title: Erythropoietin and hydroxyurea can act on early erythroid progenitors from adult human peripheral blood to modulate fetal globin mRNA levels.
abstract: Fetal hemoglobin production in adult human erythroid progenitors can be influenced by exogenous factors. In this report, we examine the effects of erythropoietin (Epo) and hydroxyurea (HU) in serum-free media on fetal (gamma-) globin mRNA levels when present during the first week of peripheral blood burst-forming unit-erythroid (BFU-E) culture. Fetal calf serum (FCS) is known to elevate gamma-globin mRNA levels in BFU-E culture and has been shown to do so even when added after the first week of culture. Removal of FCS from the first week of our BFU-E cultures did not significantly reduce gamma-globin mRNA levels, in agreement with these earlier findings. Addition of Epo to BFU-E cultures 4 days before addition of FCS led to a significant drop in gamma-globin mRNA levels; Epo addition also led to a significant increase in the number of erythroid bursts. Culture conditions, including Epo in serum-free liquid medium for 1 week followed by plating in semisolid medium containing FCS and Epo, resulted in low gamma-globin mRNA levels, similar to levels found in vivo, and high burst numbers. These conditions were used to demonstrate significant elevation of gamma-globin mRNA levels by HU present during the first week of BFU-E culture. Our findings suggest that gamma-globin mRNA levels can be influenced early in erythropoiesis by Epo and HU.
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: C J
authors.initials: CJ
authors.lastname: Stoeckert
authors.forename: M B
authors.initials: MB
authors.lastname: Green
mesh_terms: D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000737:chemistry* / Q000166:cytology*; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005914:Globins / Q000235:genetics*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics
chemical_list: D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D004921:Erythropoietin; D005914:Globins; D006918:Hydroxyurea