Hemoglobin switching in culture: evidence for a humoral factor that induces switching in adult and neonatal but not fetal erythroid cells.

Publisher Website
Google Scholar
Abstract
An erythropoietic activity that exerts a profound effect on [human] fetal Hb synthesis is present in fetal sheep sera and it attains a peak concentration at the end of the 2nd to the middle of the 3rd trimester of fetal life. The activity consistently inhibits the increased synthesis of fetal Hb in cultures of burst-forming units (BFU) from normal adults. In cultures of BFU from homozygous .beta.+-thalassemias, the activity produces a striking decline in .gamma. chain synthesis, a decline in G.gamma./A.gamma. chain synthesis ratio and an increase in .delta./.gamma. and .alpha./non-.alpha. ratios, i.e., findings suggesting a genuine .gamma.-to-.beta. switch. The activity accelerates Hb F-to-Hb A switching in neonatal BFU cultures but it has no effect on fetal Hb synthesis in cultures of BFU obtained from human fetuses. Humoral factors play a role in the regulation of the switch from fetal to adult Hb formation, and progenitor cells from various stages of ontogeny respond differently to these factors. The results are compatible with the hypothesis that Hb switching during development is mediated through a change in a developmental program which controls the responsiveness of progenitor cells to switching activities in their environment.