Identification of haemogenic endothelium as the main source of the blood-endothelium common lineage in the mouse embryo

The first endothelial and blood cells of amniote embryos appear in close association in the blood islands of the yolk sac. This association and in vitro lineage analyses have suggested a common origin from mesodermal precursors called haemangioblasts, specified in the primitive streak during gastrulation. Fate mapping and chimera studies, however, failed to provide strong evidence for a common origin in the early mouse yolk sac. Additional in vitro studies suggest instead that mesodermal precursors first generate haemogenic endothelium, which then generate blood cells in a linear sequence. We conducted an in vivo clonal analysis to determine the potential of individual cells in the mouse epiblast, primitive streak and early yolk sac. We found that early yolk sac blood and endothelial lineages mostly derive from independent epiblast populations, specified before gastrulation. Additionally, a subpopulation of the yolk sac endothelium has haemogenic activity and displays characteristics similar to those found later in the embryonic haemogenic endothelium. Our results show that the earliest endothelial and blood cell populations in the mouse embryo are specified independently, and that haemogenic endothelium first appears in the yolk sac and produces blood precursors with markers related to definitive haematopoiesis.