Progressive maturation toward hematopoietic stem cells in the mouse embryo aorta

Clusters of cells attached to the endothelium of the main embryonic arteries were first observed a century ago. Present in most vertebrate species, such clusters, or intraaortic hematopoietic clusters (IAHCs), derive from specialized hemogenic endothelial cells and contain the first few hematopoietic stem cells (HSCs) generated during embryonic development. However, some discrepancies remained concerning the spatio-temporal appearance and the numbers of IAHCs and HSCs. Therefore, the exact cell composition and function of IAHCs remain unclear to date. We show here that IAHCs contain pre-HSCs (or HSC precursors) that can mature into HSCs in vivo (as shown by the successful long-term multilineage reconstitution of primary neonates and secondary adult recipients). Such IAHC pre-HSCs could contribute to the HSC pool increase observed at midgestation. The novel insights in pre-HSC to HSC transition represent an important step toward generating transplantable HSCs in vitro that are needed for autologous HSC transplantation therapies.