Omics · study · 2026
Relative contribution of gonads and sex chromosomes to sex differences in cell-type gene expression in the mouse medial septum and sex-biased disease risk
Listed in NCBI GEO
While sex differences in the brain have traditionally been attributed to gonadal hormones, emerging evidence points to regulation by sex chromosomes.
Description
This study aims to differentiate the influence of gonads versus sex chromosomes on cellular gene expression in the mouse medial septum (MS), a critically understudied brain region. Using single nucleus RNA-sequencing and the Sex Chromosome Trisomy mouse model, we (1) quantified sex differences in cellular gene expression and (2) isolated sex-biasing effects by identifying perturbed cell types, differentially expressed genes, biological pathways, and gene networks, which were integrated with GWAS data to explore links with sex-biased human phenotypes.
Our analysis revealed that volumetric sex differences in the MS are mirrored by widespread transcriptomic changes across cell types. Critically, genetic effects displayed elevated relevance compared to sex hormones in driving sex-biased gene expression. These effects converge to regulate synaptic/neuronal development, transcriptional regulation, and cellular metabolism.
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Sex chromosome-associated DEGs were enriched for various human disorders, suggesting a cellular and mechanistic basis for their sex-biased patterns. Our findings challenge the classical gonad-centric views of sexual differentiation, as the MS displays sex-biased transcriptional regulation driven by sex chromosome-associated effects that are highly relevant for human health.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311883 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311883 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1371889 ncbi.nlm.nih.gov/bioproject/PRJNA1371889 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE311883 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].anzsrc:group:3105 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (72%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |