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首页> 外文期刊>Stem cells translational medicine. >An Atypical Human Induced Pluripotent Stem Cell Line With a Complex, Stable, and Balanced Genomic Rearrangement Including a Large De Novo 1q Uniparental Disomy
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An Atypical Human Induced Pluripotent Stem Cell Line With a Complex, Stable, and Balanced Genomic Rearrangement Including a Large De Novo 1q Uniparental Disomy

机译：具有复杂，稳定和平衡的基因组重排，包括大的De Novo 1q单亲二体性的非典型人类诱导多能干细胞系。

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Human induced pluripotent stem cells (hiPSCs) hold great promise,for cell therapy through their use as vital tools for regenerative and personalized medicine. However, the genomic integrity of hiPSCs still raises some concern and is one of the barriers limiting their use in clinical applications. Numerous articles have reported the occurrence of aneuploidies, copy number variations, or single point mutations in hiPSCs, and nonintegrative reprogramming strategies have been developed to minimize the impact of the reprogramming process on the hiPSC genome. Here, we report the characterization of an hiPSC line generated by daily transfections of modified messenger RNAs, displaying several genomic abnormalities. Karyotype analysis showed a complex genomic rearrangement, which remained stable during long-term culture. Fluorescent in situ hybridization analyses were performed on the hiPSC line showing that this karyotype is balanced. Interestingly, single-nucleotide polymorphism analysis revealed the presence of a large 1q region of uniparental disomy (UPD), demonstrating for the first time that UPD can occur in a noncompensatory context during nonintegrative reprogramming of normal fibroblasts.
机译：人类诱导的多能干细胞（hiPSC）通过用作再生和个性化医学的重要工具，有望用于细胞治疗。但是，hiPSC的基因组完整性仍引起人们的关注，并且是限制其在临床应用中使用的障碍之一。许多文章报道了在hiPSC中出现非整倍性，拷贝数变异或单点突变，并且已经开发了非整合重编程策略以最小化重编程过程对hiPSC基因组的影响。在这里，我们报告了由修饰的信使RNA的日常转染产生的hiPSC系的表征，显示出一些基因组异常。核型分析显示复杂的基因组重排，在长期培养期间保持稳定。在hiPSC品系上进行了荧光原位杂交分析，表明该核型是平衡的。有趣的是，单核苷酸多态性分析揭示了单亲二体性（UPD）的1q大区域的存在，这首次证明UPD可以在正常成纤维细胞的非整合重编程过程中以非补偿性方式发生。

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