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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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Submitted March 18, 2004
Accepted August 5, 2004
Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors
Cornelia Leberbauer, Florence Boulme, Gertrud Unfried, Johannes Huber, Hartmut Beug, and Ernst W Mullner*
Department of Medical Biochemistry, Division of Molecular Biology, Medical University of Vienna, Max F. Perutz Laboratories - University Departments at the Vienna Biocenter, Vienna, Austria
Department of Gynecological Endocrinology, Medical University of Vienna, Vienna, Austria
Institute of Molecular Pathology, Vienna, Austria
* Corresponding author; email: ernst.muellner{at}univie.ac.at.
Outgrowth, long term self renewal and terminal maturation of human erythroid progenitors derived form umbilical cord blood in serum-free medium can be modulated by steroid hormones. Homogenous erythroid cultures, as characterized by flow cytometry and dependence on a specific mixture of physiological 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 >109-fold expansion within 60 days. Terminal erythroid maturation was significantly improved by adding human serum and thyroid hormone (T3) to the differentiation medium. This resulted in highly synchronous differentiation of the cells towards 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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