| RRC ID |
47980
|
| Author |
Suzuki S, Akamatsu W, Kisa F, Sone T, Ishikawa KI, Kuzumaki N, Katayama H, Miyawaki A, Hattori N, Okano H.
|
| Title |
Efficient induction of dopaminergic neuron differentiation from induced pluripotent stem cells reveals impaired mitophagy in PARK2 neurons.
|
| Journal |
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.
|
| Volume |
483(1)
|
| Pages |
88-93
|
| Published |
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
|
| Times Cited |
26
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
BIOPHYSICS
|
| Resource |
| DNA material |
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
