Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons
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Abstract
Major depressive disorder (MDD) has an enormous impact on global disease burden, affecting millions of people worldwide and ranking as a leading cause of disability for almost three decades. Past molecular studies of MDD employed bulk homogenates of postmortem brain tissue, which obscures gene expression changes within individual cell types. Here we used single-nucleus transcriptomics to examine ~80,000 nuclei from the dorsolateral prefrontal cortex of male individuals with MDD (n = 17) and of healthy controls (n = 17). We identified 26 cellular clusters, and over 60% of these showed differential gene expression between groups. We found that the greatest dysregulation occurred in deep layer excitatory neurons and immature oligodendrocyte precursor cells (OPCs), and these contributed almost half (47%) of all changes in gene expression. These results highlight the importance of dissecting cell-type-specific contributions to the disease and offer opportunities to identify new avenues of research and novel targets for treatment.
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Within the compendium, fourteen studies had control groups that included six or more samples.
“Within our compendium, we identified a total of fourteen studies with control groups that included six or more samples5,6,15,49–59.”
From Confronting false discoveries in single-cell differential expression (2021) · cites this paper as [49]
Substantial evidence of preservation was found across all modules except INH-M1 in an snRNA-seq dataset of the PFC from donors with major depressive disorder and controls.
“Finally, we tested for the preservation of these modules in 19,425 inhibitory neurons from an snRNA-seq dataset of the PFC from donors with major depressive disorder (MDD) and controls45 (34 samples), and we found substantial evidence of preservation across all modules except INH-M1 (Figures S10C–S10E).”
From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [45]
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- Authors
- Nagy, C., Maitra, M., Tanti, A., Suderman, M., Théroux, J.-F., Davoli, M. A., Perlman, K., Yerko, V., Wang, Y. C., Tripathy, S. J., Pavlidis, P., Mechawar, N., Ragoussis, J., & Turecki, G.
- Affiliations
- Douglas Mental Health University Institute (CA)
- University of Bristol (GB)
- McGill University and Génome Québec Innovation Centre (CA)
- Centre for Addiction and Mental Health (CA)
- University of British Columbia (CA)
- University of Toronto (CA)
- Corresponding author
- Turecki, Gustavo
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2020-04-27
- Volume
- 23
- Issue
- 6
- Pages
- 771-781
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W3020538763
- Cited by
- 532
- References
- 100
- Citations by year
- 2026: 88 · 2025: 100 · 2024: 99 · 2023: 86 · 2022: 64 · 2021: 66 · 2020: 23 · 2019: 5 · 2018: 1
- FWCI
- 35.86
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, other-oa)
- eScholarship@McGill (McGill) (submittedVersion)
- Funders
- Gouvernement du Canada | Canadian Institutes of Health Research (FDN148374, EGM141899)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- major depressive disorder, dorsolateral prefrontal cortex, single-nucleus transcriptomics, oligodendrocyte precursor cells, cell type-specific gene expression, synaptic plasticity, immune function, steroid hormones, postmortem brain
- MeSH terms
- Oligodendrocyte Precursor Cells, Adolescent, Adult, Aged, Aged, 80 and over, Major Depressive Disorder, Humans, Male, Middle Aged, Neurons, Case-Control Studies, Prefrontal Cortex, Gene Regulatory Networks, Young Adult, High-Throughput Nucleotide Sequencing, Transcriptome
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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