Omics · study · 2026
Inducible XIST-mediated trisomy 21 correction uncovers a USP16-p16 senescence axis driving epileptogenesis in Down syndrome
Listed in NCBI GEO
Down syndrome (DS), caused by human chromosome 21 (HSA21) trisomy, carries elevated epilepsy risk with unknown mechanisms.
Description
We integrated clinical epidemiology, fetal brain single-nucleus RNA sequencing, patient-derived induced pluripotent stem cell (iPSC) models, cerebral organoids, and in vivo chimeric mice to dissect this link. Clinical analysis of 1,365 DS individuals exhibited an age-stratified epilepsy prevalence pattern, with higher rates in older children.
Fetal brain transcriptomes revealed neurogenesis defects, aging-related signatures, synaptic/metabolic dysregulation. We engineered an inducible XIST-mediated extra HSA21 silencing system in female DS iPSCs, showing HSA21 dosage correction reduced neural progenitor cell (NPC) senescence markers and neuronal hyperexcitability. Transcriptomic screening pinpointed USP16 as a key pro-aging candidate.
Read the rest (1 more)
Moreover, USP16 suppression and the senolytic combination dasatinib/quercetin reduced senescence-linked and hyperexcitability-associated readouts, supporting a USP16-p16-NPC aging axis as a therapeutic target for DS-associated epilepsy, with broader implications for aging-linked neurological disorders.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE322nnn/GSE322851 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322851 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1431945 ncbi.nlm.nih.gov/bioproject/PRJNA1431945 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE322851 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | 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 |