Genetic and Epigenetic Regulation of Cardiac Development: An Integrative View from Embryo to Human Pluripotent Stem Cell Models

Cardiogenesis is an exquisitely complex developmental process that unfolds through a series of tightly regulated and dynamic morphogenetic events. Proper heart development demands meticulous coordination of multiple signaling pathways, transcription factors and epigenetic mechanisms at every stage of cardiogenesis. Better understanding of the molecular regulation of cardiac development and the advances in the field of stem cell technology have paved way to the development of robust differentiation strategies to generate cardiomyocytes from pluripotent stem cells. This review provides a concise overview of key processes underlying human cardiac development, with a focus on their genetic and epigenetic regulation. It further discusses the generation of cardiomyocytes from human pluripotent stem cells, highlighting state-of-the-art differentiation protocols and detailing the genetic and epigenetic mechanisms that govern in vitro cardiomyocyte formation. By integrating insights from both in vivo human cardiac development and in vitro pluripotent stem cell-derived cardiomyocyte models, this article offers a comprehensive perspective on how embryonic cardiogenesis can be recapitulated in vitro, deepening our understanding of the molecular framework governing cardiomyocyte formation. Importantly, these insights hold significant translational potential for advancing disease modeling, drug discovery, and regenerative therapies for cardiovascular diseases.