英国剑桥生物医学研究园区Hutchison/MRC研究中心Serena Nik-Zainal等，发现人诱导多能干细胞 (hiPSC)中大量体细胞基因组变异和BCOR 突变的选择。该研究于2022年8月11日发表于国际一流学术期刊《自然—遗传学》杂志上。

他们探索了来自不同组织的人诱导多能干细胞 (hiPSC)，以深入了解单核苷酸分辨率下的基因组完整性。他们使用了来自两个大型 hiPSC 存储库的基因组测序数据，涉及 696 个 hiPSC 和子亚克隆。他们在约 72% 的皮肤成纤维细胞衍生的 hiPSC (F-hiPSC) 中发现了与紫外线 (UV) 相关的损伤，偶尔会导致大量突变（每兆碱基最多 15 个突变）。由于寡克隆成纤维细胞群，他们证明了在同一轮重编程期间衍生的独立 F-hiPSC 克隆之间存在显著的基因组异质性。相比之下，血液来源的 hiPSCs (B-hiPSCs) 的突变较少，没有紫外线损伤，但获得性 BCOR 突变的发生率很高（26.9% 的系）。

他们揭示了 F-hiPSC 和 B-hiPSC 中 BCOR 突变的强大选择压力，并提供了它们在体外产生的证据。hiPSC 的定向分化和 RNA 测序表明 BCOR 突变具有功能性后果。他们的工作强烈表明，在使用 hiPSC 之前，详细的核苷酸分辨率表征是必不可少的。

附：英文原文

Title: Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells

Author: Rouhani, Foad J., Zou, Xueqing, Danecek, Petr, Badja, Cherif, Amarante, Tauanne Dias, Koh, Gene, Wu, Qianxin, Memari, Yasin, Durbin, Richard, Martincorena, Inigo, Bassett, Andrew R., Gaffney, Daniel, Nik-Zainal, Serena

Issue&Volume: 2022-08-11

Abstract: 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 ~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 fibroblast 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.

DOI: 10.1038/s41588-022-01147-3

Source: https://www.nature.com/articles/s41588-022-01147-3