Generation of patient-derived pluripotent stem cell-lines and CRISPR modified isogenic controls with mutations in the Parkinson’s associated GBA gene

Carol X.-Q. Chen; Eric Deneault; Narges Abdian; Zhipeng You; Julien Sirois; Michael Nicouleau; Irina Shlaifer; Lorenza Villegas; Marie-Noëlle Boivin; Lydiane Gaborieau; Jason Karamchandani; Lenore K. Beitel; Edward A. Fon; Thomas M. Durcan

Stem Cell Research (Oct 2022)

Generation of patient-derived pluripotent stem cell-lines and CRISPR modified isogenic controls with mutations in the Parkinson’s associated GBA gene

Carol X.-Q. Chen,
Eric Deneault,
Narges Abdian,
Zhipeng You,
Julien Sirois,
Michael Nicouleau,
Irina Shlaifer,
Lorenza Villegas,
Marie-Noëlle Boivin,
Lydiane Gaborieau,
Jason Karamchandani,
Lenore K. Beitel,
Edward A. Fon,
Thomas M. Durcan

Affiliations

Carol X.-Q. Chen: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Eric Deneault: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Narges Abdian: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Zhipeng You: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Julien Sirois: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Michael Nicouleau: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Irina Shlaifer: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Lorenza Villegas: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Marie-Noëlle Boivin: C-BIG Biorepository (C-BIG), Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec H3A 2B4, Canada
Lydiane Gaborieau: C-BIG Biorepository (C-BIG), Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec H3A 2B4, Canada
Jason Karamchandani: C-BIG Biorepository (C-BIG), Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec H3A 2B4, Canada
Lenore K. Beitel: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Edward A. Fon: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada
Thomas M. Durcan: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada; Corresponding author.

Journal volume & issue: Vol. 64
p. 102919

Abstract

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The GBA gene encodes the lysosomal enzyme glucocerebrosidase (GCase), responsible for the hydrolysis of glucocerebroside to glucose and ceramide. Heterozygous GBA mutations have been associated with the development of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We generated two induced pluripotent stem cell (iPSC) lines from PD patients carrying heterozygous GBA W378G or N370S mutations and subsequently produced isogenic control lines using CRISPR/Cas9 genome editing. The patient-derived iPSCs and isogenic control lines maintained full pluripotency, normal karyotypes, and differentiation capacity. All iPSC lines could be differentiated into dopaminergic neurons, thus providing valuable tools for studying PD pathogenesis.

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

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