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

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Leberbauer C,Boulmé F,Unfried G,Huber J,Beug H,Müllner EW

doi

10.1182/blood-2004-03-1002

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

85-94

issue

1

eissn

0006-4971

issn

1528-0020

pii

2004-03-1002

journal_volume

105

pub_type

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