title: Motoneuron differentiation of induced pluripotent stem cells from SOD1G93A mice.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder mainly affecting motor neurons. Mutations in superoxide dismutase-1 (SOD-1) account for about 20% of familial ALS patients. A robust supply of motoneurons carrying the mutated gene would help understand the causes of motoneuron death and develop new therapeutics for the disease. Here, we established induced pluripotent stem (iPS) cell lines from SOD1G93A mice and compared their potency in motoneuron generation with normal iPS cells and mouse embryonic stem cells (E14). Our results showed that iPS cells derived from SOD1G93A mice possessed the similar potency in neuronal differentiation to normal iPS cells and E14 cells and can be efficiently driven to motoneuron-like phenotype. These cells exhibited typical neuronal morphology, expressed key motoneuron markers, including ChAT and HB9, and generated repetitive trains of action potentials. Furthermore, these neurons highly expressed human SOD-1 and exhibited shorter neurites compared to controls. The present study provides evidence that ALS-iPS cells can be used as disease models in high-throughput screening and mechanistic studies due to their ability to efficiently differentiate into specific neuronal subtypes.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Yao
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Ye
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Jian-bo
authors.initials: JB
authors.lastname: Wan
authors.forename: Jun
authors.initials: J
authors.lastname: Zhen
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Li
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
authors.forename: Huangxing
authors.initials: H
authors.lastname: Su
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Lu
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D013623:Tail; D014161:Transduction, Genetic; D014404:Tubulin / Q000378:metabolism
chemical_list: C000606290:SOD1 protein, human; D014404:Tubulin; D049452:Green Fluorescent Proteins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1