A COMMON PRECURSOR FOR PRIMITIVE ERYTHROPOIESIS AND DEFINITIVE HEMATOPOIESIS

The generation of blood cells, haematopoiesis, in the mouse embryo beg ins with the development of primitive nucleated erythroid cells in the yolk sac followed by the appearance of precursors for multiple defini tive haematopoietic lineages(1-4) The later developing lineages arise from multipotential stem cells(5,6), but the relationship of primitive erythroid cells to these other haematopoietic populations is unknown. Using an in vitro embryonic stem (ES) cell differentiation system(7), we show that primitive erythrocytes and other haematopoietic lineages arise from a common multipotential precursor that develops within emb ryoid bodies generated from differentiated ES cells, In response to va scular endothelial growth factor and c-kit Ligand these precursors giv e rise to colonies containing immature cells (blasts) expressing marke r genes characteristic of haematopoietic precursors, Many blast coloni es also expressed beta H1 and beta major globins but not Brachyury, a mesodermal marker, Kinetic analysis demonstrated that the blast colony -forming cells represent a transient population, preceding the establi shment of the primitive erythroid and other lineage-restricted precurs ors, This precursor population may represent the earliest stage of emb ryonic haematopoietic commitment.