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GSE36669
Mus musculus
15 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the current study we investigated the concept of lipid-induced toxicity as the pathogenic link that could explain the trigger of this response. We addressed this question using isolated ATMs and adipocytes from genetic and diet-induced murine models of obesity. Through transcriptomic and lipidomic analysis, we created a model integrating transcript and lipid species networks simultaneously occurring in adipocytes and ATMs and their reversibility by thiazolidinedione treatment. We show that polarization of ATMs is associated with lipid accumulation and the consequent formation of foam celllike cells in adipose tissue. Our study reveals that early stages of adipose tissue expansion are characterized by M2-polarized ATMs and that progressive lipid accumulation within ATMs heralds the M1 polarization, a macrophage phenotype associated with severe obesity and insulin resistance. Furthermore, rosiglitazone treatment, which promotes redistribution of lipids toward adipocytes and extends the M2 ATM polarization state, prevents the lipid alterations associated with M1 ATM polarization. Our data indicate that the M1 ATM polarization in obesity might be a macrophage-specific manifestation of a more general lipotoxic pathogenic mechanism. This indicates that strategies to optimize fat deposition and repartitioning toward adipocytes might improve insulin sensitivity by preventing ATM lipotoxicity and M1 polarization.
Publication Title
Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, in addition, the mechanisms underlying sublingual immunotherapy (SLIT) are still unknown.
Publication Title
Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation.
Publication Title
Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Muscle Expression of SOD1(G93A) Modulates microRNA and mRNA Transcription Pattern Associated with the Myelination Process in the Spinal Cord of Transgenic Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
sorafenib is the treatment of reference for hepatocellular carcinoma (HCC). We applied sorafenib on the human HCC cell line Huh7 and the subclone shRb, carrying a stable knock-down of the expression of the RB1 gene, a key regulator of liver carcinogenesis. Our aim was to better understand the physiologic and metabolic consequences of the exposure of HCC cells to sorafenib.
Publication Title
Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
In this study we used Genome Wide Transcriptional Modelling (GWTM) to investigate the temporal transcriptional changes during CD4 Th0, Th1 and Th2 differentiation in the first 24 hours after T cell activation. We measured the transcriptional response by RNA seq every four hours for a 24 hour time course. Overall design: WT CD4 T cells were isolated and purified from adult murine spleen. The purified CD4 cells were then set up in culture under three different conditions: Th0, Th1 and Th2. Cells were extracted at 4 hour timepoints during a 24hour timecourse and RNA was extracted for each timepoint under each condition. This RNA was further sequenced to analyse the genome wide transcriptional changes through time under each of the three conditions.
Publication Title
IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Intrinsic self-DNA triggers inflammatory disease dependent on STING.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Inflammatory diseases such as Aicardi-Goutieres Syndrome (AGS) and severe systemic lupus erythematosus (SLE) are generally lethal disorders that have been traced to defects in the exonuclease Trex1 (DNAseIII). Mice lacking Trex1 similarly die at an early age through comparable symptoms, including inflammatory myocarditis, through chronic activation of the STING (stimulator of interferon genes) pathway. Here we demonstrate that phagocytes rather than myocytes are predominantly responsible for causing inflammation, an outcome that could be alleviated following adoptive transfer of normal bone marrow into Trex1-/- mice. Trex1-/- macrophages did not exhibit significant augmented ability to produce pro-inflammatory cytokines compared to normal macrophages following exposure to STING-dependent activators, but rather appeared chronically stimulated by genomic DNA. These results shed molecular insight into inflammation and provide concepts for the design of new therapies.
Publication Title
Intrinsic self-DNA triggers inflammatory disease dependent on STING.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Activation of the STING (Stimulator of Interferon Genes) pathway by microbial or self-DNA, as well as cyclic di nucleotides (CDN), results in the induction of numerous genes that suppress pathogen replication and facilitate adaptive immunity. However, sustained gene transcription is rigidly prevented to avoid lethal STING-dependent pro-inflammatory disease by mechanisms that remain unknown. We demonstrate here that after autophagy-dependent STING delivery of TBK1 (TANK-binding kinase 1) to endosomal/lysosomal compartments and activation of transcription factors IRF3 (interferon regulatory factors 3) and NF-B (nuclear factor kappa beta), that STING is subsequently phosphorylated by serine/threonine UNC-51-like kinase (ULK1/ATG1) and IRF3 function is suppressed. ULK1 activation occurred following disassociation from its repressor adenine monophosphate activated protein kinase (AMPK), and was elicited by CDNS generated by the cGAMP synthase, cGAS. Thus, while CDNs may initially facilitate STING function, they subsequently trigger negative-feedback control of STING activity, thus preventing the persistent transcription of innate immune genes.
Publication Title
Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Inflammatory diseases such as Aicardi-Goutieres Syndrome (AGS) and severe systemic lupus erythematosus (SLE) are generally lethal disorders that have been traced to defects in the exonuclease Trex1 (DNAseIII). Mice lacking Trex1 similarly die at an early age through comparable symptoms, including inflammatory myocarditis, through chronic activation of the STING (stimulator of interferon genes) pathway. Here we demonstrate that phagocytes rather than myocytes are predominantly responsible for causing inflammation, an outcome that could be alleviated following adoptive transfer of normal bone marrow into Trex1-/- mice. Trex1-/- macrophages did not exhibit significant augmented ability to produce pro-inflammatory cytokines compared to normal macrophages following exposure to STING-dependent activators, but rather appeared chronically stimulated by genomic DNA. These results shed molecular insight into inflammation and provide concepts for the design of new therapies.
Publication Title
Intrinsic self-DNA triggers inflammatory disease dependent on STING.
Sample Metadata Fields
Specimen part
View Samples