shRNA-mediated ablation of the RING-finger protein TRIM52 from multiple glioblastoma cell lines reduces proliferation and tumorigenesis. To identify gene signatures underlying this phenomenon, transcritional profile of TRIM52 knockdown cells was compared to control cells. Upon TRIM52 ablation, we find 278 differentially regulated genes. Gene ontology analysis reveals that many of the upregulated genes are associated with glycolysis and biosynthetic processes. Overall design: U87MG glioblastoma cells were stably transduced with doxycycline-inducible shRNA constructs targeting TRIM52 (two different shRNAs) or controls (two different non-targeting shRNAs). Knockdown was induced for five days using 2µg/ml doxycycline. shRNA expressing cells were sorted based on shRNA-coupled GFP expression via flow cytometry. mRNA sequening was performed in duplicate per shRNA cell line.
Human tripartite motif protein 52 is required for cell context-dependent proliferation.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Specimen part, Cell line, Time
View SamplesCellular responses to carcinogens are typically studied in transformed cell lines, which do not reflect the physiological status of normal tissues. To address this question, we have characterized the transcriptional program and cellular responses of normal human lung WI-38 fibroblasts upon exposure to the ultimate carcinogen benzo[a]pyrene diol epoxide (BPDE). Exposure to BPDE induces a strong inflammatory response in WI-38 primary fibroblasts. Whole-genome microarray analysis shows induction of several genes related to the production of inflammatory factors, including those that encode interleukins (ILs), growth factors, and enzymes related to prostaglandin synthesis and signaling. This is the first demonstration that a strong inflammatory response is triggered in primary fibroblasts in response to a reactive diol epoxide derived from a polycyclic aromatic hydrocarbon.
Benzo[a]pyrene diol epoxide stimulates an inflammatory response in normal human lung fibroblasts through a p53 and JNK mediated pathway.
Specimen part
View SamplesWe explored the transcriptional modification induced by CD99 transfection in the osteosarcoma cell lines SaOS-2 after 0, 7 and 14 days in differentiation medium.
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Specimen part, Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors.
Specimen part
View SamplesWhile most blood lineages are assumed to mature through a single cellular and developmental route downstream of hematopoietic stem cells (HSCs), dendritic cells (DCs) can be derived from both myeloid and lymphoid progenitors in vivo. To determine how distinct progenitors can generate similar downstream lineages, we examined the transcriptional changes that accompany loss of in vivo myeloid potential as common myeloid progenitors (CMPs) differentiate into common dendritic cell progenitors (CDPs), and as lymphoid-primed multipotent progenitors (LMPPs) differentiate into all lymphoid progenitors (ALPs). Microarray studies revealed that Interferon regulatory factor 8 (IRF-8) expression increased during each of these transitions. Competitive reconstitutions using Irf8-/- bone marrow demonstrated cell-intrinsic defects in the formation of CDPs and all splenic dendritic cell subsets. Irf8-/- CMPs and, unexpectedly, Irf8-/- ALPs produced more neutrophils in vivo than their wild type counterparts at the expense of DCs. Retroviral expression of IRF-8 in multiple progenitors led to reduced neutrophil production and increased numbers of DCs, even in the granulocyte-macrophage progenitor (GMP), which does not normally possess conventional DC potential. These data suggest that IRF-8 represses a neutrophil module of development and promotes convergent DC development from multiple lymphoid and myeloid progenitors autonomously of cellular context.
IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors.
Specimen part
View SamplesCarbonyl chloride (phosgene) is a toxic industrial compound (TIC) widely used in industry for the production of synthetic products, such as polyfoam rubber, plastics, and dyes. Exposure to phosgene results in a latent (1-24 hr), potentially life-threatening pulmonary edema and irreversible acute lung injury. A genomic approach was utilized to investigate the molecular mechanism of phosgene-induced lung injury. CD-1 male mice were exposed whole-body to either air or a concentration x time (c x t) amount of 32 mg/m3 (8 ppm) phosgene for 20 min (640 mg x min/m3). Lung tissue was collected from air- or phosgene-exposed mice at 0.5, 1, 4, 8, 12, 24, 48, and 72 hr post-exposure. RNA was extracted from the lung and used as starting material for the probing of oligonucleotide microarrays to determine changes in gene expression following phosgene exposure. The data were analyzed using principal component analysis (PCA) to determine the greatest sources of data variability. A three-way analysis of variance (ANOVA) based on exposure, time, and sample was performed to identify the genes most significantly changed as a result of phosgene exposure. These genes were rank ordered by p-values and categorized based on molecular function and biological process. Some of the most significant changes in gene expression reflect changes in glutathione synthesis and redox regulation of the cell, including upregulation of glutathione S-transferase alpha-2, glutathione peroxidase 2, and glutamate-cysteine ligase, catalytic subunit (also known as -glutamyl cysteine synthetase). This is in agreement with previous observations describing changes in redox enzyme activity after phosgene exposure. We are also investigating other pathways that are responsive to phosgene exposure to identify mechanisms of toxicity and potential therapeutic targets.
Genomic analysis of murine pulmonary tissue following carbonyl chloride inhalation.
No sample metadata fields
View SamplesSulfur mustard (HD) is a vesicating agent that targets the eyes, skin, and lungs, producing skin burns, conjunctivitis, and compromised respiratory function.
Acute Gene Expression Profile of Lung Tissue Following Sulfur Mustard Inhalation Exposure in Large Anesthetized Swine.
Sex, Specimen part
View SamplesOverexpression of the AP-2 transcription factor in breast tumours has been identified as an independent predictor of poor outcome and failure of hormone therapy, even in ER positive, ErbB2 negative tumours; markers of a more favourable prognosis. To understand further the role of AP-2 in breast carcinoma, we have used an RNA interference and gene expression profiling strategy using the MCF-7 cell line as a model for ER positive, ErbB2 negative tumours with AP-2 overexpression.
AP-2gamma promotes proliferation in breast tumour cells by direct repression of the CDKN1A gene.
Cell line
View SamplesOur laboratory wanted to define the transcription profile of aged skeletal muscle. For this reason, we performed a triplicate microarray study on young (3 weeks) and aged (24 months) gatrocnemius muscle from wild-type C57B16 Mice
Transcriptional profiling of skeletal muscle reveals factors that are necessary to maintain satellite cell integrity during ageing.
Sex
View Samples