Wild-type and TP53 genetic knockout BOBSC hiPS cells were maintained in the undifferentiated state or differentiated to definitive endoderm over 72 hours, with or without 5 ppm MMS treatment at 24 hours.
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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The ability of human induced pluripotent stem cells (hiPSCs) to differentiate in vitro to each of the three germ layer lineages has made them an important developmental model and tool for tissue engineering. Here we explore the impact of inducing DNA damage at different points during differentiation. We show that, during a critical window in this program, DNA damage diverts cells from an endodermal to mesodermal fate without significant upregulation of an apoptotic program. This change in transcriptional program is driven by p53: cells lacking p53 continue to differentiate towards endoderm with high efficiency despite significant genomic damage and G2/M cell cycle arrest. Thus, DNA damage-induced upregulation of p53 decreases the efficiency of hiPSC differentiation to definitive endoderm by diverting cells towards a mesodermal fate.
提供机构：
MRC Laboratory of Molecular Biology
创建时间：
2022-02-20
