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GSE66056
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA-203 represses selection and expansion of oncogenic Hras transformed tumor initiating cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In many mouse models of skin cancer, only a few tumors typically form although many cells competent for tumorigenesis receive the same oncogenic mutations. These observations suggest a selection process for defining tumor initiating cells. Here we use quantitative mRNA- and miR-Seq to determine the impact of HRasG12V on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by HRasG12V. Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 with an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for HRas-initiated tumorigenesis. These targets include important effectors of the Ras pathway and essential genes required for cell division. Together, this study establishes a role for the loss of microRNA-203 in promoting selection and expansion of HRas mutated cells and identifies a mechanism through which microRNA-203 antagonizes HRas-mediated tumorigenesis.
Publication Title
MicroRNA-203 represses selection and expansion of oncogenic Hras transformed tumor initiating cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
Alzheimer's disease (AD) is characterized by massive neurodegeneration and multiple changes in cellular processes, including neurogenesis. Proteolytic processing of the amyloid precursor protein (APP) plays a central role in AD. Due to varying APP processing, several beta-amyloid peptides are generated. In contrast to the form with 40 amino acids, the variant with 42 amino acids is thought to be the pathogenic form triggering the pathophysiological cascade in AD. Here, we studied the transcriptomic response to increased or decreased Abeta42 levels generated in human neuroblastoma cells. Genome-wide expression profiles (Affymetrix)were used to analyze the cellular response to the changed Abeta42 and Abeta40-levels. <br></br><br></br>Human neuroblastoma cell line SH-SY5Y is a thrice cloned (SK-N-SH -> SH-SY -> SH-SY5 -> SH-SY5Y) subline of the neuroblastoma cell line SK-N-SH which was isolated and established in 1970. This cell line has 47 chromosomes. The cells possess a unique marker comprised of a chromosome 1 with a complex insertion of an additional copy of a 1q segment into the long arm, resulting in trisomy of 1q. The cell lines used in this study are SHSY5Y transfected with the constructs pCEP-C99I45F, pCEP-C99V50F, pCEP-C99 wildtype or mock transfected with an empty vector. Independent cell clones of each transfected line were used to provide biological replicates.<br></br> Overexpressed C99 I45F is intracellularly cleaved resulting in high Abeta42, but low Abeta40 levels.<br></br> Overexpressed C99V50F is intracellularly cleaved resulting in low Abeta42, but high Abeta40 levels.<br></br>Overexpressed C99 wildtype is intracellularly cleaved resulting in medium Abeta42 and Abeta40 levels<br></br>Mock is the SHSY5Y cell line transfected with the empty vector pCEP (Invitrogen) as a negative control
Publication Title
New Alzheimer amyloid beta responsive genes identified in human neuroblastoma cells by hierarchical clustering.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 1500
Description
In order to understand if early epigenetic mechanisms instruct the long-term behaviour of neural stem cells (NSCs) and their progeny, we examined the protein Uhrf1 as it is highly expressed in NSCs of the developing brain and rapidly downregulated upon differentiation. Conditional deletion of Uhrf1 in the developing cerebral cortex resulted in rather normal proliferation and neurogenesis but severe postnatal neurodegeneration. During development, deletion of Uhrf1 resulted in global DNA hypomethylation with a strong activation of the IAP family of endogenous retroviral elements, accompanied by an increase in hydroxy methyl cytosine. Downregulation of Tet enzymes rescued the IAP activation in Uhrf1 cKO cells, suggesting an antagonistic interplay between Uhrf1 and Tet on IAP regulation. As IAP upregulation persists into postnatal stages in the conditional Uhrf1 KO mice, our data show the lack of means to repress IAPs in differentiating neurons that normally never express Uhrf1. The high load of viral proteins and other transcriptional dysregulation ultimately lead to extensive postnatal neurodegeneration. Taken together, these data show that early developmental NSC factors can have long-term effects in neuronal differentiation and survival. Moreover, it highlights how specific the consequences of widespread changes in DNA methylation are for certain classes of retroviral elements. Overall design: Transcriptome analysis in control vs. Uhrf1-deficient brain
Publication Title
Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 1500
Description
In order to understand if early epigenetic mechanisms instruct the long-term behaviour of neural stem cells (NSCs) and their progeny, we examined the protein Uhrf1 as it is highly expressed in NSCs of the developing brain and rapidly downregulated upon differentiation. Conditional deletion of Uhrf1 in the developing cerebral cortex resulted in rather normal proliferation and neurogenesis but severe postnatal neurodegeneration. During development, deletion of Uhrf1 resulted in global DNA hypomethylation with a strong activation of the IAP family of endogenous retroviral elements, accompanied by an increase in hydroxy methyl cytosine. Downregulation of Tet enzymes rescued the IAP activation in Uhrf1 cKO cells, suggesting an antagonistic interplay between Uhrf1 and Tet on IAP regulation. As IAP upregulation persists into postnatal stages in the conditional Uhrf1 KO mice, our data show the lack of means to repress IAPs in differentiating neurons that normally never express Uhrf1. The high load of viral proteins and other transcriptional dysregulation ultimately lead to extensive postnatal neurodegeneration. Taken together, these data show that early developmental NSC factors can have long-term effects in neuronal differentiation and survival. Moreover, it highlights how specific the consequences of widespread changes in DNA methylation are for certain classes of retroviral elements. Overall design: Transcriptome analysis in control vs. Uhrf1-deficient brain
Publication Title
Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
- Illumina HiSeq 1000
Description
High throughput sequencing of poly-A RNA Overall design: Two-condition experiment: Control- and Chronophin shRNA (CIN/PDXP) in glioblastoma stem-like cells
Publication Title
Chronophin regulates active vitamin B6 levels and transcriptomic features of glioblastoma cell lines cultured under non-adherent, serum-free conditions.
Sample Metadata Fields
Disease, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Glioblastoma, the most aggressive and least treatable form of malignant glioma, is the most common human brain tumor. Although many regions of allelic loss occur in glioblastomas, relatively few tumor suppressor genes have been found mutated at such loci. To address the possibility that epigenetic alterations are an alternative means of glioblastoma gene inactivation, we coupled pharmacological manipulation of methylation with gene profiling to identify potential methylation-regulated, tumor-related genes. Triplicates of three short-term cultured glioblastomas were exposed to 5M 5-aza-dC for 96 hours followed by cRNA hybridization to an oligonucleotide microarray (Affymetrix U133A). We based candidate gene selection on bioinformatics, RT-PCR, bisulfite sequencing, methylation-specific PCR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Two genes identified in this manner, RUNX3 and Testin (TES), were subsequently shown to harbor frequent tumor-specific epigenetic alterations in primary glioblastomas. This overall approach therefore provides a powerful means to identify candidate tumor suppressor genes for subsequent evaluation and may lead to the identification of genes whose epigenetic dysregulation is integral to glioblastoma tumorigenesis.
Publication Title
Downregulation of RUNX3 and TES by hypermethylation in glioblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Goals of the study was to compare transcripional and phenotypic response of mouse intestinal organoid cultures to the PIK3CA(H1047R) and CTNNB1(stab) oncogenes. Overall design: Two biological replicates of organoids with transgenic tdTomato-Luciferase, tdTomato-PIK3CAH1047R, tdTomato-CTNNB1stab or td-Tomato-PIK3CAH1047R-CTNNB1stab were analysed by RNA-Seq By comparing 7-10 x 10E7 50bp paired end reads per library we identify transcriptional alterations in the intestinal epithelium following expression of each or both oncogenes,
Publication Title
Oncogenic β-catenin and PIK3CA instruct network states and cancer phenotypes in intestinal organoids.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
High-grade gliomas are amongst the most deadly human tumors. Treatment results are overall disappointing. Nevertheless, in several trials around 20% of patients respond to therapy. Diagnostic strategies to identify those patients that will ultimately profit from a specific targeted therapy are urgently needed. Gene expression profiling of untreated tumors is a well established approach for identifying biomarkers or diagnostic signatures. However, reliable signatures predicting treatment response in gliomas do not exist. Here we suggest a novel strategy for developing diagnostic signatures. We postulate that predictive gene expression patterns emerge only after tumor cells have been treated with the agent in vitro. Moreover, we postulate that enriching specimens for tumor initiating cells sharpens predictive expression patterns. Here, we report on the prediction of treatment response of cancer cells in vitro. As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC) before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated but not from untreated glioma cells allowed to predict therapy-induced impairment of proliferation of glioma cells in vitro. Prediction can be achieved with as little as 6 genes allowing for a straightforward translation into the clinic once the predictive power of the signature is shown also in vivo. Our strategy of using expression profiles from in vitro treated BTIC-enriched cultures opens new ways for trial design for patients with malignant gliomas.
Publication Title
Response-predictive gene expression profiling of glioma progenitor cells in vitro.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To investigate potential differences between strong and weak oscillators at the gene expression level we carried out a transcriptome analysis for each cell line. Our results indicate that phenotypic circadian clock differences are reflected by gene expression differences both in genes of the core network, but also in additional genes not directly associated with circadian clock functions.
Publication Title
Ras-mediated deregulation of the circadian clock in cancer.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples