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Mus musculus
4 Downloadable Samples
Illumina HiSeq 1500
Description
The study of the mechanisms leading to cardiac hypertrophy is essential to better understand cardiac development and regeneration. Pathological conditions such as ischemia or pressure overload can induce a release of extracellular nucleotides within the heart. We recently investigated the potential role of nucleotide P2Y receptors in cardiac development. We showed that adult P2Y4-null mice displayed microcardia resulting from defective cardiac angiogenesis. Here we show that loss of another P2Y subtype called P2Y6, a UDP receptor, was associated with a macrocardia phenotype and amplified pathological cardiac hypertrophy. Cardiomyocyte proliferation and size were increased in vivo in hearts of P2Y6-null neonates, resulting in enhanced post-natal heart growth. We then observed that loss of P2Y6 receptor enhanced pathological cardiac hypertrophy induced after isoproterenol injection. We identified an inhibitory effect of UDP on in vitro isoproterenol-induced cardiomyocyte hyperplasia and hypertrophy. The present study identifies mouse P2Y6 receptor as a regulator of cardiac development and cardiomyocyte function. P2Y6 receptor could constitute a therapeutic target to regulate cardiac hypertrophy. Overall design: WT and P2Y6 KO mice aged between 8 and 12 weeks were intraperitoneally injected with 50 mg/kg/day isoproterenol or saline solution, daily during 7 days, then hearts were harvested and weighted. Ventricles were then stored for RNA extraction.
Publication Title
Loss of Mouse P2Y6 Nucleotide Receptor Is Associated with Physiological Macrocardia and Amplified Pathological Cardiac Hypertrophy.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples
GSE60304- Rattus norvegicus
- 59 Downloadable Samples
Illumina ratRef-12 v1.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 29 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Delineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., PTSD-like) and resilient (i.e.,minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (421%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factorswere first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associatedwith individual differences when using the most stringent statistical threshold.
Publication Title
Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Delineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., PTSD-like) and resilient (i.e.,minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (421%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factorswere first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associatedwith individual differences when using the most stringent statistical threshold.
Publication Title
Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We analyzed the transcriptional signatures of mouse bone marrow-derived macrophages (BMDM) at different times after infection with promastigotes of the protozoan parasite Leishmania major.
Publication Title
Transcriptomic signature of Leishmania infected mice macrophages: a metabolic point of view.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are so far hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We identified miRNA-1 as top candidate differentially expressed in tumor and metastasis. Furthermore, miRNA-1 was de-regulated in 16 additional tumor entities underscoring its central role in tumor pathogenesis. Functional analyses showed an additive effect of miRNA-1 with camptothecin treatment. We used a systems-biology simulation of cellular cancer models implemented in PyBios to investigate miRNA-1 function and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options. Overall design: Examination of miRNA expression values by Illumina sequencing of matched benign, tumor and metastasis tissues of 8 colorectal cancer patients. For 4 of these patients all tissues have been resequenced to obtain mRNA expression values.
Publication Title
High-throughput miRNA and mRNA sequencing of paired colorectal normal, tumor and metastasis tissues and bioinformatic modeling of miRNA-1 therapeutic applications.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
Description
By mapping global transcription start site (TSS) and chromatin dynamics, we observed the activation of thousands of cryptic, currently non-annotated TSSs (TINATS) following DNMTi and/or HDACi treatment. The resulting transcripts encode truncated or chimeric open reading frames that can be translated into products with predicted abnormal functions or immunogenic potential. TINAT activation after DNMTi coincided with DNA hypomethylation and gain in H3K4me3, H3K9ac, and H3K27ac histone marks. In contrast, HDACi induced only canonical TSSs in association with histone acetylation, but TINATs via a yet unknown mechanism. Nevertheless, both inhibitors convergently induced unidirectional transcription from identical sites since TINATs are encoded in solitary long-terminal repeats of the endogenous retrovirus-9 family, epigenetically repressed in virtually all normal cells. Overall design: CAGE-, ChIP-, and WGB-sequencing of NCI-H1299 EGFP-NEO reporter cells after treatment with DMSO, DAC, SB939, or DAC+SB
Publication Title
DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human Polynucleotide Phosphorylase (hPNPaseold-35) is an evolutionarily conserved 35 exoribonuclease implicated in the regulation of numerous physiological processes like maintenance of mitochondrial homeostasis, mtRNA import and aging-associated inflammation.
Publication Title
Identification of genes potentially regulated by human polynucleotide phosphorylase (hPNPase old-35) using melanoma as a model.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Plant Homeo Domain (PHD) is a versatile chromatin reader/effector module which recognizes methylated, acetylated or unmodified histone substrates and regulates cellular gene expression programs. Although PHD domains shows selective epigenetic recognition of methylated, acetylated and unmodified histone substrates, there has been no previous report on its catalytic function regulating malignant transformation of cells. Here we report that PHD finger of UBR7 (Ubiquitin Protein Ligase E3 Component N-Recognin 7 (Putative)), in isolation or in context of full length protein, harbors E3 ubiquitin ligase activity towards monoubiquitination of histone H2B at lysine 120 . Knockdown of UBR7 in MCF10a and breast cancer cells decreased H2BK120ub both at the global levels and on specific genes. Conversely, overexpression of wild type, but not catalytic mutant, rescued H2BK120ub levels. Low UBR7 expression was associated with basal-like and triple negative breast cancers as well as showed poor expression in metastatic tumors. Consistently, UBR7 loss resulted in invasion properties, induced epithelial-to-mesenchymal transition and promoted metastasis. Conversely, ectopic expression of UBR7 reduced cell growth, invasion and tumor growth in mouse fat pad. Mechanistically, UBR7 reduced H2BK120ub gene body of cell-adhesion related genes as well as gene expression including on CDH4 gene. Importantly, rebuilding CDH4 levels rescued invasion phenotypes seen in UBR7-low cells. Collectively, our results establish that UBR7 PHD has novel H2B ubiquitin ligase activity and it suppresses tumor growth in basal-like breast cancers. Overall design: Triplicate total RNA profiles in Wild Type and UBR7-shRNA MCF10A Cell Line
Publication Title
Atypical plant homeodomain of UBR7 functions as an H2BK120Ub ligase and breast tumor suppressor.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare GBM transcriptome profiling (RNA-seq) after shRNA based knockdown of PRKAB1 and to compare gene expression by optimal high-throughput data analysis Overall design: Methods: Total RNA profiles of two GBM cells (scramble and PRKAB1 sh RNA treated) were generated by deep sequencing, in triplicate, using Illumina Hiseq 2000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using SYBR Green assays
Publication Title
AMP kinase promotes glioblastoma bioenergetics and tumour growth.
Sample Metadata Fields
Specimen part, Race, Subject
View Samples