24
IRUS TotalDownloads
Altmetric
A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders.
File | Description | Size | Format | |
---|---|---|---|---|
s41467-020-17876-0.pdf | Published version | 1.96 MB | Adobe PDF | View/Open |
Title: | A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders. |
Authors: | Agarwal, D Sandor, C Volpato, V Caffrey, TM Monzón-Sandoval, J Bowden, R Alegre-Abarrategui, J Wade-Martins, R Webber, C |
Item Type: | Journal Article |
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. |
Issue Date: | 21-Aug-2020 |
Date of Acceptance: | 21-Jul-2020 |
URI: | http://hdl.handle.net/10044/1/81896 |
DOI: | 10.1038/s41467-020-17876-0 |
Start Page: | 4183 |
Journal / Book Title: | Nat Commun |
Volume: | 11 |
Issue: | 1 |
Copyright Statement: | © The Author(s) 2020. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Publication Status: | Published online |
Conference Place: | England |
Open Access location: | https://www.nature.com/articles/s41467-020-17876-0 |
Appears in Collections: | Department of Brain Sciences |
This item is licensed under a Creative Commons License