Updated model of human embryonic hematopoiesis. Primitive erythroid cells are generated in the yolk sac (bottom left) and enter circulation with an intact nucleus. Macrophage progenitors appear in the chorionic plate of the placenta (middle left) and generate mature macrophages that migrate to the placental villi. Primitive erythroblasts and macrophages convene in the extravascular stroma of the placental villi to facilitate terminal maturation and enucleation of primitive RBCs and clearance of ejected nuclei (top left), in a similar manner to definitive RBC maturation in the fetal liver (bottom right). Concurrently, definitive HSCs are generated in the dorsal aorta, umbilical and vitelline arteries, and potentially in the placenta, and colonize the fetal liver for expansion and differentiation.