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Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner

ABSTRACT: Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner

PROVIDER: PRJNA527979 | ENA |

REPOSITORIES: ENA

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Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner

Project description:Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2+ lipid-associated macrophage (LAM) subset and identify markers, spatial localization, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream LAM molecular program during obesity, leading to adipocyte hypertrophy and both tissue-level and systemic hypercholesterolemia and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.

2019-06-27 | GSE128518 | GEO

Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner.

Project description: Not available

| S-EPMC7068689 | biostudies-literature

TREM2 regulates microglial lipid metabolism during aging in mice [RNA-Seq]

Project description:TREM2 is a microglial-specific gene implicated in late-onset Alzheimer's Disease (AD). Recent studies have identified that Trem2-deficient mice exhibit transcriptional changes in microglial gene expression that minimize the upregulation of lipid metabolism and lysosomal genes in AD disease models. We detect similiarly attenuated expression of lipid metabolism genes in microglia isolated from brains of aged Trem2 knockout mice.

2019-12-21 | GSE134031 | GEO

Expression data from wild type (WT) and TREM2 null alveolar macrophages (AM)

Project description:TREM-2 has been described to be a phagocytic receptor. We assessed the influence of TREM-2 on gene expression in alveolar macrophages (AM) In this data-set we characterised the differences in basal gene expression using affymetrix mouse 1.0 ST arrays between WT and TREM2-/- AM and observed TREM2 -/- AM to exhibt higher expression of opsonins 4 samples were analysed in biological duplicate (2 x WT and 2 x TREM2-/-)

2015-01-01 | E-GEOD-51378 | biostudies-arrayexpress

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

Trem2 Promotes Foamy Macrophage Lipid Uptake and Survival in Atherosclerosis

Project description:To investigate the function of Trem2 on foamy macrophage gene regulation, we generated Trem2 deficientBV2 cells using CRISPR and comparedgene expression to Trem2 sufficientcontrols in the presence or absence of cholesterol loading.

2023-05-08 | GSE231659 | GEO

TREM2 regulates microglial cell activation in response to demyelination in vivo

Project description:Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2(-/-)) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2(-/-) microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2(-/-) microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in response to tissue damage. Two STAGE (6weeks 12 weeks),

2015-07-06 | E-GEOD-70475 | biostudies-arrayexpress

TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge [bulk RNA-seq]

Project description:TREM2 is a microglial-specific gene implicated in late-onset Alzheimer's Disease (AD). Recent studies have identified that Trem2-deficient mice exhibit transcriptional changes in microglial gene expression that minimize the upregulation of lipid metabolism and lysosomal genes in AD disease models. We find that chronic phagocytic challenge from demyelination generates similiarly attenuated expression of lysosomal and lipid metabolism genes in microglia isolated from Trem2 knockout mouse brain.

2019-12-21 | GSE124266 | GEO

TREM2 regulates microglial lipid metabolism during aging in mice [RNA-Seq]

Project description:TREM2 regulates microglial lipid metabolism during aging in mice [RNA-Seq]

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Hypomorphic ASGR1 Modulates Lipid Homeostasis via SREBPs Network

Project description:Hypomorphic ASGR1 Modulates Lipid Homeostasis via SREBPs Network

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