Genetic lineage tracing identifies endocardial origin of liver vasculature

The hepatic vasculature is essential for liver development, homeostasis and regeneration, yet the developmental program of hepatic vessel formation and the embryonic origin of the liver vasculature remain unknown. Here we show in mouse that endocardial cells form a primitive vascular plexus surrounding the liver bud and subsequently contribute to a substantial portion of the liver vasculature. Using intersectional genetics, we demonstrate that the endocardium of the sinus venosus is a source for the hepatic plexus. Inhibition of endocardial angiogenesis results in reduced endocardial contribution to the liver vasculature and defects in liver organogenesis. We conclude that a substantial portion of liver vessels derives from the endocardium and shares a common developmental origin with coronary arteries.