Mammalian Development Group, Institute of Medical Biology, A*STAR, Singapore.
Science. 2013 Sep 6;341(6150):1110-2. doi: 10.1126/science.1240617.
Epigenetic alterations are increasingly recognized as causes of human cancers and disease. These aberrations are likely to arise during genomic reprogramming in mammalian preimplantation embryos, when their epigenomes are most vulnerable. However, this process is only partially understood because of the experimental inaccessibility of early-stage embryos. Here, we introduce a methodologic advance, probing single cells for various DNA-methylation errors at multiple loci, to reveal failed maintenance of epigenetic mark results in chimeric mice, which display unpredictable phenotypes leading to developmental arrest. Yet we show that mouse pronuclear transfer can be used to ameliorate such reprogramming defects. This study not only details the epigenetic reprogramming dynamics in early mammalian embryos but also suggests diagnostic and potential future therapeutic applications.
表观遗传改变越来越被认为是人类癌症和疾病的原因。这些异常可能发生在哺乳动物着床前胚胎的基因组重新编程过程中，此时它们的表观基因组最脆弱。然而，由于早期胚胎的实验不可接近性，这一过程仅部分被理解。在这里，我们引入了一种方法学上的进展，即在多个基因座探测单个细胞的各种 DNA 甲基化错误，以揭示导致嵌合小鼠的表观遗传标记维持失败的结果，这些小鼠表现出不可预测的表型，导致发育停滞。然而，我们表明，小鼠原核转移可以用来改善这种重编程缺陷。这项研究不仅详细描述了早期哺乳动物胚胎中的表观遗传重编程动态，还提出了诊断和未来潜在的治疗应用。
