Dopaminergic neurons differentiating from LRRK2 G2019S induced pluripotent stem cells show early neuritic branching defects

被引：50

作者：

Borgs, Laurence ^{[1
]}

Peyre, Elise ^{[1
]}

Alix, Philippe ^{[1
]}

Hanon, Kevin ^{[1
]}

Grobarczyk, Benjamin ^{[1
]}

Godin, Juliette D. ^{[1
]}

Purnelle, Audrey ^{[1
]}

Krusy, Nathalie ^{[1
]}

Maquet, Pierre ^{[1
,2
]}

Lefebvre, Philippe ^{[1
,3
]}

Seutin, Vincent ^{[1
]}

Malgrange, Brigitte ^{[1
]}

Laurent Nguyen ^{[1
]}

机构：

[1] Univ Liege, GIGA Neurosci, GIGA Res, B-4000 Liege, Belgium

[2] CHU Sart Tilman, Serv Neurol, Liege, Belgium

[3] CHU Sart Tilman, Serv Othorhinolaryngol, Liege, Belgium

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

END-TRACKING PROTEINS; PARKINSONS-DISEASE; FAMILIAL PARKINSONISM; SUSCEPTIBILITY; GENE; LEUCINE-RICH-REPEAT-KINASE-2; PATHOGENESIS; PENETRANCE; MUTATIONS; AUTOPHAGY;

D O I：

10.1038/srep33377

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Some mutations of the LRRK2 gene underlie autosomal dominant form of Parkinson's disease (PD). The G2019S is a common mutation that accounts for about 2% of PD cases. To understand the pathophysiology of this mutation and its possible developmental implications, we developed an in vitro assay to model PD with human induced pluripotent stem cells (hiPSCs) reprogrammed from skin fibroblasts of PD patients suffering from the LRKK2 G2019S mutation. We differentiated the hiPSCs into neural stem cells (NSCs) and further into dopaminergic neurons. Here we show that NSCs bearing the mutation tend to differentiate less efficiently into dopaminergic neurons and that the latter exhibit significant branching defects as compared to their controls.

引用

页数：11

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