Differentiation and maturation of erythroblasts

Erythropoietin/receptor (EPO/EPOR) system is a pivotal regulator of erythropoiesis. Indeed, EPO-deficient and EPOR-deficient mice are embryonic lethal. The EPOR has two dominant forms, a full-length one (EPOR-F) and a truncated one (EPOR-T), by an alternative splicing mechanism of mRNA. The EPOR-T expresses abundantly in more immature erythroid progenitor cells. The EPOR-T acts as a dominant negative regulator of EPO-signals for proliferation and anti-apoptosis in cell lines. Presumably, the EPOR-T forms a heterodimer with EPOR-F and results in inhibition of efficient EPO-signals. Transgenic mice over-expressing the EPOR-T show an anemia and a severe defect in recovery from acute anemia. This result strongly suggests that the EPOR-T acts as a negative regulator for erythropoiesis also in vivo. It was reported that a large number of erythroid precursor cells die of apoptosis under physiological concentration of EPO in mouse. At higher EPO-concentration, these erythroid precursors escape from apoptosis and mature into erythrocytes. This mechanism might allow immediate supply of a large number of erythrocytes in case of acute anemia. In such mechanism, the EPOR-T might play an important role as a regulator of EPO-induced signals in erythroid cells.