Embryonic → fetal Hb switch in humans: Studies on erythroid bursts generated by embryonic progenitors from yolk sac and liver

C. Peschle, A. R. Migliaccio, G. Migliaccio

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Abstract

The synthesis of embryonic (ζ, ε), fetal (α, γ), and adult (β) globin was evaluated in human yolk sacs (YS) and livers at different ontogenic stages (i.e., from 6 through 10-12 wk of age) by means of analytical isoelectric focusing. Globin production was comparatively evaluated in vivo (i.e., in directly labeled erythroblasts from YS and liver) and in vitro [i.e., in erythroid bursts generated in culture by erythroid burst-forming units (BFU-E) from the same erythropoietic tissues]. Erythroid bursts generated in vitro by BFU-E from 6-wk livers and YS show essentially a 'fetal' globin synthetic pattern: this is in sharp contrast to the 'embryonic' pattern in corresponding liver and YS erythroblasts directly labeled in vivo. The in vitro phenomenon suggests that (i) 6-wk BFU-E constitute a new generation of progenitors, which have already switched from an embryonic to a fetal program, and/or (ii) expression of their fetal program is induced by unknown in vitro factor(s), which may underlie the in vivo switch at later ontogenic stages. It is emphasized that 6- to 7-wk BFU-E are endowed with the potential for in vitro synthesis of not only ε and γ-chains but also some β-globin. In general, we observed an inverse correlation between the levels of ε- and β-chain synthesis. These results, together with previous studies on fetal, perinatal, and adult BFU-E, are compatible with models suggesting that in ontogeny the chromatin configuration is gradually modified at the level of the non-α gene cluster, thus leading to a 5' → 3' activation of globin genes in a balanced fashion.

Original languageEnglish
Pages (from-to)2416-2420
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume81
Issue number8 I
DOIs
StatePublished - 1984
Externally publishedYes

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