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 Blood, 1 August 2006, Vol. 108, No. 3, pp. 896-903.
Prepublished online as a Blood First Edition Paper on April 4, 2006; DOI 10.1182/blood-2005-09-3846.

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HEMATOPOIESIS

Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development

Hiroshi Sakamoto, Guoyou Dai, Kaori Tsujino, Kazuaki Hashimoto, Xin Huang, Tetsuhiro Fujimoto, Michael Mucenski, Jon Frampton, and Minetaro Ogawa

From the Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan; The 21st Century COE "Cell Fate Regulation Research and Education Unit," Kumamoto University, Kumamoto, Japan; the Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, OH; and the Institute for Biomedical Research, The Medical School, Birmingham University, Birmingham, United Kingdom.

The definitive hematopoietic cell lineages have been proposed to originate from hemogenic endothelial cells during mouse embryogenesis. c-Myb is a transcription factor that is essential for the development of definitive hematopoiesis. To investigate the functional role of c-Myb in hematopoietic cell development from endothelial cells, we introduced a c-myb transgene expressed under the control of a tetracycline-regulated promoter into the c-myb–/– embryonic stem (ES) cell line, with the aim of inducing c-Myb expression at any stage and at any level. Induction of c-Myb expression after replating c-myb–/– endothelial cells rescued the generation and proliferation of definitive hematopoietic progenitor cells, suggesting that c-Myb expression in developing endothelial cells is not a prerequisite for their hematogenic potential. Overexpression of c-Myb, however, prevented the terminal differentiation of erythrocytes and megakaryocytes and completely abolished B-lymphocyte development. Our results indicate that c-Myb is a major factor that controls differentiation as well as proliferation of hematopoietic progenitor cells derived from hemogenic endothelial cells, and that appropriate levels of c-Myb protein are strictly defined at distinct differentiation steps of each hematopoietic cell lineage.


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