Ligand-Regulated and Developmental Stage-Specific Expression Of The EPO Receptor During Human Erythroid Progenitor Cell Formation

Upon engagement of its cell surface receptor, EPO sharply regulates erythroid progenitor cell (EPC) development. Little is known concerning the dynamics of EPOR expression, however, due to its rarity in primary cells. Using EPO dosing and response studies together with a highly specific and sensitive hEPOR antibody, we provide new insight into stage and ligand dose-dependent regulation of cell surface EPOR expression among human bone marrow derived primary EPCs. Developmentally, EPOR levels peaked within a KIT^posCD36^posGPA^neg proerythroblast cohort. In contrast to prior studies using transfected murine myeloid cell lines, the limiting of EPO substantially increased EPOR levels, demonstrating ligand dependent modulation of endogenous EPOR in hEPCs. EPO dosing and withdrawal studies further showed that in early EPCs EPO efficiently supported survival but not proliferation. In GPA^pos erythroblasts EPOR levels were diminished, but GPA^pos cells nonetheless exhibited strong EPO dependency for both survival and growth. Investigations provide novel insight into regulated EPOR surface expression among developing primary EPCs, and may also aid in understanding the action modes and effects of emerging EPOR agonists and erythropoiesis stimulating agents.