Efficient induction of dopaminergic neuron differentiation from induced pluripotent stem cells reveals impaired mitophagy in PARK2 neurons
| Autor: | Hiroyuki Katayama, Atsushi Miyawaki, Naoko Kuzumaki, Nobutaka Hattori, Wado Akamatsu, Takefumi Sone, Kei-Ichi Ishikawa, Hideyuki Okano, Fumihiko Kisa, Sadafumi Suzuki |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Ubiquitin-Protein Ligases Induced Pluripotent Stem Cells Models Neurological Population Biophysics Apoptosis Biology Biochemistry Cell Line 03 medical and health sciences Neural Stem Cells Precursor cell Mitophagy medicine Humans Progenitor cell education Induced pluripotent stem cell Molecular Biology education.field_of_study Dopaminergic Neurons Dopaminergic Cell Differentiation Parkinson Disease Cell Biology Anatomy Dopaminergic neuron differentiation Cell biology Hyaluronan Receptors 030104 developmental biology medicine.anatomical_structure Neuron Reactive Oxygen Species |
| Zdroj: | Biochemical and Biophysical Research Communications. 483:88-93 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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