Background: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent signaling in cardiac cells.
Protein kinase C (PKC)ζ-mediated Gαq stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts.
Sex, Age, Specimen part
View Samples5' selective RNA-seq of 96 single cells from human nasal epithelial cells. Cells grown for 33 days at an air liquid interface. RNAseq profiling was performed with N4H4 unique molecular identifiers processed on a Fluidigm C1. Sequencing was performed on a Ion Proton (Life Technologies). Overall design: Single cell from human nasal epithelium. 5' selective RNAseq profiling, 96 cells, unique molecular identifiers, custom library preparation.
A cost effective 5΄ selective single cell transcriptome profiling approach with improved UMI design.
Specimen part, Subject
View Samples5' selective RNA-seq of 47 Single HEK293 cells RNAseq profiling with N4H4 unique molecular identifiers processed on a Fluidigm C1. Overall design: Single cell HEK293 cell 5' selective RNAseq profiling, 47 cells, unique molecular identifiers, custom library preparation.
A cost effective 5΄ selective single cell transcriptome profiling approach with improved UMI design.
No sample metadata fields
View SamplesFive libraries from 100 HEK293 cells each were prepared using a Smartseq based custom library preparation approach with unique molecular identifiers. One batch of 2 replicates (A) and one batch of 3 replicates (B) were prepared from different cell cultures. Libraries were sequenced on an Ion Proton Overall design: HEK293 cell (100 cells) 5' selective RNAseq profiling, N4H4 unique molecular identifiers, 2 replicates (A) and 3 replicates (B)
A cost effective 5΄ selective single cell transcriptome profiling approach with improved UMI design.
No sample metadata fields
View SamplesWe used Affymetrix microarrays to investigate gene expression changes in PBMCs isolated from male patients ongoing secondary prevention of CVD to determine significant modulatory effects that may have been induced by the intake of an initial dose of 8 mg of resveratrol-enriched grape extract for 6 months and then, 16 mg for a further 6 months.
One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease.
Sex, Specimen part, Time
View SamplesThe epidermal-specific ablation of Rb gene leads to increased proliferation, aberrant differentiation, and the disengagement of these processes in vivo and in vitro. These differences in phenotype are more severe with the loss of p107, demonstrating the functional compensation between pRb and p107. As p107 and p130 also exert overlapping functions in epidermis, we have generated Rb(F19/F19)K14cre;Rbl2-/- (pRb-;p130-) mice to analyze possible functional redundancies between pRb and p130. The epidermal phenotype was very similar between pRb- and pRb-;p130- mice, suggesting that pRb and p130 activities are not redundant in epidermis. Importantly, we can correlate the proliferation differences with specific changes in gene expression between pRb-, pRb-;p107- and pRb-;p130- primary keratinocytes using microarray analysis, and explain the phenotypes in the context of altered E2F expression and functionality. Our findings support a model in which the distinct retinoblastoma family members, in conjunction with E2F members, play a central role in regulating epidermal homeostasis through specific or overlapping activities.
Gene profiling approaches help to define the specific functions of retinoblastoma family in epidermis.
Specimen part
View SamplesThe squamous cell carcinomas represent the aggressive type of non melanoma skin cancer, the most frequent malignancy among human population. We have studied here the possible relationship between these two pathways in skin using epidermal-specific mutant mice. Loss of p53, but not pRb, produces spontaneous tumor development, indicating that, contrary to pRb, p53 is the predominant tumor suppressor acting in mouse epidermis. The simultaneous inactivation of pRb and p53 does not aggravate the epidermal phenotype observed in Rb-deficient mice in terms of proliferation and/or differentiation. However, in doubly deficient mice spontaneous skin tumor development is severely accelerated. The tumors are aggressive, undifferentiated and display a hair follicle origin. Detailed analysis indicates that the acceleration is mediated by premature activation of the EGFR/Akt pathway, resulting in increased angiogenesis. The molecular characteristics of this model provide valuable tools to understand epidermal tumor formation, and may ultimately contribute to the development of therapies for the treatment of aggressive squamous cancer.
Spontaneous squamous cell carcinoma induced by the somatic inactivation of retinoblastoma and Trp53 tumor suppressors.
Specimen part
View SamplesTwo olive oils only differing in the presence of maslinic acid were prepared. Using DNA microarrays, hepatic gene expression was analysed in apoE-deficient mice with a C57BL/6J genetic background
Apolipoprotein E determines the hepatic transcriptional profile of dietary maslinic acid in mice.
No sample metadata fields
View SamplesThe histone methyltransferase NSD2/WHSC1/MMSET is overexpressed in a number of solid tumors but its contribution to the biology of these tumors is not well understood. Here, we describe that NSD2 contributes to the proliferation of a subset of lung cancer cell lines by supporting oncogenic RAS transcriptional responses. Co-treatment with MEK and BRD4 inhibitors causes co-operative inhibitory responses on cell growth. While these inhibitors converge in the downregulation of genes associated with cancer-acquired super-enhancers, NSD2 inhibition complements their action by affecting the expression of clusters of genes embedded in megabase-scale regions marked with H3K36me2. Thus, combinatorial therapies using MEK or BRD4 inhibitors together with NSD2 inhibition ensure a more comprehensive inhibition of oncogenic RAS-driven transcription programs. Overall design: H1299 cells were transduced with doxycycline (dox) inducible shRNAs (sh3 or sh5) againts NSD2 and with non target shRNA (shNT). Changes in gene expression (RNA-seq) and H3K36me2 (ChIP-seq) caused by depletion of NSD2 and indicated treatments were assessed. Two replicates (Rep) for RNA-seq and three replicates for ChIP-seq were included.
NSD2 contributes to oncogenic RAS-driven transcription in lung cancer cells through long-range epigenetic activation.
No sample metadata fields
View SamplesCutaneous squamous tumors rely on autocrine/paracrine loops for proper fitness. Targeting this Achilles heel is therefore considered a potential avenue for patient treatment. However, the mechanisms that engage and sustain such programs during tumor ontogeny are poorly understood. Here, we show that two Rho/Rac activators, the exchange factors Vav2 and Vav3, control the expression of an epithelial autocrine/paracrine program that regulates keratinocyte survival and proliferation as well as the creation of an inflammatory microenvironment. Vav proteins are also critically involved in some of the subsequent autocrine signaling loops activated in keratinocytes. The genetic inactivation of both Vav proteins reduces tumor multiplicity without hampering skin homeostasis, thus suggesting that pan-specific Vav therapies may be useful in skin tumor prevention and treatment.
The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
Specimen part
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