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¹ Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
² Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
³ 21st Century COE, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
⁴ Stem Cell Biology Laboratory, Riken Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan

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.

^* Correspondence: E-mail: minetaro{at}kaiju.medic.kumamoto-u.ac.jp