Effect of normal and COX6A2-deficient human pluripotent stem cells on gene expression during cardiomyocyte differentiation.
Cardiac remodeling is the initiating factor for the development of heart failure, which can result from various cardiomyopathies. Cytochrome c oxidase subunit 6A2 (COX6A2) is one of the components of cytochrome c oxidase that drives oxidative phosphorylation. We here report a COX6A2-deficient human cardiac myocyte (CM) model that mimicked the human COX6A2 homozygous mutation and determined the effects of COX6A2 dysfunction and its underlying mechanism.COX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs.  Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility.  In addition, L-carnitine and trimetazidine significantly improved energy metabolism in the COX6A2-deficient human myocardial model. Taken together, our data provide a COX6A2-deficient human cardiomyocyte model that exhibits abnormal energy metabolism, this model represents an important tool to gain insight into the mechanism of action of energy metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of COX6A2 deficiency, and facilitate drug screening. Overall design: To investigate the function of COX6A2 in  the pathogenesis of myocardial remodeling, we established a COX6A2-deficient human cardiac myocyte (CM) model. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells at one time point. Comparative gene exprission profiling analysis of RNA-seq data for cells.