title: Identification of global regulators of T-helper cell lineage specification (BeadChip)

status: Public on Nov 20 2015

city: Turku

first: Kartiek

last: Kanduri

address: Tykistokatu 6

country: Finland

institute: Turku Centre for Biotechnology

summary: The aim of the dataset was to identify genome-wide regulators of gene expression in early differentiation of human cord blood derived CD4+ T cells cultured under Th1 (Act+IL12) and Th2 (Act+IL4) polarising conditions.

overall_design:
Total RNA from naive CD4+ T cells was compared to total RNA from cells cultured in the following three conditions:
activating (antiCD3+antiCD28)+antiIL4+antiIFNG;
activating (antiCD3+antiCD28)+IL12+antiIL4;
activating (antiCD3+antiCD28) +IL4+antiIFNG.
Samples from 3 biological replicates were analysed.

first: Subhash

last: Tripathi

first: Antti

last: Larjo

first: Henrik

last: Mannerström

first: Ubaid

last: Ullah

first: Riikka

last: Lund

last: Hawkins

first: Bing

last: Ren

first: Harri

last: Lähdesmäki

first: Riitta

last: Lahesmaa


title: RNA interference uncouples the function of a long noncoding RNA product from that of its transcription [HB2]

status: Public on Nov 12 2015

city: Cambridge

first: Suraj

last: Menon

address: Li Ka Shing Center, Robinson Way

country: United Kingdom

institute: Cambridge Research Institute, Cancer Research UK

summary:
Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is missing. We employed siRNAs to specifically target GNG12-AS1, a lncRNA overlapping the tumour suppressor DIRAS3, transcriptionally or post-transcriptionally. lncRNA transcriptional silencing by siRNA was mediated by Argounate 2 and led to the upregulation of DIRAS3 transcription through switch in  RNA polymerase II binding and active histone marks. Conversely, post-transcriptional silencing of GNG12-AS1 had no effect on DIRAS3 expression.  Thus, our findings reveal how RNAi machinery can be used to decouple the process and products of lncRNA transcription.
The goal of this study was to identify genes regulated by long noncoding RNA GNG12-AS1 in human cells

overall_design: RNA was extracted from human cells (HB2, SUM159) treated with control and GNG12-AS1 siRNAs. The analysis was performed with six biological replicates for each cell line.

first: Lovorka

last: Stojic


title: RNA interference uncouples the function of a long noncoding RNA product from that of its transcription [SUM159]


title: RNA interference uncouples the function of a long noncoding RNA product from that of its transcription: HB2 and SUM159 cells

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Epigenetic profiling in CD4 and CD8 T cells from Graves’ disease patients reveals changes in genes associated with T cell receptor signaling [gene expression]

status: Public on Nov 06 2015

city: Tartu

first: Pärt

last: Peterson

address: Ravila 19

department: Department of Biomedicine

country: Estonia

institute: University of Tartu

summary: In Graves’ disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively. Among the hypermethylated CpG sites, we specifically found enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members. The hypermethylation was accompanied with the active chromatin histone modifications as we found decreased signals of H3K4me3 and H3K27ac marks at several T cell signaling genes in ChIP-seq analysis. In addition, we found hypermethylation of the TSHR gene first intron, where several GD-associated polymorphisms are located. Our results demonstrate an involvement of dysregulated DNA methylation and histone modifications at T cell signaling genes in GD patients.

overall_design: Individuals were recruited from the Estonian Genome Center of the University of Tartu. Total RNA was extracted from sorted CD4+ (10 controls and 15 GD patients) and CD8+ (8 controls and 16 GD patients) T cells. The data collection was performed at the Estonian Genome Center Core Facility, and data analyses was done at the Institute of Biomedicine and Translational Medicine in the University of Tartu.

first: Lili

last: Milani


title: siRNA smart pool silencing of master regulators of Follicular Lymphoma transformation to DLBCL

status: Public on Nov 11 2015

city: New York

first: Mukesh

last: Bansal

state: NY

address: 1130 St. Nicholas Ave. Room 908

country: USA

institute: Columbia University

summary: Follicular lymphoma (FL) is the most common indolent subtype of non-Hodgkin’s lymphoma, with relatively long overall survival rate ranging from 6 to 10 years from time of diagnosis. However, 20-60% of FL patients undergo transformation to aggressive diffuse large B cell lymphoma (DLBCL), with a reduced median survival of about 1.2 years. The specific functional and genetic determinants of FL transformation are still elusive and only a relatively small fraction of the cases is accounted for by established, recurrent alterations in TP53, MYC and BCL6, inactivation of CDKN2A and CDKN2B, or amplification of REL. We addressed this deficiency by performing systematic analysis of a B cell specific regulatory model with FL transformation signatures, using the Master Regulator Inference algorithm (MARINa). We show that the candidate master regulators inferred by the algorithm in FL induce synthetic lethality in DLBCL cells and lead to identification of specific compound combinations inducing synergistic loss of viability in transformed DLBCL cells

overall_design: RNA was obtained from 45 samples, which included siRNA silencing of 5 single transcription factors, 5 combinations of two transcription factors and non-target control in triplicates.

first: Brygida

middle: C

last: Bisikirska

first: Yao

last: Shen

first: Julie

last: Teruya-Feldstein

first: Raju

last: Chaganti

first: Andrea

last: Califano


title: Classifying distinct grades of human non-alcoholic fatty liver disease employing a systems biology approach

status: Public on Nov 01 2015

city: Düsseldorf

first: Wasco

last: Wruck

address: Moorenstr. 5

country: Germany

institute: Universitätsklinikum Düsseldorf

summary: With an estimated prevalence of about 30% in western countries non-alcoholic fatty liver disease (NAFLD) is a major public health issue [PMID: 18956290]. NAFLD is associated with the metabolic syndrome of insulin resistance, obesity, glucose intolerance. Although many studies are pointing to an induction of insulin resistance by NAFLD causality between both phenotypes is not fully clarified. Furthermore, mechanisms leading to strongly differing progression of NAFLD have to be elucidated which range from mild steatosis up to severe steatohepatitis. Steatohepatitis might even result in liver cirrhosis and hepatocellular carcinoma. Additional complexity is introduced into the understanding of the disease by recent studies providing evidence for a direct development of carcinoma from steatosis without the formerly assumed intermediary phase of cirrhosis. Here, we investigate liver samples from patients with varying severities of steatosis in an integrative approach employing transcriptomics, serum biomarker profling, metabolomics data and systems biology models.

overall_design: Total RNA obtained from hepatocytes derived from nine obese patients with distinct grades of steatosis.

first: Wruck

last: Wasco

first: Jozefczuk

last: Justyna


title: Electrical stimulation of human embryonic stem cell derived cardiomyocytes

status: Public on Nov 05 2015

first: Gordana

last: Vunjak-Novakovic

department: Biomedical Engineering

summary: Analysis of the effect of electrical field stimulation frequency at the gene expression level. Electrical stimulation has been shown to mature nascent cardiomyocytes and alter their beating properties. The purpose of the array was to identify potential mediators of these effects.

overall_design: Total RNA was isolated from cardiomyocytes subjected to 0.5 Hz, 1 Hz, or 2 Hz continuous electrical stimulation for 7 days, compared to an unstimulated control. Three samples from each group were analyzed

first: George

last: Eng

first: Benjamin

middle: W

last: Lee


title: The Nasal Gene Expression and Childhood Atopic Asthma

city: Aurora

first: David

last: Schwartz

state: CO

address: Anschutz Medical Campus

department: Medicine

institute: University of Colorado, Anschutz Medical Campus

summary: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma versus healthy controls. We identified 119 differentially methylated regions (DMRs) and 118 differentially methylated probes (DMPs) after adjustment for age, gender, race/ethnicity, batch effects, inflation, and multiple comparisons (false discovery rate-adjusted q<0.05). Genes differentially methylated include those with established roles in asthma and atopy, components of the extracellular matrix, genes related to immunity, cell adhesion, epigenetic regulation, and airway obstruction. Hypo- and hypermethylated genes were associated with increased and decreased gene expression respectively (P<2.8x10-6 for DMRs and P<7.8x10-10 for DMPs). Quantitative analysis of methylation-expression relationships in 53 differentially expressed genes demonstrated that 32 (60%) have significant (q<0.05) methylation-expression relationships within 5kb of the gene. 10 loci selected based on the relevance to asthma, magnitude of methylation change, and asthma specific methylation-expression relationships were validated in an independent cohort of children with asthma.

overall_design: case control design with nasal epithelial cells from 36 atopic asthmatic and 33 nonatopic nonasthmatic children from the inner city

first: Ivana

middle: V

last: Yang

first: Brent

middle: S

last: Pedersen

middle: A


title: Transcriptomic profiling of the inflammatory response after trauma

city: Jena

first: S.

last: Lambeck

address: Erlanger Allee 101

institute: JUH

summary: The study was aimed to identify mechanisms linked to complicated courses after severe trauma by a systems biology approach. In severe trauma, overwhelming systemic inflammation can result in adverse events and the development of complications, including sepsis. In a prospective study, RNA samples from circulating leukocytes from patients with multiple injury (injury severity score ≥ 17) were analyzed for dynamic changes in gene expression over a period of 21 days by whole genome screening. Based on their clinical presentation, patients were divided into two subgroups: patients with secondary sepsis after trauma (n=5) and patients with systemic inflammation without infection (n=5). Expression cluster were defined by correlating gene expression data with clinical outcome parameters. Using unsupervised clustering, patients with systemic inflammation only and patients with sepsis showed a distinct expression pattern and the discrimination of clinical presentation was reflected by clustering of the samples. Explorative gene set analysis revealed robust upregulation of genes related to ‘hemoglobin metabolism/oxygen transport’ and ‘pathogenic E.coli infection’.

overall_design: 10 patients with multi-system trauma (ISS ≥ 17 points) admitted to the Division of Trauma Surgery at the University Hospital Zurich were included. Whole blood from trauma patients was collected within the first 6 h after trauma (day 0) and on days 1, 2, 3, 5, 7, 10, 14, and 21. Total cellular RNA from circulating leukocytes was isolated using PaxGene Blood RNA Kit (PreAnalytix) for transcriptome profiling. RNA from blood of trauma patients was extracted and subjected to microarray analysis for comparison of longitudinal transcriptomic responses of patients.  RNA samples of circulating leukocytes covering time points directly after admission (D0) and on the consecutive days (D1-D21) were subject to multifactorial microarray data analysis: Differences in dynamics of transcripts were assessed by contrasting time- and individual-resolved changes for sepsis and systemic inflammation without infection.

first: Daniel

last: Rittirsch

first: Sandro

last: Lindig

first: Veit

last: Schoenborn

first: Markus

last: Blaess

first: Paolo

last: Cinelli

first: Michael

last: Bauer

first: Ralf

last: Claus

first: Guido

last: Wanner


title: Nitric oxide regulates gene expression in cancers by controlling histone posttranslational modifications [PrimeView]

city: Chicago

first: Douglas

middle: David

last: Thomas

state: IL

address: 900 S Ashland Ave Room 3306

department: Medicinal Chemistry & Pharmacognosy

institute: University of Illinois at Chicago

summary: Dynamic changes in histone posttranslational modifications (PTMs) are important regulators of chromatin structure and gene transcription in both normal and disease settings. Herein, we describe a novel signaling mechanism of nitric oxide (•NO) by demonstrating its ability to modulate gene expression via alteration of histone PTMs. Having established that •NO exposure induced differential expression of approximately 6500 genes, we set out to determine if there was an epigenetic component to their regulation. •NO exposure led to alterations in the global levels of acetyl and methyl modifications at numerous lysine residues on core histones H3 and H4. Residues H3K9me2/ac were examined further and determined to have differential distribution at various loci throughout the genome in response to •NO. Changes in the enrichment levels of H3K9me2/ac at specific genes correlated with changes in the expression levels of their transcripts. Molecular mechanisms contributing to phenotypic outcomes in •NO-associated cancers remain to be well understood since traditional modes of •NO-signaling do not explain a large proportion of its impact on tumor cell behavior. Our results reveal that •NO drives a significant amount of gene expression changes epigenetically by changing the distribution of numerous histone marks.

overall_design: Cultured cells were treated with 500uM DETA/NO to examine the effects of a physiologically relevant •NO concentration on gene expression. A total of two untreated biological replicates and two •NO-treated biological replicates were harvested. The untreated samples served as control against which comparisons were made to elucidate •NO-mediated changes in the gene expression.

first: Divya

last: Vasudevan

first: Jason

middle: R

last: Hickok

first: Rhea

last: Bovee

first: Vy

last: Pham

first: Lin

middle: L

last: Mantell

first: Neil

last: Bahroos

first: Pinal

last: Kanabar

first: Xing-Jun

last: Cao

first: Mark

last: Maienschein-Cline

last: Garcia

middle: D


title: High FGFR2 expression is associated with reduced breast cancer risk and represses the estrogen response

status: Public on Nov 04 2015

first: Kerstin

last: Meyer

address: Robinson Way

department: Cancer Research UK Cambridge Institute

institute: University of Cambridge


title: Mevalonate pathway antagonist inhibits proliferation of serous tubal intraepithelial carcinoma and ovarian carcinoma in mouse models.

city: Baltimore

first: Ie-Ming

last: Shih

state: Maryland

address: 1550 Orleans St. CRB-II, Room 305

department: Pathology

institute: Johns Hopkins University School of Medicine

summary:
Statins are among the most frequently prescribed drugs because  of their efficacy and low toxicity in treating hypercholesterolemia.  Recently, statins have been reported to inhibit the proliferative activity  of cancer cells, especially those with *TP53* mutations. Since *TP53*  mutations occur in almost all of the ovarian high-grade serous carcinoma, we determined if statins suppressed tumor growth in animal models of  ovarian cancer.
Two ovarian cancer mouse models were employed. The first one was a genetically engineered model, mogp-TAg, in which the  promoter of oviduct glycoprotein-1 was used to drive the expression of SV40 T-antigen in gynecologic tissues. These mice spontaneously develop serous  tubal intraepithelial carcinomas (STICs), which are known as ovarian cancer  precursor lesions. The second model was a xenograft tumor model in which human ovarian cancer cells were inoculated into immunocompromised mice.  Mice in both models were treated with lovastatin, and effects on tumor  growth were monitored. The molecular mechanisms underlying the anti-tumor  effects of lovastatin were also investigated.
Lovastatin significantly reduced the development of STICs in  mogp-TAg mice and inhibited ovarian tumor growth in the mouse xenograft  model. Knockdown of prenylation enzymes in the mevalonate pathway  recapitulated the lovastatin-induced anti-proliferative phenotype.  Transcriptome analysis indicated that lovastatin affected the expression of  genes associated with DNA replication, Rho/PLC signaling, glycolysis, and  cholesterol biosynthesis pathways, suggesting that statins have pleiotropic  effects on tumor cells.
The above results suggest that repurposing statin drugs for  ovarian cancer may provide a promising strategy to prevent and manage this devastating disease.

overall_design: SKOV3 and OVCAR5 cells were treated with either 10uM Lovastatin or DMSO for 48 hours before harvested for gene expression array.

first: Yusuke

last: Kobayashi

first: Ren-Chin

last: Wu

first: Tian-Li

last: Wang


title: Gene expression profiles of normal human tonsillar cell subpopulations FACS sorted based on expression of cell surface markers

status: Public on Oct 29 2015

city: Vancouver

first: Catherine

last: Kang

state: British Columbia

address: 675 West 10th Avenue

country: Canada

institute: British Columbia Cancer Research Centre

summary: To characterize the progenitor-enriched CD44+NGFR+ cells present in the crypt and surface regions of the tonsil, we used an Illumina array system to analyze the transcriptome of these cells isolated from the tonsillar crypt and surface regions of three different individuals as well as the total epithelial (CD45-CD31-) populations obtained from two of these.

overall_design: To enrich for epithelial progeniors in human palatine tonsil tissue, hematopoietic and endothelial cells were depleted from freshly isolated cell suspensions derived from palatine tonsils using fluorescence-activated cell sorting (FACS). The resultant CD45-CD31- population was further fractionated into four subpopulations using antibodies against CD44 and NGFR. Based on the immunohistochemical phenotype and in vitro functional assays, CD44+NGFR+ subpopulations were identified as epithelial progenitor-enriched subsets.  Microarray profiling was used to derive gene expression signatures of CD45-CD31- subsets (total epithelial-enriched) and CD45-CD31-CD44+NGFR+ subpopulations (progenitor-enriched).

first: Sung-Yoon


title: Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis

status: Public on Oct 26 2015

city: Los Angeles

first: Anais

last: Briot

state: CA

address: 621 Charles E. Young Drive, South

department: Molecular, Cell and Developmental Biology

institute: University of California, Los Angeles

summary: While much progress has been made in identifying the mechanisms that trigger endothelial activation and inflammatory cell recruitment during atherosclerosis, less is known about the intrinsic pathways that counteract these events. Here we identified NOTCH1 as an antagonist of endothelial cell activation. NOTCH1 was constitutively expressed by adult arterial endothelium, but levels were significantly reduced by high fat diet. Furthermore, treatment of human aortic endothelial cells (HAEC) with inflammatory lipids (Ox-PAPC) and pro-inflammatory cytokines (TNFalpha and IL1beta) decreased Notch1 expression and signaling in vitro through a mechanism that requires STAT3 activation. Reduction of NOTCH1 in HAEC by siRNA, in the absence of inflammatory lipids or cytokines, increased inflammatory molecules and binding of monocytes. Conversely, some of the effects mediated by Ox-PAPC were reversed by increased NOTCH1 signaling; suggesting a link between lipid-mediated inflammation and Notch1. Interestingly, reduction of NOTCH1 by Ox-PAPC in HAEC was associated with a genetic variant previously correlated to HDL in a human GWAS. Finally endothelial Notch1 heterozygous mice showed higher diet-induced atherosclerosis. Based on these findings, we propose that reduction of endothelial NOTCH1 is a predisposing factor in the onset of vascular inflammation and initiation of atherosclerosis.

overall_design: Transcript profile from Human Aortic Endothelial Cells (HAEC) transfected with siRNA targeting NOTCH1 (n=3) or treated with Ox-PAPC (Oxidized 1-Palmitoyl-2-Arachidonoyl-sn-glycero-3-PhosphoCholine) for 6 hours (n=3) were compared to control HAEC (transfected with control siRNA and control media; n=3).

first: Mete

last: Civelek

first: Aldons

middle: J

last: Lusis

first: Judith

last: Berliner

first: M

last: Iruela-Arispe


title: IL-22 regulation of functional gene expression in salivary gland cells

status: Public on Oct 27 2015

city: Gainesville

first: cuong

last: nguyen

address: 2015 SW 16th Ave

institute: University of Florida

summary: Microarray analysis using the HumanHT-12 v4 Expression BeadChip was utilized to determine the biological function of IL-22.  The data indicate an extensive effect of IL-22 on many major molecular functions including activation of antimicrobial genes and downregulation of immune-associated pathways.  Functional studies performed in-vitro using human salivary gland cells treated with IL-22 indicated a direct effect of IL-22 on cell cycling, specifically reducing cellular proliferation at the G2-M phase by activation of STAT3.

overall_design: Total RNAs were obtained from salivary gland cells stimulated with recombinant IL-22 for 45 minutes.  Differential expression analyses were conducted using the LIMMA package from the Bioconductor project.  MTT assay, flow cytometry and western blotting were used to identify the function of IL-22 on human salivary gland cells.

first: Cuong

last: Nguyen

first: Ashok

last: Sharma


title: Effects of overexpression of hsa-miR-140-3p and its 5'isomiR in MCF10A and MDA-MB-231 breast cell lines

status: Public on Oct 31 2015

city: Heidelberg

first: Cindy

last: Körner

address: INF 580

department: Molecular Genome Analysis

institute: DKFZ

summary:
miRNAs are small noncoding RNA molecules that play an important role in post-transcriptional regulation of gene expression. Length and/or sequence variants of the same miRNA are termed isomiRs. While most isomiRs are functionally redundant compared to their canonical counterparts, so-called 5’isomiRs exhibit a shifted 5’ end and therefore a shifted seed sequence resulting in a different target spectrum. However, not much is known about the functional relevance of these isoforms.  Analysis of miRNA-seq data from breast cancer cell lines identified six pairs of highly expressed miRNAs and associated 5’isomiRs. Among them, hsa-miR-140-3p was of particular interest because its 5’isomiR showed higher expression compared to the canonical miRNA annotated in miRbase. This miRNA has previously been shown to control stemness of breast cancer cells. MiRNAseq data of breast cancer patients (TCGA dataset) showed that both the canonical hsa-miR-140-3p and its 5’isomiR-140-3p were highly expressed in patients compared to normal breast tissue. In the current work, we present the functional characterization of 5’isomiR-140-3p and the cellular phenotypes associated with its overexpression in MCF10A and MDA-MB-231 cell lines in comparison to the canonical hsa-miR-140-3p. Contrary to the effect of the canonical hsa miR 140-3p, overexpression of the 5’isomiR-140-3p led to a decrease in cell viability. The latter observation was supported by cell cycle analysis, where the 5’isomiR-140-3p but not the hsa-miR-140-3p caused cell cycle arrest in G0/G1-phase. Additionally, 5’ismoiR-140-3p overexpression was found to cause a decrease in cell migration in MCF10A cells. We identified three novel direct target genes of the 5’ isomiR-140-3p; COL4A1, ITGA6 and MARCKSL1. Finally, we have shown that knocking down these genes partially phenocopied the effects of the 5’isomiR-140-4p overexpression, where COL4A1 and ITGA6 knockdown led to reduced cell viability and cell cycle arrest, while MARCKSL1 knockdown resulted in a decrease in the migratory potential of cells.  In summary, this work presents evidence that there is a functional synergy between the canonical hsa-miR-140-3p and the newly identified 5’isomiR-140-3p in suppressing growth and progression of breast cancer by simultaneously targeting genes related to differentiation, proliferation, and migration.
With this array, we aimed to address the question which genes are regulated by either of the two forms of the miRNA.

overall_design: Samples were measured in one biological replicate of cells transfected with mimic-ctrl1 and mimic-ctrl2 (Dharmacon) as control samples and two biological replicates of cells transfected with hsa-miR-140-3p and 5'isomiR-140-3p (Exiqon) in 30nM concentration using Lipofectamin 2000 as transfection reagent.

first: Omar

last: Salem

first: Stefan

last: Wiemann


title: Gene expression in pediatric acute lymphoblastic leukemia patient-derived xenografts

status: Public on Oct 24 2015

city: Randwick

first: Duohui

last: Jing

state: NSW

address: Lowy Cancer Research Centre, UNSW

department: Leukaemia Biology

country: Australia

institute: Children’s Cancer Institute Australia

summary: In this study, pediatric ALL patient-derived xenografts (PDXs) inherently resistant to glucocorticoids were cultured in vitro. The study aims to determine discrepancy in gene expressions between different xeno strains.

overall_design: The same xenograft was innoculated into 3 mice. Spleen-harvest xenograft samples were analyzed using microarray.

first: Cara

last: Toscan

first: Richard

middle: B

last: Lock


title: Integration of genomic and proteomic data to identify candidate genes in HT-29 cells after incubation with Bifidobacterium bifidum ATCC 29521

status: Public on Oct 19 2015

city: Nanchang

first: Yaoping

last: Wu

state: Jiangxi

address: Nanchang University 235 Nanjingong Road

country: China

institute: Nanchang Univ.

summary: Identify candidate different expression genes in HT-29 cells after incubation with Bifidobacterium bifidum ATCC 29521.  The results of microarray provide importment information for different genes expression in HT-29 cell after incubation withBifidobacterium bifidum ATCC 29521, up or down-regulated.

overall_design: Total RNA extracted from HT-29 cell which incubation with Bifidobacterium bifidum ATCC 29521 compared to unincubation.

first: Baogui


title: Global Gene Expression Profiles of Fibroblasts from the Lungs of Patients with Idiopathic Pulmonary Fibrosis: The Role of CCL8

city: Seoul

first: Hyun Sub

last: Cheong

address: #1007, Teihard Hall, Sogang Univ. Baekbum-ro 35, Mapo-gu

department: Genetic Epidemiology

country: South Korea

institute: SNP Genetics, Inc.

summary: Analysis of Idiopathic pulmonary fibrosis (IPF) at gene expression level. The hypothesis tested in the present study was that Epigenetic mechanisms are likely to be associated with pathogenesis in IPF. To determine the DNA methylation change, and their effects on gene expression, we compared microarray data of DNA methylation and RNA expression. Results provide that among the genes whose DNA methylation status and RNA expression were both significantly altered between IPF-rapid and normal controls.

overall_design: Total RNA obtained from Idiopathic pulmonary fibrosis samples.

first: Jong-Uk

last: Lee

first: Choon-Sik

last: Park


title: Characterization and quantification of proteins secreted by single human embryos prior to implantation

status: Public on Oct 20 2015

city: Oxford

first: Dagan

last: Wells

address: 8000 Alec Issigonis Way

institute: University of Oxford

type:
Expression profiling by array
Genome variation profiling by array


title: CD40-mediated amplification of local immunity by keratinocytes in impaired by HPV

city: Leiden

first: Bart

last: Tummers

address: Albinusdreef 2

department: Clinical Oncology

country: Netherlands

institute: Leiden University Medical Center

summary: The interaction between the transmembrane glycoprotein surface receptor CD40 expressed by skin keratinocytes (KCs) and its T cell-expressed ligand CD154 was suggested to exacerbate inflammatory skin diseases. However, the full spectrum of CD40-mediated effects by KCs underlying this observation is unknown. Therefore, changes in gene expression after CD40 ligation of KCs were studied by microarrays. CD40-mediated activation for 2 hours stimulated the expression of a coordinated network of immune-involved genes strongly interconnected by IL8 and TNF, while after 24 hours anti-proliferative and anti-apoptotic genes were upregulated. CD40 ligation stimulated the production of chemokines that attracted lymphocytes and myeloid cells from peripheral blood mononuclear cells (PBMCs). Thus, CD40-mediated activation of KCs resulted in a highly coordinated response of genes required for the local development and sustainment of adaptive immune responses. The importance of this process was confirmed by a study on the effects of human papilloma virus (HPV) infection to the KC’s response to CD40 ligation. HPV infection clearly attenuated the magnitude of the response to CD40 ligation and consequently the KC’s capacity to attract PBMCs. The fact that HPV attenuates CD40 signalling in KCs indicates the importance of the CD40-CD154 immune pathway in boosting cellular immunity within epithelia.

overall_design: Total RNA from eight 72 hours 50 IU/ml IFNgamma pre-stimulated primary undifferentiated keratinocyte cultures, four uninfected and four HPV-positive, that were either left unstimulated, or stimulated for 2 hours with IFNgamma and Control- or CD40L-expressing L-cells (mouse fibroblasts), or stimulated for 24 hours with IFNgamma and Control- or CD40L-expressing L-cells. The stimulated samples were generated in duplo. 72 samples were generated in total.

first: Judith

middle: M

last: Boer


title: Distinct lncRNA expression profiles in the distal end of sciatic nerve after peripheral nerve injury

status: Public on Oct 17 2015

city: Tianjin China

first: Bin

last: Pan

address: 154 Anshan Road, Heping District, Tianjin, People's Republic of China

institute: Orthopedics Department of General Hospital, Tianjin Medical University

type:
Expression profiling by array
Non-coding RNA profiling by array

summary: Peripheral nerve injuries are common in modern society. The patients may suffer from partial or total loss of sensory, motor and autonomic function in the involved segments of the body. However, The molecular mechanisms of the regeneration program has not yet been definitively clarified and the comprehensive lncRNA expression signature in peripheral nerve regeneration remains fully unknown.We performed a high throughput microarray assay to detect lncRNA expression profile in the distal end of peripheral nerve at 0,3,7,14 day after injury.

overall_design: 72 C57Bl6 mice at the age around 2 months were selected and divided into 4 groups randomly depending on the time points of 0, 3, 7, 14 d after peripheral nerve injury. Each group included 18 mice of which 6 were pooled into a sample (three biological replication in one group)

first: Shi

middle: Q

last: Feng


title: Implications of the heterogeneous gene expression traits in recurrent glioblastoma

city: Suwon

first: Hyun Goo

last: Woo

address: 164 Worldcup-ro Yeongtong-gu

institute: Ajou University School of Medicine

summary: Glioblastoma multiforme (GBM) is the most aggressive and frequent primary brain tumor with dismal prognosis which might be due to the resistance to the current standard chemotherapeutic regimens and high recurrence rate even after total resection of GBM mass. Here, to gain the mechanistic insights on the altered phenotypic acquisition of recurrent tumors compared to the corresponding primary tumors, we performed gene expression profiling on the 43 cases of GBM tumors including 15 paired recurrent and primary GBMs. Unsupervised and consensus clustering analyses revealed two subtypes of G1 and G2, which were enriched with proliferation, and neuron-like gene expression traits, respectively. Most of the primary tumors were classified into G1, while the recurrent tumors were classified into both G1 and G2 groups. The gene expression of recurrent GBMs in G2 group have changed from proliferation type to neuron-like type, while the other recurrent GBMs in the G1 group showed no significant subtype change. In addition, we observed that the recurrent tumors in G1 subtype were characterized with the expression of stemness-related genes and DNA-repair genes. Of the G1 subtype classifier genes, AURKA/B and HOX genes were identified as key hub regulators. On the other hand, the recurrent G2 tumors have acquired the expression of MGMT but suppression of MSH6 gene, which may lead to TMZ resistance. The consistency of these findings could be validated with independent data sets. In summary, our molecular classification of recurrent GBMs could suggest that the differential mechanisms of drug resistance be involved in the tumor recurrence. Targeting the subtype-specific mechanisms might be a beneficial strategy for the treatment of recurrent GBMs.

overall_design: 43 GBMs (25 Primary GBMs and 18 Recurrent GBMs including 15 pairs)

first: Hyun


title: Gene expression of human blastocysts by microarrays

summary:
The use of in vitro fertilization (IVF) has revolutionized the treatment of infertility and is now responsible for 1-5% of all births in industrialized countries. During IVF, it is typical for patients to generate multiple embryos. However, only a small proportion of them possess the genetic and metabolic requirements needed in order to produce a healthy pregnancy. The identification of the embryo with the greatest developmental capacity represents a major challenge for fertility clinics. Current methods for the assessment of embryo competence are proven inefficient and the inadvertent transfer of non-viable embryos is the principal reason why most IVF treatments (approximately two-thirds) end in failure. In this study, we investigate how the application of proteomic measurements could improve success rates in clinical embryology. We describe a procedure that allows the identification and quantification of proteins of embryonic origin, present in attomole concentrations in the blastocoel, the enclosed fluid filled cavity that forms within five-day old human embryos. By using targeted proteomics, we demonstrate the feasibility of quantifying multiple proteins in samples derived from single blastocoels, and that such measurements correlate with aspects of embryo viability, such as chromosomal (ploidy) status. This study illustrates the potential of high-sensitivity proteomics to measure clinically relevant biomarkers in minute samples and, more specifically, suggests that key aspects of embryo competence could be measured using a proteomic-based strategy, with negligible risk of harm to the living embryo. Our work paves the way for the development of “next-generation” embryo competence assessment strategies, based on functional proteomics.
This subset of experiments were used to validate embryonic origin of proteins identified in the blastocoel cavity of the developing human embryo. Data from ICM and TE samples were combined to create a comprehensive list of genes expressed by the developing human blastocyst. The presence of the correlated transcript indicated embryonic origin of the protein.

overall_design: Data were obtained from a total of ten embryos. For each embryo, Inner Cell Mass and Trophectoderm were separated and distributed into three paired replicates (three ICM and three TE). Two pairs were composed of pooled cellular material from three and one pair from four blastocysts. Each replicate was analysed separately and the list of active genes were combined. Embryos used in these experiments were Day 5/6 embryos deriving from fresh treatment cycles or embryos that were thawed at Day 3 of development and then cultured to blastocyst stage.

first: Maurizio

last: Poli

first: Alessandro

last: Ori

first: Tim

last: Child

first: Souraya

last: Jaroudi

first: Katharina

last: Spath

first: Martin

last: Beck


title: Identification of miR-3189-regulated genes in HCT116 and HCT116 p53KO cells

status: Public on Oct 16 2015

city: Bethesda

first: Yuelin

middle: Jack

last: Zhu

state: MD

address: 9000 Rockville Pike

department: Genetics Branch, Center for Cancer Research

institute: NCI

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Identification of miR-3189-regulated genes in HCT116 cells

summary: Analysis of gene expression profiles regulated by miR-3189. The hypothesis in this study is that miR-3189 controls cell growth by regulating the expression of subset of genes.

overall_design: Total RNA was isolated from HCT116 cells transfected with miR-3189 mimics or control siRNA for 48hr.

first: Xiao

last: Li

first: Ashish

last: Lal


title: Molecular insight into AL cells and their subsequent dedifferentiation to primitive cell types with multilineage potency

status: Public on Oct 14 2015

city: Hangzhou

first: Chenxia

last: Hu

state: Zhejiang

address: School of Medicine; First Affiliated Hospital; Zhejiang University

institute: Zhejiang University

summary:
The sequential adipogenic differentiation and dedifferentiation processes resulted in novel stem cells that proliferated faster and retained multilineage potency; however, the mechanism underlying this cross-talk remained to be determined. In this context, we identified a number of differentially expressed genes during these processes.
Gene expression profiling was performed to obtain a deeper molecular insight into AL cells and their subsequent dedifferentiation to primitive cell types with multilineage potency. GeneChips were generated for PDMSCs, AL cells and DePDMSCs from 3 donors. We selected numerous genes which were differentially expressed in the processes.

overall_design: Expression profiling was performed for 9 samples (n = 3 donors) subdivided into 3 groups: 3X (PDMSCs), 3X (AL cells) and 3X (DePDMSCs P3) using [PrimeView] Affymetrix Human Gene Expression Array.

first: Yuchao

last: Yu


title: Genome-wide analysis of gene expression in MDA-MB-231 cells treated with cholesterol synthesis inhibitors

city: Shrewsbury

first: Andrew

last: Canter

address: Unti 46, Atcham Business Park

institute: Pathway Intermediates

summary: The hypothesis tested in this experiment was that a statin caused a larger shift in genes associated with pluripotency when compared with a Δ-24 oxidoreductase. It was theorized that the effect of the statin would be greater since the enzyme inhibition takes place proximal to the pathway branch involved in signal isoprenylation, whereas the oxidoreductase inhibits distal to this branch.

overall_design: Total RNA was obtained from MDA-MB-231 cells following 24 hour exposure to Pravastatin or Proadifen hydrochloride

first: David

last: Garnett


title: Genome-wide analysis of gene expression in Calu-1 cells treated with cholesterol synthesis inhibitors

overall_design: Total RNA was obtained from Calu-1 cells following 24 hour exposure to Pravastatin or Proadifen hydrochloride


title: Genome-wide analysis of gene expression in Calu-1 cells and MDA-MB-231 cells treated with cholesterol synthesis inhibitors

summary: The hypothesis tested in this experiment was that there would be a different response between the cell types to the bisphosphonate, the SREBP inhibitor fatostatin and an oxidoreductase inhibitor.

overall_design: Total RNA was obtained from cells following 24 hour exposure to the test agents


title: Genome-wide analysis of gene expression in cells treated with cholesterol synthesis inhibitors


title: Stimulation of endogenous FGFR2 signalling in estrogen receptor-positive breast cancer cells

status: Public on Oct 05 2015

city: Cambridge

first: Kerstin

last: Meyer

summary: Genome-wide association studies have identified a locus within the second intron of the FGFR2 gene that is consistently the most strongly associated with estrogen receptor-poisive breast cancer risk. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Previously, a systems biology approach was adopted to elucidate the regulatory networks operating in MCF-7 breast cancer cells in order to examine the role of FGFR2 in mediating risk. Here, the same approach has been employed using a number of different estrogen receptor-positive breast cancer cell lines in order to see if the previous findings are reproducible and consistent in estrogen receptor-positive disease.

overall_design: The data consists of 43 microarray samples from 5 estrogen receptor-positive cell lines (MCF-7, ZR751, T47D, SUM52PE and BT474) treated under different conditions at a time point of 6 h in order to perturb FGFR2 signalling. The data have been pre-processed in R using the beadarray package, and are presented in the form of log2 expression values. The experiment was carried out on 4 Humanv4 arrays using 12 samples per array.

first: Tom

last: Campbell


title: Identification of PARP1 target genes using microarray

status: Public on Oct 07 2015

city: DaeJeon

first: Mi Young

last: Kim

address: Biological science

institute: KAIST

summary:
Purpose:To indentify downtream effectors of PARP1, we performed microarray profiling in non-targeting or PARP1 targeting shRNA-expressing H2030-BrM3.
Results: we identifed 15 genes whose expression were decreased upon depletion of PARP1 in H2030-BrM3 cells at least by under 1.3-fold.

overall_design: RNA profiling of PARP1-depleted H2030-BrM3 was analyzed by genome-wide microarray using Illumina bead chip TotalPrep RNA amplification Kit. Biotin labeled cDNA are hybridized with Illumina HumanHT-12 V4.0 Beadchips using Illumina standard protocol.

first: Eun-Bee

last: Choi

first: Mi-Young


title: Identification of miR-3189-regulated genes in HCT116 p53KO cells

overall_design: Total RNA was isolated from HCT116 p53KO cells transfected with miR-3189 mimics or control siRNA for 48hr.


title: Genome-wide analysis of gene expression in U87MG with different succinyaltion levels

status: Public on Oct 02 2015

city: shanghai

first: feng

last: li

address: 2005, songhu road

institute: fudan university

summary: NADP+-IDH mutations-produced R-2-hydroxylglutarate induces mitochondrial hypersuccinylation that induces cancerous metabolism and apoptosis resistance. Relief of hypersuccinylation inhibits tumorigenic growth of IDH mutant-harboring cells. Determination on transcriptional level of cells which were hypersuccinyalted helped us understand the mechanism, and we tested the hypothesis that IDH1R132H mutant affects cells through inducing hypersuccinylation  by comparing R132H- overexpressing cells with cells in which the desuccinyaltase, SIRT5, were knocked down or the SIRT5 were overexpressed together with R132H.

overall_design: Total RNA obtained from cells overexpressing R132H compared to SIRT5KD cells, or R132H&SIRT5 overexpressing cells

first: Feng

first: Jianyun

last: Zhao

first: Wei

last: Xu

first: Shimin


title: LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer [array]

status: Public on Oct 01 2015

city: Atlanta

first: Jindan

state: GA

address: E330, 1760 Haygood Dr NE

department: Urology

institute: Emory University

summary: HOTAIR is up-regulated in tamoxifen-resistant breast cancer tissues compared to their primary counterparts.  Mechanistically, HOTAIR is a direct target of ER-mediated transcriptional repression and is thus restored upon the blockade of ER signaling, either by hormone deprivation or tamoxifen treatment.

overall_design: Lentiviral infected Ctrl or HOTAIR stable MCF7 cells were deprived for 3 days and then treated with ethanol or 1 nM E2 for 6h, cells were collected for RNA extraction.

first: Xingyang

last: Xue


title: Gene expression analyses of miR-99b and miR-330-3p overexpression in Natural killer cells

city: London

first: Robert

middle: Daniel

last: Petty

address: Charterhouse Square

department: Haemato-oncology

institute: Barts Cancer Institute, Queen Mary, University of London

summary: In order to define the targets of two miRNA overexpressed in NK cells in CFS/ME paitents, miRNA precursors for hsa-miR-99b and hsa-miR-330-3p were transfected in to buffy coat derived Natural Killer cells isolated by negative magnetic selection.

overall_design: Transient transfection of primary natural killer cells with microRNA precursors (hsa-miR-99b and hsa-miR-330-3p). Total RNA was isolated with Trizol 24hrs post transfection, comparison was made between precursor transfected samples and non-sense tranfections

first: R


title: Cartilage Oligomeric Matrix Protein (COMP) contributes to the development and metastasis of breast cancer

city: Lund

first: Petter

last: Storm

address: Sölvegatan 19, BMC A11

department: Developmental and Regenerative Neurobiology

country: Sweden

institute: Lund University

summary: Cartilage Oligomeric Matrix Protein (COMP) is a soluble pentameric protein expressed in cartilage and involved in collagen organization. Publicly available mRNA expression array data indicated that COMP is overexpressed in breast cancer tissue. Tissue microarrays derived from two cohorts of patients with breast cancer (n = 122 and n = 498) were immunostained, which revealed varying amounts of COMP, both in the tumor cells and surrounding stroma. High levels of COMP in tumor cells correlated, independently of other variables, with poor survival and faster recurrence (metastases). Breast cancer cells, MDA-MB-231, stably expressing COMP were injected into the mammary fat pad of SCID (CB-17/Icr-Prkdcscid/Rj) mice. Tumors expressing COMP grew to significantly larger volumes and had increased metastasis as compared to control, mock transfected, tumors. In vitro experiments confirmed that COMP expressing cells were more invasive, which was in part related to an upregulation of metalloprotease-9. Further, microarray analyses of gene expression in tumors formed in vivo showed that expression of COMP was protective against endoplasmatic reticulum stress. This observation was confirmed in vitro since COMP expressing cells showed better survival than mock when treated with brefeldin, which leads to accumulation of proteins in endoplasmatic reticulum. The mRNA pathway analyses also implicated a metabolic switch leading to a more severe Warbug effect, which was confirmed in vitro by measurement of cell respiration and lactate production. In conclusion, COMP is a novel biomarker in breast cancer, which contributes to the severity of the disease by several novel molecular mechanisms.

overall_design: Tumours from seven wildtype and seven COMP-overexpressing arrays were analysed using Illumina whole genome mouse arrays.


title: mTOR inhibitors suppress homologous recombination repair and synergize with PARP inhibitors via regulating SUV39H1 in BRCA-proficient triple-negative breast cancer

status: Public on Oct 13 2015

city: HOUSTON

first: WEI

last: MO

state: TX

address: 7435 FANNIN ST

department: SYSTEMS BIOLOGY

institute: MD ANDERSON CANCER CENTER

summary: This analysis was used to search for genes that were differentially expressed between cells treated with DMSO and those treated with the mTOR inhibitor everolimus.

overall_design: Total RNA obtained from MDA-MB-231 and BT-549 cells subjected to 48 hours treatment of everolimus (10uM) compared to DMSO.

last: Mo

first: Hui

last: Dai

first: Curtis

last: Lin

first: Qingxin

last: Liu

first: Yang

last: Peng

first: Yulong

last: Liang

first: Funda

last: Meric-Bernstam

first: Gordon

last: Mills

first: Kaiyi

first: Shiaw-Yih


title: Blood Transcriptional Signature of hyperinflammation in HIV-associated Tuberculosis

first: Rachel

last: Lai

address: The Ridgeway

department: Mycobacterial Research

institute: National Institute for Medical Research

summary: Patients with HIV-associated TB are known to experience systemic hyperinflammation, clinically known as immune reconstitution inflammatory syndrome (IRIS), following the commencement of antiretroviral therapy (ART). No prognostic markers or biomarkers have been identified to date and little is known about the mechanism mediating the hyperinflammation. We recruited a prospective cohort of 63 patients with HIV-associated TB, 33 of whom developed TB-IRIS. Of which transcriptomic profiling was performed using longitudinal whole blood RNA samples from 15 non-IRIS and 17 TB-IRIS patients. Transcriptomic signatures that distinguish patients who would eventually develop IRIS were identified as early as week 0.5 (2-5 days post-ART) and predicted a downstream activation of proinflammatory cytokines. At the peak of IRIS (week 2), transcriptomic signatures were overrepresented by innate receptor signaling pathways including toll-like receptor, IL-1 receptor and TREM-1.

overall_design: Patients are classified either as TB-IRIS and non-IRIS and longitudinal samples (week 0, 0.5, 1 and 2) were analyzed. There are a total of 107 samples across all 4 timepoints. For normalization, week 0 samples were baseline transformed to the median of all samples. For all other weeks, samples were baseline transformed either to the median of all samples or to the corresponding week 0 values. Samples 5411298027_F and 5412485008_F do not have a corresponding baseline and were therefore excluded in the analysis for the latter.

first: Graeme

last: Meintjes

last: Wilkinson


title: Rapid expansion of human epithelial stem cells suitable for airway tissue engineering

first: Vitor

middle: H

last: Teixeira

address: 5 University Street

institute: University College London

summary: Rationale: Stem cell-based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience suggests an urgent need to restore mucociliary function in the lungs following transplantation of tissue-engineered grafts, while pre-clinical studies show that seeding scaffolds with autologous mucosa improves regeneration. Recent data suggest that high epithelial cell seeding densities are required in regenerative medicine and existing techniques are inadequate to achieve coverage of clinically suitable grafts.    Objectives: To define a scalable airway epithelial cell culture system to deliver airway epithelial cells to clinical grafts.    Methods: Human respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-kinase (ROCK) inhibition. Cells were analyzed using immunofluorescence, qPCR and flow cytometry to assess airway stem cell marker expression. Differentiation capacity and ciliary beat were assessed in air-liquid interface cultures. Karyotyping and an in vivo tracheal xenograft model were used to investigate the suitability of expanded cells for tracheal reconstruction.    Measurements and Main Results: 3T3 feeder cells and ROCK inhibition allowed rapid expansion of airway basal stem cells. These cells were capable of multipotent airway differentiation in vitro, forming epithelia containing both ciliated and goblet lineages. Cilia were functional with normal beat frequency and pattern. Cultured cells repopulated a decellularized tracheal scaffold in a heterotopic tracheal transplantation xenograft model.    Conclusions: Our method addresses the clinical need to generate large numbers of airway basal epithelial cells in the time window demanded by clinical transplantation.

overall_design: Matched donor human airway epithelial cells were cultured in BEGM or on a feeder layer of mitotically inactive 3T3-J2 fibroblasts with ROCK inhibition (5uM Y-27632) for one passage (7 days).

middle: E

last: Hynds

first: Colin

last: Butler


title: Identification of Liver Receptor Homologue-1 (LRH-1)-regulated genes in HCT116 colorectal cancer cells

first: Holly

middle: Barbara

last: Kramer

address: Du Cane Road

department: Department of Surgery & Cancer

institute: Imperial College London

summary: Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor which has been implicated in the growth and development of breast, pancreatic and colorectal cancers (CRC). In order to identify novel LRH-1-regulated genes in CRC cells, we performed gene expression profiling following siRNA-mediated LRH-1 silencing in the CRC cell line HCT116.

overall_design: HCT116 cells were transfected with LRH-1 siRNA #1, #2, or with a non-targeting siRNA (siLUC) for 24 hours. Following assessment of RNA integrity, four biological replicates for each siRNA treatment were used for microarray analysis.

first: Simak

last: Ali

first: Laki

last: Buluwela


title: Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion

city: Perth

first: Sam

last: Buckberry

state: WA

address: 35 Stirling Highway, Crawley

institute: The University of Western Australia

summary: Reduced or absent cytotrophoblast invasion of the maternal uterine spiral arteries is a common clinical finding in studies of pregnancies complicated by preeclampsia, suggesting that the mechanisms behind invasion of these cells is perturbed. The placenta initially develops in a low oxygen environment of 1-2% oxygen until after the 10th week of pregnancy. During this time oxygen concentration exerts a major influence over trophoblast activity and, in vitro, hypoxia inducible factors are proposed to be one of many key regulators of first trimester trophoblast behaviour. We used a global gene expression microarray approach to identify signalling pathways involved in invasion of the first trimester trophoblast cell line HTR8/SVneo under hypoxic conditions where HIF-1 was active. Additionally, first trimester placental samples from different gestational age groups were labelled with anti HIF-1 and HIF-2 to evaluate whether HIFs are differentially expressed and localised across the period of development characterised by hypoxia (6-8 weeks) and maternal blood perfusion (10-12 weeks). Eighty-eight genes were differentially expressed between cells cultured in 1% oxygen (where HIF-1 was localised to the nucleus) and 5% oxygen (where HIF-1 was cytoplasmic). 65% of the genes were predicted to contain HIF-1α:ARNT transcription factor binding sites. Increased nuclear localisation of HIF-1α was seen in extravillous cytotrophoblasts in early first trimester compared with late, while cellular expression of HIF-2α in the villous stroma was higher in late first trimester. While HIFs and their downstream targets are clearly induced in trophoblasts during early placental development, and in vitro hypoxic conditions, the mechanism and pathways by which invasion is increased under hypoxic conditions is not clear from the gene expression profile. Further insight beyond the transcription level is required to fully understand this complex phenomenon.

overall_design: In this study we sought to elucidate the role of hypoxia-inducible genes in HTR8/SVneo invasiveness by performing global gene expression analysis under conditions where HIF-1α was predicted to be active (1% O2) and inactive (5% O2, physiological normoxia). Ambient oxygen standard culture conditions (20% O2) were also included to evaluate the effect of using 5% oxygen rather than 20% as a representation of normoxia. Particular attention was paid to the role of HIFs, which mediate the effects of hypoxia on the cell, as a key regulator of gene expression. Differential HIF-1 localization in HTR8/SVneo was confirmed under our culture conditions, and in first trimester placenta sections of different gestational ages to confirm that HIF is highly expressed in trophoblasts during different stages of differentiation. Microarray experiments were performed with and without growth factor reduced Matrigel; cells cultured on Matrigel representing an extravillous, endovascular-like phenotype of HTR8/SVneo (Highet et al., 2012) while HTR8/Svneo cultured on plastic are believed to be a phenotype resembling cells of the proximal region of cytotrophoblast columns (Kilburn et al., 2000).

first: Amanda

last: Highet

first: Sultana

last: Khoda

first: Shalem

last: Leemaqz

first: Tina

last: Bianco-Miotto

first: Elaine

last: Ellinger-Wu

first: Claire

middle: T

last: Roberts


title: Identification of Liver Receptor Homologue-1 (LRH-1)-regulated genes in colorectal cancer cells

overall_design: Refer to individual Series


title: Transriptome analysis of LNCaP/AR cell line after concomittant treatment with androgen with bicalutamide and enzalutamide

city: New York

first: Yu

last: Chen

address: 1275 York Ave, Box 20

department: Human Oncology and Pathogenesis Program

institute: Memorial Sloan Kettering Cancer Center

overall_design: LNCaP/AR cells growing in log phase were treated for 24 hours with vehicle, the androgen DHT, and DHT plus either bicalutamide or enzalutamide for 24 hours.

first: Ling

last: Cai

first: Charles

last: Sawyers

first: Deyou

last: Zheng


title: Transriptome analysis of VCAP and CWR22-Pc cell lines after concomittant treatment with androgen with bicalutamide and enzalutamide

overall_design: VCAP and CWR22-Pc cells growing in log phase were treated for 24 hours with vehicle, the androgen DHT, and DHT plus either bicalutamide or enzalutamide for 24 hours.


title: Identification of Liver Receptor Homologue-1 (LRH-1)-regulated genes in HT29 colorectal cancer cells

summary: Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor which has been implicated in the growth and development of breast, pancreatic and colorectal cancers (CRC). In order to identify novel LRH-1-regulated genes in CRC cells, we performed gene expression profiling following siRNA-mediated LRH-1 silencing in the CRC cell line HT29.

overall_design: HT29 cells were transfected with LRH-1 siRNA #1, #2, or with a non-targeting siRNA (siLUC) for 24 hours. Following assessment of RNA integrity, four biological replicates for each siRNA treatment were used for microarray analysis.


title: Genome-wide analysis of gene expression in endothelial colony forming cells and mature endothelial cells

status: Public on Sep 30 2015

city: Oslo

first: Krisztina

last: Szoke

address: Sognsvannsveien 20.

country: Norway

institute: Institute of Immunology and Norwegian Center for Stem Cell Research, Oslo University Hospital, Rikshospitalet

summary: Autologous endothelial cells are promising alternative angiogenic cell sources in trials of therapeutic vasculogenesis; in the treatment of vascular diseases and in the field of tissue engineering. A population of endothelial cells (ECs) with long-term proliferative capability can be isolated from human peripheral blood. They are called endothelial colony forming cells (ECFCs), and are considered to be an endothelial precursor population. They can be expanded in cell factories to sufficient numbers for clinical applications, but as the number of isolated primary ECs is low, the culture period required may be quite long. Another EC population that is easily available in the autologous setting and may be expanded in vitro through several population doublings are the ECs from adipose tissue (AT-ECs). Through extensive comparisons using whole-genome microarray analysis, morphology, phenotype and functional assays, we wanted to evaluate the potential of these EC populations for use in clinical neovascularization. Global gene expression profiling of ECFCs, AT-ECs and the classical EC population, human umbilical vein ECs showed that the EC populations clustered as unique populations, but very close to each other. By cell surface phenotype and vasculogenic potential in vitro and in vivo we also found the ECFCs to be extremely similar to AT-ECs. These properties, and easy access in the autologous setting, suggest that both AT-ECs and ECFCs may be useful in trials of therapeutic neovascularization. However, AT-ECs may be a more practical alternative for obtaining large quantities of autologous ECs.

overall_design: Endothelial colony forming cells (ECFCs), adiose tissue-derived endothelial cells (AT-ECs), dermal microvascular endothelail cells (DMVECs) and umbilical vein endothelial cells (HUVECs) were cultured in the same medium (EGM-2) for the comparative gene expression studies. RNA samples were obtained from each cell type from three healthy donors representing three biological replicates.

last: Szöke

first: Andreas

last: Reinisch

first: Esben

last: Østrup

first: Finn

middle: P

last: Reinholt

first: Jan

last: Brinchmann


title: Acyl-CoA synthetase 1 in differentiated adipocytes from small for gestational age neonates: Putative association with fetal programming of cellular insulin sensitivity and lipid content [ACSL1_knockdown]

city: Singapore

first: Jeremie

last: Poschmann

state: Singapore

address: 60 Biopolis street

country: Singapore

institute: Genome Institute Singapore

summary: We hypothesised that SGA as a proxy for intrauterine growth restriction promotes specific epigenetic marks and pathways, whose physiological implications may become apparent only in the fully differentiated state.

overall_design: Samples (SGA derived cell line MSC-01) were collected from umbilical cord derived mesenchymal stem cells (UC-MSC) and treated.

first: Walter

last: Stunkel


title: Acyl-CoA synthetase 1 in differentiated adipocytes from small for gestational age neonates: Putative association with fetal programming of cellular insulin sensitivity and lipid content [Set1B: adipogenesis data from year 2012]

summary:
We hypothesised that SGA as a proxy for intrauterine growth restriction promotes specific epigenetic marks and pathways, whose physiological implications may become apparent only in the fully differentiated state.
We established primary UC-MSC lines isolated from SGA and normal neonates and differentiated them into mature adipocytes.

overall_design: Samples were collected from umbilical cord derived mesenchymal stem cells (UC-MSC). A sample from each SGA (MSC-01) and control group (MSC-44).


title: Expression data from interstital murine lung fibroblasts

city: Palleja

first: Herbert

last: Auer

address: Calle Bellavista 53

country: Spain

institute: Functional GenOmics Consulting

summary: Lung alveoli form a epithelial-mesenchymal trophic unit. We performed microarray analyses on two distinct subsets of PDGFRa expressing interstitial lung fibroblast populations and idenitfied a myo (dim) and matrix (bright) fibroblast signature.

overall_design:
We isolated 2000 PDGFRa-GFP dim and bright lung fibroblasts each form single cell lung digests and subjected them to microarray analysis.
Sham operated animals do not regenerate alveolar septa but undergo surgical trauma. PNX operated animals undergo compensatory lung regrowth and regenerate alveolar sepatae. PNX+dnFGFR operated animals express a dominant negative FGFR2 mutation which inhibits myofibroblast activation and alveolar regrowth.

first: Anne-Karina

last: Perl


title: Multi-platform assessment of transcriptional profiling technologies utilizing a precise probe mapping methodology (Illumina_HT12)

status: Public on Sep 28 2015

city: St. Louis

first: Jinsheng

last: Yu

state: MO

address: 660 S. Euclid Ave.

department: Genetics

institute: Washington University School of Medicine

summary: We present a more extensive and yet precise assessment to elucidate differences and similarities in performance at numerous aspects including signal range, sensitivity to fold-change, and fidelity with TaqMan qRT-PCR. There were three levels of data examined: entire data sets, data derived from gene name annotation oriented subset of 15442 RefSeq genes, and data derived from transcript pattern defined subset of 7034 RefSeq genes.  Our results showed a fair degree of overall correlation between all 6 platforms evaluated; but, to varying degrees, two RNA-seq protocols outperformed three of the microarray platforms in most categories.  Notably, a fourth microarray platform, Agilent, was comparable, or marginally superior, to the RNA-seq protocols within these same assessments.  Furthermore, 3 platforms (Agilent and two RNA-seq methods) demonstrated over 80% concordance with the gold standard TaqMan assay in terms of fold-change accuracy.  Our study suggests that the use of transcript patterns can enhance a number of the observed cross-platform correlations, indicating a potential usefulness for similar evaluations.

overall_design: The study assessed differences and similarities in performance at numerous aspects including signal range, sensitivity to fold-change, and fidelity with TaqMan qRT-PCR. There were three levels of data examined: entire data sets, data derived from gene name annotation oriented subset of 15442 RefSeq genes, and data derived from transcript pattern defined subset of 7034 RefSeq genes.

first: Richard

last: Head


title: Maternal bile acid transporter deficiency promotes neonatal demise

status: Public on Sep 23 2015

city: Memphis

first: Geoffrey

last: Neale

state: TN

address: 262 Danny Thomas Place

department: Hartwell Center

institute: St Jude Childrens Research Hospital

summary: Intrahepatic cholestasis of pregnancy (ICP) is estimated to impact between 0.4% and 5% of pregnancies worldwide. This disease is associated with elevated maternal bile acids and frequently untoward neonatal outcomes such as respiratory distress and asphyxia. Multiple candidate genes have been implicated, but none have provided insight into the mechanisms of neonatal respiratory distress and death. Herein our studies demonstrate that maternal cholestasis (due to Abcb11 deficiency) produces 100% neonatal death within 24h due to atelectasis producing pulmonary hypoxia, which recapitulates the respiratory distress and asphyxia of human ICP. We show that these neonates have elevated pulmonary bile acids that are associated with disrupted structure of pulmonary surfactant. Maternal absence of Nr1i2 superimposed upon Abcb11 deficiency strongly increased neonatal survival and is directly related to reduced maternal bile acid concentrations. The mechanism accounting for reduced serum bile acids in the mothers deficient in both Nr1i2 and Abcb11 appears related to disrupted reabsorption of intestinal bile acids due to changes in transporter expression. These findings provide novel insights into pulmonary failure by revealing bile acids capability to disrupt the structure of surfactant producing collapsed alveoli, pulmonary failure and ultimately death. These findings have important implications for neonatal health especially when maternal bile acids are elevated during pregnancy and highlight a potential pathway and targets amenable to therapeutic intervention to ameliorate this condition.

overall_design: We used microarrays to measure changes in gene expression profiles in lung tissues from Abcb11+/- lungs after interbreeding C57BL/6 wild-type female or C57BL/6 Abcb11-/- female mice against either C57BL/6 wild-type male mice or C57BL/6 Abcb11-/- male mice to create only heterozygote offspring. We also measured profiles in liver tissues from age-matched C57BL/6 wild-type and C57BL/6 Abcb11-/- mice. Lung tissues were collected from day E17.5, E18.5 and neonatal (N0) mice. Liver tissues were collected from 1.5-month-old C57BL/6 wildtype and Abcb11-/- mice.

first: Yuanyuan

last: Zhang

first: John

last: Schuetz


title: HOTAIR lentiviral infected prostate cancer cells

first: Jindan

summary: LNCaP prostate cancer cells were infected by lentivirus expressing either ctrl or HOTAIR. The cells were cultured either in hormone-deprived condition (Ethl) or in the presence of androgen( R1881).

first: Ali

first: Jonathan

last: Zhao


title: Cellular Transcriptional Responses to Merkel cell polyomavirus T antigens

status: Public on Sep 21 2015

city: Pittsburgh

first: Kathleen

middle: F

last: Richards

state: PA

address: 5117 Centre Avenue Suite 1.8

department: Cancer Virology Program

institute: University of Pittsburgh Cancer Institute

summary: Merkel cell polyomavirus (MCV) is clonally integrated in over 80% of Merkel cell carcinomas and mediates tumor development through the expression of viral oncoproteins large T (LT) and small T antigens (sT). Viral integration is associated with signature mutations in the T antigen locus that result in deletions of carboxy-terminal replicative functions of the LT antigen. Despite these truncations, the LT LxCxE retinoblastoma (Rb) pocket protein family-binding domain is retained, and the entire sT isoform is maintained intact. To investigate the ability of MCV oncoproteins to regulate host gene expression, we performed microarray analysis on cells stably expressing tumor-derived LT, tumor-derived LT along with sT, and tumor-derived LT with a mutated Rb interaction motif. Gene expression alterations in the presence of tumor-derived LT could be classified into three main groups: genes that are involved in the cell cycle (specifically the G1/S transition), genes involved in DNA replication, and genes involved in cellular movement. The LxCxE mutant LT largely reversed gene expression alterations detected with the wild type LT, while co-expression of sT did not significantly affect these patterns of gene expression. LxCxE-dependent upregulation of cyclin E and CDK2 correlates with increased proliferation in tumor-derived LT expressing cells. We conclude that in hTERT-immortalized human fibroblasts the LXCXE motif of tumor-derived LT enhances cellular proliferation and upregulates cell cycle and immune signaling gene transcription.

overall_design: RNA was isolated from BJ-hTERT cell lines and hybridized to an Illumina chip for global gene expression analysis

first: Yuan

last: Chang

first: Patrick

middle: S

last: Moore


title: Expression data for analysis of genes affected by PAX3-FOXO1 in alveolar rhabdomyosarcoma cell line Rh4

status: Public on Sep 29 2015

city: Zurich

first: Beat

last: Schäfer

state: ZH

address: Balgrist Campus Lengghalde 5

department: Oncology

country: Switzerland

institute: University Childrens Hospital

summary:
PAX3-FOXO1 is a fusion transcription factor characteristic for the majority of alveolar rhabdomyosarcoma tumors. It is the main oncogenic driver and deregulates expression of PAX3 target genes.
The PAX3-FOXO1 target gene signature was determined in the Rh4 alveolar rhabdomyosarcoma cell line.

overall_design: Rh4 cells were transfected with siRNA directed against PAX3-FOXO1 or scrambled control. RNA was isolated from these cells after 24, 48 and 72 h.

middle: W

first: Margret

last: Ebauer

first: Marco

last: Wachtel


title: Targeting FAK and EGFR/HER-2 with small molecule inhibitors in SKBR-3 breast cancer cell

status: Public on Sep 25 2015

city: buffalo

first: Dan

last: Wang

state: NY

address: Elm & Carlton Streets

institute: RPCI

summary: Targeting FAK with two different FAK inhibitors and Lapatinib demonstrated different signaling mechanisms

overall_design: SKBR-3 cells were treated with inhibitors for 24 hours at 1 microM of Fak inhibitors (either Y15 or PF04554878, 5 microM Lapatinib or by combination of Fak inhibitor and Lapatinib at these doses. The Gene expression profiles were compared between the groups

first: Vita

last: Golubovskaya

first: William

middle: G

last: Cance

first: Xiwei

last: Chen

first: Song

last: Liu


title: Functional Changes of HepG2 cells by VECELL 3-D Culture

city: Setagaya

first: Seiichi

last: Ishida

state: Tokyo

address: 1-18-1, Kamiyoga

department: Pharmacology

country: Japan

institute: National Institute of Health Sciences

summary: VECELL 3-D insert is newly developed culture scaffold with collagen-coated ePTFE (expanded polytetrafluoroethylene) mesh. Effects of VECELL 3-D insert on the functionalities of HepG2, human hepatocellular carcinoma cell line, were analyzed.

overall_design: HepG2 cells were cultured either on normal cell culture plate (n=3) or on VECELL (n=3) for three days and total RNA were extracted. aRNA were obtained from each RNA and hybridized to HG U133A chip in duplicate.

first: Ishida

last: Seiichi


title: Global mRNA expression profiling of murine primary PDAC cells following JQ1 or SAHA monotherapy as well as JQ1-SAHA combination therapy

status: Public on Sep 20 2015

city: Munich

first: Jens

last: Siveke

address: Ismaninger Str. 22

department: 2. Med. Klinik

institute: Klinikum rechts der Isar, Technical University Munich

summary: Global mRNA expression profiles of murine primary PDAC cells following JQ1 or SAHA monotherapy as well as JQ1-SAHA combination therapy were collected using Affymetix mouse whole genome array (Mouse Genome 430A 2.0 Array) . Primary PDAC cells isolated from Ptf1aCre/+;Kras+/LSL-G12D;p53lox/lox (Kras;p53) mice were treated either with JQ1 (100 nM) or SAHA (2000 nM) or vehicle 10% (2-Hydroxypropyl)-β-cyclodextrin (Sigma-Aldrich) or as combination therapy with the indicated dosage for monotherapy. Total RNA isolation was performed after 6 hours of treatment.

overall_design: Primary PDAC cells from Ptf1aCre/+;Kras+/LSL-G12D;p53lox/lox (Kras;p53) mice treated either with JQ1, SAHA, vehicle or JQ1-SAHA combination were analyzed by global gene expression analysis.


title: hsa-miR-299-5p overexpression in CD34+ hematopoietic progenitor cells

city: Modena

first: Elena

last: Tenedini

address: Via Campi, 287

department: Biomedical Sciences

country: Italy

institute: University of Modena and Reggio Emilia

summary:
Hemopoiesis entails a series of hierarchically organized events that proceed throughout cell specification and terminates with cell differentiation. Commitment needs the transcription factors effort that, in concert with microRNAs, drives cell fate specification, answering to promiscuous patterns of gene expression by turning on lineage-specific genes and repressing alternate lineage transcripts. Therefore microRNAs and mRNAs cooperate to direct cell fate decisions. We obtained microRNAs profiles from human CD34+ hemopoietic progenitor cells and in-vitro differentiated erythroblasts, megakaryoblasts, monoblasts and myeloblasts precursors and we analyzed them together with the gene expression profiles of the same populations. We found that for most part of microRNAs specifically up-regulated in one single cell progeny an inverse correlation between microRNAs and down-regulated putative targets expression levels occurs. We chose hsa-mir-299-5p as a model to get further insights into the possible biological relevance of this microRNAs-mRNAs expression integrated analytical approach and we asked if the forced expression of a single lineage-specific microRNA is able to control the cell fate of CD34+ progenitors grown in multilineage culture conditions. Gain and loss of-function experiments established that mir-299-5p regulates hemopoietic progenitors fate modulating reciprocally megakaryocytic-granulocytic versus erythroid-monocytic differentiation and has at least two genuine targets, the transcription factors CTCF and SOX4.
CD34+ hematopoietic progenitor cells were transfected with the Amaxa Nucleofector Device, using the Human CD34 Cell Nucleofection Kit, accordingly to the manufacturer’s instructions (Amaxa Biosystem, Cologne, Germany), and 5µg of either the Pre-miR miRNA Precursor Molecule—Negative Control # 1 (NC1) or the hsa-mir-299-5p Pre-miR miRNA Precursor Molecule (299-5p) (Ambion, Austin, TX, USA) and pulsed with the program U-008.

overall_design: The dataset is composed of three independent paired experiment of 299-5p gain of-function (three hsa-299-5p Pre-miR miRNA Precursor Molecule nucleoporated samples and three paired Pre-miR miRNA Precursor Molecule—Negative Control # 1 transfected ones).

first: Enrica

last: Roncaglia


title: Whole blood gene expression profiles of patients with a past aneurysmal subarachnoid hemorrhage

status: Public on Sep 24 2015

city: Utrecht

first: Femke

middle: NG

last: van 't Hof

address: Heidelberglaan 100

institute: University medical center Utrecht

summary: Investigation of gene expression profiles in blood of previous aSAH patients, aiming to gain insight into the pathogenesis of IA and aSAH, and to make a first step towards improvement of aSAH risk prediction. The results indicate that no gene expression differences are present in blood of previous aSAH patients compared to controls, besides one differentially co-expressed gene network without a clear relevant biological function.

overall_design: We collected peripheral blood of 119 patients with aSAH at least two years prior, and 118 controls. We determined gene expression profiles using Illumina HumanHT-12v4 BeadChips. After quality control, we divided the dataset in a discovery (2/3) and replication set (1/3), identified differentially expressed genes, and applied (co-)differential co-expression to identify disease-related gene networks.

first: Ynte

last: Ruigrok

first: Jelena

last: Medic

first: Bahram

last: Sanjabi

first: Pieter

last: van der Vlies

first: Gabriel

last: Rinkel

first: Jan

last: Veldink


title: Autophagy and alternative NF-kappaB inhibition by RNAi against RELB, ATG5 or ULK1 in A549 human cancer cells

status: Public on Sep 18 2015

city: Edinburgh

first: Simon

last: Wilkinson

address: Crewe Road South

department: MRC Institute of Genetics and Molecular Medicine

institute: University of Edinburgh

summary: In order to understand the contribution of autophagy and alternative NF-kappaB signalling to transcriptional output in A549 lung cancer cells, RNAi was used to knockdown the expression of core autophagy genes (ATG5, ULK1) or the key subunit of alternative NF-kappaB RELB.

overall_design: Seven samples were prepared for each biological replicate; two sequence independent non-targeting control siRNAs were transfected as a negative control. Three sequence independent siRNAs targeting the core autophagy machinery were transfected (ATG5 si, ATG5 si(2), ULK1 si). N.B. ATG5 si(2) only partially ablates Atg5 protein expression whereas ATG si has greater efficacy. Two sequence independent siRNAs targeting RELB were transfected (RELB si, RELB si(2) ). Three independent biological replicates of all conditions were obtained, by performance of the experiment on different days.


title: CDK7-dependent Transcriptional Addiction in Triple-Negative Breast Cancer (Microarray)

city: Cambridge

first: Richard

middle: A

last: Young

state: MA

address: 9 Cambridge Center

institute: Whitehead Institute for Biomedical Research

summary: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that TNBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing a novel kinase inhibitor and CRISPR/Cas9-mediated gene editing, we show here that triple-negative but not ER/PR+ breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. TNBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An “Achilles cluster” of TNBC-specific genes are extremely sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in TNBC and CDK7 inhibition may be useful therapy for this challenging cancer.

overall_design: Expression microarrays in H3K27ac in triple-negative breast cancer +/- treatment with covalent CDK7 inhibitor THZ1 treatment

first: Yubao

last: Wang

first: Nicholas

last: Kwiatkowski

first: Brian

last: Abraham

first: Tong

middle: I

last: Lee

first: Jean

last: Zhao

first: Nathaneal

last: Gray


title: Expression data from skin of controls and patient with Curth–Macklin

city: Bogota

first: Oscar

middle: Javier

last: Ortega

state: Cundinamarca

address: Carrera 24 N° 63C-69

country: Colombia

institute: Universidad del Rosario

summary:
Ichthyosis Curth–Macklin is a rare genetic disorder that is clinically characterized by severe palmoplantar keratoderma. We have described previously a severe familial phenotype caused by a novel mutation in the KRT1 gene. In this study, we analyzed the skin of one patient using gene expression microarrays.
We used microarrays to study the differences of gene expression between normal skin and skin affected by Ichthyosis Curth-Macklin

overall_design: Skin biopsies were obtained from controls and patient, total RNA was extracted and gene expresion was determined using Gene Expression Microarrays (Affymetrix - Prime View)

first: Paul

last: Laissue

first: Dora

last: Fonseca

last: Ortega-Recalde


title: Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory mediators [452 expt: THP-1 vs BEAS 2B]

status: Public on Sep 16 2015

city: Houston

first: David

last: Loose

address: 6431 Fannin St, MSB 4.130

department: Integrative Biology & Pharm

institute: University of Texas

summary: The goal of the study was to characterize gene expression profiles of lung epithelial and THP-1 monocytic cells influenzed by exposure to poultry dust extract. Gene expression profiles were determined by DNA microarrayanalysis using Illumina Human HT-12 v4 Expression bead chip, and changes in significantly induced transcripts validated by real time quantitative RT-PCR, ELISA, Western blotting and immunohistochemical staining. Significantly induced genes included IL-8, IL-6, ICAM-1, CCL2, CCL5, TLR4 and PTGS2. Pathway analysis indicated that dust extract treatment induced changes in gene expression influenced functions related to immune and inflammatory responses.

overall_design: Cells were treated with medium alone (control) or dust extract (0.1% or 0.25%) for 1, 3 or 6 h (reference).

first: Vijay

last: Boggaram

first: Koteswara

middle: R

last: Gottipati

first: Kartiga

last: Natarajan

first: Coutney

last: Mitchell


title: Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory mediators

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory mediators [391 expt: A549 vs BEAS 2B]


title: Melanoma cell line-induced MDSC transcriptome analysis reveals a unique gene expression profile that is largely reversed to normal monocyte level by MIF inhibition

city: Louisville

first: Kavitha

last: Yaddanapudi

state: KY

address: 505 South Hancock Street

department: Medicine

institute: University of Louisville

summary: Affymetrix microaaray analysis of healthy donor monocytes cultured for 64 hours in the absence of (culture monocytes), or presence of A375 cells (A375-MDSC) or treated with MIF inihibitor, 4-IPP (MDSC+4-IPP; 100mM, day 0 and 50mM, day 2).

overall_design: Significantly modulated genes were clustered into a hierarchical representation. Each column represents one replicate, whereas each row corresponds to the expression of a particular gene across different replicates/experimental conditions.


title: Genome-wide analysis of colorectal cancer

status: Public on Sep 10 2015

city: Peking

first: wang

middle: li

last: yong

state: Peking

address: No 10 xi tou tiao, you an gate

department: medical school

institute: Capital Medical University

summary: Cancerous and paracancerous tissues of 6 cases having colorectal cancer were examined, such as  up- or down-regulated specific  cellular functions.

overall_design: Total RNA obtained from isolated cancer tissues, Illumina HumanHT-12 v4 Expression BeadChip being used. Data processing is performed with GenomeStudio 1.0.2.20706,Gene Expression Module 1.0.6.

first: Lei

last: Ding

first: Lu

last: Kong

first: Liyong

first: Leiming

last: Sui


title: The histone demethylase JMJD1A is essential to prostate cancer cells through regulation of c-Myc expression

status: Public on Sep 08 2015

city: Oxford

first: Natasha

last: Sahgal

address: Old Road Campus

department: Ludwig Institute of Cancer Research

country: United Kingdom

institute: University of Oxford

summary: Analysis of gene expresssion altered upon knockdown of histone demethylase JMJD1A in human prostate cancer cells. The objective is to elucidate the transcriptional programs that are controlled by JMJD1A in human prostate cancer.

overall_design: CWR22Rv1 prostate cancer cells were transduced with lentiviral particles encoding control pLKO.1 or JMJD1A shRNA (shJMJD1A). After 48 h, total RNAs were collected for the microarray analysis to determine the differentially expressed genes between Rv1 pLKO.1 and Rv1 shJMJD1A samples.

first: Lingling

last: Fan

first: Guihong

last: Peng

first: Ladan

last: Fazli

first: Martin

last: Gleave

first: Yuji

last: Zhang

first: Arif

last: Hussain

first: Jianfei

last: Qi


title: Akt regulates Progesterone Receptor B transcription

status: Public on Sep 04 2015

city: Chicago

first: Irene

middle: Inkyung

last: Lee

state: IL

address: 303 E. Superior St, Lurie 4-250

department: OB/GYN

institute: Northwestern University

summary: Progestins have long been used clinically for the treatment of endometrial cancers, however, the response rates to progestin therapy vary and the molecular mechanisms behind progestin insensitivity are poorly understood. We hypothesized that in PTEN mutated endometrial cancers, hyperactive Akt signaling downregulates Progesterone Receptor B (PRB) transcriptional activity, leading to overall impaired progestin responses. We report that knockdown of Akt is sufficient to upregulate a subset of PRB target genes.

overall_design: PRB-Ishikawa endometrial cancer cells were transfected with either siCtrl or siAkt1, siAkt2, and siAkt3. Cells were then serum starved overnight and then treated with either Ethanol Vehicle Control or 10 nM R5020 for 24 hrs. Each treatment was performed in triplicate.

first: J

last: Kim


status: Public on Sep 03 2015

first: Jiyang

last: Yu

address: 262 Danny Thomas Place, MS 1135

department: Computational Biology

institute: St. Jude Children's Research Hospital

summary: Gene expression profiling of ErbB2-engineered MCF10A and WT cells in 2D and 3D culture

overall_design: Gene expression profiling of ErbB2-engineered MCF10A and WT cells, 2D and 3D culture, 5 or 6 replicates

first: Ruth

last: Rodriguez-Barrueco

first: Andrea

last: Califano

first: Jose

middle: M

last: Silva


title: Expression data from  human endometrial cancer cell line AN3-CA treated with 300 nM AZD4547

status: Public on Sep 17 2015

city: Seoul

first: yeonui

last: Kwak

address: Room#2224,Building L2, Hwarangno 14-gil 5, Seongbuk-Gu

institute: Korea Institute of Science and Technology

summary:
AZD4547,pan-FGFR inhibitor, have been reported to have profound therapeutic effects on FGFR-deregulated cancers. AN3-CA is one of endometrial cancer cell lines harbouring FGFR2 mutants.  AZD4547 showed a potent antiprolierative effect on AN3-CA cells.
we used microarray to investigate transcriptome-wide change in gene expression followinig 300 nM AZD4547 treatment to explain the chemotherapeutic effect.

overall_design: compound treatment with or without ligand stimulus.


title: Inhibition of the autocrine loop IL6-JAK2-STAT3-Calprotectin as targeted therapy for HR-/HER2+ breast cancers

city: Memphis


title: Anti-tumor activity and acquired resistance mechanism of Dovitinib (TKI258) in RET rearranged lung adenocarcinoma

status: Public on Sep 01 2015

first: Kyoung-Ho

last: Pyo

address: 50 Yonseiro

department: Avison Biomedical Research Center

institute: Severance Hospital, Yonsei University College of Medicine

summary: RET rearrangement is a newly identified oncogenic mutation in lung adenocarcinoma (LADC). Activity of dovitinib (TKI258), a potent inhibitor of FGFR, VEGFR, and PDGFR, in RET-rearranged LADC has not been reported. The aims of the study are to explore anti-tumor effects and mechanisms of acquired resistance of dovitinib in RET-rearranged LADC. Using structural modeling and in vitro analysis, we demonstrated that dovitinib induced cell cycle arrest at G0/G1 phase and apoptosis by selective inhibition of RET kinase activity and ERK1/2 signaling in RET-rearranged LC-2/ad cells. Strong anti-tumor effect of dovitinib was observed in LC-2/ad tumor xenograft model. To identify the acquired resistance mechanisms to dovitinib, LC-2/ad cells were exposed to increasing concentrations of dovitinib to generate LC-2/ad DR cells. Gene set enrichment analysis of gene expression and receptor tyrosine kinase assay revealed that Src, a central gene in focal adhesion , was activated in LC-2/ad DR cells. Saracatinib, a src kinase inhibitor, suppressed ERK1/2 phosphorylation and growth of LC-2/ad DR cells. Taken together, these findings suggest that dovitinib can be a potential therapeutic option for RET-rearranged LADC, in which acquired resistance to dovitinib can be overcome by targeting Src.

overall_design: To identify potential mechanisms of acquired resistance to dovitinib, we established LC-2/ad DR cells with acquired resistance to dovitinib by exposing LC-2/ad cells to increasing doses of dovitinib. LC-2/ad DR cells showed strong resistance to dovitinib (IC50> 3 μmol/L). Next, LC-2/ad and LC-2/ad DR cells were subjected to genome-wide gene expression profiling using cDNA microarray.

first: Chan-Woo

last: Kang

first: Kang-Won

last: Jang

first: Jinyoung

last: Sohn

first: Sung-Moo

first: Hwan

first: Mi-Ran

last: Yun

first: Han-Na

first: Hye-Ryun

first: Sun-Min

last: Lim

first: Yong-Wha

last: Moon

first: Soonmyung

last: Paik

first: Joo-Hang

first: Byoung-Chul

last: Cho


title: Gastrointestinal symptoms and pathology in patients with Common variable immunodeficiency

status: Public on Sep 02 2015

city: Oslo

first: Silje

last: Fjellgård Jørgensen

address: Postboks 4950 Nydalen

department: Research institute of internal medicine

institute: Oslo University Hospital

summary: Based on the findings of increased IEL in duodenal biopsies in CVID, an overlap with celiac disease has been suggested. In the present study, increased IEL, in particular in the pars descendens of the duodenum, was one of the most frequent histopathological finding. We therefore examined the gene expression profile in pars descendens of duodenum in CVID patients with increased IEL (n=12, IEL mean 34 [range 22-56] IEL/100 EC), CVID with normal levels of IEL (n=8), celiac disease (n=10, Marsh grade 3a or above) and healthy controls (n=17) by gene expression microarray

overall_design: GI histopathological findings in 53 CVID patients that underwent upper and lower endoscopic examination were addressed. For the microarray analysis 20 CVID (8 CVID_normal and 12 CVID with incresed IEL), 10 patients with celiac diseases and 17 healthy controls were included.

last: Jørgensen


title: CD163 macrophages display mixed polarizations in discoid lupus skin

city: Dallas

first: Benjamin

last: Chong

address: 6000 Harry Hines Blvd

department: Dermatology

institute: University of Texas Southwestern

summary: To investigate changes in immune cell signatures in the transcriptomes of DLE lesional skin versus normal skin

overall_design: Comparison of the transcriptome of DLE lesional skin with normal skin

first: Lin-Chiang

last: Tseng

first: Gregory

last: Hosler

first: Noelle

last: Teske

first: Song

last: Zhang

first: Nancy

last: Olsen

first: Chandra

last: Mohan


title: YB-1 affects response to paclitaxel in TNBCs by modulation of EGR1

city: Melbourne

first: Daniel

middle: Glyn

last: Hurley

address: Level 4, Bldg 193, EEE

department: Systems Biology Laboratory

institute: The University of Melbourne

summary: For patients with triple negative breast tumours (TNBCs), lacking receptors for oestrogen, progesterone or HER2 on their cell surface, chemotherapy is the main treatment.  The taxanes, paclitaxel (PTX) and docetaxel, have become the most commonly-used chemotherapies for these kinds of breast cancer.  Although several targeted therapies are currently undergoing clinical trials for TNBC, because of the heterogeneous nature of TNBCs, it is predicted that these may often be used in combination with chemotherapy.  Therefore an understanding of the mechanisms of chemotherapy resistance will continue to be important for the treatment of these patients.

overall_design: Given the pleiotropic nature of YB-1, the aim of this study was to understand whether there were mechanisms in addition to those discussed above, by which YB-1 controls response to PTX in TNBCs.  We initially followed up two previously studied mechanisms, mediated by ABCB1/MDR1 and DUSP4.  We then proceeded to use genomics to identify novel mechanisms by which YB-1 regulates the response of TNBCs to PTX.  This analysis identified and experimentally validated EGR1, encoding the early growth response protein 1 (EGR1) as a previously undiscovered mechanism of YB-1-driven PTX resistance.

first: S

last: Fitzgerald

first: D

last: Mehta

first: I

last: Ruza

first: A

last: Shelling

first: R

last: Sullivan

first: M

last: Algie

last: Woolley

last: Braithwaite

first: C

last: Print

last: Lasham


title: Gene expression changes induced in K562 cells by the homeobox gene DLX4 and by treatment with Activin A and phorbol 12-myristate 13-acetate

city: Bonston

first: Bon

middle: Quy

last: Trinh

address: 330 Brookline Ave

institute: Beth Israel Deaconess Medical Center

summary: Homeobox genes encode transcription factors that control patterning of virtually all organ systems including the hematopoietic system. However, the role of homeobox genes in controlling development of the erythroid and megakaryocytic lineages is poorly understood. In this study, we investigated the role of the homeobox gene DLX4 in erythroid and megakaryocytic differentiation using the bipotent cell line K562 as a model. We compared the global gene expression profile of K562 cells that stably overexpressed DLX4 with that of vector-control K562 cells. As positive controls, global gene expression profiles were evaluated in vector-control K562 cells that were stimulated with Activin A (ActA) to induce erythroid differentiation and in vector-control K562 cells that were stimulated with phorbol 12-myristate 13-acetate (PMA) to induce megakaryocytic differentiation. Our study provides insights into the role of homeobox genes in controlling differentiation of the erythroid and megakaryocytic lineages.

overall_design: Three groups of samples were included: DLX4 vs Empty vector; Activin A vs None; PMA vs DMSO

middle: Q

first: Honami

last: Naora


title: Molecular profiles of Systemic Juvenile Idiopathic Arthritis patients

city: Seattle

first: Chester

middle: T

last: Ni

address: 1201 Ninth Ave

department: Systems Immunology

institute: Benaroya Research Institute

summary: Biomarker identification for diagnosis of systemic juvenile idiopathic arthritis (SJIA), an auto-inflammatory disease that presents with prolonged fevers.

overall_design: Disease vs. healthy control

last: Shenoi

first: J-N

last: Ou

first: H

middle: V

last: Gersuk

last: Wallace

first: E

last: Mellins

last: Stevens