A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders
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...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Research
2020
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| _version_ | 1797100700159705088 |
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| author | Agarwal, D Sandor, C Volpato, V Caffrey, TM Monzón-Sandoval, J Bowden, R Alegre-Abarrategui, J Wade-Martins, R Webber, C |
| author_facet | Agarwal, D Sandor, C Volpato, V Caffrey, TM Monzón-Sandoval, J Bowden, R Alegre-Abarrategui, J Wade-Martins, R Webber, C |
| author_sort | Agarwal, D |
| collection | OXFORD |
| description | 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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| first_indexed | 2024-03-07T05:41:20Z |
| format | Journal article |
| id | oxford-uuid:e5aadcab-8092-4731-848b-b8c4305f80cf |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:41:20Z |
| publishDate | 2020 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:e5aadcab-8092-4731-848b-b8c4305f80cf2022-03-27T10:25:43ZA single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disordersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e5aadcab-8092-4731-848b-b8c4305f80cfEnglishSymplectic ElementsNature Research2020Agarwal, DSandor, CVolpato, VCaffrey, TMMonzón-Sandoval, JBowden, RAlegre-Abarrategui, JWade-Martins, RWebber, CWe 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. |
| spellingShingle | Agarwal, D Sandor, C Volpato, V Caffrey, TM Monzón-Sandoval, J Bowden, R Alegre-Abarrategui, J Wade-Martins, R Webber, C A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders |
| title | A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders |
| title_full | A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders |
| title_fullStr | A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders |
| title_full_unstemmed | A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders |
| title_short | A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders |
| title_sort | single cell atlas of the human substantia nigra reveals cell specific pathways associated with neurological disorders |
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