Fig 3.

Relationship between HSCs, endothelial cells, and megakaryocytes. (A) Models of HSC emergence from the aorto-gonadal-mesonephros region during embryogenesis. Left panel, “Bipotential” model. In this model, bipotential mesodermal precursor cells give rise independently to endothelial cells lining the ventral aspect of the dorsal aorta and cells that migrate around the endothelial cells to form clusters of cells containing HSCs in the lumen of the aorta. Right panel, “Linear” model. In this model, mesodermal precursor cells give rise to specialized “hemogenic” endothelial cells lining the anterior aspect of the dorsal aorta. These cells then give rise directly to the HSC containing clusters in the dorsal aorta lumen. (B) Co-localization of megakaryocytes and HSCs at bone marrow vascular sinusoids. Diagram depicting vascular sinusoids in adult bone marrow. Mature megakaryocytes are shown in apposition to the bone marrow side of a single cell layer of endothelial cells lining the sinusoid. During megakaryocyte maturation, long cytoplasmic proplatelet extensions form and protrude into the vascular space through fenestrations in the endothelial cell layer. Fragments then are shed into the circulation where they are further processed into platelets. Hypothetical interactions between Mks and HSCs at the vascular sinusoidal niche are indicated by the green bi-directional arrow. Hypothetical low-level de novo generation of HSCs from vascular sinusoidal endothelial cells is indicated by the dashed arrow.