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

H Sakamoto, G Dai, K Tsujino, K Hashimoto, X Huang… - Blood, 2006 - ashpublications.org
H Sakamoto, G Dai, K Tsujino, K Hashimoto, X Huang, T Fujimoto, M Mucenski, J Frampton
Blood, 2006ashpublications.org
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 …
Abstract
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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