| Experiment Id | GSE247546 | Name | RIG-I sensing of self-RNA in aged endothelial cells links cellular senescence with an interferon gene signature I |
| Experiment Type | RNA-Seq | Study Type | Baseline |
| Source | GEO | Curation Date | 2024-07-08 |
| description | Senescent endothelial cells accumulate in blood vessels during aging and contribute to age-related cardiovascular disease. Identification of senescent cells is challenging as molecular changes are cell-type specific. Here, we established, benchmarked, and validated a new gene signature EndoSEN that pinpoints senescent endothelial cells. The EndoSEN signature was enriched for interferon stimulated genes (ISG) and correlated with the senescence-associated secretory phenotype (SASP) signature. SASP establishment is classically attributed to DNA damage and cGAS activation, but our results revealed a pivotal role for RNA accumulation and sensing. Mechanistically, we showed that endothelial senescence hallmarks include self-RNA accumulation, RNA sensor RIG-I upregulation, and an ISG signature. Moreover, a virtual model of RIG-I knockout in endothelial cells underscored senescence as an impacted pathway. We tested and confirmed that RIG-I knockdown was sufficient to extend the lifespan and decrease the SASP in endothelial cells. Our evidence suggests that targeting RNA sensing is a potential strategy to delay vascular aging. Cell suspensions for scRNA-seq were obtained from mouse retinas at 3 ages: 3, 12, and 23 months. Enrichment for CD31+ cells was performed using the AutoMACS. |
