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- W2083029198 abstract "OBJECTIVE: Maintaining genomic integrity of human pre implantation embryos is crucial for normal development. Genomic instabilities are common in human pre-implantation embryos, human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hIPSCs). The objective of this study is to investigate the response of pluripotent cell to genomic instabilities. DESIGN: All experiments were compared to somatic cells and performed before and after differentiation of stem cells. Ionizing Radiation (IR) was used to induce double strand DNA breaks. Nocodazole was used to disrupt microtubules to assess the mitotic checkpoint. Cell cycle profile was done after each treatment with and without differentiation. MATERIALS AND METHODS: HESCs and hIPSCs were cultured either under standard self-renewing or differentiating conditions. BJ fibroblasts were used as control. Cell cycle was assessed using Propidium Iodide. Two-sample student t-test was used for statistics. RESULTS: DNA damage experiments show that only G2/M checkpoint is active in hESCs and hIPSCs. Nocodazole experiments reveal that damaged cells can progress through the G2/M checkpoint as polyploid cells. With differentiation of hESCs and hIPSCs, cell cycle checkpoints are restored and polyploid cells are nearly eliminated. CONCLUSION: This study shows that pluripotent cells lack the G1 checkpoint and have relaxed mitotic checkpoint which are both restored upon differentiation. This relaxed checkpoint control may be important in the pre-implantation embryo to enable rapid cell divisions so that a single cell embryo can become nearly 100 cells in 5 days. Activation of these checkpoints with differentiation in the human embryo may explain some IVF failures and early miscarriages where clearing of genetically abnormal cells occurs upon implantation rather than in pluripotent state prior to implantation. Our data could also help explain how mosaic embryos self-correct post-implantation by removing abnormal cells with differentiation." @default.
- W2083029198 created "2016-06-24" @default.
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- W2083029198 date "2010-09-01" @default.
- W2083029198 modified "2023-09-30" @default.
- W2083029198 title "Lack of checkpoint control in human pluripotent stem cells: a cause for genomic instability?" @default.
- W2083029198 doi "https://doi.org/10.1016/j.fertnstert.2010.07.931" @default.
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