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GSE19197
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hypoxia is an important condition in the tumor cell microenvironment and approximately 1-1.5% of the genome is transcriptionally responsive to hypoxia with hypoxia-inducible factor-1 (HIF-1) as a major mediator of transcriptional activation. Tumor hypoxia is associated with a more aggressive phenotype of many cancers in adults, but data on pediatric tumors are scarce. By immunohistochemical analysis, HIF-1 expression was readily detectable in 18/28 primary Ewings sarcoma family tumors (ESFT), a group of highly malignant bone-associated tumors in children and young adults, which encouraged us to study the effect of hypoxia on ESFT cell lines in vitro.
Publication Title
Hypoxia modulates EWS-FLI1 transcriptional signature and enhances the malignant properties of Ewing's sarcoma cells in vitro.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Ewing Tumors (ET) are highly malignant tumors, localized in bone or soft tissue and are molecularly defined by ews/ets translocations. We identified histone methyl-transferase Enhancer of Zeste, Drosophila, Homolog 2 (EZH2) to be increased in ET. EZH2s suppressive activity maintains stemness in normal and malignant cells. Here we found EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in ET and mesenchymal stem cells. Downregulation of EZH2 by RNA interference in ET suppressed oncogenic transformation by inhibiting clonogenicity in vitro. Similarly, tumor development and metastasis in immunodeficient Rag2-/-C-/- mice was suppressed. EZH2-mediated gene silencing was shown to be dependent on histone deacetylase (HDAC) activity. Subsequent microarray analysis of EZH2 knock down, HDAC-inhibitor treatment and confirmation in independent assays revealed an undifferentiated phenotype maintained by EZH2 in ET. Downregulation of EZH2 decreased histone H3 lysine 27 trimethylation (H3K27me3) at target loci. EZH2 regulated stemness genes such as nerve growth factor receptor (NGFR) as well as genes involved in neuroectodermal differentiation (EMP1, EPHB2, GFAP, GAP43). These data suggest that EZH2 might play a central role in Ewing Tumor pathology shaping the oncogenicity and stem cell phenotype of this tumor presumably by epigenetic regulation.
Publication Title
EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
IlluminaHiSeq2500
Description
This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. Overall design: Determine changes in gene expression levels between WT and DAXX K/D prostate cancer cells by RNA-Seq (PC3 Cells).
Publication Title
The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Regulatory T (Treg) cells play an indispensable role in immune homeostasis. The development and function of Tregs are dependent on transcriptional factor Foxp3, but how constant expression of Foxp3 is maintained in Tregs is not clear. Here we show that ablation of the conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus in mice led to spontaneous lymphoproliferative disease and exacerbation of experimental autoimmune encephalomyelitis (EAE). CNS2 is required for activated Treg cells to maintain elevated Foxp3 expression, which is critical for their suppressor function and lineage stability. Mechanistically, upon TCR stimulation, NFAT binds to both CNS2 and Foxp3 promoter and mediates the interaction between CNS2 and Foxp3 promoter. Our findings demonstrated an essential role for CNS2 in maintaining the stability and function of activated Treg cells and identified NFAT as a key mediator of its function. Overall design: Gene expression was profiled in T regulatory cells (Treg) in WT and CNS2 knockout mice. CNS2 knockout mice lack a conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus. Treg cells were further sorted into Foxp3-high and Foxp3-low populations based on the expression level of Foxp3. mRNA was profiled using RNA-Seq (unstranded, polyA+, SE100) in replicate for each condition
Publication Title
Function of a Foxp3 cis-element in protecting regulatory T cell identity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) mice exhibit a large difference in a number of alcohol and drug related behaviors. This study examined the expression levels of transcripts in these strains in the cerebellum, which is a major target of ethanols actions in the CNS, in order to find differentially expressed candidate genes for these phenotypes. Cerebellum was specifically chosen due to the fact that Purkinje cell sensitivity to ethanol in these strains is highly correlated to "sleep time", the measure of ethanol sensitivity used with these strains. Naive mice were used because differences in sensitivity are observed upon initial exposure to ethanol.
Publication Title
Expression profiling identifies novel candidate genes for ethanol sensitivity QTLs.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 15 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The possible benefits of selenium (Se) supplementation are currently under investigation for prevention of certain cancers and treatment of neurological disorders. Little is known concerning the response of the brain to increased dietary Se under conditions of Se sufficiency, despite the majority of Se supplementation trials occurring in healthy subjects considered Se sufficient. We evaluated the transcriptional response of the zebrafish (Danio rerio) brain to supplementation with nutritionally relevant levels of dietary Se (sodium selenite) during conditions of assumed Se sufficiency.
Publication Title
Sex-specific transcriptional responses of the zebrafish (Danio rerio) brain selenoproteome to acute sodium selenite supplementation.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Arabidopsis MPK4 is involved in the control of antagonism between salicylic acid (SA) and ethylene (ET)/jasmonic acid (JA) pathways in the plant innate immune system as a repressor of the SA pathway, but an activator of the ET/JA pathway. Here we and use comparative microarray analysis of ctr1, ctr1/mpk4, mpk4 and wild type to show that MPK4 is required for only a narrow subset of ET regulated genes.
Publication Title
Arabidopsis systemic immunity uses conserved defense signaling pathways and is mediated by jasmonates.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Stable knockdown of NET1, a RhoGEF, was achieved in AGS Gastric Cancer cells. This gene is known to be overexpressed in the disease.
Publication Title
A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: To identify transcriptional changes by RNA-seq in tumor samples, before bevacizumab combination treatment and after bevacizumab combination treatment in both responding and non-responding recurrent glioblastoma patients Overall design: Three comparison analyses were further performed: 1.) Paired analysis of pre- and post-treated samples from responding patients; 2.) Comparison of pre-treated samples of responders vs. non-responders; 3.) Paired analysis of pre- and post-treated samples from non-responding patients The sample ''characteristics: batch'' represents a combination of the RNA-extraction date and the library-preparation date for each sample.
Publication Title
Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients.
Sample Metadata Fields
Sex, Disease, Disease stage, Subject, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from 18-month-old Ahr-knockout and wild-type mice. HSC from aged AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC.
Publication Title
Conditional deletion of Ahr alters gene expression profiles in hematopoietic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples