BMP10 Signaling Promotes the Development of Endocardial Cells from Human Pluripotent Stem Cell-Derived Cardiovascular Progenitors

The embryonic endocardium is essential for early heart development as it functions to induce trabecular myocardium, the first heart tissue to form, and is the source of the cells that make up the valves and a portion of the coronary vasculature. With this potential, human endocardial cells could provide unique therapeutic opportunities that include engineering biological valves and cell-based therapy strategies to replace coronary vasculature in damaged hearts. To access human endocardial cells, we generated a human pluripotent stem cell (hPSC)-derived endothelial population that displays many characteristics of endocardium, including expression of the cohort of genes that identifies this lineage in vivo, the capacity to induce a trabecular fate in immature cardiomyocytes in vitro, and the ability to undergo an endothelial-to-mesenchymal transition. Analyses of the signaling pathways required for development of the hPSC-derived endocardial cells identified a novel role for BMP10 in the specification of this lineage from cardiovascular mesoderm.

Automated summary

The embryonic endocardium plays a vital role in early heart development by inducing the formation of trabecular myocardium, the source of valvular cells and part of the coronary vasculature. Human endocardial cells offer unique therapeutic opportunities, such as engineering biological valves and cell-based therapy for damaged hearts. By generating hPSC-derived endothelial cells, key signaling pathways for the development of endocardial cells were identified, with a novel role for BMP10 in lineage specification.