Establishment of Disease-specific Induced Pluripotent Stem Cells with Pathological Mitochondrial DNA A8344G Mutation and Investigating the Pathogenesis of MERRF Disease
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,...
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ndltd-TW-102YM0053910122015-10-13T23:50:23Z http://ndltd.ncl.edu.tw/handle/28799457691596282111 Establishment of Disease-specific Induced Pluripotent Stem Cells with Pathological Mitochondrial DNA A8344G Mutation and Investigating the Pathogenesis of MERRF Disease 建立粒線體第8344 個核苷酸由腺嘌呤突變為鳥糞嘌呤之疾病專一性誘導型多功能幹細胞並探討肌陣攣性癲癇發作 伴破碎紅纖維病變致病機轉 Yu-Fen Lai 賴玉芬 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. Shih-Hwa Chiou Hwai-Shi Wang 邱士華 王懷詩 2014 學位論文 ; thesis 59 zh-TW |
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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.
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author2 |
Shih-Hwa Chiou |
author_facet |
Shih-Hwa Chiou Yu-Fen Lai 賴玉芬 |
author |
Yu-Fen Lai 賴玉芬 |
spellingShingle |
Yu-Fen Lai 賴玉芬 Establishment of Disease-specific Induced Pluripotent Stem Cells with Pathological Mitochondrial DNA A8344G Mutation and Investigating the Pathogenesis of MERRF Disease |
author_sort |
Yu-Fen Lai |
title |
Establishment of Disease-specific Induced Pluripotent Stem Cells with Pathological Mitochondrial DNA A8344G Mutation and Investigating the Pathogenesis of MERRF Disease |
title_short |
Establishment of Disease-specific Induced Pluripotent Stem Cells with Pathological Mitochondrial DNA A8344G Mutation and Investigating the Pathogenesis of MERRF Disease |
title_full |
Establishment of Disease-specific Induced Pluripotent Stem Cells with Pathological Mitochondrial DNA A8344G Mutation and Investigating the Pathogenesis of MERRF Disease |
title_fullStr |
Establishment of Disease-specific Induced Pluripotent Stem Cells with Pathological Mitochondrial DNA A8344G Mutation and Investigating the Pathogenesis of MERRF Disease |
title_full_unstemmed |
Establishment of Disease-specific Induced Pluripotent Stem Cells with Pathological Mitochondrial DNA A8344G Mutation and Investigating the Pathogenesis of MERRF Disease |
title_sort |
establishment of disease-specific induced pluripotent stem cells with pathological mitochondrial dna a8344g mutation and investigating the pathogenesis of merrf disease |
publishDate |
2014 |
url |
http://ndltd.ncl.edu.tw/handle/28799457691596282111 |
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