人体皮肤中的体质复制数马赛克,由诱导的多能干细胞揭示出来
Alexej Abyzov1, Jessica Mariani, Dean Palejev
1Program in Neurodevelopment and Regeneration, Yale University, New Haven, Connecticut 06520, USA.
Nature
|November 20, 2012
概括
诱导多能干细胞 (iPSCs) 重编程通常不会导致新的DNA复制数变异 (CNVs). 大多数iPSC中的CNV来源于父母皮肤细胞中先前存在的低频变异,揭示了广泛的体质马赛克.
科学领域:
- 基因组学就是基因组学.
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 诱导多能干细胞 (iPSC) 对再生医学和疾病建模至关重要.
- 有关在重编程过程中产生的遗传改变,特别是复制数变异 (CNVs) 的担忧存在.
- 了解iPSCs的遗传稳定性对于其安全的临床应用至关重要.
研究的目的:
- 研究是否将体细胞重新编程为iPSCs会导致新的副本数变异 (CNVs).
- 在人类iPSC系中观察到的CNVs的起源和频率的特征.
- 评估iPSC克隆扩张对于检测低频体内基因组变异的有用性.
主要方法:
- 全基因组和转录基因组测序20个人类iPSC线和他们的父母原发性皮肤纤维细胞.
- 下一代测序 (NGS) 用于全面的基因组分析.
- 聚合酶链反应 (PCR) 和数字滴滴PCR用于验证CNVs.
主要成果:
- 平均而言,人类iPSC系表现出两种CNV,它们的原生纤维细胞中并不存在.
- 在iPSC中,超过50%的这些CNV被确定为父母纤维细胞中低频率的体质变异.
- 这项研究表明,iPSC线反映,而不是导致,大多数CNVs,突出显示人体皮肤中广泛存在的体质马赛克.
结论:
- 重编程到iPSC并不一定会诱导新的CNV;观察到的变异通常源于源组织中的体质马赛克.
- iPSC 克隆扩张作为一种强大的工具,用于在起源组织中发现低频 CNV.
- 大约30%的纤维细胞含有体性CNV,这表明人体中存在显著的异位后基因组不稳定性.
相关概念视频
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01:24Methods of Nuclear Reprogramming
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