title: Sex-specific mRNA and miRNA expression data from Drosophila larvae, pupae and adults [miRNA]

status: Public on May 07 2014

city: Falmer

first: Fiona

last: Ingleby

address: John Maynard Smith Building

department: School of Biology

country: United Kingdom

institute: University of Sussex

summary:
Sex differences in gene expression throughout development are poorly understood, especially sex-specific expression of micro RNAs. However these patterns of gene expression could have important implications in our understanding of the underlying mechanics of sex differentiation and sexual conflict.
We extract mRNA and miRNA from male and female Drosophila melanogaster from three developmental timepoints, third larval instar, pupae and adults, and examine gene expression using microarrays. We found a large number of sex-biased mRNA transcripts at each stage of development, whereas sex-biased miRNA expression was low in larvae and pupae and more prevalent in adults.

overall_design: We isolated 2 biological replicates of each sex at each of the three developmental timepoints and extracted mRNA and miRNA from each sample, creating 12 samples of each type of RNA which were ran on GeneChip Drosophila Genome 2.0 Affymetrix microarrays to examine mRNA expression, and GeneChip miRNA 3.0 Affymetrix microarrays to examine miRNA expression.

first: Ilona

last: Flis

first: Edward

middle: H

last: Morrow


title: Shigella flexneri ntrBC and nac mutant expression analysis

status: Public on May 09 2014

city: Portland

first: Georgiana

last: Purdy

state: Or

address: 3181 SW Sam Jackson Park Rd

department: Molecular Microbiology and Immunology

country: USA

institute: OHSU

summary:
Investigate whole genome gene expression level changes in an S. flexneri ntrBC and nac mutants compared to wild type strain. NtrBC is a two component regulatory system, nac is a transcriptional activator
Mutations in ntrBC and nac result in small plaque formation in Henle cell monolayers compared to wild type bacteria. Gene expression studies were pursued to identify the genes regulated by these transcriptional regulators.

overall_design: A 9 array study using total RNA recovered from the wild type, ntrBC and nac mutant strains in three independent experiments. Bacterial RNA was isolated from infected Henle cells at four hours post-infection. Gene expression from the mutant strains was compared to that of wild type.

first: G

middle: E

first: L

middle: J

last: Runyen-Janecky

first: C

last: Waddell

first: S

middle: A

last: Pacheco


title: Sex-specific mRNA and miRNA expression data from Drosophila larvae, pupae and adults

middle: C

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

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

platform_organism:
Drosophila melanogaster
synthetic construct

overall_design: Refer to individual Series


title: Hypermethylated capped selenoprotein mRNAs in mammals

status: Public on May 14 2014

city: Montpellier

first: Edouard

last: BERTRAND

address: 1919 Route de Mendes

country: France

institute: CNRS

summary: Mammalian mRNAs are generated by complex and coordinated biogenesis pathways and acquire 5'-end m7G caps that play fundamental roles in processing and translation. Here we show that several selenoprotein mRNAs are not recognized efficiently by translation initiation factor eIF4E because they bear a hypermethylated cap. This cap modification is acquired via a 5’end maturation pathway similar to that of the small nucle(ol)ar RNAs (sn- and snoRNAs). Our findings also establish that the trimethylguanosine synthase 1 (Tgs1) interacts with selenoprotein mRNAs for cap hypermethylation and that assembly chaperones and core proteins devoted to sn- and snoRNP maturation contribute to recruiting Tgs1 to selenoprotein mRNPs. We further demonstrate that the hypermethylated-capped selenoprotein mRNAs localize to the cytoplasm, are associated with polysomes and thus translated. Moreover, we found that the activity of Tgs1, but not of eIF4E, is required for the synthesis of the GPx1 selenoprotein in vivo.

overall_design: In total 7 samples; 3 control IP (HeLa 1,2 & 9), 2 TGS1-SF IP(C2 & C2b) and 2 TGS1-LF IP(C7 & C7b)

first: Laurence

last: Wurth

first: Anne-Sophie

last: Gribling-Burrer

first: Céline

last: Verheggen

first: Michael

last: Leichter

first: Akiko

last: Takeuchi

first: Stéphanie

last: Baudrey

first: Franck

last: Martin

first: Alain

last: Krol

last: Bertrand

first: Christine

last: Allmang


title: Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts.

city: San Francisco

first: Linda

last: Giudice

state: CA

address: 513 Parnassus Ave. HSE 1619

department: OBGYN and RS

institute: University of California, San Francisco

summary: Exposure of eEC and eSF to SP in vitro increases expression of genes and secreted proteins associated with cellular migration, proliferation, viability and inhibition of cell death.

overall_design: This is a cross sectional study involving control samples versus treatment. SP (pooled from twenty donors) was first tested for dose- and time-dependent cytotoxic effects on eEC and eSF (n = 4). As exposure of eEC or eSF to 1% SP for 6 h proved to be non-toxic, a second set of eEC/eSF samples (n = 4) was treated under these conditions for transcriptome, protein and functional analysis. With a third set of samples (n = 3), we further compared the transcriptional response of the cells to SP versus fresh semen.

first: Joseph

last: Chen

first: Brittni

last: Johnson

first: David

middle: W

last: Erikson

first: Terhi

middle: T

last: Piltonen

first: Fatima

last: Barragan

first: Simon

last: Chu

first: Nargis

last: Kohgadai

first: Juan

last: Irwin

first: Warner

last: Greene

first: Nadia

middle: R

last: Roan


title: Global analysis of p53-regulated transcription reveals its direct targets and unexpected regulatory mechanisms (microarray)

status: Public on May 15 2014

city: Boulder

first: Mary

middle: Ann

last: Allen

state: Co

address: UCB 596  JSCBB

department: BioFrontiers

institute: University of Colorado

summary: HCT116 microarray done 12 hours after treatment with DMSO (control) or Nutlin

overall_design: Total RNA from HCT116 cells was harvested with an RNeasy kit (Qiagen) and analyzed on Affymetrix HuGene 1.0 ST arrays following the manufacturer’s instructions. Microarray data were processed using Partek Genomics Suite 6.6. Anova was used to call differentially expressed genes for which any isoform showed a fold change > |+/-1.5| with FDR <0.05. There were 362 genes called as upregulated and 367 genes as downregulated.

first: Robin

middle: D

last: Dowell

first: Joaquin

last: Espinosa


title: shRNA mediated knock-down of Tal1 in human Endothelial Colony Forming Cells (ECFCs)

status: Public on May 06 2014

city: Ottawa

first: Marjorie

last: Brand

state: Ontario

address: 501 Smyth Road

country: Canada

institute: Ottawa Hospital Research Institute

summary: Endothelial colony-forming cells (ECFCs) have been reported as promising cells for regenerative medicine thanks to their angiorepair properties. Transcription factors are primary determinants of the functional capacity of the cells and TAL1 has been shown as a critical regulator of endothelial lineage in both development and adult life. However, only few (three) TAL1 targets have been identified so far in mouse and human endothelial cells. This microarray experiment, where TAL1 expression was knocked-down, was designed to identify TAL1-dependent genes in primary human endothelial stem/progenitor cells.

overall_design: ECFCs were isolated from three independent cord blood samples (n=3, biological replicates) and cultured in complete EGM-2 medium. The knockdown of TAL1 was induced by infection with lentiviruses expressing an anti-TAL1 shRNA. A scrambled shRNA was used as a negative control. Cells were then harvested for RNA extraction. DNA-free total RNA was isolated with RNeasy Mini Kit and hybridized to the Affymetrix Human Gene 1.0 ST gene expression microarray.

first: Carmen

middle: G

last: Palii

first: Erinija

last: Pranckeviciene

first: Carolina

last: Perez-Iratxeta


title: microRNA expression profile in Leishmania donovani infected mouse macrophage

status: Public on Apr 25 2014

city: Kolkata

first: Syamal

last: Roy

state: West Bengal

address: 4, Raja SC Mullick Road

department: Infectious Disease and Immunology

country: India

institute: Indian Institute of Chemical Biology

summary: Infection with antimony resistant (SbR) but not with sentitive (SbS) Leishmania donovani (LD) gives rise to aggressive pathology in mammalian hosts, the cause of which is far from clear. Some intracellular pathogens exploit autophagy for their own benefit. Here we show that induction of autophagy in normal macrophages (MF) by pharmacological mediators prior to infection with SbRLD (SbRLD-MF) enhanced their growth as compared to untreated MF, unlike SbSLD-MF. Autophagy was evident in SbRLD-MF from electron microscopical studies showing double membrane-bound compartment around amastigote. In SbRLD-MF there is induction of beclin 1, which forms the platform to recruit other interacting molecules to initiate autophagy. Knocking down the beclin 1 transcription factor Nrf2 and subsequent infection with SbRLD showed significantly lower organ parasites as compared to wild type BALB/c mice. Cessation of autophagy in SbRLD-MF at the later stage of infection is coupled with induction of miR-30a, whose binding to 3'UTR of beclin 1 leads to its post-transcriptional attenuation followed by rise in intracellular Ca++ and apoptosis. SbRLD mediated translocation  of AP-1 transcription factor to the nucleus induce pri-miR-30a over-expression. Rise in Ca++ causes caspase 8 activtion leading to the cleavage of beclin 1 and initiation of apoptosis in SbRLD-MF. Apoptosis may favor parasite egress for cell to cell transmission. We also found that beclin 1 expression is present in splenocytes of kala-azar patients harbouring SbRLD but not SbSLD. Our results suggest that SbRLD has evolved a unique mechanism for its own benefit which explains, in part, the cause of aggressive pathology.

overall_design:
Peritoneal exudate macrophages were isolated from mouse, grown in 60mm plates and infected with Leishmania donovani and total RNA was isolated from cells at 12, 18 and 24 hrs post infection. Leishmania infected macrophage miRNA expression signature was generated. Cells grown on 60mm plates and infected with Leishmania.
The main objective of the microarray analysis of mmu-miRNA in antimony resistant and antimony sensitive Leishmania donovani infected macrophages are as follows:
1. To study how the expression of miRNA varies in either antimony resistant or antimony sensitive Leishmania infected macrophages as compared to the normal macrophages as a function of time. LPS was used as control.
2. To study the expression of those miRNAs which are differentially expressed in antimony resistant and antimony sensitive Leishmania infected macrophages at each time point post infection.
3. To identify those miRNAs which are responsible for degradation of autophagy initiating protein beclin 1 mRNA


title: Early and late passage endothelial cells with or without PDCD10 downregulation

status: Public on Apr 10 2014

city: Santiago de Compostela

last: Zalvide

state: A Coruña

address: CIMUS, Avda de Barcelona s/n

department: Physiology

country: Spain

institute: Universidad de Santiago de Compostela

summary: Primary cells deficient for PDCD10/CCM3 do not enter senescence as control cells. Microarray analysis was performed in cells transduced with non-targeting shRNA and CCM3 shRNA at passage 7 (early passage) and passage 11 (late passage), when control cells are already senescent.

overall_design: Primary endothelial cells were transduced either with non-target shRNA or with CCM3 shRNA. RNA was extracted at passage 7 and passage 11

first: Ana

last: Guerrero

first: Celia

last: Pombo


title: Human intestinal T cell and paired blood transcriptomes

city: Cambridge

first: Tim

last: Raine

address: Addenbrooke's Hospital, Hills Road

department: Medicine

institute: University of Cambridge

summary: The intestinal mucosa harbors the largest accumulation of T lymphocytes in the body. While these T cells play an important role in immune homeostasis, they are also implicated in triggering and maintaining pathological intestinal inflammation. In humans they are poorly characterised, and even mouse transcriptomes have been reported for only a few individual cell types, many of which lack direct human equivalents. Using expression microarrays on T cells isolated from ileal biopsies and in silico analysis, we present here an unbiased, transcriptome-wide view of function in T cell subpopulations of the healthy human intestine and delineate signalling pathways that are distinct from those seen in peripheral blood T cells.

overall_design: Paired blood and intestinal biopsies from 6 age/sex matched healthy human subjects. Intestinal biopsies processed to release intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL). All samples then used to generate T effector memory (Tem) cells of CD4+ and CD8+ subsets by flow sorting. 6 individuals; 3 cell sources per individual (blood, LPL, IEL); 2 Tem subsets per cell source (CD4+ and CD8+). 36 arrays in total

first: Arthur

last: Kaser


title: Long Intergenic Non-Coding RNA HOTAIRM1 Regulates Cell Cycle Progression During Myeloid Maturation in NB4 Promyelocytic Leukemia Cells

status: Public on Apr 30 2014

city: Worcester

first: Peter

last: Newburger

state: United States

address: 364 Plantation Street

institute: University of Massachusetts Medical School

summary:
HOTAIRM1 is a long intergenic non-coding RNA located in the human HOXA gene cluster, with gene expression highly specific for maturing myeloid cells, particularly during all-trans retinoic acid (ATRA) induction of granolopoiesis in NB4, a human t(15;17) acute promyelocytic leukemia (APL) cell line. We sought to assess the impact of HOTAIR knockdown on the global programme of gene expression underlying the granulocytic maturing process in NB4 cells.
The knockdown of HOTAIRM1 resulted in a less differentiated expression profile in the NB4 cells after 4 days of ATRA-induced granulocytic differentiation, with retained expression of many otherwise ATRA-suppressed cell cycle and DNA replication genes, as well as abated induction of cell surface leukocyte activation and defense response genes.

overall_design: The shRNA expressing vector targeting the HOTAIRM1 transcript and the control vector expressing scrambled shRNA sequence were generated based on the pLKO.3G vector backbone (Addgene). The stable cell lines derived from NB4 cells transfected with lentiviral vectors were selected by FACS sorting of GFP selection marker positive cells and isolation of single cell derived clones on soft agar plates. Biologically duplicated total RNA samples were prepared from HOTAIRM1 knockdown and the scrambled shRNA expressing control cells, plus one total RNA from each of wild type NB4 cells and HOTAIRM1 knockdown (by a different shRNA construct) cells, before and after 96 hours of ATRA (0.5 uM) induced granulocytic differentiation.

first: Xueqing

last: Zhang


title: Mesenchymal to amoeboid transition is associated with stem-like features of melanoma cells

status: Public on Apr 22 2014

city: Milan

first: Maurizio

last: Callari

address: Via Amadeo, 42

country: Italy

institute: Fondazione IRCCS Istituto Nazionale dei Tumori

summary: Cellular plasticity confers cancer cells the ability to adapt to micro-environmental changes, a fundamental requirement for tumour progression and metastasis. The epithelial to mesenchymal transition (EMT) is a transcriptional programme associated with increased cell motility and stemness. Beside EMT, the mesenchymal to amoeboid transition (MAT) has been described during tumour progression but, to date, little is known about its transcriptional control and involvement in stemness. The aim of this study is to investigate (i) the transcriptional profile associated with the MAT programme and (ii) to study whether MAT acquisition in melanoma cancer cells correlate with clonogenic potential to promote tumor growth. Our results demonstrate that MAT programme in melanoma is characterised by increased stemness and clonogenic features of cancer cells, thus sustaining tumour progression. Furthermore, these data suggest that stemness is not an exclusive feature of cells undergoing EMT, but more generally is associated with an increase in cellular plasticity of cancer cells.

overall_design: Hs294T in the presence of Ilomastat, Hs294T treated with the Rho activator Calpeptin and EphA2-overexpressing Hs294Tcells were obtained. Duplicate sample from 2 independent experiments were hybridized onto Human AffymetrixHuGene St 1.0 GeneChip array (Affymetrix).

first: Maria

middle: L

last: Taddei

first: Elisa

last: Giannoni

first: Andrea

last: Morandi

first: Luigi

last: Ippolito

first: Paolo

last: Gandellini

first: Paola

last: Chiarugi


title: Human oocytes reprogram adult somatic nuclei to diploid pluripotent stem cells

status: Public on Apr 27 2014

city: Jerusalem

first: Ido

last: Sagi

address: Givat Ram

department: Genetics

country: Israel

institute: The Hebrew University of Jerusalem

summary: The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells, holding promise for autologous cell replacement therapy. Though reprogramming of somatic cells by nuclear transfer was first demonstrated more than 60 years ago, only recently have human diploid embryonic stem cells been derived after nuclear transfer of fetal and neonatal fibroblasts. Because of the therapeutic potential of developing diploid embryonic stem cell lines from adult cells of normal and diseased human subjects, we have systematically investigated the parameters affecting efficiency and developmental potential in their derivation. We found that improvements to the oocyte activation protocol, including the use of both a kinase and a translation inhibitor, and cell culture in the presence of histone deacetylase inhibitors enable development of diploid cells to the blastocyst stage. Developmental efficiency varied significantly between oocyte donors, and was inversely related to the number of days of hormonal stimulation required to reach mature oocytes, while the daily dose of gonadotropin or the total number of MII oocytes retrieved did not affect developmental outcome. The use of diluted Sendai virus in calcium-free medium during nuclear transfer improved developmental potential, while the use of concentrated Sendai virus induced an increase in intracellular calcium and caused premature oocyte activation. Using these modifications to the nuclear transfer protocol, we successfully derived diploid pluripotent stem cell lines from both postnatal and adult somatic cells of a type 1 diabetic subject.

overall_design: Gene expression analysis was performed on a total of 5 human cell lines, including an isogenic set of 3 nuclear-transfer embryonic stem cell lines and their parental neonatal fibroblast cell line, as well as a fourth nuclear-transfer embryonic stem cell line, which was derived from adult fibroblasts from a type 1 diabetic subject.

first: Nissim

last: Benvenisty

first: Dieter

last: Egli


title: Expression data from HEK wild-type cells treated with geneticin (16uM) or left untreated

status: Public on May 01 2014

city: Zürich

first: Heithem

last: Boukari

state: Zürich

address: Gloriastrasse 32

department: Institute of Medical Microbiology

country: Switzerland

institute: University of Zurich

summary: In order to study the cellular response to aminoglycoside-induced mistranslation, we used a whole-genome microarray analysis of geneticin-treated versus untreated cells, which revealed a broad transcriptional response totaling 705 genes.

overall_design: comparison of four geneticin treated biological replicates with four untreated biological replicates (selected for a fold change > 1.2, Benjamini-Hochberg corrected p-value < 0.05)


title: Expression data from stimulated or unstimulated human CD4+ T cells incubated with edelfosine

city: Hamburg

first: Thomas

last: Streichert

address: Martinistr. 52, Campus Forschung N27, 2. OG

department: Institute For Clinical Chemistry / Central Laboratories

country: Germany

institute: University Medical Center Hamburg-Eppendorf

summary:
The cytotoxic drug edelfosine is a synthetic analog of 2-lysophosphatidylcholine. Edelfosine is incorporated by highly proliferating cells, e.g. activated immune cells. It is unknown if the described mechanisms for edelfosine action attained by in vitro approaches exclusively contribute to the observed EAE-amelioration or if edelfosine may exert additional, probably more general and possibly immunoablative effects within the setting of autoimmunity.
We used microarray analysis in order to confirm proposed mechanisms of edelfosine action, but also to discover novel effects of edelfosine in the context of immune cells.

overall_design: For gene-expression analysis enriched CD4+ T cells obtained from Buffy Coats were plated at 200,000 cells/well in 96-well plates. Cells were cultured for 30 h in X-Vivo 15 medium or X-Vivo 15 medium supplemented with 3.3 µg/ml edelfosine, 10 µg/ml edelfosine, bead particles coated with antibodies against CD2, CD3, and CD28 (Miltenyi), or 3.3 µg/ml edelfosine in combination with bead particles coated with antibodies against CD2, CD3 and CD28, respectively.

first: Pierre

last: Abramowski

first: Roland

last: Martin

first: Benjamin

last: Otto


title: Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses

city: Bethesda

first: Yuri

last: Kotliarov

state: MD

address: 4 Memorial Dr., room 134

department: CHI

institute: NHLBI

summary:
A major goal of systems biology is the development of models that accurately predict responses to perturbation. Constructing such models requires the collection of dense measurements of system states, yet transformation of data into predictive constructs remains a challenge. To begin to model human immunity, we analyzed immune parameters in depth both at baseline and in response to influenza vaccination.
Peripheral blood mononuclear cell transcriptomes, serum titers, cell subpopulation frequencies, and B cell responses were assessed in 63 individuals before and after vaccination and were used to develop a systematic framework to dissect inter- and intra-individual variation and build predictive models of postvaccination antibody responses.
Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation cell populations alone, which were validated using independent baseline time points. Most of the parameters contributing to prediction delineated temporally stable baseline differences across individuals, raising the prospect of immune monitoring before intervention.

overall_design:
According to CHI protocol 09-H1-0239, PBMC samples from 63 healthy voluntiers were collected 7 days prior  to vaccination, immediately before vaccination (day0), and at 3 time points (day1, day7 and day70) post vaccination.
The CHI Consortium

first: John

middle: S

last: Tsang

first: Pamela

last: Schwartzberg

first: Angelique

last: Biancotto

first: Zhi

last: Xie

first: Ronald

middle: N

last: Germain

first: Ena

last: Wang

first: Matthew

last: Olnes

first: Manikandan

last: Narayanan

first: Hana

last: Golding

first: Susan

last: Moir

first: Howard

middle: B

last: Dickler

first: Shira

last: Perl

first: Foo

last: Cheung


title: The noncoding RNA IPW regulates the imprinted DLK1-DIO3 locus in an induced pluripotent stem cell model of Prader-Willi syndrome

status: Public on Apr 03 2014

first: Ido

last: Sagi

summary: Parental imprinting is a form of epigenetic regulation that results in parent-of-origin differential gene expression. To study Prader-Willi syndrome (PWS), a developmental imprinting disorder, we generated patient-derived induced pluripotent stem cells (iPSCs) harboring distinct deletions in the affected region on chromosome 15. Studying PWS-iPSCs and human parthenogenetic iPSCs unexpectedly revealed substantial upregulation of virtually all maternally expressed genes (MEGs) in the imprinted DLK1-DIO3 locus on chromosome 14. Subsequently, we identified IPW, a long noncoding RNA in the critical region of the PWS locus, as a regulator of the DLK1-DIO3 region, as its over-expression in PWS and parthenogenetic iPSCs results in downregulation of the MEGs in this locus. We further show that gene expression changes in the DLK1-DIO3 region coincide with chromatin modifications, rather than DNA methylation levels. Our results suggest that a subset of PWS phenotypes may arise from dysregulation of an imprinted locus distinct from the PWS region.

overall_design: Gene expression analysis was performed on a total of 4 human cell lines, including 3 Prader-Willi Syndrome indcued pluripotent stem cell lines - derived from 3 affected individuals and one of their parental fibroblast cell line.

first: Yonatan

last: Stelzer

first: Nissim

last: Benvenisty


title: Gene expression profiles of LNCaP miR-582-5p cells and LNCaP empty vector cells.

status: Public on Apr 11 2014

city: Kyoto

first: Atsushi

last: Maeno

address: Skyo-ku Shogoin Kawahara-cho 54

department: Urology

country: Japan

institute: Kyoto University Facalty of Medicine

summary: To investigate targets of miR-582-5p that which might participate in the transition to CRPC, we evaluated the gene expression profiles of LNCaP miR-582-5p cells and LNCaP EV cells using DNA microarray analysis.

overall_design: We evaluated the gene expression profiles of LNCaP miR-582-5p cells and LNCaP EV cells using DNA microarray with GeneChip® Human Gene 1.0 ST array.

first: Takahiro

last: Inoue


title: Gene expression data from human NSCLC U1810 residual clones 9 days after a one-hour pulse treatment with cisplatin

status: Public on Apr 04 2014

city: Stockholm

first: Lovisa

last: Lundholm

address: Karolinska Biomics Center Z5:01

department: Department of Oncology-Pathology

country: Sweden

institute: Karolinska Institutet

summary:
Background: The platinum compounds cisplatin and carboplatin are the mainstay of chemotherapy for lung cancer; however, treatment failure remains a critical issue since about 60% of all non-small cell lung cancer (NSCLC) patients display intrinsic platinum resistance.
Methods: We analyzed global gene expression profiles in NSCLC clones surviving a pulse treatment with cisplatin by microarray and mapped deregulated signaling networks in silico by Ingenuity Pathway Analysis (IPA).
Results: Cisplatin-surviving NSCLC clones were demonstrated to have heterogeneous gene expression patterns both in terms of the number and the identity of the altered genes. Genes involved in Wnt signaling pathway (DKK1), DNA repair machinery (XRCC2) and cell-cell/ cell-matrix interaction (FMN1 and LGALS9) were among the top deregulated genes by microarray and were subsequently validated by q-RT-PCR. We focused on DKK1, which was previously reported to be overexpressed in NSCLC. IPA network analysis revealed coordinate up-regulation of several DKK1 transcriptional regulators (TCF4, EZH2, DNAJB6 and HDAC2) in cisplatin-surviving clones. Knockdown of DKK1 by siRNA sensitized untreated NSCLC cells to cisplatin, illustrating a putative role of DKK1 in intrinsic platinum resistance.
Conclusions: Gene expression analysis identified DKK1 as a putative cisplatin resistance marker and a potential novel therapeutic target to overcome platinum resistance in NSCLC.

overall_design: U1810 cells were sparsely seeded for clonogenic survival assay in three separate experiments (replicate 1-3), left untreated or treated with cisplatin for 1 h and then kept for 9 days to assay long-term effects of a single pulse treatment.

first: Hogir

last: Salim

first: Kristina

last: Viktorsson


title: Exon-level expression profiling in MDA-MB-231 with or without TIP-1 expression

status: Public on Apr 18 2014

city: nashville

first: Miaojun

last: Han

state: TN

address: 1161 21st Ave S

institute: Vanderbilt University

summary: MDA-MB-231 stable cell lines transfected with control shRNA or TIP-1 shRNA were cultured overnight. Total RNA of these cell lines was isolated for microarray analysis.  Try to get more information about the difference in the mRNA levels in these cell lines.

overall_design: We analyzed gene expression from 6 samples: 2 control MDA-MB-231 (two independent clones) and 4 shRNA TIP-1 MDA-MB-231 cells (2 different shRNAs to silence TIP-1 expression, each shRNA has two independent clones). We used the Affymetrix Human Gene 1.0 ST platform. Array data was processed by the Affymetrix Exon Array Computational Tool. No technical replicates were performed.

first: Hailun

first: Zhaozhong


title: HIC2 is a novel dosage-dependent regulator of cardiac development within the distal 22q11 deletion syndrome region

status: Public on Apr 02 2014

city: liverpool

first: Iain

middle: M

last: Dykes

state: Select...

address: James Parson Bl, Byrom Street,

department: Pharmacy & Biomolecular science

institute: Liverpool John Moores University

summary:
Rationale: 22q11 deletion syndrome arises from recombination between low copy repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1 associated with congenital cardiovascular disease. Deletions distal to the typically deleted region result in a similar cardiac phenotype but lack extra-cardiac features of the syndrome suggesting that a second haploinsufficient gene maps to this interval.    Objective: The transcription factor HIC2 is lost in most distal deletions as well as a minority of typical deletions.  We used mouse models to test the hypothesis that HIC2 hemizygosity causes congenital heart disease.  Methods and Results: We created a genetrap mouse allele of Hic2. The genetrap reporter was expressed in the heart throughout the key stages of cardiac morphogenesis. Homozygosity for the genetrap allele was embryonic lethal before embryonic day E10.5 while the heterozygous condition exhibited a partially penetrant late lethality. One third of heterozygous embryos had a cardiac phenotype.  Magnetic resonance imaging demonstrated a ventricular septal defect with overriding aorta.  Conditional targeting indicated a requirement for Hic2 within the Nkx2.5+ and Mesp1+ cardiovascular progenitor lineages but not in the Wnt1+ neural crest or Mef2c+ second heart field lineages. Microarray analysis revealed increased expression of BMP10.  Conclusions: Our results demonstrate a novel role for Hic2 in cardiac development. Hic2 is the first gene within the distal 22q11 interval to have a demonstrated haploinsufficient cardiac phenotype in mice. Together our data suggests HIC2 haploinsufficiency likely contributes to the cardiac defects seen in distal 22q11 deletion syndrome.
the aim of this microarray experiment was to compare gene expression changes in the E13.5 mouse heart in a conditional knockout of Hic2 (Mesp1Cre/+; Hic2FL/FL) against control.

overall_design: All samples represent pools of isolated hearts from E13.5 mouse embryos.  3 replicates of each genotype were assayed.  The genotypes are: "WT": Hic2FL/FL  "KO": Mesp1Cre/+; Hic2 FL/FL

first: Peter

last: Scambler


title: Microarray Data of cell-free RNA across pregnancy time course

city: Stanford

first: Stephen

last: Quake

address: 318 Campus Drive, E300

department: Bioengineering Dept

institute: Stanford University

summary:
Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs.  We employed high throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects.  By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA, and to monitor changes in tissue development and health.
As one such application of this approach, we performed a longitudinal study on pregnant women and analyzed their combined cell-free RNA transcriptomes across all three trimesters of pregnancy and after delivery. In addition to the presence of messenger RNA, we observed and characterized non-coding species such as long non-coding RNA and circular RNA transcripts whose presence had not been previously observed in human plasma.  We demonstrate that it is possible to track specific longitudinal phenotypic changes in both the mother and the fetus, and that it is possible to directly measure transcripts from a variety of fetal tissues in the maternal blood sample. We also studied the role of neuron specific transcripts in the blood of healthy adults and those suffering from the neurodegenerative disorder Alzheimer’s disease, and showed that disease specific neural transcripts are present at increased levels in the blood of affected patients.  Characterization of the cell-free transcriptome in its entirety may thus provide broad insights into human health and development without the need for invasive tissue sampling.

overall_design: Cell-free RNA are extracted from pregnant women on the first, second and third trimester and immediately post-partum. Temporal trends are extracted from individual patients.

first: Winston

last: Koh

first: Wenying

last: Pan

first: Charles

last: Gawad

first: H

last: Fan

first: Geoffrey

last: Kerchner

first: Tony

last: Wyss-Coray

first: Yair

last: Blumenfeld

first: Yasser

middle: Y

last: El-Sayed


title: Transcript Level Expression Profiling: anticancer pathways of Smilax Glabra rhizome extract (SW)

status: Public on Apr 09 2014

city: Beijing

first: tiantian

last: she

address: 52 Fucheng Road

department: Biochemistry and Molecular Biology

country: China

institute: Peking University Cancer Hospital & Institute

summary:
Find the possible signaling pathways which contribute to the cell growth inhibition effect of SW-treated AGS cells
Global gene expression profiling is an ideal technique to obtain useful clues for exploration of the anticancer mechanism of SW. Through comparing microarray results between solvent- and SW-treated cells, differentially expressed genes were obtained (>1.5 fold). The microarray results were validated using real-time RT-PCR. We used the KEGG database, STRING database and GO database for further ananlysis, and therefore got the possible signaling pathways underlying the anticancer effect of SW.

overall_design: We analyzed total RNA samples of solvent- and SW-treated AGS cells using the Affymetrix Human Gene 1.0 ST platform. No techinical replicates were performed.

first: Tiantian

last: She

first: Yong


title: Celecoxib induced transcriptional alterations in gastric cancer cells

status: Public on Apr 01 2014

city: Madurai

first: Kumaresan

last: Ganesan

state: Tamil Nadu

address: School of Biological Sciences,

institute: Madurai Kamaraj University

summary: Celecoxib is recognized to have chemopreventive and anti-cancer property beyond its anti-inflammatory function. Celelcoxib treatment in AGS cells down regulates Wnt/β-catenin, STAT3, RXR and ERK/MAPK signaling pathways. Transcriptional profiling after celecoxib shows differential regulation of oncogenic pathway regulated genes.

overall_design: AGS cell  were treated with celecoxib in triplicates and incubated for 24 hours. The processed samples were  hybridized in “HuGene-1_0-st” array and the differentially expressed genes were taken for pathway analysis and transcription factor enrichment analysis.

first: Jayaprakash

last: Periasamy

first: Muthulakshmi

last: Muthuswami


title: mRNA profiling of AGS Gastric Cancer cell line treated with the Homeopathy formulation, Ornithogalum

summary:
Ornithogalum is one of the therapeutic formulation used in homeopathic treatments. It is specifically used in the treatment for gastric and duodenal ulcerations. Towards understanding the anticancer mechanism, we investigated the genome-wide mRNA changes upon treating AGS Gastric Cancer cells with Ornithogalum.
We observed that totally 707 genes were significantly regulated upon Ornithogalum Treatment, among them 246 genes were upregulated and 461 genes were downregulated. The results provide insight into molecular implication and gene level expression of  AGS upon treatment with Ornithogalum.

overall_design: Total RNA was isolated from AGS gastric cancer cells treated with 0.01% of ornithogalum and ethanol control and profiled using  Affymetrix Human Gene 1.0 ST Array (HuGene-1_0-st).

first: Srigayatri

last: Pon

first: Divya

last: Rao

last: Periyasamy


title: K1 and K15 of Kaposi sarcoma-associated herpes virus are functional homologues of latent membrane protein 2A of Epstein-Barr virus

city: Neuherberg

first: Dominik

last: Lutter

address: Ingolstädter Landstraße 1

department: Institute for Diabetes and Obesity

institute: Helmholtz Zentrum München

summary: LMP2A of Epstein-Barr virus is a receptor that mimics an activated B cell receptor, BCR. K1 and K15, related receptors of Kaposi sarcoma-associated herpes virus, KSHV, are expressed in virus-associated tumors but their functions are less obvious. We addressed this uncertainty with mutant EBVs encoding the KSHV genes K1 or K15 in lieu of LMP2A and infected primary human B cells with them. K1 and K15 encoded proteins appear to have noncomplementing redundant functions in this model but our findings suggest that both KSHV proteins can replace LMP2A’s key activities contributing to the survival, activation and proliferation of B cells.

overall_design: We infected unsorted B cells with the four virus stocks, wt EBV, K1 EBV, K15 EBV or ΔLMP2A EBV, adjusted to yield similar rates of EBV-activated and growth transformed B cells. Eight days p.i. activated B cells in the lymphocyte gate were collected by FACS sorting and their RNAs analyzed with the aid of the Affymetrix GeneChip Human Gene 1.0 ST Array covering the whole transcriptome of approx. 29,000 annotated human genes. B cell preparations from four different donors were infected and analyzed accordingly.

first: Lisa

last: Steinbrück

first: Montse

last: Gustems

first: Stefanie

last: Medele

first: Thomas

middle: F

last: Schulz

first: Wolfgang

last: Hammerschmidt


title: N-octanoyl dopamine treatment of endothelial cells induces the unfolded protein response and results in hypometabolism and tolerance to hypothermia

status: Public on Mar 28 2014

city: Mannheim

first: Benito

middle: Antonio

last: Yard

address: Theodor-Kutzer-Ufer 1-3

department: Vth medical clinic

institute: University of Heidelberg

summary:
N-octanoyl dopamine (NOD), but not dopamine dose dependently induces the UPR. This was also found for other synthetic N-Acyl dopamine derivates (NADD). Induction of the UPR was dependent on the redox activity of NADD and was not caused by selective activation of a particular UPR sensor. UPR induction did not result in cell apoptosis, yet NOD strongly impaired cell proliferation by attenuation of cells in the S-G2/M phase. Long-term treatment of HUVEC with low NOD concentration showed decreased intracellular ATP concentration paralleled with activation of AMPK. These cells were significantly more resistant to cold inflicted injury.
N-octanoyl dopamine (NOD) and other synthetic N-Acyl dopamine derivates (NADD), but not dopamine dose dependently induces the UPR.
Long-term treatment of HUVEC with low NOD concentration showed decreased intracellular ATP concentration paralleled with activation of AMPK.

overall_design: Genome wide gene expression profiling, confirmatory qPCR and reporter assays were employed on human umbilical vein endothelial cells (HUVEC) to validate induction of UPR target genes and UPR sensor activation by NOD

first: E

last: Stamellou

first: J

last: Fontana

last: Wedel

last: Ntasis

first: A

last: Becker

first: P

last: Pallavi

first: K

last: Wolf

first: C

last: Sticht

first: B

middle: K

last: Krämer

first: M

last: Hafner

first: W

last: van Son


title: Expression data from 1,25(OH)2D treated human testicular cells

status: Public on Mar 14 2014

city: Graz

first: Daniela

last: Hofer

state: Styria

address: Stiftingtalstraße 24

department: Clinical Department for Endocrinology and Metabolism

country: Austria

institute: Medical University of Graz

summary:
Human testicular cells were isolated mechanically and enzymatically from testis of braindead donors and from urological samples. The expression of genes was studied at baseline and 1,25(OH)2D treated conditions.
We used microarrays to analyze the gene expression underlying vitamin D metabolism in human testis cells and identified distinct classes of up-regulated genes during this process.

overall_design: Testicular primary cells were treated with 100nM 1,25(OH)2D for 24h and gene expression studied by microarray on transcript level.

first: Karin

last: Wagner


title: Expression profiling comparisons of human CD4+ T cells treated with RORgt inhibitors

status: Public on Mar 07 2014

city: Cambridge

first: Scott

last: Davis

state: MA

address: 200 Technology Square, Suite 602

department: Tempero DPU

institute: GSK

summary: The aim of this study was to identify differential gene expression resulting from the inhibition of RORgt in human CD4+ T cells.

overall_design: Human CD4+ T cells were cultured with anti-CD3/anti-CD28 mAb for 20 to 60 hours concurrent with exposure to Vehicle (DMSO), TMP778 (0.2 uM) or TMP776 (0.2 uM).  All samples were then processed for RNA extraction, labeling, and hybridization to Affymetrix arrays.

first: Jianfei

last: Yang

first: Jill

last: Skepner

first: Radha

last: Remesh


title: Gene expression profiles of COPD and nonCOPD small airway epithelia

city: Vancouver

first: Wan

middle: L.

last: Lam

state: British Columbia

address: 675 West 10th Avenue

department: Integrative Oncology

institute: British Columbia Cancer Research Centre

summary:
Gene expression profiles in this submission were part of an integrative DNA methylation and gene expression integrative study. The goal of this study was to determine whether DNA methylation patterns were disrupted in small airway epithelia of patients with Chronic Obstructive Pulmonary Disease (COPD) compared to airways from subjects with normal lung function. No subject has cancer or asthma at time of collection. Corresponding DNA methylation profiles for these subjects can be found at GSE55454.
We concluded that methylation alterations in COPD airways may underlie disease-specific gene-expression changes (such as the Nrf2 oxidative response pathway).

overall_design: RNA isolated from bronchial brushings was processed and hybridized to Affymetrix Human Gene 1.0 ST Arrays. DNA isolated from these same samples can be found at GSE55454

first: Emily

middle: A

last: Vucic


title: Comparing Control and Schizophrenic hiPSC-derived NPCs

city: New York

first: Kristen

last: Brennand

state: NY

address: 1425 Madison Ave, 9-20B

department: Psychiatry

institute: Icahn School of Medicine at Mount Sinai

summary: Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported.  While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved.  Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue.  Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia (SCZD) generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SCZD brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SCZD might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SCZD patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SCZD hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes, reduced WNT signaling and aberrant cellular migration.

overall_design: 3 independent differentiations (biological replicates) for each of four control and four schizophrenic patients were analyzed.

first: Fred

middle: H

last: Gage

middle: J


title: DNA Methylation is Globally Disrupted and Associated with Expression Changes in COPD Small Airways

type:
Expression profiling by array
Methylation profiling by array

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

overall_design: Refer to individual Series


title: Expression data measured by Nanostring and microarray of monocyte-derived dendritic cells from healthy individuals stimulated with LPS, influenza, or IFN-beta, or left unstimulated

status: Public on May 12 2014

first: Nir

last: Hacohen

address: 7 Cambridge Center

institute: Broad Institute


title: A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation.

status: Public on Mar 04 2014

city: Hannover

first: Siarhei

last: Kandabarau

address: Carl-Neuberg-Str 1

institute: Hannover Medical School

summary: Expression data from CD34+ hematopoietic cells transduced with control or anti-SLPI shRNA, serum starved and treated with G-CSF.

overall_design: CD34+ hematopoietic cells were isolated from the bone marrow of healthy individuals, transduced with lenitvirus-based RFP-expressed shRNA constructs targeting SLPI mRNA or scrambled control shRNA. After 3 days of the transductions, RFP+ cells were sorted, serum starved for 24 hours and treated with G-CSF 10 ng/ml for 18 hours. Total RNA of sorted cells was isolated and used for Affymetrix Exome arrays.

first: Julia

last: Skokowa

first: Olga

last: Klimenkova


title: Isolation of human iPSC-derived dopaminergic progenitors by cell sorting

first: Daisuke

last: Doi

address: 53 Kawahara-cho, Shogoin, Sakyoku

department: Clinical Application

institute: Center for iPS Cell Research and Application

summary: Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson’s disease. However, iPSC-derived donor cells may inevitably contain tumorigenic or inappropriate cells. Purification of neural progenitor cells or DA neurons as suitable donor cells has been attempted, but the isolation of DA progenitor cells derived from human pluripotent stem cells has so far been unsuccessful.  Here we show human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, Corin.  we were able to develop a method for 1) scalable DA neuron induction on human laminin fragment and 2) sorting DA progenitor cells using an anti-Corin antibody. Furthermore, we determined the optimal timing for the cell sorting and transplantation. The grafted cells survived well and functioned as midbrain DA neurons in the 6-OHDA-lesioned rats, and showed minimal risk of tumor formation. The sorting of Corin-positive cells is favorable in terms of both safety and efficiency, and our protocol will contribute to the clinical application of human iPSCs for Parkinson’s disease.

overall_design: Differentiated human iPSC-derived neural progenitors just after sorting (day12 unsorted, day12 Corin+) and dopaminergic progenitors after an aggregation culture (day28 and day42, unsorted and day12-sorted, respectively), and human fetal ventral mesencephalon and dorsal mesencephalon (gestational age of 7.5 weeks) were subjected to RNA extraction and hybrdization on Affymetrix microarrays. Each sample except for human mesencephalon,  undifferentiated iPSC, and day12-unsorted, day42-sample has 3 or 4 repeats.

first: Jun

last: Takahashi


title: Pharmacologic Inhibition of Epigenetic Modification Reveals Targets of Aberrant Promoter Methylation in Ewing Sarcoma

status: Public on Mar 05 2014

city: Cincinnati

first: Michael

last: Barnes

state: OH

address: 3333 Burnet Ave

department: Rheumatology

institute: Cincinnati Childrens Hospital Medical Center

summary: Background: Ewing sarcoma, a highly aggressive tumor of children and young adults, is characterized most commonly by an 11;22 chromosomal translocation that fuses EWSR1 located at 22q12 with FLI1, coding for a member of the ETS family of transcription factors. Although genetic changes in Ewing sarcoma have been extensively researched, our understanding of the role of epigenetic modifications in this neoplasm is limited.

overall_design: Procedure: In an effort to improve our knowledge in the role of epigenetic changes in Ewing sarcoma we evaluated the in vitro antineoplastic effect of the DNA methyltransferase inhibitor 5-Aza-deoxycytidine (5-Aza-dC) and identified epigenetically silenced genes by pharmacologic unmasking of DNA methylation coupled with genome-wide expression profiling.

first: Shawnagay

last: Nestheide

last: Bridge

first: Robert

last: Frayer

first: Janos

last: Sumegi


title: Expression data from human sarcoma patient samples treated with either vehicle control or Nutlin-3a

status: Public on Mar 10 2014

city: Adelaide

first: Kathleen

middle: Irene

last: Pishas

address: Sarcoma Research group

country: Australia

institute: University of Adelaide

summary:
This study has examined the molecular mechanisms underlying sensitivity of sarcomas to Nutlin-3a, a non-genotoxic activator of the p53 pathway. Human patient material was collected immediately following surgical resection, dissected into small pieces and ex planted onto gelatin sponges immersed in media containing either vehicle control or Nutlin-3a  (10uM and/or 50uM) for 48 hours.
Nutlin-3a represents a novel targeted therapy for the treatment of sarcomas. We have examined expression profiles of genes upregulated in sarcoma patient derived tissues following nutlin-3a treatment ex vivo

overall_design: 16 samples ((Vehicle control and Nutlin-3a (10uM and 50uM) treated samples)) from 6 sarcoma patients

first: Paul

last: Neilsen

first: David

last: Callen

middle: I


title: Identification of differentially expressed genes due to LBH589 treatment in aromatase inhibitor-resistant tumors

city: Duarte

first: Shiuan

last: Chen

address: 1500 E Duarte Rd

department: Surgical Research

institute: City of Hope

summary: In order to validate the utility of a novel pathway algorithm (BD-Func), we test if an LBH589 signature based data from 3 cell lines (GSE36509) in an independent experiment in vivo.

overall_design:
Xenograft tumor treatment (see Kubo et al. 2012; PMID 23160924), microarray gene expression profiling, functional analysis using BD-Func.
Mouse xenograft (from MCF-7aro cell line) was treated with exemestane (EXE) or EXE + LBH589.


title: Combinatorial targeting of the AR for treatment of prostate cancer.

status: Public on Mar 27 2014

city: Bedford Park

first: Luke

last: Selth

state: SA

address: Flinders Drive

department: College of Medicine and Public Health

institute: Flinders University

summary:
Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease. We have previously demonstrated that sub-effective concentrations of an AR antagonist, bicalutamide, a histone deacetylase inhibitor, vorinostat (SAHA), and a hsp90 inhibitor, 17-AAG, act synergistically when combined to cause death of AR-dependent prostate cancer cells. In this study, expression profiling of human prostate cancer cells treated with bicalutamide, vorinostat (SAHA) or 17-AAG, alone or in paired combination, was employed to determine the molecular mechanisms underlying these synergistic interactions.
We used microarray analysis to determine the global molecular profile contributing to the synergistic cell death in LNCaP human prostate cancer cells caused by combinations of bicalutamide, vorinostat (SAHA), or 17-AAG.

overall_design: LNCaP human prostate cancer cells were treated for 6 hours with drug treatments as follows: vehicle control, 5 uM bicalutamide, 1 uM vorinostat (SAHA), 40 nM 17-AAG, 5 uM bicalutamide + 40 nM 17-AAG, 40 nM 17-AAG + 1 uM vorinostat (SAHA), or 5 uM bicalutamide + 1 uM vorinostat (SAHA). Each treatment was performed in sextuplicate.

first: Sarah

last: Carter

first: Margaret

last: Centenera

first: Wayne

middle: D

last: Tilley

first: Lisa

last: Butler


title: Gene expression analysis of samples from a phase II clinical trial of decitatbine in combination with carboplatin in patients with recurrent, platinum resistant epithelial ovarian cancer patients

city: Bloomington

first: Kenneth

last: Nephew

state: IN

institute: Indiana University

summary: Gene expression (by Affymetrix GeneChip Human 1.0ST) profiling of biopsy samples from recurrent, platinum resistant epithelial ovarian cancer patients before and after treatment of decitabine in combination with carboplatin.  The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in PBMC (14 paired samples), tumor (8 paired samples) and ascites (6 paired samples) (GSE31826).

overall_design: Total RNAs were extracted from patient biopsies (tumor or ascites) using TRIzol reagent, cRNA was generated, labeled and hybridized to the Affymetrix GeneChip Human GENE 1.0 ST arrays

first: Fang

last: Fang

middle: P


title: Expression data measured by microarray of monocyte-derived dendritic cells from healthy individuals stimulated with LPS, influenza, or left unstimulated

status: Public on Mar 01 2014

first: Nir

last: Hacohen

summary: Variation in individuals' responses to environmental factors is believed to influence susceptibility to complex diseases in humans. The genetic basis of such variation is poorly understood. We measured gene expression from resting and stimulated dendritic cells (DCs) derived from the peripheral blood of healthy individuals. We stimulated the primary DCs with E. coli lipopolysaccharide (LPS) or influenza virus. Using serial replicate samples, we selected genes that showed evidence of reproducibility within the serial replicates.

overall_design: We collected peripheral blood from each human donor. We isolated peripheral blood mononuclear cells by Ficoll, and magnetically sorted them for CD14+CD16- monocytes. We then differentiated the monocytes into monocyte-derived dendritic cells (MoDCs) by culturing the cells for 7 days with GM-CSF and IL-4. We stimulated the cells with E. coli lipopolysaccharide (LPS) for 5 hr or influenza (PR8 dNS1) for 10 hr. Finally, we lysed the cells and isolated total RNA for microarray.

first: Chun

last: Ye

first: Mark

last: Lee

first: Aviv

last: Regev


title: Expression data from human coronary artery endothelial cells treated with HDL components

status: Public on Feb 27 2014

city: Nashville

first: Kasey

middle: C

last: Vickers

address: 2220 Pierce Ave   358 PRB

department: Medicine

institute: Vanderbilt Univ. School of Medicine

summary:
We quantified differential gene (mRNA) expression in human coronary artery cells treated with native HDL, reconstituted HDL, lipid-free apolipoprotein A-I, small unilamellar vesicles, or PBS control.
These data were used to determine which genes are regulated by native HDL compared to components of HDL and categorize data based on shared sets of genes and distinct sets of genes regulated by each component.

overall_design: Each group had a n=5 and gene expression changes for each condition were compared to control PBS-treated HCAECs

first: Fatiha

last: Tabet


title: Study of 1,4 Butanediol response in Escherichia coli DH1

city: Berkeley

first: Aindrila

last: Mukhopadhyay

state: CA

address: 1 Cyclotron Road

department: Physical Biosciences Division

institute: Lawrence Berkeley National Laboratory

summary:
Escherichia coli DH1 cultures with treated with 6% 1,4 Butanediol for 1 hour and compared with untreated cultures
The data from this experiment was used to identify a candidate for  further study as described in Szmidt et al 2013 Utilizing a highly responsive gene, yhjX, in E. coli based production of 1,4-Butanediol submitted to Chemical Engineering Science

overall_design: 4x72k E.coli gene expression microarrays were used to study the genes that are differentialy expressed in the strain DH1 grown in defined medoin and exposed to 6% 1,4 Butanediol for one hour at mid-log growth stage.

first: Heather

last: Szmidt Middleton

first: Mario

last: Ouellet


title: Long-term culture associated gene expression changes in MSC (TGFb treatment)

status: Public on Feb 05 2014

city: Aachen

first: Wolfgang

last: Wagner

address: Pauwelsstrasse 20

department: Helmholtz Institute for Biomedical Engineering

institute: RWTH Aachen University

summary: Mesenchymal stromal cells (MSC) were isolated from human bone marrow. Here, we have compared gene expression profiles of MSC at early and late passages and upon stimulation with transforming growth factor beta 1 (TGF-b1). Stimulation was performed with 1ng/mL TGF-b1 for 1, 4, or 12 hours as indicated. The goal of this study was to determine if senescence-associated gene expression changes and TGF-b1 induced gene expression changes are related.

overall_design: 24 samples were hybridized GeneChip Human Gene 1.0 ST Arrays (Affymetrix)

first: Gudrun

last: Walenda

first: Qiong

last: Lin

first: Kurt

last: Hoffmann


title: Gene expression profiling of the adjacent airway field cancerization in early stage NSCLC

city: Houston

first: Humam

last: Kadara

state: TX

address: 2130 W. Holcombe Blvd

institute: University of Texas MD Anderson Cancer Center

summary:
Previous work has shown that lung tumors and normal-appearing adjacent lung tissues share specific abnormalities that may be highly pertinent to the pathogenesis of lung cancer. However, the global and molecular adjacent airway field cancerization in non-small cell lung cancer (NSCLC) has not been characterized before.
We sought to understand the transcriptomic architecture of the adjacent airway field canerization, in conjunction with tumors, to gain additional insights into the lung cancer biology and oncogenesis.

overall_design: We analyzed the transcriptome, using the Affymetrix Human Gene 1.0 ST platform, of matched NSCLC tumors, multiple normal airway epithelia with differential distance from the tumors as well as uninvolved normal lung tissues. We analyzed the airway field cancerization transcritpome to determine global differentially expressed cancerization profiles in adjacent airways as well as airway profiles that may be modulated by distance from tumors.

first: Suk-Young

last: Yoo

first: Ignacio

last: Wistuba


title: Gene expression patterns in response to IL-3 in human AML patient mononuclear cells

status: Public on Feb 13 2014

first: Chung

last: Kok

state: South Australia

address: North Terrace

institute: South Australia Health and Medical Research Institute

summary: Aberrant activation of β-catenin is a common event in Acute Myeloid Leukemia (AML), and is recognized as an independent predictor of poor prognosis. Although increased β-catenin signaling in AML has been associated with AML1-ETO and PML-RARα translocation products, and activating mutations in the FLT3 receptor, it remains unclear which mechanisms activate β-catenin in AML more broadly. Here, we describe a novel link between interleukin-3 (IL-3) signaling and the regulation of β-catenin in myeloid transformation and AML. Using a murine model of HoxB8 and IL-3 cooperation we show that IL-3 modulates β-catenin protein levels, and Cre-induced deletion of β-catenin abolishes IL-3 dependent growth and colony formation. In the erythroleukemic cell line TF-1.8, we observed increased β-catenin protein levels and nuclear localization in response to IL-3, which correlated with transcriptional induction of β-catenin target genes. Furthermore, IL-3 promoted β-catenin accumulation in a subset of AML patient samples, and microarray gene expression analysis of these cells revealed induction of WNT/β-catenin and TCF4 transcriptional gene signatures in an IL-3 dependent manner. This study is the first to link β-catenin activation to IL-3 and suggests that targeting IL-3 signaling may be an effective approach for the inhibition of β-catenin activity in some patients with AML.

overall_design: AML patient samples (AML1-4) were cultured in the presence or absence of hIL-3 for 6 or 16h.

first: Teresa

last: Sadras

first: Richard

last: D'Andrea

first: Michelle

last: Perugini


title: Expression data from TGFBR3 controls and TGFBR3 knockdown of SUM159 3D cultures

status: Public on Feb 06 2014

first: Harold

middle: L

last: Moses

address: 2220 Pierece Ave

department: Cancer Biology

institute: Vanderbilt Univerisity

summary: The objective of this experiment was to determine global gene expression change in triple negative cell line upon knockdown of TGFBR3.  Genotype specific differences in expression profiles have been evaluated using human HuGene1.0-ST affymetrix array.  RNA was extracted from SUM159 controls and SUM159 TGFBR3KD cells cultured in 3-dimensional in vitro system.

overall_design: Control (N=3) and TGFBR3KD (N=3) samples were hybridized to the Human gene 1.0 ST array, scanned with Affymetrix using AGCC v. 3.2.4 and then analyzed in R 3.0.1 using the oligo package.

first: Bojana

last: Jovanovic

first: J

middle: S

last: Beeler


title: The hypoxia-inducible transcription factor ZNF395 is controlled by I-kappaB kinase and activates genes involved in the innate immune response and cancer

city: Cologne

first: Gertrud

last: Steger

address: Fuerst-Pueckler-Strasse 56

institute: Institute of Virology

summary:
Activation of the hypoxia inducible transcription factor HIF-alpha and the NF-kappaB pathway promotes inflammation mediated tumor progression.
The cellular transcription factor ZNF395 was repeatedly found over expressed in various human cancers and particularly in response to hypoxia, implying a functional relevance.
To understand the biological activity of ZNF395, we identified target genes of ZNF395 by a genome-wide expression screen.
Induced ZNF395 expression let to up-regulation of a subset of interferon (IFN)-responsive genes such as IFIT1/ISG56 and IFI44 as well as genes known to be involved in cancer progression including MEF2C and MACC1.
ZNF395 requires its DNA binding domain and the two IFN-sensitive-response elements within the IFIT1/ISG56 promoter to activate.
We provide evidence that IkBa kinase-mediated phosphorylation is required to allow activation of transcription by ZNF395 but simultaneously accelerates it for proteolytic degradation to keep the activity of ZNF395 transient and weak.
We further confirm that ZNF395 is induced by hypoxia.
Thus, two crucial pathways contributing to cancers progression, i.e. hypoxia and inflammation cooperate in activation of ZNF395 at the level of transcription and post-translational modification.
Increased amounts of transcriptional active ZNF395 in cancers may support carcinogenesis by activating its target genes associated with the innate immune response and cancer.

overall_design: 4 samples treated with doxycycline-induced ZNF395 were compared to 4 untreated controls

first: Darko

last: Jordanovski

first: Christine

last: Herwartz

first: Anna

last: Pawlowski

first: Peter

last: Frommolt


title: MicroRNAs Contribute to iPSC-Somatic Donor Memory

status: Public on Jan 27 2014

city: barcelona

first: marianna

last: vitaloni

address: dr aiuguader 88,7

institute: centre of regenerative medicine of barcelona

summary: miRNA expression analysis in iPSC derived from CD133+cells from Cord Blood

overall_design: We analyzed 1 array from CBiPS b- high passage numbers; 1 array from CBiPS b- low passage numbers; 2 array from CD133+celld from Cord Blood; 1 array from ES; 1 arrays from FiPS-high passage numbers

first: Marianna

last: Vitaloni


title: MicroRNA profiling from the silica-induced pulmonary fibrosis mouse model

status: Public on Jan 29 2014

city: Nanjing

first: Chunhui

last: Ni

address: Tianyuan road No. 818

department: Department of Occupational Medicine and Environmental Health, School of Public Health

institute: Nanjing Medical University

summary:
microRNAs (miRNAs) play a critical biological role in a variety of pathophysiological processes by suppressing their target genes. However, little is known on the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis. To investigate miRNAs of interest in regulation of pulmonary fibrosis, total RNA was isolated from mice lungs collected at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure. Then, miRNA microarray was performed with one mouse lung at each time point.
miRNA microarray was performed with one mouse lung at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure to investigate the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis.

overall_design: Mouse lung tissues were selected at each time point after treatment for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogeneous populations of lungs at each fibrotic stage in order to increase the temporal resolution of expression profiles. To that end, we hand-selected lung tissues according to morphological criteria at five time-points: before silica exposure, i.e. day 0 (D0), the early inflammation phase day 3 (D3) and day 7 (D7), the late inflammation phase, day 14 (D14), the fibrosis phase,i.e. day 28 (D28) and day (D56).

first: Xiaoming

last: Ji


title: Gene expression data of hepatocytes derived from human fibroblasts, human iPSCs, and human adult hepatocytes

status: Public on Jan 22 2014

city: San Francisco

first: Saiyong

last: Zhu

address: 1650 Owens Street, GICD, 4P

institute: Gladstone Institute

summary:
Generation of human fibroblast-derived hepatocytes capable of extensive proliferation, as evidenced by significant liver repopulation of mice. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs, but shortcut reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) stage from which endoderm progenitor cells (iMPC-EPCs) and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps were able to engraft and proliferate, and acquired levels of hepatocyte function similar to adult hepatocytes.
Microarray analysis has been used to show: 1. post-transplant maturation in vivo of iMPC-Heps compared to aHeps, 2. differences between iMPC-Heps and freshly isolated aHeps in vitro, 3. similar profile of freshly isolated aHeps to aHeps and iMPC-Heps in vivo, and 4. similarities of expression levels of most, but not all, genes between iMPC-Heps and iPSC-Heps in vitro.

overall_design: We isolated repopulating nodules of iMPC-Heps and aHeps by laser-capture microscopy (LCM) around 9 months after transplantation and analyzed their gene expression on the microarray, together with RNA from in vitro samples.

first: Milad

last: Rezvani

first: Jack

last: Harbell

first: Holger

last: Willenbring

first: Sheng

last: Ding


title: Expression data from peripheral blood mononuclear cells of subjects supplemented with vitamin C

city: Rome

first: Guido

last: Leoni

address: Via Pontina

department: Bioinformatics

institute: IRBM

type:
Expression profiling by array
Expression profiling by RT-PCR

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

overall_design: Refer to individual Series


title: Bowel expression profiles of infants with gastrointestinal conditions

status: Public on Jan 21 2014

city: Hong Kong

first: Kathy

middle: YY

last: Chan

address: Rm84041, 6/F, Clinical Science Building, Prince of Wales Hospital, Shatin, N.T.

department: Paediatrics

country: Hong Kong

institute: The Chinese University of Hong Kong

summary: We have employed whole genome microarray expression profiling to identify genes differentially expressed in neonatal bowel tissues of different gastrointestinal conditions.

overall_design: Bowel tissues were collected from infants who underwent surgery treatment for necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP). Infants with other non-inflammatory, congenital intestinal conditions were employed as the Surgical-Control. Differential whole genome microarray analysis was performed.

first: P

last: NG

first: Karen

last: LI

last: CHAN

first: K

middle: T

last: LEUNG


title: Suppression and Activation of the Malignant Phenotype by Extracellular Matrix in Xenograft Models of Bladder Cancer: A Model for Tumor Cell Dormancy

status: Public on Feb 20 2014

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary: A major problem in cancer research is the lack of a tractable model for delayed metastasis. Herein we show that cancer cells suppressed by SISgel, a gel-forming normal ECM material derived from Small Intestine Submucosa (SIS), in flank xenografts show properties of suppression and re-activation that are very similar to normal delayed metastasis and suggest these suppressed cells can serve as a novel model for developing therapeutics to target micrometastases or suppressed cancer cells. Co-injection with SISgel suppressed the malignant phenotype of highly invasive J82 bladder cancer cells and highly metastatic JB-V bladder cancer cells in nude mouse flank xenografts. Cells could remain viable up to 120 days without forming tumors and appeared much more highly differentiated and less atypical than tumors from cells co-injected with Matrigel. In 40% of SISgel xenografts, growth resumed in the malignant phenotype after a period of suppression or dormancy for at least 30 days and was more likely with implantation of 3 million or more cells. Ordinary Type I collagen did not suppress malignant growth, and tumors developed about as well with collagen as with Matrigel. A clear signal in gene expression over different cell lines was not seen by transcriptome microarray analysis, but in contrast, Reverse Phase Protein Analysis of 250 proteins across 4 cell lines identified Integrin Linked Kinase (ILK) signaling that was functionally confirmed by an ILK inhibitor. We suggest that cancer cells suppressed on SISgel could serve as a model for dormancy and re-awakening to allow for the identification of therapeutic targets for treating micrometastases.

overall_design: Earlier we demonstrated that the phenotype of bladder cancer cells was radically different in 3-dimensional organotypic culture when grown on a normal extracellular matrix preparation (SISgel) as compared to that observed on a cancer-modulated permissive extracellular matrix preparation (Matrigel). SISgel is a gel-forming material derived from acellular small intestine submucosa, whereas Matrigel is a basement membrane preparation obtained from a mouse sarcoma.  On Matrigel the bladder cancer cells recapitulated the phenotype reported for the original tumor; in sharp contrast, most of the malignant properties were lost when the cells were grown on SISgel.  Cell lines derived from papillomas formed a layered structure reminiscent of normal urothelium, whereas cell lines derived from higher grade tumors formed a noninvasive layer of cells. These findings suggested that growth of cancer cells on normal ECM could provide a model to investigate the phenomenon of suppression of malignancy by normal ECM in metastasis and recurrence.     In this study we explored whether the phenotypic suppression seen in organotypic culture of bladder cancer cells on SISgel also is observed in vivo. Positive findings support the use of SISgel as a model for investigations of the dormant or suppressed tumor cell phenotype and of mechanisms by which the normal ECM exerts an inhibitory influence on tumorigenesis and metastasis. The findings strongly suggest that interactions of cancer cells with normal ECM play an important role in recurrence and metastasis and further suggest that targeting suppressed cells could represent a heretofore unexploited point of vulnerability in cancer therapy.

first: Robert

middle: E

last: Hurst

first: Paul

last: Hauser

first: Kimberly

last: Kyker

first: Jonathan

last: Heinlen

first: Jason

last: Hodde

first: Michael

last: Hiles

first: Stanley

last: Kosanke

middle: G

last: Ihnat


title: Senescence secreted factors activate Myc and sensitize pre-transformed cells to TRAIL-induced apoptosis

status: Public on Jan 15 2014

city: Illkirch; Strasbourg

first: Marco Antonio

last: Mendoza-Parra

address: 1, rue Laurent Fries

institute: IGBMC

summary: Senescent cells secrete a plethora of factors with potent paracrine signaling capacity. Strikingly, senescence, which acts as a defense against cell transformation, exerts pro-tumorigenic activities through its secretome by promoting numerous tumor-specific features, such as cellular proliferation, epithelial-mesenchymal transition and invasiveness. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has the unique activity of activating cell death exclusively in tumor cells. Given that the senescence-associated secretome supports cell transformation, we asked whether factor(s) of this secretome would establish a program required for the acquisition of TRAIL sensitivity. We found that conditioned media from several types of senescent cells (CMS) efficiently sensitized pre-transformed cells to TRAIL, while the same was not observed with normal or immortalized cells. Dynamic transcription profiling analysis of CMS-exposed pre-transformed cells revealed paracrine autoregulatory loop of senescence-associated secretome factors and a dominant role of CMS-induced MYC. Sensitization to TRAIL coincided with MYC upregulation and massive changes in gene regulation. CMS-induced MYC silenced its target gene CFLAR, encoding the apoptosis inhibitor FLIPL, thus leading to the acquisition of TRAIL sensitivity. Altogether, our results reveal that senescent cell-secreted factors exert a TRAIL sensitizing effect on pre-transformed cells by modulating the expression of MYC and CFLAR. Notably, CMS dose-dependent sensitization to TRAIL was observed with TRAIL-insensitive cancer cells and confirmed in co-culture experiments. Dissection and characterization of TRAIL-sensitizing CMS factors and the associated signaling pathway(s) may provide a mechanistic insight in the acquisition of TRAIL sensitivity and lead to novel concepts for the apoptogenic therapy of pre-malignant and TRAIL-resistant tumors.

overall_design: Pre-transformed BJEL cells were incubated with CMS for 0, 1, 3, 6, 8, 16 or 24 h respectively. Total RNA has been extracted from each time point and used for gene expression analysis (Affymetrix Human Gene 1.0 ST Arrays).

first: Jelena

last: Vjetrovic

first: Pattabhiraman

last: Shankaranarayanan

first: Marco

first: Hinrich

last: Gronemeyer


title: CytoScanHD array Data for 15 normal, 15 primary colorectal carcinomas and their 15 matched liver metastases

city: Seoul

first: SUN YOUNG

last: LEE

address: Olympicro

country: South Korea

institute: Asan Medical Center

type: Genome variation profiling by genome tiling array

summary: We performed whole exome sequencing and copy number analysis for 15 triplets, each comprising normal colorectal tissue, primary colorectal carcinoma, and its synchronous matched liver metastasis.  We analyzed the similarities and differences between primary colorectal carcinoma and matched liver metastases in regards to somatic mutations and somatic copy number alterationss (SCNAs). The genomic profiling demonstrated mutations in APC(73%), KRAS (33%), ARID1A and PIK3CA (6.7%) genes between primary colorectal and metastatic liver tumors. TP53 mutation was observed in 47% of the primary samples and 67% in liver metastatic samples. The grouped pairs, in hierarchical clustering showed similar SCNA patterns, in contrast to the ungrouped pairs. Many mutations (including those of known key cancer driver genes) were shared in the grouped pairs. The ungrouped pairs exhibited distinct mutation patterns with no shared mutations in key driver genes. Four ungrouped liver metastasis samples had mutations in DNA mismatch repair genes along with hypermutations and a substantial number of copy number of alterations. Genomically, colorectal and metastatic liver tumors were very similar. However, in a subgroup of patients, there were genetic variations in liver metastases in the loss of DNA mismatch repair genes.

overall_design: Copy number analysis of Affymetrix CytoScanHD arrays was performed for 15 primary colorectal carcinoma and 15 samples of their matched liver metastases. 15 normal samples prepared from each of the patient was used as the reference for the study. Nexus Copy number 6.1 software was used for somatic copy number alteration analysis.

first: Won-Suk

last: Lee

first: Sun-Young

first: Farhan

last: Haq

first: Deokhoon

last: Kim

first: Cui

last: Jun

first: Hui-Jong

last: Jo

first: Sung-Min

last: Ahn


title: Expression data from peripheral blood mononuclear cells of subjects supplemented with vitamin C [Affymetrix gene array analysis]

first: Guido

last: Leoni

summary:
A role of vitamin C (ascorbic acid) as an antioxidant molecule has been recognized, largely based on in vitro studies. However, more recently, the concept of “antioxidant molecule” has been reconsidered and its biological function is no longer considered to be simply due to its ability to act as “electron donors”, rather, it appears to act by modulating signaling and gene expression.
In order to gain a better understanding of the effects of vitamin C supplementation on gene expression in both physiological and pro-inflammatory conditions, we performed  a pilot explorative intervention study based on the utilization of  microarray and qPCR technologies, designed on a “in vivo-ex vivo” structure

overall_design: Five healthy subjects (three males and 2 females, aged 25-40) were recruited for a short term (five days) intervention  study. Subjects were asked to assume one tablet of Redoxon®  (Bayer), a day (containing 1 gr of ascorbate), for 5 days.  A baseline blood withdrawal was performed in fasting condition,  just before the first vitamin C tablet. Tablets were provided to the volunteers, every morning at the same hour for the following 4 days of the study. The last tablet was supplemented about 1,5  hour before the second and last blood withdrawal, performed again in fasting condition. Plasma and peripheral blood mononuclear cells (PBMNC) were obtained . PBMNC from each subject were splitted in three aliquots: one was stored in lysis buffer at -80°C and utilized to isolate RNA for the Affymetrix gene array analysis. The other two aliquots were resuspended in RPMI 1640 w/o phenol red containing 10% of autologous plasma: one was incubated with 10 ug/ml lipopolysaccharides (LPS) for 5 hours at 37°C. At the end of the incubation time, the medium was collected and stored at -80°C for the assessment of cytokine release in response to the inflammatory stimuli. RNA was extracted from the pelleted cells for gene expression analysis, using the Human NFkB Signaling 96 StellARray™ qPCR array (Lonza). The results obtained with PBMNC isolated after vitamin C supplementation (supplemented PBMNC) were compared to those obtained with PBMNC isolated before the supplementation (baseline PBMNC), for each subject.

first: R

last: Canali

first: G


title: Effects of dietary obesity in fathers on gene expression of fat in the female offspring (mRNA data)

status: Public on Jan 20 2014

city: Wallace Wurth Building, Sydney

first: Margaret

last: Morris

state: NSW

address: University of New South Wales

department: School of Medical Sciences

institute: University of New South Wales

summary: The global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed β-cell ‘dysfunction’ in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity.  Paternal high fat diet altered the expression of 211 pancreatic islet genes in adult female offspring (P < 0.001); genes belonged to 8 functional clusters, including calcium ion binding, primary metabolic processes and ATP binding, and organ/system development.  Broader KEGG pathway analysis of 2014 genes differentially expressed at the P < 0.01 level further demonstrated involvement of insulin and calcium signaling, and MAPK pathways. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies.

overall_design: F0 founders were male Sprague Dawley rats, divided into two groups: high fat (HF) and control. The HF fathers were given commercially prepared high-fat pellets (43% as fat), while the controls ate standard laboratory chow (9% as fat). The two groups of fathers had distinct phenotypes; the HF fathers were significantly heavier with increased adiposity, and they were also glucose intolerant and insulin resistant. At 15 weeks of age, fathers were mated with normal females consuming chow to generate the F1 offspring. Only female offspring were studied. Female offspring were weaned unto standard laboratory chow at 3 weeks. At 6 and 12 weeks, an intraperitoneal glucose tolerance test (IpGTT) was performed to measure blood glucose and insulin profile; at 11 weeks, an intraperitoneal insulin tolerance test was done. The body weight and adiposity of these offspring were not different between the two groups. The HF offspring had glucose intolerance and impaired glucose-induced insulin response, mainly at the acute phase, observed since 6 weeks. The IpITT was not different between groups. At 14 weeks, fat was harvested from the two groups of offspring.

first: Sheau

middle: F

last: Ng

first: Ruby

last: Lin


title: Genomic characterization of ovarian cancer spheroids

status: Public on Jan 03 2014

city: indianapolis

first: salvatore

last: condello

address: 980 west walnut street

institute: iu school of medicine

summary: Spheroids are 3D multi-cell aggregates formed in non-addherent culture conditions. In ovarian cancer (OC), they serve as a vehicle for cancer cell dissemination in the peritoneal cavity. We investigated genes and networks upregulated in three dimensional (3D) versus two-dimensional (2D) culture conditions by Affymetrix gene expression profiling and identified ALDH1A1, a cancer stem cell marker as being upregulated in OC spheroids. Network analysis confirmed ALDH1A1 upregulation in spheroids in direct connection with elements of the β-catenin pathway. A parallel increase in the expression levels of β-catenin and ALDH1A1 was demonstrated in spheroids vs. monolayers an in successive spheroid generations by using OC cell liness and primary OC cells. The percentage of Aldefluor positive cells was significantly higher in spheroids vs. monolayers in IGROV1, A2780, SKOV3, and primary OC cells. B-catenin knock-down decreased ALDH1A1 expression and chromatin immunoprecipitation demonstrated that β-catenin directly binds to the ALDH1A1 promoter. Both siRNA mediated β-catenin knock-down and a novel ALDH1A1 small molecule enzymatic inhibitor described here for the first time, decreased the number of OC spheroids (p<0.001) and cell viability. These data strongly support the role of β-catenin regulated ALDH1A1 in the maintenance of OC spheroids and of a stem cell phenotype and propose new ALDH1A1 inhibitors targeting this cell population.

overall_design: Different gene profiles were observed in ovarian cancer spheroids versus ovarian cancer monolayers. Nine samples were analyzed in triplicate. Each group is a reference.

first: Salvatore

last: Condello

first: Liyun

last: Cao

first: Daniela

last: Matei


title: Identification of IL-21-induced STAT3 dependent genes in human B cells

status: Public on Jan 09 2014

city: Darlinghurst

first: Stuart

last: Tangye

address: 384 Victoria St

department: Immunology

institute: Garvan Institute for Medical Research

summary:
IL-21 induces B cell activation, and differentiation into antibody-secreting plasmablasts in vitro. This process is abolished by loss-of function mutations in STAT3
We used microarrays to identify genes that are induced by IL-21 in a STAT3-dependent manner

overall_design: Sort-purified naïve B cells from four healthy donors and three patients with AD-HIES due to heterozygous STAT3 mutations were cultured for four days with CD40L in the presence or absence of IL-21 (50ng/ml). After four days, RNA was extracted from the harvested cells and the genetic profile was analysed by microarray.

first: Lucinda

last: Berglund


title: Lentiviral shRNA knockdown of PTK7 in lung adenocarcinoma cell lines NCI-H1299 and NCI-H2009

status: Public on Jan 01 2014

city: Palo Alto

first: Dedeepya

last: Vaka

address: 265 Campus Drive

department: Pediatrics

institute: Stanford

summary: PTK7 was identified from a meta-analysis of 1905 non-small-cell lung cancer (NSCLC) samples across 12 datasets to be one of seven genes commonly up-regulated in lung adenocarcinoma (ADC). Using ADC cell lines NCI-H1299 and NCI-H2009, disruption of PTK7 resulted in decreased cell viability and induction of apoptosis. A xenotransplantation model of the cell lines with PTK7 knock-down also resulted in decreased tumor burden. We assayed gene expression in these cell lines after PTK7 knock-down by shRNA to uncover deregulated pathways and genes.

overall_design: 8 samples were analyzed. In each cell line, we knocked down PTK7 with 2 independent hairpins, and 2 control hairpins targeting luciferase and GFP. Thus, NCI-H1299 has 2 samples of PTK7 knock-down, and 2 samples of control knock down. NCI-H2009 has similar samples.

first: Ron

last: Chen


title: Transcriptional targets of Hippo signaling in mammalian cells

status: Public on Dec 31 2013

city: Boston

first: Jianlong

last: Sun

address: 1 Blackfan Street

department: Hematology/Oncology

institute: Boston Children's Hospital

summary:
The Hippo pathway is an emerging signaling cascade involved in the regulation of organ size control.  It consists of evolutionally conserved protein kinases that are sequentially phosphorylated and activated.  The active Hippo pathway subsequently phosphorylates a transcription coactivator, YAP, which precludes its nuclear localization and transcriptional activation.  Identification of transcriptional targets of YAP in diverse cellular contexts is therefore critical to the understanding of the molecular mechanisms in which the Hippo pathway restricts tissue growth.
We used microarrays to profile the gene expression patterns upon acute siRNA knockdown of Hippo pathway components in multiple mammalian cell lines and identified a set of genes representing immediate transcriptional targets of the Hippo/Yap signaling pathway.

overall_design: Three mammalian cell lines (HEK293T, HepG2, HaCaT) were transfected with scramble siRNA controls or siRNAs against NF2 and LATS2, two core components of the Hippo pathway, simultaneously.  Total RNAs were harvested four days after transfection to reveal the gene expression pattern unsing microarry.  YAP and TAZ siRNAs were also transfected along with NF2 and LATS2 siRNAs to identify YAP/TAZ-dependent transcriptional targets upon loss of NF2/LATS2.

first: Fernando

last: Camargo


title: Effects of PSF and CTBP1-AS knockdown in prostate cancer cell lines

city: Itabashi-ku

first: Ken-ichi

last: Takayama

address: Sakaecho

institute: Tokyo Metropolitan Institute of Gerontology

summary:
Prostate cancer is the most common cancer in men and  Androgen receptor (AR) downstream signalings promote prostate cancer cell proliferation. We identified androgen-regulated long non-coding RNA, CTBP1-AS, located in the antisese region of CTBP1 gene. CTBP1-AS activate AR signaling by epigenetically repress AR-associated cofactors such as CTBP1 by interactign with RNA-binding protein PSF and recruiting HDAC complex to the target promoters.
In order to investigate the CTBP1-AS and PSF function in prostate cancer cells, we performed gene expression in AR-positive prostate cancer cell lines after siPSF or siCTBP1-AS treatment. We also treated cells with vehicle or androgen to analyzed the effects of CTBP1-AS and PSF on AR function.

overall_design: Observation of androgen dependent gene expression changes after treatmet with siRNAs targeting CTBP1-AS and PSF with microarray.

first: K

first: S

last: Inoue


title: Susceptibility to DNA damage as a molecular mechanism for non-syndromic cleft lip and palate

city: Sao Paulo

first: Lucas

last: Alvizi

state: Sao Paulo

address: Rua do Matao 277

department: Genetics and Evolutionary Biology

country: Brazil

institute: University of Sao Paulo

summary: Non-syndromic cleft lip/palate (NSCL/P) is a complex, frequent congenital malformation, determined by the interplay between genetic and environmental factors during embryonic development. Previous findings have appointed an aetiological overlap between NSCL/P and cancer, and alterations in similar biological pathways may underpin both conditions. Here, using a combination of transcriptomic profiling and functional approaches, we report that NSCL/P dental pulp stem cells exhibit dysregulation of a co-expressed gene network mainly associated with DNA double-strand break repair and cell cycle control (p = 2.88x10-2 – 5.02x10-9). This network included important genes for these cellular processes, such as BRCA1, RAD51, and MSH2, which are predicted to be regulated by transcription factor E2F1. Functional assays support these findings, revealing that NSCL/P cells accumulate DNA double-strand breaks upon exposure to H2O2. Furthermore, we show that E2f1, Brca1 and Rad51 involved in DNA repair are co-expressed in the developing embryonic orofacial primordia, and may act as a molecular hub playing a role in lip and palate morphogenesis. In conclusion, we show that cellular defences against DNA damage may take part in the pathogenesis of NSCL/P, in accordance with the hypothesis of aetiological overlap between this malformation and cancer. These results provide more information regarding the aetiology of NSCL/P and have the potential tocan potentially assist incontribute to the development of future preventive strategies.

overall_design: In order to analyze differences in gene expression between NSCL/P samples and controls we used 7 NSCL/P RNA samples extracted from dental pulp stem cells cultures and 6 control RNA samples also from dental pulp stem cells cultures, all in the same culture conditions. RNA samples were used in gene expression microarrays (Affymetrix HuGene 1.0 st chips).

first: Gerson

last: Kobayashi

first: Simone

last: Ferreira


title: Stem cell factor Sox2 regulates the tumorigenic potential in human gastric cancer cells

city: Munich

first: Stefan

last: Krebs

address: Feodor-Lynen-Str. 25

department: Gene Center

institute: Ludwig-Maximilian University

summary:
Gastric cancer is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with H. pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches.
Aberrant expression of the specific gastric differentiation marker Sox2 (sry-related HMG box 2) has been observed in stomach cancer. However, the role of Sox2 in gastric tumors has not been well established to date. To elucidate the role of Sox2 in gastric tumorigenesis, Sox2 transcriptional activity was blocked in AZ521 cells. Interestingly, inhibition of Sox2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of Sox2 also reduced the tumorigenic potential of AZ521 cells in vivo. In addition, correlation of Sox2 expression and proliferation was observed in a subset of human gastric tumours. Finally, target genes of Sox2 were for the first time identified by RNA microarray in gastric cancer cells.
Taken together, the results presented here indicate that Sox2 controls several aspects related to gastric cancer development and progression by regulating the expression of members of important signalling pathways. These findings could provide new therapeutic options for a subset of gastric cancers exhibiting Sox2 deregulation.

overall_design: Inducible dnSox2 in AZ521 cells, 4 timepoints with/without induction.

first: Katharina

last: Hütz

first: Raquel

last: Mejías-Luque

first: Katarina

last: Farsakova

first: Manfred

last: Ogris

first: Martina

last: Anton

first: Michael

last: Vieth

first: Ulrich

last: Schüller

first: Marlon

last: Schneider

first: Helmut

last: Blum

first: Ernst

last: Wagner

first: Eckhard

last: Wolf

first: Andreas

last: Jung

first: Markus

last: Gerhard


title: Gene expression from H69M versus H69 SCLC cell lines

city: BARCELONA

first: EDURNE

last: ARRIOLA

address: PASSEIG MARITIM 25-29

institute: HOSPITAL DEL MAR

summary:
H69M cells derive from H69 small cell lung cancer cells subjected to prolonged treatment with HGF. Among the whole population of cells, a subset of more fibroblastic cells was isolated (H69M-mesenchymal). In this experiment we compared expression profiles of both cell lines

Keywords: Expression Profiling by array

overall_design: We analyzed 3 arrays from each condition:H69 versus H69M SCLC cell lines

first: Edurne

last: Arriola

first: Israel

last: Cañadas


title: Gene expression of HSC39 treated with SiRNA targeting TRIM44

city: Cambridge

first: Nicholas

middle: B

last: Shannon

address: Robinson Way

department: Oncology

country: United Kingdom

institute: Cambridge Research Institute

summary: We used microarrays to further detail a transcriptional signature of TRIM44 by globally assessing genes that have changes in expression upon knockdown on TRIM44 using two independent SiRNAs targetting the gene (in duplicate) and All Stars Negative siRNA (in quadruplicate) as a control

overall_design: We performed genome-wide comparison of gene expression and identified genes that are differentially expressed in siRNA (targetting TRIM44) treated HSC39 relative to untreated cells, 4 biological replicates per condition

first: Chin-Ann

last: Ong


title: Comparative global transcriptomic profiling of mild and severe neurotrauma in an in vitro neuronal model

city: Hobart

first: Minghui Jessica

last: Chen

state: Tasmania

address: Menzies Research Institute, University of Tasmania, Private Bag 24

department: Neuroscience group

institute: Menzies Research Institute

summary: Traumatic brain injury is one of the common cause of adult permanent disability. As its physio-pathological mechanism has yet to be elucidated, by adopting microarray technique we hope to decipher the novel signaling cascades involved, and if different severity of injury would induce any form of neuronal regeneration.

overall_design: Microarray was performed on 34 arrays on Illumina Rat Ref12V1 expression beadchips. 6 control samples were adopted as universal controls, and n=3 was used for each time-points (0h, 8h, 15h, 24h and 48h) for Mild neurotrauma and (8h, 15h, 24h and 48h) for Severe neurotrauma. Only one replicate is present for 0h Severe neurotrauma.

first: Nam

last: Cheung

first: Minghui

first: Zhao

last: Peng

first: Roger

last: Chung


title: NPTX1 is a Critical Regulator of Neural Induction in Human Pluripotent Stem Cells

city: Rensselaer

first: Nathan

last: Boles

address: one Discovery Drive

country: USA

institute: Neural Stem Cell Institute

summary:
NPTX1 is a key inducer of neural lineages from the human ESC.
We used microarrays to detail the global programme of gene expression underlying neural induction by NPTX1.

overall_design: A timecourse of neural Induction from human ESC in NPTX1 shRNA expressing cells and control cells was examined.

first: Chris

last: Fasano