Switch from fetal to adult hemoglobin is associated with a change in progenitor cell population

To examine the switch from fetal to adult hemoglobin at the cellular level, erythroid progenitor cells from newborn infants and adults were cultured in methyl cellulose with erythropoietin. Individual erythroid colonies were labeled with [ ³H]leucine at various times, and globin synthesis patterns examined by gel electrophoresis and fluorography. The percent γ- or β-globin synthesis was determined from the total of γ + β, and the percent Gγ from the total of Gγ + Aγ. The nonparametric correlation coefficients of percent Gγ with percent γ or β were obtained. Each group of colonies at each time point was examined separately. In colonies from adult blood, the proportion of Gγ-synthesis did not correlate with the proportion of γ-synthesis. Colonies from newborn blood fell into two groups. Those that developed from relatively mature progenitor cells, and were seen on day 14, showed a strong negative correlation of Gγ with β-globin synthesis. However, those newborn colonies that developed from immature progenitors, and were seen later in culture (days 17 and 21), showed no correlation of Gγ with β-synthesis. These findings are compatible with a clonal model for hemoglobin switching. Fetal progenitors, in which Gγ- and β-syntheses are negatively correlated, are gradually replaced during ontogeny by adult progenitors. The adult progenitors produce more β (less γ), and the proportions of Gγ- and γ- or β-synthesis are not correlated.