Regulation of human erythropoiesis by activin A, BMP2, and BMP4, members of the TGFbeta family.
Activin A, BMP2, and BMP4, members of the TGFbeta family, have been implicated in the regulation of hematopoiesis. Here we explore and compare, for the first time in human primary cells, the role of activin A, BMP2, and BMP4 during erythropoiesis. Using in vitro erythroid differentiation of CD34(+) primary cells, we obtained the main stages of early erythropoiesis, characterized at the molecular, biochemical, and functional levels. Our results indicate that BMP2 acts on early erythroid cells and activin A on a more differentiated population. We report an insight into the mechanism of commitment of erythropoiesis by activin A and BMP2 involving two key events, increase in EPO-R and decrease in GATA2 expression. Simultaneous addition of activin A with BMP molecules suggests that BMP2 and BMP4 differently affect activin A induction of erythropoiesis. Follistatin and FLRG proteins downmodulate the effects of activin A and BMP2 on erythroid maturation.
Maguer-Satta
Véronique
V
Unité INSERM U453, Centre Léon Bérard, Lyon, France. maguer@lyon.fnclcc.fr
Bartholin
Laurent
L
Jeanpierre
Sandrine
S
Ffrench
Martine
M
Martel
Sylvie
S
Magaud
Jean-Pierre
JP
Rimokh
Ruth
R
D028341:Activins / Q000235:genetics / Q000494:pharmacology*; D018952:Antigens, CD34; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D004920:Erythropoiesis / Q000187:drug effects* / Q000235:genetics; D038681:Follistatin / Q000235:genetics / Q000494:pharmacology; D038702:Follistatin-Related Proteins / Q000235:genetics / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology
D018952:Antigens, CD34; C525718:BMP2 protein, human; C525809:BMP4 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D038681:Follistatin; D038702:Follistatin-Related Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C422405:activin A; C499469:recombinant human bone morphogenetic protein-2; D028341:Activins; D028322:Inhibin-beta Subunits