Archive · study · 2026
Transient Senescence Following Myocardial Infarction: Characterization and Functional Implications in Cardiac Remodeling [SpatialTranscriptome]
Listed in NCBI GEO
Recent studies suggest that transient premature senescence is essential for tissue remodeling.
Description
Myocardial infarction (MI) induces extensive myocardial remodeling through fibroblast-driven extracellular matrix (ECM) production. However, the characteristics and functions of the senescent cells (Sen.) following MI-induced cardiac remodeling remains elusive.
In the present study, we observed a gradual increment number of Sen. within the ischemic region over time following MI, peaking at day 7 post-MI, with a subsequent decline in both wild-type mice and p16Ink4a-CreERT2-mT/mG reporter mice within 4 weeks. Using lineage tracing in the p16 reporter mice, we found most of the transient Sen. transitioned to non-senescent state. Then we analyzed our single-nucleus (sn)-multiome and fluorescence-based (SPiDER-β-gal/p16-EGFP) spatial transcriptomics data from the infarcted heart on day 7 post-MI to identify the cellular composition of transient Sen.
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We also conducted the deconvolution of the Sen. in the integrated dataset using different computational techniques. Additionally, we generated a reference (query dataset) based on SPiDER-βGal/p16-EGFP positivity and mapped it back to the snMultiome dataset. Through all approaches, we found fibroblasts and the subpopulation late myofibroblasts (MF) constituted a major proportion of Sen.
In the snMultiome dataset, we explored the features of senescent late MF through differentially expressed genes/peaks and transcriptional binding motif analysis, and found the senescent late MF exhibited enhanced contractile properties and reduced ECM production capability compared with non-senescent late MF. These findings were supported by in vitro experiments showing that ischemia-induced senescent MF exhibited reduced soluble collagen production compared to TGF-β1-induced non-senescent MF.
Additionally, in vivo studies revealed worsened cardiac function post-MI following senolytics administration compared to the vehicle group.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296301 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296301 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1258877 ncbi.nlm.nih.gov/bioproject/PRJNA1258877 ↗
project · from NCBI GEO
Topics
- Stated by source
- Mus musculus · Other
- From keywords
- Life Sciences
- Inferred from text
- Cardiac remodeling 75% · Heart 75% · Myocardial infarction 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE296301 | 8 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:cardiac-remodeling | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:myocardial-infarction | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:other | 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 |