we performed genome-wide expression analyses for investigating novel genetic environmental changes.
Effect of adiponectin on kidney crystal formation in metabolic syndrome model mice via inhibition of inflammation and apoptosis.
Specimen part, Treatment
View SamplesWe re-analyzed gene expression in the primordial germ cell (PGC) specification pathway in vitro, by using previously deposited microarray data.
Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells.
Sex
View SamplesWe examined whether SATB1 functions as a global gene regulator in order to maintain the aggressive phenotype of the MDA-MB-231 cell line. We compared the gene expression profiles between control_shRNA-MDA-MB-231 cells, which express SATB1 at high levels, and SATB1_shRNA1-MDA-MB-231 in which the level of SATB1 was greatly downregulated by RNAi technology. This comparative studies were performed using two different platforms (Codelink and Affymetrix genechip) with two culture conditions either on plastic dish (2D) or on matrigel (3D) which allows cells to form a breast-like morphology only for non-aggressive cells.
SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis.
No sample metadata fields
View SamplesTraditional rice varieties found in India have many desirable characteristics. Amongst them, their differential responses to abiotic and biotic stresses are of great agricultural importance. Drought or osmotic stress is one of the major abiotic stresses afflicting crop plants in India. Indigenous varieties like Dagad deshi have been found to be drought resistant and, thereby, are being studied in great detail by plant breeders and biotechnologists alike. In this study, we have analyzed the transciptomes of two contrasting cultivars, i.e. Dagad deshi (tolerant) and IR20 (susceptible), under control and stress conditions to elucidate the differences in their responses to drought stress using Affymetrix microarray platform.
Reference genes for accurate gene expression analyses across different tissues, developmental stages and genotypes in rice for drought tolerance.
Specimen part, Time
View Sampleswe performed RNA sequencing analysis using 10 tissue samples from human prostate and evaluated efficiency and accuracy of eRNA on mRNA-seq data analysis. Overall design: We sequenced mRNAs from the 10 human tissue samples. After that, we identified mRNAs in these samples against known human genes.
eRNA: a graphic user interface-based tool optimized for large data analysis from high-throughput RNA sequencing.
No sample metadata fields
View SamplesChronic hepatitis C virus (HCV) infection is now routinely treated with interferon (IFN)-free regimens composed of directly acting antiviral (DAA) agents. Changes in hepatic and peripheral innate and adaptive immune function during DAA therapy associate with achieving a sustained virologic response (SVR). The present study explored the impact of cirrhosis on host endogenous interferon pathways during DAA therapy. mRNA and micro-RNA (miRNA) expression profiling was performed on paired pre- and end-of-treatment (EOT) liver biopsies from subjects treated with a 2 DAA regimen (sofosbuvir/ledipasvir [SOF/LDV]) for 12 weeks (n=4, 3 with cirrhosis) or a 3 DAA regimen (SOF/LDV with GS-9669 or GS-9451) for 6 weeks (n=6, 0 with cirrhosis). Nine of ten subjects achieved SVR, with one relapse in the GS-9669 treatment arm (ISHAK fibrosis 4). Hepatic interferon-stimulated gene expression was down-regulated in the liver of all subjects, with no observable impact of cirrhosis or duration of treatment. Hepatic down-regulation of all type-III IFNs was observed (IFNL1, IFNL2, IFNL3, IFNL4-G), while IFNA2 expression, undetectable in all subjects pre-treatment, was detected in 3 of 9 subjects at EOT (all 3 achieved SVR). Only the subject who relapsed had detectable IFNL4-G expression in EOT liver. No change in IFNB1, IFNG, or IFNA5 expression was observed, and expression of other type-I IFNs (IFNA1, IFNA4, IFNA5, IFNA6, IFNA8, IFNA16, IFNA17) was not detected pre- or post-treatment. While expression of multiple miRNAs changed in liver tissue over the course of treatment, most miRNAs previously associated with HCV replication, innate interferon signaling, and hepatic fibrosis did not change significantly. Conclusions: Changes in the host IFN-response during DAA therapy associate with favorable treatment outcome regardless of composition and duration of therapy or extent of hepatic fibrosis.
Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis.
No sample metadata fields
View SamplesEndothelial cell activation and dysfunction underlie many vascular disorders, including atherosclerosis and inflammation. Here, we show that interleukin (IL)-4 markedly induced vascular cell adhesion molecule (VCAM)-1, both in cultured endothelial cells and in the intact endothelium in mice. Combined treatment with IL-4 and tumor necrosis factor (TNF)- alpha resulted in further, sustained induction of VCAM-1 expression. IL-4-mediated induction of VCAM-1 and secondary monocyte adhesion was predominantly regulated by the transcription factor, STAT6. Genome-wide survey of IL-4-mediated STAT6 binding from sequential chromatin-immunoprecipitation with deep-sequencing (ChIP-seq) in endothelial cells revealed regions of transient and sustained transcription factor binding. By combining DNA microarrays and ChIP-seq at the same time points, the majority of IL-4-responsive genes were shown to be STAT6-dependent and associated with direct STAT6 binding to their promoter. IL-4-mediated stable binding of STAT6 led to sustained target gene expression. Moreover, our strategy led to the identification of a novel functionally important STAT6 binding site within -16 kb upstream of the VCAM-1 gene. Taken together, these findings support a critical role for STAT6 in mediating IL-4 signal transduction in endothelial cells. Identification of a novel IL-4-mediated VCAM-1 enhancer may provide a foundation for targeted therapy in vascular disease (ChIP-seq data not submitted to GEO).
Genome-wide approaches reveal functional interleukin-4-inducible STAT6 binding to the vascular cell adhesion molecule 1 promoter.
Treatment
View SamplesLineage plasticity is a major mechanism driving prostate cancer progression and antiandrogen therapy resistance. Deletions or mutations in phosphatase and tensin homolog (PTEN) and TP53 tumor suppressor genes have been linked to lineage plasticity in prostate cancer. Fusion-driven overexpression of the E-twenty-six transformation specific (ETS)-related gene (ERG), encoding an oncogenic transcription factor, is observed in approximately 50% of all prostate cancers, yet its role in prostate cell lineage determination remains elusive. Here we demonstrate that transgenic expression of prostate cancer-associated ERG blocks Pten and Trp53 mutation-induced decreased expression of Ar and its downstream target genes and loss of luminal epithelial cell identity in the mouse prostate. Integrative analyses of ERG chromatin-immunoprecipitation sequencing (ChIP-seq) and transcriptome data show that ERG suppresses expression of a subset of cell cycle-promoting genes and RB phosphorylation, which in turn causes repression of E2F1-mediated expression of non-epithelial lineage genes. Xenograft studies show that PTEN/TP53 double mutated prostate tumors are responsive to the cyclin-dependent kinase 4 or 6 (CDK4/6) inhibitor palbociclib, but resistant to the AR inhibitor enzalutamide, while ERG/PTEN/TP53 triple-mutated prostate tumors behave completely opposite. Our studies identify ERG and the repressed cell cycle gene signature as intrinsic inhibitors of PTEN/TP53 double mutation-elicited lineage plasticity in prostate cancer. Our findings also suggest that ERG fusion can be utilized as a biomarker to guide the treatment of PTEN/TP53-mutated, RB1-intact prostate cancer with either antiandrogen or anti-CDK4/6 therapies. Overall design: Prostate tissue from mice with 1) prostate specific PTEN deletion, p53 R172H mutation with loss of heterozygosity, or 2) prostate specific PTEN deletion, p53 R172H mutation with loss of heterozygosity and transgenic ERG expression were harvested at 4-5 months. RNA was isolated from tissue and RNA-seq experiments were then performed for both genotype samples in triplicates. Differentially expressed genes were identified by comparing genotype #1 and genotype #2.
<i>TMPRSS2-ERG</i> Controls Luminal Epithelial Lineage and Antiandrogen Sensitivity in <i>PTEN</i> and <i>TP53</i>-Mutated Prostate Cancer.
Specimen part, Subject
View SamplesExosomes, endosome-derived membrane microvesicles, contain a specific set of RNA transcripts that are involved in cell-cell communication and hold a great potential as disease biomarkers. To systemically characterize exosomal RNA profiles, we performed RNA sequencing analysis using three human plasma samples and evaluated efficacies of small RNA library preparation protocols from 3 manufacturers. Overall design: We tested the six samples (A1 and A2, B1 and B2, C1 and C2) using two small RNA library preparation kits: NEBNext Multiplex Small RNA library Prep Set from New England Biolab (NEB) and NEXTflex Small RNA Sequencing Kit from Bioo Scientific (BS). We also tested Illumina’s TrueSeq Small RNA Sample Preparation Kit (ILMN) in sample A1 and A2. Together, we tested these plasma samples by sequencing 14 indexed libraries. This study allowed direct comparison of current small RNA library preparation protocols and identified the most suitable strategy for future exosomal RNA sequencing analysis.
Characterization of human plasma-derived exosomal RNAs by deep sequencing.
Specimen part
View SamplesMutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin null mouse model exhibited increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divided significantly faster when compared with wild type cells, with suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors, and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in brain tumor patients.
Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival.
Cell line, Treatment
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