Human γ-globin is highly expressed in βH1-globin–expressing definitive proerythroblasts. (A) Mice with a single copy of the human β-globin locus¹⁸  were assayed by qPCR for gene expression of murine (top) and human (bottom) β-globin genes. Levels of globin transcripts are graphed as the percentage of total β-globin message measured from that locus. The left 3 samples are from primitive erythroid cells sorted from fetal blood (Ter119⁺ c-kit⁻). The middle 3 samples are from sorted definitive proerythroblasts (Ter119^lo c-kit⁺) from fetal liver or BM. The right 2 samples are cultured E9.5 yolk sac EMP in erythroid maturation media. Error bars derived from the SEM of 3 independent experiments. (B) Three erythroid lineages emerge during mammalian embryogenesis. Two of these lineages, primitive erythroid and EMP-definitive erythroid, originate in the yolk sac. The AGM and other sites generate the HSC that colonize the liver and eventually the BM. Primitive erythroid precursors mature in the circulation, while EMP- and HSC-derived BFU-E mature in the liver of the fetus. Different patterns of β-globin expression in the mouse, human, and of the transgenic human genes in mice characterize these different forms of erythropoiesis (Figures 3, 7A).^44,46-48  Genes are presented in their order within the β-globin locus. Grayed gene names signify no expression in that lineage. †While the yolk sac is the only reported site of EMP emergence precirculation, EMP may also be produced elsewhere and obscured from detection by the presence of EMP in circulating blood. *Maturational globin switching is observed in the first 2 lineages in mouse where βH1-globin or transgenic human γ-globin decrease in prevalence as erythroid precursors mature. ⋀β-globin is the major β-globin expressed in adult humans, however, rare γ-globin–expressing F cells are also found in the circulation.