Erythropoiesis: an overview

Abstract

Red blood cell production is dynamic and highly regulated. The normal red cell life-span is approximately 120 days requiring, at equilibrium, a daily replacement of 0.8% to 1.0% of the circulating red cell pool. Balanced pro- duction and destruction maintain the red cell mass within relatively narrow limits. An immediate erythropoietic response is triggered when tissue oxy- genation is compromised due to blood loss or a shortened red cell life-span, or when demand increases for oxygen-carrying capacity. Erythrocytes arise primarily from the CD34+ pluripotent hematopoietic stem cells of the bone marrow. These progenitor stem cells constitute approx- imately 0.1% of the nucleated cells in the bone marrow, only about 5% of which are in cycle at any one time. The stem cell pool maintains itself,with little if any depletion, by asymmetric division into a committed colony-form- ing unit (CFU) and another stem cell. The quiescent stem cell remains in the G0 or G1 phase of the cell cycle, protected from genotoxic events and with extended time for DNA repair [1]. Cytokine binding to cell-surface receptors triggers stem cell activation. The early CFU have a higher proliferative rate but a more limited self-renewal rate than stem cells. The progeny of pluripotent CFU are heterogeneous, the result of a stochastic process with the possibility of more than one cell type evolving from early CFU progenitors; proliferation and survival are regulated by cytokines [2, 3]. Although most hematopoietic stem cells reside in the bone marrow, a small number circulate in the periph- eral blood, as do some of the early CFU cells.