GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296300/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296300GEOGSEfalseTransient Senescence Following Myocardial Infarction: Characterization and Functional Implications in Cardiac Remodeling [snMultiome]Recent studies suggest that transient premature senescence is essential for tissue remodeling. 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. 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.2026/09/01GSE296300GSM8968320GSM8968317GSM8968316GSM8968319GSM8968318GSM8968313GSM8968315GSM896831424247296300Mus musculus