Cardiac Induction of Embryonic Stem Cells by a Small Molecule Inhibitor of Wnt/β-Catenin Signaling

In vitro differentiation of embryonic stem cells is tightly regulated by the same key signaling pathways that control pattern formation during embryogenesis. Small molecules that selectively target these developmental pathways, including Wnt, and BMP signaling may be valuable for directing differentiation of pluripotent stem cells toward many desired tissue types, but to date only few such compounds have been shown to promote cardiac differentiation. Here, we show that XAV939, a recently discovered small molecule inhibitor of Wnt/beta-catenin signaling, can robustly induce cardiomyogenesis in mouse ES cells. Our results suggest that a timely administration of XAV939 immediately following the formation of mesoderm progenitor cells promotes cardiomyogenic development at the expense of other Embryonic Stem Cells mesoderm derived lineages, including the endothelial, smooth muscle, and hematopoietic lineages. Given the critical role that Wnt/beta-catenin signaling plays in many aspects of embryogenesis and tissue regeneration, XAV939 is a valuable chemical probe to dissect in vitro differentiation of stem cells and to explore their regenerative potential in a variety of contexts.