Collaboration between WNT and BMP signaling promotes hemoangiogenic cell development from human fibroblast-derived...

Induced pluripotent stem (iPS) cells are generated by nuclear reprogramming of mature cells to a pluripotent state, and show biological properties of embryonic stem (ES) cells. The observation that human (h)ES cells generate hemoangiogenic progeny, defined by their high-level expression of KDR and low-level expression of PDGFRalpha (KDR(+)PDGFRalpha(lo)) via WNT and BMP signaling during 5-8 days of differentiation in a serum-free environment led us to address how hiPS cells give rise to hemoangiogenic progeny. In the presence of WNT3a, four hiPS cell lines derived from human skin fibroblasts commonly generated KDR(+) and/or PDGFRalpha(+) progeny by day 8 of differentiation. Endogenous BMP signaling was required for the WNT3a-directed upregulation of hemogenic cell development and the hemoangiogenic activity was confined in all cases to the KDR(+)PDGFRalpha(lo) fraction. Thus, iPS cells derived from human skin fibroblasts resemble hES cells in the generation of hematopoietic and endothelial cells in vitro.