Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants

被引：196

作者：

Paull, Daniel ^{[1
]}

Emmanuele, Valentina ^{[2
]}

Weiss, Keren A. ^{[1
]}

Treff, Nathan ^{[3
]}

Stewart, Latoya ^{[1
]}

Hua, Haiqing ^{[1
,4
]}

Zimmer, Matthew ^{[1
]}

Kahler, David J. ^{[1
]}

Goland, Robin S. ^{[4
]}

Noggle, Scott A. ^{[1
]}

Prosser, Robert ^{[5
]}

Hirano, Michio ^{[2
]}

Sauer, Mark V. ^{[5
,6
]}

Egli, Dieter ^{[1
]}

机构：

[1] New York Stem Cell Fdn Lab, New York, NY 10032 USA

[2] Columbia Univ, Dept Neurol, New York, NY 10032 USA

[3] Reprod Med Associates New Jersey, Morristown, NJ 07960 USA

[4] Columbia Univ, Coll Phys & Surg, Naomi Berrie Diabet Ctr, New York, NY 10032 USA

[5] Columbia Univ, Coll Phys & Surg, Ctr Womens Reprod Care, New York, NY 10019 USA

[6] Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA

来源：

NATURE | 2013年 / 493卷 / 7434期

关键词：

MEIOTIC SPINDLE; HUMAN EMBRYOS; CELL-LINES; STEM-CELLS; MOUSE; SEGREGATION; MTDNA; VITRIFICATION; MICROTUBULES; DEFICIENCY;

D O I：

10.1038/nature11800

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 beta-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.

引用

页码：632 / +

页数：8

共 47 条

[1]

ASRM, 2012, FERTIL STERIL

[2] Detection and quantification of heteroplasmic mutant mitochondrial DNA by real-time amplification refractory mutation system quantitative PCR analysis: A single-step approach [J].