Project 461703

During the development of blood vessels in the embryo some of the blood vessel lining cells, called hemogenic endothelial cells, become blood stem cells, which then create the circulating blood system. Little is known about what signals drive some endothelial cells to become blood cells. Even less is known about how other cells in the embryo regulate this process to ensure adequate blood production over a lifetime. The programs that are activated to make blood stem cells is key to understanding how endothelial cells choose their fate. We have identified a gene called Sash1 that sends signals from different cell types to promote the endothelial cells to make blood stem cells. The purpose of this project is to take this information and understand how Sash1 generates signals from other cell types to activate hemogenic endothelial cells. Blood stem cell transplantation is critical for adults with leukemia and other cancers to be able to replenish a normal blood system after treatment with chemotherapy or radiotherapy. Recently there has been some progress in making new blood stem cells in a dish, but there is still much work to be done to create normal blood stem cells in a dish. Our research will help identify external chemicals that help to make blood stem cells from endothelial cells, which we hope will provide a new source of blood stem cells for transplantation for various kinds of blood diseases. Understanding what signals coax the endothelial cells to become blood stem cells, and what other cell types are required for this process is critical in understanding mechanisms of blood stem cell formation and improving treatments for blood and other cancers.