Abstract
In the embryonic heart, endocardial cells undergo both endothelial-to-mesenchymal transition and endothelial-to-hematopoietic transition in parallel under the control of Nkx2-5/Notch signaling, thereby giving rise to both endocardial cushion mesenchyme and hematopoietic progenitors. These hemogenic cells subsequently differentiate into macrophages with high phagocytic activity through Dhrs 3-mediated suppression of retinoic acid signaling, and play a distinct role in endocardial cushion remodeling and cardiac valve formation. In this review, we summarize the current understanding of these lineage relationships and molecular mechanisms, highlight species-specific differences, and species-specific differences, and discuss the physiological significance of endocardial hematopoiesis in cardiac development.