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Series GSE171999 Query DataSets for GSE171999
Status Public on Apr 13, 2021
Title Phenotypic manifestation of alpha-synuclein strains derived from Parkinson’s disease and multiple system atrophy in human dopaminergic neurons
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Althougha-synuclein is implicated in the pathogenesis of Parkinson’s disease and related disorders, it remains unclear whether specific conformations or levels ofa-synuclein assemblies are toxic and how they cause progressive loss of human dopaminergic neurons. To address this issue, we used iPSC-derived dopaminergic neurons with a-synuclein triplication or controls where endogenous a-synuclein was imprinted into synthetic or disease-relevant conformations. We used a-synuclein fibrils generated de novo or amplified from homogenates of brains affected with Parkinson’s disease (n=3) or multiple system atrophy (n=5). We found that a 2.5-fold increase in a-synuclein levels in a-synuclein gene triplication neurons promoted seeded aggregation in a dose and time-dependent fashion, which was associated with a further increase in a-synuclein gene expression. Progressive neuronal loss was observed only in a-synuclein triplication neurons seeded with brain-amplified fibrils. Transcriptomic analysis and isogenic correction of a-synuclein triplication revealed that intraneuronalalpha-synuclein levels solely and sufficiently explained vulnerability to neuronal death
Overall design RNASeq experiment to compare the SNCA triplication iPSC line (n=3 biological replicates per condition) at baseline and after induction of alpha-synuclein aggregation for 1 and 2 weeks. This was done to investigate whether there are transcriptomic changes upon alpha-synuclein aggregation within neurons using SNCA Triplication line (SFC831-03-03) when compared to their corresponding baseline Non-seeded controls (NSC) using three different types of fibrils: de novo generated fibrils (FIB), MSA amplified Fibrils (MSA) or PD amlpified Fibrils (PD) at 1 microM. A total of 24 different human iPSC samples were sequenced on the Novaseq 6000 platform.
Contributor(s) Tanudjojo B, Shaikh S, Fenyi A, Bousset L, Agarwal D, Marsh J, Zois C, Herman-Ackah S, Fischer R, Sims D, Melki R, Tofaris GK
Citation(s) 34155194
Submission date Apr 13, 2021
Last update date Jul 14, 2021
Contact name Devika Agarwal
Organization name University of Oxford
Department The MRC Weatherall Institute of molecular medicine
Lab Centre for Computational Biology
Street address JR hospital, Headley way
City Oxford
ZIP/Postal code OX3 9DS
Country United Kingdom
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (24)
GSM5239580 WK1_R1_NSC
GSM5239581 WK1_R2_NSC
GSM5239582 WK1_R3_NSC
BioProject PRJNA721677
SRA SRP314679

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Supplementary file Size Download File type/resource
GSE171999_RAW.tar 138.9 Mb (http)(custom) TAR (of TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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