Erythroblasts from Friend virus infected‐ and phenylhydrazine‐treated mice accurately model erythroid differentiation

The dynamics of gene expression during terminal erythroid differentiation have been examined in three murine models; the erythroleukaemia cell line HCD‐57 and splenic erythroblasts isolated from mice treated with either the anaemia‐inducing strain of Friend virus (FVA cells) or the haemolytic agent phenylhydrazine (PHZ cells). In response to erythropoietin (EPO) and haemin, HCD‐57 cells proliferated and synthesized haemoglobin, but failed to complete terminal differentiation as indicated by lack of change in both gene expression and morphological appearance. In contrast, EPO‐induced terminal differentiation in FVA and PHZ cells in vitro was accompanied by increases in haemoglobin positivity, morphological maturation and a shared pattern of gene expression. EPO receptor (EPO‐R) mRNA levels peaked before globin gene expression which was maximal at 24 h. Peak GATA‐1 and EKLF mRNA levels also preceded the globin gene peak, but the highest NF‐E2 levels coincided with maximal globin levels, suggesting a role for NF‐E2 in the maintenance, rather than the initiation of globin gene expression. Peak expression of δ‐aminolaevulinic acid synthase (ALAS) coincided with peak globin expression. FVA and PHZ cells represent more effective models than the HCD‐57 cell line for the investigation of erythroid gene expression during EPO‐regulated terminal erythropoiesis.