Omics · study · 2026
Inducible XIST-mediated trisomy 21 correction uncovers a USP16-p16 senescence axis driving epileptogenesis in Down syndrome [scRNA-Seq]
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.
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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/GSE324nnn/GSE324211 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324211 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1434181 ncbi.nlm.nih.gov/bioproject/PRJNA1434181 ↗
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% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE324211 | 10 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[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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 |