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Characterization of altered molecular mechanisms in Parkinson’s disease through cell type–resolved multiomics analyses

Authors: Andrew J. Lee; Changyoun Kim; Seongwan Park; Jaegeon Joo; Baekgyu Choi; Dongchan Yang; Kyoungho Jun; +7 Authors

Characterization of altered molecular mechanisms in Parkinson’s disease through cell type–resolved multiomics analyses

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder. However, cell type–dependent transcriptional regulatory programs responsible for PD pathogenesis remain elusive. Here, we establish transcriptomic and epigenomic landscapes of the substantia nigra by profiling 113,207 nuclei obtained from healthy controls and patients with PD. Our multiomics data integration provides cell type annotation of 128,724 cis-regulatory elements (cREs) and uncovers cell type–specific dysregulations in cREs with a strong transcriptional influence on genes implicated in PD. The establishment of high-resolution three-dimensional chromatin contact maps identifies 656 target genes of dysregulated cREs and genetic risk loci, uncovering both potential and known PD risk genes. Notably, these candidate genes exhibit modular gene expression patterns with unique molecular signatures in distinct cell types, highlighting altered molecular mechanisms in dopaminergic neurons and glial cells including oligodendrocytes and microglia. Together, our single-cell transcriptome and epigenome reveal cell type–specific disruption in transcriptional regulations related to PD.

Country
United States
Keywords

Gene Expression Profiling, Dopaminergic Neurons, 616, 610, Humans, Parkinson Disease, Multiomics, Transcriptome, Neuroscience

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
downloads
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50
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102
35
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