Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions.
Transcriptomics of post-stroke angiogenesis in the aged brain.
Sex, Age, Specimen part
View SamplesWe have generated a mouse model for tumor initiation carrying a mutation in APC and lacking IKKa in intestinal epithelial cells. IKKa-deficient intestinal cells primarily failed to generate adenomas, and the few adenomas arising in this background displayed a significant reduction in cell proliferation. Using an in vitro model for intestinal tumoroids (derived from adenoma initiating cells), we have performed RNA sequencing of wild type and IKKa-deficient intestinal tumoroids. This has demonstrated that epithelial IKKa controls transcription of stem cell-related genes and genes associated with proliferation and apoptosis. Overall design: RNA sequencing of IKKa WT and KO tumoroids, done in triplicates
IKKα is required in the intestinal epithelial cells for tumour stemness.
Specimen part, Cell line, Subject
View SamplesRecently, we described a new animal model of CNS primitive neuroectodermal tumors (CNS-PNET), which was generated by orthotopic transplantation of human Radial Glial (RG) cells into NOD-SCID mice’s brain sub- ventricular zone. In the current study we conducted comprehensive RNA-Seq analyses to gain some insights on the mechanisms underlying tumorigenesis in this mouse model of CNS-PNET. Here we show that the RNA-Seq profiles derived from these tumors cluster with those reported for patients’ PNETs. Overall design: RNA-seq of tumors from central nervous system primitive neuroectodermal tumor (CNS PNET) animal model
Stabilization of HIF-1α and HIF-2α, up-regulation of MYCC and accumulation of stabilized p53 constitute hallmarks of CNS-PNET animal model.
Specimen part, Disease stage, Subject
View Samplesmmunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as operationally tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter fingerprint of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for ?d T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4+CD25+ T-cells and Vd1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning.
Multiparameter immune profiling of operational tolerance in liver transplantation.
No sample metadata fields
View SamplesHere, using genome wide analysis, we demonstrate that canonical mRNA is processed post-transcriptionally through an alternative cleavage and polyadenylation mechanism. As a result of this process, the downstream cleavage fragment of the 3'UTR remains uncapped and stable This finding indicates that different parts of gene mRNA are separate and independent, by re-annotating the human transcriptome using this model, we provide a new overview of the function and impact of microRNA (miRNA) Our results shed new light on the mammalian transcriptome and show that what were considered as 3'UTRs are in fact autonomous RNA fragments. Overall design: Examination of mRNA levels and cleavage across transcripts in U2OS and 293 cell types (3 replicates each)
Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments.
Treatment, Subject
View SamplesBACKGROUND: Many age-associated disorders (including diabetes, cancer, and neurodegenerative diseases) are linked to mitochondrial dysfunction, which leads to impaired cellular bioenergetics and increased oxidative stress. However, it is not known what genetic and molecular pathways underlie differential vulnerability to mitochondrial dysfunction observed among different cell types.
Molecular basis for vulnerability to mitochondrial and oxidative stress in a neuroendocrine CRI-G1 cell line.
Cell line
View SamplesThe aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from nave and BCG vaccinated mice. The differences between nave and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals.
Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb).
Sex, Age, Specimen part
View SamplesThe PAT-seq approach was utilised to determine the gene expression changes over the cell-cycle of wildtype and delta-set1 yeast strains. The cell were synchronised by alpha-factor arrest and cell-cycle release Overall design: Analysis gene expresson across the S. cerevisiae cell cycle.
Coordination of Cell Cycle Progression and Mitotic Spindle Assembly Involves Histone H3 Lysine 4 Methylation by Set1/COMPASS.
Cell line, Subject, Time
View SamplesAnalysis of aldosterone-producing adenoma (APA) samples from patients with primary hyperaldosteronism. These APAs have a somatic mutation in either KCNJ5, CACNA1D, or ATP1A1. Results provide insight into the different mechanisms each mutation may cause leading to elevated aldosterone production in APA.
Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension.
Specimen part, Disease, Disease stage
View SamplesTumors contain a fraction of cancer stem cells that maintain the propagation of the disease. The CD34CD38_ cells, isolated from acute myeloid leukemia (AML), were shown to be enriched leukemic stem cells (LSC). We isolated the CD34CD38_ cell fraction from AML and compared their gene expression profiles to the CD34CD38 cell fraction, using microarrays. We found 409 genes that were at least twofold over- or underexpressed between the two cell populations. These include underexpression of DNA repair, signal transduction and cell cycle genes, consistent with the relative quiescence of stem cells, and chromosomal aberrations and mutations of leukemic cells. Comparison of the LSC expression data to that of normal hematopoietic stem cells (HSC) revealed that 34% of the modulated genes are shared by both LSC and HSC, supporting the suggestion that the LSC originated within the HSC progenitors. We focused on the Notch pathway since Jagged-2, a Notch ligand was found to be overexpressed in the LSC samples. We show that DAPT, an inhibitor of gamma-secretase, a protease that is involved in Jagged and Notch signaling, inhibits LSC growth in colony formation assays. Identification of additional genes that regulate LSC self-renewal may provide new targets for therapy.
Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells.
Specimen part
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