Abstract 19865: Transcriptional Landscape of Cardiomyocyte Maturation

Abstract

Introduction: The term “development” refers to the process of growing to maturity. While decades of progress in developmental cardiology contributed to our understanding of heart development, the efforts were mostly focused on early aspects of development such as cardiomyocyte (CM) differentiation, which is completed at mid-gestation. However, CM maturation, a later developmental process required to generate adult CMs, remains largely unknown. The lack of the knowledge may be attributed to the fact that the process typically takes place over a long period of time after terminal differentiation. Results: Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and found a large number of genes whose expression shifts gradually and continuously throughout the stages. Based on the datasets, we generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs). This analysis revealed discrete sets of key transcriptional regulators and pathways that are temporally activated or suppressed over the course of CM maturation. We developed a GRN-based program named MatStatCM that informs the status of CM maturation at the molecular level. The MatStatCM demonstrated that pluripotent stem cell-derived CMs undergo maturation early in culture, but are arrested at the late embryonic stage, accompanied by aberrant expression of key transcription factors. Conclusions: Our study provides a foundation for understanding CM maturation.