PNAS:哺乳动物卵母细胞发育蛋白质组研究突破

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          2010年9月27日,北京生命科学研究所(NIBS)高绍荣博士实验室Proc. Natl. Acad. Sci. USA杂志在线发表题为“Proteome of mouse oocytes at different developmental stages”的文章。文章阐述了不同发育阶段小鼠卵母细胞的蛋白质组学特点,为进一步鉴定卵母细胞重编程因子打下基础。

          卵母细胞具有非常强的重编程能力,它可以在短短几个细胞周期内把高度分化的体细胞重编程为了具有全能性的克隆胚胎并可以进一步发育成为克隆动物。然而卵母细胞中究竟有什么重要的重编程因子还不清楚,要想了解哪些蛋白是卵母细胞重编程过程所需要的蛋白,就需要对卵母细胞蛋白质组做深入研究。但是由于取材的限制,已知的卵母细胞蛋白表达图谱只发现几百种蛋白。本课题组在应用LC-MS蛋白质谱方法对每组7000个未成熟的GV卵母细胞、成熟的MII卵母细胞和受精卵进行研究,该研究在GV、MII、受精卵中分别鉴定发现了2781、2973、2082种蛋白,同时也分析了不同发育阶段卵母细胞对应的表达丰富的信号通路。

          该研究是至今在哺乳动物卵母细胞发育中最丰富的蛋白质组研究。卵母细胞和受精卵的蛋白质组研究对于受精过程DNA去甲基化和重编程的机理研究,并且对于促进特定转录因子介导的重编程即iPS的诱导效率都有深远的意义,因为研究组发现在成熟的卵母细胞中比其他时期表达更多的转录因子和染色体重构因子。同时也发现了卵母细胞发育和受精所需要的许多营养物质和信号通路,为了解胚胎早期发育、体外培养卵母细胞和不孕不育的研究和治疗提供了一定的基础。

          NIBS博士生王淑芳为该文章的第一作者,该论文的其它作者包括寇朝辉,景志毅,张郁,郭欣政博士,董梦秋博士。英国爱丁堡大学的Ian Wilmut教授和我所研究员高绍荣博士为本论文的共同通讯作者,该项研究由科技部和北京市政府资助,在北京生命科学研究所完成

          推荐英文摘要:

          PNASdoi: 10.1073/pnas.1013185107

          Proteome of mouse oocytes at different developmental stages
          Shufang Wanga,b, Zhaohui Koua, Zhiyi Jinga, Yu Zhanga, Xinzheng Guoa, Mengqiu Donga, Ian Wilmutc,1, and Shaorong Gaoa,1

          aNational Institute of Biological Sciences (NIBS), Beijing 102206, People's Republic of China;
          bCollege of Life Science, Beijing Normal University, Beijing 100875, People's Republic of China; and
          cScottish Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom

          The mammalian oocyte possesses powerful reprogramming factors, which can reprogram terminally differentiated germ cells (sperm) or somatic cells within a few cell cycles. Although it has been suggested that use of oocyte-derived transcripts may enhance the generation of induced pluripotent stem cells, the reprogramming factors in oocytes are undetermined, and even the identified proteins composition of oocytes is very limited. In the present study, 7,000 mouse oocytes at different developmental stages, including the germinal vesicle stage, the metaphase II (MII) stage, and the fertilized oocytes (zygotes), were collected. We successfully identified 2,781 proteins present in germinal vesicle oocytes, 2,973 proteins in MII oocytes, and 2,082 proteins in zygotes through semiquantitative MS analysis. Furthermore, the results of the bioinformatics analysis indicated that different protein compositions are correlated with oocyte characteristics at different developmental stages. For example, specific transcription factors and chromatin remodeling factors are more abundant in MII oocytes, which may be crucial for the epigenetic reprogramming of sperm or somatic nuclei. These results provided important knowledge to better understand the molecular mechanisms in early development and may improve the generation of induced pluripotent stem cells.


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