VCAM-1+ macrophage subset as ‘educators’ in fetal liver for transition to definitive hematopoiesis

Hematopoietic ontogeny has been well studied and are described in the literature as waves of activity (1). Intuitively, it is expected that early hematopoiesis will begin in the yolk sac since the early embryo will need support from blood cells, commonly termed the first wave (2). Consistent with the need for blood cells during the first wave, this period produces nucleated erythrocytes to ensure sufficient oxygenation. The second wave begins to generate a broader population of primitive hematopoiesis that can produce myeloid and lymphoid cells. This begins to prepare the nascent hematopoietic stem cells (HSCs) to leave the embryonic niche of early development to the fetal liver. The HSCs that are permanent after birth and throughout the life of an individual are populated in the bone marrow during the third wave of embryonic hematopoiesis in the aorta gonad-mesonephros (AGM) region (3).