['Interaction between sinusoidal endothelial cells and hepatocytes is a prerequisite for liver function. Upon tissue loss, both liver cell populations need to be regenerated. Repopulation occurs in a coordinated pattern, first through the regeneration of parenchyme (hepatocytes), which then produces vascular endothelial growth factor (VEGF) to enable the subsequent angiogenic phase. The signals that instruct hepatocytes to induce timely VEGF remain unidentified. Given that liver is highly vascularized, we reasoned that fluctuations in oxygenation after tissue loss may contribute to the coordination between hepatocyte and sinusoidal endothelial cell proliferation. To prevent drops in oxygen after hepatectomy, mice were pretreated with inositol trispyrophosphate (ITPP), an allosteric effector of hemoglobin causing increased O'] Does hypoxia-driven Hif2a coordinate mouse liver regeneration by coupling parenchymal growth to vascular expansion?