Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution
Abstract Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. The pathological hallmark of PD is loss of dopaminergic neurons and the presence of aggregated α-synuclein, primarily in the substantia nigra pars compacta (SNpc) of the midbrain. However, the molecular mechanism...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
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| Series: | Molecular Neurodegeneration |
| Online Access: | https://doi.org/10.1186/s13024-023-00699-0 |
| _version_ | 1797233273985826816 |
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| author | Araks Martirosyan Rizwan Ansari Francisco Pestana Katja Hebestreit Hayk Gasparyan Razmik Aleksanyan Silvia Hnatova Suresh Poovathingal Catherine Marneffe Dietmar R. Thal Andrew Kottick Victor J. Hanson-Smith Sebastian Guelfi William Plumbly T. Grant Belgard Emmanouil Metzakopian Matthew G. Holt |
| author_facet | Araks Martirosyan Rizwan Ansari Francisco Pestana Katja Hebestreit Hayk Gasparyan Razmik Aleksanyan Silvia Hnatova Suresh Poovathingal Catherine Marneffe Dietmar R. Thal Andrew Kottick Victor J. Hanson-Smith Sebastian Guelfi William Plumbly T. Grant Belgard Emmanouil Metzakopian Matthew G. Holt |
| author_sort | Araks Martirosyan |
| collection | DOAJ |
| description | Abstract Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. The pathological hallmark of PD is loss of dopaminergic neurons and the presence of aggregated α-synuclein, primarily in the substantia nigra pars compacta (SNpc) of the midbrain. However, the molecular mechanisms that underlie the pathology in different cell types is not currently understood. Here, we present a single nucleus transcriptome analysis of human post-mortem SNpc obtained from 15 sporadic Parkinson’s Disease (PD) cases and 14 Controls. Our dataset comprises ∼84K nuclei, representing all major cell types of the brain, allowing us to obtain a transcriptome-level characterization of these cell types. Importantly, we identify multiple subpopulations for each cell type and describe specific gene sets that provide insights into the differing roles of these subpopulations. Our findings reveal a significant decrease in neuronal cells in PD samples, accompanied by an increase in glial cells and T cells. Subpopulation analyses demonstrate a significant depletion of tyrosine hydroxylase (TH) enriched astrocyte, microglia and oligodendrocyte populations in PD samples, as well as TH enriched neurons, which are also depleted. Moreover, marker gene analysis of the depleted subpopulations identified 28 overlapping genes, including those associated with dopamine metabolism (e.g., ALDH1A1, SLC6A3 & SLC18A2). Overall, our study provides a valuable resource for understanding the molecular mechanisms involved in dopaminergic neuron degeneration and glial responses in PD, highlighting the existence of novel subpopulations and cell type-specific gene sets. |
| first_indexed | 2024-03-08T12:34:41Z |
| format | Article |
| id | doaj.art-ac5a812e7fc64915b2e68e33cecdd4a4 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-04-24T16:13:33Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-ac5a812e7fc64915b2e68e33cecdd4a42024-03-31T11:35:30ZengBMCMolecular Neurodegeneration1750-13262024-01-0119112410.1186/s13024-023-00699-0Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolutionAraks Martirosyan0Rizwan Ansari1Francisco Pestana2Katja Hebestreit3Hayk Gasparyan4Razmik Aleksanyan5Silvia Hnatova6Suresh Poovathingal7Catherine Marneffe8Dietmar R. Thal9Andrew Kottick10Victor J. Hanson-Smith11Sebastian Guelfi12William Plumbly13T. Grant Belgard14Emmanouil Metzakopian15Matthew G. Holt16VIB Center for Brain & Disease Research, KU LeuvenUK Dementia Research Institute, Department of Clinical Neurosciences, University of CambridgeVIB Center for Brain & Disease Research, KU LeuvenVerge GenomicsArmenian Bioinformatics InstituteArmenian Bioinformatics InstituteUK Dementia Research Institute, Department of Clinical Neurosciences, University of CambridgeVIB Center for Brain & Disease Research, KU LeuvenVIB Center for Brain & Disease Research, KU LeuvenLaboratory for Neuropathology, Department of Imaging and Pathology and Leuven Brain Institute, KU Leuven, and Department of Pathology, UZ LeuvenVerge GenomicsVerge GenomicsVerge GenomicsUK Dementia Research Institute, Department of Clinical Neurosciences, University of CambridgeThe Bioinformatics CROUK Dementia Research Institute, Department of Clinical Neurosciences, University of CambridgeVIB Center for Brain & Disease Research, KU LeuvenAbstract Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. The pathological hallmark of PD is loss of dopaminergic neurons and the presence of aggregated α-synuclein, primarily in the substantia nigra pars compacta (SNpc) of the midbrain. However, the molecular mechanisms that underlie the pathology in different cell types is not currently understood. Here, we present a single nucleus transcriptome analysis of human post-mortem SNpc obtained from 15 sporadic Parkinson’s Disease (PD) cases and 14 Controls. Our dataset comprises ∼84K nuclei, representing all major cell types of the brain, allowing us to obtain a transcriptome-level characterization of these cell types. Importantly, we identify multiple subpopulations for each cell type and describe specific gene sets that provide insights into the differing roles of these subpopulations. Our findings reveal a significant decrease in neuronal cells in PD samples, accompanied by an increase in glial cells and T cells. Subpopulation analyses demonstrate a significant depletion of tyrosine hydroxylase (TH) enriched astrocyte, microglia and oligodendrocyte populations in PD samples, as well as TH enriched neurons, which are also depleted. Moreover, marker gene analysis of the depleted subpopulations identified 28 overlapping genes, including those associated with dopamine metabolism (e.g., ALDH1A1, SLC6A3 & SLC18A2). Overall, our study provides a valuable resource for understanding the molecular mechanisms involved in dopaminergic neuron degeneration and glial responses in PD, highlighting the existence of novel subpopulations and cell type-specific gene sets.https://doi.org/10.1186/s13024-023-00699-0 |
| spellingShingle | Araks Martirosyan Rizwan Ansari Francisco Pestana Katja Hebestreit Hayk Gasparyan Razmik Aleksanyan Silvia Hnatova Suresh Poovathingal Catherine Marneffe Dietmar R. Thal Andrew Kottick Victor J. Hanson-Smith Sebastian Guelfi William Plumbly T. Grant Belgard Emmanouil Metzakopian Matthew G. Holt Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution Molecular Neurodegeneration |
| title | Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution |
| title_full | Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution |
| title_fullStr | Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution |
| title_full_unstemmed | Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution |
| title_short | Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution |
| title_sort | unravelling cell type specific responses to parkinson s disease at single cell resolution |
| url | https://doi.org/10.1186/s13024-023-00699-0 |
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