Human fibroblasts, IPSCs and NPCs mitochondrial raw sequence reads

In this study, we performed mtDNA deep sequencing during the transition from parental fibroblasts to reprogrammed iPSC and to differentiated neuronal precursor cells (NPCs) obtained from controls and patients affected by mitochondrial disorders carrying pathogenic mutations either in mtDNA or nDNA. Our results indicate that at each step, mtDNA variants, including those potentially pathogenic, fluctuate emerging or disappearing. Our results strongly suggest to including mtDNA analysis as an unavoidable assay to obtain fully certified usable iPSCs and NPCs.

本研究中，我们对亲本成纤维细胞向重编程诱导多能干细胞（induced pluripotent stem cells, iPSC）的转化过程，以及从对照个体与携带线粒体DNA（mitochondrial DNA, mtDNA）或核DNA（nuclear DNA, nDNA）致病性突变的线粒体疾病患者中获取的分化神经元前体细胞（neuronal precursor cells, NPCs）开展了线粒体DNA深度测序。研究结果显示，在每一个转化阶段，线粒体DNA变异（包括潜在致病性变异）均会发生动态波动，表现为出现或消失。本研究结果有力表明，若要获得经完全认证的可用诱导多能干细胞与神经元前体细胞，必须将线粒体DNA分析作为一项不可或缺的检测项目。