A change in fate: lymphatic vessels reprogrammed to blood vessels

Blood circulation requires the vascular system, the vast network of arteries and veins through which blood is pumped. In a parallel network, known as the lymphatic system, lymph fluid, which contains a mixture of immune cells, bacteria, fat, and other debris, is circulated through specialized lymphatic vessels. The lymphatic system plays a critical role in helping the immune system fight off foreign pathogens in the body. Though the development of lymphatic vessels and blood vessels is completely separate in the body, researchers at the University of Pennsylvania in Philadelphia recently uncovered a novel mechanism that distinguishes whether vessels have a lymphatic or vascular fate. Led by Dr. Mark, Kahn, the research team found that mice lacking the signaling protein SLP76 have blood rather than lymph flowing through lymphatic vessels. By looking closely at the vessels, they showed that the endothelial cells lining the vessels were reprogrammed to assume a vascular fate. Further, they found that the presence of blood per se did not induce the change to blood vessels, but rather the sheer force caused by blood flow induced the transformation. Blood flow caused a decrease in the transcription factor PROX1, which is required to specify cells to the lymphatic fate. Their results uncover for the first time the role of fluid dynamics in determining endothelial cell identity.