Interspecies somatic cell nuclear transfer is dependent on compatible mitochondrial DNA and reprogramming factors

Yan Jiang, Richard Kelly, Amy Peters, Helena Fulka, Adam Dickinson, Daniel Mitchell, Justin St John

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    Abstract

    Interspecies somatic cell nuclear transfer (iSCNT) involves the transfer of a nucleus or cell from one species into the cytoplasm of an enucleated oocyte from another. Once activated, reconstructed oocytes can be cultured in vitro to blastocyst, the final stage of preimplantation development. However, they often arrest during the early stages of preimplantation development; fail to reprogramme the somatic nucleus; and eliminate the accompanying donor cell s mitochondrial DNA (mtDNA) in favour of the recipient oocyte s genetically more divergent population. This last point has consequences for the production of ATP by the electron transfer chain, which is encoded by nuclear and mtDNA. Using a murine-porcine interspecies model, we investigated the importance of nuclear-cytoplasmic compatibility on successful development. Initially, we transferred murine fetal fibroblasts into enucleated porcine oocytes, which resulted in extremely low blastocyst rates (0.48 ); and failure to replicate nuclear DNA and express Oct-4, the key marker of reprogramming. Using allele specific-PCR, we detected peak levels of murine mtDNA at 0.14+/-0.055 of total mtDNA at the 2-cell embryo stage and then at ever-decreasing levels to the blastocyst stage (
    Original languageEnglish
    Article numbere14805
    Number of pages12
    JournalPLoS ONE
    Volume6
    Issue number4
    DOIs
    Publication statusPublished - 2011

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