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| Status |
Public on Mar 10, 2021 |
| Title |
Sex and cell-specific gene expression in corticolimbic brain regions associated with psychiatric disorders revealed by bulk and single-nuclei RNA sequencing |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background
There are sex-specific differences in the prevalence, symptomology and course of psychiatric
disorders. However, preclinical models have primarily used males, such that the molecular
mechanisms underlying sex-specific differences in psychiatric disorders are not well established.
Methods
In this study, we compared transcriptome-wide gene expression profiles in male and female rats
within the corticolimbic system, including the cingulate cortex, nucleus accumbens medial shell
(NAcS), ventral dentate gyrus and the basolateral amygdala (n=22-24 per group/region).
Findings
We found over 3,000 differentially expressed genes (DEGs) in the NAcS between males and
females. Of these DEGs in the NAcS, 303 showed sex-dependent conservation DEGs in humans and
were significantly enriched for gene ontology terms related to blood vessel morphogenesis and
regulation of cell migration. Single nuclei RNA sequencing in the NAcS of male and female rats
identified widespread sex-dependent expression, with genes upregulated in females showing a
notable enrichment for synaptic function. Female upregulated genes in Astrocytes, Drd3+MSNs
and Oligodendrocyte were also enriched in several psychiatric genome-wide association studies
(GWAS). Interpretation
Our data provide comprehensive evidence of sex- and cell-specific molecular profiles in the NAcS.
Importantly these differences associate with anxiety, bipolar disorder, schizophrenia, and cross-
disorder, suggesting an intrinsic molecular basis for sex-based differences in psychiatric disorders
that strongly implicates the NAcS.
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| Overall design |
Single nucleus RNA sequencing of the Nucleus Accumbens shell in male and female rats.
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| Contributor(s) |
O’Toole N, Fitzgerald E, Zhang T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Mar 09, 2021 |
| Last update date |
May 11, 2023 |
| Contact name |
Nicholas O'Toole |
| E-mail(s) |
otoolen@gmail.com
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| Organization name |
Douglas Mental Health University Institute
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| Street address |
6875 Boulevard Lasalle
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| City |
Verdun |
| State/province |
QC |
| ZIP/Postal code |
H4H 1R3 |
| Country |
Canada |
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| Platforms (1) |
| GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA708353 |
| SRA |
SRP310020 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE168599_RAW.tar |
311.7 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
| GSE168599_new_metadata.xlsx |
70.6 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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