Abstract 900

As a hematopoietic cytokine, human erythropoietin (EPO) is required for precursor cell proliferation and differentiation into red blood cells. EPO activates hematopoietic stem cells by transmitting signals through two EPO receptors (EPORs), which trigger an intracellular phosphorylation cascade. To define whether EPOR expression and function are similar or different in hematopoietic stem cells obtained from distinct tissues, we compared EPOR mRNA expression, BFU-E, CFU-GM, and CFU-GEMM formation in cultures of fetal human liver (FHL) and human umbilical cord blood (CB) CD34+CD38-cell populations. The amounts of EPOR mRNA levels were equivalent in both FHL and CB CD34+CD38- derived cells. In contrast, the number of CB BFU-E colonies, in the presence of EPO, was three times greater than the number of similar colonies in FHL after 14 days in culture. The number of CFU-GM colonies in FLH and CB cultures were the same. These results suggest that FHL and CB stem cell erythropoiesis require the presence of EPO. Although FHL formed BFU-E colonies in response to EPO in a dose-dependent fashion, the lower number of colonies may imply the number and/or function of EPORs on FLH cells are different than on CB cells. Further characterization of FHL EPORs should facilitate our understanding of the interaction between EPO and EPOR during early human hematopoiesis.

This work was supported in part by USPHS MH46815 and the Children's Research Center of Michigan