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PLoS ONE:Bmi1赋予造血干细胞抗氧化应激的能力

  1. Bmi1
  2. HSCs
  3. PLoS ONE

来源:生物谷 2012-11-18 07:07

多梳复合物(PcG)蛋白是干细胞的一般调节因子。Bmi1基因编码了多梳抑制复合体1(polycomb repressive complex 1,PRC1) 的一个核心元件,在长期培养期间,它维持了造血干细胞(HSCs)的再生能力。之前的研究就已经发现,逆转录病毒介导了Bmi1的过表达。然而在体内,Bmi1的过表达对HSCs的影响还不明确。

多梳复合物(PcG)蛋白是干细胞的一般调节因子。Bmi1基因编码了多梳抑制复合体1(polycomb repressive complex 1,PRC1) 的一个核心元件,在长期培养期间,它维持了造血干细胞(HSCs)的再生能力。之前的研究就已经发现,逆转录病毒介导了Bmi1的过表达。然而在体内,Bmi1的过表达对HSCs的影响还不明确。

近日,来自日本千叶大学的研究人员Atsushi Iwama等人发现,Bmi1能够赋予造血干细胞抗氧化应激的能力。相关研究成果于5月11日发表在PLoS ONE

在这项研究里,他们创建了一个老鼠品系,在这个品系中,Bmi1能够在内源性Rosa26启动子的控制下,以一个造血细胞特异性的形式有条件的过量表达。

虽然Bmi1的过表达不会显著的影响造血作用的稳定,在体外培养的时,它促进了HSCs的扩增;在连续移植期间,它能有效的保护HSCs免于失去再生能力。

而且,Bmi1的过表达不会影响被电离辐射所诱导的DNA损伤应答。与此相反,在氧化应激下,这种HSCs仍能维持其多能性,并且其抗氧化应激的能力比控制组更好。

出乎意料的是,Bmi1的过表达不会影响细胞内活性氧(ROS)水平。

Atsushi Iwama表示,本次研究结果表明,Bmi1的过表达给予了细胞抗压能力,尤其是HSCs对氧化应激的抗性。Bmi1还增强了HSCs的再生能力,这表明Bmi1定位于ROS信号通路的下游,并负调控ROS信号。(生物谷Deepblue编译)

Bmi1 Confers Resistance to Oxidative Stress on Hematopoietic Stem Cells

Shunsuke Nakamura, Motohiko Oshima, Jin Yuan, Atsunori Saraya, Satoru Miyagi, Takaaki Konuma, Satoshi Yamazaki, Mitsujiro Osawa, Hiromitsu Nakauchi, Haruhiko Koseki, Atsushi Iwama.

The polycomb-group (PcG) proteins function as general regulators of stem cells. We previously reported that retrovirus-mediated overexpression of Bmi1, a gene encoding a core component of polycomb repressive complex (PRC) 1, maintained self-renewing hematopoietic stem cells (HSCs) during long-term culture.However, the effects of overexpression of Bmi1 on HSCs in vivo remained to be precisely addressed.In this study, we generated a mouse line where Bmi1 can be conditionally overexpressed under the control of the endogenous Rosa26 promoter in a hematopoietic cell-specific fashion (Tie2-Cre;R26StopFLBmi1).Although overexpression of Bmi1 did not significantly affect steady state hematopoiesis, it promoted expansion of functional HSCs during ex vivo culture and efficiently protected HSCs against loss of self-renewal capacity during serial transplantation.Overexpression of Bmi1 had no effect on DNA damage response triggered by ionizing radiation. In contrast, Tie2-Cre;R26StopFLBmi1 HSCs under oxidative stress maintained a multipotent state and generally tolerated oxidative stress better than the control.Unexpectedly, overexpression of Bmi1 had no impact on the level of intracellular reactive oxygen species (ROS).Our findings demonstrate that overexpression of Bmi1 confers resistance to stresses, particularly oxidative stress, onto HSCs.This thereby enhances their regenerative capacity and suggests that Bmi1 is located downstream of ROS signaling and negatively regulated by it.

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