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GSE75793
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Dysregulation of vascular stiffness and cellular metabolism occur early in pulmonary hypertension (PH). Yet, the mechanisms by which biophysical properties of extracellular matrix relate to metabolic processes and downstream PH phenotypes remain undefined. In cultured endothelial and smooth muscle cells and confirmed in PH-diseased human samples, we found that ECM stiffening activates the mechanosensitive factors YAP/TAZ to increase glycolysis and induce glutaminase (GLS) expression and glutaminolysis. Glutaminolysis replenishes aspartate for anabolic biosynthesis, thus sustaining proliferation and migration within stiff ECM. In vitro GLS inhibition blocks aspartate production, consequently reprogramming entire cellular proliferative pathways, while aspartate restores proliferation. In a rat model in vivo, GLS inhibition prevents hemodynamic and histologic manifestations of PH. Thus, mechanical ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis a paradigm that advances our understanding of the connections of mechanical stimuli with dysregulated vascular metabolism and identifies new metabolic drug targets in PH.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To identify the molecular mechanisms and environmental inducers contributing to reprogramming of hepatocytes into progenitors in HCC context, we used the HepaRG cell line as model.
Publication Title
Inflammatory cytokines promote the retrodifferentiation of tumor-derived hepatocyte-like cells to progenitor cells.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Peeling Skin Disease (PSD; OMIM 270300) is an inflammatory ichthyosis due to homozygous loss-of-function mutations in Corneodesmosin (CDSN) and characterized by lifelong patchy peeling of the skin associated with eczema, food allergy and severe itching. The pathophysiology of PSD is still poorly known. The initial event of the disease, the detachment of the SC due to a CDSN deficiency, leads to an impairment of the permeability barrier which could in turn trigger erythema, pruritus and atopic manifestations by mechanisms not entirely elucidated. Cdsn-deficient mouse models are interesting tools to decipher these underlying mechanisms. In order to explore the still poorly known pathophysiological mechanisms of PSD, we analyzed the cutaneous transcriptome of two epidermis-specific Cdsn-deficient mouse models representative of early (occurrence of the permeability defect in Cdsnep-/- E18.5 embryos) and chronic (permanent permeability defect in Cdsniep-/- adult mice) phases of the disease
Publication Title
No associated publication
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Peeling Skin Disease (PSD; OMIM 270300) is an inflammatory ichthyosis due to homozygous loss-of-function mutations in Corneodesmosin (CDSN) and characterized by lifelong patchy peeling of the skin associated with eczema, food allergy and severe itching. The pathophysiology of PSD is still poorly known. The initial event of the disease, the detachment of the SC due to a CDSN deficiency, leads to an impairment of the permeability barrier which could in turn trigger erythema, pruritus and atopic manifestations by mechanisms not entirely elucidated. Cdsn-deficient mouse models are interesting tools to decipher these underlying mechanisms. In order to explore the still poorly known pathophysiological mechanisms of PSD, we analyzed the cutaneous transcriptome of two epidermis-specific Cdsn-deficient mouse models representative of early (occurrence of the permeability defect in Cdsnep-/- E18.5 embryos) and chronic (permanent permeability defect in Cdsniep-/- adult mice) phases of the disease
Publication Title
No associated publication
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The initiation of the mucosal immune response in Peyers patch (PP) relies on the sampling, processing and efficient presentation of foreign antigens by dendritic cells (DC). PP DC encompass five subsets, among which CD11b+ conventional DC (cDC) and LysoDC have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here, we have studied the genetic relatedness of the different subsets of PP cDC at steady state and under TLR7 ligand stimulation. We also provide the transcriptional profiles of subepithelial TIM-4- and interfollicular TIM-4+ macrophages.
Publication Title
Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Murine Genome U74A Array (mgu74a)
Description
Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in presence of Leukaemia Inhibitory Factor (LIF). LIF starvation leads to apoptosis of some of the ES-derived differentiated cells, together with p38a MAP kinase activation. Apoptosis, but not morphological cell differentiation, is blocked by a p38 inhibitor, PD 169316. To further understand the mechanism of action of this compound, we have identified its specific targets by microarray studies. We report on the global expression profiles of genes expressed at three days upon LIF withdrawal (d3) compared to pluripotent cells and of genes whose expression is modulated at d3 under anti-apoptotic conditions. We showed that at d3 without LIF cells express, earlier than anticipated, specialized cell markers and that when the apoptotic process was impaired, expression of differentiation markers was altered. In addition, functional tests revealed properties of anti-apoptotic proteins not to alter cell pluripotency and a novel role for metallothionein 1 gene which prevents apoptosis of early differentiated cells.
Publication Title
Apoptosis and differentiation commitment: novel insights revealed by gene profiling studies in mouse embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The exposure to and contamination by Persistent Organic Pollutants (POPs), which include pesticides used worldwide and polyaromatic hydrocarbons, is detrimental to human health and diverse ecosystems. Although most mechanistic studies have focused on single compounds, living organisms are exposed to multiple environmental xenobiotics, simultaneously, throughout their lives. The experimental evidence useful for assessing the effects of exposure to pollutant mixtures is scarce. We investigated the effects of exposure to a combination of two POPs, which employ different xenosensors, on global gene expression in a human hepatocyte cell model, HepaRG.
Publication Title
Two persistent organic pollutants which act through different xenosensors (alpha-endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin) interact in a mixture and downregulate multiple genes involved in human hepatocyte lipid and glucose metabolism.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Dendritic cells (DCs) are the sentinels of the mammalian immune system and they undergo a complex maturation process mediated by activation upon pathogen detection. Recent studies described the analysis of activated DCs by transcriptional profiling, but translation regulation was never taken in account. Therefore, the nature of the mRNAs being translated at various stages of DC activation was determined with the help of translational profiling, which is the sucrose gradient fractionation of polysomal-bound mRNAs combined to microarrays analysis. Total and polysomal-bound mRNA populations were compared in immature (0h) and LPS-stimulated (4h and 16h) human monocyte-derived DCs with the help of Affymetrix microarrays. Biostatistical analysis indicated that 296 mRNA molecules are translationally regulated during DC-activation. The most abundant biological process among the regulated mRNAs was protein biosynthesis, indicating the existence of a negative feedback loop regulating translation. Interestingly, a cluster of 17 ribosomal proteins were part of the regulated mRNAs, indicating that translation may be fine-tuned by particular components of the translational machinery. Our observations highlight the importance of translation regulation during the immune response, and may favour the identification of novel gene clusters or protein networks relevant for immunity. Our study also provides information on the possible absence of correlation between gene expression and real protein production in DCs.
Publication Title
Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Guanabenz is an FDA approved drug for hypertension. It has been shown also to be an inhibitor of GADD34, the stress-inducible cofactor of PP1. GADD34 has been shown to play a key role in controlling cytokine production in MEFs and dendritic cells.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples