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Cited by 319

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

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

Open access
Agarwal, Devika, Sandor, Cynthia, Volpato, Viola, Caffrey, Tara M., Monzón-Sandoval, Jimena, Bowden, Rory, Alegre-Abarrategui, Javier, Wade-Martins, Richard, Webber, Caleb·2020·Nature Communications

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.

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Metadata

Authors
Agarwal, D., Sandor, C., Volpato, V., Caffrey, T. M., Monzón-Sandoval, J., Bowden, R., Alegre-Abarrategui, J., Wade-Martins, R., & Webber, C.
Venue
Nature Communications
Published
2020-08-21
Volume
11
Issue
1
Pages
4183-4183
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3080632072
Cited by
319
References
43
FWCI
11.55
Type
journal article
Language
en
Open access
gold

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Agarwal, D., Sandor, C., Volpato, V., Caffrey, T. M., Monzón-Sandoval, J., Bowden, R., Alegre-Abarrategui, J., Wade-Martins, R., & Webber, C. (2020). A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders. Nature Communications. https://doi.org/10.1038/s41467-020-17876-0

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