In order to study the microglia contribution in neurodegeneration more specifically we established a mouse model of prion disease in which the 79A murine prion strain was introduced by an intraperitoneal route into BALB/cJFms-EGFP/- mice, which express Enhanced Green Fluorescent Protein (EGFP) under control of the C-fms operon. Samples were taken at time points during disease progression and histological analysis of the brain and transcriptional analysis of isolated microglia was carried out. The analysis of isolated microglia revealed a disease specific, highly pro-inflammatory signature in addition to an up-regulation of genes associated with metabolism, respiratory stress and DNA repair. This study strongly supports the growing recognition of the importance of microglia within the prion disease process and identifies the nature of the response through gene expression analysis of isolated microglia.
Defining the Microglia Response during the Time Course of Chronic Neurodegeneration.
Sex, Specimen part
View SamplesNAP - neuroprotective peptide demonstrates increase in neuronal survival when injected into the hippocampus of rats in the model of epilepsy
The microtubule interacting drug candidate NAP protects against kainic acid toxicity in a rat model of epilepsy.
No sample metadata fields
View SamplesTo better understand the temporal dynamics of gene expression during normal murine lung development we characterized global gene expression at 26 time points in three common inbred strains of mice (A/J, C57BL/6J, and C3H/HeJ). The data set provides a unique resource for identifying patterns of gene expression changes during normal lung development and for investigating the developmental origins of respiratory disease.
Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development.
Specimen part
View SamplesWe sought to ascertain the time-course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE nave individuals, and determine if the magnitude of any response was associated with exercise induced muscle damage. Sixteen RE nave males were recruited, 8 underwent 2 sessions of 5x30 maximum, isokinetic knee extensions (180.s-1) separated by 48 hrs. Muscle biopsies of the vastus lateralis were taken at baseline and 24 hrs after each exercise bout. Eight individuals acted as non-exercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray, and binding of HSP27 and B-crystallin to insoluble proteins by immunohistochemistry as a measure of muscle damage. In control subjects, no probesets were significantly altered (FDR<0.05) and HSP27 and B-crystallin binding remained unchanged throughout the study. In exercised subjects, significant inter-subject variability following the initial bout of RE was observed in the muscle transcriptome, with greatest changes occurring when HSP27 and B-crystallin binding was elevated. Following the second bout of RE, the transcriptome response was more consistent among subjects revealing a cohort of probesets associated with immune activation, the suppression of oxidative metabolism and protein ubiquitination as differentially regulated. The results reveal that the initial transcriptional response to RE is highly variable in RE nave volunteers, is associated with muscle damage, and unlikely to reflect longer-term adaptations to RE training. These results highlight the importance of considering multiple time-points when determining the transcriptional response to RE and associated physiological adaptation.
Transient transcriptional events in human skeletal muscle at the outset of concentric resistance exercise training.
Sex, Specimen part, Subject, Time
View SamplesBased on the results of numerous clinical and preclinical analyses, the transcription factor HIF-1a has been identified as an important tumor-promoting factor and is considered to be an attractive target for cancer therapy. To further deconstruct the molecular nature of HIF-1as role in tumorigenesis, we have applied lentiviral shRNA transduction to establish HIF-1a-deficient gastric cancer cells. Interestingly, functional analyses failed to show a significant growth defect of HIF-1a-deficient gastric cancer cells in vitro and in vivo. These observations led us to propose that stable inactivation of HIF-1a resulted in efficient compensation enabling cell growth and, ultimately, tumor progression in a HIF-1a-independent manner. To better understand the mechanisms that control this compensation, we performed transcriptomics of control (scrambled (SCR)) and HIF-1a-deficient (HIF) gastric cancer cells.
Annexin A1 sustains tumor metabolism and cellular proliferation upon stable loss of HIF1A.
Specimen part, Cell line
View SamplesPrior studies using DNA microarray platforms have shown alterations of gene expression profiles (GEPs) of marrow cells in myelodysplastic syndromes (MDS). Using the increased sensitivity and accuracy of high-throughput RNA sequencing (RNA-Seq) for detecting and quantifying mRNA transcripts, our study has demonstrated novel significant differences in GEPs between MDS and normal CD34+ marrow cells with 41 genes identified as disease classifiers. Additionally, two main clusters of GEPs distinguished patients based on their major clinical features, particularly between those whose disease remained stable (sMDS) vs patients whose illness transformed to acute myeloid leukemia within 12 months (tMDS). The genes whose expression was associated with disease outcome were involved in functional pathways and biologic processes highly relevant for MDS. Exomic analysis identified MDS-associated pathogenic mutations in virtually all patients tested. MDS subgroups with spliceosome mutations demonstrated distinct differential isoform usage and expression and consequent dysregulation of distinct biological functions. This combination of clinical, transcriptomic and exomic findings provides valuable molecular insights into the mechanisms underlying MDS and its progression to a more aggressive stage and also facilitates prognostic characterization of MDS patients. Overall design: RNA-Seq was performed on CD34+ hematopoietic stem cells derived from healthy individuals and patients with myelodysplastic syndrome.
Distinct transcriptomic and exomic abnormalities within myelodysplastic syndrome marrow cells.
Specimen part, Disease, Subject
View SamplesThe experiment aims to identify transcriptional effects of Infliximab (an anti-TNF antibody) and CDP870 on human cell lines
mTNF reverse signalling induced by TNFα antagonists involves a GDF-1 dependent pathway: implications for Crohn's disease.
Cell line, Treatment, Time
View SamplesThe epidemic character of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA), especially the geographically widespread clone USA300, is poorly understood. USA300 isolates carry a type IV staphylococcal chromosomal cassette mec (SCCmec) element conferring -lactam antibiotic class resistance and a putative pathogenicity island, ACME (arginine catabolic mobile element).
The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus.
No sample metadata fields
View SamplesQuiescent and dividing hemopoietic stem cells (HSC) display marked differences in their ability to move between the peripheral circulation and the bone marrow. Specifically, long-term engraftment potential predominantly resides in the quiescent HSC subfraction, and G-CSF mobilization results in the preferential accumulation of quiescent HSC in the periphery. In contrast, stem cells from chronic myeloid leukemia (CML) patients display a constitutive presence in the circulation. To understand the molecular basis for this, we have used microarray technology to analyze the transcriptional differences between dividing and quiescent, normal, and CML-derived CD34+ cells.
Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources.
Specimen part, Disease, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.
Age, Specimen part, Treatment
View Samples