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The Nuclear Orphan Receptor TR4 Promotes Proliferation of Myeloid Progenitor Cells¹

Nicolás P. Koritschoner², Jaime Madruga, Signe Knespel, Gitta Blendinger, Birgit Anzinger, Albrecht Otto, Martin Zenke³ and Petr Bartnk

Max-Delbrück-Center for Molecular Medicine, D-13122 Berlin, Germany [N. P. K., J. M., S. K., G. B., B. A., A. O., M. Z., P. B.], and Institute of Molecular Genetics, 166 37 Prague 6, Czech Republic [P. B.]

Nuclear receptors represent key regulators in cell proliferation, differentiation, and development. Here we demonstrate that the nuclear orphan receptor TR4 is highly expressed in hematopoietic cells and tissues and have analyzed the impact of TR4 in this cell compartment. We show that TR4, when ectopically expressed in bone marrow cells via retrovirus vector, promotes proliferation of myeloid progenitor cells. Cells represent promyelocytes as judged by morphological features, expression of cell surface molecules, and specific markers like Mim-1 and CAAT/enhancer binding protein ß. We also demonstrate that the growth promoting activity of TR4 is not exclusively dependent on its association with DNA, because expression of a mutated TR4 version devoid of its DNA binding domain exhibits a similar proliferative potential as wild-type TR4. In conclusion, these data position the orphan receptor TR4 as an important regulator of myeloid progenitor cell proliferation and development.

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