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.
Migliaccio
G
G
Department of Hematology, Istituto Superiore di Sanità, Rome, Italy.
Migliaccio
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AR
D000328:Adult; D000818:Animals; D001790:Blood Physiological Phenomena; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003470:Culture Media; D004357:Drug Synergism; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA
D003115:Colony-Stimulating Factors; D003470:Culture Media; D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors