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SRP069052
Homo sapiens
73 Downloadable Samples
IlluminaHiSeq2500
Description
CSL is a key transcription factor, mostly acting as a repressor. While known as main effector of Notch signaling, it can also play Notch-independent functions. Despite the wide interest in CSL, the mechanisms responsible for its own regulation have been little studied. We recently showed that CSL down-modulation in human dermal fibroblasts (HDFs) leads to conversion into cancer associated fibroblasts, which promote keratinocyte tumor development. We show here that levels of CSL gene transcription differ among HDF strains derived from many different individuals, with negative correlation with genes involved in DNA damage/repair. CSL expression in all tested strains is negatively regulated by stress / DNA damaging insults caused by UVA, Reactive Oxygen Species (ROS), smoke extract and doxorubicin treatment. p53, a key effector of the DNA damage response, functions as common negative regulator of CSL gene transcription, through both suppression of CSL promoter activity and, indirectly, through increased p21 expression. CSL was previously shown to bind p53 suppressing its activity. The present findings indicate that p53, in turn, decreases CSL expression, which can serve to enhance p53 activity in the acute response of cells to DNA damaging cancer-threatening conditions. Overall design: RNA sequencing of 46 human foreskin fibroblasts
Publication Title
Negative control of CSL gene transcription by stress/DNA damage response and p53.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BACKGROUND: p53 is an important tumor suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated.
Publication Title
A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dysregulated Wnt signalling is seen in approximately 30% of hepatocellular cancers, thus finding pathways downstream of activation of Wnt signalling is key. Using cre lox technology we have deleted the the adenomatous polyposis coli tumour suppressor protein (Apc) within the adult mouse liver and observed a rapid increase in nuclear beta-catenin and C-Myc. This is associated with an induction of proliferation leading to hepatomegally within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes we analysed the impact of inactivating Apc in the context of deficiency of the potentially key effectors beta-catenin and c-Myc. beta-catenin loss rescues both the proliferation and hepatomegally phenotypes following Apc loss. However c-Myc deletion, which rescues the phenotypes of Apc loss in the intestine, had no effect on the phenotypes of Apc loss. The consequences of deregulation the Wnt pathway within the liver are therefore strikingly different to those observed within the intestine, with the vast majority of Wnt targets beta-catenin dependent but c-Myc independent in the liver.
Publication Title
B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 46 Downloadable Samples
- Illumina HiSeq 2000
Description
Hundreds of immune cell types work in coordination to maintain tissue homeostasis. Upon infection, dramatic changes occur with the localization, migration and proliferation of the immune cells to first alert the body of the danger, confine it to limit spreading, and finally extinguish the threat and bring the tissue back to homeostasis. Since current technologies can follow the dynamics of only a limited number of cell types, we have yet to grasp the full complexity of global in vivo cell dynamics in normal developmental processes and disease. Here we devise a computational method, digital cell quantification (DCQ), which combines genomewide gene expression data with an immune cell compendium to infer in vivo dynamical changes in the quantities of 213 immune cell subpopulations. DCQ was applied to study global immune cell dynamics in mice lungs at ten time points during a 7-day time course of flu infection. We find dramatic changes in quantities of 70 immune cell types, including various innate, adaptive and progenitor immune cells. We focus on the previously unreported dynamics of four immune dendritic cell subtypes, and suggest a specific role for CD103+CD11b- cDCs in early stages of disease and CD8+ pDC in late stages of flu infection. Overall design: To study pathogenesis of Influenza infection, C57BL/6 mice (5 weeks) were infected intranasally with 4x103 PFU of influenza PR8 virus. We measured using RNA-Seq global gene expression in lung tissue at ten time points during a 7-day time course of infection, two infected individuals in each time point and four un-infected individuals as control. The lung organ was removed and transferred immediately into RNA Latter solution (Invitrogen).
Publication Title
Digital cell quantification identifies global immune cell dynamics during influenza infection.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject, Time
View Samples- Mus musculus
- 28 Downloadable Samples
- Illumina HiSeq 2000
Description
Hundreds of immune cell types work in coordination to maintain tissue homeostasis. Upon infection, dramatic changes occur with the localization, migration and proliferation of the immune cells to first alert the body of the danger, confine it to limit spreading, and finally extinguish the threat and bring the tissue back to homeostasis. Since current technologies can follow the dynamics of only a limited number of cell types, we have yet to grasp the full complexity of global in vivo cell dynamics in normal developmental processes and disease. Here we devise a computational method, digital cell quantification (DCQ), which combines genomewide gene expression data with an immune cell compendium to infer in vivo dynamical changes in the quantities of 213 immune cell subpopulations. DCQ was applied to study global immune cell dynamics in mice lungs at ten time points during a 7-day time course of flu infection. We find dramatic changes in quantities of 70 immune cell types, including various innate, adaptive and progenitor immune cells. We focus on the previously unreported dynamics of four immune dendritic cell subtypes, and suggest a specific role for CD103+CD11b- cDCs in early stages of disease and CD8+ pDC in late stages of flu infection. Overall design: To better understand the physiological role of these differential dynamic changes in the DCs, we measured the genome-wide RNA expression of all four DC subpopulations from lung of influenza infected mice at four time points following infections (two mice per time-point). For sorting dendritic cells from lungs, the lungs from infected and control uninfected C57BL/6J mice were immersed in cold PBS, cut into small pieces in 5 ml DMEM media containing 10% Bovine Fetal Serum, the cell suspensions were grinded using 1ml syringe cup on a 70 µm cell strainers (BD Falcon). The cells were washed with ice cold PBS. Remaining red blood cells were lysed using ammonium chloride solution (Sigma). Cells were harvested, immersed 1ml FACS buffer [PBS+2% FBS, 1mM EDTA], Fc receptors were blocked with anti-mouse CD16/CD32, washed with FACS buffer and divided into two tubes for sorting cDC and pDC cells.
Publication Title
Digital cell quantification identifies global immune cell dynamics during influenza infection.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 47 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chronic exposure to cigarette smoke condensate in vitro induces epithelial to mesenchymal transition-like changes in human bronchial epithelial cells, BEAS-2B.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BEAS-2B cells have been treated with low doses (20g/ml) of CSC for 4 months. As negative control BEAS-2B cells were treated with DMSO (the CSC solvent). Non-treated cells were cultivated in parallel.
Publication Title
Chronic exposure to cigarette smoke condensate in vitro induces epithelial to mesenchymal transition-like changes in human bronchial epithelial cells, BEAS-2B.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Exercise has a positive effect on overall health. This study was performed to get an overview of the effects of mixed exercise training on skeletal muscl
Publication Title
Identification of human exercise-induced myokines using secretome analysis.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The study seeks to identify the epigenetic changes caused by exposure of to cigarette smoke condensate. To this goal human bronchial epithelial cells, BEAS-2B, were treated with 5-aza-2deoxycitidine and trychostatin A (5AzaC/TSA) subsequent to a chronic exposure (1 month) to cigarette smoke condensate (CSC). As negative control served BEAS-2B cells that were untreated or treated with CSC/DMSO for one month without the subsequent application of 5Aza/TSA.
Publication Title
Chronic exposure to cigarette smoke condensate in vitro induces epithelial to mesenchymal transition-like changes in human bronchial epithelial cells, BEAS-2B.
Sample Metadata Fields
Treatment
View Samples- Saccharomyces cerevisiae
- 16 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Natural grape-juice fermentations involve the sequential development of different yeast species which strongly influence the chemical and sensorial traits of the final product. In the present study,we aimed to examine the transcriptomic response of Saccharomyces cerevisiae to the presence of Hanseniaspora guilliermondii wine fermentation.
Publication Title
Genomic expression program of Saccharomyces cerevisiae along a mixed-culture wine fermentation with Hanseniaspora guilliermondii.
Sample Metadata Fields
Treatment, Time
View Samples