RRC ID 50015
著者 Yahata N, Matsumoto Y, Omi M, Yamamoto N, Hata R.
タイトル TALEN-mediated shift of mitochondrial DNA heteroplasmy in MELAS-iPSCs with m.13513G>A mutation.
ジャーナル Sci Rep
Abstract Induced pluripotent stem cells (iPSCs) are suitable for studying mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations. Here, we generated iPSCs from a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with the m.13513G>A mutation. The patient's dermal fibroblasts were reprogrammed, and we established two iPSC clones with and without mutant mtDNA. Furthermore, we tried to decrease mutant mtDNA level in iPSCs using transcription activator-like effector nucleases (TALENs). We originally engineered platinum TALENs, which were transported into mitochondria, recognized the mtDNA sequence including the m.13513 position, and preferentially cleaved G13513A mutant mtDNA (G13513A-mpTALEN). The m.13513G>A heteroplasmy level in MELAS-iPSCs was decreased in the short term by transduction of G13513A-mpTALEN. Our data demonstrate that this mtDNA-targeted nuclease would be a powerful tool for changing the heteroplasmy level in heteroplasmic iPSCs, which could contribute to elucidation of the pathological mechanisms of mitochondrial diseases caused by mtDNA mutations.
巻・号 7(1)
ページ 15557
公開日 2017-11-14
DOI 10.1038/s41598-017-15871-y
PII 10.1038/s41598-017-15871-y
PMID 29138463
PMC PMC5686150
MeSH Adolescent Animals DNA, Mitochondrial / genetics* Fibroblasts / metabolism Fibroblasts / pathology Humans Induced Pluripotent Stem Cells / metabolism* Induced Pluripotent Stem Cells / pathology MELAS Syndrome / genetics* MELAS Syndrome / pathology Male Mitochondria / genetics Mitochondria / pathology Mitochondrial Diseases / genetics* Mitochondrial Diseases / pathology Mutation / genetics Patients Transcription Activator-Like Effector Nucleases / genetics
IF 3.998
引用数 16
リソース情報
遺伝子材料 pCAGGS (RDB08938)