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GSE57801
Mus musculus, Drosophila melanogaster
71 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 35 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Recent data suggests that common genetic risk for metabolic disorders such as obesity may be human-specific and exert effects through the central nervous system. To overcome the limitation of human tissue access for study, we have generated induced human pluripotent stem cell (hiPSC)- derived neuronal cultures which recapture many features of hypothalamic neurons within the arcuate nucleus. Here we have comprehensively characterized this model across development and benchmarked these neurons to in vivo events. We also demonstrate their utility in study of obesity risk variants. The dynamic transcriptome across neuronal maturation was examined using microarray and RNAseq methods at 9 time points. K-means clustering of the longitudinal data was conducted to identify co-regulation and miRNA control of biological processes. The transcriptomes were compared to those of 103 samples from 13 brain regions reported in the Genotype-Tissue Expression database (GTEx) using principal components analysis. Genes with proximity to body mass index (BMI)-associated genetic variants were mapped to the developmentally expressed genesets, and enrichment significance was assessed with Fishers exact test. The human neuronal cultures have a transcriptional and physiological profile of NPY/AgRP hypothalamic neurons. The neuronal transcriptomes were highly correlated with adult hypothalamus as compared to any other brain region from the GTEx. Also, roughly 25% of the transcripts showed changes in expression across maturation stages and potential co-regulation of biological processes that mirror neuronal development in vivo. These developmentally expressed genes were significantly enriched for genes in proximity to BMI-associated variants.
Publication Title
Molecular Profiling of Human Induced Pluripotent Stem Cell-Derived Hypothalamic Neurones Provides Developmental Insights into Genetic Loci for Body Weight Regulation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
EZH2 is frequently over-expressed in aggressive and metastatic solid tumors, including castration resistant prostate cancer (CRPC). We sought to determine EZH2-dependent gene expression programmes in prostate cancer progression, and found an intriguing functional switch of EZH2 from a repressor to an activator during CRPC development.
Publication Title
EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The highly aggressive muscle cancer alveolar rhabdomyosarcoma (ARMS) is one of the most common soft tissue sarcoma of childhood, yet the outcome for unresectable and metastatic disease is dismal and unchanged for nearly 3 decades. To better understand the pathogenesis of this disease and to facilitate novel preclinical approaches, we previously developed a conditional mouse model of ARMS by faithfully recapitulating the genetic mutations observed in the human disease, i.e. activation of Pax3:Fkhr fusion gene with either p53 or Cdkn2a inactivation. In this report we show that this model recapitulates the immunohistochemical profile and the rapid progression of the human disease. We demonstrate that Pax3:Fkhr expression increases during late preneoplasia, but that tumor cells undergoing metastasis are under apparent selection for Pax3:Fkhr expression. At a whole genome level, a cross-species gene set enrichment analysis and metagene projection study showed that our mouse model is most similar to human ARMS when compared to other pediatric cancers. We have defined an expression profile conserved between mouse and human ARMS as well as a Pax3:Fkhr signature, including the target gene, SKP2. We further identified 7 druggable kinases over-expressed across species. The data affirms the accuracy of this genetically engineered mouse model.
Publication Title
Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Arabidopsis thaliana
- 45 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The focus of this study was to identify changes in host gene expression induced by the transcription-dependent function of the viral AC2 protein, and induced by the interaction of AC2/C2 with SnRK1.2 (AtAKIN11).
Publication Title
Altered expression of Arabidopsis genes in response to a multifunctional geminivirus pathogenicity protein.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Rattus norvegicus
- 46 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Gene expression along the crypt-villus (C-V) axis was analyzed using cryostat sectioning to isolate fractions representing the crypts (bottom) and villus tops (top). These fractions were used for analyzing gene expression in iron replete Wistar rats (++), iron deficient Wistar rats (low iron), and in iron deficient Wistar rats fed iron for 3 and 6 days (iron-fed). Differences were observed between the crypts and villus tops in the expression of genes associated with Wnt and BNP signaling, cell proliferation and apoptosis, lipid and iron transport and metabolism. Gene expression in villus crypts and tops was also compared between Wistar and Belgrade rats (bb) and Belgrade rats fed iron (iron-fed) particularly as related to iron absorption and metabolism to define the affects of the mutation in DMT1 in the Belgrade rat on the expression of genes related to iron absorption and metabolism and the response to iron feeding.
Publication Title
Hypoxia-inducible factor-2α and iron absorptive gene expression in Belgrade rat intestine.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BRD4 Inhibition of spindle cell malignant peripheral nerve sheath tumor (sMPNST) tumor cells
Publication Title
BET bromodomain inhibition triggers apoptosis of NF1-associated malignant peripheral nerve sheath tumors through Bim induction.
Sample Metadata Fields
Specimen part, Treatment
View Samples