1. Mouse Model of Chromosome Mosaicism Reveals Lineage-Specific Depletion of Aneuploid Cells and Normal Developmental Potential
- Author
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Niels Van der Aa, Elia Fernandez Gallardo, Helen Bolton, Magdalena Zernicka-Goetz, Thierry Voet, Parveen Kumar, Sarah J. L. Graham, and Koen Theunis
- Subjects
Genetics ,Fetus ,animal structures ,030219 obstetrics & reproductive medicine ,Lineage (genetic) ,business.industry ,Obstetrics and Gynecology ,Chromosome ,Germline mosaicism ,Embryo ,02 engineering and technology ,General Medicine ,021001 nanoscience & nanotechnology ,Cell biology ,stomatognathic diseases ,03 medical and health sciences ,Spindle checkpoint ,0302 clinical medicine ,medicine.anatomical_structure ,embryonic structures ,Medicine ,Blastocyst ,Ploidy ,0210 nano-technology ,business - 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.
- Published
- 2016