Abstract
Haemoglobin switching in humans provides a unique model for investigating the mechanisms underlying expression of a develop-mentally regulated gene family. Numerous studies have focused on the switch from fetal to adult (that is, γ → β) globin1,2, but little is known about the embryonic → fetal (that is, ζ → α and ε → γ) switches, as well as the transition from ‘primitive’ yolk sac to ‘definitive’ liver erythropoiesis3–7. Here we have studied the embryonic→fetal haemoglobin switches in yolk sac, liver and circulating blood erythroblasts from 25 embryos and 6 fetuses. Globin synthesis was also evaluated in purified ‘primitive’ and ‘definitive’ erythroblasts. Primitive erythroblasts synthesize essentially ζ and ε chains at 5 weeks and α- and ε-globin with a minor aliquot of ζ and γ chains at 6–7 weeks, whereas definitive erythroblasts produce α and γ + β-globin at 6 weeks but only α and γ + β chains from 8 weeks onward. In both lineages the ζ → α and the ε → γ switches are asynchronous, the former preceding the latter. Furthermore, ζ- and β-globin synthesis is restricted to primitive and definitive erythroblasts respectively. These findings are discussed in terms of a monoclonal model for haemoglobin switching in early human ontogeny.
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Peschle, C., Mavilio, F., Carè, A. et al. Haemoglobin switching in human embryos: asynchrony of ζ → α and ε → γ-globin switches in primitive and definitive erythropoietic lineage. Nature 313, 235–238 (1985). https://doi.org/10.1038/313235a0
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DOI: https://doi.org/10.1038/313235a0
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