Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Brain microvessel: Alzheimer disease vs normal

ABSTRACT: The enigma that is Alzheimer's disease (AD) continues to present daunting challenges for effective therapeutic intervention. The lack of disease-modifying therapies may, in part, be attributable to the narrow research focus employed to understand this complex disease. Most studies into disease pathogenesis are based on a priori assumptions about the role of AD lesion-associated proteins such as amyloid-? and tau. However, the complex disease processes at work may not be amenable to single-target therapeutic approaches. Genome-wide expression studies provide an unbiased approach for investigating the pathogenesis of complex diseases like AD. A growing literature suggests a role for cerebrovascular contributions to the pathogenesis of AD. The objective of the current study is to examine human brain microvessels isolated from AD patients and controls by microarray analysis. Differentially expressed genes with more than 2-fold change are used for further data analysis. Gene ontology analysis and pathway analysis algorithms within GeneSpringGX are employed to understand the regulatory networks of differentially expressed genes. Twelve matched pairs of AD and control brain microvessel samples are hybridized to Agilent Human 4 × 44 K arrays in replication. We document that more than 2,000 genes are differentially altered in AD microvessels and that a large number of these genes map to pathways associated with immune and inflammatory response, signal transduction, and nervous system development and function categories. These data may help elucidate heretofore unknown molecular alterations in the AD cerebromicrovasculature. Two condition experiment, diseased vs normal, our study included 12 pairs of biological replicates and each pair was repeated with dye swap making total of 24 double channel hybridizations. we excluded 4 samples for not passing QC. So 20 samples were included in the data analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Uzma Qaisar

PROVIDER: E-GEOD-45596 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Gene expression profiling in Alzheimer's disease brain microvessels.

Wang Shu S Qaisar Uzma U Yin Xiangling X Grammas Paula P

Journal of Alzheimer's disease : JAD 20120101 1

The enigma that is Alzheimer's disease (AD) continues to present daunting challenges for effective therapeutic intervention. The lack of disease-modifying therapies may, in part, be attributable to the narrow research focus employed to understand this complex disease. Most studies into disease pathogenesis are based on a priori assumptions about the role of AD lesion-associated proteins such as amyloid-β and tau. However, the complex disease processes at work may not be amenable to single-target ...[more]

PMID: 22531426

Similar Datasets

Project description:Transcriptional profiling of LNCaP prostate cancer cells comparing control siRNA-treated LNCaP cells with LNCaP cells treated with siRNAs targeting Prostate Cancer Associated Transcript-1 (PCAT1), an uncharacterized long non-coding RNA. High-throughput sequencing of polyA+ RNA (RNA-Seq) in human cancer shows remarkable potential to identify both novel disease-specific markers for clinical uses and uncharacterized aspects of tumor biology, particularly non-coding RNA (ncRNA) species. To illustrate this approach, we employed RNA-Seq on a cohort of 102 prostate tissues and cells lines and found that aberrant expression profiles of novel tissue-specific ncRNAs distinguished benign, cancerous, and metastatic tumors. Among these, a novel prostate-cancer specific ncRNA (termed PCAT-1) defined a subset of aggressive cancers with low expression of the epigenetic regulator EZH2, a component of the Polycomb Repressive Complex 2 (PRC2) commonly upregulated in metastatic cancers. In vitro assays for core PRC2 genes indicated that the PRC2 complex directly binds and represses PCAT-1, and that the PCAT-1 transcript reciprocally binds PRC2, suggesting a regulatory feedback mechanism. Importantly, knockdown of PCAT-1 in cells with high levels of endogenous PCAT-1 transcript showed changes in cell proliferation and transcriptional regulation of several key biological processes, including cell cycle. Finally, we showed that ncRNA expression signatures, including PCAT-1, were effective for the non-invasive detection of prostate cancer, and that high ncRNA expression signature values correlate with high-grade histology. The findings presented herein establish the utility of RNA-Seq to comprehensively identify unannotated ncRNAs that define human disease states and characterize PCAT-1 as a novel regulator of cell proliferation mechanistically linked to PRC2 and contributory to translational clinical tests for prostate cancer. Two-condition experiment: Control-siRNA-treated versus PCAT1-siRNA-treated LNCaP cells. Biological replicates: 3 control replicates, 3 treatment replicates.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease characterized by late diagnosis and treatment resistance. Recurrent genetic alterations in defined genes in association with perturbations of developmental cell signaling pathways have been associated with PDAC development and progression. Here, we show that GATA6 contributes to pancreatic carcinogenesis during the temporal progression of pancreatic intraepithelial neoplasia by virtue of Wnt pathway activation. GATA6 is recurrently amplified by both quantitative-PCR and fluorescent in-situ hybridization in human pancreatic intraepithelial neoplasia and in PDAC tissues, and GATA6 copy number is significantly correlated with overall patient survival. Forced overexpression of GATA6 in cancer cell lines enhanced cell proliferation and colony formation in soft agar in vitro and growth in vivo, as well as increased Wnt signaling. By contrast siRNA mediated knockdown of GATA6 led to corresponding decreases in these same parameters. The effects of GATA6 were found to be due to its ability to bind DNA, as forced overexpression of a DNA-binding mutant of GATA6 had no effects on cell growth in vitro or in vivo, nor did they affect Wnt signaling levels in these same cells. A microarray analysis revealed the Wnt antagonist Dickopf-1 (DKK1) as a dysregulated gene in association with GATA6 knockdown, and direct binding of GATA6 to the DKK1 promoter was confirmed by chromatin immunoprecipitation and electrophoretic mobility shift assays. Transient transfection of GATA6, but not mutant GATA6, into cancer cell lines led to decreased DKK1 mRNA expression and secretion of DKK1 protein into culture media. Forced overexpression of DKK1 antagonized the effects of GATA6 on Wnt signaling in pancreatic cancer cells. These findings illustrate that one mechanism by which GATA6 promotes pancreatic intraepithelial neoplasia is by virtue of its activation of canonical Wnt signaling via regulation of DKK1. AsPC1 and A13A cells were stably transfected with a lentivirus expressing mock shRNA or shRNA to GATA6. Each control/shRNA pair (total 4 samples) was analyzed by two-color microarray and the genes commonly dysregulated in both cell lines identified.

Project description:Pseudomonas aeruginosa is a gram negative pathogen that infects acute wounds such as third degree skin injury and chronic wounds such as diabetic ulcers. Within infection sites, this pathogen exists in specific structures termed as biofilms. Biofilms contribute to enhanced resistance of microorganisms to the host defense and antibiotic treatments. Flagella, pilli and chaperon usher pathway (cup) fimbriae provide initial attachment to host tissue during biofilm development. pvcA-D operon codes for proteins which synthesize a secondary metabolite called paerucumarin. Paerucumarin is an isonitrile functionalized cumarin which is not extensively analyzed. We recently showed that paerucumarin enhances the expression of cup genes and biofilm development. We hypothesize that besides the cup genes pvcA-D operon regulates other P. aeruginosa genes. To test this hypothesis, we compared the transcriptome of P. aeruginosa strain MPAO1 with its pvcA mutant (MPAO1/pvcA). In comparison with MPAO1, 53 genes were differentially expressed in pvcA which included 19 up-regulated and 34 down-regulated genes. Functional characterization of differentially expressed genes indicated that 20 of these genes have been reported as iron regulated genes. Real time PCR confirmed these results and indicated that the expression of pvcAD operon is iron independent. However traditional chrome azurol S (CAS) iron binding assay showed that paerucumarin binds iron either within supernatants of MPAO1 or in solution. In addition, exogenously added paerucumarin enhances the expression of iron repressed genes pvdS and pvdA. Similarly, the level of pvdS gene expression in MPAO1?pvcA was significantly reduced as compared to MPAO1. Further analysis confirmed that paerucumarin binds iron in MPAO1 but does not deliver it inside the cell. The growth of a PAO1 double mutant strain (?pvdD?pchA), defective in iron scavenging systems, grown in iron deficient medium was restricted. However, the growth was restricted even further upon addition of exogenous paerucumarin to bacterial cultures. These results suggest that paerucumarin chelates iron but does not function as an iron scavenging system. 4 biological replicates of each strain were randomly paired

Dataset Information

Brain microvessel: Alzheimer disease vs normal

Publications

Gene expression profiling in Alzheimer's disease brain microvessels.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets