論文 - 詳細
| RRC ID | 47980 |
|---|---|
| 著者 | Suzuki S, Akamatsu W, Kisa F, Sone T, Ishikawa KI, Kuzumaki N, Katayama H, Miyawaki A, Hattori N, Okano H. |
| タイトル | Efficient induction of dopaminergic neuron differentiation from induced pluripotent stem cells reveals impaired mitophagy in PARK2 neurons. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Patient-specific induced pluripotent stem cells (iPSCs) show promise for use as tools for in vitro modeling of Parkinson's disease. We sought to improve the efficiency of dopaminergic (DA) neuron induction from iPSCs by the using surface markers expressed in DA progenitors to increase the significance of the phenotypic analysis. By sorting for a CD184high/CD44- fraction during neural differentiation, we obtained a population of cells that were enriched in DA neuron precursor cells and achieved higher differentiation efficiencies than those obtained through the same protocol without sorting. This high efficiency method of DA neuronal induction enabled reliable detection of reactive oxygen species (ROS) accumulation and vulnerable phenotypes in PARK2 iPSCs-derived DA neurons. We additionally established a quantitative system using the mt-mKeima reporter system to monitor mitophagy in which mitochondria fuse with lysosomes and, by combining this system with the method of DA neuronal induction described above, determined that mitophagy is impaired in PARK2 neurons. These findings suggest that the efficiency of DA neuron induction is important for the precise detection of cellular phenotypes in modeling Parkinson's disease. |
| 巻・号 | 483(1) |
| ページ | 88-93 |
| 公開日 | 2017-1-29 |
| DOI | 10.1016/j.bbrc.2016.12.188 |
| PII | S0006-291X(16)32262-8 |
| PMID | 28057485 |
| MeSH | Apoptosis Cell Differentiation / physiology Cell Line Dopaminergic Neurons / cytology* Dopaminergic Neurons / metabolism* Humans Hyaluronan Receptors / metabolism Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism* Mitophagy / physiology Models, Neurological Neural Stem Cells / cytology Neural Stem Cells / metabolism Parkinson Disease / etiology Parkinson Disease / metabolism Parkinson Disease / pathology Reactive Oxygen Species / metabolism Ubiquitin-Protein Ligases / metabolism* |
| IF | 2.985 |
| 引用数 | 26 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY BIOPHYSICS |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 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 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |