Over-expression of c-Myb increases the frequency of hemogenic precursors in the endothelial cell population.
Definitive hematopoiesis has been proposed to arise from hemogenic endothelial cells during mouse embryogenesis. The c-myb proto-oncogene is essential for the development of definitive hematopoiesis and was reported to be activated in hemogenic endothelial cells. To investigate whether c-Myb is involved in regulating the development of hemogenic endothelial cells, we conditionally induced c-myb over-expression during the in vitro differentiation of embryonic stem cells. VE-cadherin+ CD45- cells inducibly expressing c-Myb showed an increase in multilineage colony formation as well as an augmented capacity of the colony forming cells to self-renew in vitro under the condition that only the endogenous c-myb gene was expressed during differentiation of hematopoietic cells. Over-expression of c-Myb in the endothelial population led to activation of genes associated with definitive hematopoiesis such as Runx1, Hoxb4, Mll and Etv6. Our data provide evidence that c-Myb is able to exert an effect in endothelial cells which fosters the establishment of their hemogenic potential.
Dai
Guoyou
G
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Sakamoto
Hiroshi
H
Shimoda
Yuri
Y
Fujimoto
Tetsuhiro
T
Nishikawa
Shin-Ichi
S
Ogawa
Minetaro
M
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004627:Embryonic Induction / Q000235:genetics; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D020570:Genes, myb / Q000502:physiology*; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D014162:Transfection