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GSE48939
Mus musculus
23 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Protein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a bottom-up approach to infer pathways in the genetic regulation of lipid metabolism by the UPR.
Publication Title
Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Protein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a bottom-up approach to infer pathways in the genetic regulation of lipid metabolism by the UPR.
Publication Title
Temporal clustering of gene expression links the metabolic transcription factor HNF4α to the ER stress-dependent gene regulatory network.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The CREB binding protein inhibitor ICG-001 suppresses pancreatic cancer growth
Publication Title
The CREB-binding protein inhibitor ICG-001 suppresses pancreatic cancer growth.
Sample Metadata Fields
Cell line, Treatment
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Dam identification (DamID) is a powerful technique to generate genome-wide maps of chromatin protein binding. Due to its high sensitivity it is particularly suited to study the genome interactions of chromatin proteins in small tissue samples in model organisms such as Drosophila. Here we report an intein-based approach to tune the expression level of Dam and Dam-fusion proteins in Drosophila by addition of a ligand to fly food. This helps to suppress toxic effects of Dam. In addition we describe a strategy for genetically controlled expression of Dam in a specific cell type in complex tissues. We demonstrate the utility of the latter by generating a glia-specific map of Polycomb in small samples of brain tissue. Overall design: RNA sequencing of 3 samples, each using 2 biological replicates.
Publication Title
Inducible DamID systems for genomic mapping of chromatin proteins in Drosophila.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 44 Downloadable Samples
- Illumina HiSeq 2000
Description
The DNA-binding protein, Ikaros, functions as a potent tumor suppressor and hematopoietic regulator. However, the mechanisms by which Ikaros functions in the nucleus remain largely undefined, due in part to its atypical DNA-binding properties and partnership with the poorly understood Mi-2/NuRD complex. In this study, we extended our analysis of thymocyte development and lymphomagenesis in a mouse strain containing a specific deletion of Ikaros zinc finger 4, which exhibits a select subset of abnormalities observed in Ikaros null mice. By examining thymopoiesis in vivo and in vitro, numerous abnormalities were observed. RNA-sequencing revealed that each developmental stage is characterized by mis-regulation of a limited number of genes, with a strong preference for genes modulated in a stage-specific manner. Strikingly, individual genes and pathways rarely exhibited Ikaros-dependence at all developmental stages. Instead, the most consistent feature of aberrantly expressed genes was a reduced magnitude of expression level change during a developmental transition. These results and others suggest that Ikaros may not be a dedicated and consistent activator or repressor of a defined set of genes. Instead, its primary function may be to support the dynamic range of gene expression changes during developmental transitions via atypical molecular mechanisms that remain undefined. Overall design: RNA-Seq of T cells at varying developmental stages and T cells expressing activated Notch in WT and Ikzf1-dF4/dF4 mutant backgrounds
Publication Title
Regulation of gene expression dynamics during developmental transitions by the Ikaros transcription factor.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The development, homeostasis and function of B lymphocytes involve multiple rounds of B cell receptor (BCR)-controlled proliferation and prolonged maintenance. We analyzed the role of transcription factor Zfx, a recently identified regulator of stem cell maintenance, in B cell development and homeostasis. Conditional Zfx deletion in the bone marrow blocked B cell development at the pre-BCR selection checkpoint. Zfx deficiency in peripheral B cells caused impaired generation of the B-1 cell lineage, accelerated B cell turnover, depletion of mature recirculating cells, and delayed T-dependent antibody responses. Zfx-deficient B cells showed normal proximal BCR signaling, but impaired BCR-induced proliferation and survival. This was accompanied by aberrantly enhanced and prolonged integrated stress response, and delayed induction of Cyclin D2 and Bcl-xL proteins. Thus, Zfx restrains the stress response and couples antigen receptor signaling to B cell expansion and maintenance during development and peripheral homeostasis.
Publication Title
Transcription factor Zfx controls BCR-induced proliferation and survival of B lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Sentrix MouseRef-8 Expression BeadChip (Target ID)
Description
KRAS mutations are present at a high frequency in human cancers. The development of therapies targeting mutated KRAS requires cellular and animal preclinical models. We exploited adeno-associated virus-mediated homologous recombination to insert the KRAS G12D allele in the genome of mouse somatic cells. Heterozygous mutant cells displayed a constitutively active Kras protein, marked morphologic changes, increased proliferation and motility but were not transformed. On the contrary, mouse cells in which we overexpressed the corresponding KRAS cDNA were readily transformed. The levels of Kras activation in knock-in cells were comparable with those present in human cancer cells carrying the corresponding mutation. KRAS-mutated cells were compared with their wild-type counterparts by gene expression profiling, leading to the definition of a "mutated KRAS-KI signature" of 345 genes. This signature was capable of classifying mouse and human cancers according to their KRAS mutational status, with an accuracy similar or better than published Ras signatures. The isogenic cells that we have developed recapitulate the oncogenic activation of Kras occurring in cancer and represent new models for studying Kras-mediated transformation. Our results have implications for the identification of human tumors in which the oncogenic KRAS transcriptional response is activated and suggest new strategies to build mouse models of tumor progression.
Publication Title
Knock-in of oncogenic Kras does not transform mouse somatic cells but triggers a transcriptional response that classifies human cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
To investigate possible smRNAs linked to TMM silencing by single-stranded and double-stranded silencers, we determined sequences of smRNAs by the Illumina high-throughput sequencing platform and compared silencing efficiency of different strategies. We found that single-stranded silencer alone could promote the production of smRNAs. Overall design: smRNA profiles of 2-week-old wide type seedlings (WT) and different silencers were generated by Illumina Genome Analyzer IIx.
Publication Title
Transcriptional silencing of Arabidopsis endogenes by single-stranded RNAs targeting the promoter region.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 60 Downloadable Samples
- Illumina HiSeq 2000
Description
Midbrain dopaminergic (mDA) neurons degenerate in Parkinson's disease and are one of the main targets for cell replacement therapies. A comprehensive view of the signals and cell types contributing to mDA neurogenesis is not yet available. By analyzing the transcriptome of the mouse ventral midbrain at tissue and single-cell level during mDA neurogenesis we found that three recently identified radial glia types (Rgl 1-3) contribute to different key aspects of mDA neurogenesis. While Rgl3 expressed most extracellular matrix components and multiple ligands for various pathways controlling mDA neuron development, such as Wnt and Shh, Rgl1-2 expressed most receptors. Moreover, we found that specific transcription factor networks explain the transcriptome expression profiles and suggest a function for each individual radial glia type. Overall design: Triplicate tissue samples from each combination of embryonic day E11.5, E12.5, E13.5, and E14.5 with brain region alar plate, dorsal midbrain, ventral forebrain, ventral hindbrain, and ventral midbrain.
Publication Title
The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation.
Sample Metadata Fields
Specimen part, Subject
View Samples