Traditional 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 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.
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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.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Molecular classification of mature aggressive B-cell lymphoma using digital multiplexed gene expression on formalin-fixed paraffin-embedded biopsy specimens.
Sex, Age, Specimen part, Disease
View SamplesThe most frequent mature aggressive B-cell lymphomas are diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Patients suffering from molecularly defined BL (mBL) but treated with a regimen developed for DLBCL show an unfavorable outcome compared to mBL treated with chemotherapy regimens for BL. Distinguishing BL from DLBCL by conventional histopathology is challenging in lymphomas that have features common to both diseases (aggressive B-cell lymphoma unclassifiable with features of DLBCL and BL [intermediates]). Moreover, DLBCL are a heterogeneous group of lymphomas comprising distinct molecular subtypes: the activated B-cell (ABC)-like, the germinal center B-cell-like (GCB) and the unclassifyable subtype as defined by gene expression profiling (GEP). Attempts to replace GEP with techniques applicable to formalin-fixed paraffin-embedded (FFPE) tissue led to algorithms for immunohistochemical stainings (IHS). Disappointingly, the algorithms yielded conflicting results with respect to their prognostic potential, raising concerns about their validity. Furthermore, IHS algorithms did not provide a fully resolved classification: They did not identify mBL; nor did they separate ABC from unclassified DLBCL.
Molecular classification of mature aggressive B-cell lymphoma using digital multiplexed gene expression on formalin-fixed paraffin-embedded biopsy specimens.
Sex, Age, Specimen part
View SamplesThe replication of a genomic region during S-phase can be highly dynamic between cell types that differ in transcriptome and epigenome. Replication timing has been positively correlated with several histone modifications that occur at active genes, while repressive histone modifications mark late replicating regions. This raises the question if chromatin modulates the initiating events of replication. To gain insights into this question we have studied the function of heterochromatin protein 1 (HP1), a reader of to the repressive histone lysine 9 methylation of H3, in genome-wide organization of replication. Cells with reduced levels of HP1 show an advanced replication timing of centromeric repeats in agreement with the model that repressive chromatin mediates the very late replication of large clusters of constitutive heterochromatin. Surprisingly however regions with high levels of interspersed repeats on the chromosomal arms in particular on chromosome 4 and in pericentromeric regions of chromosome 2 behave differently. Here loss of HP1 results in delayed replication timing. The fact that these regions are bound by HP1 suggests a direct effect. Thus while HP1 mediates very late replication of centromeric DNA it is also required for early replication of autosomal regions with high levels of repeats. This observation of opposing functions of HP1 suggests a model where repeat inactivation on autosomes is required for proper activation of origins of replication that fire early, while HP1 mediated repression at constitutive heterochromatin is required to ensure replication of centromeric repeats at the end of S phase.
Heterochromatin protein 1 (HP1) modulates replication timing of the Drosophila genome.
Sex, Specimen part
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 SamplesDuplication of eukaryotic genomes during S phase is coordinated in space and time. In order to identify zones of initiation and cell-type as well as gender-specific plasticity of DNA replication, we profiled replication timing, histone acetylation and transcription throughout the Drosophila genome. We observed two waves of replication initiation with many distinct zones firing in early and multiple, less defined peaks at the end of S phase, suggesting that initiation becomes more promiscuous at the end of S phase. A comparison of different cell types revealed widespread plasticity of replication timing on autosomes. Most occur in large regions but only half coincide with local differences in transcription. In contrast to confined autosomal differences, a global shift in replication timing occurs throughout the single male X chromosome. Unlike in females, the dosage compensated X chromosome replicates almost exclusively early. This difference occurs at sites which are not transcriptionally hyperactivated, but show increased acetylation of lysine 16 of histone H4. This suggests a transcription-independent, yet chromosome-wide process related to chromatin. Importantly, H4K16ac is also enriched at initiation zones as well as early replicating regions on autosomes during S phase. Together, our data reveal novel organizational principles of DNA replication of the Drosophila genome and imply chromatin structure as a determinant of replication timing locally and chromosome-wide.
Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome.
Sex
View SamplesChronic infection with the bacterial pathogen Helicobacter pylori is a risk factor for the development of gastric cancer, yet remains asymptomatic in a majority of individuals. We report here that the C57Bl6 mouse model of experimental infection with the closely related H. felis recapitulates this wide range in host susceptibility. A majority of infected mice develop premalignant lesions such as gastric atrophy, compensatory epithelial hyperplasia and intestinal metaplasia, whereas a minority is completely protected from preneoplasia. Protection is associated with the failure to mount an IFN-gamma response to the infection and an associated high Helicobacter burden. We demonstrate that IFN-gamma is essential for clearance of Helicobacter, but also mediates the formation of preneoplastic lesions. We further provide evidence that IFN-gamma triggers a specific transcriptional program in murine gastric epithelial cells in vitro and in vivo, and induces their preferential transformation to the hyperplastic phenotype. In summary, our data suggest a dual role for IFN-gamma in Helicobacter pathogenesis that could provide an explanation for the differential susceptibility to H. pylori-induced gastric pathology in the human population.
The CD4+ T cell-mediated IFN-gamma response to Helicobacter infection is essential for clearance and determines gastric cancer risk.
Treatment
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