Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TREM2 Drives Microglia Response to Amyloid-β via SYK-dependent and -independent Paths [DAP12KI scRNA-seq]

ABSTRACT: TREM2 Drives Microglia Response to Amyloid-β via SYK-dependent and -independent Paths [DAP12KI scRNA-seq]

PROVIDER: PRJNA864840 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR20738280_1.fastq.gz	Fastqsanger.gz
	SRR20738280_2.fastq.gz	Fastqsanger.gz
	SRR20738281_1.fastq.gz	Fastqsanger.gz
	SRR20738281_2.fastq.gz	Fastqsanger.gz
	SRR20738282_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 14

Similar Datasets

TREM2 Drives Microglia Response to Amyloid-β via SYK-dependent and -independent Paths [SYK and TREM2 scRNA-seq]

Project description:TREM2 Drives Microglia Response to Amyloid-β via SYK-dependent and -independent Paths [SYK and TREM2 scRNA-seq]

| PRJNA801111 | ENA

TREM2 Drives Microglia Response to Amyloid-β via SYK-dependent and -independent Paths [SYK and TREM2 scRNA-seq]

Project description:Genetic studies have highlighted microglia as pivotal in orchestrating Alzheimer’s disease (AD). Microglia that adhere to Aβ plaques acquire a transcriptional signature, “diseaseassociated microglia” (DAM), which largely emanates from the TREM2-DAP12 receptor complex that transmits intracellular signals through the protein tyrosine kinase SYK. The human TREM2R47H variant associated with high AD risk fails to activate microglia via SYK. We found that SYK-deficient microglia cannot encase Aβ plaques, accelerating brain pathology and behavioral deficits. SYK deficiency impaired the PI3K-AKT-GSK3β-mTOR pathway, incapacitating anabolic support required for attaining the DAM profile. However, SYK-deficient microglia proliferated and advanced to an Apoe-expressing prodromal stage of DAM; this pathway relied on the adaptor DAP10, which also binds TREM2. Thus, microglial responses to Aβ involve non-redundant SYK- and DAP10-pathways. Systemic administration of an antibody against CLEC7A, a receptor that directly activates SYK, rescued microglia activation in mice expressing the TREM2R47H allele, unveiling new options for AD immunotherapy.

2022-10-10 | GSE195518 | GEO

TREM2 Drives Microglia Response to Amyloid-β via SYK-dependent and -independent Paths

Project description:TREM2 Drives Microglia Response to Amyloid-β via SYK-dependent and -independent Paths

| PRJNA864837 | ENA

TREM2 Drives Microglia Response to Amyloid-β via SYK-dependent and -independent Paths [DAP12KI scRNA-seq]

2022-10-10 | GSE210257 | GEO

TREM2 Drives Microglia Response to Amyloid-β via SYK-dependent and -independent Paths

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

2022-10-10 | GSE210258 | GEO

Expression data from WT and TREM2 deficient microglia in a mouse model of Alzheimer's disease

Project description:We examined the role of TREM2 on microglia responses to amyloid-beta deposition in a mouse model of Alzheimer's disease Microglia were FACS-purified from 8.5 month old WT, Trem2-/-, 5XFAD, and Trem2-/- 5XFAD mice

2015-03-13 | E-GEOD-65067 | biostudies-arrayexpress

TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways.

Project description:Genetic studies have highlighted microglia as pivotal in orchestrating Alzheimer's disease (AD). Microglia that adhere to Aβ plaques acquire a transcriptional signature, "disease-associated microglia" (DAM), which largely emanates from the TREM2-DAP12 receptor complex that transmits intracellular signals through the protein tyrosine kinase SYK. The human TREM2R47H variant associated with high AD risk fails to activate microglia via SYK. We found that SYK-deficient microglia cannot encase Aβ plaques, accelerating brain pathology and behavioral deficits. SYK deficiency impaired the PI3K-AKT-GSK-3β-mTOR pathway, incapacitating anabolic support required for attaining the DAM profile. However, SYK-deficient microglia proliferated and advanced to an Apoe-expressing prodromal stage of DAM; this pathway relied on the adapter DAP10, which also binds TREM2. Thus, microglial responses to Aβ involve non-redundant SYK- and DAP10-pathways. Systemic administration of an antibody against CLEC7A, a receptor that directly activates SYK, rescued microglia activation in mice expressing the TREM2R47H allele, unveiling new options for AD immunotherapy.

| S-EPMC9625082 | biostudies-literature

Cortical single-cell RNA sequencing of the microglia specific TREM2 inducible mouse models in the middle stage of amyloid deposition

Project description:We induced TREM2 expression at 2 months of age in our 5xFAD/TREM2 mouse models and harvested the animals at 5 months of age. The single cells from the cortex were isolated and subjected to the single-cell RNA seq to investigate the effects of TREM2 on microglia transcriptomic profiles in the middle stage of amyloid development. Our data showed that TREM2-WT induced the mTOR/EIF2 signaling pathways and restricted the disease associated microglia (DAM) signature. In contrast TREM2-R47H variant significantly upregulated the MHC class II molecules, enriched the antigen presentation pathway, and exacerbated a signature of antigen presentation contributing to enhanced amyloid pathology.

2020-11-11 | GSE161227 | GEO

Cortical single-cell RNA sequencing of the microglia specific TREM2 inducible mouse models in the early stage of amyloid deposition

Project description:We induced TREM2 expression at birth in our 5xFAD/TREM2 mouse models and harvested the animals at 3.5 months of age. The single cells from the cortex were isolated and subjected to the single-cell RNA seq to investigate the effects of TREM2 on microglia transcriptomic profiles in the early stage of amyloid development. Our data showed that TREM2-WT, to a lesser extent of TREM2-R47H, restricted the disease associated microglia (DAM) signature at this stage.

2020-11-11 | GSE161224 | GEO

Blood-borne macrophages contribute to Alzheimer's disease modification through a TREM2-independent pathway

Project description:Microglia and monocyte-derived macrophages (MDM) are key players in coping with Alzheimer's disease (AD). In amyloidosis mouse models, activation of microglia was found to be TREM2-dependent. Here, using Trem2-/-5xFAD mice, we assessed whether MDM act via a TREM2-dependent pathway. We adopted a treatment protocol targeting the programmed cell death ligand-1 (PD-L1) immune checkpoint, previously shown to modify AD via MDM involvement. Blocking PD-L1 in Trem2-/-5xFAD mice resulted in cognitive improvement and reduced levels of water-soluble amyloid beta (Aβ)1-42 with no effect on amyloid plaque burden. Single-cell RNA sequencing revealed that MDM, derived from both Trem2-/- and Trem2+/+5xFAD mouse brains, express a unique set of genes encoding scavenger receptors (e.g. Mrc1, Msr1). Blocking monocytes trafficking using anti-CCR2 antibody completely abrogated the cognitive improvement induced by anti-PD-L1 in Trem2-/-5xFAD mice, and similarly but to lower extent in Trem2+/+5xFAD mice. These results highlight a TREM2-independent disease-modifying activity of MDM in amyloidosis mouse model.

2021-10-24 | GSE176085 | 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