Purpose of review: The present study review examines the current understanding of the ontogeny of erythropoiesis with a focus on the emergence of the embryonic (primitive) erythroid lineage and on the similarities and differences between the primitive and the fetal/adult (definitive) forms of erythroid cell maturation.
Recent findings: Primitive erythroid precursors in the mouse embryo and cultured in vitro from human embryonic stem cells undergo 'maturational' globin switching as they differentiate terminally. The appearance of a transient population of primitive 'pyrenocytes' (extruded nuclei) in the fetal bloodstream indicates that primitive erythroblasts enucleate by nuclear extrusion. In-vitro differentiation of human embryonic stem cells recapitulates hematopoietic ontogeny reminiscent of the murine yolk sac, including overlapping waves of hemangioblast, primitive, erythroid, and definitive erythroid progenitors. Definitive erythroid potential in zebrafish embryos, like that in mice, initially arises prior to, and independent of, hematopoietic stem cell emergence in the region of the aorta. Maturation of definitive erythroid cells within macrophage islands promotes erythroblast-erythroblast and erythroblast-stromal interactions that regulate red cell output.
Summary: The study of embryonic development in several different model systems, as well as in cultured human embryonic stem cells, continues to provide important insights into the ontogeny of erythropoiesis. Contrasting the similarities and differences between primitive and definitive erythropoiesis will lead to an improved understanding of erythroblast maturation and the terminal steps of erythroid differentiation.