期刊
NATURE GENETICS
卷 54, 期 9, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41588-022-01147-3
关键词
-
资金
- Cancer Research UK Advanced Clinician Scientist Award [C60100/A23916]
- Dr Josef Steiner Cancer Research Award 2019
- Medical Research Council
- Cancer Research UK Pioneer Award
- Wellcome Intermediate Clinical Fellowship [WT100183]
- NIHR-BRC Cambridge core grant [BRC-125-20014]
- UK Regenerative Medicine Platform [MR/R015724/1]
The study explores human induced pluripotent stem cells derived from different tissues, finding UV-related damage and mutations in skin fibroblast-derived cells, while blood-derived cells show a high prevalence of acquired mutations.
We explored human induced pluripotent stem cells (hiPSCs) derived from different tissues to gain insights into genomic integrity at single-nucleotide resolution. We used genome sequencing data from two large hiPSC repositories involving 696 hiPSCs and daughter subclones. We find ultraviolet light (UV)-related damage in similar to 72% of skin fibroblast-derived hiPSCs (F-hiPSCs), occasionally resulting in substantial mutagenesis (up to 15 mutations per megabase). We demonstrate remarkable genomic heterogeneity between independent F-hiPSC clones derived during the same round of reprogramming due to oligoclonal fibro-blast populations. In contrast, blood-derived hiPSCs (B-hiPSCs) had fewer mutations and no UV damage but a high prevalence of acquired BCOR mutations (26.9% of lines). We reveal strong selection pressure for BCOR mutations in F-hiPSCs and B-hiPSCs and provide evidence that they arise in vitro. Directed differentiation of hiPSCs and RNA sequencing showed that BCOR mutations have functional consequences. Our work strongly suggests that detailed nucleotide-resolution characterization is essential before using hiPSCs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据