Use of expression data to analyse ovarian cancer often yields long lists of genes that do not agree across various studies. Copy number however is more stable and can reliable predict important regions of change. Using matched copy number and expressiion data helps accurately identify novel drivers of ovarian cancer.
Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.
Age, Disease stage
View SamplesTo define the molecular regulators of metastasis of triple-negative breast cancer, we conducted a rigorous characterization of four isogenic populations of MDA-MB-231 human triple-negative breast cancer cells that display a range of intrinsic spontaneous metastatic capacities in immuno-deficient mice, from non-metastatic to highly metastatic to lung, liver, spleen and spine. PAT-Seq gene expression profiling of primary tumor cells identified the fibroblast growth factor homologous factor, FGF13, as a candidate metastatic virulence gene highly upregulated in aggressively metastatic MDA-MB-231HM tumors. Overall design: Gene expression analysis from PAT-Seq of 4 increasingly metastatic breast cancer xenograft tumours
Functional and genomic characterisation of a xenograft model system for the study of metastasis in triple-negative breast cancer.
Specimen part, Subject
View SamplesGenerating human serotonergic neurons from fibroblasts
Generation of functional human serotonergic neurons from fibroblasts.
No sample metadata fields
View SamplesThe evolutionarily conserved Wnt/?-catenin signaling pathway plays a fundamental role during metazoan development, regulating numerous processes including cell fate specification, cell migration, and stem cell renewal. Wnt ligand binding leads to stabilization of the transcriptional effector ?-catenin and upregulation of target gene expression to mediate a cellular response. During larval development of the nematode Caenorhabditis elegans, Wnt/?-catenin pathways act in fate specification of two hypodermal cell types, the ventral vulval precursor cells (VPCs) and the lateral seam cells. Because little is known about targets of the Wnt signaling pathways acting during larval VPC and seam cell differentiation, we sought to identify genes regulated by Wnt signaling in these two hypodermal cell types. We conditionally activated Wnt signaling in larval animals and performed cell type?specific "mRNA tagging" to enrich for VPC and seam cell?specific mRNAs, and then used microarray analysis to examine gene expression compared to control animals. Two hundred thirty-nine genes activated in response to Wnt signaling were identified, and we characterized 50 genes further. The majority of these genes are expressed in seam and/or vulval lineages during normal development, and reduction of function for nine genes caused defects in the proper division, fate specification, fate execution, or differentiation of seam cells and vulval cells. Therefore, the combination of these techniques was successful at identifying potential cell type?specific Wnt pathway target genes from a small number of cells and at increasing our knowledge of the specification and behavior of these C. elegans larval hypodermal cells.
Identification of Wnt Pathway Target Genes Regulating the Division and Differentiation of Larval Seam Cells and Vulval Precursor Cells in Caenorhabditis elegans.
Specimen part
View SamplesUMR106-01 osteoblastic cells are a model for studying bone mineralization. We have shown that mineralization is temporally synchronized within cultures grown under defined conditions . Cells are plated at time zero and differentiate into osteoblastic phenotype by 64 h later. If an exogenous phosphate source is added to the cultures, the cells form and deposit hydroxyapatite mineral within distinct extracellular supramolecular lipid protein complexes termed biomineralization foci (BMF) starting 12 h later. Mineralization is largely complete by 24 h later (88 h after plating). We have also shown that AEBSF, covalent serine protease inhibitor, blocks mineralization within BMF and inhibits the fragmentation of several proteins related to biomineralization. The present experiment was designed to test whether AEBSF treatment for 12 h has an effect on transcription by UMR106-01 osteoblastic cells. AEBSF is known to inactivate several serine proteases including SKI-1 (site 1, subtilisin kexin protease-1).SKI-1 functions intracellularly to activate transmembrane bound transcription factor precursors releasing the transcriptionally active N-terminal portions to imported into the nucleus. Thus, if AEBSF blocks transcription of mineralization related genes, it would support a role for SKI-1 in gene regulation in mineralizing UMR106-01 osteoblastic cells.
Inhibition of proprotein convertase SKI-1 blocks transcription of key extracellular matrix genes regulating osteoblastic mineralization.
Cell line
View SamplesTumor progression is associated with an immunosuppressive microenvironment that consists of several elements, such as regulatory T cells, type 2 macrophages and myeloid-derived suppressor cells. Here, we identify for the first time a BDCA1+CD14+ population of immunosuppressive cells that resides both in the blood and tumor of melanoma patients. We demonstrated that the presence of these cells in dendritic cell (DC)-based anti-tumor vaccines significantly suppresses CD4+ T cells in an antigen-specific manner. In an attempt to reveal the mechanism of this suppressive activity, we noticed that BDCA1+CD14+ cells express elevated levels of the check-point molecule PD-L1, which thereby hinders T cell proliferation. Importantly, although this suppressive BDCA1+CD14+ population expresses markers of both BDCA1+ DCs and monocytes, functional, transcriptome and proteome analyses clearly revealed that they comprise a unique population of cells that is exploited by tumors to evade immunity. Thus, targeting these cells may improve the efficacy of cancer immunotherapy. Overall design: mRNA profiles of BDCA1+ DCs, BDCA1+CD14+ cells and monocytes, isolated from 3 healthy volunteers, were generated by deep RNA sequencing using HiSeq 2000 System (TruSeq SBS KIT-HS V3,Illumina)
Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines.
No sample metadata fields
View SamplesPseudomonas aeruginosa (P. aeruginosa) lung infection is a significant cause of mortality in patients with cystic fibrosis (CF). Most CF patients acquire unique P. aeruginosa strains from the environment; however clonal strains have been identified in CF communities in several countries. Two clonal strains infect 10% to 40% of patients in three CF clinics in mainland eastern Australia. The expression profiles of four planktonically-grown isolates of one Australian clonal strain (AES-1), and four nonclonal CF P. aeruginosa isolates were compared to each other and to the reference strain PAO1 using the Affymetrix P. aeruginosa PAO1 genome array, to gain insight into properties mediating the enhanced infectivity of AES-1. The isolates were subsequently grown as 3-day old biofilms and similarly extracted for RNA and compared as above. Data analysis was carried out using BIOCONDUCTOR software.
Gene expression characteristics of a cystic fibrosis epidemic strain of Pseudomonas aeruginosa during biofilm and planktonic growth.
No sample metadata fields
View SamplesThe objective of this experiment was to determine global gene expression change in triple negative cell line upon knockdown of TGFBR3. Genotype specific differences in expression profiles have been evaluated using human HuGene1.0-ST affymetrix array. RNA was extracted from SUM159 controls and SUM159 TGFBR3KD cells cultured in 3-dimensional in vitro system.
Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer.
Cell line
View SamplesMycobacterium bovis is an intracellular pathogen that causes tuberculosis in cattle. Following infection, the pathogen resides and persists inside host macrophages by subverting host immune responses via a diverse range of mechanisms. Here, a high-density bovine microarray platform was used to examine the bovine monocyte-derived macrophage transcriptome response to M. bovis infection relative to infection with the attenuated vaccine strain, M. bovis Bacille CalmetteGurin. Differentially expressed genes were identified (adjusted P-value 0.01) and interaction networks generated across an infection time course of 2, 6 and 24 h. The largest number of biological interactions was observed in the 24 h network, which exhibited small-worldscale-free network properties. The 24 h network featured a small number of key hub and bottleneck gene nodes, including IKBKE, MYC, NFKB1 and EGR1 that differentiated the macrophage response to virulent and attenuated M. bovis strains, possibly via the modulation of host cell death mechanisms. These hub and bottleneck genes represent possible targets for immunomodulation of host macrophages by virulent mycobacterial species that enable their survival within a hostile environment.
Key Hub and Bottleneck Genes Differentiate the Macrophage Response to Virulent and Attenuated Mycobacterium bovis.
Sex, Age, Specimen part, Treatment, Time
View SamplesBackground: Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix GeneChip Bovine Genome Array with features representing more than 23,000 gene transcripts and over 19,000 gene probe sets.
Genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis reveals suppression of host immune genes.
Sex, Specimen part
View Samples