Figure 1. VEGF-A promotes an endothelial cell fate in human cardiac progenitor cells. Lui et al. identified VEGF-A as a paracrine factor that promotes endothelial cell differentiation from human cardiac progenitor cells. Endothelial cells contribute to the coronary artery and vein as well as endocardial compartments of the heart.

[I] Schematic representation of cardiac progenitor cell origins in the developing mouse embryo (pink). The first (red) and second (green) heart fields are shown at various stages of early embryonic development. The two fields make distinct regional and lineage contributions to the heart: right atrium (RA), left atrium (LA), right ventricle (RV) and left ventricle (LV). The second heart field makes major contributions to the outflow tract (OFT).

[II] ISL LIM homeobox 1 (ISL1)+ human cardiac progenitor cells can give rise to three cardiovascular cell lineages: cardiomyocytes, smooth muscle cells and endothelial cells. Lui et al. identified an intermediate population of endothelial cells, derived from the OFT of nine-week-old human fetal hearts (arrow), that resemble human embryonic stem cell (hESC)-derived ISL1+ endothelial cell progenitors. VEGF-A can promote in vitro differentiation of both types of multipotent progenitors (endogenous intermediate endothelial cells and ISL1+ cells derived from hESCs) toward an endothelial cell fate. In a mouse model, subcutaneous injection of human OFT-derived progenitor cells overexpressing VEGF-A from a synthetic modified RNA led to endothelial cell specification as well as the proliferation and survival of these cells in vivo.

(Figure based on Figure 3b in Buckingham, M. et al., Nat. Rev. Genet. 6, 826-837; 2005.)