Induced pluripotent stem cells (iPSCs) for modeling mitochondrial DNA disorders.
Induced pluripotent stem cells (iPSCs) for modeling mitochondrial DNA disorders.
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DOI：
10.1007/978-1-4939-2288-8_24
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Prigione, Alessandro
中科院分区：
文献类型：
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作者：
Prigione, Alessandro
线粒体DNA(MtDNA)缺陷是遗传病的常见原因，最低患病率为每5000人中有1人。这些疾病通常表现为神经学特征，表现出高度的临床变异性，并且缺乏有效的治疗。存活的疾病模型将是阐明基因/表型关系和改进疾病管理的关键。然而，线粒体遗传学的特殊性阻碍了动物模型的产生，目前的细胞模型不携带患者的核背景，也不表现出有丝分裂后神经元等分化细胞的特征。因此，迫切需要开发创新的建模系统，以便正确地解决适当的人类靶细胞类型中核和线粒体基因组之间的相互作用。因此，从线粒体DNA疾病患者中建立诱导多能干细胞(IPSCs)似乎是一种很有前途的方法。患者来源的IPSCs将包含患者原始的核和线粒体DNA，并能够分化为身体的任何细胞类型，包括有丝分裂后神经元。在这里，我们讨论了应用IPSC技术模拟衰弱的mtDNA疾病的潜在优势和关键挑战。
Defects in mitochondrial DNA (mtDNA) are a frequent cause of genetic disease, with a minimum prevalence of 1 in 5,000 individuals. These disorders often present with neurological features, exhibit high clinical variability, and lack effective treatments. Viable disease models would be critical to elucidate the genotype/phenotype relationship and improve disease management. However, the peculiarities of mitochondrial genetics have hampered the generation of animal models, and current cellular models do not carry the nuclear background of the patients and do not exhibit the features of differentiated cells such as postmitotic neurons. Hence, the development of innovative modeling systems is highly needed in order to correctly address the interplay between the nuclear and mitochondrial genome within the appropriate human target cell types. The establishment of induced pluripotent stem cells (iPSCs) from patients affected by mtDNA disorders thus appears as a promising approach. Patient-derived iPSCs would contain both the original nuclear and mitochondrial DNA of the patients and would be capable of differentiating into any cell type of the body, including postmitotic neurons. Here we discuss the potential advantages and critical challenges for the application of the iPSC technology for modeling debilitating mtDNA diseases.