Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors.
Outgrowth, long-term self-renewal, and terminal maturation of human erythroid progenitors derived from umbilical cord blood in serum-free medium can be modulated by steroid hormones. Homogeneous erythroid cultures, as characterized by flow cytometry and dependence on a specific mixture of physiologic proliferation factors, were obtained within 8 days from a starting population of mature and immature mononuclear cells. Due to previous results in mouse and chicken erythroblasts, the proliferation-promoting effect of glucocorticoids was not unexpected. Surprisingly, however, androgen had a positive effect on the sustained expansion of human female but not male erythroid progenitors. Under optimal conditions, sustained proliferation of erythroid progenitors resulted in a more than 10(9)-fold expansion within 60 days. Terminal erythroid maturation was significantly improved by adding human serum and thyroid hormone (3,5,3'-triiodothyronine [T3]) to the differentiation medium. This resulted in highly synchronous differentiation of the cells toward enucleated erythrocytes within 6 days, accompanied by massive size decrease and hemoglobin accumulation to levels comparable to those in peripheral blood erythrocytes. Thus, obviously, different ligand-activated nuclear hormone receptors massively influence the decision between self-renewal and terminal maturation in the human erythroid compartment.
Leberbauer
Cornelia
C
Max F. Perutz Laboratories, The University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Division of Molecular Biology, Medical University of Vienna, Vienna, Austria.
Boulmé
Florence
F
Unfried
Gertrud
G
Huber
Johannes
J
Beug
Hartmut
H
Müllner
Ernst W
EW
D000728:Androgens / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003907:Dexamethasone / Q000494:pharmacology; D004900:Erythroblasts / Q000166:cytology / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008297:Male; D012727:Sex Characteristics; D019089:Stem Cell Factor / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology*; D013997:Time Factors; D014285:Triiodothyronine, Reverse / Q000494:pharmacology; D014470:Umbilical Cord / Q000166:cytology / Q000187:drug effects
D000728:Androgens; D016895:Culture Media, Serum-Free; D019089:Stem Cell Factor; D013256:Steroids; D004921:Erythropoietin; D014285:Triiodothyronine, Reverse; D003907:Dexamethasone