PLURIPOTENT STEM-CELLS CONSTITUTIVELY EXPRESSING A NORMAL ERYTHROPOIETIN RECEPTOR GIVE RISE TO NORMAL HEMATOPOIESIS IN LETHALLY IRRADIATED RECIPIENT MICE

The cellular mechanism by which the stem cell differentiates toward an individual myeloid lineage is unknown. To determine whether lineage-s pecific cytokines are involved in stem cell determination, murine bone marrow cells were infected with a retroviral vector carrying a murine erythropoietin receptor (EpoR) cDNA. Infected marrow cells were trans planted into lethally irradiated syngeneic recipient mice, and the eff ect of Epo was studied on EpoR-expressing pluripotent stem cell determ ination. The graft contained, among myeloid cells, around 100 CFU-S-12 , half of which were retrovirally infected. One month after grafting, the bone marrow of mice reconstituted with EpoR-infected cells contain ed 50 times more infected multipotent progenitors than mice reconstitu ted with control bone marrow cells. However, this number returned to n ormal 45 days after the graft. No variation was observed in peripheral blood, bone marrow, and spleen cellularities or in committed progenit ors in the bone marrow and in the spleen when Neo or EpoR reconstitute d mice were assayed. When Epo was delivered into reconstituted mice on e month after grafting, Epo had no differential effect in EpoR or Neo reconstituted mice. This study emphasizes the in vivo Epo proliferativ e response of multipotent progenitors expressing a normal EpoR gene an d shows that, in vivo as in vitro, the differentiation of these multip otent progenitors is not preferentially oriented toward erythropoiesis .