Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of ADAR1 silencing in human monocyte-derived macrophages

ABSTRACT: Adenosine deaminase acting on RNA 1 (ADAR1) regulates mRNA fate and function through adenosine-to-inosine (A-to-I) RNA editing and RNA-binding activities. While its role in innate immunity is well established, the broader regulatory functions of ADAR1 in macrophages remain poorly defined. Here, we systematically profiled ADAR1 expression across human immune cells and identified a marked enrichment in macrophages, driven by selective usage of an alternative transcription start site during monocyte-to-macrophage differentiation. ADAR1 binds, edits, and modulates key macrophage targets involved in efferocytosis, endocytosis, lysosomal processing, lipid metabolism, and proliferation in an isoform-specific manner. We further demonstrate that ADAR1 levels and activity are dynamically regulated in adipose tissue and liver during the progression of metabolic disease. Linked to this, macrophage specific ablation of ADAR1 co-cultured in organotypic 3D primary human spheroids and exposed to metabolic stress resulted in an exacerbated lipid accumulation phenotype. Finally, we identify a lipid-associated macrophage-specific upregulation of ADAR1 in adipose tissue following weight loss interventions, mechanistically driven by free fatty acids. These findings uncover a previously unrecognized role for ADAR1 in lipid-buffering, scavenging, and proliferative macrophage functions, extending its biological relevance beyond canonical interferon-mediated immunity and establishing ADAR1 as a key regulator of macrophage adaptation in metabolic disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE307402 | GEO | 2026/02/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from cultured mouse macrophages isolated from Hilpdaflox/flox (WT) and HilpdaΔMΦ (KO) mice treated with a mixture of fatty acids

Project description:Obesity leads to a state of chronic low-grade inflammation that features accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid droplet accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids. Decreased lipid storage in HILPDA-deficient macrophages could be rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory and metabolic parameters, despite markedly reducing lipid accumulation in macrophages. Overall, we find that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis in macrophages that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Our data question the contribution of lipid droplet accumulation in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.

2019-12-19 | GSE142295 | GEO

Mouse peritoneal macrophages treated with three different fatty acids

2019-12-19 | GSE142294 | GEO

ADAR1 Regulates Lipid Remodeling through MDM2 to Dictate Ferroptosis Sensitivity

Project description:Triple-negative breast cancer (TNBC), lacking expression of estrogen, progesterone, and HER2 receptors, is aggressive and lacks targeted treatment options. An RNA editing enzyme, adenosine deaminase acting on RNA 1 (ADAR1), has been shown to play important roles in TNBC tumorigenesis. We posit that ADAR1 functions as a homeostatic factor protecting TNBC from internal and external pressure, including metabolic stress. We tested the hypothesis that the iron-dependent cell death pathway, ferroptosis, is a ADAR1-protected metabolic vulnerability in TNBC by showing that ADAR1 knockdown sensitizes TNBC cells to GPX4 inhibitors. By performing single-reaction monitoring-based liquid chromatography coupled to mass spectrometry (LC-MS) to measure intracellular lipid contents, we showed that ADAR1 loss increased the abundance of polyunsaturated fatty acid phospholipids (PUFA-PL), of which peroxidation is the primary driver of ferroptosis. Transcriptomic analyses led to the discovery of the proto-oncogene MDM2 contributing to the lipid remodeling in TNBC upon ADAR1 loss. A phenotypic drug screen using a ferroptosis-focused library was performed to identify FDA-approved cobimetinib as a drug-repurposing candidate to synergize with ADAR1 loss to suppress TNBC tumorigenesis. By demonstrating that ADAR1 regulates the metabolic fitness of TNBC through desensitizing ferroptosis, we aim to leverage this metabolic vulnerability to inform basic, pre-clinical, and clinical studies to develop novel therapeutic strategies for TNBC.

2025-01-13 | GSE286185 | GEO

Targeting immunosuppressive macrophages overcomes PARP-inhibitor resistance in BRCA1-associated triple-negative breast cancer

Project description:Despite objective responses to PARP inhibition and improvements in progression-free survival compared to standard chemotherapy in patients with BRCA-associated triple-negative breast cancer (TNBC), benefits are transitory. Using high dimensional single-cell profiling of human TNBC, here we demonstrate that macrophages are the predominant infiltrating immune cell type in BRCA-associated TNBC. Through multi-omics profiling we show that PARP inhibitors enhance both anti- and pro-tumor features of macrophages through glucose and lipid metabolic reprogramming driven by the sterol regulatory element-binding protein 1 (SREBP-1) pathway. Combined PARP inhibitor therapy with CSF-1R blocking antibodies significantly enhanced innate and adaptive anti-tumor immunity and extends survival in BRCA-deficient tumors in vivo and is mediated by CD8+ T-cells. Collectively, our results uncover macrophage-mediated immune suppression as a liability of PARP inhibitor treatment and demonstrate combined PARP inhibition and macrophage targeting therapy induces a durable reprogramming of the tumor microenvironment, thus constituting a promising therapeutic strategy for TNBC.

2021-03-25 | PXD015804 | Pride

Disruption of macrophage polarization promote adipocyte disfunction via APOE-APP Intercellular communication

Project description:Human exposure to endocrine disrupting chemicals (EDCs) such as plasticizers contributes to part of metabolic disorders especially in children and adolescents. Immune cells especially macrophages were essential targets of plasticizers, however their roles on plasticizers induced metabolic disorders and the underlying mechanism were poorly elucidated. Here we reported that dicyclohexyl phthalate (DCHP), one substitute for di-2-ethylhexyl phthalate (DEHP), prepubertal exposure decreased adipose tissue mass and increased plasma triglycerides in mice. Mechanistically, adipose tissue macrophages, particularly lipid associated macrophages (LAM), played key role in this systemic metabolic disorder. Phthalates facilitated the formation of LAMs. And LAMs communicated with adipocyte precursors, especially adipose progenitor cells, via APOE-APP interaction, leading to abnormal adipogenesis. Blocking LAMs formation via macrophage-specific PPARγ knockout enabled adaptive adipogenesis, ameliorating DCHP-induced metabolic disorder. Our data highlights the essential role of LAMs in inhibiting adaptive adipogenesis, supplying a scientific basis for EDCs associated metabolic disorder, especially environmental related lipodystrophy.

2025-01-01 | GSE283751 | GEO

DCHP targets lipid associated macrophages to disrupt lipid metabolism via crosstalk with adipocyte precursor cells

Project description:The role of lipid associated macrophages (LAMs) in metabolic homeostasis remains an important yet understudied aspect of adipose tissue. Here, we report a potential new regulatory mechanism by which LAM control adipose tissue homeostasis, involving the endocrine disrupting chemical (EDC) dicyclohexyl phthalate (DCHP) and resulting in altered metabolic regulation. Prepubertal DCHP exposure decreased adipose tissue mass and increased plasma triglycerides in mice. Mechanistically, DCHP facilitated the formation of LAMs. And LAMs communicated with adipocyte precursors, especially adipose progenitor cells, via ApoE-APP interaction, leading to abnormal adipogenesis. Blocking LAMs formation via macrophage-specific PPARγ knockout enabled adaptive adipogenesis, ameliorating DCHP-induced metabolic disorder. Our data highlight the essential role of LAMs in inhibiting adaptive adipogenesis, providing a scientific basis for EDC-induced metabolic dysfunction and phthalates toxicity.

2024-11-01 | GSE246564 | GEO

Single cell RNA sequencing of peritoneal cells from macrophage-Cd36-/- and macrophage-Cd36 fl/fl mice at the resolution phase of sterile inflammation.

Project description:Monocytes and macrophages as components of innate immunity are critical for both homeostasis and inflammation. The scavenger receptor CD36, highly expressed in macrophages, promotes immunological responses mediated by recognition of molecular patterns on pathogens or endogenous ligands on apoptotic cells. CD36 mediated lipid uptake also allows metabolic adaptations that influence macrophage phenotype and polarization. CD36 binds diverse lipids including fatty acids and various lipoproteins, which could exert differential effects on macrophage conversion. Previous studies reported opposite outcomes due to CD36-mediated lipid uptake; macrophages converted to either an inflammatory or an alternatively activated phenotype. To determine the role of this receptor in vivo in the presence of physiological lipid sources, we created macrophage-specific CD36 knockout mice. Using zymosan-induced peritonitis to activate immune cells, we show through single cell RNA sequencing analysis that a broad variety of resident and infiltrated immune cells are present in the peritoneum 72h after the initial stimulus. CD36 deficiency did not affect the numbers of cells during the infiltration and resolution phases, but CD36 deficiency altered the macrophage transcriptome. Pathways related to innate immunity, antigen presentation and oxidative phosphorylation were upregulated in macrophages with CD36 deficiency, whereas those related to efferocytosis, adaptive immunity and B cell activation were downregulated. Despite these gene changes, neither immunoglobulin production nor peritoneal efferocytosis was altered by macrophage CD36 deficiency, nor were there changes in the numbers of circulating white blood cells. Thus, CD36 deficiency does not reduce the inflammatory phenotype of induced peritoneal macrophages.

2024-05-31 | GSE210795 | GEO

TGM2-deficient macrophages exhibited a significant upregulation of pro-inflammatory signatures.

Project description:Macrophages are essential for tissue homeostasis, orchestrating the initiation and resolution of both innate and adaptive immunity with profound impacts on protective immunity and immune-mediated pathological damage. Macrophages are heterogeneous subsets. During the inflammatory response, they include both pro-inflammatory subsets and subsets that promote inflammation resolution, and different macrophage subsets play distinct roles in the dynamic processes at different time points. In the current study, we found that a subset of TGM2+ macrophages with inflammation-resolving properties gradually increases during the inflammation resolution phase in the LPS-induced endotoxin shock model. The peak expression of the TGM2 gene occurs mainly during the inflammation resolution phase. Additionally, transcriptome analysis revealed that compared with wild-type (WT) macrophages, TGM2-deficient macrophages exhibited a significant upregulation of pro-inflammatory signatures and a marked downregulation of lipid metabolic synthesis processes. In lipid rescue experiments, we found that the elevated inflammation phenotype of TGM2-deficient macrophages could be restored. Moreover, a significant anti-inflammatory function of this macrophage subset was observed in mouse models of severe disease, enterocolitis, and endotoxin shock. We uncover an inflammatory remodeling of the neuro-metabolic landscape in macrophages, whereby serotonin induces TGM2-mediated serotonylation of in AKT1.

2025-12-15 | GSE313189 | GEO

Transcriptome analysis of mice adipose tissues

Project description:We report that the HF/HS-mediated functional enrichment of genes of immunity and inflammation is driven toward normal by the AOF supplementation Obesity may not constantly associate with metabolic disorders and mortality later in life, raising the challenging concept of healthy obesity. Here, high fat-high sucrose (HF/HS) feeding produces hyperglycaemia and hypercholesterolemia, increases oxidative stress, elevates endotoxemia, expands adipose tissue (with enlarged adipocytes, macrophage infiltration and accumulation of cholesterol and oxysterols), and reduces lifespan of obese mice. Despite persistence of obesity, supplementation with an antioxidant formulation normalizes plasma lipids and endotoxemia, prevents macrophage recruitment in adipose tissue, reduces adipose accumulation of cholesterol and cholesterol oxides, and extends lifespan. The HF/HS-mediated functional enrichment of genes of immunity and inflammation (in particular response to lipopolysaccharides) is driven towards normal by the antioxidant formulation. It is concluded that the limitation of immune cell infiltration in adipose tissue on the long term by an antioxidant formulation can increase lifespan independently of body weight and fat storage. It constitutes the hallmark of a healthy adiposity trait.

2019-07-09 | GSE120748 | GEO

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

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