Senescence rewires microenvironment sensing to facilitate anti-tumor immunity (scRNA-Seq)
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ABSTRACT:
PROVIDER: PRJNA928712 | ENA |
REPOSITORIES: ENA
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Project description:Senescence rewires microenvironment sensing to facilitate anti-tumor immunity
| PRJNA928706 | ENA
Project description:Senescence rewires microenvironment sensing to facilitate anti-tumor immunity (bulk RNA-Seq)
| PRJNA838824 | ENA
Project description:Cellular senescence involves a stable cell cycle arrest coupled to a secretory program that, in some instances, stimulates the immune clearance of senescent cells. Using an immune competent tumor model in which senescence triggers CD8 T cell-mediated tumor rejection, we show that senescence also remodels cell surface proteome to alter how they sense environmental factors, as exemplified by Type II interferon gamma (IFN-γ). Compared to proliferating cells, senescent cells upregulate IFN-γ receptor, become hypersensitized to microenvironmental IFN-γ, and more robustly induce antigen presenting machinery -effects also recapitulated in human tumor cells treated with senescence-inducing drugs. Disruption of the IFN-γ sensing by senescent cells blunts their immune-mediated clearance without disabling their characteristic secretory program or immune cell recruitment. Our results demonstrate that senescent cells have an enhanced ability to both send and receive environmental signals, and imply that each process is required for their effective immune surveillance.
2023-01-28 | GSE223874 | GEO
Project description:Cellular senescence involves a stable cell cycle arrest coupled to a secretory program that, in some instances, stimulates the immune clearance of senescent cells. Using an immune competent tumor model in which senescence triggers CD8 T cell-mediated tumor rejection, we show that senescence also remodels cell surface proteome to alter how they sense environmental factors, as exemplified by Type II interferon gamma (IFN-γ). Compared to proliferating cells, senescent cells upregulate IFN-γ receptor, become hypersensitized to microenvironmental IFN-γ, and more robustly induce antigen presenting machinery -effects also recapitulated in human tumor cells treated with senescence-inducing drugs. Disruption of the IFN-γ sensing by senescent cells blunts their immune-mediated clearance without disabling their characteristic secretory program or immune cell recruitment. Our results demonstrate that senescent cells have an enhanced ability to both send and receive environmental signals, and imply that each process is required for their effective immune surveillance.
2023-01-17 | GSE203140 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-01-27 | GSE223875 | GEO
Project description:Cellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments (CCFs) in senescent cells. The activation of cGAS, in turn triggers the production of SASP factors via Stimulator of interferon genes (STING), thereby promoting paracrine senescence. We demonstrate that diverse stimuli of cellular senescence engage the cGAS-STING pathway in vitro and we show cGAS-dependent regulation of senescence upon irradiation and oncogene activation in vivo. Our findings provide insights into the mechanisms underlying cellular senescence by establishing the cGAS-STING pathway as a crucial regulator of senescence and the SASP.
2017-06-20 | GSE100102 | GEO
Project 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.
2024-06-26 | GSE247585 | GEO
Project 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.
2024-06-26 | GSE247546 | GEO
Project 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.
2024-06-26 | GSE248603 | GEO
Project description:Senescent endothelial cells accumulate in blood vessels during aging and produce the senescence-associated secretory phenotype (SASP). Age-related cardiovascular disease is promoted by SASP chronic inflammation. SASP establishment has been attributed to DNA damage and cGAS activation through cytoplasmic chromatin fragments. Therefore, DNA sensing has been extensively studied in cellular senescence; RNA sensing, on the other hand, remains unexplored. Here, we uncover a pivotal role for RNA accumulation and sensing in endothelial senescence. Our study suggests that intracellular RNA accumulation is a hallmark of senescent endothelial cells. This is associated with activation of RIG-I RNA sensing, and IRF7-driven IFN innate immune response. Moreover, our results revealed that inhibition of IRF7 or RIG-I were sufficient to extend the lifespan and functionality of endothelial cells. These data link the IFN gene signature with RNA accumulation/sensing in senescent endothelium and suggest IRF7 and RIG-I as potential therapeutic targets to delay vascular aging.
2023-10-23 | GSE160166 | GEO