Human embryonic hemopoiesis: control mechanisms underlying progenitor differentiation in vitro.
In order to investigate differences in control mechanisms between embryonic and adult hemopoiesis, we have studied the sensitivity of human embryonic progenitors (5-8 weeks postconception) to either positive (erythropoietin (Ep), granulocyte-macrophage colony-stimulating factor (GM-CSF) and insulin-like growth factor 1 (IGF-1] or negative (tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma] in vitro regulators of adult hemopoietic differentiation. Growth stimulators were analyzed under serum-deprived conditions whereas growth inhibitors were investigated in serum-supplemented culture. Formation of granulocyte-macrophage colonies from embryonic progenitors was induced by GM-CSF but inhibited by TNF and IFN-gamma. Early erythroid progenitors resemble adult erythroid burst-forming cells (BFU-E) in their sensitivity to Ep and TNF but differ in their lack of response to GM-CSF or other adult sources of burst-promoting activity, and absence of inhibition by IFN-gamma. IGF-1 promoted erythroid burst formation in the absence of insulin, but did not have Ep-like activity. These data indicate that embryonic and adult erythroid progenitors differ at least in terms of in vitro sensitivity to GM-CSF and IFN-gamma and suggest that different cellular response to control signals may underlie the differences observed in vivo between embryonic and adult hemopoiesis.
D002454:Cell Differentiation; D002478:Cells, Cultured; D002999:Clone Cells; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D005314:Embryonic and Fetal Development; D004921:Erythropoietin / Q000494:pharmacology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma