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GSE29420
Saccharomyces cerevisiae
3 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The yeast PMR1 (ATP2C1) gene codes for the eukaryotic prototype of a high affinity P-type ATPase required for Ca2+/Mn2+ transport into the Golgi. Cells lacking PMR1 exhibit multiple genetic interactions with genes involved in DNA recombination and replication, a fact that is not yet understood. We find that deletion of PMR1 causes a delay in DNA replication initiation, progression and G2/M transition and induces the transcriptional up-regulation of genes involved in cell cycle regulation, including CLB5 and SWE1. Interestingly, pmr1 clb5 double mutants exhibit a dramatic delay in DNA replication and increased DNA breakage, while endoreplication and the formation of multi-nucleated, giant yeast is observed in pmr1 swe1 cells. Because these phenotypes can be attributed to impeded Mn2+-pump function, we provide a model in which Mn2+ interferes with Mg2+ in the nucleus, and vice versa, Mg2+ interferes with Mn2+ in the Golgi. Consequently, cell cycle progression is challenged by aberrant catalytic activities of enzymes involved in replication and protein glycosylation.
Publication Title
Impaired manganese metabolism causes mitotic misregulation.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
We sequenced mRNA from two preparations of isolated Notch-responsive ductal pancreas cells and compared transcript expression to all other non-Notch-responsive cells from each sample to charactarize zebrafish centroacinar cells. Overall design: Determination of gene expression levels in centroacinar cells and non-centroacinar cells from adult pancreas.
Publication Title
Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 222 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.
Publication Title
Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tumor growth and metastasis is controlled by paracrine signaling between cells of the tumor microenvironment and malignant cells. Cancer-associated fibroblasts (CAFs), are functionally important components of the tumor microenvironment. Although some steps involved in the cross-talk between these cells are known, there is still a lot that is not clear. Thus, the addition of, the consideration of microenvironment in the development of the disease, to the clinical and pathological procedures (currently admitted as the consistent value cancer treatments) could lay the foundations for the development of new treatment strategies to control the disease.
Publication Title
Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here that Snail1 plays also a key role in tumor associated fibroblasts since is necessary for enhancement by these cells on epithelial cells tumor invasion. Snail1 expression in fibroblast requires signals derived from tumor cells such as TGF-b; reciprocally, in fibroblasts Snail1 organizes a complex program that favors collective invasion of epithelial cells at least in part by the secretion of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine tumor-derived cancer associated fibroblasts to promote tumor invasion is associated to Snail1 expression and obliterated by Snail1 depletion. In vivo experiments show that tumor cells co-transplanted with Snail1 depleted fibroblasts show lower invasion than those xenografted with control fibroblasts. Finally Snail1 depletion in mice prevents the formation of breast tumors and decreased their invasion. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to its effect in EMT but dependent on its expression in stromal fibroblasts where it orchestrates its activation and the crosstalk with epithelial cells.
Publication Title
Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Description
Purpose: Characterize the role of the coactivator subunit TAF9b during differentiation of embryonic stem cells into motor neurons as well in mouse newborn spinal column tissues. Overall design: RNA-seq comparing WT and TAF9B KO mouse ES cells differentiated into motor neurons. RNA-seq comparing WT and TAF9B KO mouse newborn spinal column tissues. ChIP-seq mapping TAF9b and RNA Pol II binding sites in in vitro differentiated motor neurons.
Publication Title
Core promoter factor TAF9B regulates neuronal gene expression.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Although heterochromatin is enriched with repressive traits, it is also actively transcribed, giving rise to large amounts of non-coding RNAs. Although these RNAs are responsible for the formation and maintenance of heterochromatin, little is known about how their transcription is regulated. Here we show that the Snail1 transcription factor represses pericentromeric transcription, acting through the H3K4 deaminase LOXL2. Since Snail1 plays a key role in the epithelial to mesenchymal transition (EMT), we analyzed the regulation of mouse heterochromatin transcription in this process. At the onset of EMT, one of the major structural heterochromatin proteins, HP1a, is transiently released from heterochromatin foci in a Snail1/LOXL2dependent manner during EMT, concomitantly with a down-regulation of major satellite transcription. Global transcriptome analysis indicated that ectopic expression of heterochromatin transcripts affects the transcription profile of EMT-related genes. Additionally, preventing the down-regulation of major satellite transcripts compromised the migratory and invasive behavior of mesenchymal cells. We propose that Snail1 regulates heterochromatin transcription through the histone-modifying enzyme, LOXL2, thus creating the favorable transcriptional state necessary for completing EMT.
Publication Title
Regulation of heterochromatin transcription by Snail1/LOXL2 during epithelial-to-mesenchymal transition.
Alternate Accession IDs
Sample Metadata Fields
Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 9 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The conserved FACT (FAcilitates Chromatin Transcription) complex is a chromatin-reorganizing complex that promotes RNAPII transcription through chromatin templates by interacting with histones. It facilitates promoter activation by nucleosome eviction, and transcription elongation by nucleosome disruption and reassembly ahead and behind the RNAP. It also has a role in replication not fully understood yet. Genome-wide microarray analyses in spt16-11 and pob3-7 strains revealed a set of genes whose mRNA levels were altered with respect to the WT levels. These include 48 up-regulated and 80 down-regulated genes that are common to both strains. The up-regulated genes were longer and expressed at lower levels than the genome average whereas the down-regulated genes were more similar to the average of the genome.
Publication Title
The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Mutation or deletion of Neurofibromin (NF1), an inhibitor of RAS signaling, frequently occurs in epithelial ovarian cancer (EOC), supporting therapies that target downstream RAS effectors, such as the RAF-MEK-ERK pathway. However, no comprehensive studies have been carried out testing the efficacy of MEK inhibition in NF1-deficient EOC. Here, we performed a detailed characterization of MEK inhibition in NF1-deficient EOC cell lines using kinome profiling and RNA sequencing. Our studies showed MEK inhibitors were ineffective at providing durable growth inhibition in NF1-deficient cells due to kinome reprogramming. MEKi-mediated destabilization of FOSL1 resulted in induced expression of RTKs and their downstream RAF and PI3K signaling overcoming MEKi therapy. MEKi synthetic enhancement screens identified BRD2 and BRD4 as integral mediators of the MEKi-induced RTK signatures. Inhibition of BET proteins using BET bromodomain inhibitors (BETi) blocked MEKi-induced RTK reprogramming, indicating BRD2 and BRD4 represent promising therapeutic targets in combination with MEKi to block resistance due to kinome reprogramming in NF1-deficient EOC. Overall design: Examination of the global effects on transcription in response to trametinib (GSK212) in A1847 cells.
Publication Title
Intrinsic Resistance to MEK Inhibition through BET Protein-Mediated Kinome Reprogramming in NF1-Deficient Ovarian Cancer.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
A great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models. In this study, we examined gene expression changes during chronic exposure to morphine during maturation and differentiation of zebrafish CNS.
Publication Title
Whole-genome expression profile in zebrafish embryos after chronic exposure to morphine: identification of new genes associated with neuronal function and mu opioid receptor expression.
Alternate Accession IDs
Sample Metadata Fields
Treatment
View Samples