FIG 1.

Ontogeny of hematopoiesis. The origin of human blood cells begins in the mesoderm of the extraembryonic yolk sac around the third week of embryogenesis and is known as the primitive stage. The emergence of blood cells from the hemogenic endothelium begins within the yolk sac in week 5 during the prodefinitive (second) stage and is regulated by dorsal-ventral polarity and Notch signaling. Blood cell production then transitions to the ventral wall of the aorta at around the seventh to eighth week during the definitive stage and is regulated by the transcription factor Runx1 in a process known as the endothelial-to-hematopoietic transition (EHT), where HSCs are first identified. After the eighth week of gestation, early blood cells seed the liver, thymus, and spleen until the seventh month of gestation, when hematopoiesis transitions to the bone marrow. After this time, the bone marrow becomes the sole site for platelet and red and white blood cell formation.