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).^1,2 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 serutn (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.