Exosomes packaged chromatin with dynamic H3R26me2s modification prevents cellular inflammation by blocking the cGAS-STING pathway.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1000450 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25472808_1.fastq.gz | Fastqsanger.gz | |||
| SRR25472808_2.fastq.gz | Fastqsanger.gz | |||
| SRR25472809_1.fastq.gz | Fastqsanger.gz | |||
| SRR25472809_2.fastq.gz | Fastqsanger.gz | |||
| SRR25470046_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 28 |
Similar Datasets
Project description:Exosomes DNA derived from genomic and mitochondrial could modulate type I IFN expression by triggering the cGAS-STING pathway. However, the chromatin modification of secreted exosomes involved in this process is largely unknown. Here, we could detect the histone H3R26me and H3K27ac in the components of secreted exosomes, meanwhile, a global decrease of H3R26 symmetric dimethylation (H3R26me2s) accompanied by the lowering enrichment of H3K27ac, and this distribution pattern was able to be verified by decreased H3R26me2s leading to the reduction of H3K27ac. Furthermore, these fragmented chromatins trans-located into cytoplasmic could repress cGAS-STING induction of IFNβ1 expression, which is further packaged into the exosomes. Collectively, our findings elucidate a novel pathway that which cells can actively transport the chromatin fragments of altered histone arginine methylation to alleviate the stimulation by damaged DNA. We perform RNA-seq to analysis the changes of gene expression in cells treated with bleomycin.
2024-07-31 | GSE239629 | GEO
Project description:Exosomes DNA derived from genomic and mitochondrial could modulate type I IFN expression by triggering the cGAS-STING pathway. However, the chromatin modification of secreted exosomes involved in this process is largely unknown. Here, we could detect the histone H3R26me and H3K27ac in the components of secreted exosomes, meanwhile, a global decrease of H3R26 symmetric dimethylation (H3R26me2s) accompanied by the lowering enrichment of H3K27ac, and this distribution pattern was able to be verified by decreased H3R26me2s leading to the reduction of H3K27ac. Furthermore, these fragmented chromatins trans-located into cytoplasmic could repress cGAS-STING induction of IFNβ1 expression, which is further packaged into the exosomes. Collectively, our findings elucidate a novel pathway that which cells can actively transport the chromatin fragments of altered histone arginine methylation to alleviate the stimulation by damaged DNA. We perform ChIP-seq to analysis the changes of histone modification in cells treated with bleomycin.
2024-07-31 | GSE239628 | GEO
Project description:Exosomes packaged chromatin with dynamic H3R26me2s modification prevents cellular inflammation by blocking the cGAS-STING pathway [RNA-seq]
| PRJNA1000453 | ENA
Project description:Exosomes packaged chromatin with dynamic H3R26me2s modification prevents cellular inflammation by blocking the cGAS-STING pathway [CUT&Tag-seq]
| PRJNA1000452 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-07-31 | GSE239630 | GEO
Project description:Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease. Multiple factors can contribute to ageing-associated inflammation, however the molecular pathways transducing aberrant inflammatory signalling and their impact in natural ageing remain poorly understood. Here we show that the cGAS-STING signalling pathway, mediating immune sensing of DNA, is a critical driver of chronic inflammation and functional decline during ageing. Blockade of STING suppresses the inflammatory phenotypes of senescent human cells and tissues, attenuates ageing-related inflammation in multiple peripheral organs and the brain in mice, and leads to an improvement in tissue function. Focusing on the ageing brain, we reveal that activation of STING triggers reactive microglia transcriptional states, neurodegeneration and cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity in old microglia defining a mechanism by which cGAS-STING signalling is engaged in the ageing brain. Single-nuclei RNA-sequencing (snRNA-seq) of microglia and hippocampi of a newly developed cGAS gain-of-function mouse model demonstrates that engagement of cGAS in microglia is sufficient to direct ageing-associated transcriptional microglia states leading to bystander cell inflammation, neurotoxicity and impaired memory capacity. Our findings establish the cGAS-STING pathway as a critical driver of ageing-related inflammation in peripheral organs and the brain, and reveal blockade of cGAS-STING signalling as a potential strategy to halt (neuro)degenerative processes during old age.
2023-08-20 | GSE234421 | GEO
Project description:Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease. Multiple factors can contribute to ageing-associated inflammation, however the molecular pathways transducing aberrant inflammatory signalling and their impact in natural ageing remain poorly understood. Here we show that the cGAS-STING signalling pathway, mediating immune sensing of DNA, is a critical driver of chronic inflammation and functional decline during ageing. Blockade of STING suppresses the inflammatory phenotypes of senescent human cells and tissues, attenuates ageing-related inflammation in multiple peripheral organs and the brain in mice, and leads to an improvement in tissue function. Focusing on the ageing brain, we reveal that activation of STING triggers reactive microglia transcriptional states, neurodegeneration and cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity in old microglia defining a mechanism by which cGAS-STING signalling is engaged in the ageing brain. Single-nuclei RNA-sequencing (snRNA-seq) of microglia and hippocampi of a newly developed cGAS gain-of-function mouse model demonstrates that engagement of cGAS in microglia is sufficient to direct ageing-associated transcriptional microglia states leading to bystander cell inflammation, neurotoxicity and impaired memory capacity. Our findings establish the cGAS-STING pathway as a critical driver of ageing-related inflammation in peripheral organs and the brain, and reveal blockade of cGAS-STING signalling as a potential strategy to halt (neuro)degenerative processes during old age.
2023-08-20 | GSE234420 | GEO
Project description:Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease. Multiple factors can contribute to ageing-associated inflammation, however the molecular pathways transducing aberrant inflammatory signalling and their impact in natural ageing remain poorly understood. Here we show that the cGAS-STING signalling pathway, mediating immune sensing of DNA, is a critical driver of chronic inflammation and functional decline during ageing. Blockade of STING suppresses the inflammatory phenotypes of senescent human cells and tissues, attenuates ageing-related inflammation in multiple peripheral organs and the brain in mice, and leads to an improvement in tissue function. Focusing on the ageing brain, we reveal that activation of STING triggers reactive microglia transcriptional states, neurodegeneration and cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity in old microglia defining a mechanism by which cGAS-STING signalling is engaged in the ageing brain. Single-nuclei RNA-sequencing (snRNA-seq) of microglia and hippocampi of a newly developed cGAS gain-of-function mouse model demonstrates that engagement of cGAS in microglia is sufficient to direct ageing-associated transcriptional microglia states leading to bystander cell inflammation, neurotoxicity and impaired memory capacity. Our findings establish the cGAS-STING pathway as a critical driver of ageing-related inflammation in peripheral organs and the brain, and reveal blockade of cGAS-STING signalling as a potential strategy to halt (neuro)degenerative processes during old age.
2023-08-20 | GSE234419 | GEO
Project description:Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease. Multiple factors can contribute to ageing-associated inflammation, however the molecular pathways transducing aberrant inflammatory signalling and their impact in natural ageing remain poorly understood. Here we show that the cGAS-STING signalling pathway, mediating immune sensing of DNA, is a critical driver of chronic inflammation and functional decline during ageing. Blockade of STING suppresses the inflammatory phenotypes of senescent human cells and tissues, attenuates ageing-related inflammation in multiple peripheral organs and the brain in mice, and leads to an improvement in tissue function. Focusing on the ageing brain, we reveal that activation of STING triggers reactive microglia transcriptional states, neurodegeneration and cognitive decline. Cytosolic DNA released from perturbed mitochondria elicits cGAS activity in old microglia defining a mechanism by which cGAS-STING signalling is engaged in the ageing brain. Single-nuclei RNA-sequencing (snRNA-seq) of microglia and hippocampi of a newly developed cGAS gain-of-function mouse model demonstrates that engagement of cGAS in microglia is sufficient to direct ageing-associated transcriptional microglia states leading to bystander cell inflammation, neurotoxicity and impaired memory capacity. Our findings establish the cGAS-STING pathway as a critical driver of ageing-related inflammation in peripheral organs and the brain, and reveal blockade of cGAS-STING signalling as a potential strategy to halt (neuro)degenerative processes during old age.
2023-08-20 | GSE234417 | GEO
Project description:Type I interferon (IFN) signalling is tightly controlled. Upon recognition of DNA by cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) translocates along the endoplasmic reticulum (ER)-Golgi axis to induce IFN signalling. Afterwards, signal termination is achieved through autophagic degradation of STING, or STING recycling by retrograde COPI-mediated transport. Here we identify the GTPase ARF1 as a negative regulator of cGAS-STING signaling. Heterozygous ARF1 missense mutations cause a novel type I interferonopathy associated with enhanced IFN stimulated gene production. Expression of patient-derived, GTPase-defective, ARF1 in cell lines and primary cells results in increased cGAS-STING dependent type I IFN signalling. Mechanistically, mutated ARF1 both induces activation of cGAS by aberrant mitochondrial DNA, and promotes accumulation of active STING at the Golgi/ERGIC due to defective COPI retrograde transport. Our data establish ARF1 as a key factor in cGAS-STING homeostasis, which is required to maintain mitochondrial integrity and promote STING recycling.
2022-06-23 | MSV000089711 | MassIVE