多梳復(fù)合物(PcG)蛋白是干細(xì)胞的一般調(diào)節(jié)因子,。Bmi1基因編碼了多梳抑制復(fù)合體1(polycomb repressive complex 1,，PRC1) 的一個(gè)核心元件,，在長期培養(yǎng)期間,，它維持了造血干細(xì)胞(HSCs)的再生能力,。之前的研究就已經(jīng)發(fā)現(xiàn),，逆轉(zhuǎn)錄病毒介導(dǎo)了Bmi1的過表達(dá),。然而在體內(nèi),，Bmi1的過表達(dá)對HSCs的影響還不明確。
近日,，來自日本千葉大學(xué)的研究人員Atsushi Iwama等人發(fā)現(xiàn),，Bmi1能夠賦予造血干細(xì)胞抗氧化應(yīng)激的能力。相關(guān)研究成果于5月11日發(fā)表在PLoS ONE,。
在這項(xiàng)研究里,，他們創(chuàng)建了一個(gè)老鼠品系，在這個(gè)品系中,，Bmi1能夠在內(nèi)源性Rosa26啟動(dòng)子的控制下,，以一個(gè)造血細(xì)胞特異性的形式有條件的過量表達(dá)。
雖然Bmi1的過表達(dá)不會顯著的影響造血作用的穩(wěn)定,，在體外培養(yǎng)的時(shí),，它促進(jìn)了HSCs的擴(kuò)增；在連續(xù)移植期間，它能有效的保護(hù)HSCs免于失去再生能力,。
而且,，Bmi1的過表達(dá)不會影響被電離輻射所誘導(dǎo)的DNA損傷應(yīng)答。與此相反,，在氧化應(yīng)激下,，這種HSCs仍能維持其多能性，并且其抗氧化應(yīng)激的能力比控制組更好,。
出乎意料的是,，Bmi1的過表達(dá)不會影響細(xì)胞內(nèi)活性氧(ROS)水平。
Atsushi Iwama表示,，本次研究結(jié)果表明,，Bmi1的過表達(dá)給予了細(xì)胞抗壓能力，尤其是HSCs對氧化應(yīng)激的抗性,。Bmi1還增強(qiáng)了HSCs的再生能力,，這表明Bmi1定位于ROS信號通路的下游，并負(fù)調(diào)控ROS信號,。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0036209
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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.
