myocytes; Mitochondria
• ISSN: 1226-4512; 2093-3827

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.