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 Blood, 1 January 2005, Vol. 105, No. 1, pp. 85-94.
Prepublished online as a Blood First Edition Paper on September 9, 2004; DOI 10.1182/blood-2004-03-1002.

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HEMATOPOIESIS

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

Cornelia Leberbauer, Florence Boulmé, Gertrud Unfried, Johannes Huber, Hartmut Beug, and Ernst W. Müllner

From the Max F. Perutz Laboratories, The University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Division of Molecular Biology, Medical University of Vienna, Austria; Department of Gynecological Endocrinology, Medical University of Vienna, Austria; and Institute of Molecular Pathology, 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 109-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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