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Blood. 2005 Jan 1;105(1):85-94. Epub 2004 Sep 9.

Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors.

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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.


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.

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