Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Upregulated c-JUN induces aberrant transposable element mobilization, cGAS-STING activation and cell death in Alzheimer's disease

ABSTRACT: Upregulated c-JUN induces aberrant transposable element mobilization, cGAS-STING activation and cell death in Alzheimer's disease

PROVIDER: PRJNA881750 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR21619400_1.fastq.gz	Fastqsanger.gz
	SRR21619400_2.fastq.gz	Fastqsanger.gz
	SRR21619401_1.fastq.gz	Fastqsanger.gz
	SRR21619401_2.fastq.gz	Fastqsanger.gz
	SRR21619402_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 123

Similar Datasets

Upregulated c-JUN induces aberrant transposable element mobilization, cGAS-STING activation and cell death in Alzheimer's disease

Project description:In this study we leveraged several lines of AD patient derived induced Pluripotent Stem Cells (iPSCs) and differentiated them into hippocampal neuronal progenitors, hippocampal CA3 neurons and cerebral organoids. Our goals were to i) investigate the transcriptional networks altered in the AD lines at the different developmental stages (progenitors, neurons, organoids), ii) link the altered gene regulatory networks to aberrant AP-1 activity, and iii) to profile TEs aberrantly active in the AD lines, with the goal of identifying a mechanism for TE derepression and to unveil the consequences that this process has on neuronal physiology. With these experiments, we demonstrate that many of the genes differentially expressed between the AD lines the healthy controls are c-JUN targets. Further, we find that most of the aberrantly de-repressed TEs harbor the AP-1 binding motif, and that aberrant TE mobilization leads to cytoplasmic accumulation of RNA-DNA hybrids, observed both in the progenitors and in the organoids. Importantly this phenomenon elicits cGAS-STING activation and ultimately cell-death. Notably, by using a c-JUN peptide that inhibits c-JUN phosphorylation, we demonstrate that c-JUN inhibition in the AD lines is sufficient to rescue the expression of many differentially expressed genes, and to significantly reduce aberrant TE mobilization, cytoplasmic RNA-DNA accumulation, cGAS-STING activation and cell death.

2023-09-07 | GSE213610 | GEO

JUN upregulation drives aberrant transposable element mobilization, associated innate immune response, and impaired neurogenesis in Alzheimer's disease.

Project description:Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death in AD progenitors and neurons. Notably, inhibiting c-Jun effectively blocks all these downstream molecular processes and rescues neuronal death and the impaired neurogenesis phenotype in AD progenitors. Our findings open new avenues for identifying therapeutic strategies and biomarkers to counteract disease progression and diagnose AD in the early, pre-symptomatic stages.

| S-EPMC10696058 | biostudies-literature

Transcriptome analysis of JUN overexpressed or JUN inactivated fibroblasts

Project description:To examine the effects of phosphorylated JUN-mediated enhancers activation on gene expression, we conducted RNA-seq analysis in JUN wildtype (WT) or JUN inactive mutant (JUN AA) overexpressed MRC5 cells. The expression levels of genes associated with JUN-activated enhancers are significantly upregulated in JUN WT cells rather than in JUN AA cells. To quantify the effects of JUN inactivation on gene expression, we also performed RNA-seq analysis in JNKi-treated induced CAFs (iCAFs). We observed that JNKi significantly reduced expression levels of JUN-activated enhancers-associated genes.

2022-12-09 | GSE196351 | GEO

Gene induction in STAT1-/- fibroblasts transduced with lentiviruses expressing human cGAS

Project description:The hypothesis tested was that lentiviral driven cGAS expression activates antiviral gene expression. Cells were transduced with lentiviruses expressing cGAS or a control (firefly luciferase). Total RNA was harvested 48 h post-transduction and processed for Illumina BeadArray.

2013-12-01 | E-GEOD-52241 | biostudies-arrayexpress

Genome-wide maps of H3K27ac, H3K4me1, JUN and p-JUN in JUN overexpressed or JUN inactivated fibroblasts

Project description:To further dissect whether and how activated JUN reconfigures the chromatin landscape, we performed Chromatin Immunoprecipitation (ChIP)-seq analyses for H3K4me1 and H3K27ac. Based on the significant increase of H3K27ac levels at H3K4me1+ sites, we identified 3,017 JUN-activated enhancers in JUN WT cells. In contrast, JUN AA fails to significantly induce H3K27ac accumulation at these regions. Their enrichment levels at JUN-activated enhancers were significantly decreased after JNKi treatment. Besides, these enhancers are directly driven by JUN, especially phosphorylated JUN.

2022-12-09 | GSE196345 | GEO

Genome-wide maps of H3K27ac, H3K4me1, JUN and p-JUN in JUN overexpressed or JUN inactivated fibroblasts

Project description:Genome-wide maps of H3K27ac, H3K4me1, JUN and p-JUN in JUN overexpressed or JUN inactivated fibroblasts

| PRJNA804495 | ENA

Microglial cGAS Deletion Preserves Intercellular Communication and Alleviates Amyloid-β-Induced Pathogenesis of Alzheimer's Disease

Project description:This study investigates the impact of microglial cGAS deficiency on gene expression in the 5xFAD mouse cerebrum tissues, using the NanoString Neuroinflammation panel. The relevent publication is PMID: 39908354

2025-05-11 | GSE296510 | GEO

Microglial cGAS Deletion Preserves Intercellular Communication and Alleviates Amyloid-β-Induced Pathogenesis of Alzheimer's Disease

Project description:This study investigates the impact of microglial cGAS deficiency on gene expression in the 5xFAD mouse cerebrum tissues, using the single cell sequencing method. The relevant publication is PMID: 39908354

2025-06-07 | GSE296662 | GEO

cGAS maintains basal antiviral state

Project description:Upon recognition of aberrantly located DNA, the innate immune sensor cGAS activates STING/IRF-3-driven antiviral responses. Here we characterized the ability of a specific variant of the cGAS-encoding gene MB21D1, rs610913, to alter cGAS-mediated DNA sensing and viral infection. rs610913 is a frequent G>T polymorphism resulting in a P261H exchange in the cGAS protein. Data from the International Collaboration for the Genomics of HIV suggested that rs610913 nominally associates with HIV-1 acquisition in vivo. Molecular modeling of cGAS(P261H) hinted towards the possibility for an additional binding site for a potential cellular co-factor in cGAS dimers. However, cGAS(WT) or cGAS(P261H)-reconstituted THP-1 cGAS KO cells shared steady-state expression of interferon-stimulated genes (ISGs), as opposed to cells expressing the enzymatically inactive cGAS(G212A/S213A). Accordingly, cGAS(WT) and cGAS(P261H) cells were less susceptible to lentiviral transduction and infection with HIV-1, HSV-1, and Chikungunya virus as compared to cGAS KO- or cGAS(G212A/S213A) cells. Upon DNA challenge, innate immune activation appeared to be mildly reduced upon expression of cGAS(P261H) compared to cGAS(WT). Finally, DNA challenge of PBMCs from donors homozygously expressing rs610913 provoked a trend towards a slightly reduced type I IFN response as compared to PBMCs from GG donors. Taken together, the steady-state activity of cGAS maintains a base-line antiviral state rendering cells more refractory to ISG-sensitive viral infections. rs610913 failed to grossly differ phenotypically from the wild-type gene, suggesting that cGAS(P261H) and wild-type cGAS share a similar ability to sense viral infections in vivo.

2022-05-25 | GSE203334 | GEO

Gene expression profiling of Jun -/- and Jun +/+ facial motor neurons

Project description:To determine target genes, biological functions of Jun and mechanisms of gene regulation by Jun in regenerating neurons, gene expression profiling was carried out of axotomized and uninjured facial motor neurons in floxed c-Jun mice crossed with nestin-cre mice. Nestin-promoter-driven Cre ensures deletion of Jun in the central nervous system including facial motor neurons. KO animals were Jun Flox/Fox Cre+, while WT animals were Jun Flox/Flox, Cre-.

2021-11-17 | GSE162977 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data