Analysis of human hemoglobin switching in MEL x human fetal erythroid cell hybrids

The switch from fetal to adult globin synthesis in man was studied using heterospecific cell hybrids between human fetal erythroblasts and mouse erythroleukemia cells. When erythroblasts from first trimester fetuses were used the hybrids expressed a fetal program of human globin expression. While in continuous culture, these hybrids switched from predominantly fetal to almost exclusively adult globin expression, providing direct evidence that switching can occur within a single cell lineage. Sequential studies of globin expression at a single cell level and subcloning experiments suggested that the switch reflects a progressive increase in the generation of beta + cells from gamma + cells. Hybrids formed with erythroblasts of second trimester fetuses switched faster than those produced with cells of first trimester fetuses. The findings suggest that the human gamma to beta switch is controlled by a developmental clock-like mechanism, which appears to be associated with chromosome 11.