Author:
Sheta Razan,Teixeira Maxime,Idi Walid,Pierre Marion,de Rus Jacquet Aurelie,Emond Vincent,Zorca Cornelia E.,Vanderperre Benoît,Durcan Thomas M.,Fon Edward A.,Calon Frédéric,Chahine Mohamed,Oueslati Abid
Abstract
AbstractThe use of human derived induced pluripotent stem cells (hiPSCs) differentiated to dopaminergic (DA) neurons offers a valuable experimental model to decorticate the cellular and molecular mechanisms of Parkinson’s disease (PD) pathogenesis. However, the existing approaches present with several limitations, notably the lengthy time course of the protocols and the high variability in the yield of DA neurons. Here we report on the development of an improved approach that combines neurogenin-2 programming with the use of commercially available midbrain differentiation kits for a rapid, efficient, and reproducible directed differentiation of hiPSCs to mature and functional induced DA (iDA) neurons, with minimum contamination by other brain cell types. Gene expression analysis, associated with functional characterization examining neurotransmitter release and electrical recordings, support the functional identity of the iDA neurons to A9 midbrain neurons. iDA neurons showed selective vulnerability when exposed to 6-hydroxydopamine, thus providing a viable in vitro approach for modeling PD and for the screening of small molecules with neuroprotective proprieties.
Funder
Canadian Institutes of Health Research
Fonds de Recherche du Québec - Santé
Société Parkinson du Québec
Publisher
Springer Science and Business Media LLC
Cited by
5 articles.
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