The production of erythrocytes is a tightly regulated process. During steady state hematopoiesis, approximately 1010 red blood cells are produced per hour in the bone marrow to maintain the hemoglobin level within fairly narrow limits. Production can be rapidly increased in the setting of ongoing blood loss or hemolysis.
Erythropoiesis begins with the differentiation of a small pool of pluripotent stem cells into the most primitive erythroid progenitors. These progenitors develop into recognizable erythroid precursors, which subsequently follow a specific differentiation program that culminates in the emergence of mature erythrocytes. This process is driven by successive combinations of transcription factors that dictate the expression of adhesion and hematopoietic growth factor receptors (HGFRs):
●Adhesion receptors play an important role in the localization and release of maturing cells from specific niches in bone marrow.
●Hematopoietic growth factors (HGFs), such as those for interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and Stem Cell Factor (SCF, also called c-kit ligand or Steel factor), are important for the amplification of progenitor cells.
Erythropoietin (EPO) is a growth factor essential for the amplification and terminal differentiation of erythroid progenitors and precursors. Information concerning the control of EPO expression by hypoxia has provided new insight into the regulation of erythropoiesis. (See 'Hypoxia and EPO expression' below and "Molecular pathogenesis of congenital polycythemic disorders and polycythemia vera", section on 'Oxygen sensor'.)