Omics · study · 2026
Sex-Dependent Effects of Neonatal Hyperoxia on Prefrontal Cortex Development
Listed in NCBI GEO
Premature infants often require oxygen therapy, which increases the risk of bronchopulmonary dysplasia and long-term cognitive impairment.
Description
The prefrontal cortex (PFC), essential for higher-order cognition, may be particularly vulnerable to neonatal hyperoxia, yet the cellular and molecular effects remain unclear. We exposed C57Bl/6 mouse pups to hyperoxia (85% O₂) or normoxia from postnatal days 1–14 and performed single nucleus RNA and ATAC sequencing of the PFC, complemented by oligodendrocyte progenitor cell assays and validation in mouse and human brain tissues.
Hyperoxia reduced L4/5 intratelencephalic projecting glutamatergic neurons in females and mature oligodendrocytes in males, accompanied by consistent repression of myelination genes proteolipid protein 1 (Plp1) and myelin basic protein (Mbp) and altered chromatin accessibility. Oligodendrocyte transcription factor 2 (Olig2) was induced in both sexes, whereas lysine demethylase 3A (Kdm3a) activation was female specific.
Read the rest (2 more)
Hyperoxia activated Netrin-1 signaling in males and disrupted tumor protein p53 (TP53)-regulated metabolic pathways in females. Oligodendrocyte progenitor cell proliferation and differentiation were inhibited in vitro, and human bronchopulmonary dysplasia PFC samples recapitulated these core alterations. Together, these findings demonstrate that neonatal hyperoxia disrupts PFC development through sex-dependent effects on neuronal differentiation, oligodendrocyte maturation, and transcriptional regulation.
Concordant mouse-human myelination deficits highlight the pathological relevance of oxygen exposure and underscore the importance of considering sex as a biological variable in preterm brain injury.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE331nnn/GSE331357 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE331357 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1467750 ncbi.nlm.nih.gov/bioproject/PRJNA1467750 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Genome binding/occupancy profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE331357 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |