Establishment of Disease-specific Induced Pluripotent Stem Cells with Pathological Mitochondrial DNA A8344G Mutation and Investigating the Pathogenesis of MERRF Disease

• Main Authors: Yu-Fen Lai, 賴玉芬
• Other Authors: Shih-Hwa Chiou
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/28799457691596282111

碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 102 === Myoclonus epilepsy associated with ragged-red fibers (MERRF) syndrome, which results from an A to G transition of nucleotide 8344 in the mitochondria tRNALsy gene, is characterized by myoclonus epilepsy, generalized seizures, ataxia and myopathy. Recently, induced pluripotent stem cells (iPSCs) have been generated from somatic cells obtained from patients with various diseases, but not for MERRF. In this study, we established the iPSCs from patients with MERRF syndrome for disease modeling and studying diseases with complex mechanisms. MERRF-specific iPSCs (MERRF-iPSCs) have the hallmarks of pluripotency and can be differentiated into all three germ layers. We find that morphology and function of mitochondria are abnormal in MERRF-iPSCs when compare with human embryonic stem cells (hESCs). Furthermore, we differentiated these iPSCs into cardiomyocytes. Our data showed that morphology of mitochondria are swollen and distorted cristae in the MERRF-cardiomyocytes. In addition, the generation of ROS and fragmentation of mitochondrial in MERRF-cardiomyocytes are both higher than ESCs-cardiomyocytes and control iPSCs-cardiomyocytes. However, the autophagy phenomenon is not significantly different between MERRF-cardiomyocytes and normal cardiomyocyte. We then addressed that apoptosis may be play an important role in mechanism of MERRF. We will keep elucidating disease mechanisms in MERRF in our future work.