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Series GSE109706 Query DataSets for GSE109706
Status Public on Mar 01, 2018
Title Parkinson’s Disease Genetic Risk in a Midbrain Neuronal Cell Line
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary In genome-wide association studies of complex diseases, many risk polymorphisms are found to lie in non-coding DNA and likely confer risk through allele-dependent differences in gene regulatory elements. However, because distal regulatory elements can alter gene expression at various distances on linear DNA, the identity of relevant genes is unknown for most risk loci. In Parkinson’s disease, at least some genetic risk is likely intrinsic to a neuronal subpopulation of cells in the brain regions affected. In order to compare neuron-relevant methods of pairing risk polymorphisms to target genes as well as to further characterize a single-cell model of a neurodegenerative disease, we used the portionally-dopaminergic, neuronal, mesencephalic-derived cell line LUHMES to dissect differentiation-specific mechanisms of gene expression. We compared genome-wide gene expression in undifferentiated and differentiated cells with genome-wide histone H3K27ac and CTCF-bound regions. Whereas promoters and CTCF binding were largely consistent between differentiated and undifferentiated cells, enhancers were mostly unique. We matched the differentiation-specific appearance or disappearance of enhancers with changes in gene expression and identified 22,057 enhancers paired with 6,388 differentially expressed genes by proximity. These enhancers are enriched with at least 13 transcription factor response elements, driving a cluster of genes involved in neurogenesis. We show that differentiated LUHMES cells, but not undifferentiated cells, show enrichment for PD-risk SNPs. Candidate genes for these loci are largely unrelated, though a subset is linked to synaptic vesicle cycling and transport, implying that PD-related disruption of these pathways is intrinsic to dopaminergic neurons.
 
Overall design Lund human mesencephalic cells (LUHMES) can be propagated as cycling undifferentiated neural progenitor cells or induced to differentiate into dopaminergic neurons. We cultured and propagated LUHMES cells (undifferentiated cells) and induced differentiation for 6 days (differentiated cells). We isolated RNA from undifferentiated and differentiated cells in order to compare gene expression (RNA-seq), CTCF binding location (ChIP-seq), and enhancer/promoter (H3K27Ac ChIP-seq) activity in the two states.
 
Contributor(s) Coetzee GA, Pierce SE, Tyson T
Citation(s) 29486295
Submission date Jan 26, 2018
Last update date Mar 26, 2019
Contact name Gerry A. Coetzee
E-mail(s) gerry.coetzee@vai.org
Phone 6162345305
Organization name Van Andel Research Institute
Department Center for Neurodegenerative Science
Lab Gerry Coetzee
Street address 333 Bostwick Ave NE
City Grand Rapids
State/province MI
ZIP/Postal code 49503
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (20)
GSM2948717 LUHMES undifferentiated RNA-seq Sample 1
GSM2948718 LUHMES undifferentiated RNA-seq Sample 2
GSM2948719 LUHMES undifferentiated RNA-seq Sample 3
Relations
BioProject PRJNA431771
SRA SRP131485

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Supplementary file Size Download File type/resource
GSE109706_ChIP-seq_processed_data.tar.gz 2.1 Gb (ftp)(http) TAR
GSE109706_RNA-seq_processed_data.tar.gz 309.7 Mb (ftp)(http) TAR
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Raw data are available in SRA
Processed data are available on Series record

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