title: Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants.
abstract: 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.
authors.affiliation: The New York Stem Cell Foundation Laboratory, New York, NY 10032, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Paull
authors.forename: Valentina
authors.initials: V
authors.lastname: Emmanuele
authors.forename: Keren A
authors.initials: KA
authors.lastname: Weiss
authors.forename: Nathan
authors.initials: N
authors.lastname: Treff
authors.forename: Latoya
authors.initials: L
authors.lastname: Stewart
authors.forename: Haiqing
authors.initials: H
authors.lastname: Hua
authors.forename: Matthew
authors.initials: M
authors.lastname: Zimmer
authors.forename: David J
authors.initials: DJ
authors.lastname: Kahler
authors.forename: Robin S
authors.initials: RS
authors.lastname: Goland
authors.forename: Scott A
authors.initials: SA
authors.lastname: Noggle
authors.forename: Robert
authors.initials: R
authors.lastname: Prosser
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Mark V
authors.initials: MV
authors.lastname: Sauer
authors.forename: Dieter
authors.initials: D
authors.lastname: Egli
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D015925:Cryopreservation; D004272:DNA, Mitochondrial / Q000235:genetics*; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D053652:Nuclear Transfer Techniques / Q000592:standards*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial