Sandor, Cynthia ![]() ![]() ![]() |
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Abstract
While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson’s disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes. The PD LRRK2-G2019S associated profile was positively matched with expression changes induced by the Parkinsonian neurotoxin rotenone and opposed by those induced by clioquinol, a compound with demonstrated therapeutic efficacy in multiple PD models. No functional convergence amongst DE genes was observed following a similar comparison using non-purified iPSC-derived DaN-containing populations, with cellular heterogeneity appearing a greater confound than genotypic background.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Additional Information: | This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Publisher: | Oxford University Press |
ISSN: | 0964-6906 |
Date of First Compliant Deposit: | 21 October 2020 |
Date of Acceptance: | 29 November 2016 |
Last Modified: | 02 May 2023 18:47 |
URI: | https://orca.cardiff.ac.uk/id/eprint/135796 |
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