Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PLCG2 modulates TREM2 expression and signaling in response to Alzheimer’s disease pathology 

ABSTRACT: PLCG2 modulates TREM2 expression and signaling in response to Alzheimer’s disease pathology 

PROVIDER: PRJNA1234569 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR32653937_1.fastq.gz	Fastqsanger.gz
	SRR32653937_2.fastq.gz	Fastqsanger.gz
	SRR32653938_1.fastq.gz	Fastqsanger.gz
	SRR32653938_2.fastq.gz	Fastqsanger.gz
	SRR32653939_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 48

Similar Datasets

PLCG2 modulates TREM2 expression and signaling in response to Alzheimer’s disease pathology 

Project description:Phospholipase C gamma 2 (PLCG2) is an intracellular effector of microglial cell surface receptors, including TREM2. Variants which alter PLCG2 activity impact Alzheimer’s disease (AD) risk, but the effects of PLCG2 deficiency in AD remain unclear.

2025-05-14 | GSE291648 | GEO

PLCG2 Regulates Divergent Microglial Functions via TREM2-Dependent and -Independent Signaling

Project description:PLCG2 Regulates Divergent Microglial Functions via TREM2-Dependent and -Independent Signaling

| PRJNA602826 | ENA

PLCG2 Regulates Divergent Microglial Functions via TREM2-Dependent and -Independent Signaling

Project description:We use genetically engineered human iPSC-derived microglia-like cells (iMG) to show that TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, and lipid metabolism following myelin challenge. Loss of TREM2 or PLCγ2 signaling leads to a shared signature of transcriptional dysregulation that underlies these phenotypes. However, PLCγ2 also signals downstream of Toll-like receptors to mediate inflammatory responses in a TREM2-independent manner. Therefore, PLCγ2 activity regulates divergent microglial functions via distinct TREM2-dependent and -independent signaling and may be involved in the transition to a microglial state associated with neurodegenerative disease.

2020-05-24 | GSE144120 | GEO

The impact of reduced PLCG2 expression on microglial biology and disease pathology in a murine model of Alzheimer’s disease

Project description:Differential expression analysis identified inflammation-related pathways in AD samples with reduced PLCG2 expression

2025-01-01 | GSE196502 | GEO

TREM2 is a global regulator of microglia energetic and biosynthetic metabolism during steady state and in Alzheimer’s disease

Project description:The most common form of senile dementia, Alzheimer’s disease (AD), is characterized by Aβ plaques and neurofibrillary tangles in the CNS. AD genetic studies have identified high-risk hypomorphic variants in TREM2, a myeloid cell surface receptor that enables concerted microglial responses to Aβ plaques and neuronal cell death, including proliferation, survival, clustering and phagocytosis. How TREM2 promotes these responses is not known. Here, we demonstrate that TREM2 drives mTOR signaling, which maintains high ATP levels, supports biosynthetic pathways and suppresses AMPK phosphorylation and autophagy. In vitro, TREM2-deficient macrophages undergo dramatically increased autophagy and die in response to growth factor limitation or ER stress. Excessive autophagy is also evident in microglia from Trem2-/- 5XFAD mice and in post-mortem specimens from AD patients carrying TREM2 risk variants. Metabolic derailment, autophagy and cell death can be circumvented by engaging alternative energy production pathways. Thus, restoring microglial energetic and anabolic levels may be a future therapeutic avenue for TREM2-associated neurological disease.

2017-08-15 | GSE98563 | GEO

Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and -independent cellular responses in Alzheimer’s disease [7 months]

Project description:Glia have been implicated in Alzheimer’s disease (AD) pathogenesis. Variants of the microglia receptor TREM2 increase AD risk and activation of “disease-associated microglia” (DAM) is dependent on TREM2 in mouse models of AD. We surveyed gene expression changes associated with AD pathology and TREM2 in 5XFAD mice and human AD by snRNA-seq. We confirmed the presence of Trem2-dependent DAM and identified a novel Serpina3n+C4b+ reactive oligodendrocyte population in mice. Interestingly, remarkably different glial phenotypes were evident in human AD. Microglia signature was reminiscent of IRF8-driven reactive microglia in peripheral nerve injury. Oligodendrocyte signatures suggested impaired axonal myelination and metabolic adaptation to neuronal degeneration. Astrocyte profiles indicated weakened metabolic coordination with neurons. Notably, the reactive phenotype of microglia was less palpable in TREM2 R47H and R62H carriers than in non-carriers, demonstrating a TREM2 requirement in both mouse and human AD, despite the marked species-specific differences.

2019-12-31 | GSE140510 | GEO

Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and -independent cellular responses in Alzheimer’s disease [15 months]

2019-12-31 | GSE140399 | GEO

Enhancing TREM2 expression activates microglia and modestly mitigates Tau pathology and neurodegeneration

Project description:TREM2, a microglia-specific receptor, is strongly associated with Alzheimer’s disease (AD) risk and modulates microglial responses critical to AD pathogenesis. However, its role in tauopathy and neurodegeneration remains unclear. Here, by using a PS19 tauopathy mouse model with inducible overexpression of human wild-type TREM2 (TREM2-WT) or the R47H variant (TREM2-R47H), we show that TREM2-WT overexpression modestly reduces soluble phosphorylated tau (p-tau) levels and mildly preserves neuronal integrity, whereas TREM2-R47H fails to impact p-tau levels or neurodegeneration. Single-cell RNA sequencing revealed that TREM2-WT enhances disease-associated microglia (DAM) signatures, while TREM2-R47H drives the MHCII+ microglial phenotypes. These findings demonstrate that TREM2-WT confers modest benefits in tauopathy models, whereas TREM2-R47H exhibits reduced functionality. Our study underscores the therapeutic potential of enhancing TREM2 activity to modulate microglial responses and mitigate neurodegeneration in AD.

2025-04-02 | GSE285713 | GEO

TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease

Project description:CD33-/- and/or TREM2-/- mice were crossed with the 5xFAD mouse model of Alzheimer’s disease to generate single and double CD33/TREM2 knock-out mice on 5xFAD background. Transcriptome and gene expression analyses were performed to analyze the impact of CD33 and/or TREM2 knock-out on the transcriptome of microglia in the context of amyloid pathology. The results revealed that CD33 and/or TREM2 knock-out reprogrammed microglial gene expression signatures in 5xFAD mice in an age-dependent manner. Differential gene expression in 5xFAD;CD33-/- microglia depended on the presence of TREM2. These data suggest that TREM2 acts downstream of CD33.

2019-06-11 | GSE132508 | GEO

TREM2-activating antibodies abrogate the negative pleiotropic effects of the Alzheimer’s disease variant TREM2R47H on murine myeloid cell function

Project description:Triggering receptor expressed on myeloid cells 2 (TREM2) is an orphan immune receptor expressed on cells of myeloid lineage such as macrophages and microglia. The rare–variant R47H TREM2 is associated with an increased risk for Alzheimer’s disease (AD), supporting the hypothesis that TREM2 loss of function may exacerbate disease progression. However, a complete knockout of the TREM2 gene in different genetic models of neurodegenerative diseases has been reported to result in both protective and deleterious effects on disease-related endpoints and myeloid cell function. Here, we describe a TREM2R47H transgenic mouse model and report that even in the absence of additional genetic perturbations, this variant clearly confers a loss of function on myeloid cells. The TREM2R47H variant–containing myeloid cells exhibited subtle defects in survival and migration and displayed an unexpected dysregulation of cytokine responses in a lipopolysaccharide challenge environment. These subtle phenotypic defects with a gradation in severity across genotypes were confirmed in whole-genome RNA-Seq analyses of WT, TREM2−/− and TREM2R47H myeloid cells under challenge conditions. Of note, TREM2-activating antibodies that boost proximal signaling abrogated survival defects conferred by the variant and also modulated migration and cytokine responses in an antibody-, ligand-, and challenge-dependent manner. In some instances, these antibodies also boosted wildtype myeloid cell function. Our studies provide a first glimpse into the boost in myeloid cell function that can be achieved by pharmacological modulation of TREM2 activity that can potentially be ameliorative in neurodegenerative diseases such as AD.

2018-12-20 | GSE124097 | 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