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GSE65496
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Developmental checkpoints in stem/progenitor cells are critical to the determination, commitment and differentiation into distinct lineages. Cancer cells often retain expression of lineage-specific checkpoint proteins, but their potential impact in cancer remains elusive. T lymphocytes mature in the thymus following a highly orchestrated developmental process that entails the successive rearrangements and expression of T-cell receptor (TCR) genes. Low affinity recognition of self-peptide/MHC complexes (self-pMHC) presented by thymic epithelial cells by the TCR of CD4+CD8+ (DP) cortical thymocytes transduces positive selection signals that ultimately shape the developing T cell repertoire. DP thymocytes not receiving these signals die by lack of stimulation whereas those that recognize self-pMHC with high affinity undergo TCR-mediated apoptosis and negative selection. In T-cell acute lymphoblastic leukaemia (T-ALL), leukaemic transformation of maturating thymocytes results from the acquisition of multiple genetic and epigenetic alterations in oncogenes and tumour suppressor genes, that disrupt the normal regulatory circuits and drive clonal expansion of differentiation-arrested lymphoblasts. We show here that TCR triggering by negatively-selecting self-pMHC prevented T-ALL development and leukaemia maintenance in mice. Induction of TCR signalling by high affinity self-pMHC or treatment with monoclonal antibodies to the CD3 signalling chain (anti-CD3) caused massive leukaemic cell death and a gene expression program resembling that of thymocyte negative selection. Importantly, anti-CD3 treatment hampered leukaemogenesis in mice transplanted with either mouse or patient-derived T-ALLs. These data provide a rationale for targeted therapy based on anti-CD3 treatment of T-ALL patients and demonstrate that endogenous developmental checkpoint proteins are amenable to therapeutic intervention in cancer cells.
Publication Title
Triggering the TCR Developmental Checkpoint Activates a Therapeutically Targetable Tumor Suppressive Pathway in T-cell Leukemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
PI3K (phosphoinositide 3-kinase)/AKT and RAS/MAPK (mitogen-activated protein kinase) pathway coactivation in the prostate epithelium promotes both epithelial–mesenchymal transition (EMT) and metastatic castration-resistant prostate cancer (mCRPC), which is currently incurable. To study the dynamic regulation of the EMT process, we developed novel genetically defined cellular and in vivo model systems from which epithelial, EMT and mesenchymal-like tumor cells with Pten deletion and Kras activation can be isolated. When cultured individually, each population has the capacity to regenerate all three tumor cell populations, indicative of epithelial–mesenchymal plasticity. Despite harboring the same genetic alterations, mesenchymal-like tumor cells are resistant to PI3K and MAPK pathway inhibitors, suggesting that epigenetic mechanisms may regulate the EMT process, as well as dictate the heterogeneous responses of cancer cells to therapy. Among differentially expressed epigenetic regulators, the chromatin remodeling protein HMGA2 is significantly upregulated in EMT and mesenchymal-like tumors cells, as well as in human mCRPC. Knockdown of HMGA2, or suppressing HMGA2 expression with the histone deacetylase inhibitor LBH589, inhibits epithelial–mesenchymal plasticity and stemness activities in vitro and markedly reduces tumor growth and metastasis in vivo through successful targeting of EMT and mesenchymal-like tumor cells. Importantly, LBH589 treatment in combination with castration prevents mCRPC development and significantly prolongs survival following castration by enhancing p53 and androgen receptor acetylation and in turn sensitizing castration-resistant mesenchymal-like tumor cells to androgen deprivation therapy. Taken together, these findings demonstrate that cellular plasticity is regulated epigenetically, and that mesenchymal-like tumor cell populations in mCRPC that are resistant to conventional and targeted therapies can be effectively treated with the epigenetic inhibitor LBH589. Overall design: RNA was extracted from pooled Epithelial, EMT and Mesenchymal-like tumor cells isolated by FACS sorting CD45-CD31-Ter119-EpCAM+GFP-, CD45-CD31-Ter119-EpCAM+GFP+, and CD45-CD31-Ter119-EpCAM-GFP+ cells, respectively, from the prostates of 10-12 week old Pb-Cre+/-;PtenL/L;KrasG12D/+;Vim-GFP (CPKV) mice (n=17) and separated into two technical replicates. Paired-end sequencing data with read lengths of 100 bp were generated using the Illumina HiSeq2000 system.
Publication Title
HDAC inhibition impedes epithelial-mesenchymal plasticity and suppresses metastatic, castration-resistant prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 114 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rationale: Despite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm on the immune system. Few studies assessed hydrocortisone impact on the transcriptional response in shock, and we are lacking data in burns. Objectives: To assess the hydrocortisone-induced transcriptional modulation in severe burn shock, particularly on the immune response. Methods: We collected whole blood samples (n= 117) during a randomized controlled trial assessing the efficacy of hydrocortisone administration on burn shock. Using whole genome microarrays, we first compared burn patients from the placebo group (n=15) to healthy volunteers (n=13) to describe the transcriptional modulation induced by burn shock over the first week. Then we compared burn patients randomized for either hydrocortisone administration (n=15) or placebo (n=15) to assess hydrocortisone-induced modulation. Measurements and Main Results: Study groups were similar in terms of severity and major outcomes, but shock duration (significantly reduced in the hydrocortisone group). Many genes (n=2250) were differentially expressed between burn patients and healthy volunteers, with 85% of them exhibiting a profound and persistent modulation over seven days. Interestingly, we showed that hydrocortisone enhanced the shock-associated repression of adaptive, but also innate immunity. Conclusions: We found that the initial host response to burn shock encompasses a wide and persistent modulation of gene expression, with profound modulation of pathways associated with metabolism and immunity. Importantly, hydrocortisone administration may worsen the immunosuppression associated with severe injury. These data should be taken into account in the risk ratio of hydrocortisone administration in patients with inflammatory shock.
Publication Title
Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment, Subject
View Samples- Triticum aestivum
- 15 Downloadable Samples
- Affymetrix Wheat Genome Array (wheat)
Description
Alloplasmic lines provide a unique tool to study the nucleo-cytoplasmic interactions. Alloplasmic lines T183 and T195 were developed through the introgression of the cytoplasm from Aegilops uniaristata (T183) and Aegilops squarrosa (T195) in the nuclear background of Triticum aestivum cv. Chris. Alloplasmic line TH237 was produced introgressing the Hordeum chilense accession H7 cytoplasm into the nuclear background of Triticum aestivum accession T20. Fifty seeds for each sample in pots of 11 cm diameter and grown in controlled conditions under 600E m-2 s1 high light intensity in a daily regime of 12 h light at 22C and 12 h darkness at 15C. Plants were bulked from each pot and three biological replicate used for the transcriptomics Fully expanded second leaves were collected two weeks from sowing in the middle of the light period and used for transcriptomic analysis.
Publication Title
Cytoplasmic genome substitution in wheat affects the nuclear-cytoplasmic cross-talk leading to transcript and metabolite alterations.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Loss of the tumor suppressor CHD5 frequently occurs during neuroblastoma progression.
Publication Title
The chromatin remodeling factor CHD5 is a transcriptional repressor of WEE1.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HiSeq 2500
Description
Using RNA-sequencing analysis of peripheral blood cells from 11 cervical cancer patients, 21 cervical intraepithelial neoplasia patients and 19 healthy controls, we identified a group of differentially expressed genes. A real time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to the validation of candidate markers in the blood of 115 patients and 46 healthy controls. The results suggest that a six-gene predictor set (GZMB, NDUFA1, GPR84, NUAK1, AGAP1 and CIR1) can be used as candidate genes for the detection of cervical cancer. Overall design: The mRNA profiles of peripheral blood cells from 11 cervical cancer patients, 21 cervical intraepithelial neoplasia patients and 19 healthy control participants were sequenced using Illumina 2500.
Publication Title
Discovery of candidate gene expression signatures in peripheral blood for the screening of cervical cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
microRNA-155 acts as an oncogenic miRNA in B-cell lymphoproliferative disorders including Waldenstrom Macroglobulinemia (WM) and Chronic Lymphocytic Leukemia (CLL).
Publication Title
LNA-mediated anti-miR-155 silencing in low-grade B-cell lymphomas.
Sample Metadata Fields
Cell line
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA-Seq analysis was performed to assess how a glucose-supplemented diet and/or a hyl-2 mutation altered the transcriptome. Comparison analysis of transcripts associated with anoxia sensitive animals (hyl-2(tm2331) mutation or a glucose diet) revealed 199 common transcripts encoded by genes with known or predicted functions involving innate immunity, cuticle function (collagens) or xenobiotic and endobiotic phase I and II detoxification system. Overall design: mRNA profiles of OP50-fed C. elegans, glucose-fed C. elegans (N2 strain), OP50-fed C. elegans altered in ceramide metabolism (due to a hyl-2(tm2031) mutation), and glucose-fed C. elegans altered in ceramide metabolism were generated by RNA-Seq, in triplicate, using an Illumina HiSeq2000. Transcriptome data were then used for a comprehensive quantitative analysis of differential gene regulation in hyl-2(tm2031) and glucose-fed C. elegans.
Publication Title
Glucose or Altered Ceramide Biosynthesis Mediate Oxygen Deprivation Sensitivity Through Novel Pathways Revealed by Transcriptome Analysis in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: We aimed to identify ZAT18 target genes and characterize functions of ZAT18 during plant drought tolerance Methods: A total amount of 3 µg RNA was used for generation of sequencing libraries using NEBNext® Ultra™ RNA Library Prep Kit for Illumina® (NEB, USA) following manufacturer’s recommendations and index codes were added to attribute sequences to each sample. After cluster generation, the library preparations were sequenced on an Illumina Hiseq platform and 125 bp/150 bp paired-end reads were generated. Clean reads were obtained by removing low quality reads, reads containing adapter and ploy-N from raw data. At the same time, Q20, Q30 and GC content the clean data were calculated. Index of the Arabidopsis genome was built using Bowtie v2.2.3 and paired-end clean reads were aligned to the reference genome using TopHat v2.0.12. HTSeq v0.6.1 was used to count the reads numbers mapped to each gene. And then FPKM (Fragments Per Kilobase of transcript sequence per Millions base pairs sequenced) of each gene was calculated based on the length of the gene and reads count mapped to this gene. Differential expression analysis of drought stress versus control condition was performed using the DESeq R package (1.18.0). Results:In total, eight samples with two biological replicates per genotype/treatment combination were used for RNA sequencing analysis. At least 2 G clean bases were generated for each sample. Comparative analysis revealed that 1777 genes were transcriptionally affected by AtZAT18 trasngene or drought treatment. The results showed that overexpression of AtZAT18 modulated expression level changes of 423 and 561genes under control and drought stress conditions, respectively. Drought stress treatment changed expression of 971 genes with 768 up-regulated and 203 down-regulated. Overall design: In this study, wild type Arabidopsis and two lines of AtZAT18 transgenic plants were grown in moist soil for 7 days. Drought stress was imposed by withholding water for 10 days. The rosette leaves of control and drought treated Col-0 and AtZAT18 transgenic plants were then collected for RAN isolation. AtZAT18 transgenic plant and Col WT were used by deep sequencing, in duplicate
Publication Title
The Arabidopsis Cys2/His2 zinc finger transcription factor ZAT18 is a positive regulator of plant tolerance to drought stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Our work demonstrated that miR-183 cluster regulates IFN production and signaling
Publication Title
A conserved miRNA-183 cluster regulates the innate antiviral response.
Sample Metadata Fields
Cell line
View Samples