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学科主题: 临床医学
题名:
The fused in sarcoma protein forms cytoplasmic aggregates in motor neurons derived from integration-free induced pluripotent stem cells generated from a patient with familial amyotrophic lateral sclerosis carrying the FUS-P525L mutation
作者: Liu, Xinxiu1; Chen, Jiayu2; Liu, Wenchao1; Li, Xiaogang3; Chen, Qi2; Liu, Tao1; Gao, Shaorong2; Deng, Min1
关键词: Amyotrophic lateral sclerosis ; Induced pluripotent stem cells ; FUS mutation ; Motor neuron ; Protein aggregation ; Episomal vectors
刊名: NEUROGENETICS
发表日期: 2015-07-01
DOI: 10.1007/s10048-015-0448-y
卷: 16, 期:3, 页:223-231
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity ; Clinical Neurology
研究领域[WOS]: Genetics & Heredity ; Neurosciences & Neurology
关键词[WOS]: CORD BLOOD ; ALS ; INCLUSIONS ; EXPRESSION ; REVEALS ; VECTOR ; OCT4 ; GENE
英文摘要:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons (MNs) and has no effective treatment. Mutations in the fused in sarcoma (FUS) gene and abnormal aggregation of FUS protein have been reported in ALS. However, the mechanisms involved in ALS are poorly understood. Clinical drug trails have failed due to a lack of appropriate disease models, including a lack of access to MNs from ALS patients. Induced pluripotent stem (iPS) cells derived from patients with ALS provide an indispensable resource for in vitro mechanistic studies and for future patient-specific cell-based therapies. Previous reports demonstrated that viral-based ALS-iPS cells generated from fibroblasts harvested from Caucasian populations are ideal for basic research; however, ALS-iPS cells are precluded from cell-based therapeutic applications because of the risks associated with the integration of viral sequences into the genome and inconvenience associated with dermal biopsies. To establish a model for use in clinical applications, using episomal vectors, we generated an integration-free iPS cell line from peripheral blood mononuclear cells (PBMCs) harvested from a familial ALS (FALS) patient carrying the FUS-P525L mutation and a healthy control. Furthermore, we successfully differentiated ALS patient-specific iPS cells into MNs and subsequently detected cytoplasmic mislocalization and formation of FUS protein aggregates in MNs due to the FUS-P525L mutation. Our findings offer a cell-based disease model for use in further elucidating ALS pathogenesis and provide a tool for exploring gene repair coupled with cell replacement therapy.

语种: 英语
所属项目编号: 81473042 ; 31171048 ; 81072374 ; 7112146 ; 2009A04
项目资助者: National Natural Foundation of China ; Beijing Municipal Natural Science Foundation ; Beijing Nova Program
WOS记录号: WOS:000356532700008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52666
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Peking Univ, Med Res Ctr, Hosp 3, Beijing 100191, Peoples R China
2.Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China
3.Peking Univ, Dept Neurol, Hosp 3, Beijing 100191, Peoples R China

Recommended Citation:
Liu, Xinxiu,Chen, Jiayu,Liu, Wenchao,et al. The fused in sarcoma protein forms cytoplasmic aggregates in motor neurons derived from integration-free induced pluripotent stem cells generated from a patient with familial amyotrophic lateral sclerosis carrying the FUS-P525L mutation[J]. NEUROGENETICS,2015,16(3):223-231.
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