A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders

Devika Agarwal, Cynthia Sandor, Viola Volpato, Tara M. Caffrey, Jimena Monzón-Sandoval, Rory Bowden, Javier Alegre-Abarrategui, Richard Wade-Martins and Caleb Webber ()
Additional contact information
Devika Agarwal: University of Oxford
Cynthia Sandor: Cardiff University
Viola Volpato: Cardiff University
Tara M. Caffrey: University of Oxford
Jimena Monzón-Sandoval: Cardiff University
Rory Bowden: Wellcome Trust Centre for Human Genetics
Javier Alegre-Abarrategui: University of Oxford
Richard Wade-Martins: University of Oxford
Caleb Webber: University of Oxford

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract We describe a human single-nuclei transcriptomic atlas for the substantia nigra (SN), generated by sequencing approximately 17,000 nuclei from matched cortical and SN samples. We show that the common genetic risk for Parkinson’s disease (PD) is associated with dopaminergic neuron (DaN)-specific gene expression, including mitochondrial functioning, protein folding and ubiquitination pathways. We identify a distinct cell type association between PD risk and oligodendrocyte-specific gene expression. Unlike Alzheimer’s disease (AD), we find no association between PD risk and microglia or astrocytes, suggesting that neuroinflammation plays a less causal role in PD than AD. Beyond PD, we find associations between SN DaNs and GABAergic neuron gene expression and multiple neuropsychiatric disorders. Conditional analysis reveals that distinct neuropsychiatric disorders associate with distinct sets of neuron-specific genes but converge onto shared loci within oligodendrocytes and oligodendrocyte precursors. This atlas guides our aetiological understanding by associating SN cell type expression profiles with specific disease risk.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17876-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17876-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17876-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().