The switching from hemoglobin F to hemoglobin A formation in man: parallels between the observations in vivo and the findings in erythroid cultures.

The findings from studying Hb F synthesis in BFUe cultures parallel the findings in vivo. The BFUe's which are explanted from fetuses and neonates and seeded in culture behave as if they are already preprogrammed, in vivo, to follow a defined behavior in culture and produce erythroblasts with programs very similar to those of the cells in vivo. In the adult, the discrepancy between the low in vivo Hb F expression and the enhanced Hb F synthesis in culture can be explained on the same basis by which the appearance of F cells in vivo is explained: the normal in vivo environment is such that few cells take the F cell path; in vitro the environmental conditions are such as to induce formation of many F+ committed progeny from BFUe's. The studies in culture have revealed certain important clues about the cellular regulation of Hb F: they provided evidence that the regulatory events take place at the level of progenitor cells and evidence that the adult BFUe is a bipotent cell having the potential to form either F+A producing cells or only A producing cells. Studies in erythroid cultures have uncovered the phenomenon of asynchrony of Hb F and Hb A synthesis during the maturation of erythroblasts and have been used to investigate models of commitment to F cell formation. In general the culture of the erythroid progenitor cells offers opportunities to ask questions about regulation of Hb F to Hb A switching and to get answers which are relevant to regulation in vivo.