Publication Date:
2012-12-21
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paull, Daniel -- Emmanuele, Valentina -- Weiss, Keren A -- Treff, Nathan -- Stewart, Latoya -- Hua, Haiqing -- Zimmer, Matthew -- Kahler, David J -- Goland, Robin S -- Noggle, Scott A -- Prosser, Robert -- Hirano, Michio -- Sauer, Mark V -- Egli, Dieter -- England -- Nature. 2013 Jan 31;493(7434):632-7. doi: 10.1038/nature11800. Epub 2012 Dec 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The New York Stem Cell Foundation Laboratory, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23254936" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line
;
Cells, Cultured
;
Cryopreservation
;
DNA, Mitochondrial/*genetics
;
Embryonic Development
;
Embryonic Stem Cells/cytology/metabolism
;
Genotype
;
Humans
;
Mitochondria/genetics/metabolism
;
Nuclear Transfer Techniques/*standards
;
*Oocytes/cytology/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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