1. Dopaminergic neurons differentiating from LRRK2 G2019S induced pluripotent stem cells show early neuritic branching defects
- Author
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Juliette D. Godin, Philippe Alix, Benjamin Grobarczyk, Elise Peyre, Philippe Lefebvre, Kevin Hanon, Audrey Purnelle, Nathalie Krusy, Vincent Seutin, Laurent Nguyen, Laurence Borgs, Pierre Maquet, Brigitte Malgrange, GIGA-Neurosciences [Université Liège], GIGA [Université Liège], and Université de Liège-Université de Liège
- Subjects
0301 basic medicine ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Induced Pluripotent Stem Cells ,Biology ,Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Neural Stem Cells ,Mesencephalon ,Neurites ,Animals ,Humans ,Induced pluripotent stem cell ,Cells, Cultured ,ComputingMilieux_MISCELLANEOUS ,LRRK2 Gene ,Multidisciplinary ,Dopaminergic Neurons ,Dopaminergic ,Parkinson Disease ,Phenotype ,LRRK2 ,Molecular biology ,Neural stem cell ,In vitro ,Pathophysiology ,3. Good health ,Cell biology ,030104 developmental biology ,Mutation ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2016
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