| Summary: | 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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