Hemoglobin F synthesis in vitro: evidence for control at the level of primitive erythroid stem cells.

The in vitro regulation of fetal hemoglobin (HbF was investigated in clones of cultured adult human erythroid cells by in situ immunofluorescent identification of the hemoglobins synthesized. Formation of Hb F-containing clones was enhanced by erythropoietin and by culture conditions favoring the proliferation of less-differentiated stem cells of the burst-forming-unit type. Burst-forming units differed in their capacity to direct Hb F synthesis in their terminally differentiated progeny. A class of early precursors that can produce descendent stem cells with or without commitment to Hb F production was identified. The findings suggest that the capability for expression of Hb F in terminally differentiated cells of the adult is determined at the level of less-differentiated erythroid stem cells with characteristics of burst-forming units. It is proposed that the regulation of Hb F synthesis in vivo is also linked to the process of differentiation of the erythroid stem cells and that the patterns of Hb F synthesis during ontogeny reflect the attainment of progressively higher levels of differentiation of erythroid stem cells as development proceeds.