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Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants

zhangxia111 添加于 2012/12/21 14:45:54  1025次阅读 | 0次推荐 | 0个评论

Mitochondrial DNA mutations transmitted maternally within the oocyte cytoplasm often cause life-threatening disorders. Here we explore the use of nuclear genome transfer between unfertilized oocytes of two donors to prevent the transmission of mitochondrial mutations. Nuclear genome transfer did not reduce developmental efficiency to the blastocyst stage, and genome integrity was maintained provided that spontaneous oocyte activation was avoided through the transfer of incompletely assembled spindle–chromosome complexes. Mitochondrial DNA transferred with the nuclear genome was initially detected at levels below 1%, decreasing in blastocysts and stem-cell lines to undetectable levels, and remained undetectable after passaging for more than one year, clonal expansion, differentiation into neurons, cardiomyocytes or β-cells, and after cellular reprogramming. Stem cells and differentiated cells had mitochondrial respiratory chain enzyme activities and oxygen consumption rates indistinguishable from controls. These results demonstrate the potential of nuclear genome transfer to prevent the transmission of mitochondrial disorders in humans.

作 者:Daniel Paull,Valentina Emmanuele,Keren A. Weiss,Nathan Treff,Latoya Stewart, Haiqing Hua, Matthew Zimmer, David J. Kahler, Robin S. Goland, Scott A. Noggle, Robert Prosser, Michio Hirano, Mark V. Sauer & Dieter Egli
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学科领域:生命科学 » 遗传学与生物信息学 » 基因组学
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原文链接:http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11800.html
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相关报道: http://paper.sciencenet.cn/htmlpaper/20131241349652827316.shtm
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