Development and differentiation of the erythroid lineage in mammals

• In the developing embryo mouse hematopoiesis emerges in three waves.
• Erythroid cell maturation occurs through five distinct stages.
• Erythropoietin and stem cell factor are essential for sufficient red cell production.
• Erythropoietin rescues erythroid progenitors from apoptosis to maintain red cell numbers.
• Erythroid progenitors undergo increased self-renewal in response to stress conditions.

The red blood cell (RBC) is responsible for performing the highly specialized function of oxygen transport, making it essential for survival during gestation and postnatal life. Establishment of sufficient RBC numbers, therefore, has evolved to be a major priority of the postimplantation embryo. The “primitive” erythroid lineage is the first to be specified in the developing embryo proper. Significant resources are dedicated to producing RBCs throughout gestation. Two transient and morphologically distinct waves of hematopoietic progenitor-derived erythropoiesis are observed in development before hematopoietic stem cells (HSCs) take over to produce “definitive” RBCs in the fetal liver. Toward the end of gestation, HSCs migrate to the bone marrow, which becomes the primary site of RBC production in the adult. Erythropoiesis is regulated at various stages of erythroid cell maturation to ensure sufficient production of RBCs in response to physiological demands. Here, we highlight key aspects of mammalian erythroid development and maturation as well as differences among the primitive and definitive erythroid cell lineages.