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GSE27674
Pseudomonas aeruginosa
4 Downloadable Samples
Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Many Gram-negative bacteria employ cell-to-cell communication mediated by N-acyl homoserine lactones (quorum sensing) to control expression of a wide range of genes including, but not limited to, genes encoding virulence factors. Outside the laboratory, the bacteria live in complex communities where signals may be perceived across species. We here present a newly found natural quorum sensing inhibitor, produced by the pseudomonads Pseudomonas sp. B13 and Pseudomonas reinekei MT1 as a blind end in the biodegradation of organochloride xenobiotics, which inhibits quorum sensing in P.aeruginosa in naturally occurring concentrations. This catabolite, 4-methylenebut-2-en-4-olide, also known as protoanemonin, has been reported to possess antibacterial properties, but seems to have dual functions. Using transcriptomics and proteomics, we found that protoanemonin significantly reduced expression of genes and secretion of proteins known to be under control of quorum sensing in P.aeruginosa. Moreover, we found activation of genes and gene products involved in iron starvation response. It is thus likely that inhibition of quorum sensing, as the production of antibiotics, is a phenomenon found in complex bacterial communities.
Publication Title
Protoanemonin: a natural quorum sensing inhibitor that selectively activates iron starvation response.
Sample Metadata Fields
Compound
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes: RET, VHL, NF1, and subunits B, C and D of succinate dehydrogenase (SDH). The proteins encoded by these multiple genes regulate distinct functions. To identify molecular interactions between the distinct pathways we performed expression profiling of a large cohort of pheochromocytomas. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1?. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1? activity in tumors.
Publication Title
A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Here we report the characterization of a novel role for the retinoblastoma protein (pRb) as a regulator of osteoblast adhesion. Abrogation of pRb in osteoblasts resulted in aberrant cadherin expression and loss of adherens junctions. This produced defects suggestive of a transformed phenotype such as impaired cell-to-cell adhesion, loss of contact-dependent growth arrest, and the capacity to evade anoikis. This also resulted in profound abnormalities in bone structure. Consistent with this, microarray analyses showed that pRb regulates a wide repertoire of osteoblast cell adhesion genes. In addition, pRb loss also resulted in altered expression and function of several known regulators of cellular adhesion and adherens junction assembly, such as the Rho GTPase Rac1 and the merlin tumor suppressor. Taken together, our results show that pRb controls cell adhesion by regulating the expression and adherens junction components and by regulating the function of molecules involved in adherens junction assembly and stability.
Publication Title
A role for the retinoblastoma protein as a regulator of mouse osteoblast cell adhesion: implications for osteogenesis and osteosarcoma formation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
IlluminaHiSeq2000
Description
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Four histopathological patterns of MS have been described. Pattern II is characterized by infiltrating macrophages and T-cells and by antibody and complement deposition. Transcriptome analysis of three patern II demyelinating brain lesions from a multiple sclerosis patient using RNA sequencing demonstrated the presence of mRNA transcripts for genes specific of activated macrophages, T and B cells as well as genes coding for immunoglobulins, complement proteins and some pattern II associated proteins, providing additional evidence supporting pattern II demyelination. Overall design: Examination of 3 different demyelinating lesions identified by Immunohistopathology.
Publication Title
Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500
Description
BRAF oncogene is mutated in ~50% of human cutaneous melanomas. The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway fuelling cancer growth. The inhibitors of BRAF V600E (BRAFi), lead to massive and high response rate. However, BRAFi-resistant cells that operate as a cellular reservoir for relapses severely limits the duration of the clinical response. The recent depiction of these resistant cells did not identify druggable targets to ensure long-term survival under BRAFi. Here, we identify the aryl hydrocarbon receptor (AhR) as a target to eradicate resistant cells. We show that BRAFi bind to AhR on a new site, named beta-pocket, and reprogram gene expression independently of its partner ARNT. beta-pocket activation induces a pigmentation signature, which is associated to BRAFi-induced cell death of sensitive BRAF V600E melanoma cells and tumour shrinkage. Intriguingly, in resistant cells, BRAFi does not induced a pigmentation signature since these cells display another AhR program; AhR-ARNT dependant. By this way, AhR directs several key BRAFi-resistant genes. At single cell level, this constitutive activation of AhR-ARNT is identified in rare cells before BRAFi-treatment of melanoma tumours and an enrichment of these alpha-cells is observed under BRAFi. Our data strongly suggest that an endogenous AhR ligand activates AhR-ARNT via the canonical AhR pocket (alpha-pocket), thus favouring BRAFi-resistant gene expression. Importantly, we identify the clinically compatible AhR antagonist, the resveratrol (RSV), able to abrogate the deleterious constitutive activation of AhR and to reduce the cellular reservoir for the relapse. Taken together, this work reveals that constitutive AhR signalling drives BRAFi resistance and constitutes a therapeutic target to achieve long-term patient survival under BRAFi. More broadly, the constitutive activation of AhR by endogenous ligands is in line with the ability of UV radiations to generate potent AhR ligands and to favour melanoma onset. Overall design: Total RNA isolated from 12 human melanoma cell lines (501Mel) after different treatments was subjected to multiplexed RNA-sequencing using Illumina NextSeq500 sequencing tehnology.
Publication Title
Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal of the study was to understand whether mitochondrial-driven epigenetic changes regulate gene expression. Mitochondrial metabolism has been implicated in epigenetics but the extent to which this impacts gene expression is unclear. Here we show that loss of mitochondrial DNA (mtDNA) results in locus-specific alterations in histone acetylation, DNA methylation and expression of a subset of genes. Most of these changes are rescued by restoring mitochondrial electron transport in a way that maintains the oxidative tricarboxylic acid cycle, but not reactive oxygen species or ATP production, or by modulating the mitochondrial pool of acetyl-CoA. Changes in acetyl-CoA and histone acetylation precede overt mitochondrial dysfunction and significant changes in gene expression and DNA methylation. This suggests that acetyl-CoA levels signal mitochondrial status to the nucleus. Differentially expressed genes with altered histone marks or DNA methylation regulate amino acid degradation, which likely compensates for the changes in acetyl-CoA and one carbon metabolism. These have the potential to further affect methylation reactions, redox control and nucleotide levels. These results illustrate the extent to which mitochondria impact cell physiology through epigenetic remodeling.
Publication Title
Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 33 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
This study was designed to address key questions concerning the use of alternative protein sources for animal feeds and addresses aspects such as their nutrient composition and impact on gut function, the immune system and systemic physiology. We used casein (CAS), partially delactosed whey powder (DWP), spray dried porcine plasma (SDPP), soybean meal (SBM), wheat gluten meal (WGM) and yellow meal worm (YMW) as protein sources.
Publication Title
Multi-Level Integration of Environmentally Perturbed Internal Phenotypes Reveals Key Points of Connectivity between Them.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The goal was to identify the differently expressed genes between laryngeal tumor and nonmalignant surrounding mucosa
Publication Title
Transcriptome Analysis Identifies ALCAM Overexpression as a Prognosis Biomarker in Laryngeal Squamous Cell Carcinoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 40 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This experiment was carried out in the context of a pharmacogenetic study of long-term (4-year follow-up) response to Interferon-beta treatment in two cohorts of Italian Multiple Sclerosis patients, to identify genetic variants (SNPs) that may influence response to IFN-beta. We integrated results from meta-analysis of the two cohorts with gene expression profiling of IFN stimulated PBMCs from 20 healthy controls and eQTL analyses, to look at possible enrichment of IFN-beta induced genes with genes mapped by top-ranking meta-analyzed SNPs.
Publication Title
Pharmacogenetic study of long-term response to interferon-β treatment in multiple sclerosis.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples