論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCAGGS (RDB08938) |