Filters
Technology
Platform
SRP194327
Drosophila melanogaster
73 Downloadable Samples
Illumina HiSeq 2500
Description
Ageing populations pose one of the main public health crises of our time. Reprogramming gene expression by altering the activities of sequence-specific transcription factors (TF) can ameliorate deleterious effects of age. Here we explore how a circuit of TFs coordinates pro-longevity transcriptional outcomes, which reveals a multi-tissue and multi-species role for an entire protein family: the E-twenty-six (ETS) TFs. In Drosophila, reduced insulin/IGF signalling (IIS) extends lifespan by coordinating activation of Aop, an ETS transcriptional repressor, and Foxo, a Forkhead transcriptional activator. Aop and Foxo bind the same genomic loci, and we show that, individually, they effect similar transcriptional programmes in vivo. In combination, Aop can both moderate or synergise with Foxo, dependent on promoter context. Moreover, Foxo and Aop oppose the activities of Pnt, an ETS transcriptional activator, effecting a transcriptomic programme that correlates lifespan outcomes. Directly limiting Pnt extended lifespan, suggesting this is how Aop and Foxo promote longevity. The lifespan-limiting role of Pnt appears to be balanced by a requirement for metabolic regulation in young flies, in which the Aop-Pnt-Foxo circuit determines nutrient storage, and Pnt regulates lipolysis and responses to nutrient stress. Molecular functions are conserved amongst ETS TFs, suggesting others may also affect ageing. We show that Ets21C limits lifespan, functioning in the same genetic network as Foxo and IIS. Other ETS TFs appear to play roles in fly ageing in multiple contexts, since inhibiting the majority of the family in intestine, adipose or neurons extended lifespan. We expand the repertoire of lifespan-limiting ETS TFs in C. elegans, confirming their conserved function in ageing. Altogether this study reveals that roles of ETS TFs in physiology and lifespan are conserved throughout the family, both within and between species. Overall design: foxo, aopACT and pntP1 overexpression in S106 D. melanogaster, polyA RNAseq.
Publication Title
Longevity is determined by ETS transcription factors in multiple tissues and diverse species.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 17 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Commercial brewing yeast strains are exposed to a number of potential stresses including oxidative stress. The aim of this investigation was to measure the physiological and transcriptional changes of yeast cells during full-scale industrial brewing processes with a view to determining the environmental factors influencing the cells oxidative stress response. Cellular antioxidant levels were monitored throughout an industrial propagation and fermentation and microarray analysis was employed to determine transcriptional changes in antioxidant-encoding and other stress response genes. The greatest increase in cellular antioxidants and transcription of antioxidant-encoding genes occurred as the rapidly fermentable sugars glucose and fructose were depleted from the growth medium (wort) and the cell population entered the stationary phase. The data suggest that, contrary to expectation, the oxidative stress response is not influenced by changes in the dissolved oxygen concentration of wort but is initiated as part of a general stress response to growth-limiting conditions, even in the absence of oxygen. A mechanism is proposed to explain the changes in antioxidant response observed in yeast during anaerobic fermentation. The results suggest that the yeast cell does not experience oxidative stress, per se, during industrial brewery handling. This information may be taken into consideration when setting parameters for industrial brewery fermentation.
Publication Title
The oxidative stress response of a lager brewing yeast strain during industrial propagation and fermentation.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Retinopathy of prematurity (ROP) is a disorder of the developing retina of preterm infants. ROP can lead to blindness due to abnormal angiogenesis that is the result of suspended vascular development and vaso-obliteration leading to severe retinal stress and hypoxia. We tested the hypothesis that a combined treatment with two human progenitor populations, the CD34+ cells, bone marrow-derived, and the endothelial colony-forming cells (ECFCs) synergistically protected the developing retinal vasculature in a murine model of ROP, the oxygen-induced retinopathy (OIR)., CD34+ cells alone, ECFCs alone, or a combination thereof were injected intravitreally at either P5 or P12 and pups were euthanized at P17. Retinas from OIR mice injected with ECFCs or the combined treatment revealed formation of the deep vascular plexus (DVP) while still in hyperoxia, with normal appearing connections between the superficial vascular plexus (SVP) and the DVP. The combination therapy prevented aberrant retinal neovascularization and was more effective anatomically and functionally at rescuing the ischemia phenotype than either cell type alone. The beneficial effect of the cell combination was the result of their ability to orchestrate an acceleration of vascular development and more rapid ensheathment of pericytes on the developing vessels.
Publication Title
Progenitor cell combination normalizes retinal vascular development in the oxygen-induced retinopathy (OIR) model.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Gene 1.0 ST Array (chigene10st)
Description
Integrins have long been known to have a role in adhesion of neural stem cells within the neuroepithelium, but little is known about their role in regulating stem cell behaviour through signalling. We aimed to investigate the effect of integrin-beta 1 signalling (itgb1) on these cells by transfection of a constitutively active itgb1. This creates a heterogenous pattern of expression allowing the study of cell-autonomous and non-cell autonomous effects.
Publication Title
Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- NextSeq 500
Description
Three different progenitor cell subsets in subcutaneous and visceral adipose tissues derived from 5 obese patients were subjected to AmpliSeq transcriptome profiling. Transcriptomic profiles were analyzed to compare progenitor cell subsets and the impact of subcutaneous and visceral adipose tissue location. Overall design: Transcriptomic profiling of 3 different progenitor cell types in subcutaneous and visceral adipose tissues derived from 5 obese patients (3X2X5=30 samples).
Publication Title
Lobular architecture of human adipose tissue defines the niche and fate of progenitor cells.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
The developmental potential of human pluripotent stem cells suggests that they can produce disease-relevant cell types for biomedical research. However, substantial variation has been reported among pluripotent cell lines, which could affect their utility and clinical safety. Such cell-line specific differences must be better understood before one can confidently use embryonic stem (ES) or induced pluripotent stem (iPS) cells in translational research. Towards this goal we have established genome-wide reference maps of DNA methylation and gene expression for 20 previously derived human ES lines and 12 human iPS cell lines, and we have measured the in vitro differentiation propensity of these cell lines. This resource enabled us to assess the epigenetic and transcriptional similarity of ES and iPS cells and to predict the differentiation efficiency of individual cell lines. The combination of assays yields a scorecard for quick and comprehensive characterization of pluripotent cell lines.
Publication Title
Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Analysis of gene expression in pathologically confirmed glioblastoma (GBM) samples. These data were used to test a classifier that was generated to distinguish GBM tumor samples with loss of neurofibromin 1 (NF1) function
Publication Title
A machine learning classifier trained on cancer transcriptomes detects NF1 inactivation signal in glioblastoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from 18-month-old Ahr-knockout and wild-type mice. HSC from aged AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC.
Publication Title
Conditional deletion of Ahr alters gene expression profiles in hematopoietic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2500
Description
Hoxb8 mutant mice show compulsive behavior similar to trichotillomania, a human obsessive-compulsive-spectrum disorder. The only Hoxb8 lineage-labeled cells in the brains of mice are microglia, suggesting that defective Hoxb8 microglia caused the disorder. What is the source of the Hoxb8 microglia? It has been posited that all microglia progenitors arise at embryonic day (E) 7.5 during yolk sac hematopoiesis, and colonize the brain at E9.5. In contrast, we show the presence of two microglia subpopulations: canonical, non-Hoxb8 microglia and Hoxb8 microglia. Unlike non- Hoxb8 microglia, Hoxb8 microglia progenitors appear to be generated during the second wave of yolk sac hematopoiesis, then detected in the aorto-gonad-mesonephros (AGM) and fetal liver, where they are greatly expanded, prior to infiltrating the E12.5 brain. Further, we demonstrate that Hoxb8 hematopoietic progenitor cells taken from fetal liver are competent to give rise to microglia in vivo. Although the two microglial subpopulations are very similar molecularly, and in their response to brain injury and participation in synaptic pruning, they show distinct brain distributions which might contribute to pathological specificity. Non-Hoxb8 microglia significantly outnumber Hoxb8 microglia, but they cannot compensate for the loss of Hoxb8 function in Hoxb8 microglia, suggesting further crucial differences between the two subpopulations. Overall design: Green (non-Hoxb8, control) and yellow (Hoxb8, experimental) microglia data sets
Publication Title
Correction: Two distinct ontogenies confer heterogeneity to mouse brain microglia (doi: 10.1242/dev.152306).
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 194 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Chronic lymphocytic leukemia (CLL) is a common and heterogeneous disease. An accurate prediction of outcome is highly relevant for the development of personalized treatment strategies. Microarray technology was shown to be a useful tool for the development of prognostic gene expression scores. However, there are no gene expression scores which are able to predict overall survival in CLL based on the expression of few genes that are better than established prognostic markers. We correlated 151 CLL microarray data sets with overall survival using Cox regression and supervised principal component analysis to derive a prognostic score. This score based on the expression levels of eight genes and was validated in an independent group of 149 CLL patients by quantitative real time PCR. The score was predictive for overall survival and time to treatment in univariate Cox regression in the validation data set (both: p<0.001) and in a multivariate analysis after adjustment for 17p and 11q deletions and the IgVH-status. The score achieved superior prognostic accuracy compared to models based on genomic aberrations and IgVH-status and may support personalized therapy.
Publication Title
An eight-gene expression signature for the prediction of survival and time to treatment in chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples