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GSE43334
Homo sapiens
12 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Stringent regulation of the interferon signaling pathway is essential for maintaining the immune response to pathogens and tumors. The transcription factor STAT1 is a crucial mediator of this response. Here we show that hCAF1/CNOT7 regulates class I and II interferon pathways at different crucial steps. In resting cells hCAF1 can control STAT1 trafficking by interacting with the latent form of STAT1 in the cytoplasm. IFN treatment induces STAT1 release, suggesting that hCAF1 may shield cytoplasmic STAT1 from undesirable stimulation. Consistent, hCAF1 silencing enhances STAT1 basal promoter occupancy associated with increased expression of a subset of STAT1-regulated genes. Consequently, hCAF1 knockdown cells exhibit an increased protection against viral infection and reduced viral replication. Furthermore, hCAF1 participates in the extinction of the IFN signal, through its deadenylase activity, by speeding up the degradation of some STAT1-regulated mRNAs. Since abnormal and unbalanced JAK/STAT activation is associated with immune disorders and cancer, hCAF1 could play a major role in innate immunity and oncogenesis, contributing to tumor escape.
Publication Title
hCAF1/CNOT7 regulates interferon signalling by targeting STAT1.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Bone is the most common metastatic site in ER+ patients, however bone metastases are technically challenging to biopsy and analyse. Difficulties concern both tumour tissue acquisition and techniques for analysis and RNA extractions. Patient-derived xenografts (PDX) of BC bone metastases have not been reported yet. For the first time we established PDX models from bone metastatic biopsies of patients progressing on ET and treated by vertebroplasty. PDX models were analysed at transcriptomic level and compared to patient’s early primary tumours to identify new therapeutic targets associated with endocrine resistance in the metastatic setting.
Publication Title
PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance.
Sample Metadata Fields
Disease, Disease stage, Treatment
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
Illumina HiSeq 2500
Description
Cancer cells have abnormal gene expression profiles, however, the transcription factors and the architecture of the regulatory network that drive cancer specific gene expression is often not known. Here we studied a model of Ras-driven invasive tumorigenesis in Drosophila epithelial tissues and combined in vivo genetics with high-throughput sequencing and computational modeling to decipher the regulatory logic of tumor cells. Surprisingly, we discovered that the bulk of the tumor specific gene expression is driven by an ectopic network of a few transcription factors that are overexpressed and/or hyperactivated in tumor cells. These factors are Stat, AP-1, the bHLH proteins Myc and AP-4, the nuclear hormone receptor Ftz-f1, the nuclear receptor coactivator Taiman/AIB1, and Mef2. Notably, many of these transcription factors are also hyperactivated in human tumors. Bioinformatics analysis predicted that these factors directly regulate the majority of the tumor specific gene expression, that they are interconnected by extensive cross-regulation, and that they show a high degree of co-regulation of target genes. Indeed, the factors of this network were required in multiple epithelia for tumor growth and invasiveness and knock-down of individual factors caused a reversion of the tumor specific expression profile, but had no observable effect on normal tissues. We further found that the Hippo pathway effector Yki/Sd was strongly activated in tumor cells and initiated cellular reprogramming by activating several transcription factors of this network. Thus, modeling regulatory networks identified an ectopic yet highly ordered network of master regulators that control tumor cell specific gene expression. Overall design: RNA-seq gene expression profiling across Drosophila 3rd instar larval wild type wing discs and genetic perturbations of wts.
Publication Title
An Ectopic Network of Transcription Factors Regulated by Hippo Signaling Drives Growth and Invasion of a Malignant Tumor Model.
Sample Metadata Fields
Subject, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The oocytes of many species, both invertebrate and vertebrate, contain a large collection of localized determinants in the form of proteins and translationally inactive maternal mRNAs. However, it is unknown whether mouse oocytes contain localized MmRNA determinants and what mechanisms might be responsible for their control. We collected intact MII oocytes, enucleated MII oocyte cytoplasts (with the spindle removed), and spindle-chromosome complexes which had been microsurgically removed. RNA was extracted, amplified, labeled, and applied to microarrays to determine if any MmRNA determinants were localized to the SCC.
Publication Title
Association of maternal mRNA and phosphorylated EIF4EBP1 variants with the spindle in mouse oocytes: localized translational control supporting female meiosis in mammals.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of gene-probe expression data (FPKM) for mouse skin using single-end read RNA-seq Overall design: RNA was collected and analyzed for 2 biological replicates each from 3 developmental stages (E18.5, P3, 10 weeks)
Publication Title
RNA-seq studies reveal new insights into p63 and the transcriptomic landscape of the mouse skin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We developed a Tet-inducible system to express deltaNp63alpha isoform under the control of keratin 5 promoter. Transgenic mice, which were Bigenic (BG) developed a severe skin phenotype with abnormal keratinocyte differentiation and defects in hair follicle development and cycling. Skin samples from transgenic animals and wild type animals were analyzed for global transcriptome changes.
Publication Title
Abnormal hair follicle development and altered cell fate of follicular keratinocytes in transgenic mice expressing DeltaNp63alpha.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
To define target genes of the intestine-restricted transcription factor (TF) CDX2 in intestinal stem cells, we performed chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq). We used RNA-sequencing to profile gene expression changes during cell differentiation from mouse intestinal stem cells to mature villus cells, as well as genes perturbed in intestinal stem cells upon loss of Cdx2. We find thousands of genes that change in expression during cell differentiation, including known stem cell and mature markers. Upon loss of Cdx2, hundreds of genes are up and down-regulated in intestinal stem cells, some of which are also bound by CDX2 nearby and constitute candidate direct target genes. Overall design: CDX2 ChIP-Seq analysis of isolated mouse intestinal stem cells. RNA seq analysis of control mouse villus cells, control intestinal stem cells and Cdx2-deleted intestinal stem cells.
Publication Title
Distinct Processes and Transcriptional Targets Underlie CDX2 Requirements in Intestinal Stem Cells and Differentiated Villus Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Under stress conditions mammalian cells activate compensatory mechanisms to survive and maintain cellular function. During catabolic conditions, such as low nutrients, systemic inflammation, cancer or infections, protein breakdown is enhanced and aminoacids are released from muscles to sustain liver gluconeogenesis and tissues protein synthesis. Proteolysis in muscle is orchestrated by a set of genes named atrophy-related genes. A system that is activated both in short and prolonged stress conditions is the family of Forkhead Box (Fox) O transcription factors. Here, we report that muscle-specific deletion of FoxO members resulted in protection from muscle loss because FoxO family is required for induction of autophagy-lysosome and ubiquitin-proteasome systems. Importantly, FoxOs are required for Akt activity but not for mTOR signalling underlining the concept that FoxOs are upstream mTOR for the control of protein breakdown when nutrients are lacking. Moreover, FoxO family controls the induction of critical genes belonging to several fundamental stress response pathways such as unfolded protein response, ROS detoxification and translational regulation. Finally, we identify a set of novel FoxO-dependent ubiquitin ligases including the recent discovered MUSA11 and a new one, which we named Specific of Muscle Atrophy and Regulated by Transcription (SMART). Our findings identify the critical role of FoxO in regulating a variety of genes belonging to pathways important for stress-response under catabolic conditions.
Publication Title
Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of gene expression changes during mouse salivary gland development using RNA-Seq Overall design: RNA was collected and analyzed for at least two biological replicates each from six developmental timepoints (E14.5, E16.5, E18.5, P5, 4 weeks, 12 weeks)
Publication Title
RNA-seq based transcriptomic map reveals new insights into mouse salivary gland development and maturation.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples