Next Generation Sequencing of PD-iPSC derived midbrain dopaminergic(mDA) neurons treated with CDC (C021 dihychloride) or BAG (BAG 956)

Purpose: The goals of this study are to identify cellular pathways to recover a-syn aggregation-mediated toxicity induced in response to CDC or BAG treatment on PD-iPSC derived mDA neurons. Methods: mRNA profiles of 30-day-old PD-mDA neurons with CDC or BAG treatment for 1 day were generated by deep sequencing, in duplicate, using Illumina HiSeq. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. Conclusions: Our study represents the detailed analysis of mDA neuronal transcriptomes in response to CDC or BAG treatments, with biologic replicates, generated by RNA-seq technology. Our results show that CDC or BAG treatment could rescue the toxcity from a-syn aggregation via purine metabolism / ion transport pathways. Overall design: mRNA profiles of 30-day-old PD-mDA neurons DMSO, bluelight + DMSO or bluelight with CDC or BAG treatment for 1 day (Bluelight - 34 µW/mm2 at 470 nm, 0.17 Hz, 0.5s, 24hrs - is used for inducing alpha-synuclein aggregation)