Early hemopoietic differentiation: the action of multi-CSF is complemented by lineage specific growth factors

Although mechanisms controlling differentiation of hemopoietic stem and early progenitor cells are still poorly understood, it is generally conceded that a pivotal role is played by hemopoietic growth factors (HGFs). However, in-vitro analysis of their action on early progenitors may be obscured by cell-cell interaction, as well as by the presence of fetal bovine serum (FBS). To overcome these limitations, we investigated the action of pure multipotent or lineage-specific HGFs on purified progenitors grown in FBS-free cultures. In the murine system, highly purified progenitors were cultured in the presence of multipotent colony-stimulating factor (multi-CSF, also termed interleukin-3), erythropoietin (Ep) and macrophagic-CSF (M-CSF). Each HGF was unable by itself to induce significant colony growth. However, combined addition of multi-CSF and either Ep or M-CSF gave rise only to pure erythroid or macrophagic colonies, respectively. Partly purified human progenitors were challenged by human granulomonocytic-CSF (GM-CSF), pluripotent CSF (PPO, also termed granulocytic-CSF, G-CSF) and Ep. Here again, each HGF was unable per se to promote colony growth, but combined addition of GM-CSF or PPO and Ep gave rise only to pure erythroid colonies. These results support a model of early hemopoietic differentiation according to which multi-lineage HGFs represent "competence" GFs, the action of which is complemented by lineage-specific "progression" HGFs.