April 27, 2010 - Scientists here have identified molecular pathways that lead to the differentiation of arteries and veins from pluripotent stem cells. The team, led by Jun K. Yamashita, an associate professor at the Center for iPS Cell Research and Application (CiRA) and the Institute for Frontier Medical Sciences, both at Kyoto University, found that a pair of signaling factors known as Notch and B-catenin are involved in driving undifferentiated cells to take on vascular fates. Their findings are now published in The Journal of Cell Biology.

Although it is widely known that arteries and veins are the principal types of blood vessels, the developmental steps that lead to their formation have long been a mystery. Yamashita has been focused on dissecting this process of vasculogenesis at the molecular level using pluripotent cells, such as embryonic stem (ES) and induced pluripotent stem (iPS) cells.

In this most recent study, the team built on prior work that showed how the signaling factor cyclic AMP (cAMP) is involved in specifying arterial (rather than venous) differentiation. Looking for downstream targets, they found that a pair of known signaling factors, Notch and B-catenin, work together to steer cells toward an arterial fate, adding two new pieces to the increasingly complex picture of vascular specification.

This new understanding of how converging signaling pathways drive artery specification may one day contribute to the development of stem cell-based regenerative therapies for such diseases as ischemic heart disease or cancer, as well as for the development of drugs specifically targeting blood vessels.