Over-expression of c-Myb increases the frequency of hemogenic precursors in the endothelial cell population
Over-expression of c-Myb increases the frequency of hemogenic precursors in the endothelial cell population
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DOI：
10.1111/j.1365-2443.2006.00985.x
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发表时间：
2006-08-01
期刊：
影响因子：
2.1
通讯作者：
Ogawa, Minetaro
中科院分区：
文献类型：
--
作者：
Dai, Guoyou;Sakamoto, Hiroshi;Ogawa, Minetaro
在小鼠胚胎发育过程中，血源性内皮细胞被认为具有明确的造血功能。原癌基因c-myb对于最终的造血细胞的发育是必不可少的，并且被报道在血源性内皮细胞中被激活。为了研究c-Myb是否参与调控血源性内皮细胞的发育，我们在胚胎干细胞的体外分化过程中有条件地诱导c-myb的过度表达。诱导表达c-Myb的Ve-cadherin(+)CD45(-)细胞在造血细胞分化过程中仅表达内源性c-myb基因的情况下，可增加多系集落形成，增强集落形成细胞的体外自我更新能力。C-Myb在内皮细胞中的过度表达导致与特定造血相关的基因激活，如RUNX1、HOXB4、MLL和ETV6。我们的数据提供了证据，证明c-Myb能够在内皮细胞中发挥作用，促进其造血潜力的建立。
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.