Filters
Technology
Platform
SRP123455
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
NGS technology was used for high-throughput profiling of the transcriptome by comparing satellite cells lacking or not HDAC4. Overall design: Total RNA was isolated from control and HDAC4 KO satellite cells in growth conditions
Publication Title
HDAC4 regulates satellite cell proliferation and differentiation by targeting P21 and Sharp1 genes.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
While gene regulatory networks involved in cardiogenesis have been characterized, the role of bioenergetics remains less studied. Here we show that until midgestation, myocardial metabolism is compartmentalized, with a glycolytic signature restricted to compact myocardium contrasting with increased mitochondrial oxidative activity in the trabeculae. HIF1a regulation mirrors this pattern, with expression predominating in compact myocardium and scarce in trabeculae. By midgestation, the compact myocardium downregulates HIF1a and switches toward oxidative metabolism. Deletion of the E3 ubiquitin ligase Vhl results in HIF1a hyperactivation, disrupting metabolic compartmentalization and blocking the midgestational shift toward oxidative phosphorylation. Moreover, the altered glycolytic signature induced by HIF1 trabecular activation precludes regulation of genes essential for cardiac conduction system establishment. Our findings reveal VHL-HIF-mediated metabolic compartmentalization in the developing heart and the connection between metabolism and myocardial differentiation. These results highlight the importance of bioenergetics in ventricular myocardium specialization and its potential relevance to congenital heart disease. Overall design: RNA was isolated from individual E12.5 embryonic hearts after removal of the atria and valvular region. KOs and control littermates were matched by somite count, and a total number of 3 KOs and 3 controls from 3 independent litters were used. For RNA extraction, QIAzol Lysis Reagent (Qiagen; CA; USA) and the miRNeasy Mini Kit (Qiagen; CA; USA) were used. RNA was quantified and its purity checked with a NanoDrop ND-1000 spectophotometer (Thermo Scientific; MA; USA). RNA integrity was verified with an Agilent 2100 Bioanalyzer (Agilent Technologies; CA; USA). Index-tagged cDNA libraries were constructed from 500 ng of total RNA using the TruSeq RNA Sample Preparation v2 Kit (Illumina; CA; USA). Libraries were quantified by Quant-iTâ„¢ dsDNA HS assay in a Q-bit fluorometer (Life Technologies; CA; USA). Average library size and size distribution were determined by DNA 1000 assay in an Agilent 2100 Bioanalyzer. Libraries were normalized to 10nM using 10mM Tris-HCl, pH8.5 containing 0.1% Tween 20 and then applied to an Illumina flow cell for cluster generation (True Seq SR Cluster Kit V2 cBot) and sequencing-by-synthesis. Single reads of length 75bp were generated with the TruSeq SBS Kit v5 (Illumina; CA; USA) on the Genome Analyzer IIx platform, following the standard RNA sequencing protocol. Reads were further processed using the CASAVA package (Illumina; CA; USA) to split reads according to adapter indexes and produce fastq files.
Publication Title
Myocardial VHL-HIF Signaling Controls an Embryonic Metabolic Switch Essential for Cardiac Maturation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
Sentrix Human-6 Expression BeadChip
Description
New and effective therapeutical options are available for the treatment of Rheumatoid Arthritis. One of such treatments is rituximab, and chimeric anti-CD20 antibody that selectively depletes the CD20+ B cell subpopulation.
Publication Title
Identification of candidate genes for rituximab response in rheumatoid arthritis patients by microarray expression profiling in blood cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HiSeq 2500
Description
Rift Valley fever virus (RVFV) causes major outbreaks among livestock, characterized by “abortion storms” in which spontaneous abortion occurs in almost 100% of pregnant ruminants. Humans can also become infected with mild symptoms that can progress to more severe symptoms, such as hepatitis, encephalitis, and hemorrhagic fever. The goal of this study was to use RNA-sequencing (RNA-seq) to analyze the host transcriptome in response to RVFV infection. G2/M DNA damage checkpoint, ATM signaling, mitochondrial dysfunction, regulation of the antiviral response, and integrin-linked kinase (ILK) signaling were among the top altered canonical pathways with both the attenuated MP12 strain and the fully virulent ZH548 strain. Although several mRNA transcripts were highly upregulated, an increase at the protein level was not observed for the selected genes, which was at least partially due to the NSs dependent block in mRNA export. Inhibition of ILK signaling, which is involved in cell motility and cytoskeletal reorganization, resulted in reduced RVFV replication, indicating that this pathway is important for viral replication. Overall, this is the first global transcriptomic analysis of the human host response following RVFV infection, which could give insight into novel host responses that have not yet been explored. Overall design: The study included triplicate samples of HSAEC cells infected with Mock, MP12, or ZH548 strains of RVFV, and collected at 3, 9, and 18 hourse post-infection. There are a total of 27 samples.
Publication Title
Phosphoproteomic analysis reveals Smad protein family activation following Rift Valley fever virus infection.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent signaling in cardiac cells.
Publication Title
Protein kinase C (PKC)ζ-mediated Gαq stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 44 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
We sought to find a gene-expression multigene predictor of response to infliximab therapy in Rheumatoid Arthritis patients. Using internal and external cross-validation systems we have built and validated an 8-gene predictor for response to infliximab.
Publication Title
An eight-gene blood expression profile predicts the response to infliximab in rheumatoid arthritis.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Metformin, a commonly used drug prescribed to treat type-2 diabetes, has been found to extend health span and delay cancer incidence and progression. Here, we report that starting chronic treatment with low dose of metformin (0.1% w/w in diet) at one year of age extends health and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with low dose metformin mimicked some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced LDL and cholesterol levels. At a molecular level, metformin increased AMP-activated protein kinase activity without attenuation of the mitochondrial electron transport chain activities. Metformin treatment resulted in lower chronic inflammation and increased antioxidant protection, suggesting that the ability of metformin to improve health of laboratory animals may stem from these factors. Our results support that metformin supplementation could be beneficial in extending health and lifespan in humans.
Publication Title
Metformin improves healthspan and lifespan in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiScanSQ
Description
Macrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomics and proteomics approaches. We identified a common pattern of genes transcriptionally regulated that overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens with several inflammatory pathways corresponding to primary (triggered by pattern recognition receptors) and secondary (induced by proinflammatory cytokines) responses. We also show that the Toll-like receptor family member, CD180 is downregulated by the stimulation of macrophages, but not monocytes, with the spirochete. Silencing Cd180 results in increased phagocytosis while tempering the production of the proinflammatory cytokine, TNF. Cd180-silenced cells produced increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases the CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response. Overall design: Genome-wide changes in gene Expression in mouse bone marrow-derived macrophages stimulated with Borrelia burgdorferi or left unstimulated were generated by RNAseq.
Publication Title
Regulation of macrophage activity by surface receptors contained within Borrelia burgdorferi-enriched phagosomal fractions.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 878 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Identifying immune correlates of protection and mechanisms of immunity accelerates and streamlines the development of vaccines. RTS,S/AS01E, the most advanced malaria vaccine, has moderate efficacy in African children. In contrast, immunization with sporozoites under antimalarial chemoprophylaxis (CPS immunization) can provide 100% sterile protection in naïve adults. We used systems biology approaches to identify correlates of vaccine-induced immunity based on transcriptomes of peripheral blood mononuclear cells from subjects immunized with RTS,S/AS01E or chemo-attenuated sporozoites stimulated with parasite antigens in vitro. Specifically, we used samples of subjects from two age cohorts and 3 African countries participating in an RTS,S/AS01E pediatric phase 3 trial and malaria-naïve subjects participating in a CPS trial. We identified both pre-immunization and post-immunization transcriptomic signatures correlating with protection. Signatures were validated in independent children and infants from the RTS,S/AS01E phase 3 trial and subjects from an independent CPS trial with high accuracies (>70%). Transcription modules revealed interferon, NF-B, TLR, and monocyte-related signatures associated with protection. Pre-immunization signatures suggest the potential for strategies to prime the immune system before vaccination towards improving vaccine immunogenicity and efficacy. Finally, signatures of protection could be useful to determine efficacy in clinical trials, accelerating vaccine candidate testing. Nevertheless, signatures should be tested more extensively across multiple cohorts and trials to demonstrate their universal predictive capacity.
Publication Title
Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
During sexual dimorphism, the loss of one entire X chromosome in Drosophila males is achieved largely via a broad genome-wide aneuploid effect. Exploring how MSL proteins and two large non coding RNAs (roX1 and roX2) modulate trans-acting aneuploid effect for equality to females, we employ a system biology approach (microarray) to investigate the global aneuploid effect of maleless(mle) mutation by disrupting MSL binding. A large number of the genes (144) that encode a broad spectrum of cellular transport proteins and transcription factors are located in the autosomes of Drosophila melanogaster.
Publication Title
Drosophila maleless gene counteracts X global aneuploid effects in males.
Sample Metadata Fields
No sample metadata fields
View Samples