In this study, we used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted cardiomyocyte proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing cardiomyocyte apoptosis. Rather, we found that AAV9:hYAP stimulated adult cardiomyocyte proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated cell cycle gene expression, enhanced TGF-signaling, and activated of components of the inflammatory response.Cardiac specific YAP activation after MI mitigated myocardial injury after MI, improved cardiac function and mouse survival. These findings suggest that therapeutic activation of hYAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI.
Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine MI model.
Specimen part
View SamplesRNAseq profiling of 10 time points during germination in Arabidopsis, from freshly harvested seed, through mature seed, stratification, germination and to post-germination. Overall design: Total RNA was extracted from Arabidopsis seeds at 10 time points during germination in triplicate. The time points were: freshly harvested seed (H), seeds following 15 days of ripening (0 h), seeds after; 1 h of stratification (1 h S), 12 h of stratification (12 h S), 48 h of stratification (48 h S), followed by seed collected 1 hour into the light (1 h SL), 6 hours into the light (6 h SL), 12 hours into the light (12 h SL), 24 hours into the light (24 h SL) and 48 hours into the light (48 h SL).
Extensive transcriptomic and epigenomic remodelling occurs during Arabidopsis thaliana germination.
Specimen part, Subject, Time
View SamplesGlucosamine proved to be a potent, broad-spectrum inhibitor of IL-1beta. Of the 2,813 genes whose transcription was altered by IL-1beta stimulation (p<0.0001), glucosamine significantly blocked the response in 2,055 (~73%). Glucosamine fully protected the chondrocytes from IL-1-induced expression of inflammatory cytokines, chemokines and growth factors as well as proteins involved in PGE2 and NO synthesis. It also blocked the IL-1-induced expression of matrix specific proteases such as MMPs -3,-9,-10,-12 and ADAMTS-1.
Exogenous glucosamine globally protects chondrocytes from the arthritogenic effects of IL-1beta.
Age
View SamplesGene expression profiling based classification of DLBCL patients versus healthy donors provides insights on transcriptional regulation processes.
T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells.
Sex, Age, Specimen part
View SamplesThis data provides evidence that elevation of cAMP levels has a dramatic effect on the transcriptome of yeast cells, with particular emphasis on mitochondrial function and the promotion of ROS production
cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation.
Treatment
View SamplesTranscriptome analysis of peritoneal lavage of mice infected with T. gondii
Differential gene expression in mice infected with distinct Toxoplasma strains.
Sex, Specimen part
View SamplesWe used microarrays to detail the global gene expression signature of PDAC and to identify distinct up- and down-regulated transcripts in these tumors compared to control pancreas. We also established from this dataset the metabolic signature of PDAC in order to define new metabolic therapeutic target for pancreatic cancer.
Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma.
Sex, Age, Specimen part
View SamplesInnate sensing of viruses by dendritic cells (DCs) is critical for the initiation of anti-viral adaptive immune responses. Virus, however, have evolved to suppress immune activation in infected cells. We now analyze the susceptibility of different populations of dendritic cells to viral infections. We find that circulating human CD1c+ DCs support infection by HIV and influenza virus. Viral infection of CD1c+ DCs is essential for virus-specific CD8+ T cell activation and cytosolic sensing of the virus. In contrast, circulating human CD141+ DCs and pDCs constitutively limit viral fusion. The small GTPase RAB15 mediates this differential viral resistance in DC subsets through selective expression in CD141+ DCs and pDCs. Therefore, dendritic cell sub-populations evolved constitutive resistance mechanisms to mitigate viral infection during induction of antiviral immune response. Overall design: Examination of transcriptional profiles in 4 DC subsets purified from 3 donors using RNASeq
Constitutive resistance to viral infection in human CD141<sup>+</sup> dendritic cells.
No sample metadata fields
View SamplesInterleukin (IL)-17 plays an important and protective role in host defence and has been demonstrated to orchestrate airway inflammation by cooperating with and inducing proinflammatory cytokines. Mircoarrays were used to identify immediate-early/ primary response IL-17A-dependent gene transcripts in primary human bronchial ASM cells from mild asthmatic and healthy individuals.
IL-17A mediates a selective gene expression profile in asthmatic human airway smooth muscle cells.
Sex, Age, Specimen part, Treatment, Subject, Time
View SamplesGhrelin, an orexigenic gut-derived peptide, is gaining increasing attention due to its multifaceted role in a number of physiological functions, including metabolism, cardiovascular health, stress and reproduction. Ghrelin exists in circulation primarily as des-acylated and acylated ghrelin. Des-acyl ghrelin, until recently considered to be an inactive form ghrelin, is now known to have independent physiological functionality. However, the relative contribution of acyl and des-acyl ghrelin to reproductive development and function is currently unknown. Here we used ghrelin-O-acyltransferase (GOAT) knockout (KO) mice that have no measurable levels of endogenous acyl ghrelin and chronically high levels of des-acyl ghrelin, to characterise how the developmental and life-long absence of acyl ghrelin affects ovarian development and reproductive capacity. We have combined ovarian transcriptome analysis using RNA sequencing with measures of ovarian morphometry, as well as with the assessment of markers of reproductive maturity and the capacity to breed. Our data show pronounced specific changes in the ovarian transcriptome in the juvenile GOAT KO ovary, indicative of advanced ovarian development. These changes corresponded with diminished ovarian reserve in the juvenile and adult ovaries of these mice, due to a continuous reduction in the number of small follicle populations. These changes did not affect the timing of puberty onset or reproductive capacity under optimal conditions. These data suggest that an absence of acyl ghrelin does not prevent reproductive success but that appropriate levels of acyl and des-acyl ghrelin may be necessary for optimal ovarian maturation. Overall design: 4 WT and 4 GOAT KO ovaries were used for this analysis
Acylated Ghrelin Supports the Ovarian Transcriptome and Follicles in the Mouse: Implications for Fertility.
Age, Specimen part, Cell line, Subject
View Samples