Cho Sung Woo, Kim Hyoung Kyu, Sung Ji Hee, Kim Yeseul, Kim Jae Ho, Han Jin
Division of Cardiology, Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Cardiac & Vascular Center, Goyang 10380, Korea.
Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutics Center, Inje University College of Medicine, Busan 47392, Korea.
Korean J Physiol Pharmacol. 2022 Sep 1;26(5):357-365. doi: 10.4196/kjpp.2022.26.5.357.
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 (, , , , and in mESC-derived cells, and and in hiPSC-derived cells) and cardiac maturation (, , , and in mESC-derived cells, and and in hiPSC-derived cells). Therefore, our findings show the importance of MEM in cardiac maturation.
肌原纤维和线粒体的同步发育对于多能干细胞（PSC）的心脏分化至关重要。具体而言，心肌细胞中线粒体能量代谢（MEM）的发育对于心脏跳动功能至关重要。尽管先前的研究报道MEM与心脏分化相关，但对于心脏分化过程中MEM调控的过程和时间仍知之甚少。在这里，我们对小鼠胚胎干细胞（mESC）和人诱导多能干细胞（hiPSC）心脏分化特定阶段的细胞进行了转录组分析。我们选择了在心脏谱系定向时强烈上调且在心脏成熟过程中呈时间依赖性上调的MEM基因，并确定了蛋白质-蛋白质相互作用网络。值得注意的是，发现MEM蛋白与心脏成熟相关蛋白而非心脏谱系定向相关蛋白密切相互作用。此外，发现MEM蛋白主要与心肌收缩蛋白而非心脏转录因子相互作用。我们鉴定了几个参与心脏谱系定向（mESC来源的细胞中的 、 、 、 、 ，以及hiPSC来源的细胞中的 和 ）和心脏成熟（mESC来源的细胞中的 、 、 、 ，以及hiPSC来源的细胞中的 和 ）的候选MEM调控基因。因此，我们的研究结果表明MEM在心脏成熟中的重要性。
