Human and murine erythropoiesis. At birth, erythropoiesis occurs throughout the human skeleton, although over time hematopoietic activity is confined to the sternum and pelvic region of most adults. Likewise, in adult mice the bone marrow is the major organ, with the majority of hematopoietically active cells typically present in the femur and tibia, though this is dependent on the age and strain of the mouse. Erythropoiesis from the multipotent hematopoietic stem cell (HSC) through to the mature red blood cell is shown to allow comparison of human and mouse cell surface phenotypes. The time at which these markers are expressed and lost at the cell surface is very similar between species indicating that as a first approximation the mechanisms used to control cell expansion, differentiation, and removal of precursors may not differ greatly. Developing erythroid cells respond to signals from stromal cells of the bone marrow or spleen. Erythroblasts are organized into erythroblastic islands that consist of macrophages surrounded by developing erythroid precursors.^144,145  Macrophages provide many of the cellular mediators that control erythropoietic activity: GM-CSF, IL-3, and stem cell factor (SCF) generate colony-forming unit erythroid macrophage-granulocyte megakaryocyte (CFU-GEMM) and burst-forming unit erythroid (BFU-E), whereas TGF-β, TNF-α, and MIP1-α inhibit cell cycle activity¹⁴⁶  and BFU-E development. Other factors that negatively regulate numbers include proapoptotic activity initiated by interaction of the Fas receptor (CD95) with Fas ligand (CD95L).^147,148  Expression of caspases also results in cleavage of GATA-1 and loss of its antiapoptotic activity.¹⁴⁸  Secretion of Epo induces the expansion of colony-forming unit erythroid (CFU-E) and initiates differentiation through a number of erythroid-specific events. SCF and Epo synergize to drive the proliferation of human erythroid progenitors and precursors^150,151  and induce anti-apoptotic activity.^152,153  In human and mouse erythropoiesis, levels of the transferrin receptor (CD71) peak when the highest transport of transferrin-bound iron is required for synthesis of heme from protoporphyrin. During erythroid precursor maturation an increase in expression of glycophorin A (gpA) in humans or Ter119 in mice is coupled with a drop in CD71 expressed at the cell surface. This loss of CD71 indicates reduced proliferation and heme synthesis with continued differentiation into reticulocytes.