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
リソース情報
遺伝子材料 pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)