title: Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development.
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.
authors.affiliation: Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Guoyou
authors.initials: G
authors.lastname: Dai
authors.forename: Kaori
authors.initials: K
authors.lastname: Tsujino
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Michael
authors.initials: M
authors.lastname: Mucenski
authors.forename: Jon
authors.initials: J
authors.lastname: Frampton
authors.forename: Minetaro
authors.initials: M
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D020598:Proto-Oncogene Proteins c-myb / Q000032:analysis / Q000235:genetics* / Q000502:physiology*
chemical_list: D020598:Proto-Oncogene Proteins c-myb