 Subsequent differentiation stages (proerythroblast to orthochromatic erythroblast) involve a decrease in cell size and eventual expulsion of the nucleus, and are likely dependent upon EpoR signaling only for their survival.In addition, some evidence on macrocytosis in hypoxic stress (when Epo can increase 1000-fold) suggests that mitosis is actually "skipped" in later erythroid stages, when EpoR expression is low/absent, in order to provide emergency reserve of red blood cells as soon as possible.Such data, though sometimes circumstantial, argue that there is limited capacity to proliferate specifically in response to Epo (and not other factors).