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Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential

Author

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  • Helen Bolton

    (Development and Neuroscience and Gurdon Institute, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK)

  • Sarah J. L. Graham

    (Development and Neuroscience and Gurdon Institute, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK)

  • Niels Van der Aa

    (University of Leuven, KU Leuven)

  • Parveen Kumar

    (University of Leuven, KU Leuven)

  • Koen Theunis

    (University of Leuven, KU Leuven)

  • Elia Fernandez Gallardo

    (University of Leuven, KU Leuven)

  • Thierry Voet

    (University of Leuven, KU Leuven
    Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Sanger Institute)

  • Magdalena Zernicka-Goetz

    (Development and Neuroscience and Gurdon Institute, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK)

Abstract

Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.

Suggested Citation

  • Helen Bolton & Sarah J. L. Graham & Niels Van der Aa & Parveen Kumar & Koen Theunis & Elia Fernandez Gallardo & Thierry Voet & Magdalena Zernicka-Goetz, 2016. "Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11165
    DOI: 10.1038/ncomms11165
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    Cited by:

    1. Cerys E. Currie & Emma Ford & Lucy Benham Whyte & Deborah M. Taylor & Bettina P. Mihalas & Muriel Erent & Adele L. Marston & Geraldine M. Hartshorne & Andrew D. McAinsh, 2022. "The first mitotic division of human embryos is highly error prone," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Shuangyi Xu & Ning Wang & Michael V. Zuccaro & Jeannine Gerhardt & Rajan Iyyappan & Giovanna Nascimento Scatolin & Zongliang Jiang & Timour Baslan & Amnon Koren & Dieter Egli, 2024. "DNA replication in early mammalian embryos is patterned, predisposing lamina-associated regions to fragility," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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