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Insertion/deletion and microsatellite alteration profiles in induced pluripotent stem cells
Stem Cell Reports ( IF 5.9 ) Pub Date : 2021-09-23 , DOI: 10.1016/j.stemcr.2021.08.017
Satoshi Kamimura 1 , Tomo Suga 1 , Yuko Hoki 1 , Misato Sunayama 1 , Kaori Imadome 1 , Mayumi Fujita 1 , Miki Nakamura 1 , Ryoko Araki 1 , Masumi Abe 1
Affiliation  

We here demonstrate that microsatellite (MS) alterations are elevated in both mouse and human induced pluripotent stem cells (iPSCs), but importantly we have now identified a type of human iPSC in which these alterations are considerably reduced. We aimed in our present analyses to profile the InDels in iPSC/ntESC genomes, especially in MS regions. To detect somatic de novo mutations in particular, we generated 13 independent reprogramed stem cell lines (11 iPSC and 2 ntESC lines) from an identical parent somatic cell fraction of a C57BL/6 mouse. By using this cell set with an identical genetic background, we could comprehensively detect clone-specific alterations and, importantly, experimentally validate them. The effectiveness of employing sister clones for detecting somatic de novo mutations was thereby demonstrated. We then successfully applied this approach to human iPSCs. Our results require further careful genomic analysis but make an important inroad into solving the issue of genome abnormalities in iPSCs.



中文翻译:


诱导多能干细胞中的插入/缺失和微卫星改变谱



我们在此证明,小鼠和人类诱导多能干细胞 (iPSC) 中的微卫星 (MS) 改变均有所增加,但重要的是,我们现在已经鉴定出一种类型的人类 iPSC,其中这些改变大大减少。我们目前的分析旨在分析 iPSC/ntESC 基因组中的 InDels,尤其是 MS 区域。为了特别检测体细胞从头突变,我们从 C57BL/6 小鼠的相同亲本体细胞部分中产生了 13 个独立的重编程干细胞系(11 个 iPSC 和 2 个 ntESC 系)。通过使用具有相同遗传背景的细胞组,我们可以全面检测克隆特异性的改变,并且重要的是,通过实验验证它们。由此证明了采用姐妹克隆检测体细胞从头突变的有效性。然后我们成功地将这种方法应用于人类 iPSC。我们的结果需要进一步仔细的基因组分析,但在解决 iPSC 基因组异常问题方面取得了重要进展。

更新日期:2021-10-12
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