title: Genome-wide analysis of hepatic cells upon infection with Hepatitis B virus (HBV) or Hepatitis D virus (HDV)

status: Public on Jan 30 2018

first: Yi

last: Ni

address: Im Neuenheimer Feld 344

department: Infectious Diseases

institute: University hospital Heidelberg

summary:
The same entry pathway is shared by HBV and HDV. Both viruses attach to hepatocytes via heparansulfate proteoglycan and utilize sodium taurocholate co-transporting polypeptide (NTCP) for a specifc entry. This specific entry step is inhibited by Myrcludex B, a 47-aa lipopeptide myristoylated at the N-terminus. Here we compared the cellular response in the gene expression level triggerred by both viruses. The microarray data shows that HBV infection leads to a silent response but HDV infection triggers high level of innate response such as inteferon-stimulated genes (ISG) expression. Moreover, the response depends on the hepatic cell lines used for infection. Compared to HepG2 cells, HuH7 can not induce ISG even infected by HDV.
Abstract of manuscript:   Background & aims: Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify the responsible sensor and evaluate the effect of IFN on HDV replication.  Methods: HDV and HBV susceptible hepatoma cell lines and primary human hepatocytes (PHH) were used for infection studies. Viral markers and cellular gene expression were analyzed at different time points after infection. Pattern recognition receptors (PRRs) required for HDV-mediated IFN activation and the impact on HDV replication were studied using stable knock-down or overexpression of the PRRs.   Results: Microarray analysis revealed that HDV but not HBV infection activated a broad range of interferon stimulated genes (ISGs) in HepG2NTCP cells. HDV strongly activated IFN-β and IFN-λ in cell lines and PHH. HDV induced IFN levels remained unaltered upon RIG-I or TLR3 knock-down, but were almost completely abolished upon MDA5 depletion. Conversely, overexpression of MDA5 but not RIG-I and TLR3 in Huh7.5NTCP cells partially restored ISG induction. During long-term infection, IFN levels gradually diminished in both HepG2NTCP and HepaRGNTCP cell lines. MDA5 depletion had little effect on HDV replication despite dampening HDV-induced IFN response. Moreover, treatment with type I or type III IFNs did not abolish HDV replication.   Conclusions: Active replication of HDV induces an IFN-β/λ response, which is predominantly mediated by MDA5. This IFN response and exogenous IFN treatment have only a moderate effect on HDV replication in vitro indicating the adaption of HDV replication to an IFN activated state.

overall_design: HuH7 or HepG2 cell line stably expressing virus receptor human NTCP were generated and named as HuH7-hNTCP and HepG2-hNTCP. Both cells were infected with HBV or HDV for 9 days and then total RNA were exacted. Infection in the presence of Myrcludex B or uninfected cells were used as the control.

first: Zhenfeng

last: Zhang

first: Stephan

last: Urban

first: Holger

last: Sültmann


title: Roles of the Brca2 and Wapl complexes with Pds5 in sister chromatid cohesion, cohesin localization, and gene expression [RNA-seq]

status: Public on Feb 05 2018

city: Saint Louis

first: Dale

last: Dorsett

state: MO

address: 1100 South Grand Boulevard

department: Biochemistry and Molecular Biology

country: USA

institute: Saint Louis University School of Medicine

type: Expression profiling by high throughput sequencing

summary: RNA expression was measured by RNA-seq in Drosophila ML-DmBG3-c2 cells depleted for proteins involved in sister chromatid cohesion, and in developing third instar wing discs with or withough brca2 gene mutations

overall_design:
RNA expression in depleted cells was compared to mock treated cells and RNA expression in wing discs from brca2 mutant Drosophila was compared to expression in wing discs without brca2 mutations

This series includes mock RNAi treated samples re-used from GSE100547.


title: PPARδ elicits ligand-independent repression of 2 Trefoil Factor Family to limit prostate cancer growth

status: Public on Jan 29 2018

city: Derio

first: Ana

middle: Maria

last: Aransay

state: BIZKAIA

address: Parque tecnologico de Bizkaia, Building 801-A

department: Genome Analysis Platform

country: Spain

institute: CIC bioGUNE

summary:
Cancer Res; 78(2); 399-409. ©2017
The nuclear receptor PPAR-β/δ (PPARD) has essential roles in fatty acid catabolism and energy homeostasis as well as cell differentiation, inflammation, and metabolism. However, its contributions to tumorigenesis are uncertain and have been disputed. Here, we provide evidence of tumor suppressive activity of PPARD in prostate cancer through a noncanonical and ligand-independent pathway. PPARD was downregulated in prostate cancer specimens. In murine prostate epithelium, PPARD gene deletion resulted in increased cellularity. Genetic modulation of PPARD in human prostate cancer cell lines validated the tumor suppressive activity of this gene in vitro and in vivo Mechanistically, PPARD exerted its activity in a DNA binding-dependent and ligand-independent manner. We identified a novel set of genes repressed by PPARD that failed to respond to ligand-mediated activation. Among these genes, we observed robust regulation of the secretory trefoil factor family (TFF) members, including a causal and correlative association of TFF1 with prostate cancer biology in vitro and in patient specimens. Overall, our results illuminate the oncosuppressive function of PPARD and understanding of the pathogenic molecular pathways elicited by this nuclear receptor.Significance: These findings challenge the presumption that the function of the nuclear receptor PPARβ/δ in cancer is dictated by ligand-mediated activation.

overall_design: Genome-wide changes in gene expression of pC3 cells versus pC3-PPARD expressing cells and pC3-PPARD expressing cells with GW501516.

first: Arkaitz

last: Carracedo

first: Natalia

last: Martín

middle: R

last: Cortazar

middle: M


title: Roles of the Brca2 and Wapl complexes with Pds5 in sister chromatid cohesion, cohesin localization, and gene expression

status: Public on Feb 04 2018

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design:
Refer to individual Series

Grant information: Alvin J Siteman Cancer Center, Washington University School of Medicine, grant no. 8074-88


title: Global lncRNA/mRNA expression analysis of colorectal tumor and non-tumor samples from 6 colorectal cancer patients

status: Public on Jan 20 2018

city: Guangzhou

first: Feng

last: He

state: Guangdong

address: 1# Panfu Road

department: Department of General Surgery

country: China

institute: Guangzhou First People's Hospital, the Second Affiliated Hospital of South China University of Technology

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

summary: Given the role of lncRNAs and mRNAs in tumor pathogenesis, we set out to identify transcripts that potentially drive colorectal tumorigenesis. To do this, we performed microarray analysis on matched colorectal tumor and non-tumor samples from 6 colorectal cancer patients, and determined their lncRNA and mRNA expression profiles with Agilent microarrays (Arraystar Human LncRNA Array v3.0).

overall_design: Fresh colorectal tumor samples and matched non-tumor samples (obtained from unaffected colorectal at least 5 cm from the tumor) from 6 colorectal cancer patients were selected randomly for microarray analysis.

first: Zhuanpeng

last: Chen

first: Jie

last: Cao


title: Global gene expression profiling in A549 cells exposed to TCDD, CH223191 or TCDD+CH223191 for 6 h

status: Public on Jan 25 2018

city: Brno

first: Jirina

last: Prochazkova

address: Kralovopolska 135

department: Cytokinetics

country: Czech Republic

institute: Institute of Biophysics CAS

summary:
Comparison of expression profiles detected in A549 cells exposed to DMSO, TCDD, CH223191 or their combination
Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling in order to analyse TCDD- induced changes in A549 transcriptome, both sensitive and non-sensitive to co-treatment with AhR inhibitor CH223191. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us i) to identify candidate genes, which expression status acutely (e.g. Aldh1a3, Grem1, Hipk2, Tiparp), or with a delay (Cdh1, Dkk1, Bmp6), reflects exposure of lung cancer cells to TCDD,  ii) to predict processes/pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), as well as iii) putative TFs (e.g. Stat, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation.

overall_design: Control DMSO-treated A549 cells compared with A549 cells acutely exposed to TCDD, CH223191 or their combination, respectively

first: Jiri

last: Klema

first: Miroslav

last: Machala


title: Natural killer cells promote fetal development through the secretion of growth-promoting factors

status: Public on Jan 04 2018

city: Hefei

first: Zhou

last: Yonggang

state: Anhui

address: 443 HuangShan Road

department: School of Life Science and Medical Center

institute: University of Science and Technology of China

summary:
Natural killer (NK) cells are present in large populations at the maternal-fetal interface during early pregnancy, but their roles in fetal growth are unclear. Here, we identify a CD49a+Eomes+ subset of NK cells that have the capability to secrete growth-promoting-factors (GPF), including pleiotrophin, osteoglycin and osteopontin in both humans and mice. Decreases in this GPF-secreting NK subset impair fetal development, and leads to fetal growth restriction. The transcriptional factor Nfil3 but not T-bet affects the function and the number of this decidual NK subset. The crosstalk of the HLA-G-ILT2-KIR2DL4 axis promotes the GPF-secreting function of this NK subset. Adoptive transfer of these induced CD49a+Eomes+NK cells can reverse the impaired fetal growth and rebuild an appropriate local microenvironment. These findings reveal new properties of NK cells in promoting fetal growth as well as novel approaches for therapeutically administering NK cells to reverse restricted nourishments within the microenvironment during early pregnancy.
To investigate novel molecular signatures of human decidual NK cells, we performed microarray analysis on dNK cells (CD3−CD56+CD49a+CD49b−) and pNK cells (CD3−CD56+CD49a−CD49b+). dNK cells were purified from first-trimester deciduas. pNK cells were purified from adult peripheral blood mononuclear cells. Samples were collected from healthy adult donors after obtaining informed consent according to the Ethics Committee of the University of Science & Technology of China.

overall_design: We performed human microarray analysis on purified NK cells from normal human decidua during the first trimester of pregnancy; peripheral blood NK cells were used as controls.

first: Binqing

last: Fu

first: Yonggang

last: Zhou

first: Xiang

first: Xianhong

last: Tong

first: Xiuxiu

last: Xu

first: Zhongjun

last: Dong

first: Rui

last: Sun

first: Zhigang

last: Tian

first: Haiming

last: Wei


title: IER5 is a novel Notch target gene that contributes to the effects of Notch on breast cancer stem / progenitor cells

status: Public on Jan 08 2018

city: Cambridge

first: Suraj

last: Menon

address: Li Ka Shing Center, Robinson Way

country: United Kingdom

institute: Cambridge Research Institute, Cancer Research UK

summary: The Notch signalling pathway has been implicated in the development and progression of numerous malignancies, including breast cancer. In breast cancer, the transcriptional programs elicited by Notch activation and the target genes responsible for mediating the downstream effects of the pathway remain poorly understood.  Here, we characterise the immediate cellular consequences of Notch activation in breast cancer cells and identify a panel of direct Notch targets with potential relevance in the disease. One key direct transcriptional target of Notch in this context is IER5. Functionally, IER5 activation in breast cancer contributes to the effects of Notch signalling on the self-renewal and proliferative potential of breast cancer stem and progenitor cells.  High levels of IER5 mRNA may be an important biomarker indicative of Notch activation in the disease.

overall_design: Four treatment conditions were compared in triplicate: no treatment (control), EDTA, γ-secretase inhibition (gsi) and the combination of EDTA and GSI (edtagsi)

first: Sarah-Jane

last: Dawson


title: Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis

status: Public on Jan 01 2018

city: Cape Town

first: Hanif

last: Esmail

address: Anzio Road

country: South Africa

institute: University of Cape Town

summary:
Analysis of transcriptional differences between HIV infected persons with evidence of latent tuberculosis (TB) infection by Quantiferon Gold-in-tube, with and without evidence of subclinical TB disease on FDG-PET/CT scan.

Tuberculosis is classically divided into two clinical states: latent infection and active disease.  One-quarter of the global population is considered latently infected but diagnostic tests poorly predict the small proportion that will progress to disease.  We recruited 35 asymptomatic, HIV-1 infected adults with latent TB by current diagnostic criteria, who underwent [18F]-fluoro-2-deoxy-D-glucose positron emission/computed tomography; ten had pulmonary abnormalities consistent with subclinical disease and were significantly more likely to progress.  As positive control, we recruited 15 HIV-1 infected adults with symptomatic microbiologically confirmed active pulmonary TB, age, sex and CD4 matched to the 35 participants undergoing FDG-PET/CT.

By whole-blood transcriptomic profiling we characterised 82-transcripts distinguishing those with subclinical pathology from those without. Transcripts representing the classical complement pathway were overabundant in both subclinical and active TB.

We have demonstrated that latent TB is not a homogenous condition and defined a distinct high-risk subgroup with evidence of subclinical disease.  These findings point the way to the future development of more predictive diagnostic tests.

overall_design: Total RNA extracted from whole blood of 35 HIV infected participants with evidence of latent TB (10 with subclinical pathology on PET/CT and 25 without) and 15 HIV infected participants with active TB

first: Rachel

middle: P

last: Lai

first: Katalin

middle: A

last: Wilkinson

first: Christine

last: Graham

first: Anna

middle: K

last: Coussens

first: Stuart

last: Horswell

first: Maia

last: Lesosky

first: Clifton

middle: E

last: Barry III

first: Anne

last: O'Garra

first: Robert

middle: J


title: Chemokine expression in the early response to injury in human airway epithelial cells

status: Public on Jan 14 2018

city: Chicago

first: Steven

last: White

state: IL

address: 5841 S. Maryland Ave

department: Medicine

institute: University of Chicago

summary: Basal airway epithelial cells (AEC) constitute stem/progenitor cells within the central airways and respond to mucosal injury in an ordered sequence of spreading, migration, proliferation, and dif-ferentiation to needed cell types. However, dynamic gene transcription in the early events after mucosal injury has not been studied in AEC. We examined gene expression using microarrays following mechanical injury (MI) in primary human AEC grown in submersion culture to generate basal cells and in the air-liquid interface to generate differentiated AEC (dAEC) that include goblet and ciliated cells. A select group of ~150 genes was in differential expression (DE) within 2 - 24 hr after MI, and enrichment analysis of these genes showed over-representation of functional categories related to inflammatory cytokines and chemokines. Network-based gene prioritization and network reconstruction using the PINTA heat kernel diffusion algorithm demonstrated highly connected networks that were richer in differentiated AEC compared to basal cells. Similar ex-periments done in basal AEC collected from asthmatic donor lungs demonstrated substantial changes in DE genes and functional categories related to inflammation compared to basal AEC from normal donors. In dAEC, similar but more modest differences were observed. We demon-strate that the AEC transcription signature after MI identifies genes and pathways that are im-portant to the initiation and perpetuation of airway mucosal inflammation. Gene expression oc-curs quickly after injury and is more profound in differentiated AEC, and is altered in AEC from asthmatic airways. Our data suggest that the early response to injury is substantially different in asthmatic airways, particularly in basal airway epithelial cells.

overall_design: Total RNA obtained from primary (AEC) and differentiated (dAEC) human airway epithelial cells subjected to 2, 8 or 24 hours in vitro mechanical injury compared to sham control. Cells were collected from six asthmatic donated lungs and cultured separated in submission or air liquid interface condition prior to injury.

first: Bingqing

last: Xie

first: Bharathi

last: Laxman

first: Natalia

last: Maltsev


title: Identification of Androgen Receptor Modulators in a Prostate Cancer Cell Line Microarray Compendium

status: Public on Jan 24 2018

city: Research Triangle Park

first: Christopher

last: Corton

state: NC

address: 109 TW Alexander Dr.

institute: US-EPA

summary: High-throughput transcriptomic (HTTr) technologies are increasingly being used to screen environmental chemicals in vitro to identify molecular targets and provide mechanistic context for regulatory testing. The androgen receptor (AR, NR3C4) regulates male sexual development, is involved in the pathogenesis of a number of cancers, and is often the target of endocrine disruptors. Here, we describe the development and validation of a novel gene expression biomarker to identify AR-modulating chemicals using a pattern matching method. AR biomarker genes were identified by their consistent expression after exposure to 4 AR agonists and opposite expression after exposure to 4 AR antagonists. A genetic filter was used to include only those genes that were regulated by AR. Most of the resulting 51 biomarker genes were shown to be directly regulated by AR as determined by ChIP-Seq analysis of AR-DNA interactions. The biomarker was evaluated as a predictive tool using the fold-change rank-based Running Fisher algorithm which compares the expression of AR biomarker genes under various treatment conditions. Using 163 comparisons from cells treated with 98 chemicals, the biomarker gave balanced accuracies for prediction of AR activation or AR suppression of 97% or 98%, respectively. The biomarker was able to correctly classify 16 out of 17 AR reference antagonists including those that are “weak” and “very weak”. Predictions based on comparisons from AR-positive LAPC-4 cells treated with 28 chemicals in antagonist mode were compared to those from an AR pathway model based on 11 in vitro high-throughput screening assays that queried different steps in AR signaling. The balanced accuracy was 93% for suppression. Using our approach, we identified conditions in which AR was modulated in a large collection of microarray profiles from prostate cancer cell lines including 1) AR constitutively active mutants or knockdown of AR, 2) depletion of androgens by castration or removal from media, and 3) modulators that work through indirect mechanisms including suppression of AR expression. These results demonstrate that the AR gene expression biomarker could be a useful tool in HTTr to identify AR modulators in large collections of microarray data derived from AR-positive prostate cancer cell lines.

overall_design: LAPC4 cells were cultured in IMDM media (GIBCO) supplemented with 5% FBS (Omega Scientific) and 1x penicillin/streptomycin/glutamine (GIBCO). Cells were plated at 7.5x10^5 cells per well in 1mL media in 24-well plates. After 48 hours, media was replaced with dosing solutions containing DMSO (0.05%), R-1881 (0.33nM) alone or with one of 28 chemicals at the indicated doses. After 6 hours of exposure, media was removed, cells were rinsed with PBS and frozen in Buffer RLT (Qiagen). Experiments were conducted in triplicate (3 individual experiments performed on separate days). Global gene expression was evaluated by microarray analysis. Total RNA was isolated and purified with the RNeasy MinElute column protocol (Qiagen GmbH, Hilden, Germany), evaluated for integrity using an Agilent RNA 6000 Nano chip on an Agilent 2100 Bioanalyzer (Agilent Technologies GmbH, Berlin, Germany), and quantitated using the NanoDrop spectrophotometer (NanoDrop Technologies, Wilmington, DE). After randomization, samples were hybridized in a blinded manner onto Human HT-12 v4 Expression BeadChip arrays (Illumina, San Diego, CA) in the EPA NHEERL Genomics Research Core Laboratory using standard Illumina protocols. Arrays were scanned, and raw data (.idat files) were obtained using Illumina iScan software (v3.3.28) and analyzed using Illumina GenomeStudio® and Partek Genomics Suite Software.

first: John

last: Rooney

first: Brian

last: Chorley

first: Nicole

last: Kleinstreuer

first: J

middle: C


title: cDNA microarray data after Pseudomonas aeruginosa (PAO1) infection in normal human nasal epithelial (NHNE) cells

status: Public on Jan 12 2018

city: Seoul

first: Yung Jin

last: Jeon

address: 101, Daehak-ro

country: South Korea

institute: Seoul National University Hospital

summary:
A special immune system exists at distinct respiratory epithelium to combat invasion by Pseudomonas aeruginosa (PAO1). This study aimes to determine if interleukin-17C (IL-17C) is correlated with acute PAO1 infection in human nasal epithelium and to prove the role of IL-17C on iron sequestration during PAO1 infection.
IL-17C has antipseudomonal effect by lowering iron sequestration and reducing siderophore activity. IL-17C could be efficient mediator to control PAO1 infection in human nasal epithelium.

overall_design: To evaluate the change of gene expressions after PAO1 infection, we performed gene expression analysis using Platform Illumina HumanHT-12 v4 Expression BeadChip (Illumina, Inc., San Diego, CA). The data were processed using the robust multi-array analysis algorithm, which performs a background correction, a normalization step, and a probe-level summary.

first: Hyun

last: Kim

first: Yung


title: Detailed comparison of retroviral vectors and promoter configurations for stable and high transgene expression in human induced pluripotent stem cells

city: Kiel

first: Franz-Josef

last: Müller

address: Niemannsweg 147

department: Klinik für Psychiatrie und Psychotherapie

country: Germany

institute: Zentrum für Integrative Psychiatrie Kiel

summary: Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes. Lentiviral vectors (LV) pseudotyped with VSV-G were superior to gammaretroviral and alpharetroviral vectors and other envelopes tested. The short elongation factor 1α (EFS) promoter mediated the most robust expression, while expression levels were lower from the potent but more silencing-prone spleen focus forming virus (SFFV) promoter. Both full length (A2UCOE) and minimal (CBX3) UCOE juxtaposed to two physiological and one viral promoter reduced transgene silencing with equal efficiency. However, a promoter-specific decline in expression levels was not entirely prevented. Upon differentiation of transgene-positive iPSC into endothelial cells, A2UCOE.EFS and CBX3.EFS vectors maintained highest transgene expression in a larger fraction of cells as compared to all other constructs tested here. The function of UCOE diminished but did not fully counteract vector silencing and possibilities for improvements remain. Nevertheless, the CBX3.EFS in a LV background exhibited the most promising promoter and vector configuration for both high titer production and long-term genetic modification of human iPSC and their progeny.

overall_design: Comparison of undifferetiated hiPSC in which the transgene cassette was excised, hESC controls an fibroblasts

first: Dirk

last: Hoffmann


title: Targeting ribonucleotide reductase by 3-AP in primary effusion lymphoma

city: New Orleans

first: Zhiqiang

last: Qin

state: LA

address: 1700 Tulane Ave

institute: LSUHSC-NO

summary: KSHV is a principal causative agent of primary effusion lymphoma (PEL) which is lacking of effective treatment. Our previous data have showed that HGF/c-MET pathway is highly active within KSHV+ PEL cells and plays important role in tumor cell survival/growth. By using microarray analysis, we have identified the global gene profile controlled by HGF/c-MET pathway within KSHV+ PEL cell-lines and several novel “druggable” candidates closely related to cancer cell survival/growth, including ribonucleotide reductase (RR). We continue to use microarray analysis to identify the gene profile affected within PEL cells exposure to RR inhibitor, 3-AP.

overall_design: PEL cells were treated with vehicle control or RR inhibitor 3-AP (2.5 µM) for 48 h, and the gene expression signature was compared to respective vehicle controls

first: Lu

last: Dai

first: Jovanny

last: Zabaleta


title: Human WM35 melanoma cell line treated with ciclopirox and crizotinib

city: Houston

first: Wencai

last: Ma

address: 7455 Fannin st

institute: MD Anderson Cancer Center

summary: To generate drug signatures in human WM35 melanoma cell line. WM35 cell line was plated at 4 x 105 cells/mL overnight and treated with ciclopirox or crizotinib at 75% inhibitory concentrations (IC75, determined previously at 72h of treatment) or DMSO (vehicle) for 8h or 24h before harvest.

overall_design: To find out whether drug signatures generated in human melanoma cell lines are predictive of outcome in melanoma patients, we generated ciclopirox and crizotinib signatures in cell lines WM35 . The expression of drug signatures were then tested by using GSSA (Gene Signature Survival Analysis) method to find out correlation with clinical outcome of melanoma patients.

first: Lili

last: Du

last: Wang

first: R

last: Davis

first: Kenneth

middle: Y

last: Tsai


title: Reversible reprogramming of memory Tfh cell function during chronic HIV infection

city: Cleveland

first: Rafick

last: Pierre-Sekaly

state: OH

address: 2103 Cornell Avenue

department: Pathology

institute: Case Western Reserve University

summary: The purpose of this study was to determine differences in gene expression profiles between proliferating memory Tfh cells from elite controller (EC) and chronic aviremic HIV-infected treated (CA) individuals. We have observed significant changes in the gene expression profile between memory Tfh cells from these two patient groups and the data suggests that memory Tfh cells from CA subjects have increased IL-2 mediated signaling and are polarized towards a Th1 phenotype.

overall_design:
CFSE labeled and sorted circulating memory Tfh cells were placed in coculture with sorted memory B cells at equal numbers in the presence of SEB. After 5 days, both CFSElo and CFSEhi memory Tfh cells were sorted for gene array analysis. Cells were collected and lysed for RNA extraction. Reverse transcription reactions were performed to obtain cDNAs which were hybridized to the Illumina Human HT-12 version 4 Expression BeadChip according to the manufacturer’s instruction, and quantified using an Illumina iScan System. The data were collected with Illumina GenomeStudio software.

Please note that sample titles represent;
LH (leuka healthy),
ST (successfully treated HIV infected individual),
LTNP (long-term non-progressor)

and correspond to the following names used in the assocated manuscript;
LH --> HC (healthy control),
ST --> CA (chronic aviermic treated individual),
LTNP --> EC (elite controller)

first: Rafael

last: Cubas

first: Julien

last: van Grevenynghe

first: Saintedym

last: Wills

first: Lela

last: Kardava

middle: H

last: Santich

first: Clarisa

last: Buckner

first: Roshell

last: Muir

first: Virginie

last: Tardif

first: Carmen

last: Nichols

first: Francesco

last: Procopio

first: Zhong

last: He

first: Talibah

last: Metcalf

first: Khader

last: Ghneim

first: Michela

last: Locci

first: Petronela

last: Ancuta

first: Jean-Pierre

last: Routy

first: Lydie

last: Trautmann

first: Yuxing

last: Li

first: Adrian

middle: B

last: McDermott

first: Richard

last: Koup

first: Constantinos

last: Petrovas

first: Stephen

last: Migueles

first: Mark

last: Connors

first: Georgia

middle: D

last: Tomaras

first: Susan

last: Moir

first: Shane

last: Crotty

first: Haddad

last: Elias


title: Generating IGF1 signatures in human melanoma cell lines by activation of IGF1 or ihibition of IGF1R

first: Wencai

last: Ma

summary: To generate IGF1 signatures in human melanoma cell lines. Recombinant human IGF1 (rhIGF1) was added to WM35, known to be responsive to rhIGF1, whereas constitutive IGF1 signaling in Mel-624 was abrogated by siRNA directed against the IGF1 receptor (siIGF1R). Experiments were performed in triplicate in normoxia (O2 concentration, 21%) and hypoxia (1% O2), because hypoxia has been suspected to play an adverse role in melanoma. After generating GEP data, we created signatures of genes significantly (p ≤0.0001, q ≤0.05) and consistently upregulated in rhIGF1-treated WM35 cells, or similarly downregulated in siIGF1R-treated Mel-624 cells, as compared to control cells at the same O2 concentration.

overall_design: To find out whether IGF1 signatures generated in human melanoma cell lines are predictive of outcome in melanoma patients, we generated IGF1 signatures in two cell lines WM35 and Mel-624. The expression of IGF1 signatures were then tested by using GSSA (Gene Signature Survival Analysis) method to find out correlation with clinical outcome of melanoma patients.

first: Zhiqiang

last: Wang

first: R

last: Davis

first: Kenneth

last: Tsai


title: Human WM35 melanoma cell line treated with trifluorothymidine(TFT) and lactimidomycin(LTM)

summary: To generate drug signatures in human WM35 melanoma cell line. WM35 cell line was plated at 4 x 105 cells/mL overnight and treated with trifluridine or lactimidomycin at 75% inhibitory concentrations (IC75, determined previously at 72h of treatment) or DMSO (vehicle) for 8h or 24h before harvest.

overall_design: To find out whether drug signatures generated in human melanoma cell lines are predictive of outcome in melanoma patients, we generated trifluorothymidine(TFT) and lactimidomycin(LTM) signatures in cell lines WM35 . The expression of drug signatures were then tested by using GSSA (Gene Signature Survival Analysis) method to find out correlation with clinical outcome of melanoma patients.

first: Lili

last: Du


title: Global cellular biological processes modulated by Dasatinib treatment in renal cell carcinoma

city: Shanghai

first: Meiyu

last: Geng

address: 555 Zuchongzhi Road

institute: Shanghai Institute of Material Medica

summary: We used microarrays to probe the global programme of gene expression under treatment with Dasatinib in Caki-1 and 769-P cells and identified distinct classes of up- and down-regulated genes during this process

overall_design: We treated Caki-1 and 769-P cells with DMSO or Dasatinib at 1uM for 6, 12 and 24 hours


title: Correlating Gene Signatures with Outcome to find Features and Drugs Relevant to Cancer

overall_design: Refer to individual Series


title: Human A375 melanoma cell line treated with trifluorothymidine (TFT) and lactimidomycin (LTM)

summary: To generate drug signatures in human A375 melanoma cell lines. A375 cell line was plated at 4 x 105 cells/mL overnight and treated with trifluridine or lactimidomycin at 75% inhibitory concentrations (IC75, determined previously at 72h of treatment) or DMSO (vehicle) for 8h or 24h before harvest.

overall_design: To find out whether drug signatures generated in human melanoma cell lines are predictive of outcome in melanoma patients, we generated trifluorothymidine(TFT) and lactimidomycin(LTM) signatures in cell lines A375 . The expression of drug signatures were then tested by using GSSA (Gene Signature Survival Analysis) method to find out correlation with clinical outcome of melanoma patients.


title: lncRNA NDRG1-OT1 downstream gene microarray

status: Public on Dec 31 2017

city: Taipei

first: Liang-Chuan

last: Lai

state: Taiwan

address: 1 Jen-Ai Road, Sec 1

department: Physiology

country: Taiwan

institute: National Taiwan University

summary: To investigate the target gene of lncRNA NDRG1-OT1 in breast cancer

overall_design: To over-express NDRG1-OT1, the MCF7 cell line was transfected with pcDNA3.1(+)-NDRG1-OT1 plasmid using jetPRIME transfection reagent (Polyplus-transfection SA) according to manufacturer’s instructions.


title: Oncogenic KRAS mediates amino acid metabolism during nutrient stress via regulation of NRF2 and ATF4 in NSCLC [shKRAS low Q]

status: Public on Dec 30 2017

city: Palo Alto

first: E.

middle: Alejandro

last: Sweet-Cordero

state: CA

address: 265 Campus Drive

department: Pediatrics

institute: Stanford University

summary: Glutamine is a key nutrient for tumor cells that supports nucleotide and amino acid biosynthesis, replenishes the TCA cycle intermediates and contributes to redox metabolism. We identified oncogenic KRAS as a critical regulator of the response to glutamine deprivation in NSCLC. Full activation of the ATF4 stress response pathway is dependent on expression of NRF2 downstream of oncogenic KRAS in NSCLC. Through this mechanism, KRAS alters amino acid uptake and metabolism and sustains mTORC1 signaling during nutrient stress. Furthermore, we identified regulation of asparagine synthetase (ASNS) as a key effect of oncogenic KRAS signaling via ATF4 during glutamine deprivation, and a potential therapeutic target in KRAS mutant NSCLC.

overall_design: 8 Samples were analyzed.  There were no biological replicates; instead, different cells lines cultured in similar conditions were used. Cells were cultured in low glutamine (0.5mM Q)  for 72 hrs where indicated.

first: Dana

last: Gwinn

first: Alex

middle: G

last: Lee

first: Alejandro


title: Comparative analysis of the transcriptome responses of zebrafish embryos after exposure to low concentrations of essential and non-essential metals.

status: Public on Dec 27 2017

city: Aachen

first: Laura

last: Sonnack

address: Forckenbeckstr. 6

institute: Fraunhofer IME

summary: Metal toxicity is a global environmental challenge. Fish are particularly prone to metal exposure, which can be lethal or can cause sublethal physiological impairments. The objective of this study was to improve our understanding on how adverse effects of essential and non-essential metals in early life stage zebrafish may be explained by changes in the transcriptome after exposure to non-toxic levels. We therefore studied the effects of three different metals at low concentrations in zebrafish embryos by transcriptomics analysis. The study design compared exposure effects caused by different metals at different developmental stages (pre-hatch and post-hatch). Wild-type embryos were exposed to solutions of low concentrations of copper (CuSO4), cadmium (CdCl2) and cobalt (CoSO4) until 96 h post-fertilization (hpf) and microarray experiments were carried out to determine transcriptome profiles at 48 and 96 hpf. We found that the toxic metal cadmium affected the expression of more genes at 96 hpf than 48 hpf. The opposite effect was observed for the essential metals cobalt and copper, which also showed enrichment of different GO terms. Genes involved in neuromast and motor neuron development, were significantly enriched, agreeing with our previous results showing motor neuron and neuromast damage in the embryos. Our data provide evidence that the response of the transcriptome of fish embryos to metal exposure differs for essential and non-essential metals.

overall_design: Zebrafish embryos exposed to 3.3 mg/L cadmium treatment (C3), 3.6 mg/L cobalt treatment (C3) and 6.1 µg/L copper treatment (C3) with additional ISO water controls (C0); Two developmental stages 48 hpf and 96 hpf; 48 hpf three replicates and 96 hpf four replicates

first: Thorsten

last: Klawonn

first: Ralf

last: Kiehuber

first: Henner

last: Hollert

first: Christoph

last: Schäfers

first: Martina

last: Fenske


title: Regulation of mammary luminal cell differentiation and tumorigenesis by p38α

status: Public on Dec 28 2017

city: Barcelona

first: Camille

last: Stephan Otto Attolini

state: Select a State or Province

address: Baldiri Reixac 10

department: Biostatistics and bioinformatics Unit

institute: IRB Barcelona

summary: Mammary stem and progenitor cells are essential for mammary gland homeostasis and are also candidates for cells of origin of mammary tumors. Here, we provide evidence that the protein kinase p38a is required for the differentiation of luminal progenitor cells through modulation of the transcription factors Runx1 and Foxa1. Moreover, using a mouse model for breast cancer initiated by luminal cells, we show that p38a downregulation in mammary epithelial cells reduces tumorigenesis, which correlates with reduced numbers of tumor-initiating cells. Our results identify p38a as a key regulator of luminal progenitor cell fate that facilitates mammary tumor formation.

overall_design: Total RNA was collected from luminal population of the mammary gland purified by FACs from p38a-lox, MMTV-Cre vs MMTV-Cre and p38a-lox, MMTV-Cre, MMTV-PyMT vs MMTV-Cre, MMYV-PyMT mice. Cells were sorted on  TRIzol® Plus RNA Purification Kit (Life Technologies).Total RNA was extracted using RNAeasy Micro Kit (Quiagen).

first: Ivan

last: del Barco Barrantes

last: Stephan-Otto Attolini


title: Gene expression profile in gastric cancer cells by Verteporfin (VP)

status: Public on Dec 26 2017

first: YUNYONG

last: PARK

address: 84 Heukseok-ro

institute: ChuangAng University

summary: Verteporfin (trade name Visudyne) is a medication used as a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye associated with conditions such as the wet form of macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 689 nm[1] in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels. Recently, it was reported that VP has chemotherapeutic effect in cancer. To identify the gene expression profile in gastric cancer cells by VP, we performed microarray.

overall_design: VP was treated to gastric cancer cells, AGS and MKN45 cell. Eath group is trplicate sample (DMSO=3, VP Treat=3).

first: Myoung-Hee

last: Kang

first: Yun-Yong

last: Park


title: MO-OH-Nap and SAHA induce distinct patterns of gene expression in the multiple myeloma cell line U266.

city: Buffalo

first: Qiang

last: Hu

state: NY

address: Elm & Carlton Streets

institute: Roswell Park Cancer Institute

summary: Tropolones are small organic compounds with metal-directing moieties. Functionally, tropolones inhibit the proliferation of cancer cell lines, possibly through the inhibition of metalloenzymes such as select histone deacetylases (HDACS). Pan-HDAC inhibitors are therapeutically beneficial in the treatment of multiple myeloma albeit with significant side-effects likely owning to their lack of specificity. It was therefore hypothesized that tropolones might have anti-myeloma activities. To this end, a series of novel a-substituted tropolones were evaluated for cytotoxic effects in multiple myeloma cells. While all tested tropolones showed some level of toxicity, MO-OH-Nap had consistently low EC50 values between 1-11 mM in all three cell lines tested and was used for subsequent experiments. MO-OH-Nap was found to induce apoptosis in a concentration-dependent manner. Time course experiments demonstrated that MO-OH-Nap promotes caspase cleavage in a time-frame that was distinct from the pan-HDAC inhibitor SAHA. Furthermore, MO-OH-Nap- and SAHA-treated cells possess unique gene expression patterns, suggesting they promote apoptosis via different mechanisms. In particular, MO-OH-Nap increases the expression of markers associated with endoplasmic reticulum stress and the unfolded protein response. Synergistic cytotoxic effects were observed when cells were treated with the combination of MO-OH-Nap and the proteasome inhibitor bortezomib. However, treatment with MO-OH-Nap did not abrogate the bortezomib-induced increase in aggresomes, consistent with an HDAC6-independent mechanism for the observed synergy. Collectively, these finding support further investigation into the usefulness of a-substituted tropolones as anti-myeloma agents.

overall_design: U266 cells were treated with DMSO (24 hours), SAHA (24 hours), MO-OH-Nap (24 hours) or MO-OH-Nap (48 hours). Experiments were performed in triplicate for each of the four treatment groups, yielding a total of 12 samples Following 24 or 48 hr incubations, RNA was extracted and used for microarray analysis with the Illumina HumanHT-12 v4 Expression BeadChip. Data were analyzed with R language and Bioconductor packages. Microarray data normalization, background correction and quality control were carried out with the Bioconductor package “lumi”. The R package “limma” was used to perform differential gene expression analysis of the normalized microarray data. The significant differentially expressed genes (DEG) had a p-value less than 0.05 and fold change with a cut off of 1.5.

first: Sarah

last: Holstein


title: Human A375 melanoma cell line treated with ciclopirox and crizotinib

first: Wencai

last: Ma

summary: To generate drug signatures in human A375 melanoma cell lines. A375 cell line was plated at 4 x 105 cells/mL overnight and treated with ciclopirox or crizotinib at 75% inhibitory concentrations (IC75, determined previously at 72h of treatment) or DMSO (vehicle) for 8h or 24h before harvest.

overall_design: To find out whether drug signatures generated in human melanoma cell lines are predictive of outcome in melanoma patients, we generated ciclopirox and crizotinib signatures in cell lines A375 . The expression of drug signatures were then tested by using GSSA (Gene Signature Survival Analysis) method to find out correlation with clinical outcome of melanoma patients.

first: Lili

last: Du

first: Zhiqiang

last: Wang

first: R

last: Davis

first: Kenneth

last: Tsai


title: Oncogenic KRAS mediates amino acid metabolism during nutrient stress via regulation of NRF2 and ATF4 in NSCLC [shKRAS high Q]

first: E.

last: Sweet-Cordero

overall_design: 8 Samples were analyzed.  There were no biological replicates; instead, different cells lines cultured in similar conditions were used. Cells were cultured in standard tissue culture glutamine concentrations (4mM Q) for 72 hrs where indicated.

first: Dana

last: Gwinn

first: Alex

last: Lee

first: Alejandro


title: Oncogenic KRAS mediates amino acid metabolism during nutrient stress via regulation of NRF2 and ATF4 in NSCLC

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


title: Analysis of immediate-early induced target genes of the BMP and WNT pathways in human ES cells

status: Public on Dec 07 2017

city: Münster

first: Boris

last: Greber

address: Von-Esmarch-Str. 54

institute: Max Planck Institute for Molecular Biomedicine

summary: Human ES cells respond to activation of the BMP and WNT signaling by upregulating target genes. A 4h time-point following signaling factor stimulation was chosen to reveal immediate-early induced genes which are likely to be direct targets.

overall_design: Human ES cells were subjected to short-term signaling factor treatments to reveal immediate-early induced gene expression.


title: Comparative cardiac induction time-courses using WT, EOMES KO, and EOMES TET-ON human ES cells

summary: This study compares cardiac induction time-courses using (i) wild-type hESCs subjected to a standard directed differentiation protocol, (ii) EOMES knockout hESCs subjected to the same protocol, and (iii) EOMES KO / TET-ON hESCs subjected to a TET-ON protocol.

overall_design: Total RNA was isolated in a time course manner from the three distinct series of differentiating samples (day 0 until day 7 of differentiation).

first: Martin

last: Pfeiffer


title: Mycobacterium tuberculosis Exploits a Molecular Off Switch of the Immune System for Intracellular Survival

status: Public on Dec 21 2017

city: London

first: Maurice

last: Berk

address: St Mary's Campus

institute: Imperial College London

summary: Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human macrophages by subversion of immune mechanisms. Although these immune evasion strategies are well characterised functionally, the underlying molecular mechanisms are poorly understood.  Here we show that during infection of human whole blood with M. tuberculosis, host gene transcriptional suppression, rather than activation, is the predominant response. Spatial, temporal and functional characterisation of repressed genes revealed their involvement in pathogen sensing and phagocytosis, degradation within the phagolysosome and antigen processing and presentation. To identify mechanisms underlying suppression of multiple immune genes we undertook epigenetic analyses. We identified significantly differentially expressed microRNAs with known targets in suppressed genes. In addition, after searching regions upstream of the start of transcription of suppressed genes for common sequence motifs, we discovered novel enriched composite sequence patterns, which corresponded to Alu repeat elements, transposable elements known to have wide ranging influences on gene expression.  Our findings suggest that to survive within infected cells, mycobacteria exploit a complex immune “molecular off switch” controlled by both miRNAs and Alu regulatory elements.

overall_design: 2 cohorts of blood samples infected with Mycobacterium tuberculosis and the same with Mycobacterium bovis BCG - Discovery and Validation. Experimental  (discovery: n=4 donors; validation: n=6 donors for Mycobacterium tuberculosis), discovery set n=4; validation set n=5 for M. bovis BCG infection experiments). Replicates for each sample were not included but multiple timepoints for RNA extraction from each experimental donor were inlcuded. Timepoints for gene expression analysis included (Discovery set 0, 6, 24, 48, 72, 96 h; Validation set 0, 24, 48, 72, 96 h). Uninfected whole blood samples served as matched controls at each time point.

first: Ulrich

last: von Both

first: Paul-Michael

last: Agapow

first: Joseph

last: Wright

first: Anna

last: Git

first: Melissa

middle: S

last: Hamilton

first: Greg

last: Goldgof

first: Nazneen

last: Siddiqui

first: Evangelos

last: Bellos

first: Victoria

first: Lachlan

last: Coin

first: Sandra

last: Newton

first: Michael

last: Levin


title: Oncogenic KRAS mediates amino acid metabolism during nutrient stress via regulation of NRF2 and ATF4 in NSCLC [low versus high Q]

first: E.

last: Sweet-Cordero

overall_design: 8 Samples were analyzed.  There were no biological replicates; instead, different cells lines cultured in similar conditions were used. Controls were cultured in standard tissue culture glutamine concentrations (4mM Q), while low glutamine (0.5mM Q) was used for 72 hrs where indicated.

first: Dana

first: Alex


title: Integrative genomic and cellular analyses of blood and T cells from HIV-1 controllers reveal a low inflammatory profile associated with strong HIV-specific adaptive responses [Whole Blood]

status: Public on Dec 20 2017

city: Paris

first: Hakim

last: hocini

address: 101 Rue de Tolbiac

country: France

institute: INSERM

summary: Without treatment, HIV-1 infection is characterized in the majority of individuals by a detectable HIV replication and a rapid decline in CD4+ T lymphocytes leading to AIDS.  However, a minority of patients, called “HIV Controllers” (HIC), maintains spontaneous control of HIV replication and for a large part, normal CD4+ T cell counts. The mechanisms leading to this spontaneous virus control are not fully known. We used gene expression and functional cellular analyses to compare EC and chronically HIV-1 infected individuals with controlled virus replication under combined antiretroviral therapy (cART). In the blood, EC individuals are characterized by a low inflammation, a down modulation of NK inhibitory cell signaling and an up regulation of T-cell activation gene expression profiles. Interestingly, in contrast to cART individuals, this balance persists following in vitro stimulation of cells from HIC with HIV antigens. This favourable genetic profile in HIC was also consistent with functional analyses showing a bias towards a Th1 and cytotoxic T cell profile and a lower production of inflammatory cytokines. Finally, taking advantage of the characterization of HIC based upon their in vitro CD8+ T lymphocyte capacity of killing HIV-infected cells, we show that unsupervised genetic analysis of differentially expressed genes fits clearly with this cytotoxic activity allowing the characterization of a specific signature of HIC individuals. Globally, these results reveal significant features of HIC making the bridge between cellular function and gene signatures and the regulation of inflammation and killing capacity of HIV-specific CD8+T cells. Moreover, these genetic profiles are consistent through analyses performed from whole blood to PBMC and at the T-cell population levels. Likely, these data help to define the goals of immunotherapeutic approaches in the perspective of HIV-1 functional cure. These strategies would need to induce both strong HIV-1-specific immune responses whereas minimizing inflammation.

overall_design: Whole blood, PBMC and CD4/CD8 mRNA of HIV-1 controllers and HAART patients

first: Yves

last: LEVY

first: Rodolphe

last: THIEBAUT

last: Hocini

first: Asier

last: Saez–Cirion


title: Characterization and molecular mechanistic study of a therapeutic peptide functionalized nanobioconjugate inhibiting the p53-HDM2 interaction in Retinoblastoma

city: Bangalore

first: madavan

last: vasudevan

state: Karnataka

address: Kasturi Nagar

country: India

institute: Theomics International Private Limited

summary: Prepared peptide conjugate nanoparticles for retinoblastoma cancer therapy

overall_design: Retinoblastoma cell line treated with gold nanoparticles and gold nanoparticles conjugated with HDM2 peptide

first: Sushma

last: Kalmodia

first: Sowmya

last: Parameswaran

first: Subramanian

last: Krishnakumar

first: Madavan

last: Vasudevan

first: Kirti

last: Kulkarni


title: Antigen presenting cells of myeloid origin

city: Bonn

first: Joachim

last: Schultze

state: NRW

address: Carl-Troll-Strasse 31

department: Genomics and Immunoregulation

institute: LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)

summary:
Transcriptional profiles of four different myeloid antigen presenting cell (APC) subsets (BDCA-1+ circulating myeloid dendritic cells, CD14+ monocytes, and in vitro generated immature and mature monocyte-derived dendritic cells) were used for comprehensive transcriptome analysis. Based on the gene expression profiling data, a quantitative relationship between myeloid APC in functionally related gene spaces was established.
Keywords = myeloid antigen presenting cells
Keywords = dendritic cell subsets
Keywords: repeat sample

first: Alexey

last: Popov

middle: L


title: Hsa-miR-500a-5p target discovery

status: Public on Nov 27 2017

city: Bron

first: Hector

last: Hernandez-Vargas

state: Rhone

address: 36 bis Rue de la Batterie

institute: Genomics Consulting

summary:
Hsa-miR-500a-5p (miR500a) activity has been associated with breast cancer survival.
We used gene expression arrays (Illumina HumanHT-12 V4.0) to discover relevant targets of miR500a.

overall_design: MiR500a was overexpressed (mimics) or suppressed (inhibitor) in two breast cancer cell lines (MCF7 and T47D). Triplicates or quadruplicates of each condition were used for RNA extraction after 2 days of transfection and gene expression analyses.

first: H

first: D

last: Degli Esposti


title: Expression profiling of blood from pulmonary tuberculosis patient and healthy controls

status: Public on Dec 06 2017

city: Tongliao

first: Batudeligen

last: Duan

state: Inn Mongolian

address: 1742 Huolinhe Street

department: Affiliated hospital of Inner Mongolian University for the nationalities

institute: Institute of clinical pharmacology of traditional Mongolian Medicine

summary:
Pulmonary tuberculosis is a multigene disease, and some of the genes affect the development of Pulmonary tuberculosis. The study wants to find different expression genes in blood from Pulmonary tuberculosis patient and normal people who have genetic relationship wtih each other.
We used microarrays to detail the global programme of gene expression in the blood between Pulmonary tuberculosis patient's and normal people's who have genetic relationship wtih each other.

overall_design: Blood from  Pulmonary tuberculosis patient and normal people who have genetic relationship wtih each other were selected for RNA extraction and hybridization on Affymetrix microarrays.


title: Enabling phenotypic drug discovery for neurological mitochondrial DNA disorders with patient-derived neural progenitor cells

city: Berlin

first: Nancy

last: Mah

address: Augustenburger Platz 1

department: Berlin-Brandenburger Centrum für Regenerative Therapien (BCRT)

institute: Charité - Universitätsmedizin Berlin

summary: Mitochondrial DNA (mtDNA) mutations predominantly cause neurological diseases. Searching for therapeutic strategies is hindered by the absence of viable neural model systems due to the challenges of engineering mtDNA. We demonstrate that neural progenitor cells (NPCs), rapidly obtained from human induced pluripotent stem cells (iPSCs), retain the parental mtDNA profile and exhibit mitochondrial maturation coupled with a metabolic switch away from glycolysis. Altered calcium homeostasis and mitochondrial hyperpolarization, both potential causes of neural impairment, were observed in iPSC-derived NPCs from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C). Phenotype-based high-content screenings (HCS) with FDA-approved compounds were then carried out, leading to the identification of possible innovative counteracting agents. We propose iPSC-derived NPCs, displaying mild proliferative properties and proper genotype/metabotype, as a bona fide model system for the establishment of personalized phenotypic drug discovery for untreatable mtDNA disorders affecting the nervous system.

overall_design: In the first part of the work, Neural Induction (NI) NPCs were generated from PSCs (hESCs and iPSCs) and compared to NPCs derived using a rosette-based approach (rNPCs) and NPCs derived ex vivo from adult human brain (eNPCs). In the second part of the work, control fibroblasts, control PSCs, and control NI NPCs were compared to fibroblasts, iPSCs, and NI NPCs derived from three patients carrying a mutation in the mitochondrial gene MT-ATP6 (m.9185T>C).

first: Alessandro

last: Prigione


title: Transcriptome analysis of GIST430 and GIST882 cells transfected with nontargeting microRNA or with miR-494

status: Public on Nov 09 2017

city: SEOUL

first: SeongJu

last: Yun

address: Sinchon-dong

institute: Yonsei University

summary: Gene expression microarry by using GIST430 and GIST882 cells with or without miR-494 treatment

overall_design: GIST430 and GIST882 cells were transfected with either nontargeting siRNA or miRNA-494 and harvested after 72 hours. Total RNA obtained from

first: WonKyu

last: Kim

first: Hoguen


title: SNAIL1-mediated Downregulation of FOXA Proteins Facilitates the Inactivation of Transcriptional Enhancer Elements at Key Epithelial Genes in Colorectal Cancer Cells

status: Public on Nov 10 2017

city: Lübeck

first: Hauke

last: Busch

state: Schleswig-Holstein

address: Ratzeburger Allee 160

department: Lübeck Institute of Experimental Dermatology

institute: University of Lübeck

summary: Converting epithelial into mesenchymal cells through epithelial-mesenchymal transition (EMT) requires massive changes in gene expression. How this is brought about is currently not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anti-correlated in transcriptomes of colorectal tumors and cell lines. In two cellular EMT models, ectopically expressed Snail1 downregulates FOXA factors and directly represses FOXA1. To elucidate how FOXA factors contribute to the control of epithelial gene expression, we determined by ChIP-seq data analysis FOXA chromosomal distribution in relation to chromatin structural features characterizing distinct states of transcriptional activity. This revealed a preferential localization of FOXA1 and FOXA2 to transcriptional enhancers at signature genes that distinguish epithelial from mesenchymal colon tumors. To validate the significance of this association, we investigated the impact of FOXA factors on structure and function of transcriptional enhancers at the epithelial genes CDH1, CDX2 and EPHB3. Expression of dominant negative FOXA2 led to chromatin condensation at these enhancer elements. Site- directed mutagenesis of FOXA binding sites in reporter gene constructs and by genome- editing in situ impaired enhancer activity and completely abolished the active chromatin state of the EPHB3 enhancer. Conversely, expression of FOXA factors in cells with inactive CDX2 and EPHB3 enhancers led to chromatin opening and de novo deposition of the H3K4me1 and H3K27ac marks. These findings establish the pioneer function of FOXA factors at enhancer regions of epithelial genes and demonstrate their essential role in maintaining enhancer structure and function. Thus, by repressing FOXA family members, Snail1 targets transcription factors at strategically important positions in gene-regulatory hierarchies which may facilitate transcriptional reprogramming during EMT.

overall_design: Total RNA was extracted in biological triplicates from parental LS174T colorectal carcinoma cells and LS174T cell clones subjected to CRISPR/Cas9 genome editing targeting the FOXA1 locus

first: Melanie

last: Boerries

first: Andreas

last: Hecht

first: Sabine

last: Jaegle


title: Integrative genomic and cellular analyses of blood and T cells from HIV-1 controllers reveal a low inflammatory profile associated with strong HIV-specific adaptive responses [PBMC]

first: Hakim

last: hocini

first: Yves

last: LEVY

first: Rodolphe

last: THIEBAUT

last: Hocini

first: Asier

last: Saez–Cirion


title: Integrative genomic and cellular analyses of blood and T cells from HIV-1 controllers reveal a low inflammatory profile associated with strong HIV-specific adaptive responses [CD4/CD8]


title: Global gene expression profile of reprogrammed osteosarcoma cell lines, iG-292 and iSaos-2.

status: Public on Dec 09 2017

city: Kuala Lumpur

first: Pei Feng

last: Choong

address: PPUKM-MAKNA Cancer Centre

department: Research

country: Malaysia

institute: MAKNA

summary:
To establish a genomewide gene expression profile of OS-derived induced pluripotent stem cell lines (OS-iPSC): iG-292 and iSaos-2, against the parental cell lines, G-292 and Saos-2.
OS cell lines were first reprogrammed into pluripotent state by retroviral transduction of OSKM. Six OS-iPSC clones and four parental OS cell lines were subjected to mRNA microarray analysis (Affymetrix Human PrimeView Chip).

overall_design: Six OS-iPSC clones were relatively compared with four parental OS cell lines

first: Choong

last: Feng

first: The

last: Xin

first: Ong

last: Kiat

first: Cheong

last: Keng


title: nc886, a TGF-β-induced non-coding RNA, suppresses the microRNA pathway in ovarian cancer

status: Public on Nov 08 2017

city: HOUSTON

first: Hyun-Sung

last: Lee

state: TX

address: One Baylor Plaza

department: Surgery

institute: BAYLOR COLLEGE OF MEDICINE

summary: Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated, but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis/mesenchymal subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. nc886's high expression is associated with the poor prognosis of 285 patients in an OC cohort. Herein we have found in OC that nc886 expression is induced by TGF-β and that nc886 binds to the enzyme Dicer to inhibit the processing of miRNA precursors into mature forms. By preventing the miRNA pathway, nc886 emulates TGF-β in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. We report nc886 as a novel molecular link between the TGF-β and miRNA pathways.

overall_design: Pre-clinical study.

first: Hyun

first: Yong

first: Ju


title: Comprehensive analysis of genomic G-quadruplex forming oligonucleotides homologous to NHEIII1 of c-MYC promoter on leukemia cell growth inhibition and c-MYC expression

status: Public on Dec 01 2017

city: Louisville

first: Eric

middle: Christian

last: Rouchka

state: Kentucky

address: 522 East Gray Street

department: Biochemistry and Molecular Genetics

institute: University of Louisville

summary: The c-MYC onco-protein regulates a large array of genes playing an important role in basic cell functions.  Because of its central role in growth regulation, c-MYC expression must be tightly regulated. The NHEIII1 located upstream of the P1 promoter regulates up to 80% of c-MYC transcription, and includes a C/G rich region (Pu27) which forms a G-quadruplex structure.  We have identified seventeen genomic G-quadruplex-forming motifs which have more than 90% identity with Pu27 found on different chromosomes throughout the human genome. Of thirteen members of the Pu27 family tested, all interact specifically with NHEIII1 sequence and inhibit leukemic cells proliferation to differing degrees. Further characterization of three Pu27 homologous sequences (Pu5-, Pu9- and Pu27) reveals a dose/time dependent response on growth inhibition in four leukemia cell lines and down regulation of c-MYC at RNA and protein level.  The three Pu27 family members selectively alter expression of genes involved in cell cycle progression/regulation, DNA damage/repair and histone modification. In conclusion, we have identified sixteen genomic G-quadruplex-forming sequences homologous to Pu27 of c-MYC promoter sharing the same structure and function.  It is likely that these sequences play important biologic roles in c-MYC regulation and provide an ideal tool for targeted cancer therapy.

overall_design:
A total of 39 samples were hybridized, representing triplicates with untreated (unt) at 0h, 24h, 48h, and 72h, and three (3) oligonucleotide treatments: Pu27, Pu9-, and Pu5- at three (3) timepoints: 24h, 48h, and 72h (3+3x3x4=39).  This includes: Untreated (wild type) at 0, 24, 48, and 72 hr; Treated with the Pu5- oligonucleotide sequence TGGGGAGGGTGGGGAGGGTGGTGAGGGTGGGGAGGGGGAAGG at 24, 48, and 72hr; Treated with the Pu9- oligonucleotide sequence GGGTGGGGAGGGTGGGGAAG at 24, 48, and 72hr; and Treated with the Pu27 oligonucleotide sequence TGGGGAGGGTGGGGAGGGTGGGGAAGG at 24, 48, and 72hr.
The complete data matrix including control probes (49,495 data rows) is included as a Series supplementary file.

first: Francine

last: Rezzoug

first: Shelia

last: Thomas

last: Waigel

first: Donald

last: Miller


title: Altered intestinal functions and increased local inflammation in insulin-resistant obese subjects: a gene-expression profile analysis.

status: Public on Nov 30 2017

city: Quebec

first: Yohan

last: Bossé

state: Quebec

address: 2725, chemin Sainte-Foy

country: Canada

institute: Laval University

summary: Metabolic alterations relevant to postprandial dyslipidemia were previously identified in the intestine of obese subjects with systemic insulin resistance. These dysregulations were closely associated with an amplification of intestinal lipogenesis and lipoprotein output, which was triggered by insulin resistance likely sustained by oxidative stress and inflammation. The aim of the study was to identify the genes deregulated by the presence of systemic insulin resistance in the intestine of severely obese subjects. Transcripts from duodenal samples of insulin-sensitive (HOMA-IR<3, n=9) and insulin-resistant (HOMA-IR>7, n=9) obese subjects were assayed by microarray (Illumina HumanHT-12). The small intestine exhibits a highly specific mRNA expression profile that was similar between insulin-sensitive and insulin-resistant individuals. A total of 195 annotated genes were identified as differentially expressed between these two groups with a fold change higher than 1.2. Metabolic pathway analysis revealed that 36 differently expressed genes were directly involved in known intestinal functions, including digestion, extracellular matrix, endocrine system, immunity, inflammation/oxidative stress and cholesterol metabolism. Several signaling pathways involved in immunity and inflammation were significantly enriched in differently expressed genes and were predicted to be activated in the intestine of insulin-resistant subjects. Using stringent criteria (Fold change>1.5; FDR<0.05), only three genes were found to be significantly and differently expressed in the intestine of insulin-resistant compared to insulin-sensitive subjects: the transcripts of the insulinotropic glucose-dependant peptide (GIP) and of the β-microseminoprotein (MSMB) were significantly reduced, but that of the humanin like-1 (HNL1) protein was significantly increased. These results underline that systemic insulin resistance is associated with an amplification of local inflammatory process and remodeling of key intestinal functions. Genes identified in this study are potentially triggered throughout the development of intestinal metabolic alterations, which could contribute to dyslipidemia, a component of metabolic syndrome and diabetes.

first: Levy

last: Emile

first: Veilleux

last: Alain

first: Bossé

last: Yohan


title: Identification differentially expressed genes in the mouse testis caused by Prss55 deficiency

status: Public on Nov 28 2017

city: Shanghai

first: Chunling

last: Shen

address: 197 Ruijin No.2 Road

department: Research Center for Experimental Medicine

institute: Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

summary: Testes from three wt and three Prss55-/- mice were used for gene expression analysis using whole mouse genome 4 × 44 k microarray (Agilent Technologies). A total of 72 genes were identified to be differentially expressed significantly (p < 0.05, fc ≥ 2). Fold changes of ten genes (seven up-regulated genes and three down-regulated genes) were examined by qRT-PCR for data validation.

overall_design: Total RNAs were extracted from testes of wt and Prss55-/- mice (n = 3 each genotype, 6-8 weeks old).

first: Xuan

last: Shang

first: Zhugang

last: Wang


title: The influence of Chelidonine on gene expression in the head and neck carcinoma cell line FaDu

city: Wuerzburg

first: Marianne

last: Schmidt

state: Outside U.S. & Canada

institute: University of Wuerzburg, Dept. of Otorhinolaryngology

summary: It has been shown, that the Chelidonine has growth and invasion inhibiting properties on head and neck carcinoma cell lines. The affymetrix prime view array was used to gain a first view on the influence of chelidonine on gene expression of head and neck cancer cells.

overall_design: FaDu cells were grown for 48 hrs with or without the EC50 dose and 10 µM of chelidonine

first: Ruth

last: Herrmann


title: Integrative genomic and cellular analyses of blood and T cells from HIV-1 controllers reveal a low inflammatory profile associated with strong HIV-specific adaptive responses

first: Hakim

last: hocini

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

overall_design: Refer to individual Series


title: Expression diversity between prostate cancer cell line PC3 and circulating tumor cell derived from PC3

status: Public on Nov 01 2017

city: Xi'an

first: chen

last: shao

state: Shanxi

address: West changle road No.169

department: Department of Urology

institute: The Fourth Military Medical University

summary: Circulating tumor cells (CTCs) are a group of cells detached from primary cancer and poured into blood. Compared with local cancer cells, CTCs display more invasive ability to colonize distant organs. During the process of releasing CTCs, not only morphogical changes in cancer cells, up/down regulation of some critical molecules may contribute to its potential to spread to other locations.

overall_design: Total RNA of CTCs and its parental cell PC3 was extracted using Trizol reagent, then molecular hybridization was performed on Affymetrix microarrays. 3 times repetition were carried on for each group to improve credibility of expression profiles. Moreover, expression of PC3 was treated as control group.

first: Chen

last: Shao

first: Juntao

last: Yue


title: Expression data from endothelial cells induced from bone marrow mesenchymal stem cells with SCD1 overexpression

status: Public on Nov 07 2017

first: Jie

last: Tao

address: haining road 100

institute: Shanghai General Hospital

summary:
Bone marrow mesenchymal stem cells (BM-MSCs) are of multi-differentiating potential and has been demonstrated to have the ability to differentiate into endothelial cells. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in lipid metabolism, which can convert saturated fatty acids into unsaturated fatty acids. We used lentivirus to transfected SCD1 gene into BM-MSCs and found that overexpression of SCD1 could promote the differentiation of BM-MSCs into endothelial cells.
We used microarrays to detect the differential gene expression profile of endothelial induced BM-MSCs with SCD1 overexpression.

overall_design: We transfected bone marrow mesenchymal stem cells with a constructed SCD1 lentivirus and detected that BM-MSCs successfully overexpressed SCD1. After 3 days of endothelial induction in the overexpression group and control group, RNA extraction and hybridization on Affymetrix microarrays were performed.

first: Yuanshan

last: Lu

first: Yao


title: Universal corneal epithelial-like cells derived from human pluripotent stem cells in xeno-free and albumin-free condition

status: Public on Nov 23 2017

city: Taipa

first: Jung

middle: Woo

last: Park

state: Macau

department: Faculty of Health Sciences

institute: University of Macau

summary: Time course experiment of the CEC differentiation. Samples collected from differentiation 0, 2, 4, 6, 8 weeks.

overall_design: A total RNA was harvested from the differentiating cells every two weeks, starting from the undifferentiated H9 to week 8 differentiated cells.

first: Juan

last: Yang


title: CD40L and TNF both activate the classical NF-kappaB pathway, which is not required for the CD40L induced alternative pathway in endothelial cells

status: Public on Nov 29 2017

city: Vienn

first: Rainer

last: de Martin

state: Vienna

address: Schwarzspanierstr. 17

department: Vascular Biology and Thrombosis Research

country: Austria

institute: Medical University of Vienna

summary: Here, we have compared the gene  expression repertoire of CD40L (CD154) and TNF stimulated HUVEC and report that unexpectedly,  apart from a stronger response to TNF, no major qualitative differences could be observed. This  applies for the period of up to six hours, a time where the alternative pathway has already been  activated. Analysis of the early events after receptor engagement revealed that both TNF and CD40L  activate the classical NF-kappaB pathway, and confirm activation of the alternative by the latter.  Furthermore, using genetic and pharmacological inhibition of the classical pathway we show that  activation of the alternative occurs independently of the former. This reveals novel insights into NF-  kappaB signaling by CD40L and TNF in endothelial cells

overall_design: Human Umbilical Vein Endothelial Cells (HUVEC) in passage 4 were seeded in 6 well plates, 80.000 cells/cm2. After reaching post-confluency, the cells were stimulated with 50ng/ml sMCD40L (Enzo Life Sciences) or 10ng/ml TNF (R&D) for 0, 0.5, 1, 2.5, and 6 hours. The experiment was done in triplicates. Total RNA was isolated using the Qiagen RNA Plus Universal mini Kit. Samples were then pooled, and processed for analysis using the Affymetrix PrimeView Human Gene Expression Arrays according to the manufacturer's instructions

first: J

last: Basilio

last: Seigner

first: U

last: Resch


title: Transcriptomic analysis of human fetal microglia during mid-trimester gestation

status: Public on Nov 21 2017

city: Singapore

first: jinmiao

last: chen

address: 8A Biomedical Grove, #04-06 Immunos

country: Singapore

institute: Singapore Immunology Network

summary: Microarray analysis of human fetal microglia from the mid-trimester period was performed. DEGs were identified between early and late stages of the mid-trimester gestation. Genes expressed in the human fetal microglia were also compared with mouse microglia core signature.

overall_design: RNA was extracted from microglia from 14 weeks to 24 weeks gestation human fetuses' brain. Gene expression analysis was done to observe DEGs and differential pathway analysis between the early and late stage.

first: Donovan

last: Low

first: Florent

last: Ginhoux


title: Effect of neutrophils and vincristine on RL follicular lymphoma cells

status: Public on Oct 31 2017

city: Lyon

first: Taghreed

last: Hirz

address: 8 Avenue Rockefeller

institute: Cancer research center of Lyon

summary: Analysis of gene expression levels in non-Hodgkin lymphoma (NHL) cells exposed to neutrophils and chemotherapy. We aimed to see the impact of normal peripheral blood neutrophils on the sensitivity of lymphoma B cells to anticancer agents. The results provide insight into the genes that may be involved in the mechanism by which neutrophils attenuate the sensitivity of lymphoma B cell to chemotherapy.

overall_design: RL cells were cultured alone or co-cultured with neutrophils, in the presence or absence of vincristine for 2 hours. RL cells were purified after labeling with anti-human CD15-Biotin then anti-Biotin Microbeads followed by magnetic column separation. Total RNA was extracted and analyzed. The experiment was performed in triplicate.

first: Kamel

last: Chettab

first: Charles

last: Dumontet


title: Molecular classification of tumour cells in a patient with intravascular large B-cell lymphoma

status: Public on Nov 15 2017

city: Vienna

first: Wolfgang

middle: Michael

last: Bauer

address: Waehringerguertel 18-20

department: Dermatology

summary:
Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal LBCL. It is characterized by the proliferation of tumour cells exclusively intraluminally in small blood vessels of different organs.
We used microarray-based analysis of gene expression of tumour cells isolated from a patient with primary manifestation of the lymphoma in the skin and compared it with various other diffuse LBCLs (DLBCLs) as well as a previously published DLBCL classifier.

overall_design: CD20+CD45+HLA-DR+ tumor cells were FACS sorted from a lesional skin biopsy of the patient and compared to FACS sorted tumor cells from (1) affected lymph nodes from patients with DLBCL (3 samples from patients with DLBCL, nonGCB type; three samples from patients with DLBCL, GCB type) and (2) tumor cells from two patients with primary cutaneous LBCL, leg type.

middle: M

first: Maximilian

last: Aichelburg

first: Johannes

last: Griss

first: Cathrin

last: Skrabs

first: Ingrid

last: Simonitsch-Klupp

first: Ana-Iris

last: Schiefer

first: Harald

last: Kittler

first: Ulrich

last: Jäger

last: Zeyda

first: Robert

last: Knobler

first: Georg

last: Stingl


title: EWS/FLI confers tumor cell synthetic lethality to CDK12 inhibition in Ewing sarcoma

status: Public on Oct 18 2017

city: Cambridge

first: Gabriela

last: Alexe

state: MA

address: 415 Main St.

department: Computational Biology and Bioinformatics

institute: Broad Institute

summary:
Many cancer types are driven by oncogenic transcription factors that act by inducing aberrant gene expression programs. Unfortunately, transcription factors have been notoriously difficult to drug. Alternative approaches would be to inhibit the aberrant transcriptional programs indirectly or to identify synthetic lethal dependencies in the context of the transcription factor abnormality.
We screened THZ1, a recently reported CDK7/12/13 transcriptional inhibitor, in a cancer cell line collection to identify biomarkers of response.  EWS/FLI-driven Ewing sarcoma cells were identified to be markedly sensitive to this compound. We determined that the primary target of THZ1 in Ewing sarcoma is CDK12 using genetic approaches and a new selective CDK12/13 inhibitor, THZ531.

overall_design: We performed global gene expression profiling to investigate the effects of THZ531 on transcriptional programs in Ewing sarcoma. We profiled two highly sensitive Ewing sarcoma cell lines A673 and TC32. Samples were treated in duplicate with DMSO or THZ531 at 100 nM or 500 nM for 6 hours.

first: Kimberly

last: Stegmaier


title: Expression data from Pseudomonas aeruginosa phosphomimetic and phosphoablative AlgR

status: Public on Oct 03 2017

city: Aurora

first: Michael

last: Schurr

state: CO

department: Microbiology

institute: University of Colorado School of Medicine

summary: The Pseudomonas aeruginosa response regulator AlgR is critical for the organism's virulence and controls up to 155 different genes. In order to determine which genes are controlled by phosphorylated and unphosphorylated AlgR, phosphomimetic and phosphoablative alleles were recombined onto the chromosome of PAO1. The algR gene was mutated at aspartate 54 to asparagine (D54N) for the phosphoablative allele and mutated at aspartete 54 to glutamate (D54E) for the phosphomimetic allele. These alleles were recombined into the PAO1 chromosome.

overall_design: Three replicates of the wild-type strain PAO1, PAO1 algRD54N and PAO1 algRD54E were compared after growth for 16 hrs in LB medium.


title: Human cytomegalovirus reprograms hematopoietic progenitor cells into immunosuppressive monocyte to achieve latency

city: Nanjing

first: HONGWEI

last: LIANG

state: Jiangsu Province

address: Qixia District, Xianlin Road No.163

institute: Nanjing University

summary:
HCMV NR-1 infection reprograms human CD34+ HPCs into long-life, NO-producing, immune suppressive Mo-MDSC-like cells at the late stage of infection
We used microarray to detail the gene expression of human CD34+ HPCs and long-life, NO-producing, immune suppressive Mo-MDSC-like cells at the late stage of infection

overall_design: The human CD34+ HPCs were selected, RNA was extracted after HCMV NR-1 successfully established latency in HPCs and HPCs without HCMV infection. We sought to obtain the gene expression in human CD34+ HPCs before and after HCMV infection.

first: Dihan

last: Zhu

first: Ke

last: Zen


title: Methylation and expression profiles of monocytes in monozygotic twins: role in Myasthenia Gravis [expression profiling]

status: Public on Nov 22 2017

city: Paris

first: Sonia

last: Berrih-Aknin

state: State...

address: 105  Boulevard de l’Hôpital

department: Sorbonne Universités

institute: UPMC - Inserm UMRS 974, CNRS FRE3617

summary: Myasthenia gravis (MG) is a relatively rare autoimmune neuromuscular disorder. Monozygotic twin studies indicate that discordance rate in MG is about 70-60%, suggesting that despite identical DNA unknown factors contribute to disease development. The aim of the current study was to identify novel disease-associated genes in purified monocytes, including both genes associated with predisposition or with disease course, using the unique model of MZ twins. Thus the transcriptome and methylome were compared between twins discordant and concordant for the diseases, as well as MG singletons, and healthy controls. Several transcripts associated with immune homeostasis and inflammation resolution were highlighted in the current study.  High similarity between the healthy and the MG discordant twins found, suggest that genetic predisposition may have a stronger contribution then previously assumed. In addition, results suggest that numerous small changes in expression and DNA methylation might contribute to disease onset making it more difficult to pick up

overall_design: The transcriptome and methylome were compared between twins discordant and concordant for Maysthenia Gravis, as well as MG singletons, and healthy controls

first: Shimrat

last: Mamrut

first: Nili

last: Avidan

first: Frederique

last: Truffault

first: Elsebeth

last: Staun-Ram

first: Mélinée

last: Frenkian

first: Ariel

last: Miller


title: FoxO1 inhibition by apelin/APJ signaling in endothelial cells

status: Public on Oct 02 2017

city: New Haven

first: hyung

last: chun

state: CT

address: 300 George St Room 770H

department: Internal Medicine

institute: Yale University

summary: Evaluation of gene transcripts that are downstream of apelin/APJ and FoxO1 signaling in HUVECs

overall_design: Duplicates per group, subjected to: 1) control siRNA, 2) apelin and APJ siRNA, and 3) FoxO1 siRNA

first: Hyung

last: Chun


title: Time-dependent regulation of cellular programming of monocytes by NCOR2 [Illumina array]

status: Public on Dec 19 2017

city: Bonn

first: Joachim

last: Schultze

address: Carl-Troll-Strasse 31

institute: LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)

type:
Expression profiling by array
Third-party reanalysis

summary: Whole transcriptome profiling (Illumina Microarray) of human ex vivo lymphocytes and monocytes, as well as of human monocyte-derived cells generated in vitro by activating CD14+ monocytes with MCSF, GMCSF or the combination of GMCSF and IL4

overall_design:
B, T and NK cells, CD45+ lin- HLA-DR[high] cells as well as CD14+ monocytes were FACS-sorted from blood of human healthy donors. Some CD14+ monocytes were later activated in vitro with either GMCSF or MCSF alone for 72 hours to obtain Mo-GMCSF or Mo-MCSF cells, respectively, or with the combination of GMCSF and IL4. For the latter, monocytes were activated either from the beginning with GMCSF and IL4 for in total 72 or 144 hours to obtain Mo-GMCSF[IL4 (0-72h)] or Mo-GMCSF[IL4 (0-144h)] cells, respectively, or first alone with GMCSF for 72 hours and then for further 72 hours with GMCSF and IL4. Different combined datasets were generated, partly containing also public data (GSE35457) of human ex vivo monocytes and dendritic cells
This study involves third-party_reanalysis of samples from the publicly available dataset GSE35457.  See third-party_reanalysis supplementary files below.

first: Jil

last: Sander

first: Susanne

middle: V

last: Schmidt

first: Branko

last: Cirovic

first: Naomi

last: McGovern

first: Olympia

last: Papantonopoulou

first: Anna-Lena

last: Hardt

first: Anna

last: Aschenbrenner

first: Christopf

last: Kreer

first: Thomas

last: Quast

first: Alex

last: Xu

first: Lisa

last: Schmidleithner

first: Heidi

last: Theis

first: Lan

last: Do

first: Mario

last: Lauterbach

first: Jonas

last: Schulte-Schrepping

first: Patrick

last: Günther

first: Jia

last: Xue

first: Kevin

last: Baßler

last: Ulas

first: Kathrin

last: Klee

first: Stefanie

last: Herresthal

first: Wolfgang

last: Krebs

first: Bianca

last: Martin

first: Eicke

last: Latz

first: Kristian

last: Händler

last: Kraut

first: Waldemar

last: Kolanus

first: Marc

last: Beyer

first: Christine

last: Falk

first: Sven

last: Burgdorf

first: Nicholas

middle: A

last: Melosh

first: Florent

last: Ginhoux

first: Evan

last: Newell

first: Andreas

last: Schlitzer


title: Expression data from CRL-5889 xenograft tumors

status: Public on Sep 08 2017

first: Hongbin

last: Ji

address: YueYang Rd

institute: SIBCB

summary:
We identified a recurrent gene fusion TRA2B-DNAH5 in human lung squamous cell carcinoma. This gene fusion can promote tumor growth in CRL-5889 xenograft tumors.
Microarary was performed to identify these differential genes which may mediate the tumor promotive function of TRA2B-DNAH5 fusion.

overall_design: One human lung squamous carcinoma cell line CRL-5889 with or without TRA2B-DNAH5 fusion expression was used to do the xenograft assay in nude mice.  4 weeks later, we harvested the tumors and extract total RNAs for microarray analyses.

first: Zhaoyuan

last: Fang

first: Fei

last: Li


title: Regulation of microRNA in myositis skeletal muscle after exercise (mRNA)

city: Washington

first: Kanneboyina

last: Nagaraju

state: District of Columbia

address: 111 Michigan Ave NW

institute: Children's National Health System

summary: To identify changes in skeletal muscle microRNA expression after exercise and associate the identified microRNAs with mRNA and protein expression to disease-specific pathways in polymyositis and dermatomyositis

overall_design: Total RNA obtained from vastus lateralis before and after 12 weeks of endurance exercise (n = 3) compared to before and after nonexercise, control group (n = 3)

first: Jessica

middle: F

last: Boehler

first: Marshall

middle: W

last: Hogarth

first: Matthew

last: Barberio

first: James

last: Novak

first: Svetlana

last: Ghimbovschi

first: Kristy

last: Brown

first: Li

last: Munters

first: Ingela

last: Loell

first: Yi-Wen

last: Chen

first: Helene

last: Alexanderson

first: Ingrid

middle: E

last: Lundberg


title: Expression anaylsis of human mesenchymal and endothelial cells

status: Public on Sep 06 2017

city: Heidelberg

first: Laura

last: Milde

state: Baden-Württemberg

address: Im Neuenheimer Feld 280

department: Vascular Oncology and Metastasis

institute: German Cancer Research Center

summary: Analysis of differences in gene expression between different cell types of the vascular niche. Looking for candidates, that could potentially be up-or downregualted in the different cell types

overall_design: Total RNA was obtained from whole cell lysates of human mesenchymal and endothelial cells from various tissues

first: Martin

last: Teichert

first: Zulfiyya

last: Hasanov

first: Hellmut

last: Augustin


title: Pharmacological Targeting of a Metabolic Co-Dependency Pathway in Brain Cancers

city: La Jolla

first: Genaro

middle: R.

last: Villa

state: CA

address: 9500 Gilman Drive

department: Molecular and Medical Pharmacology

institute: David Geffen School of Medicine at UCLA

summary: Mutations in growth factor receptor signaling pathways are common in cancer, including in tumors that arise from or metastasize to the brain. However, most small-molecule inhibitors targeting growth factor receptors have failed to show efficacy for brain cancers, potentially due to inability to achieve sufficient drug levels in the CNS. Targeting non-oncogene tumor co-dependencies provides an alternative approach, particularly if drugs with high brain penetration can be identified. Here we demonstrate that EGFR-mutant cancers, including a highly lethal form of brain cancer glioblastoma (GBM), are remarkably dependent on cholesterol for survival, rendering them sensitive to Liver X receptor (LXR) agonist-dependent cell death. We show that LXR-623, a clinically viable, highly brain-penetrant LXRα-partial/LXRβ-full agonist selectively kills GBM cells in an LXRβ- and cholesterol-dependent fashion, causing massive tumor regression and prolonged survival in mouse models. Thus, a metabolic co-dependency provides a pharmacological means to kill growth factor-activated cancers in the CNS.

overall_design: U87EGFRvIII (U87vIII) and Normal Human Astrocyte (NHA) cells were treated with DMSO control or LXR-623 5 uM for 24 hr. Total RNA was isolated in triplicate for each condition using the RNeasy Plus Mini Kit (QIAGEN). Primeview affymetrix arrays were obtained from Affymetrix, and labeled samples were hybridized and scanned, and gene expression was analyzed in the UCSD VA/VMRF Microarray and NGS Core. The data were robust multiarray average (RMA) normalized in R using the affy package.

middle: R

first: Paul

last: Mischel


title: Transcriptome profiling of remote ischaemic preconditioning effects for heart surgery

status: Public on Sep 01 2017

city: Jena

first: S.

last: Lambeck

address: Erlanger Allee 101

institute: JUH

summary:
Despite advances in surgery support there are unmet needs for cardiopulmonary bypass (CPB) patients being at risk of perioperative ischemia. Remote ischemic preconditioning (RIPC) is considered as adjuvant therapy, but its effects are still underexplored. Thus, we monitored transcriptomic responses from the RIPC procedure during and after cardiac surgery in a pilot study, comprising 34 samples and 10 for validation from patients. We systematically compared the response between CTRL and RIPC including individual effects and dynamics.
We gratefully acknowledge the support from the study participants as part of the clinical trial (ClinicalTrials.gov ID: NCT01067703). Different individual and time-resolved patterns were found for preconditioned patients (RIPC) comprising alternated cytokine, ribosomal and stress related genes. This was confirmed by a tailored method for ranking candidates by integrating variance and expression changes at once.

overall_design: RNA from blood of RIPC or CTRL patients was extracted and subjected to microarray analysis for comparison of transcriptomic responses of patients undergoing CPB. RNA samples of circulating leukocytes covering time points before (T1), directly after CPB (T2) and on the first postoperative day (T3) were subject to multifactorial microarray data analysis: Differences in dynamics of transcripts were assessed by contrasting time-specific and individual-resolved changes.

first: Sandro

last: Lindig

first: Sebastian

middle: N

last: Stehr


title: Global gene expression profiling and senescence biomarker analysis of hESC exposed to H2O2 induced non-cytotoxic oxidative stress

status: Public on Aug 30 2017

first: Hui

last: Shi

address: Downing Street

department: Department of Physiology, Development and Neuroscience

institute: University of Cambridge

summary:
Human embryonic stem cells (hESCs) potentially offer new routes to study, on the basis of the Developmental Origins of Health and Disease (DOHaD) concept, how the maternal environment during pregnancy influences the offspring health and can predispose to chronic disease in later life. Reactive Oxygen Species (ROS), antioxidant defences, and cellular redox status state play an important role in the regulation of gene expression and are involved in diabetes and metabolic syndromes as in aging.
We designed an in vitro cell model of oxidative stress by exposing hESCs to hydrogen peroxide (H2O2) for 72h. To resemble the period of preimplantation embryonic development, we have analysed the global gene expression profiles of hESCs (HUES3) exposed to non-cytotoxic H2O2 concentrations (see main text), using Illumina HT-12 v4 expression beadarray.

overall_design: Human ESCs in four conditions, each in triplicate, 12 datasets in total; Four conditions: control, 4µM, 8µM and 16µM

first: Maria

last: Barandalla

last: Xiao

first: Silvia

last: Colleoni

first: Cesare

last: Galli

first: Pietro

last: Lio

first: Matthew

last: Trotter

first: Giovanna

last: Lazzari


title: Expression data from different time points of developing natural killer cells in vitro

city: hefei

first: YANG

last: WU

state: anhui

address: feixi

department: immunology

institute: USTC

summary:
The development of natural killer (NK) cells relies on the regulation of transcription factors and its function are controled by intergrating signals from the related receptors.To fully understand the scheme of NK cell development and find out useful new transcription factors and receptors, we conducted the microchips.
We used microarrays to identify up-regulated transcription factors during different differentiation stages and related receptors in the last stage.

overall_design: We collected the cells at different time points, from the first week to the fifth week, during the differentiation process from cord blood CD34 positive cells to NK cells in vitro.

first: Yang

last: Wu

first: Haiming

last: Wei


title: Preclinical evaluation of the BET bromodomain inhibitor BAY 1238097 for the treatment of lymphoma

status: Public on Sep 05 2017

city: Bellinzona

first: Francesco

last: Bertoni

state: Ticino

address: Via V. Vela 6

department: Lymphoma & Genomics Research Program

country: Switzerland

institute: IOR

summary: The epigenome is often deregulated in cancer and treatment with inhibitors of bromodomain and extra-terminal proteins, the readers of epigenetic acetylation marks, represents a novel therapeutic approach. Here, we have characterized the anti-tumour activity of the novel bromodomain and extra-terminal (BET) inhibitor BAY 1238097 in preclinical lymphoma mod- els. BAY 1238097 showed anti-proliferative activity in a large panel of lym- phoma-derived cell lines, with a median 50% inhibitory concentration between 70 and 208 nmol/l. The compound showed strong anti-tumour efficacy in vivo as a single agent in two diffuse large B cell lymphoma mod- els. Gene expression profiling showed BAY 1238097 targeted the NFKB/ TLR/JAK/STAT signalling pathways, MYC and E2F1-regulated genes, cell cycle regulation and chromatin structure. The gene expression profiling sig- natures also highly overlapped with the signatures obtained with other BET Bromodomain inhibitors and partially overlapped with HDAC-inhibitors, mTOR inhibitors and demethylating agents. Notably, BAY 1238097 presented in vitro synergism with EZH2, mTOR and BTK inhibitors. In conclusion, the BET inhibitor BAY 1238097 presented promising anti-lym- phoma preclinical activity in vitro and in vivo, mediated by the interference with biological processes driving the lymphoma cells. Our data also indicate the use of combination schemes targeting EZH2, mTOR and BTK along- side BET bromodomains.

overall_design: GEP analysis of one lymphoma cell lines with and without treatment

first: Elena

last: Bernasconi

first: Eugenio

last: Gaudio

first: Andrea

last: Rinaldi


title: Early introduction of oral paricalcitol in renal transplant recipients.

city: Oslo

first: Hege

last: Pihlstrøm

address: P.B. 4950 Nydalen

department: Department of Transplant Medicine

country: Norway

institute: Oslo University Hospital, Rikshospitalet

summary: In stable renal transplant recipients with hyperparathyroidism, the vitamin D agonist paricalcitol reduces the level of proteinuria. Animal studies have indicated possible anti-fibrotic and anti-inflammatory effects of paricalcitol. We hypothesised that early introduction of paricalcitol in de novo renal transplant recipients would reduce proteinuria and counteract development of fibrosis in the allograft.

overall_design: A single centre, prospective, randomized, open label trial investigating the additional effect of paricalcitol 2ug/day to standard care was performed. Participants were included 8 weeks after engraftment irrespective of PTH-level and followed for 44 weeks. Microarray analyses were performed in kidney biopsies at study end for the investigation of potential effects on gene expression profile.

middle: K

first: Hallvard

last: Holdaas

first: Francesca

last: Gatti


title: 4-phenylbutyrate treatment prevents amyloid formation and restores β-cell function in mice overexpressing human islet amyloid polypeptide.

status: Public on Sep 26 2017

city: Barcelona

first: Joan Marc

last: Servitja

state: Catalonia

address: Rosselló, 153

institute: IDIBAPS

summary:
4-phenylbutyrate (PBA) is a chemical chaperone that has been shown to ameliorate β-cell dysfunction associated with hIAPP overexpression. The aim of the study was to investigate the in vivo effects of PBA in transgenic mice overexpressing hIAPP.
We used microarrays to determine gene expression changes in pancreatic islets from mice overexepressing hIAPP and treated with PBA during 12 weeks.

overall_design: 8 weeks old wild type and hIAPP transgenic mice were treated with PBA (1g/kg/day) dissolved in water for 12 weeks. Pancreatic islets were isolated at sacrifice. RNA was extracted and hybridized on Affymetrix microarrays.

first: Joel

last: Montané

first: Sara

last: de Pablo

first: Anna

last: Novials

first: Joan-Marc