Retinoic acid signaling in heart development: Application in the differentiation of cardiovascular lineages from human pluripotent stem cells

Retinoic acid (RA) signaling plays an important role during heart development in establishing anteroposterior polarity, formation of inflow and outflow tract progenitors, and growth of the ventricular compact wall. RA is also utilized as a key ingredient in protocols designed for generating cardiac cell types from pluripotent stem cells (PSCs). This review discusses the role of RA in cardiogenesis, currently available protocols that employ RA for differentiation of various cardiovascular lineages, and plausible transcriptional mechanisms underlying this fate specification. These insights will inform further development of desired cardiac cell types from human PSCs and their application in preclinical and clinical research. In this article, Devalla and colleagues outline the role of retinoic acid (RA) signaling in the heart and provide an overview of human pluripotent stem cell-based cardiac differentiation approaches that employ RA. They offer new insights into molecular mechanisms underpinning the function of RA signaling and discuss the crosstalk with wingless-related integration site (WNT) and bone morphogenetic protein (BMP) signaling in cardiac cell fate specification.