Model of erythropoiesis based on erythropoietin (EPO) suppression of erythroblast apoptosis and macrophage enhancement of erythroblast proliferation. In the CFU-E and early erythroblast stages, erythroid progenitor cells become dependent on EPO for prevention of apoptosis (EPO Dependence). Before the EPO-dependent period, the erythroid progenitors survive without EPO (Before EPO Dependence). Cells surviving transit through the EPO-dependent period (After EPO Dependence) complete one cell division and enucleate becoming reticulocytes (bottom rows of cells). EPO-dependent cells are heterogeneous, with the most dependent cells on the right side of each diagram and least dependent cells on the left. Surviving cells are indicated by intact nuclei, whereas cells undergoing apoptosis from insufficient EPO are indicated by fragmented nuclei. Although the actual number of EPO-dependent generations is unknown, 3 generations of EPO-dependent progenitors are shown for normal macrophage numbers and function (A), and 2 generations are shown for absent or decreased macrophage function (B).