Project description:To investigate the role of Matrin 3 (MATR3) in the innate immune response we analyzed and compared MATR3 KO Clones versus wildtype HAP1 cells.

2024-05-15 | GSE216825 | GEO

MATRIN3 deficiency leads to cGAS-STING activation

Project description:To determine the direct targets of MATR3 in human HAP1 cells, we performed PAR-CLIP.

2024-05-15 | GSE262647 | GEO

MATRIN3 deficiency leads to cGAS-STING activation

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-05-15 | GSE216830 | GEO

MATRIN3 deficiency leads to cGAS-STING activation (NanoString)

Project description:To investigate the role of Matrin 3 (MATR3) in innate immune response, we analyzed and compared MATR3 KO clones versus wildtype HAP1 cells.

2024-05-15 | GSE216829 | GEO

cGAS/STING drives ageing-related inflammation and neurodegeneration III

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

cGAS/STING drives ageing-related inflammation and neurodegeneration II

2023-08-20 | GSE234419 | GEO