Environmental enrichment has been shown to induce wholescale alterations to the gene expression profile of experimental animals
The impact of environmental enrichment on the murine inflammatory immune response.
Sex, Age
View SamplesAnalysis of gene expression in Mouse E14-TG2a.IV strain ES cells Overall design: Single end RNA-seq analysis of PolyA selected RNA from E14-TG2a.IV ES cells
Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment.
Specimen part, Subject
View SamplesThe human genome contains approximately 27,700 CpG islands (CGIs). Most are associated with promoters and their DNA is nearly always unmethylated. By contrast, CGIs lying within the bodies of genes usually become methylated during differentiation and development. CGIs also normally become methylated at X-inactivated and imprinted genes and abnormally methylated in genome rearrangements and in malignancy. In such circumstances, methylation of CGIs is often associated with RNA transcripts reading through these elements but the relationship of this RNA to methylation of CGIs is not clear. Here we investigated a previously described form of a-thalassemia caused by a genome rearrangement leading to abnormal transcription and DNA methylation of the CGI at the promoter of the a-globin gene. We show that transcription per se is responsible for DNMT3B-mediated methylation of the globin CGI, and that this is a general mechanism responsible for methylation of most intragenic CpG islands. Overall design: CapSeq was performed on day 7 in vitro differentiated EBs containing the human gene sequence of RHBDF1 with (RHBDF1+P; chr16:47,861-63,210, hg18) or without (RHBDF1-P; chr16:47,911-60,819, hg18) its promoter in the a recombination mediated cassette exchange (RMCE) system established within the mouse a-globin locus (Lynch et al., 2012, DOI: 10.1038/emboj.2011.399 ) to map transcription initiation sites within the transgene. Please note that the Cap-seq methods captures the 5' end of any short RNA that was Capped, capturing both coding and non-coding RNA.
DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease.
Specimen part, Cell line, Subject
View SamplesEvaluation of specific coordinated pattern of transcriptional events consistent with anti-myeloma activity of FK866 (chemical Nampt inhibitor)
Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition.
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View SamplesGene expression profiling leading to the identification of novel components in the EDS1/PAD4-regulated defence pathway
Salicylic acid-independent ENHANCED DISEASE SUSCEPTIBILITY1 signaling in Arabidopsis immunity and cell death is regulated by the monooxygenase FMO1 and the Nudix hydrolase NUDT7.
Age, Specimen part, Time
View SamplesLiposarcoma is the most common soft tissue sarcoma, accounting for about 20% of cases. Liposarcoma is classified into 5 histologic subtypes that fall into 3 biological groups characterized by specific genetic alterations. To identify genes that contribute to liposarcomagenesis and to better predict outcome for patients with the disease, we undertook expression profiling of liposarcoma. U133A expression profiling was performed on 140 primary liposarcoma samples, which were randomly split into training set (n=95) and test set (n=45). A multi-gene predictor for distant recurrence-free survival (DRFS) was developed using the supervised principal component method. Expression levels of the 588 genes in the predictor were used to calculate a risk score for each patient. In validation of the predictor in the test set, patients with low risk score had a 3-year DRFS of 83% vs. 45% for high risk score patients (P=0.001). The hazard ratio for high vs. low score, adjusted for histologic subtype, was 4.42 (95% confidence interval 1.26-15.55; P=0.021). The concordance probability for risk score was 0.732. Genes related to adipogenesis, DNA replication, mitosis, and spindle assembly checkpoint control were all highly represented in the multi-gene predictor. Three genes from the predictor, TOP2A, PTK7, and CHEK1, were found to be overexpressed in liposarcoma samples of all five subtypes and in liposarcoma cell lines. Knockdown of these genes in liposarcoma cell lines reduced proliferation and invasiveness and increased apoptosis. Thus, genes identified from this predictor appear to have roles in liposarcomagenesis and have promise as therapeutic targets. In addition, the multi-gene predictor will improve risk stratification for individual patients with liposarcoma.
Expression profiling of liposarcoma yields a multigene predictor of patient outcome and identifies genes that contribute to liposarcomagenesis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia.
Disease, Disease stage, Subject
View SamplesChronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by chromosomal aberrations of prognostic significance. Recent studies showed that gain of chromosome 2p is a recurrent lesion in CLL. We investigated the 2p gain and its relationship with prognostic biomarkers in a prospective series of 287 early-stage CLLs (Binet A). The 2p gain was detected by FISH in 17 patients (6%) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e. del(11)(q23) and del(17)(p13) (P=0.002) as well as unmutated (UM) status of IGHV (P<110-4) and CD38 (P<110-4) and ZAP-70 positive expression (P=0.003) were significantly more prevalent in 2p gain cases. Furthermore, 2p gained patients showed a significantly higher occurrence of stereotyped HCDR3 sequences compared to 2p normal CLLs (P=0.009). Among the stereotyped subsets, the incidence of subset #1 in 2p positive patients was significantly higher than that found in the remaining CLLs (P=0.031). Finally, gene expression profiling analysis identified a number of genes significantly upregulated in 2p gain CLLs. Among those located at 2p, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Our study indicates that 2p gain is a recurrent lesion in early CLL, correlated with the major biological and cytogenetic risk markers of the disease. Moreover, we provide insights to define novel candidate genes that may play additional pathogenetic roles in CLL.
Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia.
Disease, Disease stage, Subject
View SamplesThis experiment contains the transcriptomic dataset that constitutes part of an integrated transcriptomic and proteomic study monitoring the response of exponential phase E. coli O157:H7 Sakai cultures upon an abrupt downshift in temperature and water activity (from 35°C aw 0.993 to 14°C aw 0.967).
Physiological Response of Escherichia coli O157:H7 Sakai to Dynamic Changes in Temperature and Water Activity as Experienced during Carcass Chilling.
Time
View SamplesThe pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we demonstrate the variation of host gene expression which underlies the contrasting hepatic pathology observed between two inbred mouse strains following schistosome infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in BALB/c and CBA mice during an active Schistosoma japonicum infection. Here, we show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. Generally, up-regulated genes were largely associated with immune and inflammatory responses, antigen processing and cytokine/chemokine activity. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with significantly greater accumulation of neutrophils at granulomatous regions, compared to CBA mice. In contrast, up-regulated expression of eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the greater degree of liver damage in these mice. Genes involved in fibrosis showed similar levels of expression in both mouse strains. Genes associated with Th1 and Th2 responses showed no significant differences in expression between strains. These results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. Furthermore, this improved understanding of schistosome immunopathogenesis in the murine model will provide the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.
Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models.
Sex, Age, Specimen part, Time
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