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SRP061607
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
- 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
- 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
- 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- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We established whether partner transcription factor binding, chromatin structure, or gene expression is compromised upon loss of partner factors cdx2 or hnf4a in mouse intestinal villi
Publication Title
Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Changes ins organellar gene expression trigger retrograde signalling. Prolyl-tRNA synthetase (PRORS1) is located in chloroplasts and mitochondria. Thus, prors1-2 mutants are impaired in chloroplast and mitochondrial gene expression.
Publication Title
Identification of target genes and transcription factors implicated in translation-dependent retrograde signaling in Arabidopsis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- NextSeq500
Description
To determine whether the intestine-restricted transcription factor (TF) CDX2 functionally interacts with the endoderm-wide TF HNF4A, we crossed tissue-specific conditional Cdx2 and Hnf4a knockout mice to generate compound mutant mice. We used RNA-sequencing to profile gene expression changes in compound mutant mice compared to control mice. The compound mutant mice had a significantly worse phenotype than either single mutant, and gene expression was significantly perturbed in compound mutants compared to control mice. Overall design: Total RNA isolated from control and compound mutant (Hnf4a-del;Cdx2-del) jejunal mouse intestinal epithelium was prepared for sequencing using the TruSeq RNA Sample Preparation Kit (Illumina) according to the manufacturer''s instructions. 75-base-pair single-end reads were sequenced on an Illumina NextSeq 500 instrument. The data include 2 independent biological replicates per genotype.
Publication Title
Transcription factors GATA4 and HNF4A control distinct aspects of intestinal homeostasis in conjunction with transcription factor CDX2.
Sample Metadata Fields
No sample metadata fields
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