This SuperSeries is composed of the SubSeries listed below.
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Specimen part, Cell line
View SamplesAberrant cell proliferation, a hallmark of most cancers, requires the escape from intrinsic antitumour barriers. Primary among these is the DNA damage response (DDR). In both cell culture-models and in early stages of tumorigenesis in vivo, activated oncogenes induce DNA replication stress and DNA double-strand breaks (DSBs), leading to DDR activation and p53-dependent apoptosis and/or senescence. The means by which tumour-initiating cells, also termed cancer stem cells (CSCs), circumvent this oncosuppressive response is unknown. Here we demonstrate that the ZEB1 transcription factor provides breast CSCs with the ability to withstand an aberrant mitogenic activity. Its forced expression in human mammary epithelial cells is sufficient to alleviate DNA replicative stress and to decrease the production of reactive oxygen species, an important contributor to DDR and oncogene-induced senescence. Consistently, human breast cancer cells with endogenous ZEB1 expression show two characteristic features: low levels of DSBs and DDR markers, reflecting mitigation of the DNA replication stress, and a low p53 mutation frequency, reflecting a weak selective pressure for inactivation. Using high-throughput sequencing analysis of controlled cellular models, we further demonstrate that ZEB1 delays the onset of structural chromosomal instability (CIN), a known consequence of replicative stress and prevents the emergence of chromosome 8p deletions and 8q amplifications, two prevalent abnormalities in high-grade breast cancers. Supporting these findings, ZEB1 expression discriminates human breast tumours by their copy number alterations (CNAs) and chromosome 8 aberrations. We propose that the tumorigenic potential of CSCs relies upon their unique capacity to tolerate oncogenic stimuli through the alleviation of DNA replication stress.
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Specimen part
View SamplesUsing a mouse model overexpressing human SNCA and profiling the striatal transcriptome, we assessed gene-environment interactions to reveal perturbations in gene expression and their modulation through chronic unpredictable mild stress (CUMS) exposure. Overall design: Using a 2x2 factorial design, we cross-compared a line of transgenic mice overexpressing human SNCA with wildtype animals, and the effects of chronic unpredictable mild stress (CUMS) with standard housing conditions. Employing RNA-seq, we profiled gene expression in the striatum of 6-month-old female animals.
Distinct Stress Response and Altered Striatal Transcriptome in Alpha-Synuclein Overexpressing Mice.
Age, Specimen part, Cell line, Subject
View SamplesUsing a mouse model overexpressing human SNCA and profiling the striatal transcriptome, we assessed gene-environment interactions to reveal perturbations in gene expression and their modulation through chronic unpredictable mild stress (CUMS) exposure. Overall design: Using a 2x2 factorial design, we cross-compared a line of transgenic mice overexpressing human SNCA with wildtype animals, and the effects of chronic unpredictable mild stress (CUMS) with standard housing conditions. Employing RNA-seq, we profiled gene expression in the striatum of 6-month-old female animals.
Distinct Stress Response and Altered Striatal Transcriptome in Alpha-Synuclein Overexpressing Mice.
Age, Specimen part, Cell line, Subject
View Samples5 arrays from obese insulin-resistant and lean insulin-sensitive females adipose tissue at fasting and after 3h hyperinsulinemia
Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects.
Sex, Specimen part
View SamplesTwo pancreatic cancer cell lines with different metastatic and growth potential were compared under hypoxic conditions and under normal atmospheric oxygen pressure. The FG cell lines shows very few metastases and slow growth in mouse xenograft models. L3.6pl, derived from FG by cycles re-implantation of metastatic cells obtained after orthotopic tumor growth in nude mice, shows high motility, aggressive growth and very high metastatic potential
Hypoxia-independent gene expression mediated by SOX9 promotes aggressive pancreatic tumor biology.
No sample metadata fields
View SamplesThe stromal microenvironment plays a vital role in cancer initiation and progression. We performed a comparative expression profiling of pulmonary MSC derived from NSCLC and corresponding normal lung tissue of 5 newly diagnosed patients. The analysis indicated variable expression of genes involved in DNA repair, apoptosis, proliferation or angiogenesis between NSCLC-MSC and NLT-MSC.
Mesenchymal stem cells in non-small cell lung cancer--different from others? Insights from comparative molecular and functional analyses.
Specimen part, Subject
View SamplesVascular permeability reflects changes in the function of the endothelium, its interendothelial junctions and transcellular delivery. Here, we show that common molecular mechanisms exist between VEGF and histamine in regulating vascular hyperpermeability. Crosstalk between downstream signaling of VEGF and histamine receptors are involved in calcium signaling and cell proliferation. Understanding the molecular mechanisms of vascular permeability is crucial in order to reduce vascular hyperpermeability and oedema in various pathological conditions and in VEGF therapy. Overall design: In despite of the substantial knowledge of VEGF and histamine signal transduction and their physiological responses, molecular mechanisms inducing endothelial cell permeability and proliferation have remained inconclusive. To monitor the transcriptional alteration of proteins known to regulate the endothelial permeability, next-generation RNA sequencing was used. Fold changes of several genes known to regulate calcium signaling, cell adhesion, cell proliferation, ion flux and immune response were compared between the permeabilizing agents.
Differential regulation of angiogenic cellular processes and claudin-5 by histamine and VEGF via PI3K-signaling, transcription factor SNAI2 and interleukin-8.
No sample metadata fields
View SamplesThe 14-week experiment included three groups: 1) the Acute Cpn group, with one C. pneumoniae inoculation at the age of 9 wks; 2) the Chronic Cpn group, with three C. pneumoniae inoculations at the age of 9, 11, and 13 wks; and 3) the control group, with three SPG inoculations at the age of 9, 11, and 13 wks. The mice were sacrificed at the age of 14 wks. The 24-week experiment included four groups: 1) the recurrent A. actinomycetemcomitans infection group, with ten A. actinomycetemcomitans inoculations once a week from the age of 14 to 23 wks; 2) the chronic C. pneumoniae infection group, with three C. pneumoniae inoculations at the age of 9, 11, and 13 wks; 3) the combined chronic C. pneumoniae and recurrent A. actinomycetemcomitans infection group, with three C. pneumoniae inoculations at the age of 9, 11, and 13 wks, and ten A. actinomycetemcomitans inoculations once a week from the age of 14 to 23 wks; and 4) the control group, with three SPG inoculations at the age of 9, 11, and 13 wks, and ten 0.9% NaCl inoculations once a week from the age of 14 to 23 wks. The mice were sacrificed at the age of 24 wks.Epididymal and inguinal AT gene expression was analyzed using an Illumina Mouse WG-6 v2.0 platform.
The effect of proatherogenic pathogens on adipose tissue transcriptome and fatty acid distribution in apolipoprotein E-deficient mice.
Sex, Age, Specimen part
View SamplesBlood from subjects with cardioembolic stroke and controls was collected, and the RNA extracted was interrogated and whole genome U133 Affymetrix Arrays. Twenty-three control samples and sixty-nine cardioembolic stroke samples were assayed.
Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic.
Specimen part, Subject
View Samples