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GSE41910
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Few studies have investigated heterogeneity of selection response in replicate lines subjected to equivalent selection. We developed 4 replicate lines of mice based on high levels of voluntary wheel running (high runner or HR lines) while also maintaining 4 non-selected control lines. This led to the unexpected discovery of the HR mini-muscle (HRmini) phenotype, recognized by a 50% reduction in hindlimb muscle mass, which became fixed in 1 of the 4 HR selected lines.
Publication Title
Gene expression profiling of gastrocnemius of "minimuscle" mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Quantitative Analysis of cortical transcriptomes through Next Generation Sequencing (RNA-Seq) from wild-type mice, wild-type mice treated with IL1b (200 ng/mouse, 14h), IL-1R8-/- mice and IL-1R8-/- mice treated with IL1b antagonist Anakinra (25 mg/kg per day for 3 consecutive days, i.p. administration). mRNA profiles of cortical tissue from adult wild-type mice, wild-type mice treated with IL1b (200 ng/kg, 14h), IL-1R8-/- mice (Garlanda et al., 2004), and IL-1R8-/- mice treated with Anakinra (25 mg/kg per day for 3 consecutive days, i.p. administration) were generated by next-generation sequencing (RNA-seq) using Illumina HiSeq 2500 apparatus in paired-end configuration (2x125bp). Each condition was assessed in triplicate (12 mRNA-seq libraries) and, to reduce biological variability, each mRNA library was generated from pooled total RNA isolated from cortical tissue of 3 individual mice. In total, 9 mice per condition were used. Libraries were stranded and multiplexed. To increase sequencing depth, libraries were sequenced in two different lanes. All the libraries were loaded in each of the two lanes. Quality control of the raw data was performed with FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). Libraries were trimmed for adapter removal using Trimmomatic (Bolger et al., 2014) and mapped to reference genome (Ensembl GRCm38) using TopHat2 (Kim et al., 2013) and Bowtie2 (Langmead et al., 2009). Library sizes of primary mapped reads were between 70 and 96 million reads. Samtools was used to manipulate BAM files (Li et al., 2009). For calling of differentially expressed genes (DEG), mapped reads were counted with HTSeq v0.6.1 (Anders et al., 2014) and count tables were analysed using DeSeq2 v1.10.1 R-package (Love et al., 2014) with a design of one factor with four levels (“wild-type”, “wild-type + IL1?”, “IL-1R8-/-”, “IL-1R8-/- + Anakinra"), and differences between groups were tested using contrasts for wild-type + IL1b versus wild-type; IL-1R8-/- versus wild-type; IL-1R8-/- + Kineret versus wild-type. For consideration of differentially regulated genes between conditions, we used adjusted p-value < 0.1 or adjusted p-value < 0.05 as indicated in the manuscript. Overall design: mRNA profiles in adult mouse cerebral cortex of wild type (WT), WT mice treated with IL1b (200 ng/kg, 14h), IL-1R8-/- mice, and IL-1R8-/- mice treated with IL1b antagonist Anakinra (25 mg/kg per day for 3 consecutive days, i.p. administration) were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500. Each sample was prepared by pooling cortical tissue from 3 idenpendent mice.
Publication Title
Lack of IL-1R8 in neurons causes hyperactivation of IL-1 receptor pathway and induces MECP2-dependent synaptic defects.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The complete specrtum of genes that are subject to regulation by Hnf1b in mouse kidney cells is not known.
Publication Title
Transcription Factor Hepatocyte Nuclear Factor-1β Regulates Renal Cholesterol Metabolism.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- NextSeq 500
Description
Neutrophils represent a fundamental mechanism of antimicrobial resistance and inflammation 1. Moreover, neutrophils have emerged as important players in the activation, orchestration and regulation of adaptive immune responses2,3. Neutrophils are a component of the tumor microenvironment (TME) and have been prevalently shown to promote progression 4-6. On the other hand, unleashed neutrophilic effectors have also been reported to mediate anti-cancer resistance7-11. Antibody-mediated depletion used to investigate the role of neutrophils in tumor progression suffers from limitations, including duration, specificity and perturbation of the system12. We therefore used a genetic approach to investigate the role of neutrophils in primary 3-methylcholanthrene (3-MCA)-induced sarcomagenesis. Neutrophils were found to play an essential role in resistance against primary carcinogenesis by driving an interferon-? dependent type 1 immune response. Neutrophil-dependent macrophage production of IL-12p70 led to type 1 polarization of CD4- CD8- unconventional aß T cells (UTCaß) in the TME. Single cell RNAseq analysis and in vivo evidence from two preclinical sarcoma models highlight the antitumor potential of a UTCaß subset. In the TCGA cohort of human undifferentiated pleomorphic sarcomas (UPS), unlike other sarcomas, granulocyte-colony stimulating factor receptor (CSF3R) expression and a neutrophil signature were associated with better outcome and with a type 1 immune response. The positive association between high neutrophil infiltration and improved clinical outcome was confirmed in an independent UPS cohort by immunohistochemistry. Thus, neutrophils, by driving a type 1 immune response and polarization of UTCaß, mediate resistance against murine and human sarcomas. Overall design: two experimental conditions, two biological replicates for each condition
Publication Title
Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
Members of the JNK pathway have been found to be mutated in human breast cancer. Mouse studies examining JNK loss in different tissues have demonstrated that the JNK pathway can play a role in cancer. Using and autochthonous mouse model, we found that JNK deficiency on a p53-null background resulted in more rapid tumor onset. To learn more about these tumors we generated cells lines and performed various in vitro assays, as well as RNAseq in hope of finding differentially expressed genes that may explain the differences we observed in vivo. Overall design: Tumors were harvested from mice and cells lines were established from them. RNA was isolated from established tumor cell lines.
Publication Title
The cJUN NH<sub>2</sub>-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 109 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blind, placebo controlled study in current heavy smokers to compare modulating effects of intermittent versus continuous low dose ASA on gene signatures of smoking and lung cancer from nasal brushings. Fifty-four participants were randomized to intermittent ASA (ASA 81 mg daily for one week alternating with placebo daily for one week) or continuous ASA (81 mg daily) for 12 weeks. The primary endpoint was modulation of a smoking gene signature in nasal brushings. Other [JB1] endpoints included modulation of nasal and bronchial gene signatures for smoking, lung cancer and chronic obstructive pulmonary disease (COPD) and changes in cyclooxygenase (COX)- and 5-lipoxygenase (LOX)-mediated arachidonic acid (ARA) metabolism.
Publication Title
Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial.
Sample Metadata Fields
Sex, Age, Subject, Time
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human umbilical cord Whartons jelly stem cells (WHJSC) are gaining attention as a possible clinical source of mesenchymal stem cells for use in cell therapy and tissue engineering due to their high accessibility, expansion potential and plasticity. However, the cell viability changes that are associated to sequential cell passage of these cells are not known. In this analysis, we have identified the gene expression changes that are associated to cell passage in WHJSC.
Publication Title
Evaluation of the cell viability of human Wharton's jelly stem cells for use in cell therapy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Compare the behaviour of two populations of non-hematopoetic stem cells (MSC and MAPC) isolated from human bone marrow. The effect of culture conditions on the behaviour of MSC was also characterised by isolating MSC and then culturing the cells for 96h in MAPC growth conditions
Publication Title
Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Multiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from 17 MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA. Taken together, these results showed that genomic heterogeneity, both at the DNA and RNA level, is a hallmark of MM transition from diagnosis to relapse.
Publication Title
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sample Metadata Fields
Sex, Specimen part
View Samples