Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons

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 expre...

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Published in:Nature neuroscience Vol. 23; no. 6; pp. 771 - 781
Main Authors: Nagy, Corina, Maitra, Malosree, Tanti, Arnaud, Suderman, Matthew, Théroux, Jean-Francois, Davoli, Maria Antonietta, Perlman, Kelly, Yerko, Volodymyr, Wang, Yu Chang, Tripathy, Shreejoy J, Pavlidis, Paul, Mechawar, Naguib, Ragoussis, Jiannis, Turecki, Gustavo
Format: Journal Article
Language:English
Published: United States Nature Publishing Group 01.06.2020
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Brain
Case-Control Studies
Depressive Disorder, Major - metabolism
Gene expression
Gene Regulatory Networks
Glial stem cells
High-Throughput Nucleotide Sequencing - methods
Hormones
Humans
Immune response
Male
Mental depression
Middle Aged
Neurons
Neurons - metabolism
Nuclei (cytology)
Oligodendrocyte Precursor Cells - metabolism
Oligodendrocytes
Precursors
Prefrontal cortex
Prefrontal Cortex - metabolism
Steroid hormones
Steroids
Synaptic plasticity
Transcriptome
Young Adult
ISSN:1097-6256, 1546-1726, 1546-1726
Online Access:Get full text
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Summary: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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ISSN:1097-6256
1546-1726
1546-1726
DOI:10.1038/s41593-020-0621-y