Erythropoiesis

Erythropoiesis is the production of haemoglobin-containing red blood cells for oxygen delivery to the tissues. Approximately 1011-1012 red cells are produced each day, and this remarkable productivity under stable conditions is also complemented by the capacity for rapid and substantial expansion when required. This chapter describes the developmental origins of primitive and definitive erythropoiesis in the yolk sac, the fetal liver and the bone marrow. Our current understanding of the mechanisms of erythroid lineage specification from multipotent haemopoietic stem cells remains incomplete, but key erythroid-specific transcription factors (e.g. GATA2, GATA1, KLF1, NF-E2) are known to be critical in directing erythroid-specific transcription. Characteristic changes in morphology, gene expression, and cell surface markers allow the identification of erythroid cells at different stages of their maturation. At a systems level, the hormone erythropoietin is the principal regulator of erythroid activity. Following upregulation of its transcription by Hypoxia-Inducible Factor, erythropoietin permits an expansion of the pool of erythroid precursors and accelerated red cell maturation. This, together with coordinated iron absorption/delivery, provides an appropriate response to hypoxia caused by red cell loss. An appreciation of the normal mechanisms of erythropoiesis fosters a logical approach to the investigation of anaemia. Here we highlight those parts of the process that are amenable to clinical testing.