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

TitleSingle-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons.
Publication TypeJournal Article
Year of Publication2020
AuthorsNagy C, Maitra M, Tanti A, Suderman M, Théroux J-F, Davoli MAntonietta, Perlman K, Yerko V, Wang YChang, Tripathy SJ, Pavlidis P, Mechawar N, Ragoussis J, Turecki G
JournalNat Neurosci
Volume23
Issue6
Pagination771-781
Date Published2020 06
ISSN1546-1726
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Depressive Disorder, Major, Gene Regulatory Networks, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Neurons, Oligodendrocyte Precursor Cells, Prefrontal Cortex, Transcriptome, Young Adult
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.

DOI10.1038/s41593-020-0621-y
Alternate JournalNat Neurosci
PubMed ID32341540
Grant ListFDN148374 / / CIHR / Canada
EGM141899 / / CIHR / Canada