title: Expression profiling of Ascl1-reprogrammed P12 Müller glia compared with freshly dissociated progenitors and Müller glia

city: SEATTLE

first: THOMAS

last: REH

address: 1959 NE PACIFIC STREET

department: BIOLOGICAL STRUCTURE

institute: UNIVERSITY OF WASHINGTON

summary:
Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia cells (MG) that activate the proneural factor Achaete-scute homolog 1 (Ascl1/Mash1) and de-differentiate into progenitors cells. In contrast, mammalian MG have a limited regenerative response and fail to upregulate Ascl1 after injury. To test whether Ascl1 could restore a neurogenic potential to mammalian MG, we over-expressed Ascl1 in dissociated mouse MG cultures and intact retinal explants. Ascl1-infected MG upregulate retinal progenitor-specific genes, while downregulating glial genes. Furthermore, Ascl1 remodeled the chromatin at its targets from a repressive to active configuration. MG-derived progenitors differentiated into cells that exhibited neuronal morphologies, expressed retinal subtype-specific neuronal markers, and displayed neuron-like physiological responses. These results indicate that a single transcription factor, Ascl1, can produce a neurogenic state in mature Muller glia.
Expresssion profiling was used to determine the genes that were changed after Ascl1 infection of P12 cultured Müller glia compared with those present in P0 progenitors and P7-P21 Müller glia

overall_design: Retinas were dissociated and FAC-sorted from Hes5-GFP mice at P0, P7, P10, P14 or P21 and submitted for profiling. WT Retinas were dissociated at P12, grown for 1 week in culture, and infected with lentiviruses expressing Ascl1 or GFP for four days. Total RNA was extracted and submitted for profiling.

first: Julia

last: Pollak

first: Thomas

last: Reh


title: Downstream targets of ID1 transcription factor in Non-Small Cell Lung Carcinoma (NSCLC)

status: Public on Apr 15 2013

city: Tampa

first: Jonathan

last: Nguyen

state: FL

department: Tumor Biology

country: USA

institute: Moffitt Cancer Centre & Research Institute

summary: ID-1, known as inhibitor of differentiation or a helix loop helix transcription factor which lack the basic DNA binding domain. It is known to bind to bHLH transcription factor and inhibit those bHLH to bind to the promoter thus inhibiting further transcription. Overexpression of ID-1 has been correlated with a variety of human cancers including breast, prostate, pancreatic, ovarian, endometrial, bladder cancer and melanomas. Recently known that if ID-1 is depleted, it abrogates cell proliferation, invasion and migration of cells in NSCLC. Further ID-1 expression is induced by Nicotine and EGF through the activation of nAChRs and EGFR. Here microarray analysis was done to compare differential gene expression patterns upon nicotine and EGF stimulation of A549 and H1650 cells and how ID1 depletion changes these patterns. We find that multiple genes are affected and the role of these genes in lung cancer will be elucidated. In this study we show that ID-1 regulates the expression of three genes STMN3, TPD52 and GSPT1 in NSCLC by activating the promoter of these genes either directly or indirectly. We also show that depletion of STMN3, TPD52 and GSPT1 prevented Nicotine and EGF induced cell proliferation, invasion and migration of cells  in NSCLC.

overall_design: Two cell lines (A549, H1650) each having 5 samples.

first: Sajitha

last: Nair

first: Deepak

last: Perumal

first: Srikumar

middle: P

last: Chellappan


title: Glioma cells oxygen response

status: Public on Apr 05 2013

city: La tronche

first: didier

last: wion

address: fortuné ferrini

country: France

institute: INSERM

summary: Transcriptomic analyses of the oxygen response of two glioma cell lines at 20% versus 0.3% O2, and 3% vs 0.3% O2 in the presence or absence of serum

overall_design: 22 samples are analysed with three or more biological replicates in different O2 concentrations.

first: Marie

middle: F

last: Nissou

first: Michele

last: El Atifi

first: Audrey

last: Guttin

first: Jean-Paul

last: Issartel

first: François

last: Berger

first: Didier

last: Wion


title: Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment leads to defects in hematopoietic stem cell function.

status: Public on Apr 04 2013

city: Chapel Hill

first: Sarah

last: Stein

state: NC

address: 450 West Dr.

department: Lineberger Comprehensive Cancer Center

institute: University of North Carolina at Chapel Hill

summary: Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment results in gene expression changes in lineage-Flk2-c-kit+Sca-1+ cells from mouse bone marrow.

overall_design: We analyzed lineage-Flk2-c-kit+Sca-1+ cells from the bone marrow of p65 wild-type or knockout mice using the Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.

first: Albert

middle: S

last: Baldwin


title: An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells Methylation Data for In Vitro Model

city: New York

first: Daniel

last: Rohle

state: NY

address: 1275 York Avenue

department: The Human Oncology and Pathogenesis Program

institute: Memorial Sloan Kettering Cancer Center

summary: The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1) which is mutated in multiple human cancers. Here, we examine the role of mutant IDH1 in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen dose-dependently blocked the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). Under conditions of near complete R-2HG inhibition, the mIDH1 inhibitor induced demethylation of histone H3K9M3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant - but not IDH1-wildtype – glioma cells without appreciable changes in genome wide DNA methylation. These data suggest that mIDH1 may promote glioma growth through mechanisms beyond its well-characterized epigenetic effects.

overall_design: Samples were maintained in either DMSO or 1.5uM 5198 for 2 passages up to 20 passages. Biological replicates for each passage and treatment was collected and genomic DNA was extracted and analyzed on the Illumina 450K Methylation platform for a total of 16 samples.

middle: A

first: Ingo

middle: K

last: Mellinghoff


title: Survival transcriptome in coenzyme Q deficiency syndrome

city: Sevilla

first: Daniel Jose

last: Moreno Fernandez-Ayala

address: Carretera de Utrera, Km. 1

country: Spain

institute: Universidad Pablo de Olavide

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

overall_design: Refer to individual Series

middle: J

last: Fernández-Ayala

first: Ignacio

last: Guerra

first: Maria

middle: V

last: Cascajo

first: Angela

last: Gavilán

first: Salvatore

last: DiMauro

first: Michio

last: Hirano

first: Leonardo

last: Salviati

first: Rafael

last: Artuch

last: de Cabo

first: Plácido

last: Navas


title: An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells

type:
Expression profiling by array
Methylation profiling by array


title: EWS/ATF1 activates Fos and induces soft tissue sarcomas [Affymetrix].

city: Tokyo

first: Yasuhiro

last: Yamada

address: 7-3-1 Hongo, Bunkyo-ku

department: Department of Molecular Pathology

country: Japan

institute: University of Tokyo

summary: Clear cell sarcoma (CCS) is an aggressive soft tissue malignant tumor characterized by a unique t(12; 22) translocation, leading to the expression of a chimeric EWS/ATF1 fusion gene.  However, little is known about the mechanisms underlying how EWS/ATF1 is involved in the development of CCSs.  In addition, the cells of origin for CCSs remain to be determined.  We generated EWS/ATF1-inducible mice, and examined the effects of EWS/ATF1 expression in adult cells.  We show that the forced expression of EWS/ATF1 results in the development of EWS/ATF1-dependent sarcomas in mice.  The histology of EWS/ATF1-induced sarcomas resembles that of CCSs and EWS/ATF1-induced tumor cells express CCS-markers, such as S100, Sox10, and Mitf.  A lineage tracing experiment revealed that such sarcomas are derived from neural crest-lineage cells.  Finally, we found that EWS/ATF1 directly induces Fos in an ERK-independent manner, and demonstrated that the increased Fos expression is important for the active cell proliferation in not only EWS/ATF1-induced sarcomas, but also in human CCSs.  Our results indicate that FOS, as well as EWS/ATF1 itself, could be a promising therapeutic target for the treatment of EWS/ATF1-related sarcomas.

overall_design: Tumor cell lines were exposed to different concentrations of doxycycline, and total RNAs were isolated at 24 hours after the doxycycline exposure. Total RNAs were also isolated directly from a tumor developed in a EWS/ATF1-inducible mouse given doxycycline for 3 months. The doxycycline concentration and time point for each sample is EWS-ATF1_control; 0 microg/ml (no dox), 24 hours after the exposure, EWS-ATF1_24h_highDox; 0.2 microg/ml, 24 hours after the exposure and EWS-ATF1_tumor1; a tumor was resected from a EWS/ATF1-inducible mouse given doxycycline for 3 months.

first: Kazunari


title: An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells Methylation Data for Xenograft Samples

overall_design: Xenograft experiments were carried out with treatment cohorts of vehicle, 150mg/kg/day, 450mg/kg/day. After the indicated tumors were harvested and genomic DNA was extracted and analyzed by the Illumina 450k Methylation array.


title: Expression data from a human MLL-AF6 positive AML cell line

status: Public on Apr 03 2013

city: Boston

first: Amit

last: Sinha

state: MA

address: 44 Binney St

department: Pediatric Oncology

institute: Dana-Farber Cancer Institute

summary:
The MLL gene on chromosome 11 fuses to the AF6 gene on chromosome 6 in a balanced chromosomal translocation that is characetristic of certain adult and pediatric human leukemias. We established a murine leukemia model of MLL-AF6 using the retroviral MLL-AF6 contruct in a bone marrow transplantation system.
The ML2 human MLL-AF6 positive leukemia cell line was used for gene expression profiling to assess the transctiptional profile in MLL-AF6 leukemias.

overall_design: RNA was extracted from the ML2 cell line cultured under standard conditionswith TRIZOL (Invitrogen), purified using RNAeasy(Qiagen) and hybridized onto Affymetrix arrays.

first: Aniruddha

last: Deshpande

first: Scott

last: Armstrong


title: The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map

status: Public on Apr 02 2013

city: Seattle

first: James

middle: William

last: MacDonald

state: WA

address: 4225 Roosevelt Way NE

department: Environmental and Occupational Health Sciences

institute: University of Washington

summary: The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 → Eomes → Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism.

overall_design: To determine the role of Eomes in the propagation of the protomap to cortical plate neurons, used microarray analysis of E14.5 cortex from five wild type and three Eomes knockout mice.

first: Gina

middle: E

last: Elsen

first: Rebecca

middle: D

last: Dodge

first: Francesco

last: Bedogni

first: Ray

last: Danza

first: Branden

middle: R

last: Nelson

first: Naoko

last: Shiba

first: Steven

middle: L

last: Reiner

first: Robert

last: Hevner


title: SOX11 Gene Expression Profiling

city: Barcelona

first: Virginia

last: Amador

address: Rossello 153

institute: IDIBAPS

summary: The neural transcription factor SOX11 is overexpressed in aggressive lymphoid neoplasms mainly in mantle cell lymphoma (MCL), but its functional role in malignant B-cells is unknown. To identify target genes transcriptionally regulated by SOX11 in malignant lymphoid cells, we have used Gene Expression Profiling (GEP) after SOX11 silencing in MCL cell lines.

overall_design:
Differential gene expression between Z138-shSOX11 and Z138-shControl MCL cell lines.

To determine the transcriptional programs regulated by SOX11, we first generated an MCL cellular model with reduced SOX11 protein levels by infecting MCL cell lines with lentiviral particles carrying shRNA plasmids specifically targeting SOX11 (shSOX11.1 and shSOX11.3). Next, we compared the GEP of shSOX11 and shControl Z138 stable transduced clones using the Affymetrix U133+2.0 microarrays.

first: Maria

middle: C

last: Vegliante

first: Jara

last: Palomero

first: Pedro

last: Jares

first: Elias

last: Campo


title: Common gene expression profile in the mitochondrial syndrome of coenzyme Q deficiency

first: Daniel Jose

last: Moreno Fernandez-Ayala

summary: Coenzyme Q10 deficiency syndrome includes a clinically heterogeneous group of mitochondrial diseases characterized by low content of CoQ10 in tissues. The only currently available treatment is supplementation with CoQ10, which improves the clinical phenotype in some patients but does not reverse established damage. We analyzed the transcriptome profiles of fibroblasts from different patients irrespective of the genetic origin of the disease. These cells showed a survival genetic profile apt at maintaining growth and undifferentiated phenotype, promoting anti-apoptotic pathways, and favoring bioenergetics supported by glycolysis and low lipid metabolism. WE conclude that the mitochondrial dysfunction caused byCoQ10 deficiency induces a stable survival adaptation of somatic cells from patients.

overall_design:
All samples in triplicate.
We compare the gene expresion of human derman fibroblast to fibroblast from 4 different patient diagnosed with the human syndrome of coenzyme Q10 deficiency.

first: Daniel

middle: M

last: Fernández-Ayala

first: Ignacio

last: Guerra

first: María

last: Cascajo

first: Angela

last: Gavilan

first: Salvatore

last: DiMauro

first: Michio

last: Hirano

first: Leonardo

last: Salviati

first: Rafael

last: Artuch

last: de Cabo

first: Plácido

last: Navas


title: Expression data (U133 Plus 2.0) from fibroblast like synoviocytes from patients with rheumatoid arthritis (RA-FLS) stimulated by DcR3

city: Kobe

first: Koji

last: Fukuda

address: 7-5-1 Kusunoki, Chuo

department: Department of Orthopaedic Surgery

institute: Kobe University Graduate School of Medicine

summary:
Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT, and TL1A. DcR3 was recently reported not only to act as a decoy receptor for these TNFRs but also to play a role as a ligand for the pathogenesis of RA.
We hypothesized that DcR3 regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by the ligation of DcR3.

overall_design: RA-FLS were obtained from 4 RA patients (sample1-4). Each sample was incubated with control IgG1 or human DcR3-Fc. Gene expression in RA-FLS stimulated by DcR3-Fc was compared with that of their respective unstimulated controls.

first: Yasushi

last: Miura

first: Toshihisa

last: Maeda

first: Masayasu

last: Takahashi

first: Shinya

last: Hayashi

first: Masahiro

last: Kurosaka


title: Effects of exercise on gene expression level in human NK Cells

city: Irvine

first: Shlomit

last: Radom-Aizik

state: CA

address: 101 Academy

department: Pediatrics

institute: University of California, Irvine

summary:
We tested the hypothesis on the mechanisms responsible for the early control of NK cell function by identifying a discrete set of genes in circulating NK cells that were altered by exercise.
Exercise leads to a rapid change in the profile of gene expression in NK cells.

overall_design: Twelve healthy men (20-29 yr old) performed 10 2-min bouts of cycle ergometer exercise interspersed with 1-min rest at a constant work equivalent to about 77% of VO2max. A baseline blood sample was taken before the and immediately after the exercise.  NK cells were isolated from PBMC using a negative magnetic cell separation methods (Miltenyi Biotec Kit #130-092-657 and the autoMACS® Pro Separator). Total RNA was extracted using TRIzol®.  For this study we used Affymetrix plus 2  (total of 24 chips).

first: Dan

last: Cooper


title: SMRT compounds abrogate cellular phenotypes of Ataxia Telangiectasia in neural derivatives of patient specific hiPSCs

status: Public on Apr 01 2013

city: Los Angeles

first: William

last: Lowry

address: 621 Charles Young

institute: UCLA

summary:
gene expression profiling of WT fibroblasts, hiPSCs, and NPCs compared to the same cell types isolated from patients with Ataxia Telangiectasia
gene expression profiling was carried out with Affymetrix Hg133 2.0 plus chips

overall_design: fibroblasts, hiPSCs, hESCs, and NPCs were isolated and compared by gene expression

first: Peiyee

last: Lee


title: An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells Expression data for Xenograft Samples

first: Daniel

last: Rohle

overall_design: Two xenograft experiments were carried out, one with treatment cohorts of vehicle and 450mg/kg, and the other with vehicle, 150mg/kg/day, and 450mg/kg/day. After the indicated time tumors were harvested and total RNA was extracted and analyzed by the Affymetrix U133 plus 2 array.

first: Ingo

last: Mellinghoff


title: Gene expression profiling of Non-small cell lung cancer in Taiwan

status: Public on Apr 10 2013

city: Taipei

first: Yih-Jyh

last: Shann

address: No.155, Sec.2, Linong Street

country: Taiwan

institute: Nation Yang-Ming University

summary: This study focus on the expression signature between tumor and adjacent normal tissues.

overall_design: Tumor(T) and adjacent normal(N) tissue pairs from 25 stage I lung adenocarcinoma patients were selected for RNA extraction and hybridization on microarrays.

first: Su

last: Li-Jen

first: Shann

last: Yih-Jyh

first: Huang

last: Chi-Ying


title: Expression data from human lymphocytes

city: Stanford

first: Leng

last: Han

address: 265 Campus Dr

institute: Stanford University

summary:
Baseline gene expression of human lymphocytes 24 hours after 5 Gy gamma irradiation
We used microarrays to detail the global gene expression of human lymphocytes after irradiation

overall_design: Compare the gloable gene expression of human lymphocyte 24 hours after exposure to doses between 0 and 5 Gy γ rays

first: Won

middle: H

first: Joseph

last: Wu


title: Arf Tumor Suppressor and miR-205 Regulate Cell Adhesion and Formation of Extraembryonic Endoderm from Pluripotent Stem Cells

city: Memphis

first: David

last: Finkelstein

state: TN

address: 332 N. Lauderdale St.

department: Computational Biology

institute: St Jude Children's Research Hospital

summary: Induction of the Arf tumor suppressor in response to hyperproliferative stress following oncogene activation activates a p53-dependent transcriptional program that limits the expansion of incipient cancer cells.  Although Arf is not expressed in most tissues of fetal or young adult mice, it is physiologically expressed in the fetal yolk sac, a tissue derived from the extraembryonic endoderm.  We demonstrate that expression of the mouse p19Arf protein marks late stages of extraembryonic endoderm differentiation in cultured embryoid bodies derived from either embryonic stem cells or induced pluripotent stem cells, and that Arf inactivation specifically delays the differentiation of the extraembryonic endoderm lineage, but not the formation of other germ cell lineages from pluripotent progenitors.  Arf is required for the timely induction of extraembryonic endodermal cells in response to Ras/Erk signaling and, in turn, acts through p53 to ensure extraembryonic endoderm lineage development, but not maintenance.  Remarkably, a significant temporal delay in extraembryonic endoderm differentiation detected during the maturation of Arf-null embryoid bodies is rescued by enforced expression of miR-205, a micro-RNA up-regulated by p19Arf and p53.  Introduction of miR-205 into Arf-null embryonic stem cells rescues defective ExEn formation and elicits a program of gene expression that controls the migration and adhesion of embryonic endodermal cells.  This occurs, at least in part, through atypical regulation of genes that control the epithelial-to-mesenchymal transition in cancer cells.  Our findings suggest that noncanonical and canonical roles of Arf in extraembryonic endoderm development and tumor suppression, respectively, may be conceptually linked through mechanisms that govern cell-to-cell attachment and migration.

overall_design: 4 samples  total two each at two time points in ESC development  At each time point one sample was treted with miR-205 and the other with a GFP control vector

first: Chunliang

last: Li

first: Charles

last: Sherr


title: Transient treatment with epigenetic modifiers yields stable neuroblastoma stem cells resembling aggressive large-cell neuroblastomas

city: Philadelphia

first: Eric

last: Rappaport

state: PA

address: 3615 Civic Center Blvd

institute: Children's Hospital of Philadelphia

summary: Cancer stem cells (CSCs) are plastic in nature, a characteristic that hampers cancer therapeutics.  Neuroblastoma (NB) is a pediatric tumor of neural crest origin, and half of the cases are highly aggressive.  By treating NB cell lines (SKNAS, SKNBE(2)C, CHP134, SY5Y) with epigenetic modifiers for a short time followed by sphere-forming culture conditions, we have established stem cell-like NB cells that are phenotypically stable for over a year.  These cells are characterized by their high expression of stemness factors, stem cell markers, and open chromatin structure.  We referred to these cells as induced CSC (iCSC).  SKNAS iCSC and SKNBE(2)C iCSC clones (as few as 100 cells) injected subcutaneously into SCID/Beige mice formed tumors, and in one case, SKNBE(2)C iCSC metastasized to the adrenal gland, suggesting their increased metastatic potential.  SKNAS iCSC xenografts showed the histologic appearance of totally undifferentiated “large-cell” NBs (LCNs), the most aggressive and deadly form of NB in humans.  Immunohistochemical analyses showed that SKNAS iCSC xenografts expressed high levels of the stem cell marker CXCR4, while the SKNAS monolayer cell xenografts did not.  The patterns of CXCR4 and MYC expression in SKNAS iCSC xenografts resembled those in the LCNs.  The xenografts established from the NB iCSCs shared two common features: the LCN phenotype and high-level MYC/MYCN expression.  These observations suggest that NB cells with large and vesicular nuclei, representing their open chromatin structure, are indicative of stem cell-like tumor cells, and that epigenetic changes may have contributed to the development of these most malignant NB cells.

overall_design: Gene expression profiles of SKNAS monolayer culture, sphere culture and iCSC culture were comparatively analyzed to examine the stem cell phenotype of each culture condition.

first: Naohiko

last: Ikegaki

first: Hiroyuki

last: Shimada

first: Autumn

last: Fox

first: Paul

last: Regan

first: Joshua

last: Jacobs

first: Sakeenah

last: Hicks

first: Xao

middle: X

last: Tang


title: Expression data from LNCaP cells treated with DHT and enzalutamide

city: Santiago

first: Ivan

middle: Esteban

last: Alfaro

address: Zañartu 1482

department: Molecular Innovation and Drug Discovery

country: Chile

institute: Fundacion Ciencia y Vida

summary:
Enzalutamide (formerly MDV3100 and available commercially as Xtandi), a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling:  (1) binding of androgens to AR, (2) AR nuclear translocation, and (3) association of AR with DNA.
Here we used Affymetrix human genome microarray technology to investigate the global programme of gene expression of LNCaP cells in response to enzalutamide alone and in the context of DHT-stimulated androgen receptor gene expression.

overall_design: LNCaP cells were grown in RPMI 1640 supplemented with 5% hormone depleted FBS and treated with vehicle (control sample) , DHT (100 nM), enzalutamide (1 or 10 µM) or DHT (100 nM) plus enzalutamide (1 or 10 µM)for 16 hours for RNA extraction and hybridization. Each condition was done in triplicate.

first: Javier

last: Guerrero

first: Francisco

last: Gomez

first: Andrew

last: Protter

first: Sebastian

last: Bernales


title: C/EBPa gene signature

city: Singapore

first: Daniel

middle: G

last: Tenen

address: 14 Medical Drive, #12-01

department: Cancer Science Institute of Singapore

country: Singapore

institute: National University of Singapore

summary: We defined the C/EBPa signature characterized by a set of genes which are upregulated upon C/EBPa activation. In order to identify the C/EBPa signature, we performed microarray gene expression analysis of K562 cells stably expressing p42-C/EBPa-ER after activating the C/EBPa construct to translocate to the nucleus for 6 hours with beta-estradiol.

overall_design: The gene expression profile was performed in K562 p42-C/EBPa-ER expressing cells treated with beta-estradiol (n=4) or EtOH vehicle control (n-4) for 6 hours. Induction of nuclear localization of C/EBPa-ER fusion protein was achieved by addition of 1 uM beta-estradiol as indicated into the culture medium.

first: Adam

last: Liss

first: Meritxell

last: Alberich-Jordà

first: Chia

last: Ooi

first: Polina

last: Zjablovskaja

first: Touati

last: Benoukraf

first: Hanna

last: Radomska

first: Chen

last: Ju

first: Mengchu

last: Wu

first: Martin

last: Balastik

first: Ruud

last: Delwel

first: Tomas

last: Brdicka

first: Patrick

last: Tan


title: Gene expression profile of pediatric AML

first: Hitoshi

last: Ichikawa

address: 5-1-1 Tsukiji, Chuo-ku

institute: National Cancer Center Research Institute

summary: Gene expression data were obtained from 130 pediatric AML patients who were enrolled on the AML99 study conducted by the Japanese Childhood AML Cooperative Study Group.

overall_design: RNA samples obtained at the time of diagnosis were analyzed using GeneChip Human Genome U133 plus 2.0 array (Affymetrix).

first: Aoi

last: Jo

first: Sachiyo

last: Mitani


title: Low SLC22A7 expression in noncancerous liver promotes hepatocellular carcinoma occurrence - a prospective study

city: Bunkyo-ku

first: Kaoru

last: Mogushi

state: Tokyo

address: 2-1-1 Hongo

department: Intractable Disease Research Center

institute: Juntendo University

summary:
Background & Aims: The recurrence determines the postoperative prognosis of patients with hepatocellular carcinoma (HCC). It is unknown whether de novo HCCs derive from the liver with disability of an organic anion transport. This study was designed to elucidate the link between such transporters and the multicentric occurrence (MO) after radical hepatectomy.

Results: SLC22A7 expression was the best predictor of metastasis-free survival (MFS) as judged by the GA (Fold, 0.726; P=0.001). High SLC22A7 gene expression in noncancerous tissue prevent HCC occurrence after hepatectomy (Odds Ratio (OR), 0.2; 95%CI, 0.1-0.6; P=0.004). Multivariate analyses of MFS revealed the independent risk factor to be SLC22A7 expression (OR, 0.3; 95%CI, 0.1-1.0, P=0.043). Low SLC22A7 expression caused MO of HCC significantly (log-rank, P=0.001). In the validation study, multivariate analyses of MFS revealed the independent risk factor to be SLC22A7 expression (OR, 0.5; 95%CI, 0.3-0.8; P=0.012). As judged by Gene set-enrichment analysis, SLC22A7 down-regulation associated with mitochondrion (P=0.008; false discovery rate (FDR)=0.199; normalized enrichment score (NES) =1.804), oxidoreductase activity (P=0.006; FDR=0.157; NES=1.854) and fatty acid metabolic process (P=0.021; FDR=0.177; NES=1.723). Sirtuin3 also determined MFS (P= 0.018).

Conclusions: These pathways involving SLC22A7 dysfunction may promote the occurrence of HCC.

overall_design: The 49 noncancerous liver tissues of HCC patients within Milan criteria, treated at our institution between January 2004 and August 2008, were examined as a training set by genome-wide gene expression analysis (GA). Cox proportional hazards regression analyses for MO-free survival (MFS) were performed to estimate the risk factors. Using the independent two institutional cohorts of 134 patients between September 2008 and December 2009, a validation study was employed using tissue microarrays.

first: Atsushi

last: Kudo

first: Tadatoshi

last: Takayama

first: Satoshi

last: Matsumura

first: Daisuke

last: Ban

first: Takumi

last: Irie

first: Takanori

last: Ochiai

first: Noriaki

last: Nakamura

first: Hiroshi

last: Tanaka

first: Naohiko

last: Anzai

first: Michiie

last: Sakamoto

first: Shinji

first: Shigeki

last: Arii


title: Time course analysis of gene expression in BCR-stimulated splenic wild type and TAK1-/- B cell

status: Public on Mar 31 2013

city: Yokohama

first: Hisaaki

last: Shinohara

address: 1-7-22 Suehiro-cho

department: RCAI

institute: RIKEN

summary:
The activation signaling of transcription factor nuclear factor-kB (NF-kB) plays central role for immune system.  One of key kinase mediating this pathway is TAK1 in adaptive and innate immunity.
However, role of TAK1 in B cell receptor signaling is still unclear. To know effects of TAK1-deletion on the gene expression induced by anti-IgM, we performed the time course analysis in comparison of wild type with TAK1-deleted splenic B cells.

overall_design: Splenic B cells were purified by depleting CD43+ cells. Purified B Cells were stimulated with 10 µg/ml of anti-IgM for 1, 3, 6, or 24hr.  Two replicated samples were analysed. Unstimulated cells (0) were control.

first: Takeshi

last: Nagashima


title: Molar and incisor development

city: Illkirch

first: Doulaye

last: Dembele

address: 1 rue Laurent Fries

department: Biopuces

institute: IGBMC

summary: One of the key questions in developmental biology is how from universally shared molecular mechanisms and pathways, is it possible to generate organs displaying similar or complementary functions, with a wide range of different shapes or tissue organization? The dentition represents a valuable system to address the issues of differential molecular signatures generating specific tooth types. We performed a comparative transcriptomic analysis of developing murine lower incisors, mandibular molars and maxillary molars at the developmental cap stage (E14.5) prior to recognizable tooth shape and cusp pattern.

overall_design: We compared gene expression profiles in developing murine lower incisor and molars, as well as between the lower and upper (mandibular and maxillary) first molars

first: Virginie

last: Laugel-Haushalter

first: Marie

last: Paschaki

first: Christelle

last: Thibault-Carpentier

last: Dembélé

first: Pascal

last: Dollé

first: Agnès

last: Bloch-Zupan


title: Convergence of oncogenic and hormone receptor pathways promotes pro-metastatic phenotypes.

city: PHILADELPHIA

first: Adam

last: Ertel

address: 233 S 10TH ST

department: Cancer Biology

institute: Thomas Jefferson University

summary:
Cyclin D1b is a splice variant of the cell cycle regulator Cyclin D1 and is known to harbor divergent and highly oncogenic functions in human disease. While Cyclin D1b is induced during disease progression in many cancer types, the mechanisms underlying Cyclin D1b function remain poorly understood.  Herein, models of human disease were utilized to resolve the downstream pathways requisite for the pro-tumorigenic functions of Cyclin D1b. Specifically, it was shown that Cyclin D1b modulates the expression of a large transcriptional network that cooperates with AR signaling to enhance tumor cell growth and invasive potential.  Notably, Cyclin D1b promoted AR-dependent activation of genes associated with metastatic phenotypes. Further exploration determined that transcriptional induction of SNAI2 (Slug) was essential for Cyclin D1b- mediated proliferative and invasive properties, implicating Slug as a critical driver of disease progression. Importantly, Cyclin D1b expression highly correlated with that of Slug in clinical samples of advanced disease. Further, in vivo analyses provided strong evidence that Slug enhances both tumor growth and homing to distal soft tissues. Collectively, these findings reveal the underpinning mechanisms behind the pro-tumorigenic functions of Cyclin D1b, and demonstrate that the convergence of the Cyclin D1b-AR and Slug pathways results in the activation of processes critical for the promotion of lethal tumor phenotypes.
Analysis of transcriptomes under the control of individual D-type cyclin isoforms in the hormone dependent prostate cancer cell line LNCaP in the presence and absence of androgen.

overall_design: LNCaP cells cultured in charcoal dextran treated media were transduced with virus encoding Cyclin D1a, Cyclin D1b, or control GFP for 24 hours in biological triplicate.  Cells were then stimulated with either 1nM DHT or 0.01% EtOH (vehicle control) for 16 hours and harvested for RNA

first: Michael

last: Augello

first: Craig

last: Burd

first: Ruth

last: Birbe

first: Chris

last: McNair

last: Magee

first: Daniel

last: Frigo

first: Kristen

last: Wilder-Romans

first: Mark

last: Shikrut

first: Sumin

last: Han

first: Danielle

last: Jerrigan

first: Jeffrey

last: Dean

first: Alessandro

last: Fatatis

first: Donald

middle: P

last: McDonnell

first: Tapio

last: Visakorpi

first: Felix

middle: Y

last: Feng

first: Karen

last: Knudsen


title: Gene expression data from oncogene transformed murine prostate epithelial cell lines

last: Ertel

summary:
Primary prostate epithelial cell cultures were established from the VENTRAL prostates of FVB mice .  Cells were transduced with retroviral expression vectors encoding a single distinct oncogene (c-Myc, Ha-Ras (V-12), v-Src and NeuT, an activating mutant of ErbB2).   Individual colonies of oncogene-transduced cells were selected and characterized.  These cell lines demonstrate contact-independent growth characteristics in soft agar and in immune competent mice.
To further characterize the molecular genetic signaling pathways regulated by specific oncogenes in prostate epithelial cells

overall_design: mRNA was prepared from the oncogene transformed PEC cell lines, 12 samples(each oncogene has 3 lines) and 3 normal prostate epithelial cell controls in good condition.

first: Xiaoming

last: Ju

first: Mathew

last: Casimiro

first: Paolo

last: Fortina

last: Lisanti

first: Richard

last: Pestell


title: EWS/ATF1 activates Fos and induces soft tissue sarcomas from neural crest-derived cells.

city: Tokyo

first: Yasuhiro

last: Yamada

address: 7-3-1 Hongo, Bunkyo-ku

institute: University of Tokyo

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

overall_design: Refer to individual Series

first: Kazunari


title: The Plasma Cell Signature in Autoimmune Disease (I)

status: Public on Mar 28 2013

city: Gaithersburg

first: Christopher

middle: Allen

last: Morehouse

state: MD

address: One Medimmune Way

institute: Medimmune LLC

summary: Objective: Production of pathogenic autoantibodies by self-reactive plasma cells (PC) is a hallmark of autoimmune diseases. Investigating the prevalence of PC in autoimmune disease and their relationship with known pathogenic pathways may increase our understanding of the role of PC in disease progression and treatment response.    Methods: We developed a sensitive gene expression based method to overcome the challenges of measuring PC using flow cytometry. Whole genome microarray analysis of sorted cellular fractions identified a panel of genes, IGHA, IGJ, IGKC, IGKV, and TNFRSF17, expressed predominantly in PC. The sensitivity of the PC signature score created from the combined expression levels of these genes was assessed through ex vivo experiments with sorted cells.  This PC gene expression signature was used for monitoring changes in PC levels following anti-CD19 therapy; evaluating the relationship between PC and other autoimmune disease-related genes; and estimating PC levels in affected blood and tissue from multiple autoimmune diseases.   Results:  The PC signature was highly sensitive and capable of detecting as few as 300 PCs.   The PC signature was reduced over 90% in scleroderma patients following anti-CD19 treatment and this reduction was highly correlated (r = 0.77) with inhibition of collagen gene expression. Evaluation of multiple autoimmune diseases revealed 30-35% of lupus, rheumatoid arthritis, and scleroderma patients with increased PC levels.     Conclusion: This newly developed PC signature provides a robust and accurate method to measure PC levels in the clinic. Our results highlight subsets of patients across multiple autoimmune diseases that may benefit from PC depleting therapy.

overall_design: To examine gene expression in purified cellular fractions, normal human blood was collected from 2 donors as per institutional policy. The granulocyte (CD15+), monocyte (CD14+), T cell (CD3+), B cell (Non-PC gated, CD19+), and PC (CD27++CD38++) fractions from peripheral blood were separated. White blood cells were washed with FACS buffer (PBS + 0.5%BSA + 2mM EDTA (Gibco)) and incubated with 20% heat-inactivated FBS for 10-15 minutes on ice. The following mAbs were added directly to the cells: CD15 (HI98); CD14 (M5E2), CD3 (UCHT1), CD27 (M-T271), CD38 (HB7), and DAPI (Molecular probes). Cells were sorted on a Becton Dickinson FACS Aria II flow cytometer. All sorted fractions were collected in FACS buffer, centrifuged, and the resulting cell pellet was suspended in RNA lysis buffer (Ambion).

middle: A


title: The Plasma Cell Signature in Autoimmune Disease (II)

overall_design: MI-CP200 is a Phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of escalating single IV doses of MEDI-551 in adult subjects with scleroderma. In this study, 5 cohorts of subjects (n=25) received 1 of 5 single IV doses of MEDI-551 (0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg) or placebo. Twenty-four healthy donor control samples are also included.


title: The Plasma Cell Signature in Autoimmune Disease


title: Expression data from human Huntington fibroblasts

city: padova

first: andrea

last: bozzato

address: via bassi

country: Italy

institute: university

summary:
Gene expression profile comparison from fibroblasts of Huntington individuals and normal ones
We used microarrays to detail the global gene expression of fibroblasts from Huntington patients

overall_design: Comparison between six Huntington human fibroblasts and three normal controls. All individuals were aged and sex matched. In fact they are all males with the subsequent ages: 28, 48, 57 for the controls and 38, 63, 57, 47, 38, 37 for the HD patients. The average age is comparable.

first: Andrea

last: Bozzato

first: Giuseppe

last: Borsani


title: 1,25-dihydroxyvitamin D3-induced genes in mouse mixed neuron-glial cell cultures

status: Public on Mar 25 2013

city: La tronche

first: didier

last: wion

address: fortuné ferrini

institute: INSERM

summary: Transcriptomic response of mouse mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin D3

overall_design: 6 samples are analysed with three biological replicates in two conditions, control versus 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)

first: M

middle: F

last: Nissou

last: El Atifi

first: JP

last: Issartel

first: F

last: Berger

first: D

last: Wion


title: Buccals are likely to be a more informative surrogate tissue than blood for epigenome-wide association studies

city: London

first: Robert

last: Lowe

address: 4 Newark Street

department: Blizard Institute

country: United Kingdom

institute: QMUL

type: Methylation profiling by genome tiling array

type: Methylation profiling by high throughput sequencing


title: DNA Methylation data from early human B-cell development

status: Public on Mar 26 2013

city: Seoul

first: Seung-Tae

last: Lee

state: - None -

address: 50 Iron-Dong KanangmGu

department: Laboratory Medicine & Genetics

country: South Korea

institute: Samsung Medical Center

summary:
A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network. Nucleic Acids Res. 2012 Dec;40(22):11339-51.
We examined DNA methylation and RNA expression status during early B-cell development by sorting multiple replicates of four separate stages of pre-B cells derived from normal human fetal bone marrow and applied high-dimension DNA methylation scanning and expression arrays.
We identified a distinct development-dependent demethylation signature which has gene expression regulatory properties for pre-B cells, and provide a catalog reference for the epigenetic changes that occur in pre-B-cell leukemia and other B-cell-related diseases.

overall_design: Human fetal bone marrow was obtained, and using flow cytometry antibodies, four populations of B-cell developmental stages including stage 1 (S1; predominantly multipotent progenitors before lineage commitment and common lymphoid progenitors), stage II (S2; pre-B-I cells), stage 3 (S3; pre-B-II cells) and stage 4 cells (S4; immature B cells). For 8 indibiduals, DNAs and RNAs were isolated and the methylation and expression changes during early B-cell development were identified using the Illumina HumanMethylation450 Beadchip (Illumina) and GeneChip Human Gene 1.0 ST Array (Affymetrix).

first: Yuanyuan

last: Xiao

first: Joseph

last: Wiemels


title: A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network.


title: Genome wide analysis of skin cancer cell gene expresison exposed to stromal cancer associated fibroblasts in 3D gel matrix

status: Public on Mar 23 2013

first: Hemant

last: Kocher

address: Charterhouse Square

institute: Barts and the London

summary: SCC12 cells were seeded ontop of organotypic gels with HN-CAF (head and neck carcinoma associated fibroblasts). Differential gene expression was analysed between cancer cells not exposed to CAFs or non-invading cancer cells exposed to CAFs.

overall_design: Squamous cell cancer organotypics were constructed by embedding CAFs in collagen Matrigel matrix with SCC 12cells added on top. Gene expression was compared between non-invaded cancer cells and cancer cells not expoesd to CAFs.

first: S

last: Hooper

first: E

last: Sahai


title: Expression data from IGF-1R targeting in 33 NCI-H526 SCLC (small-cell lung cancer) xenografts

status: Public on Mar 30 2013

city: Villejuif

first: Charles

last: Ferté

address: 114 rue Edouard Vaillant

department: Medical Oncology

institute: Gustave Roussy

summary:
Insulin-like growth factor receptor-1 (IGF-1R) inhibition could be a relevant therapeutic approach in small cell lung cancer (SCLC) given the importance of an IGF-1R autocrine loop and its role in DNA damage repair processes. We assessed IGF-1R and pAkt protein expression in 83 SCLC human specimens. The efficacy of R1507 (a monoclonal antibody directed against IGF-1R) alone or combined with cisplatin or ionizing radiation (IR) was evaluated in H69, H146 and H526 cells in vitro and in vivo. Innovative genomic and functional approaches were conducted to analyze the molecular behavior under the different treatment conditions. A total of 53% and 37% of human specimens expressed IGF-1R and pAkt, respectively. R1507 demonstrated single agent activity in H146 and H526 cells but not in H69 cells. R1507 exhibited synergistic effects with both Cisplatin and IR in vitro. The triple combination R1507-Cisplatin-IR led to a dramatic delay in tumor growth compared to Cisplatin-IR in H526 cells. Analyzing the apparent absence of antitumoral effect of R1507 alone in vivo, we observed a transient reduction of IGF-1R staining intensity in vivo, concomitant to the activation of multiple cell surface receptors and intracellular proteins involved in proliferation, angiogenesis and survival. Finally, we identified that the nucleotide excision repair pathway (NER) was mediated after exposure to R1507-CDDP and R1507-IR in vitro and in vivo. In conclusion, adding R1507 to the current standard Cisplatin-IR doublet reveals remarkable chemo- and radiosensitizing effects in selected SCLC models and warrants to be investigated in the clinical setting.
We used microarrays to investigate the effect of IGF-1R targetting on the global gene expression.

overall_design:
Gene expression data from H526 xenografts under various treatment and time conditions
Total mRNA from 33 NCI-H526 SCLC (small-cell lung cancer) xenografts was hybridized to Affymetrix HGU133 Plus 2.0 expression arrays. Log2 gene expression values were calculated using RMA. (A) To identify the molecular mechanisms involved in the response to R1507 alone along the treatment time, we performed global gene expression profiling in H526 xenografts at the following time points: baseline (vehicle), R1507 day 1 and R1507 day 7.  (B) To identify the molecular mechanisms involved in the response to CDDP- and IR-R1507 combinations, we performed global gene expression profiling on mice bearing H526 xenografts treated with the following treatment conditions: vehicle, R1507 CDDP, IR, CDDP-R1507 and IR-R1507.

first: Eric

last: Deutsch


title: Modeling tumor subtypes in vivo using lineage restricted transgenic shRNA

city: Fitzroy

first: Carl

last: Walkley

state: Victoria

address: 9 Princes St

country: Australia

institute: St. Vincent's Institute of Medical Research

summary: Expression analysis from two genetically engineered mouse models of osteosarcoma determine the expression profile of mouse osteosarcoma Human osteosarcoma (OS) is comprised of three different subtypes: fibroblastic, chondroblastic and osteoblastic. We previously generated a mouse model of fibroblastic OS by conditional deletion of p53 and Rb in osteoblasts. Here we report an accurate mouse model of the osteoblastic subtype using shRNA-based suppression of p53. Like human OS, tumors frequently present in the long bones and preferentially disseminate to the lungs; features less consistently modeled using Cre:lox approaches. Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using different technology. This demonstrated that the effects of Cre:lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma. Through the use of complementary genetic modification strategies we have established a model of a distinct clinical subtype of OS that was not previously represented and more fully recapitulated the clinical spectrum of this human tumor.

overall_design: 4 primary tumors from Cre:lox OS model; 4 primary tumors from shRNA OS model.

first: A

middle: J

last: Mutsaers

last: Ng

middle: K

last: Baker

last: Russell

last: Chalk

last: Wall

first: B

last: Liddicoat

first: P

middle: W

last: Ho

first: J

last: Slavin

first: T

last: Martin

first: L

last: Purton

first: R

last: Dickins

first: C


title: Cell-autonomous function of Runx1 transcriptionally regulates megakaryocytic maturation in mice (expression)

status: Public on Mar 22 2013

city: Rechovot

first: Ram

last: Jaschek

address: P.O Box 26

country: Israel

institute: Weizmann Institute of Science

summary: RUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 and p300 identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif. The data provides the first example of genome-wide Runx1/p300 occupancy in maturating FL-MK, unravels the Runx1-regulated program controlling MK maturation in vivo and identifies its bona fide regulated genes. It advances our understanding of the molecular events that upon mutations in RUNX1 lead to the predisposition to familial platelet disorders and FPD-AML.

overall_design: Gene expression profiles of mature megakaryocytes taken from fetal livers of megakaryocyte-specific Runx1 knockout mice, using Runx1F/F/Pf4-Cre mice versus control (WT) mice.

first: Niv

last: Pencovich


title: Transcriptomic analysis of murine embryos lacking endogenous retinoic acid signaling

first: Doulaye

last: Dembele

summary: Retinoic acid (RA), an active derivative of the liposoluble vitamin A (retinol), acts as an important signaling molecule during embryonic development, regulating phenomenons as diverse as anterior-posterior axial patterning, forebrain and optic vesicle development, specification of hindbrain rhombomeres, pharyngeal arches and second heart field, somitogenesis, and differentiation of spinal cord neurons. This small molecule directly triggers gene activation by binding to nuclear receptors (RARs), switching them from potential repressors to transcriptional activators. The repertoire of RA-regulated genes in embryonic tissues is poorly characterized. We performed a comparative analysis of the transcriptomes of murine wild-type and Retinaldehyde Dehydrogenase 2 null-mutant (Raldh2-/-) embryos - unable to synthesize RA from maternally-derived retinol - using Affymetrix DNA microarrays. Transcriptomic changes were analyzed in two embryonic regions: anterior tissues including forebrain and optic vesicle, and posterior (trunk) tissues, at early stages preceding the appearance of overt phenotypic abnormalities. Several genes expected to be downregulated under RA deficiency appeared in the transcriptome data (e.g. Emx2, Foxg1 anteriorly, Cdx1, Hoxa1, Rarb posteriorly), whereas reverse-transcriptase-PCR and in situ hybridization performed for additional selected genes validated the changes identified through microarray analysis. Altogether, the affected genes belonged to numerous molecular pathways and cellular/organismal functions, demonstrating the pleiotropic nature of RA-dependent events. In both tissue samples, genes upregulated were more numerous than those downregulated, probably due to feedback regulatory loops. Bioinformatic clustering analysis allowed us to extract groups of genes displaying similar behaviors in mutant tissue samples. These data give an overview of the gene expression changes occurring under a state of embryonic RA deficiency, and provide new candidate genes and pathways for a better understanding of retinoid-dependent molecular events.

overall_design: Two sets of samples were used for analyzing transcriptome changes in Raldh2-/- embryos. The rostral part of the head (including the anterior forebrain, optic vesicles, and overlying tissues), was collected from wild-type and mutant embryos at the 14 somite stage.The posterior tissues were analyzed at the 4 somite stage, and samples were collected from a transverse section plane excluding all tissues from the level of the first branchial arch.

first: Marie

last: Paschaki

first: Carole

last: Schneider

first: Muriel

last: Rhinn

first: Christelle

last: Thibault-Carpentier

last: Dembelé

first: Karen

last: Niederreither

first: Pascal

last: Dollé


title: Genome-wide mapping of IL-2 regulated target genes and IL-2 activated STAT5 binding sites in Kit225 human leukemia cells.

status: Public on Mar 21 2013

city: Debrecen

first: Zsuzsanna

middle: S.

last: Nagy

address: Nagyerdei krt. 98

department: Biochemistry and Molecular Biology

country: Hungary

institute: University of Debrecen

type: Genome binding/occupancy profiling by genome tiling array


title: Comparison of bone-marrow mesenchymal stromal cells from multiple myeloma patients and healthy donors

city: Brussels

first: Thibaud

last: André

address: Boulevard de Waterloo, 121

country: Belgium

institute: ULB - Jules Bordet Insitute

summary: It is now well established that bone marrow (BM) constitutes a microenvironment required for differentiation. Bone marrow mesenchymal stromal cells (BM-MSCs) strongly support MM cell growth, by producing a high level of Interleukin-6 (IL-6), a major MM cell growth factor. BM-MSCs also support osteoclastogenesis and angiogenesis. Previous studies have suggested that the direct (VLA-4, VCAM-1, CD44, VLA-5, LFA-1, syndecan-1,…) and indirect interactions (soluble factors) between MM plasma cells and BM-MSCs result in constitutive abnormalities in BM-MSCs. In particular, MM BM-MSCs express less CD106 and fibronectin and more DKK1, IL-1β and TNF-α as compared with normal BM-MSCs.  In order to gain a global view of the differences between BM-MSCs from MM patients and healthy donors, we used gene expression profiling to identify genes associated to the transformation of MM BM-MSCs.

overall_design: BM-MSCs were isolated from 3 healthy donors and 4 untreated multiple myeloma patients.  Total RNA from BM-MSCs was exctracted and hybridyzed on Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array. Amplification, hybridization and scanning were done according to standard Affymetrix protocols (www.affymetrix.com). CEL files were normalized with RMA method.

first: N

last: Meuleman

first: B

last: Stamatopoulos

last: De Bruyn

first: K

last: Pieters

first: D

last: Bron

last: Lagneaux


title: IL-2 induced gene expression changes in Kit225 human leukemia cell lines

summary: Identify IL-2 mediated genes in Kit225 cells.

overall_design: IL-2 withdrawn cells were treated with IL-2 or left untreated for 3 hours and then subjected to gene expression microarray analysis.

middle: S


title: Hippocampal expression data from WT, KO, R270X, and G273X mice at 4 and 9 weeks

city: Houston

first: Peng

last: Yu

state: TX

address: 1 Baylor Plaza

institute: BCM

summary:
Mecp2 loss-of-function has been associated with altered gene expression in many tissues. We characterized gene expression changes within the hippocampi of 3 different Mecp2 loss-of-function mouse models.
These studies were used to identify transcriptional differences between these mutants when the mice are largely asymptomatic (4 weeks of age) or have developed overt phenotypes (9 weeks).

overall_design:
Hippocampal expression data from WT (Mecp2+/y), KO (Mecp2-/y), R270X (Mecp2-/y,R270XTg), and G273X (Mecp2-/y,G273XTg) mice at 4 and 9 weeks
At total of 32 microarrays were performed: 4 animals of each genotype at both 4 weeks and 9 weeks of age.

first: Steven

last: Baker

first: Huda

last: Zoghbi


title: Expression data from CtBP knockdown MCF-7 cells

status: Public on Mar 20 2013

city: bethesda

first: Lijun

last: Di

address: 41 center dr

institute: NCI

summary: CtBP is a global co-repressor by serving as transcriptional factor in multiple pathways. CtBP functioned as transcriptional factor by recruiting other cofactors such as G9a, HDAC1 and PcG proteins. CtBP is found to be over enriched in several type of tumor samples. To dipict the role of CtBP in globally regulating gene expression, we applied gene microarray technology to find out what subgroups of genes are mainly affected.

overall_design: 6 MCF-7 cell samples, 3 with CtBP knockdown and 3 with control knock down.

first: Li-jun

first: Kevin

last: Gardner


title: Gene expression profile of the human T-ALL cell line JURKAT after TYK2 and STAT1 knockdown

status: Public on Mar 18 2013

city: Boston

first: Takaomi

last: Sanda

address: 450 Brookline Ave

institute: Dana-Farber Cancer Institute

summary: Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the JAK tyrosine kinase family, TYK2, and its downstream effector STAT1 in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently demonstrated TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK kinase activity induced T-ALL cell death. Activation of this TYK2-STAT1 pathway in T-ALL cell lines occurs by gain-of-function TYK2 mutations or activation of IL-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the anti-apoptotic protein BCL2. These findings indicate that in many T-ALL cases, the leukemic cells are dependent upon the TYK2-STAT1-BCL2 pathway for continued survival, supporting the development of molecular therapies targeting TYK2 and other components of this pathway.

overall_design: Human T-ALL cell line JURKAT cells were transduced with TYK2 (TYK2#2 or #3), STAT1 (STAT1#2 or #3) or control shRNAs (GFP and Luc). Experiment was done in biological duplicate ("dup1" and "dup2") . A total of 12 RNA samples (4 control, 4 TYK2 knockdown and 4 STAT1 knockdown) were used for microarray gene expression analysis.

first: A

middle: T

last: Look


title: Expression data from Control, HIRA and CABIN1 knockdown cells

city: Glasgow

first: Peter

middle: D.

last: Adams

address: Switchback Rd, Bearsden

institute: University of Glasgow, Beatson Institute for Cancer Research

summary:
The mammalian HIRA/UBN1/ASF1a complex is a histone chaperone complex that is conserved from yeast (Saccharomyces cerevisiae) to humans. This complex preferentially deposits the histone variant H3.3 into chromatin in a DNA replication-independent manner and is implicated in diverse chromatin regu- latory events from gene activation to heterochromatinization. In yeast, the orthologous complex consists of three Hir proteins (Hir1p, Hir2p, and Hir3p), Hpc2p, and Asf1p. Yeast Hir3p has weak homology to CABIN1, a fourth member of the human complex, suggesting that Hir3p and CABIN1 may be orthologs. Here we show that HIRA and CABIN1 interact at ectopic and endogenous levels of expression in cells, and we isolate the quaternary HIRA/UBN1/CABIN1/ASF1a (HUCA) complex, assembled from recombinant proteins. Mutational analyses support the view that HIRA acts as a scaffold to bring together UBN1, ASF1a, and CABIN1 into a quaternary complex. We show that, like HIRA, UBN1, and ASF1a, CABIN1 is involved in heterochromatinization of the genome of senescent human cells. Moreover, in proliferating cells, HIRA and CABIN1 regulate overlapping sets of genes, and these genes are enriched in the histone variant H3.3. In sum, these data demonstrate that CABIN1 is a functional member of the human HUCA complex and so is the likely ortholog of yeast Hir3p.
We used microarrays to detail the global programme of gene expression after knockdown of HIRA and CABIN1 in 3 replicates

overall_design: HeLa cells were nucleofacted with Dharmacon control siRNA and siRNA to HIRA and CABIN1 and RNA was isolated 72 hours after transfection.

first: Taranjit

last: Rai

first: Tony

last: McBryan

middle: D


title: Expression data from Control, AKT and RAS transduced cells

status: Public on Mar 19 2013

summary:
Mutations in both RAS and the PTEN/PIK3CA/AKT signaling module are found in the same human tumors. PIK3CA and AKT are downstream effectors of RAS, and the selective advantage conferred by mutation of two genes in the same pathway is unclear. Based on a comparative molecular analysis, we show that activated PIK3CA/AKT is a weaker inducer of senescence than is activated RAS. More-over, concurrent activation of RAS and PIK3CA/AKT impairs RAS-induced senescence.
We used microarrays to detail the global programme of gene expression after transduction of AKT and RAS

overall_design: IMR90 cells were transfected with Control, AKT and RAS retrovirus containing medium in 4 replicates.  Fibroblasts were drug selected and kept in drug for duration of experiments.

first: Alyssa

middle: L

last: Kennedy

first: Jennifer

last: Morton

first: Indrani

last: Manoharan

first: David

middle: M

last: Nelson

first: Nigel

middle: B

last: Jamieson

first: Jeff

last: Pawlikowski

first: Brendan

last: Doyle

first: Karin

last: Oien

first: Greg

middle: H

last: Enders

first: Rugang

last: Zhang

first: Owen

last: Sansom


title: Gene expression levels in immortalized B cells from 131 unrelated CEPH-Utah grandparents treated under ER stress.

city: Philadelphia

first: Renuka

last: Nayak

address: 3516 Civic Center Blvd

institute: HHMI, University of Pennsylvania

summary: We used microarrays to examine gene expression levels from 131 unrelated CEPH-Utah grandparents with either DMSO or tunicamycin.

overall_design: We measured gene expression levels in immortalized B cells from 131 unrelated CEPH-Utah grandparents.  Each individual was treated for 8 hours with either DMSO or with 4 ug/ml of tunicamycin.  Gene expression was measured.

middle: R

first: Michael

last: Kearns

first: Vivian

middle: G

last: Cheung


title: Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults

city: Irvine

first: Shlomit

last: Radom-Aizik

address: 101 Academy

institute: University of California, Irvine

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

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

overall_design: Refer to individual Series

first: Dan

last: Cooper


title: Gene expression in pluripotent and TSKM-iPS induction cells.

city: Beijing

first: Tao

last: Cai

address: No. 7 Science Park Road, Zhongguancun Life Science Park

country: China

institute: National Institute Of Biological Sciences, Beijing (NIBS)

summary:
We found that Tet1 (T) can substitute Oct4 and initiates somatic cell reprogramming in combination with Sox2 (S), Klf4 (K) and c-Myc (M). Moreover, the TSKM secondary reprogramming can proceed rapidly with widespread accompanying increase of 5hmC and 5mC at TSS and ES-active regulation regions followed by 5mC-5hmC pattern switchand, and the activation of endogenous Oct4 and Nanog was Tet1 and 5hmC involved in this process.
We used microarray to explore the global expression change during the reprogramming process

overall_design: Examination of gene expression change in 3 different cell lines covering the main stages during the reprogramming process

first: Yawei

last: Gao

first: Jiayu

last: Chen

first: Shaorong


title: Early parity-induced gene expression in total mammary epithelial cells in mice

status: Public on Mar 17 2013

city: Basel

first: Tim

last: Roloff

address: Maulbeerstrasse 66

department: Functional Genomics

country: Switzerland

institute: FMI

summary: This study examined the effect of early pregnancy on the gene expression profile of total isolated mammary epithelial cells in mice.

overall_design: Total mammary epithelial cells were isolated from parous and age-matched virgin control mice. Four independent replicates were assessed per treatment group, resulting in a total of 8 samples.

first: Fabienne

last: Meier-Abt

first: Stephane

last: Thiry

first: Mohamed

last: Bentires-Alj


title: Early parity-induced gene expression in total mammary epithelial cells and mammary cell subtypes in mice


title: Early parity-induced gene expression in mouse mammary cell subtypes

summary: This study examined the effect of early pregnancy on the gene expression profiles of stromal and various epithelial mammary cell subpopulations in mice.

overall_design: Mammary cell subpopulations were isolated from parous and age-matched virgin control mice. Three independent replicates were assessed per cell subpopulation and treatment group, resulting in a total of 35 samples.


title: Knockdown effect of CDK8 and CDK19 in HeLa S3 cell

status: Public on Mar 16 2013

city: San Diego

first: Taiki

last: Tsutsui

state: California

address: 9500 Gilman Dr

department: CMM

institute: UCSD

summary: Mediator complex has been known as pivotal regulator of RNA polymerase II. Mediator complex has two CDK subunits in vertebrates, named CDK8 and CDK19.  To elucidate functional difference between CDK8 and CDK19 in human cell, we employ siRNA mediate knockdown assay using HeLa S3 cell line. According to this assay these CDKs possess highly redundancy in HeLa S3 cell transcription regulation mechanism but in several genes, each CDK shows gene specific regulatory function.

overall_design: HeLa S3 cells were seeded on 6-well plate at 4 x 104 cells per well in 2ml antibiotic free DMEM medium before 24hr transfection. We transfect siRNA using Lipofectamine 2000 (invitrogen) according to its manual and siRNA final concentration in the medium was 20nM. After culturing for 48hr, transfection medium was changed to fresh antibiotic containing medium. Then the cells were incubated for additional 12hr and then RNA was prepared using RNeazy column (QIAGEN). Five μg of prepared RNA was subjected to the gene expression analysis using Human Genome U133 Plus 2.0 (Affymetrix) followed by characterizations with GeneSpring software (Agilent) and Pathway Analysis software (Ingenuity).  In this analysis we employ two individual siRNA against each CDK and three replicates in each condition.

first: Yosiaki

last: Ohkuma


title: Expression data comparing KYSE-140 ESCC cell line CD90+ and CD90- cells

city: Hong Kong

first: Stephanie

last: Ma

address: Rm 47, 1/F, Lab Block, Faculty of Medicine Bldg, 21 Sassoon Rd, Pok Fu Lam

department: School of Biomedical Sciences

country: Hong Kong

institute: The University of Hong Kong

summary: To identify candidate genes involved in enhanced tumorigenicity and metastasis of CD90+ esophageal tumor-initiating cells.

overall_design: The esophageal squamous carcinoma cell (ESCC) cell line KYSE-140 was sorted into CD90+ and CD90- populations by flow cytometry. Total RNA was analyzed on Affymetrix Human Genome U133 Plus GeneChip 2.0 arrays.


title: Synergistic effects of TRAIL and taurolidine on soft tissue sarcoma cell lines

city: Essen

first: Ludger

last: Klein-Hitpass

address: Virchowstr. 173

department: Universitaetsklinikum

country: Germany

institute: Institut fuer Zellbiologie

summary:
Microarray analysis revealed differential gene expression patterns of rhabdomyosarcoma (A-204), leiomyosarcoma (SK-LMS-1) and epithelioid cell sarcoma (VA-ES-BJ) cells treated with TRAIL and/or taurolidine.
To explore new therapeutic options in the treatment of sarcomas, we tested the antibiotic taurolidine (TRD) on A-204, SK-LMS-1 and VA-ES-BJ carcinoma cell lines alone and in combination with rhTRAIL (TNF related apoptosis-inducing ligand). Gene expression was analysed by RNA microarray.

overall_design: Cell lines were treated with Taurolidine, Trail and a combination of both and compaired to untreated cells

first: L

first: K

last: Harati

first: A

last: Daigeler


title: Gene expression of cultured HUVECs submitted to different shear stress in the presence or absence of stent procedure

city: Milan

first: Jonica

last: Campolo

state: Milan

address: Piazza Ospedale Maggiore 3

department: CardioThoraco and Vascular, Niguarda Hospital

institute: CNR Institute of Clinical Phisiology

summary:
Many studies have characterized the results of shear stress changes on cultured endothelial cells in different bioreactor systems. However it is still unclear how an invasive intervention like stent procedure may influence the transcriptional response of endothelium.
To study the simultaneous effects of shear stress changes and stent application on endothelial gene expression, we have used an experimental apparatus of laminar flow bioreactor (LFB) system with human cultured endothelial cells exposed or not exposed to stent procedure with different flow conditions. Microarray analysis was evaluated in each experimental protocol.

overall_design: HUVECs (2nd and 5th passage) covered on Thermanox slides were submitted to static, low and physiological (0, 1, 5 and 10 dyne/cm2) shear stress in absence (AS) or presence (PS) of stent in LFB system for 24h. Affymetryx analysis has been performed in duplicate by Consortium for Genomic Technologies (Cogentech; Milan, Italy)

first: Federico

last: Vozzi

first: Lorena

last: Cozzi

first: Silvana

last: Penco

first: Oberdan

last: Parodi


title: Microarray analysis of MCF7 cells treated with NSC 59687 (Oxyphenisatin Acetate)

status: Public on Mar 13 2013

city: Frederick

first: Luke

middle: Hunter

last: Stockwin

address: Ft. Detrick

department: DTP

country: USA

institute: NCI Frederick

summary:
NSC 59687 (oxyphenisatin acetate) is a novel anti-cancer agent with selectivity for breast and ovarian cell lines
To elucidate the transcripts differentially regulated following treatment with Oxyphenisatin acetate (NSC 59687)

overall_design: MCF7 cells were treated with 10 microM NSC 59687 for 24 hours followed by RNA extraction, cDNA synthesis and microarray analysis using Affymetrix huU133 plus 2.0 arrays

first: Dianne

last: Newton


title: Neuroblastoma cell line profiling

city: Amsterdam

first: Richard

last: Volckmann

state: Noord-Holland

address: van der Boechorststraat 6a

department: Laboratory of Experimental Oncology and Radiobiology

country: Netherlands

institute: msterdam UMC and University of Amsterdam

summary:
24 standard human Neuroblastoma Cell lines were profiled without applying any transfections in order to measure the expression profiles.
Keywords: cell line, neuroblastoma, mRNA profiling.

This dataset can be visualized and analyzed in the R2 platform: http://r2.amc.nl

overall_design: 24 human Neuroblastoma cell line samples were analyzed


title: Gene expression of CpG-activated memory B cells

city: Rochester

first: Stephen

last: Welle

address: 601 Elmwood Avenue

institute: University of Rochester

summary: During the human B cell (Bc) recall response, rapid cell division results in multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined with cytokines, causes Bc activation and division in vitro and increased CD27 surface expression in a sub-population of Bc. We hypothesized that the proliferating CD27lo subpopulation, which has a lower frequency of antibody-secreting cells (ASC) than CD27hi plasmablasts, provides alternative functions such as cytokine secretion, costimulation, or antigen presentation. We performed genome-wide transcriptional analysis of CpG activated Bc sorted into undivided, proliferating CD27lo and proliferating CD27hi subpopulations. Our data supported an alternative hypothesis, that CD27lo cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27lo and CD27hi Bc differentiation.

overall_design: 18 B cell samples from 6 subjects. From each subject, 3 in vitro B cell populations were isolated: undivided cells, proliferating cells with low CD27 (marker of antibody secretion), proliferating cells with high CD27

first: Alicia

last: Henn

first: Martin

last: Zand


title: Human gene expression altered by Human cytomegalovirus (HCMV) Entry

status: Public on Mar 15 2013

city: Los Angeles

first: ANYOU

last: WANG

address: Gonda BLDG

department: Human Genetics

institute: UCLA

summary:
human foreskin fibroblasts were infected with HCMV
We monitor cellular gene expression network altered by HCMV entry using Affymetrix Human Genome U133 Plus 2.0 Array

overall_design: 2 time points were measured, 5min, 25min

first: Anyou

last: Wang


title: Expression data from mouse ES cells after control RNAi (scramble siRNAs) or RNAi specific for Kdm6a treatment.

city: Seattle

first: Joel

last: Berletch

address: 1959 NE Pacific St.

department: Pathology

institute: University of Washington

summary: To address the functional role of KDM6A in the regulation of Rhox genes, male and female mouse ES cells were transfected with a mixture of three small interfering RNA duplexes, each of which targets a different region of Kdm6a mRNA. We found that Kdm6a knockdown in mouse ES cells caused a decrease in expression of a subset of Rhox genes, Rhox6 and 9. Furthermore, Rhox6 and 9 expression was decreased in female ES cells but not male ES cells indicating that KDM6A regulates Rhox gene expression in a sexually dimorphic manner.

overall_design: Mouse ES cells were treated by Invitrogen scramble siRNA duplexes or specific siRNA duplexes and used for RNA extraction and hybridization on Affymetrix microarrays. Four RNA samples from two independent double-RNAi treatments and two single-RNAi treatment in undifferentiated female ES cells PGK12.1, and RNA samples from two single-RNAi treatments in undifferentiated male ES cells WD44 were assayed for expression changes by arrays.

first: Xinxian

last: Deng

first: Christine

last: Disteche


title: Expression data by BRD7552 treatment in PANC-1 cells

status: Public on Mar 10 2013

city: Cambridge

first: Yuan

last: Yuan

address: 7 Cambridge center

institute: Broad Institute

summary:
Three master regulatory transcription factors Pdx1, MafA and Ngn3 have the ability to transdifferentiate pancreatic acinar cells to insulin-producing beta cells in mice. BRD7552 was identified as a small-molecule inducer that can upregulate the expression of Pdx1 in PANC-1 cells by high-throughput qPCR screening.
We used microarrays to illustrate the mechnism of BRD7552 for PDX1 and insulin induction.

overall_design: PANC-1 cells were treated with BRD7552 at 5uM, the mininal concentration for the maximal induction of Pdx1. The RNA was isloated at two time points 6-hour and 72-hour.

first: B

last: Wagner


title: PRAME induced inhibition of retinoic acid receptor signaling-mediated differentiation - a possible target for ATRA response in AML without t(15;17)

city: Berlin

first: Lars

last: Bullinger

address: Augustenburger Platz 1

department: Hematology, Oncology and Tumorimmunology

institute: Charité

summary: Purpose: In acute myeloid leukemia (AML) without retinoic acid receptor (RAR) rearrangement the effect of all-trans retinoic acid (ATRA) is still poorly understood despite an association of NPM1 mutation and ATRA response. Recently, PRAME (preferentially expressed antigen in melanoma) has been shown to be a dominant repressor of RAR-signaling.   Experimental design: Thus, we further investigated ATRA response mechanisms, especially the impact of PRAME expression on ATRA-responsiveness by profiling gene expression in K562 cell lines.  Results: Our data revealed a PRAME-expression associated gene pattern to be significantly enriched for genes involved in the retinoic acid metabolic process. In leukemia cell line models we could demonstrate that retinoic acid-regulated cell proliferation and differentiation are impacted by PRAME expression.  Conclusions: PRAME seems to impair differentiation and to increase proliferation likely via blocking RAR-signaling, which might be reversed by ATRA.

overall_design: For the cell line model GEP was performed using Affymetrix Human Genome U133plus2.0 Array technology according to the manufacturer’s recommendations as previously reported. siRNA and scrRNA treated as well as ATRA treated K562 cells stemming from independent experiments were profiled. Using the BRB Array Tools software package fluorescence ratios were normalized by applying the RMA algorithm and supervised ClassComparison PathwayClassComparison analyses were performed.

first: Jochen

last: Greiner


title: Whole Genome Expression after Hypoxia and  Reoxygenation in the Newborn Mouse Lung, Brain and Eye

city: Oslo

first: Ståle

last: Nygård

address: Institute for Experimental Medical Research, Oslo University Hospital - Ulleval

country: Norway

institute: University of Oslo

summary: Perinatal asphyxia is detrimental to the newborn baby and the use of supplemental oxygen during resuscitation may worsen the prognosis of these babies. The mechanism behind hyperoxic injury is not fully understood and our aim was to investigate four oxygen therapies following hypoxia and these effects on transcriptional activity.

overall_design: A microarray study was performed on 62 C57BL/6 mice randomized into four hypoxia groups (FiO2 0.08, 120 min) reoxygenated with FiO2 0.21, 0.40, 0.60 and 1.0 (30 min), and into two normoxia groups (FiO2 0.21,120 min) reoxygenated with FiO2 0.21 or 1.0, which served as control groups. A 150 min observation time in normoxia followed before animal sacrificing and lung, brain and eye tissue were stored in RNA Later before the microarray analysis were performed.

first: Embjørg

last: Wollen


title: rhSTIP1 induced SAMD1/5 pathway

status: Public on Mar 09 2013

city: TauYau

first: Yun-Shien

last: Lee

state: Taiwan

address: TauYau

department: Dept. Biotechnology

country: Taiwan

institute: Ming Chuan Univ

summary: Stress-induced phosphoprotein 1 (STIP1), a co-chaperone that organizes other chaperones- heat shock proteins (HSP), was recently shown to be secreted by human ovarian cancer cells to induce cell proliferation. In neuronal tissues, binding to prion protein was required for STIP1 to activate the ERK (extracellular regulated MAP kinase) signaling pathways. However, in this study, we found that STIP1 stimulated cell proliferation of ovarian cancer via a bone morphogenetic protein (BMP) signaling pathway, not through the prion-ERK pathway. The STIP1 binding to a BMP receptor, ALK2 (activin A receptor, type II-like kinase 2), was necessary and sufficient to stimulate cancer cell proliferation. The binding of STIP1 to ALK2 activated the SMAD signaling pathway, leading to transcriptional activation of ID3 (inhibitor of DNA binding 3) that promotes cell proliferation. In conclusion, ovarian cancer tissues secrete STIP1 into the local environment and eventually into blood circulation of patients. In an autocrine and/or paracrine fashion, secreted STIP1 stimulates cancer cell proliferation by binding to ALK2 and activating the SMAD-ID3 signaling pathways. Elucidation of the mechanism by which STIP1 stimulates cancer cell proliferation may pave the way for developing novel therapeutic strategies for treatment of ovarian cancer.

overall_design:
SKOV3 cell,treated without rhSTIP1
SKOV3 cell,treated with rhSTIP1
SKOV3 cell,treated without rhSTIP1-2
SKOV3 cell,treated with rhSTIP1-2


title: Expression data from human multiple myeloma cells with or without IRE1-XBP1 silencing

city: Toronto

first: Rodger

middle: E

last: Tiedemann

state: ON

address: 610 University Avenue

department: Medical Oncology and Hematology

country: Canada

institute: University Health Network, University of Toronto, Princess Margaret Cancer Centre

summary: We used microarrays to develop gene signatures for XBP1 and IRE1 in myeloma cells to explore the role of this UPR/differentiation pathway in proteasome inhibitor resistance.

overall_design: RPMI-8226 and JJN3 human myeloma cells were infected with lentivirus expressing non-targeted (NT) shRNA, shIRE1 or shXBP1 and processed for RNA extraction and hybridization on Affymetrix microarrays. Cells without lentiviral infection were processed as controls for gene expression changes related to the cellular response to lentivirus.


title: 20 mM EtOH on hESCs.

first: Yong

last: Kim

address: 10833 Le Conte Ave

summary: We studied alcohol's effect on human embryonic stem cell line, H9. Our main objective was to delineate the molecular mechanisms that are involved in changing the differentiation potential of hESCs.

overall_design: Undifferentiated and differentiated (Embryoid bodies) hESCs were treated with 0 or 20 mM EtOH in duplicate for 24 hours.

first: Jeffrey

first: Omar

last: Khalid


title: Cell reprogramming requires silencing of a core subset of Polycomb targets.

city: Milano

first: Pasquale

last: Laise

address: Via Adamello,16

institute: IEO

summary: Transcription factor (TF)-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSC) is associated with genome-wide changes in chromatin modifications. Polycomb-mediated histone H3 lysine-27 trimethylation (H3K27me3) has been proposed as a defining mark that distinguishes the somatic from the iPSC epigenome. Here, we dissected the functional role of H3K27me3 in TF-induced reprogramming through the inactivation of the H3K27 methylase EZH2 at the onset of reprogramming. Our results demonstrate that surprisingly the establishment of functional iPSC proceeds despite global loss of H3K27me3. iPSC lacking EZH2 efficiently silenced the somatic transcriptome and differentiated into tissues derived from the three germ layers. Remarkably, the genome-wide analysis of H3K27me3 in Ezh2 mutant iPSC cells revealed the retention of this mark on a highly selected group of Polycomb targets enriched for developmental regulators controlling the expression of lineage specific genes. Erasure of H3K27me3 from these targets led to a striking impairment in TF-induced reprogramming. These results indicate that PRC2-mediated H3K27 trimethylation is required on a highly selective core of Polycomb targets whose repression enables TF-dependent cell reprogramming.

overall_design: Genechip microarray analysis was performed respectively on 4 Ezh2 +/+ iPSC clones (control), 4 Ezh2 ∆SET/∆SET iPSC clones (experimental), 3 independent preparations of wild type MEF (reference) and one sample of E14Tg2a embryonic stem cells (reference) using Affymetrix Mouse Gene 1.0 ST arrays. Labeling, hybridization, and washing were performed according to Affymetrix guidelines

first: Giulia

last: Fragola

first: Pierre-Luc

last: Germain

first: Alessandro

last: Cuomo

last: Blasimme

first: Fridolin

last: Gross

first: Elena

last: Signaroldi

first: Gabriele

last: Bucci

first: Cesar

last: Sommer

first: Giancarlo

last: Pruneri

first: Giovanni

last: Mazzarol

first: Tiziana

last: Bonaldi

first: Gustavo

last: Mostoslavsky

first: Stefano

last: Casola

first: Giuseppe

last: Testa


title: Functional DNA methylation is accompanied by chromatin accessibility [methylation]

status: Public on Mar 08 2013

first: Kurinji

last: Pandiyan

address: 1441 Eastlake Avenue NOR 7344

department: Department of Urology - Norris Comprehensive Cancer Center

institute: University of Southern California

summary: Analysis of nucleosome positioning and chromatin state by using CpG methyltransferase M.SssI to methylate nuclei. Unmethylated regions that gain methylation (low to high beta value) are known to be accessible and nucleosome depleted. Method used to study changes after epigenetic drug treatments identified that majority of demethylation events are not accompanied by chromatin accessibility changes.

overall_design: Intact nuclei are harvested from cells and treated with M.SssI. DNA is then extracted, bisulfite converted and run on an Infinium methylation array, along with a no-enzyme control. Background subtracted beta values (listed below) are used to determine regions that have gained methylation on enzyme treatment compared to the control - and these are used to infer chromatin state

first: Gangning

last: Liang


title: AcceSssIble: an array-based assay for the study of chromatin accessibility and DNA methylation using the CpG methyltransferase SssI

summary: Analysis of nucleosome positioning and chromatin state by using CpG methyltransferase M.SssI to methylate nuclei. Unmethylated regions that gain methylation (low to high beta value) are known to be accessible and nucleosome depleted.


title: Effect of Ribavirin on Viral Kinetics and Liver Gene Expression in Chronic Hepatitis C

city: Bethesda

first: Yaron

last: Rotman

address: 10 Center Drive, Bldg 10, Room 9C434

department: Liver Diseases Branch

institute: NIH, NIDDK

summary: Background/Aims: Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C.  Methods: 70 treatment-naïve patients were randomized to 4 weeks of ribavirin (1000-1200 mg/d) or none, followed by PEG-IFN alfa-2a and ribavirin at standard doses and durations. Patients were randomized to undergo a liver biopsy either 24 hours before, or 6 hours after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by the nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10.  Results: After four weeks of ribavirin monotherapy, HCV levels decreased by 0.5±0.5 log10 (p=0.009 vs. controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting the induction of ISGs by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs. 22% non-responders, p=0.01; early virological response, 100% vs. 68%, p=0.03, sustained virological response 83% vs. 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC.   Conclusion: Ribavirin is a weak antiviral but its clinical effect in combination with PEG-IFN seems to be mediated by a separate, indirect mechanism, which may act to reset the interferon responsiveness in HCV-infected liver. Ribavirin pretreatment does not alter the clinical outcome of subsequent combination therapy.

overall_design: Analysis of liver biopsy samples from 52 patients under 4 different treatment conditions.


title: AcceSssIble Assay to Study the Chomatin Accessibility and DNA Methylation

type:
Methylation profiling by array
Expression profiling by array

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

overall_design: Refer to individual Series


title: Gene expression analysis of human CD4+ T cells differentiated into Th17 cells in the presence of high-salt

status: Public on Mar 07 2013

city: New Haven

first: Markus

last: Kleinewietfeld

address: 300 George St

institute: Yale

summary:
Th17 cells are believed to be a critical cell population for driving autoimmune diseases. However, environmental factors that are directly related to the development of Th17 cells are largely unknown.
High-salt (NaCl) concentrations enhance Th17 differentiation of human naive CD4+ T cells in vitro. The aim of the study was to analyse the changes in gene expression induced by high-salt conditions during Th17 differentiation.

overall_design: Naive human CD4+ T cells were in vitro differentiated into Th17 cells in the presence or absence of high-salt. We arrayed 2 different donors for each condition (control & high-salt).

first: Arndt

last: Manzel

first: Nir

last: Yosef

first: Ralf

middle: A

last: Linker

first: Dominik

middle: N

last: Muller

first: David

last: Hafler


title: Gene-expression profile of Id2+ versus Id2KO KLRG1lo cells during infection

city: San Diego

first: John

middle: Adam

last: Best

address: 9500 Gilman Dr

institute: UCSD

summary: CD8+ T cells play a crucial role in the clearance of intracellular pathogens through the generation of cytotoxic effector cells that eliminate infected cells and long-lived memory cells that provide enhanced protection against reinfection. We have previously shown that the inhibitor of E protein transcription factors, Id2, is necessary for accumulation of effector and memory CD8+ T cells during infection. Here we show that CD8+ T cells lacking Id2 did not generate a robust terminally-differentiated KLRG1hi effector population, but displayed a cell-surface phenotype and cytokine profile consistent with memory precursors, raising the question as to whether loss of Id2 impairs the differentiation and/or survival of effector-memory cells. We found that deletion of Bim rescued Id2-deficient CD8+ cell survival during infection. However, the dramatic reduction in KLRG1hi cells caused by loss of Id2 remained in the absence of Bim, such that Id2/Bim double-deficient cells form an exclusively KLRG1loCD127hi memory precursor population. Thus we describe a role for Id2 in both the survival and differentation of normal CD8+ effector and memory populations.

overall_design: Gene-expression analysis of Wild-type, Id2KO, Id2KOBimKO and BimKO effector CD8+ cells on day 6 of Listeria infection. 2 or more replicates per sample were analyzed.

first: Jamie

last: Knell

first: J

first: Nicholas

last: Lind

first: Edward

last: Yang

first: Louise

last: D'Cruz

first: Ananda

last: Goldrath


title: Transcriptional profile of AML xenografts treated with either PBS or a combination of decitabine and cytarabine

status: Public on Mar 06 2013

city: Birmingham

first: sarah

last: leonard

address: Edgbaston

department: School of cancer sciences

institute: University of Birmingham

summary: The Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D).

overall_design: PBS vs each drug combination

first: Sarah

last: Leonard


title: PRC1 coordinates timing of sexual differentiation of female primordial germ cells

status: Public on Mar 14 2013

city: Basel

first: Tim

last: Roloff

address: Maulbeerstrasse 66

institute: FMI

summary: In mammals, sex differentiation of primordial germ cells (PGCs) is determined by extrinsic cues from the environment1. In female PGCs, expression of Stimulated by retinoic acid 8 (Stra8) and meiosis are induced in response to retinoic acid (RA) provided by the mesonephroi2-4. Given the widespread role of RA signaling during development8,9, the molecular mechanism specifying the competence of PGCs to timely express Stra8 and enter meiosis are unknown2,10. Here we identify gene dosage dependent roles in PGC development for Ring1 and Rnf2, two central components of the Polycomb Repressive Complex 1 (PRC1)11,13. Both paralogs are essential for PGC development between day 10.5 and 11.5 of gestation. Rnf2 is subsequently required in female PGCs for maintaining high levels of Oct4 and Nanog expression6, and for preventing premature induction of meiotic gene expression and entry into meiotic prophase. Chemical inhibition of RA signaling partially suppresses precocious Oct4 down-regulation and Stra8 activation in Rnf2-deficient female PGCs. Chromatin immunoprecipitation analyses show that Stra8 is a direct target of PRC1 and PRC2 in PGCs. These data demonstrate the importance of PRC1 gene dosage in PGC development and in coordinating the timing of sex differentiation of female PGCs by antagonizing extrinsic RA signaling.

overall_design: Gene expression of mouse primordial germ cells was analysed using Affymetrix microarray. Primodial germ cells were purified from embryos carrying Oct4(deltaPE)-GFP transgene by FACS.

first: Shihori

last: Yokobayashi

first: Hubertus

last: Kohler

middle: C

first: Antoine

last: Peters


title: Identification of targets regulated by HSF1 in response to HSP90 inhibitors

first: Yaoyu

last: Chen

state: MASSACHUSETTS

address: 250 Massachusetts Ave

institute: Novartis institution of biomedical research

summary: A375 cells with inducible knockdown HSF1 with and without HSP90 inhibitor treatment

overall_design: A375 cells were seeded in 6-well plates for 3d with 100ng/ml doxycycline prior to treatment with 0.1% DMSO or 100nM HSP990 for 3h

first: Jinyun

first: Wenlai

last: Zhou


title: Genome-wide mRNA expression analysis of the impact of electron radiation on Daltons lymphoma ascites cells in vivo

status: Public on Mar 05 2013

city: Madurai

first: Kumaresan

last: Ganesan

state: Tamil Nadu

address: School of Biological Sciences,

department: Genetics

country: India

institute: Madurai Kamaraj University

summary:
The gene expression changes induced upon electron radiation in cancer cells is largely unexplored. We investigated the effect of electron radiation generated from 8 MeV Microtron in Daltons lymphoma ascites (DLA) cells bearing mice model. Mice implanted with DLA cells in their peritoneal cavity were exposed to 2 Gy dose of electron radiation. 48 Hours after irradiation, tumor cells were harvested from peritoneal cavity of both treatment-naive and total body irradiated mice.
Microarray based genome-wide mRNA profiling approach was used to identify the differentially expressed genes between control and treated groups. 249 genes were found altered in DLA cells upon electron irradiation, of which 176 genes were upregulated and 73 genes were downregulated. The microarray results from this study were validated using reverse transcriptase PCR (RT-PCR) for selected candidate genes. In summary, total body irradiation with 8 MeV electrons has potential to inhibit the tumor cell proliferationin in vivo lymphoma model with the changes in specific signaling pathways and gene expression.

overall_design: Mice implanted with DLA cells in their peritoneal cavity were exposed to 2 Gy dose of electron radiation. Total RNA was isolated from DLA cells retrieved from  control (treatment-naive) and irradiated mice (2 Gy) at 48 hours after radiation exposure.

first: Ramani

last: Gopal


title: Gene x environment effect of serotonin transporter genotype and acute stressor on amygdala gene expression

city: Muenster

first: Christa

last: Hohoff

address: Albert-Schweitzer-Campus 1, A9

department: Psychiatry

institute: University of Muenster

summary:
The amygdala is a prominent region of the brain processing stress-related emotion and vigilance. Additionally it is known that the serotonergic system is strongly involved in stress response and adaptation. The serotonin transporter (5-HTT) as key regulator of serotonergic activity in the brain is associated with stress-related neuropsychiatric disorders as well as heightened trait anxiety/dysphoria and exaggerated response to fear and environmental stress in humans. Also 5-HTT knockout mice display increased anxiety- and depression-related behaviors, altered stress reactivity and stress-coping abilities, gene expression differences and altered dendritic morphology.
We measured immediate reactions to an acute stressor in 5-HTT knockout mice vs. wildtypes using microarrays for genome wide gene expression profiling in the amygdala and identified different functional clusters dependent on condition and genotype.

overall_design: Global amygdalar gene expression profiles were compared between 5-HTT knockout vs. wildtype mice in the conditions control vs. acute stressor in a total sample of 20 (5 biological replicates per genotype and condition).

first: Ali

last: Gorji

first: Sylvia

last: Kaiser

first: Edith

last: Willscher

first: Eberhard

last: Korsching

first: Oliver

last: Ambrée

first: Volker

last: Arolt

first: Klaus-Peter

last: Lesch

first: Norber

last: Sachser

first: Jürgen

last: Deckert

first: Lars

last: Lewejohann


title: Epigenome analysis of buccal cells from monozygotic and dizygotic twins

city: NEDLANDS

first: David

last: Martino

state: Western Australia

address: Perth Childrens Hospital, 15 Hospital Avenue

institute: Telethon Kids Institute

summary: Using the Infinium HM450 platform, we have performed a longitudinal study of DNA methylation at birth and age 18 months in DNA from buccal swabs from 10 monozygotic (MZ) and 5 dizygotic (DZ) twin pairs from the Peri/postnatal Epigenetic Twins Study (PETS) cohort.

overall_design: Beta methylation measurements from bisulphite-converted DNA and raw intensity values from 53 samples. Samples were collected at birth ('_B') or 18 months ('_18m'). Data were preprocessed using the Minfi package in R by the 'illumina' method and normalized to control probes. Subset quantile normalization was performed on type 1 and type 2 probes. Probes failing P detection cutoff of <0.01 were removed. Probes on the X and Y chromosomes have been removed from the processed data. Outlier samples were removed. Between-array quantile normalization was performed to arrive at the final data set of 330168 probes and 53 samples.

middle: J

first: Richard

last: Saffery

first: Jeff

last: Craig