Roles of MicroRNAs and Transcription Factors in the Maturation of Mesc-Differentiated Cardiomyocytes

ESCderived cardiomyocytes receive increasing attention because of their value in seeking healing methods for cardiovascular diseases. For many of these applications, mature cardiomyocytes are a prerequisite. Therefore, it is essential to understand the maturation process of ESC-derived cardiomyocytes. In this study, we profiled the genome wide mRNA and microRNA expression during the cardiomyocyte-specific differentiation of murine ESCs in order to identify cardiomyocyte maturation related genes and their functions. In total, we found 63 genes specifically related to the analysed maturation process. Functional analysis of these genes suggested an important role of cell adhesion in the cardiomyocytes-specific maturation process. Deciphering of the gene expression regulatory mechanisms during the maturation process is an important aspect. Various bioinformatics sources for target information of transcription factors and microRNAs combined with the detected gene expression patterns were applied to distinguish regulators involved in the gene expression regulation of maturation related genes. Overall 14 transcription factors were identified. Focusing on cell adhesion related pathways, the three transcription factors Ctcf, Trp53, Creb3 and two groups of microRNAs could be highlighted as core regulators for Mapk7, Itgb1, Col4a1 and Bcl2, which are part of these pathways. This study presents an overview of the gene expression changes at the early maturation phase of ESC-derived cardiomyocytes. The function of maturation related genes indicates the importance of cell adhesion during the cardiomyocyte maturation. These results suggest the possibility of getting more control of cardiomyocyte maturation by interfering cell adhesion, i.e. through identified transcription factors and microRNAs.