HbF and HbA production in erythroid cultures from human fetuses and neonates

The synthesis of γ- and β-globin chains was investigated in erythroid cultures from first and second trimester fetuses as well as neonates in order to examine whether the differences in production of HbA and F in the fetal and newborn ontogenetic stages reflect in vivo predetermined differences in commitment among erythroid progenitors. Cultures of erythroid progenitors from first and second trimester fetuses (12 experiments) produced amounts of HbF that were similar to those synthesized in vivo by fetal liver erythro-blasts and reticulocytes (range of HbF production: in vivo, 84%-93%; in culture, 80%-94%). There was no difference in HbF synthesis in cultures of fetal liver or peripheral blood-origin progenitors from the same fetus. In cultures of circulating progenitors from full-term newborns (nine experiments), amounts of fetal hemoglobin that are expected for the newborn ontogenetic stage (range of HbF in culture: 55%-80% of total Hb) and that are close to the levels of HbF production in cord-blood reticulocytes of the same fetuses, were observed. Varying the concentration of erythropoietin by 40-fold produced only minor changes in the proportion of γ and β chain synthesis in culture. The findings show that the fetal or newborn erythroid stem cells are programmed in vivo for expressing the characteristic, for each ontogenetic stage, pattern of non-α-globin synthesis. This is consistent with the proposition that the regulation of γ- and β-chain synthesis during development takes place at the level of erythroid progenitor cells rather than in the terminally mature erythron.