The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs.
The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs.
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线粒体DNA变异在人iPSCs重编程和神经元分化过程中波动的相关性
DOI：
10.1016/j.stemcr.2021.06.016
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发表时间：
2021-08-10
影响因子：
5.9
通讯作者：
Tiranti V
中科院分区：
文献类型：
--
作者：
Palombo F;Peron C;Caporali L;Iannielli A;Maresca A;Di Meo I;Fiorini C;Segnali A;Sciacca FL;Rizzo A;Levi S;Suomalainen A;Prigione A;Broccoli V;Carelli V;Tiranti V
可诱导多能干细胞(IPSCs)的产生是一项革命性的技术，可以生产用于疾病建模、药物筛选和细胞治疗的多能患者特异性细胞系。核DNA(NDNA)的完整性是允许IPSCs使用的强制性条件，而线粒体DNA(MtDNA)的质量控制很少包括在IPSCs的验证过程中。在这项研究中，我们在从父母成纤维细胞到重编程的IPSC和从对照组和受线粒体疾病影响的患者获得的分化神经前体细胞(NPC)的转变过程中进行了mtDNA深度测序。在每一步，线粒体DNA变异，包括那些潜在的致病基因，在出现和消失之间波动，其中一些具有功能含义。我们强烈建议将线粒体DNA分析作为获得完全认证的可用的IPSCs和NPC的不可避免的测试。线粒体DNA深度测序是ipSCs的质量控制中必需的步骤mtDNA变体在从成纤维细胞/PBMC到ipSCs和NPC的每一步都会波动，mtDNA变体会极大地影响iPSC的表型，反映出它们的健康结果可能会被误解，如果不评估mtDNA变体的存在，Tiranti和他的同事们注意到iPSCs的质量控制很少包括对线粒体中存在的一种小环状分子线粒体DNA(MtDNA)的分析。然而，线粒体DNA变异对IPSCs的最终表型有很大影响。他们强调了IPSC来源的神经元前体也可以呈现mtDNA变体，并强调了筛选mtDNA的极端重要性。
The generation of inducible pluripotent stem cells (iPSCs) is a revolutionary technique allowing production of pluripotent patient-specific cell lines used for disease modeling, drug screening, and cell therapy. Integrity of nuclear DNA (nDNA) is mandatory to allow iPSCs utilization, while quality control of mitochondrial DNA (mtDNA) is rarely included in the iPSCs validation process. 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. At each step, mtDNA variants, including those potentially pathogenic, fluctuate between emerging and disappearing, and some having functional implications. We strongly recommend including mtDNA analysis as an unavoidable assay to obtain fully certified usable iPSCs and NPCs. mtDNA deep sequencing is mandatory in quality control of iPSCs mtDNA variants fluctuate at each step from fibroblasts/PBMC, to iPSCs and NPCs mtDNA variants greatly affect iPSC phenotype, reflecting their healthiness Results could be misinterpreted if mtDNA variants presence has not been assessed Tiranti and colleagues observed that quality control of iPSCs rarely includes the analysis of mitochondrial DNA (mtDNA), a small circular molecule present in the mitochondria. However, mtDNA variants greatly affect the final phenotype of iPSCs. They highlighted that iPSC-derived neuronal precursors could also present mtDNA variants and underlined the paramount importance of screening mtDNA.
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影响因子：
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作者：
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通讯作者：
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通讯作者：
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