Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.
Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.
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DOI：
10.1038/ncomms11165
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发表时间：
2016-03-29
影响因子：
16.6
通讯作者：
Zernicka-Goetz M
中科院分区：
文献类型：
--
作者：
Bolton H;Graham SJL;Van der Aa N;Kumar P;Theunis K;Fernandez Gallardo E;Voet T;Zernicka-Goetz M
大多数人类植入前胚胎是整倍体和非整倍体细胞的嵌合体。为了确定非整倍体细胞的命运和嵌合胚胎的发育潜力，我们在这里建立了一个小鼠染色体嵌合模型。通过在4 - 8细胞分裂期间用纺锤体组装检查点抑制剂处理胚胎，我们有效地产生非整倍体细胞，导致胚胎在植入期发育期间死亡。包含非整倍体和整倍体细胞的嵌合胚胎的活胚胎成像和单细胞跟踪显示，非整倍体细胞的命运取决于谱系：胎儿谱系中的非整倍体细胞通过凋亡被消除，而胎盘谱系中的非整倍体细胞则表现出严重的增殖缺陷。总的来说，非整倍体细胞的比例从囊胚期开始逐渐减少。最后，我们发现嵌合胚胎具有充分的发育潜力，只要它们含有足够的整倍体细胞，这一发现对临床胚胎活力的评估具有重要意义。整倍体和非整倍体细胞嵌合胚胎的发育潜力尚不清楚。在这里，作者创建了一个小鼠染色体嵌合模型，表明胎儿中的非整倍体细胞通过凋亡被消除，发育潜力依赖于足够的整倍体细胞的存在。
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. The developmental potential of mosaic embryos of euploid and aneuploid cells is unknown. Here, the authors create a mouse model of chromosome mosaicism, showing that aneuploid cells in the fetus are eliminated by apoptosis and developmental potential is dependent on the presence of sufficient euploid cells.