city: Basel

first: Tobias

last: Heckel

address: Grenzacherstr. 124

department: pRED

institute: Roche

summary:
We used microarrays to detail the transcriptome-wide gene expression changes underlying chemical conversion of human fibroblasts into induced Schwann Cells over a time period of 39 days. We compared then the expression profiles of these induced Schwann Cells to primary Schwann cells.
The gene expression results analyzed in this study are further described in Thoma et al. (2014) Chemical conversion of human fibroblasts into functional Schwann cells. Under submission

overall_design: Human fibroblasts were selected at successive stages of the chemical conversion process towards induced Schwann cells for RNA extraction and hybridization on Affymetrix HG-U133_plus_2 microarrays.

first: Eva

middle: C

last: Thoma


title: Expression data from odontogenic tumours

status: Public on Dec 02 2014

city: Turku

first: Kristiina

last: Heikinheimo

address: Lemminkäisenkatu 2

department: Department of Oral and Maxillofacial Surgery

country: Finland

institute: University of Turku

summary: The aim of the study was to elucidate the cellular origin of ameloblastoma and keratocystic odontogenic tumour, neoplasms believed to arise from dental epithelial cells, by carrying out a genome-wide expression analysis.

overall_design: Total RNA from 27 fresh tumour samples of 15 conventional intraosseous ameloblastomas and 12 sporadic keratocystic odontogenic tumours, and 8 control samples were hybridized on Affymetrix® GeneChip Human Genome U 133 Plus 2.0 arrays. The key findings were verified by quantitative real-time PCR (QPCR) and immunohistochemistry.

first: Asta

last: Laiho


title: Reinforced STAT3 activity sustains self-renewal of human embryonic stem cells in a naive-like state

status: Public on Dec 01 2014

city: Bron

first: Pierre-Yves

last: Bourillot

address: 18 Avenue du Doyen Lépine

country: France

institute: INSERM U1208

summary:
Only rodent embryonic stem (ES) cells can self-renew in the pristine state of pluripotency called the naive or ground state. Human ES (hES) cells self-renew in the so-called primed state of pluripotency, which is an obstacle to research, hindering cost-effective cultivation in media devoid of animal-derived products, genetic stability, and genome engineering. Here we show that forced expression of a hormone-dependent STAT3-ERT2, in combination with LIF and inhibitors of MEK and GSK3beta, allows hES cells to escape from the primed state, and enter a new state designated as TL2i, characterized by the activation of STAT3 target genes, regular passaging by single cell dissociation, and the expression of naive state-specific transcription factors.
We used microarrays to analyse the gene expression changes occuring during the adaptation to the naive culture conditions. We then compared our dataset to previously published dataset of mouse ESc and EpiSc, human primed and naive ESc, and human embryos.

overall_design:
Human ES cells were genetically modified to overexpress the STAT3-ERT2 transcription factor. The modified cells were then cultured, on MEFs, in different conditions : (i) F = bFGF, (ii) TL =  LIF + Tamoxifen, (iii) TL2i = LIF + Tamoxifen + MEK inhibitor +GSK3b inhibitor.
We overexpressed STAT3-ERT2 in two different human ES cell lines : the H9 cell line and a cell line newly derived in our lab, designated Oscar. We analysed two clones H9-STAT3T-ERT2 (cl2 and cl14) and one clone Oscar-STAT3-ERT2. The TLOscar wer reverted to bFGF culture condition. We included three biological replicates per condition.

first: Hongwei

last: Chen

first: Pierre

last: Savatier


title: Expression data from human femoral artery atherosclerotic lesions

city: Kuopio

first: Einari

last: Aavik

address: Neulaniementie 2

department: A.I. Virtanen Institute

institute: University of Eastern Finland

summary:
Paired samples from human femoral artery lesions were obtained during intravascular surgery exploiting Silverhawk device
Microarrays were used to identify genes differentially regulated in human femoral artery atherosclerotic and corresponding restenotic plaques

overall_design: Human femoral atherosclerotic lesions collected during atherectomy

first: Olli

last: Leppänen

first: Kaisa

last: Häkkinen

first: Ulrich

last: Beschorner

first: Thomas

last: Zeller

first: Seppo

last: Ylä-Herttuala


title: The DNMT1 associated lncRNA Dali is an epigenetic regulator of neural differentiation [2]

status: Public on Dec 03 2014

city: Oxford

first: Vladislava

last: Chalei

address: Sherrington building, Parks road

department: MRC FUnctional Genomics Unit, Department of Physiology, Anatomy and Genetics

country: United Kingdom

institute: University of Oxford

summary: Many intergenic long noncoding RNA (lncRNA) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic lncRNAs commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal RNA-dependent roles of Dali, a conserved central nervous system expressed intergenic lncRNA. Dali is transcribed downstream of the Pou3f3 transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally, Dali transcript regulates transcription of the Pou3f3 locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the POU3F3 protein. Dali interacts with the DNMT1 DNA methyltransferase in mouse and human and regulates DNA methylation status of CpG island-associated promoters in trans. These results demonstrate, for the first time, that a single intergenic lncRNA controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes.

overall_design: Proliferating and retinoic acid (RA-) differentiated N2A cells stably transfected with a non-targeting (scrambled) control vector were compared to proliferating and RA-differentiated N2A cells stably transfected with a Dali knockdown construct. Three biological replicates of each cell type and condition were analysed on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.

first: Stephen

middle: N

last: Sansom

first: Lesheng

last: Kong

first: Sheena

last: Lee

first: Juan

last: Montiel

first: Keith

middle: W

last: Vance

first: Chris

middle: P

last: Ponting


title: Gene expression profile (GEP) of siRNA-JARID2 CD34+ cells

city: Modena

first: Rossella

last: Manfredini

address: Via Gottardi 100

department: Life Sciences

country: Italy

institute: Centre for Regenerative Medicine

summary:
JARID2 is a chromatin remodeler, member of the Jumonji family of transcription factor genes that belongs to the polycomb repressive complex 2 (PRC2) (Peng JC et al. Cell 2009) and is frequently deleted in leukemic transformation of chronic myeloid malignancies (Puda A et al. Am J Hematol. 2012). In this work, we compared gene expression profile (GEP) of CD34+ cells from Primary Myelofibrosis (PMF) patients with healthy donors and we found JARID2 among downregulated genes. In addition, integrative analysis of gene and miRNA profiles highlighted JARID2 as a shared target of several miRNAs aberrantly expressed in PMF CD34+ cells. Since the role of JARID2 in normal and malignant hematopoiesis has never been investigated, we performed JARID2 silencing experiments on normal Cord Blood (CB) CD34+ cells to evaluate its involvement in proliferation and commitment. Therefore, CD34+ cells were transfected with a mixture of 3 Silencer Select siRNAs targeting JARID2 mRNA and with a non-targeting siRNA as control (NegCTR). The expression level of JARID2 in control samples and JARID2-siRNA cells was assessed by QRT-PCR at 24h (RQ 0,2 ± SEM 0,036, p <.001) and 48h (RQ 0,32 ± SEM 0,026, p<.001) after the last nucleofection.
Flow cytometric analysis of CD41 Megakaryocyte (MK) lineage differentiation marker performed on serum-free multilineage culture at day 8, 10 and 12 pointed out that JARID2 inhibition induces a significant increase in the MK fraction compared to NegCTR sample. In addition, we demonstrated that JARID2 silencing induces a remarkable increase in percentage of CFU-megakaryocyte (CFU-MK) colonies and a strong decrease of non-megakaryocyte colonies (CFU non-MK) in collagen-based clonogenic assay. Moreover, morphological evaluation of May-Grunwald-Giemsa (MGG)–stained cytospins of TPO treated cells at day 8, 10 and 12 after the last nucleofection clearly displayed a considerable enrichment in MK precursors at different stages of maturation in JARID2-siRNA sample compared to NegCTR. Finally, to better characterize changes in gene expression induced by JARID2 gene silencing, we performed mRNA expression profile microarray analysis in NegCTR and JARID2-siRNA CD34+ cells.

overall_design: Gene expression profile (GEP) was performed on total RNA derived from three independent experiments at 24h after the last nucleofection.

first: Valentina

last: Pennucci

first: Ruggiero

last: Norfo

first: Roberta

last: Zini

first: Simona

last: Salati

first: Elisa

last: Bianchi

first: Zelia

last: Prudente

first: Giorgia

last: Sacchi

first: Samantha

last: Ruberti

first: Enrico

last: Tagliafico


title: 6KR-EGFR expressing MCF7 following EGF or HRG stimulation

city: Yokohama

first: Mariko

last: Okada-Hatakeyama

state: KANAGAWA

address: 1-7-22 Suehiro-cho, Tsurumi-ku

department: IMS

country: Japan

institute: RIKEN

summary: EGF and HRG, growth factor ligands for EGFR and ErbB3/4 receptor, induce transient and sustained ERK activity associated with cellular proliferation and differentiation of MCF-7 cells, respectively. To rigorously analyze the effect of ERK signal duration for mRNA expression dynamics and its relationship with cell determination, we modified the EGF-triggered ERK signal duration by changing the EGFR activation dynamics by impairing the ubiquitination and degradation process. Mutation of the six lysine residues (6KR; K692, K713, K730, K843, K905 and K946) of the EGFR responsible for ubiquitin conjugation has shown sustained phosphorylation of the receptor (Huang et al, 2006; Goh et al, 2010). Therefore we constructed the MCF-7 cell lines that stably express 6KR EGFR (6KR), and analyzed signaling and mRNA expression dynamics in response to EGF and HRG.

overall_design: 6KR-EGFR (6KR) expressing MCF7 human breast cancer cells were stimulated by the growth hormone (epidermal growth factor (EGF) or heregulin (HRG)). Control was set as non-treated cells.


title: Gene expression profiles of lymphoma cells in homozygous Tet2 gene trap mice and CD4+ control cells.

city: Tsukuba

first: Hideharu

last: Muto

state: Ibaraki

address: 1-1-1 Tennodai

department: Hematology

institute: University of Tsukuba

summary:
TET2 is an enzyme for converting methylcytosine (mC) to hydorxymethylcytosine (hmC) and its mutations have been frequently found in myeloid malignancies and T-cell lymphoma in humans. We analyzed Tet2 gene trap mice and found that homozygous mice developed T-cell lymphoma with follicular helper T-cell-like features.
To examine comprehensive gene expression patterns of lymphoma cells, We performed gene expression analysis using lymphoma cells in homozygousTet2 gene trap mice and CD4+ control cells.

overall_design: Two pairs of total RNA were extracted from CD4+ lymphoma-developed splenocytes in homozygous Tet2 gene trap mice and CD4+ splenocytes in wild type control mice. Gene expression array was performed with these 4 samples.

first: Mamiko

last: Sakata-Yanagimoto

first: Genta

last: Nagae

first: Yasuyuki

last: Miyake

first: Terukazu

last: Enami

first: Yuhei

last: Kamada

first: Kazuhiko

last: Uchiba

first: Naoshi

last: Obara

first: Kazumi

last: Suzukawa

first: Naoya

last: Nakamura

first: Hiroyuki

last: Aburatani

first: Seishi

last: Ogawa

first: Shigeru

last: Chiba


title: Gene expressional comparison of in vitro adipocyte models vs. in vivo eWAT

city: Debrecen

first: Zoltan

last: Simandi

address: Egyetem ter 1

department: BMBI

country: Hungary

institute: University of Debrecen

summary:
Comparison of gene expression level of 3T3-L1, PMEF and ES cell derived adipocytes to eWAT samples.
We used microarray to investigate the gene expressional differences between different cellular models of adipocyte differentiation vs. in vivo eWAT tissues

overall_design: 3T3-L1 cells, Primary Mouse Embryonic Fibroblasts (PMEFs) and mouse embryonic stem cells (mESCs) were differentiated to adipocytes as it is described in details in the manuscript. eWAT tissues has been isolated from healthy wild-type mice. Each in biological triplicates.

first: Ixchelt

last: Monroy

first: Szilard

last: Poliska

first: Laszlo

last: Nagy


title: p38 MAPK activation upregulates pro-inflammatory pathways in skeletal muscle cells from insulin resistant type 2 diabetic patients

city: Newcastle

first: Mark

last: Walker

address: Framlington Place

department: Institute of Cellular Medicine

institute: Newcastle University

summary:
Skeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake is decreased in differentiated diabetic myotubes in keeping with a retained genetic/epigenetic defect of insulin action.
Microarray analysis was used to investigate differences in gene expression with differentiation in diabetic cultures compared to controls.

overall_design: Muscle biopsies were obtained from type 2 diabetics with a family history of type 2 diabetes and clinical evidence of marked insulin resistance and age-and BMI-matched controls. Muscle cell cultures were derived from these biopsies and RNA extracted from both myoblasts and myotubes for gene expression analysis.

first: Audrey

last: Brown


title: Expression data from D3, siSCR, siPRMT1 and siPRMT8 ES cell derived neurons

summary:
PRMT1 and PRMT8 knockdown D3 embryonic stem cells were generated (siPRMT) or as a control, scrambled sequence was introduced (siSCR).
We used microarray to investigate the effect of PRMT1 and PRMT8 in early embryonic neurogenesis.

overall_design: PRMT1 and PRMT8 knockdown D3 embryonic stem cells were generated (siPRMT1 or 8) or as a control, non-modified (D3) cells were used. We also used non target control, this case scrambled sequence was introduced (siSCR). Samples were collected at day 16 of differentiation and used for microarray. Three replicates each.

first: Z

first: L


title: Chronic SAHA in mouse frontal cortex

city: New York

first: Javier

last: Gonzalez-Maeso

state: NY

address: One Gustave L. Levy Place

department: Psychiatry

country: USA

institute: Mount Sinai School of Medicine

summary:
We employed microarray analysis to compare gene expression profiles in mice chronically treated with the HDAC inhibitor SAHA.
Several of the differentially expressed genes were specifically associated to mechanisms that govern cellular assembly and/or synaptic connectivity

overall_design: Mice were chronically (21 days) treated with SAHA (Suberoylanilide hydroxamic acid; vorinostat) (20 mg/kg ip), or vehicle, and sacrificed one day after the last injection. The day of the experiment, mice were sacrificed by cervical dislocation, and bilateral frontal cortex was dissected.

first: Mitsumasa

last: Kurita

first: Li

last: Shen

first: Tearina

last: Chu


title: DNA methylation study in breast cancer [methylation]

status: Public on Nov 30 2014

city: Hannover

first: Jessica

last: Rößler

address: Carl-Neuberg Str. 1

department: Pathology

country: Germany

institute: Medical School Hannover

type: Methylation profiling by genome tiling array

summary: Addressing the still unresolved question of the existence of CIMP in breast cancer DNA methylation alterations among histological breast cancer subtypes were examined by applying the HM450K BeadChip of Illumina Inc., covering about 480,000 single CpG sites. In addition to the occurrence of the hypermethylator phenotype in breast cancer, its relation to genetic instability and histological subtypes was investigated.

overall_design: Bisulfite converted DNA from 32 fresh-frozen primary breast tissue samples and 4 breast cancer cell lines were hybridized onto the HumanMethylation 450K BeadChip from Illumina Inc. Additionally, 28 of these primary samples were analyzed by array-based comparative hybdridization (aCGH).

first: Ulrich

last: Lehmann

first: Ole

last: Ammerpohl

first: Jana

last: Gutwein

first: Doris

last: Steinemann


title: Differential gene expression in neuroblastoma cells after transfection with control siRNA or linc00467 siRNA

city: Randwick, Sydney

first: Tao

last: Liu

state: NSW

address: Lowy Cancer Research Centre UNSW

country: Australia

institute: Children's Cancer Institute Australia

summary:
N-Myc oncoprotein induces neuroblastoma by modulating gene transcription, and long noncoding RNAs exert biological effects by regulating gene expression. We have found that one of long noncoding RNAs modulated by N-Myc is linc00467.
We analysed the target genes of the long noncoding RNA linc00467 in neuroblastoma cells.

overall_design: Neuroblastoma BE(2)-C cells were transfected with control siRNA or linc00467 siRNA. RNA was extracted from the cells 48 hours after siRNA transfections, and subjected to differential gene expression studies with Affymetrix microarrays.

first: T


title: DNA methylation study in breast cancer

type: Genome variation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Wide methylation analysis in vestibular schwannoma [Infinium HumanMethylation450 BeadChip]

city: Badalona

first: Miguel

last: Torres-Martin

state: Barcelona

address: Carretera de Canyet, s/n

department: Clinical Genomics Unit

country: Spain

institute: Hospital Universitari Germans Trias i Pujol

summary: Vestibular schwannomas are intracranial tumors that affects unilateral and sporadically or bilateral when is associated to Neurofibromatosis type 2 syndrome. The hallmark of the disease is the biallelic inactivation by NF2 gene mutation or LOH of chromosome 22q, where this gene harbors. In this work, we used  Infinium HumanMethylation 450K BeadChip  microarrays in a series of 36 vestibular schwannomas, 4 non-vestibular schwannomas and 5 healthy nerves. Our results shows a trend to hypomethylation in schwannomas. Furthermore, HOX genes, located at 4 clusters in the genome, displayed hypomethylation in numerous CpG sites in vestibular but not in non-vestibular schwannomas. Additionally, several microRNA and protein-coding genes were found hypomethylated at promoter regions and confirmed by expression analysis; including miRNA-199a1, miRNA-21, MET and PMEPA1. We also detected methylation patterns that might be involved in alternative transcripts of several genes such as NRXN1 or MBP; that would increase the complexity of methylation-expression. Overall, our results shows specific epigenetic signatures in several coding genes and microRNA that could be used in the finding of potential therapeutic targets.

overall_design: 36 vestibular schwannomas, 4 non-vestibular schwannomas and 5 control healthy nerves were used in Infinium HumanMethylation450 BeadChip microarray.

first: Luis

last: Lassaletta

first: Barbara

last: Melendez

first: Juan

middle: A

last: Rey


title: Wide methylation analysis in vestibular schwannoma


title: Large hypomethylated blocks related to large heterochromatin regions as a universal defining epigenetic alteration in human solid tumors

city: Baltimore

first: Winston

last: Timp

state: MD

address: 3400 N. Charles St. Clark 102A

department: Biomedical Engineering

institute: Johns Hopkins University

summary: Examined methylation status using HumanMethylation450 BeadChip for samples from 5 different tissue of normal, hyperplastic, adenoma, cancer and metastatic samples.

overall_design: Bisulfite converted DNA from the samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip.

first: Rafael

middle: I

last: Irizarry

first: Andrew

last: Feinberg


title: Global gene expression analysis of human fibroblasts from whole body

status: Public on Nov 26 2014

city: Chiba

first: Youichi

last: Higuchi

address: 6-5-1 Kashiwanoha, Kashiwa

institute: Research Center for Innovative Oncology National Cancer Center Hospital East

summary:
Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their phenotypical diversity has not been sufficiently explored. The aim of this study was to elucidate the phenotypical diversity of human fibroblasts within the whole body.
Global gene expression analysis of 63 human primary fibroblasts from 13 organs elucidated that fibroblasts from the gastrointestinal tract showed a remarkably distinct character compared to that seen in other organs. Furthermore, gastrointestinal fibroblasts were created by topologically diverse subgroups of fibroblasts depending on their organ and histoanatomical site in the gastrointestinal walls.

overall_design: Global gene expression analysis was performed on 63 human primary fibroblasts from 13 anatomical organs. Of these, 32 fibroblasts from gastrointestinal organs were obtained from a pair of 2 histoanatomical sites, including the submucosal layer (submucosal fibroblasts: SMFs) and subperitoneal layer (subperitoneal fibroblasts: SPFs). Using hierarchical clustering analysis, identifiable phenotypical subgroups of fibroblasts were elucidated and the phenotypical character of each subgroup was analyzed.

first: Motohiro

last: Kojima

first: Genichiro

last: Ishii

first: Kazuhiko

last: Aoyagi

first: Hiroki

last: Sasaki

first: Atsushi

last: Ochiai


title: Polyunsaturated dietary fats decrease mortality and bacterial load during septic S. aureus infection, and improve neutrophil function in mice

status: Public on Nov 24 2014

city: Little Rock

first: Intawat

last: Nookaew

address: 4301 W Markham St

department: Department of Biomedical Informatics

institute: University of Arkansas for Medical Sciences

summary: Severe infections and sepsis is an increasing clinical problem that cause prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of antibiotic resistance is increasing and it is therefore critical to find new therapies for sepsis. Staphylococcus aureus (S. aureus) is a major cause of septic mortality. Neutrophils play a major role in defense against bacterial infections. We have recently shown that a saturated high fat diet decreases survival in septic mice, but the mechanisms behind remain elusive. The aim of the present study was to investigate how the dietary fat composition affects survival and neutrophils function after experimental septic infection in mice.  We found that, after S. aureus infection, mice fed polyunsaturated high fat diet (HFD/P) for 8 weeks had increased septic survival and decreased bacterial load compared with mice fed saturated HFD (HFD/S), and similar to that of mice given low fat diet (LFD). Furthermore, uninfected mice fed HFD/P had increased number of Ly6G+ neutrophils in bone marrow. In addition, mice fed HFD/P had a higher number Ly6G+ neutrophils recruited to the site of inflammation after peritoneal injection of thioglycollate.   In conclusion, polyunsaturated dietary fat increased both survival and the efficiency of the bacterial clearance during septic S. aureus infection. Moreover, this diet enhanced the number and chemotaxis of neutrophils, a key component of the immune response to S. aureus infections.

overall_design: Mice (non-infected) fed saturated high fat diet, low fat diet, or polyunsaturated high fat diet

first: Sara

last: Svahn

first: Louise

last: Grahnemo

first: Maria

last: Johansson

first: John-Olov

last: Jansson

first: Karl

last: Wendt

first: Vilborg

last: Palsdottir

first: Erik

last: Schele

first: Anna

last: Benrick

first: Niklas

last: Andersson

first: Britt

last: Gabrielsson


title: GM-CSF induced gene-regulation in human monocytes

status: Public on Nov 27 2014

city: Muenster

first: Toni

last: Weinhage

address: Roentgenstraße 21

department: Department of Pediatric Rheumatology and Immunology

institute: University Hospital of Muenster

summary: Human and murine studies showed that granulocyte macrophage colony-stimulating factor (GM-CSF) exerts beneficial effects in intestinal inflammation. To explore whether GM-CSF mediates its effects via monocytes, we analyzed effects of GM-CSF on monocytes in vitro and assessed the immunomodulatory potential of GM-CSF-activated monocytes (GMaM). We used microarray technology and functional assays to characterize GMaM in vitro and used a mouse model of colitis to study GMaM functions in vivo.

overall_design: Peripheral blood monocytes where cultured 16 h with media containing AB serum (control monocytes) or media containing 10 ng/mL GM-CSF and AB serum (GM-CSF activated monocytes). In three independent experiments, total RNA from GMaM and control monocytes was isolated and processed for microarray hybridization.

first: Jan

last: Däbritz

first: Georg

last: Varga

first: Timo

last: Wirth

first: Karoline

last: Walscheid

first: Anne

last: Brockhausen

first: David

last: Schwarzmaier

first: Markus

last: Brückner

first: Matthias

last: Ross

first: Dominik

last: Bettenworth

first: Johannes

last: Roth

middle: M

last: Ehrchen

first: Dirk

last: Foell


title: Human ESC-based modeling of pediatric gliomas by K27M mutation in histone H3.3 variant

status: Public on Nov 21 2014

first: Viviane

last: Tabar

state: New York

address: 1275 York Avenue

department: Department of Neurosurgery

institute: Memorial Sloan-Kettering Cancer Center

summary: Human diffuse intrinsic pontine gliomas (DIPG) are an aggressive form of pediatric brain tumors that arise in the pons in young children thus resulting in significant morbidity and very poor survival. Recent data suggest that mutations in the histone H3.3 variant are often found in these tumors, though the mechanism of their contribution to oncogenesis remains to be elucidated. Here we report that the combination of constitutive PDGFRA activation and p53 suppression as well as expression of the K27M mutant form of the histone H3.3 variant leads to neoplastic transformation of hPSC-derived neural precursors. Our study demonstrates that human ES cells represent an excellent platform for the modeling of human tumors in vitro and in vivo, which could potentially lead to the elucidation of the molecular mechanisms underlying neoplastic transformation and the identification of novel therapeutic targets.

overall_design: Human ES cells were differentiated to NPCs and lentivirally transduced with a combination of constitutively active PDGFRA (D842V), sh-p53, and WT or K27M mutant form of histone H3.3 variant.

first: Kosuke

last: Funato


title: Expression data from siSCR and siPRMT1 ES cells

first: Zoltan

last: Simandi

summary:
The major type of protein arginine methyltransferase is PRMT1. Since the growth of embryos from Prmt1−/− mice was arrested shortly after implantation, PRMT1 must play a critical role in early mouse development.
We used microarray to investigate the effect of PRMT1 in early embryonic development.

overall_design: PRMT1 knockdown D3 embryonic stem cells were generated (siPRMT) or as a control, scrambled sequence was introduced (siSCR). To avoid any feeder-cell contamination, the cells were passaged at least 3 times on 0.1% gelatin coated plates before the experiments. Samples were collected and used for microarray from undifferentiated mouse embryonic stem cells, four-day old aggregated embrioid bodies and 12h atRA or DMSO treated embrioid bodies. Three replicates each.

first: Z

first: L

last: Nagy


title: Analysis of 3D- and TRIB1-dependent gene expression in prostate cancer cells

city: Tokyo

first: Tetsuo

last: Mashima

address: 3-8-31, Ariake,Koto-ku

institute: JFCR

summary: A capability to proliferate under the three-dimensional (3D) conditions is a characteristic property of cancer. Therefore, factors that regulate the 3D growth are considered rational targets for cancer therapy. We analyzed  gene expression profile of human prostate cancer PC3 cells which were cultured in normal 2D conditions or in spheroid  culture conditions (3D). The analysis suggested that the sheroid conditions would mimic a part of tumor-like 3D conditions. In addition, we analyzed genes regulated by TRIB1, a candidate oncogene in PC3 cells by comparing the gene expression profiles between control (shGFP)-treated and TRIB1 shRNA- (shTRIB1-1 and shTRIB1-2) treated cells. Our analysis identified a subset of genes that are downstream of TRIB1 in prostate cancer cells.

overall_design: To compare gene expression between 2D and 3D, we prepared PC3 cells  which were cultured in normal 2D conditions or in spheroid  culture conditions (3D) (PC3_2D and PC3_spheroid). To analyze TRIB1-dependent genes, we prepared PC3 cells that expressed control shRNA (shRNA to GFP) or 2 TRIB1 shRNAs (PC3_shGFP, PC3_shTRIB1-1, PC3_shTRIB1-2).

first: Hiroyuki

last: Seimiya


title: Novel DNA methylation targets in oral rinse samples predict survival of patients with oral squamous cell carcinoma

status: Public on Nov 25 2014

city: Cincinnati

first: Scott

last: Langevin

state: OH

address: 160 Panzeca Way, ML0056

department: Department of Environmental Health

institute: University of Cincinnati College of Medicine

summary: Epigenome-wide association study (EWAS) of oral rinse samples from a cohort of 82 oral squamous cell carcinoma (OSCC) patients. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in oral rinse samples.

overall_design: Bisulphite lsconverted DNA from the 82 oral rinse samples were hybridized to the Illumina Infinium HumanMethylation450 Beadchip

first: S

first: K

middle: T

last: Kelsey


title: IDH2 mutation induced histone and DNA hypermethylation is progressively reversed by small molecule inhibition

status: Public on Nov 19 2014

city: Cambridge

first: Andrew

last: Kernytsky

state: Massachusetts

address: 38 Sidney St

institute: Agios

summary: Mutations of IDH1 (R132) and IDH2 (R172 and R140), which produce an oncometabolite 2-hydroxyglutarate (2HG), have been identified in several tumors including acute myeloid leukemia (AML).  Recent studies have shown that expression of the IDH mutant enzymes results in high levels of 2HG and a block in cellular differentiation that can be reversed with IDH-mutant specific small molecule inhibitors. To further understand the role of IDH mutations in cancer, we conducted mechanistic studies in the TF-1/IDH2 R140Q erythroleukemia model system and found that IDH2 mutant expression caused both histone and genomic DNA methylation changes that can be reversed when IDH2 mutant activity is inhibited. Specifically, histone hypermethylation is rapidly reversed within days whereas reversal of DNA hypermethylation proceeds in a progressive manner over the course of weeks. Pathway enrichment analysis revealed several pathways involved in tumorigenesis of leukemia and lymphoma, indicating a selective modulation of relevant cancer genes by IDH mutations.  As methylation of DNA and histones is closely linked to mRNA expression and differentiation, these results indicate that IDH2 mutant inhibition may function as a cancer therapy via short-term histone demethylation and long-term DNA demethylation at genes involved in differentiation and tumorigenesis.

overall_design: TF-1 cells with and without IDH2/R140Q expression were treated with DMSO or AGI-6780, an inhibitor of IDH2/R140Q for 7 to 28 days. Genomic DNA was extracted and analyzed by the Illumina 450k Methylation array.

first: Katharine

last: Yen


title: The permanent reduction of TIA proteins molds expression transcriptome in HeLa cells.

city: Cantoblanco

first: Juan

middle: Carlos

last: Oliveros

state: Madrid

address: Darwin 3

institute: CNB, CSIC

summary: Background: Our recent studies strongly suggest that remodeling in the control of gene expression contributes to the progression of cell phenotypes associated to the transient and permanent knock-down of T-cell intracellular antigen 1(TIA1) and TIA1 related/like (TIAR/TIAL1) proteins. In particular, our studies have been focused on transcriptomic profiling of TIA-depleted HeLa cells using transient RNA interference (siRNA-mediated) and genome-wide microarray approaches Results: This study provides, for the first time, TIA1 and TIAR linked-transcriptomic analysis by using RNA-Seq next generation sequencing technology. Illumina RNA-Seq was used to survey transcriptome profiles from permanent TIA1 and TIAR-(shRNA-mediated) deficient HeLa cells. Analysis of the transcriptomes with the Cufflinks tool revealed that differentially expressed genes, isoforms produced by alternative splicing and/or promoter usage as well as microRNAs generated a great transcriptomic heterogeneity which might reflect the complexity linked to these cell phenoypes. The data of differential expression were validated by using genome-wide microarrays and QPCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment analysis revealed over-representation of genes associated with cell differentiation, multicellular organismal development, signal transduction, axon guidance and cell adhesion and under-representation of genes associated with positive regulation of migration, cell adhesion, response to organic substance, prostaglandin metabolic process and blood coagulation. Conclusions: Taken together, our observations point out towards an inhibitory role of TIA proteins in cell proliferation and growth, there appears to be an apparent molecular discrepancy regarding the effects of TIA proteins based on whether the proteins are depleted transiently (siRNA-mediated) or permanently (shRNA-mediated), suggesting the existence of clonal selection mechanisms of cellular populations in permanently TIA1/TIAR-depleted HeLa cells.

overall_design: For each cell type, three biological replicates were prepared and hybridized to Affymetrix GeneChips (HG U133plus2). 3+3 hybridizations in total for a single comparison KO vs WT.

first: Mario

last: Núñez

first: Carmen

last: Sánchez-Jiménez

first: José

last: Izquierdo


title: Gene expression profiling of NSCLC cell lines upon TGFb-induced epithelial-mesenchymal transition (EMT)

city: South San Francisco

first: Yuting

last: Sun

state: CA

address: 1 DNA Way

department: Discovery Oncology

institute: Genentech

summary: Epithelial-mesenchymal transition has been implicated in tumor metasisi, cancer drug resistance and cancer stem cell features.  In this study, we examined gene expression profiles of three non-small cell lung cancer cell lines, before and after experimentally induced EMT.

overall_design: We modeled epitheial-mesenchyml transition by culturing A549, HCC827 and NCI-H358 cells in the presence of TGFb for three weeks, and compared gene expression profiles of the paretnal cells and cells after EMT.

first: Anneleen

last: Daemen

first: Leisa

last: Johnson

first: Jeffrey

last: Settleman


title: Temporal stability and determinants of white blood cell DNA methylation in the Breakthrough Generations Study

status: Public on Nov 12 2014

city: London

first: James

last: Flanagan

state: London

address: Hammersmith Hospital, Du Cane Rd

department: Surgery and Cancer

institute: Imperial College London

summary:
Background: Epigenome-wide association studies (EWAS) using measurements of blood DNA methylation are performed to identify associations of methylation changes with environmental and lifestyle exposures, and with risk of developing disease. However, little is known about the variation of methylation markers in the population and their stability over time, both important factors in the design and interpretation of EWAS.
Methods: We estimated the intraclass correlation coefficient (ICC) for each probe on the Illumina 450K methylation array in paired samples collected approximately six years apart from 92 participants in the Breakthrough Generations Study. We also evaluated relationships with age, reproductive and hormonal history, weight, alcohol intake and smoking.
Results: Approximately 17% of probes on the 450K array had an ICC>0.50 and were considered stable variable methylated probes (stable-VMPs). Stable-VMPs were enriched for probes located in "shores" bordering CpG islands, and at approximately 1.3kb downstream from the transcription start site in the transition between the unmethylated promoter and methylated gene body. Both cross-sectional and longitudinal data analyses provided strong evidence for associations between changes in methylation levels and ageing. Smoking-related probes at 2q37.1 and AHRR were stable-VMPs and, as previously reported, related to time since quitting smoking. We also observed an excess of associations between methylation and weight changes beyond those expected by chance.
Conclusion: Our results provide support for the use of WBC DNA methylation as a biomarker of exposure in EWAS. Larger studies, preferably with repeated measures over time, will be required to establish associations between specific probes and exposures.

overall_design:
The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across  485,577 CpGs . Samples included each sample taken at baseline and a second blood sample taken on average 6 years later, we include 4 pairs of duplicate samples and in vitro methylated (100%) and unmethylated (0%) control DNA samples.
Bisulphite converted DNA was hybridized to the Illumina Infinium 450k Human Methylation Beadchip

first: Montserrat

last: Garcia-Closas


title: A Randomized, Placebo-Controlled Study to Evaluate SRT2104, a Selective SIRT1 Activator, in Patients with Moderate to Severe Psoriasis

first: Mayte

last: Suarez-Farinas

address: 1425 Madison Ave, L2-70C, Box 1077,

institute: Mount SinaiSchool of Medicine

summary: Activation of Sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, is an unexplored therapeutic approach for treatment of inflammatory diseases. The goal of this study was to evaluate the clinical activity and tolerability of multiple doses of SRT2104, a selective activator of SIRT1, in patients with moderate to severe psoriasis after day 84 of treatment. Forty patients were randomized 4:1 to three escalating doses of SRT2104 (250, 500, 1000 mg/d SRT2104 or placebo). Across all SRT2104 groups, 34.6% of patients (9 out of 26; 90% CI 18.0%-54.2%, p<0.0001) achieved good to excellent histological improvement based on skin biopsies taken at baseline and day 84.  To evaluate the changes in expression profile with treatment and to identify pathways involved in histological improvement, a subset of 22 Pre and Post treatment biopsies from 11 patients (4 Placebo, 7 Active Treatment) were hybridized to hgu133plus2 chips. Improvement in histology was associated with modulation of IL-17 and TNF-_ signaling pathways and keratinocyte differentiation target genes. Various studies suggest a crucial role of TNF_ and IL-17 in psoriasis pathogenesis and IL-17/TNF_ synergism induces a strong induction of differentially expressed genes in psoriasis, thus advocating a crucial role of IL-17/TNF_ combination in the molecular basis of disease (Chiricozzi et al., 2010).  In the current study, broad scale gene expression profiling revealed that SRT2104 significantly reduced known IL-17 and TNF_ responsive genes including SERPINB4, S100A12, SERPINB3, kynu etc. even though the sample size for this analysis was small. One of the most highly modulated genes by SRT2104 included Kynu, a gene that regulates tryptophan metabolism, known to confer antibacterial effector functions (Daubener and MacKenzie, 1999). Interestingly kynu is part of the etanercept residual genomic profile that is not modulated by etanercept therapy even though clinical efficacy is achieved. Possibly, SRT2104 may be modulating the lipid barrier of the epidermis of psoriatic skin via modulation of keratinocyte diferentiation genes, which would be consistent with the observed improvement in skin histology. These results indicate a combinatorial effect of SRT2104 on TNF_, and IL-17 inflammatory signaling pathways and keratinocyte differentiation that could be a contributing factor towards improvement in clinical scores by the SIRT1 activator, SRT2104.

overall_design: Paired  Pre (Day 1) and Post (Day 84) Treatment samples were obtained from 4 Placebo Patients and 7 patients treated with SRT2104 at 3 different doses (250, 500, 1000 mg).

middle: G

last: Krueger

first: Eric

last: Jacobson


title: Cigarette Smoking Reduces DNA Methylation Levels at Multiple Genomic Loci but the Effect is Partially Reversible upon Cessation

first: Tsun-Po

last: Yang

address: Wellcome Trust Genome Campus

department: Human Genetics

institute: Wellcome Trust Sanger Institute

summary: DNA methylation is an epigenetic event whose pattern is altered frequently in a wide variety of human diseases. Smoking affects DNA methylation possibly leading to abnormal expression of a broad spectrum of genes which in turn may result to the various side effects and diseases associated with smoking. The long term effects of smoking have been widely studied but the mechanism(s) by which those effects may be reversible by smoking cessation are not clearly understood. Here, we conducted an epigenome-wide association study in peripheral-blood DNA in 464 individuals who were current, former and never-smokers. We identified 15 distinct loci (10 of which were novel) where DNA methylation was reduced in smokers and was reversed (but did not reach non-smoking levels) upon smoking cessation within 12 weeks. Although the functional impact of this reversal of DNA methylation is still not understood, this study illustrates the potential of epigenomics to provide insights into mechanisms of environmental and lifestyle exposures, and to suggest new avenues for clinical intervention

overall_design: Bisulfite converted DNA from the 464 samples were hybridized to the Illumina Infinium HumanMethylation450 BeadChip

first: Loukia

last: Tsaprouni

first: T

first: Jordana

last: Bell

first: Katherine

middle: J

last: Dick

first: Stavroula

last: Kanoni

last: Nisbet

first: Ana

last: Viñuela

first: Elin

last: Grundberg

first: Christopher

last: Nelson

first: Eshwar

last: Meduri

first: Alfonso

last: Buil

first: Francois

last: Cambien

first: Christian

last: Hengstenberg

first: Jeanette

last: Erdmann

first: Heribert

last: Schunkert

first: Alison

middle: H

last: Goodall

first: Willem

last: Ouwehand

first: Emmanouil

last: Dermitzakis

first: Tim

middle: D

last: Spector

first: Nilesh

last: Samani

first: Panos

last: Deloukas


title: Identification and characterization of retinoic acid-responsive genes in mouse kidney development

status: Public on Nov 14 2014

city: Kyoto

first: Eisuke

last: Nishida

address: Kitashirakawa, Sakyo-ku

department: Department of Cell and Developmental Biology

institute: Graduate School of Biostudies, Kyoto University

summary: Retinoic acid (RA) signaling regulates a variety of developmental processes through controlling the expression of numerous genes. Here, we have identified and characterized RA-responsive genes in mouse kidney development. Analysis of isolated embryonic kidneys cultured in the presence and absence of RA identified 33 candidates of RA-responsive genes. Most of these candidate genes were down-regulated by treatment with the RA receptor antagonist. Many of them have potential binding sites for Elf5, one of the RA-responsive genes, in their promoter region. Whole-mount in situ hybridization demonstrated that specific expression of Elf5 in the ureteric trunk depends on RA. RA-dependent expression in the ureteric trunk was also demonstrated for the sodium channel subunit Scnn1b, which has been shown to be the marker gene of the collecting duct. In contrast, the expression of Ecm1, Tnfsf13b and IL-33 was detected in the stromal mesenchymal cells. Both Tnfsf13b and IL-33 were previously shown to cause NF-κB activation. We have demonstrated that the inhibition of NF-κB signaling with specific inhibitors suppresses branching morphogenesis of the ureteric bud. Our study thus identifies and characterizes RA-dependent upregulated genes in kidney development, and suggests an involvement of NF-κB signaling in the branching morphogenesis.

overall_design:
To obtain genome-wide gene expression profiles of kidneys cultured in 10% FBS DMEM, serum-free DMEM, and serum-free DMEM with RA, we performed microarray analysis on RNA prepared from these three samples.
Total RNA was prepared using the RNeasy Mini Kit (QIAGEN) according to the manufacturer's instruction. Synthesis of cDNA, in vitro transcription and biotin labeling cRNA, and hybridization to GeneChip Mouse Gene 1.0 ST array (Affymetrix) were performed according to Affymetrix protocols.

first: Mami

last: Takayama

first: Koichi

last: Miyatake


title: Gene expression data from murine M1 and M2 macrophages

city: Seoul

first: Yi Rang

address: 101, daehak-ro Jongro-gu

department: Microbiology and Immunology

country: South Korea

institute: Seoul National University College of Medicine

summary:
Macrophages have distinct characteristics depending on their microenvironment. We performed proteomic analysis between M1 and M2 macrophages and found that cellular metabolism is the key regulator of macrophage function.
We used microarray to support proteomic data between M1 and M2 macrophages.

overall_design: M1 macrophages are obtained using cell sorting of CD45+MHCII+CD8a-F4/80+ population from C57BL/6J bone marrow cell derived heterogenous cells under GM-CSF conditioning for 7 days. M2 macrophages are differentiated with 20% L929 cell supernatant for 7 days and sorted from CD45+F4/80+CD11b+ population.

first: Seung

last: Seok

first: Yi

middle: R


title: Distinct phenotype and function of anergic CD8+ T cells produced by Treg-cell suppression.

status: Public on Nov 11 2014

first: Masahide

last: Hamaguchi

address: 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku

department: Department of Endocrinology and Metabolism

institute: Kyoto Prefectural University of Medicine, Graduate School of Medical Science

summary: Four conditions of cultured CD8+ T cells were analyzed with Affymetrix HG-U133-Plus-2.0 microarrays.

overall_design: Peripheral blood samples were obtained from healthy individuals (all of them had CMV-IgG Ab). Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient with Ficoll-Paque (GE Healthcare). All donors provided written informed consent before sampling according to the Declaration of Helsinki. The present study was approved by the institutional ethics committee of Osaka University. CD8+ T cells were purified from PBMCs using CD8 Microbeads (Miltenyi Biotec). Treg cells were sorted as CD25highCD4+ T cells (highest 3% of CD25+CD4+ T cells) with FACS Aria II and Regulatory T cell Isolation kit (Miltenyi Biotec) from PBMCs. Antigen-specific CD8+ T cells were induced as described previously with some modifications. Melan-A-specific CD8+ T cells were detectable by MHC/peptide tetramers (Tet+CD8+ T cells). Tet+CD8+ T cells induced at CD8+ T cells: Treg cells ratio, 1:0.5 and 1:0 were sorted by FACSAria II (BD Bioscience), and subjected to Gene Chip Human Genome U133 Plus 2.0 Array. The data were preprocessed with RMA (Robust Multichip Average) normalization. Genes reportedly associated with CD8+ T-cell dysfunction such as anergy and exhaustion were selected. These gene expressions were compared among 4 groups, Tet(+) with Treg, Tet(+) w/o Treg, Tet(-) with Treg and Tet(-) w/o Treg.

first: Yuka

last: Maeda

first: Hiroyoshi

last: Nishikawa

first: Shimon

last: Sakaguchi


title: Molecular profiling of functional interactions between pre-osteoblastic and breast carcinoma cells

status: Public on Nov 23 2014

city: Tel Aviv

first: Metsada

last: Pasmanik-Chor

address: Ramat Aviv

department: Biology

country: Israel

institute: Tel Aviv University

summary: The relationships between cancer cells and the microenvironment play a critical role in cancer growth and development. The bone stroma consists of mesenchymal stem cells (MSCs) and mature osteoblasts that promote cancer growth. Yet it is not completely understood what are the molecular processes guiding cancer cells progression to the bone. In this study, a co-culture assay and subsequent gene profiling arrays were used to compare the gene expression profile of a pre-osteoblastic cell line (MBA-15) with that of a mammary adenocarcinoma (DA3) cells. Following co-culture, cells were separated by magnetic beads based on the expression of CD326 antigen. RNA was purified and hybridized on gene expression array. The gene expression pattern changes were followed by qRT-PCR. We demonstrate that co-cultured DA3 cells express elevated levels of genes that regulate growth and responses to both hormonal stimulus and wounding, as well as reduced expression of genes related to lipid metabolism. Also, co-cultured pre-osteoblastic cells showed reduced expression of cell-junction genes. The study presents a simplified model system, composed of pre-osteoblastic and mammary cancer cells, that potentially mimics the molecular interactions in the tumor microenvironment which contribute to tumor-progression.

overall_design: Gene expression was studied in 2 mouse cell lines: MBA-15, a pre-osteoblastic stromal cell line, and DA3, a mammary adenocarcinomal cell line. The interaction between these 2 cell lines was also analysed by gene expression.  The experiment was performed in duplicates (see Date in the Sample characteristics field).

first: Chen

last: Glait-Santar

first: Varda

last: Oron-Karni

first: Dafna

last: Benayahu


title: Plasmid-free Chlamydia trachomatis elicit lowered inflammation, delayed apoptosis, and reduced chemoattractant expression in HeLa cells compared to plasmid-containing wild type

city: Hamilton

first: Dan

last: Sturdevant

state: MT

address: 903 S 4th street

department: NIAID

institute: NIH

summary: Chlamydia trachomatis serovariants are responsible for either Trachoma, the leading cause of infectious blindness or sexually transmitted disease, wherein the endocervix is the most frequently infected site in women. Disease caused by Chlamydia typically involves chronic inflammation and scarring.  Recent work with a live-attenuated A2497 plasmid deficient vaccine strain (A2497-) demonstrated protection in nonhuman primates against trachoma and a lack of measurable ocular pathology in A2497- infected monkeys. We therefore performed host cell transcriptome analysis of Hela cells infected with A2497 plasmid-containing (A2497) and A2497- Chlamydia over time. Our results indicate that relative to wild type A2497, the A2497- variant illicits a transcriptome response indicative of lowered inflammation response a delayed apoptosis response, a reduction in immune cell recruitement cytokine expression and a reduction in genes involved in cell proliferation and or fibrosis-like activities. The data provided here suggests a model that may explain how plasmid deficient chlamydia may provide an immuno-protective response without the pathology normally seen with plasmid-containing bacteria.

overall_design: Ct infection with and without plasmid time series

first: Stephen

middle: F

last: Porcella

first: John

last: Carlson

first: Daniel

middle: E

first: Gail

middle: L

first: Kimmo

last: Virtaneva

first: William

last: Whitmire

first: Grant

last: McClarty

first: Laszlo

last: Karia

first: Harlan

last: Caldwell


title: TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia

city: Copenhagen

first: Bo

last: Porse

address: Ole Maaloesvej 5

department: Finsen Centre

country: Denmark

institute: Rigshospitalet

summary:
The aim of the study was to investigate the role of TGIF1 in MLL-AF9 transformed cells
Members of the TALE (Three-amino acid loop extension) family of atypical homeodomain-containing transcription factors are prominent downstream effectors of oncogenic fusion proteins generated from translocations involving the mixed lineage leukemia (MLL) gene. A particular well-characterized member of this protein family is MEIS1, which together with HOXA proteins, orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). Although TALE family proteins are mainly described as transcriptional activators TGIF1 (TGF-β induced factor) / TGIF2 are considered as transcriptional repressors. However, as their function in MLL-rearranged AML is largely unknown, we tested the potential importance of TGIF1 in the maintenance of MLL-rearranged AML. We find that expression of TGIF1 in MLL-AF9 transformed cells (MAF9) leads to cell cycle exit and differentiation in vitro and delayed leukemic onset in vivo. In accordance, MLL-rearranged patient blasts display lower levels of TGIF1 and TGIF1 expression in general correlates positively with survival. Mechanistically, we show that TGIF1 interferes with a MEIS1-dependent transcriptional program by associating to MEIS1-bound region in a competitive manner. Collectively, these findings demonstrate that TALE family members can act both positively and negatively on transcriptional programs responsible for the maintenance of MLL-rearranged AML.

overall_design: We GFP-sorted MLL-AF9 transformed cells transduced with pMIG or pMIG-TGIF1

first: Anton

last: Willer


title: Global gene expression profile of gastric antrum tissue of patients with eosinophilic gastritis

first: Marc

last: Rothenberg

address: 3333 Burnet Ave. MLC-7028

department: Allergy

institute: Cincinnati Children's Hospital Medical Center

summary: Significant recent progress has been made with understanding eosinophilic gastrointestinal disorders (EGIDs) yet most studies have focused on eosinophilic esophagitis (EoE). Herein, we aimed to provide fundamental information about the molecular characteristics of eosinophilic gastritis (EG).

overall_design: RNA was isolated from gastric biopsies from control patients (n=5) and patients with EG (n=5) followed by hybridization on Affymetrix microarrays.

first: Julie

first: Margaret

last: Collins

first: Emily

last: Stucke

first: Phillip

last: Putnam

first: James

last: Franciosi

first: J

last: Abonia


title: Assessment of patient-derived tumour xenografts (PDXs) as a discovery tool for cancer epigenomics [methylation profiling by array]

city: Toronto

first: Paul

last: Guilhamon

state: ON

address: 686 Bay Street

country: Canada

institute: SickKids

summary: Illumina Infinium 450k Human DNA Methylation BeadChip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in Osteosarcoma and Colon Cancer PDXs

overall_design: Bisulphite converted DNA from each sample was hybridised to the Illumina Infinium 450k Human Methylation BeadChip.


title: Expression data of cardiac and gastrocnemius muscles of tumor bearing C26 mouse

status: Public on Nov 10 2014

city: Sydney

first: David

middle: Cho Yau

last: Fung

state: New South Wales

address: Gate 10, Botany Street

institute: University of New South Wales

summary:
We surveyed the transcriptomes of the whole heart and whole gastrocnemius muscle taken from two different types of Balb/c-DBAj hybrid mice (10-11 weeks old). The colon cancer bearing mice are called C26. The NTB are the non-tumor bearing mice.
This dataset includes Affymetrix expression data collected from the biological triplicates of heart and gastrocnemius from both C26 and NTB mice.

overall_design: The experimental combinatorics is 3 biological replicates x 2 muscle types x 2 murine models

first: P

last: Polly

first: D

middle: C


title: Profile of differential expression and DNA methylation status in choriodecidua of women affected with severe endometriosis [DNA methylation]

city: Paris

first: Céline

last: Méhats

address: 24 rue du Faubourg St jacques

institute: Inserm

summary:
Endometriosis is a common gynecological disease that affects 10-20% of women in child-bearing age. It is defined by the presence of endometrial tissues outside the uterus. The causes remain elusive, but the endometrium of these patients differs profoundly from that of disease-free subjects.
During pregnancy, the maternal-fetal interface is built onto decidualized endometrium. We investigated whether this interface is normal when the subjects suffer of endometriosis and showed remarkly properties of eutopic endometrium from endometriosis-affected women to spontaneously develop endometriotic-like lesions within direct contact to non-uterine tissues.

overall_design: Methylation analysis was conducted on three distinct pools of three choriodecidua DNAs from women suffering of severe endometrosis and three distinct pools of healthy choriodecidua from eighteen pregnant women in total. These women were delivered at term by cesarean section for feto-pelvic disproportion or scarred uterus, after an uncomplicated pregnancy.

first: Louis

last: Marcellin


title: Expression and methylation profiles of choriodecidua from pregnant women affected with deep endometriosis

type:
Expression profiling by array
Methylation profiling by array

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

overall_design: Refer to individual Series


title: Expression data from human non-alcoholic fatty liver disease stages

status: Public on Nov 07 2014

city: Alnarp

first: Itziar

last: Frades

address: Sundsvägen 14

department: Plant Protection Biology

country: Sweden

institute: Swedish University of Agricultural Sciences

summary: Global gene expression patterns of 2 human steatosis and 9 human non-alcoholic steatohepatitis (NASH) together with their respective control patterns were analyzed to define the non-alcoholic fatty liver disease (NAFLD) progression molecular characteristics and to define NASH early markers from steatosis.

overall_design: Human liver samples of steatosis and non-alcoholic steatohepatitis were selected for RNA extraction and hybridization on Affymetrix microarrays.


title: Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic fatty liver disease

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation.

status: Public on Nov 29 2014

city: Vancouver

first: Carolyn

last: Brown

state: British Columbia

address: 2350 Health Sciences Mall

department: Medical Genetics

institute: University of British Columbia

summary: X-chromosome inactivation (XCI) achieves dosage compensation between males and females through the silencing of the majority of genes on one X chromosome, with approximately 15% of genes reported to show inactive X (Xi) expression.  We examined the interplay between ChromHMM states, CpG density, expression and DNAm from over 1800 female samples with the Illumina 450K array.  The interaction between CpG density and histone marks differed between the active X (Xa) and the Xi, with X-linked promoters reflecting transcriptional status, while the Xi showed lower DNAm than the Xa at all non-promoter regions.  Promoter DNAm was used to determine a novel XCI status for more than 100 transcription start sites and a comparison across 27 tissues revealed the majority of genes were consistently subject to XCI.  Inter-female and twin data supported a model of predominately cis-acting influences on escape, or variable escape, from XCI.  Increased promoter DNAm at escape genes correlated with decreased relative Xi expression up to ~15% female DNAm but above this threshold DNAm was not correlated with the stability of silencing.  Xi DNAm was ~12% lower than Xa DNAm within the gene bodies of subject genes and between genes while there was equivalent DNAm at escape genes.  In addition to offering insight into sex-specific difference in disease, female X chromosomes provide the opportunity to compare euchromatin and heterochromatin of allelic regions within the same nuclear environment and demonstrate the correlation of DNAm with transcription and the influences of CpG density and chromatin marks.

overall_design: This cohort consist of genomic DNA extracted from 927 indiviudals representing 5 tissues, bisulphite converted and hybridized to the Illumina Infinium HumanMethylation450 Beadchip for genome wide DNA methylation profiling from only the X chromosome.

first: Allison

last: Cotton

first: E

last: Price

first: Meaghan

last: Jones

first: Michael

middle: S

last: Kobor


title: MRX34 Biomarker study in animals bearing Hep3B orthotopic liver tumors

status: Public on Nov 05 2014

city: Austin

first: Christopher

last: Daige

address: 2150 Woodward street, suite 100

institute: Mirna Therapeutics


title: Mutant WT1 is Associated with DNA Hypermethylation of PRC2 Targets in AML and Responds to EZH2 Inhibition

status: Public on Nov 04 2014

city: Palo Alto

first: Subarna

last: Sinha

address: 450 Serra Mall

department: Computer Science

institute: Stanford University

type: Methylation profiling by high throughput sequencing

summary: Genome wide DNA methylation profiling of THP1, THP1 expressing WT1 mutant, THP1 expressing IDH2 mutant, CTS cells and AML patient with WT1 mutant. The Illumina Infinium 450K Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 485,000 CpGs.

overall_design: Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2

first: Daniel

last: Thomas


title: Expression data from human subcutaneous adipocytes

city: Sagamihara

first: Takahiro

last: Yamaguchi

institute: Acel, Inc

summary:
An Affimetrix GeneChip Human Genome U133 Plus 2.0 Array was used to study the effect of oleoylethnolamide on gene expression.
The addition of 0.01 mM oleoylethanolamide (OEA) to human subcutaneous adipocytes significantly affected the expression of 1013 genes, with 556 being up-regulated and 457 being down-regulated.

overall_design: Human subcutaneous adipocytes were incubated with oleoylethanolamide (0.01 mM). After 24 hr, the gene expression in human subcutanous adipocytes was analyzed using Affymetrix microarrays.

first: Yuzo

last: Nakagawa-Yagi


title: Expression profile of osteoclasts treated with bisphosphonates

status: Public on Nov 06 2014

city: New York

first: Tony

last: Yuen

address: One Gustave L. Levy Place

institute: Icahn School of Medicine at Mount Sinai

summary: Bisphosphonates are the mainstay of therapy worldwide for osteoporosis.  They inhibit the activities of the osteoclasts, the bone resorption cells.  While bisphosphonates are known to block farnesyl pyrophsophate synthase to exert their anti-resorptive action, the detailed mechanism is not well understood.  Examining the change in expression profile before and after bisphosphonate treatment in the osteoclasts might shed some light on the biological pathways that are perturbed.

overall_design: Osteoclastic precursor cells were treated with (or without) bisphosphonates (alendronate or risedronate) during their differentiation into mature osteoclasts.


title: The induced APL cells generated by the transplantation of PML-RARA-transduced human CD34+ hematopoietic cells into immunodeficient mice

city: Isehara

first: Hiromichi

last: Matsushita

state: Kanagawa

address: 143 Shimokasuya

institute: Tokai University School of Medcine

summary: A humanized in vivo APL model has been established utilizing the retroviral transduction of PML-RARA into human CD34+ hematopoietic cells and the transplantation of these cells into immunodeficient mice. The resultant leukemia recapitulated human APL phenotypically, and was clustered in the same category as human APL samples in the gene expression analysis.

overall_design: CD34+ cells from human cord blood were retrovirally transduced with PML-RARA. They were then intravenously injected into a tail vein of nine- to 20-week-old NOD/Shi-SCID/IL-2Rγnull (NOG) mice which were irradiated with 220 cGy of X-rays. Three to four months later, the CD45+/ CD33+/ EGFP+ cells were sorted from the bone marrow for a microarray analysis. Two human APL/M3 AML samples were utilized for a comparison with these cells.

first: Takashi

last: Yahata

first: Yin

last: Sheng

first: Yoshihiko

last: Nakamura

first: Yukari

last: Muguruma

first: Hideyuki

last: Matsuzawa

first: Masayuki

last: Tanaka

first: Hideki

last: Hayashi

first: Tadayuki

last: Sato

first: Anar

last: Damdinsuren

first: Makoto

last: Onizuka

first: Mamoru

last: Ito

first: Hayato

last: Miyachi

first: Pier

middle: P

last: Pandolfi

first: Kiyoshi

last: Ando


title: the whole-genome methylation profile of esophageal squamous cell carcinoma

status: Public on Nov 03 2014

city: guangzhou

first: xufeng

last: li

state: guangdong

address: gongye avenue 253

department: oncology center of zhujiang hospital

country: China

institute: Southern Medical University

summary: Both genetic and epigenetic aberrations are linked by intricate crosstalk, and can either individually or in synergy lead to the development of cancer. Accumulating evidence suggests that epigenetic changes such as alterations in DNA methylation play a crucial role in ESCC. We performed a Illumina Infinium HumanMethylation450 BeadChip to examine the global methylation signature of esophageal squamous cell carcinoma of Chinese patients.

overall_design: DNA methylation profiles of esophageal squamous cell carcinoma (4 samples), paired adjacent normal surrounding tissues (4 samples) and normal esophagus mucosa from healthy individuals (4 samples) were generated using Infinium methylation 450K BeadChips from Illumina (Illumina, San Diego, USA).

first: Xu

last: Li

first: Chun

middle: Y

last: Jiang

first: Ji

last: Zhang

first: Yan

last: Zheng


title: Whole blood DNA methylation samples from HIV positive men [2013 study]

city: Los Angeles

first: Steve

last: Horvath

address: 695 Charles E. Young Drive South, Box 708822

institute: University of California, Los Angeles

summary: Genome wide DNA methylation profiles of whole blood from HIV positive men. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 480,000 CpGs. Dataset included 120 subjects from the USA but because of missing clinical characteristics only 109 subjects were used in the scientific publication. The study analyzed the effect of HIV viral load on host DNA methylation levels.

overall_design:
Bisulphite converted DNA from the 120  HIV positive men were hybridised to the Illumina Infinium 450k Human Methylation Beadchip. Subjects had different levels of HIV viral load.

This dataset reports DNA methylation data set on 120 subjects that were generated in 2013 (while the other data set of 24 subjects reports DNA methylation data generated in 2012).

Details on what each sample characteristics and their values represent are provided in the 'characteristics_readme.txt' file.

Please cite PMID: 25969563.

first: Andrew

last: Levine


title: Prenatal arsenic exposure and the epigenome: Identifying sites of 5-methyl cytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes

city: Old Pittsboro Rd.

first: Jose Daniel

last: Rojas Rojas

state: NC

address: MHRC 0032

department: Environmental Science and Engineering

institute: University of North Carolina at Chapel Hill

summary: Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from mothers enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gomez Palacio, Mexico who were exposed to a range of drinking water arsenic concentrations (0.456-236 µg/L). Changes in iAs-associated DNA 5-methyl cytosine methylation were assessed across 424,935 CpG sites representing 18,761 genes and were compared to corresponding expression levels and birth outcomes. In the context of arsenic exposure, a total of 2,705 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyzes identified DNA methylation changes that were most predictive of gene expression levels. Specifically, CpG methylation within CpG islands positioned within the first exon and 200bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of seven of these genes were associated with differences in birth outcomes including gestational age, placental weight and head circumference. These data highlight the complex interplay between DNA methylation and functional changes in gene expression and health outcomes and underscore the need for functional analyzes coupled to epigenetic assessments.

overall_design: 48 DNA methylation profiles were obtained but only 38 samples corresponding to samples also analyzed for gene expression (see Rager 2014) were further normalized and used in the publication from the Biomarkers of Arsenic (BEAR) cohort were analyzed for DNA methylation profiles.

first: Daniel

last: Rojas

first: Julia

last: Rager

first: Lisa

last: Smeester

first: Kathryn

middle: A

last: Bailey

first: Zuzana

last: Drobnà

first: Marisela

last: Rubio-Andrade

first: Miroslav

last: Styblo

first: Gonzalo

last: Garcia-Vargas

first: Rebecca

last: Fry


title: Human Liver Illumina Inf 450 DNA methylation data

summary: Genome wide DNA methylation profiles of human Liver tissue. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 485,000 CpGs. Dataset includes 79 samples from Germany. The goal of the study was to evalute the relationship between body mass index and DNA methylation levels.

overall_design: Bisulphite converted DNA from the 79 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.

first: Jochen

last: Hampe

first: Ole

last: Ammerpohl


title: Human adipose Illumina Inf 450 DNA methylation data

summary: Genome wide DNA methylation profiles of human adipose tissue. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 485,000 CpGs. Dataset includes 32 samples from Germany. The goal of the study was to evalute the relationship between body mass index and DNA methylation levels.

overall_design: Bisulphite converted DNA from the 32 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.


title: Expression data from non-small cell lung carcinoma (NSCLC)

city: Pittsburgh

first: Victoria

last: Plamadeala

state: Pennsylvania

address: 2516 Jane St

institute: Precision Therapeutics

summary: The analytical validation of a 15 gene prognostic signature for early-stage, completely resected, non-small-cell lung carcinoma that distinguishes between patients with good and poor prognoses.

overall_design:
Matched fresh frozen (FF) and RNALater (RNAL)-treated NSCLC specimens from 43 distinct patients were employed in this study.  Each specimen was split into 2 biological replicates, equaling 172 samples (86 FF, 86 RNAL) in total which were analyzed via microarray.  Microarray output was used to calculate the risk score (risk of recurrence) using a previously-described signature. Concordance (in risk category – high, low) and correlation (in risk score) between the FF and RNAL specimens was calculated. After concordance and correlation between FF and RNAL specimens was established, RNAL specimens only were used to evaluate the analytical performance of the signature. Accuracy was evaluated using 34 samples, comparing signature concordance and correlation between the clinical laboratory and a reference laboratory. Precision was evaluated using 8 samples (4 high risk, 4 low risk), accounting for both intra-run and inter-run concordance. Analytical sensitivity was evaluated using 1 sample, assessed at 3 different RNA input amounts. Analytical specificity was evaluated using 2 samples (1 high risk, 1 low risk).
Contributor: Precision Therpeutics, Inc.


title: Coding mutations and loss-of-imprinting in human pluripotent cells derived by nuclear transfer and defined factors [DNA methylation profiling]

city: Jerusalem

first: Ido

last: Sagi

address: Givat Ram

department: Genetics

institute: The Hebrew University of Jerusalem

summary: Human pluripotent stem cells can be derived from somatic cells by forced expression of defined factors, and more recently by nuclear-transfer into human oocytes, revitalizing a debate on whether one reprogramming approach might be advantageous over the other. Here we compared the genetic and epigenetic stability of human nuclear-transfer embryonic stem cell (NT-ESC) lines and isogenic induced pluripotent stem cell (iPSC) lines, derived from the same somatic cell cultures of fetal, neonatal and adult origin. Both cell types shared similar genome-wide gene expression and DNA methylation profiles. Importantly, NT-ESCs and iPSCs have comparable numbers of de novo coding mutations but significantly higher than parthenogenetic ESCs. Similar to iPSCs NT-ESCs displayed clone- and gene-specific aberrations in DNA methylation and allele-specific expression of imprinted genes, similarly to iPSCs. The occurrence of these genetic and epigenetic defects in both NT-ESCs and iPSCs suggests that they are inherent to reprogramming, regardless of the underlying technique.

overall_design: Genome-wide DNA methylation profiling by Illumina Infinium HumanMethylation 450K Beadchip was performed on a total of 21 human cell lines, including: an isogenic set of 3 nuclear-transfer embryonic stem cell (NT-ESC) lines, 2 RNA-reprogrammed induced pluripotent stem cell (iPSC) lines and their parental neonatal fibroblast cell line; an isogenic set of 1 NT-ESC line, 6 iPSC lines and their parental adult fibroblast cell line (derived from a type 1 diabetic subject); as well as 7 control embryonic stem cell (ESC) lines.

first: Bjarki

last: Johannesson

first: Mitsutoshi

last: Yamada

first: Nissim

last: Benvenisty

first: Dieter

last: Egli


title: Human muscle Illumina Inf 450 DNA methylation data

first: Steve

last: Horvath

summary: Genome wide DNA methylation profiles of human muscle tissue. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 485,000 CpGs. Dataset includes 26 samples from Germany. The goal of the study was to evalute the relationship between body mass index and DNA methylation levels.

overall_design: Bisulphite converted DNA from the 26 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.


title: M12-28: MRX34 Biomarker study in animals bearing HuH7 orthotopic liver tumors [Affymetrix]

first: Christopher

last: Daige

summary: To identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34

overall_design:
HuH7 cells were surgically implanted into the livers of Nod/Scid mice and allow to grow for multiple weeks.  Once serum AFP levels reached levels consistent with tumor growth of ~80-100 mg,
animals were subjected to a single IV injection of MRX34.  Twenty-four hours later animals were sacrificed, tumors resected and RNA isolated for subsequent microarray analysis.

first: Chris

first: David

last: Brown


title: Obesity accelerates epigenetic aging of human liver

type:
Methylation profiling by array
Expression profiling by array


title: Transcriptome profiling of T-lymphoblastic leukemia of childhood [gene expression]

city: Hamburg

first: Thomas

last: Streichert

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

department: Institute For Clinical Chemistry / Central Laboratories

institute: University Medical Center Hamburg-Eppendorf

summary: The purpose of this study was the principal investigation and frequency of RTK expression in primary T-ALLs. Primary initial  T-ALLs were assessed regarding their transcriptome-wide expression profiles and screend for prominent RTK expression.

overall_design: Naive primary T-ALL samples were evaluated with regard to global mRNA expression and screened for prominent RTK expression. The dataset was used to investigate RTK expression frequencies in T-ALLs.

first: Martin

last: Horstmann

first: Benjamin

last: Otto


title: Epigenome analysis of control and KLF4-overexpressing podocytes

status: Public on Nov 01 2014

city: Shinjuku-ku

first: Hiroyuki

last: Sasamura

state: Tokyo

address: 35 Shinanomachi

department: Internal Medicine

institute: Keio University School of Medicine

summary: Genome wide DNA methylation profiling of control (vector-transfected) and KLF4-overexpressing human podocytes (parental cell line: Saleem et al. JASN 13:630, 2002). The Illumina HumanMethylation450 Beadchip was used to obtain DNA methylation profiles.

overall_design: Bisulphite converted DNA samples from control (vector-transfected, n=1) and KLF4-overexpressing human podocytes (n=1) were hybridised to the Illumina HumanMethylation450 Beadchip and DNA methylation was compared.

first: Kaori

last: Hayashi


title: Expression data from human induced pluripotent stem cells derived retinal pigment epithelium (hiPSC-RPE)

city: Kurashiki

last: Kamao

state: Okayama

address: 577 Matsushima

department: Ophthalmology

institute: Kawasaki Medical School

summary:
We generated hiPSCs from patients fibloblast with retinitis pigmentosa (RP) using retrovirus and Sendai virus vectors, which we differentiated into hiPSC derived retinal pigment epithelium using two different methods (SDIA and SFEB methods).
We investigated whether these hiPSC-RPE colonies, which were differentiated from various cell lines and methods, showed similar gene expression patterns to those of native RPE.

overall_design: We classified hiPSC-RPE, hiPSCs, and fibroblasts from RP patients, hRPE (commercially available human fetal RPE, Lonza) , ARPE19 (a human RPE cell line), and other human tissues from 54,675 probe sets using microarray data.

first: Akiko

last: Suga

first: Takeya

last: Kasukawa

first: Kenichiro

last: Uno


title: Identification of genes regulated by HSF1 in control and heat-shocked cells

city: Ube

first: Eiichi

last: Takaki

state: Yamaguchi

address: minami-kogushi, 1-1-1

institute: Yamaguchi university

summary: To examine the regulation of HSF1-mediated gene expression in control and heat shock conditions, we performed DNA microarray analysis.

overall_design: mRNA levels in control and heat-shocked MEF cells, which were infected with adenovirus expressing scramble RNA or HSF1 short hairpin RNA, were analyzed by DNA microarray analysis using GeneChip Mouse Gene 1.0 ST Array (Affymetrix).

first: Ryosuke

last: Takii

first: Akira

last: Nakai


title: Bone Marrow Monocyte/Macrophage Derived Activin A Mediates the Osteoclastogenic Effects of IL-3 in Myeloma

city: Parma

first: Nicola

last: Giuliani

address: Via Gramsci,14

department: Medicina Clinica e Sperimentale

institute: Università degli Studi di Parma

summary: Myeloma bone disease is characterized by tremendous bone destruction with suppressed bone formation. IL-3 is a multifunctional cytokine that increases myeloma cell growth and osteoclast proliferation while inhibiting osteoblast differentiation. While IL-3 appears to be an attractive therapeutic target for myeloma, attempts at targeting IL-3 have been unsuccessful due to IL-3’s effects on normal hematopoiesis. Thus identification of IL-3’s downstream effects in MMBD is important for effective targeting of this cytokine in MM. Here we demonstrated that treatment of myeloma patient CD14+ bone marrow monocyte / macrophages with IL-3 induces high levels of Activin A (ActA), a pluripotent TGF-β superfamily member that, like IL-3, modulates MMBD by enhancing osteoclastogenesis and inhibiting osteoblasts.  We show that IL-3 induced osteoclastogenesis is mediated by ActA and is RANKL independent. Additionally, IL-3 induced ActA secretion is greatest early in osteoclastogenesis and ActA acts early in osteoclastogenesis. Therefore we suggest that therapies targeting ActA production should block IL-3’s effects in myeloma bone disease.

overall_design: Investigate the mediators of IL-3’s effects on bone remodeling in myeloma we performed gene expression profiling using Affymetrix GeneChip analysis of IL-3 treated CD14+ peripheral blood from healthy donor.

first: Rebecca

last: Silbermann

first: Marina

last: Bolzoni

first: Paola

last: Storti

first: Benedetta

last: Palma

first: Daniela

last: Guasco

first: Sabrina

last: Bonomini

first: Judy

last: Anderson

first: G

last: Roodman


title: Gene expression affected by miR-147

city: Spartanburg

first: Timothy

last: Yeatman

state: SC

address: 101 E Wood St.

institute: Gibbs Cancer Center & Research Institute

summary: The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer progression and may promote resistance to therapy. An analysis of patients (n = 71) profiled with both gene expression and a global microRNA assessment (~ 415 miRs) identified miR-147 as highly anti-correlated with an EMT gene expression signature score and postulated to reverse EMT (MET).We have found that miR-147 induced cancer cells to undergo MET phenotypically. It's necessary to investigate the genes affected by miR-147 to understand the mechanism.

overall_design: RNA extracted from miR-147 and non-coding miR transiently transfected HCT116 cells; gene expression then assayed using the Affymetrix GeneChip U133 Plus2.0 platform.

first: Chang

last: Lee


title: Early and dynamic changes in gene expression in septic shock patients: a genome wide approach

city: Lyon

first: Marie-Angélique

last: Cazalis

address: Pl, Arsonval

institute: LCR HCL-bioMérieux

summary: Background: As early and appropriate care of severe septic patients is associated with better outcome, understanding of very first events in the disease process is needed. Pan-genomic analyses offer an interesting opportunity to study global genomic response within the very first hours after sepsis.   The objective of this study was to investigate the systemic genomic response in severe Intensive Care Unit (ICU) patients and determine whether patterns of gene expression could be associated with clinical severity evaluated by severity score.   Methods: Twenty-eight ICU patients were enrolled at the onset of septic shock. Blood samples were collected within 30 minutes, 24 and 48 hours after shock and genomic response was evaluated using microarrays. The genome wide expression pattern of blood leukocytes was sequentially compared to healthy volunteers and after stratification based on SAPSII score to identify potential mechanisms of dysregulation.   Results: Septic shock induces a global reprogramming of the whole leukocyte transcriptome affecting multiple functions and pathways (> 71% of the whole genome was modified). Most altered pathways were not significantly different between SAPSII-high and SAPSII-low groups of patients. However the magnitude and the duration of these alterations were different between these two groups. Importantly, we observed that the more severe patients did not exhibit the strongest modulation. This indicates that some regulation mechanisms leading to recovery seem to take place at early stage.   Conclusion: In conclusion, both pro- and anti-inflammatory processes, measured at the transcriptomic level, are induced within the very first hours after septic shock. Interestingly, the more severe patients did not exhibit the strongest modulation. This highlights that, not only the responses mechanisms by themself but mainly their early and appropriate regulation, are crucial for patient recovery. This reinforces the idea that an immediate and tailored aggressive care of patients, aimed at restoring an appropriately regulated immune response, may have a beneficial impact on outcome.

overall_design: Twenty-eight ICU patients were enrolled at the onset of septic shock. Blood samples were collected within 30 minutes, 24 and 48 hours after septic shock and compared to twenty-five healthy volunteers

first: Marie

first: Alain

last: Lepape

first: Fabienne

last: Venet

first: Florence

last: Frager

first: Bruno

last: Mougin

first: Malick

last: Paye

first: Alexandre

last: Pachot

first: Guillaume

last: Monneret

first: Julien

last: Textoris


title: Global gene expression profiling human and Chimpanzee induced pluripotent stem (iPS) cell

status: Public on Oct 31 2014

city: kumamoto

first: Makoto

last: Hamasaki

address: honjo 2-2-1

institute: Kumamoto univ

summary: Gene expression study of human and Chimpanzee iPS cell.

sample_organism:
Pan troglodytes
Homo sapiens

overall_design: Affymetrix GeneChip Human Genome U133 Plus 2.0 Array were used to examine differentially expressed genes between human and chimpanzee iPS cells

first: Y

last: Fujie

first: N

last: Fusaki

first: T

last: Katayama

first: M

last: Soejima

last: Soga

first: H

last: Ban

last: Hasegawa

first: S

last: Tamashita

last: Kimura

last: Suzuki

last: Matsuzawa

last: Akari

last: Era


title: Expression data of human tympanic membrane cells and epidermal keratinocytes [mRNA]

city: Lorenskog

first: Peder

last: Aabel

address: Sykehusvn. 27

department: ENT

country: Norway

institute: Akershus University Hospital

summary:
The data set compares the gene expression of two types of keratinocytes from the tympanic membrane and epidermis of the body. Healthy human samples were harvested for the analysis.
Cells were cultivated to evaluate the effekt of keratinocytes only. 626 Chip Ids considered differentially expressed between the cell types. Enrichment tests show genes related to migration are over-represented in the highly expressed genes of TMK vs. EK.

overall_design: Six samples were analysed in total. Each cell type in biological triplicates. Genes of p-value <0.05 and fold change of ≥ 1.5 were considered significant.

first: Magnus

last: von Unge

first: Ole

middle: K

last: Olstad


title: Genome-wide DNA methylation analysis in permanent atrial fibrillation

status: Public on Oct 28 2014

city: Beijing

first: Jian

last: Zhou

address: Gongtinan Road 8

institute: Chaoyang Hospital

summary: Atrial fibrillation (AF) is the most common sustained arrhythmia with increased risk of stroke and congestive heart failure. AF is a highly genetic heterogeneous disease, but a large proportion of AF cannot be explained by genetic variants only. Some risk factors of AF, tendentious heritable phenomenon, potentially reversible conditions and some subtypes without DNA sequence variation all indicate the participation of DNA methylation in the pathogenesis of AF.

overall_design: Bisulphite converted DNA from the 11 left atrium samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip GPL13534

first: Jie

last: Gao

first: Song

last: Gu

first: Pixiong

last: Su


title: Expression data from SKOV3ip1 cells treated with MORAB-003 antibody

city: Houston

first: Prahlad

last: Ram

state: TEXAS

address: 7435 Fannin Street

institute: UT MD Anderson

summary:
MORAB-003 significantly upregulated a number of genes involved in autophagic processing, including GABARAPL2, LC3II (MAP1LC3B), ATG3, ATG4B, and BECN1, while expression of the oncogenic factor PIK3C3 was downregulated.
We used microarrays to detail the global programme of gene expression underlying growth inhibition of ovarian cancer cells treated with MORAB-003

overall_design:
microarray analysis of SKOV3ip1 cells with and without MORAb-003 treatment was performed under the following conditions: 1) cells plated in folate-free medium (7 days), 2) cells plated in medium with physiological levels of folic acid (2-10 nm) (7 days), 3) cells with physiological levels of folic acid (7 days) and 003 antibody (24 hours), 4) cells with physiologic levels of folic acid (7 days) and control 004 antibody (24 hours); 5) cells with physiological levels of folic acid (7 days) and MORAb003 antibody (24 hours) . For each condition, a single cell growth was carried out and an RNA sample was extracted. Three aliquots from each RNA sample were then hybridized to Affymetrix U133 2 arrays, for a total of 15 arrays.
time course 7days and 24 hours

first: Whitney

last: Graybill

first: Anil

last: Sood


title: SOX11-positive and SOX11-knockdown xenograft derived tumor Gene Expression Profilings

city: Barcelona

first: Virginia

last: Amador

state: Barcelona

address: Rossello 153

department: Pathology

institute: IDIBAPS

summary:
The neural transcription factor SOX11 is overexpressed in aggressive lymphoid neoplasms mainly in mantle cell lymphoma (MCL). We have recently demonstrated SOX11 tumorigenic potential in vivo by showing a significant reduction on tumor growth of SOX11-knockdown MCL cells in xenograft experiments, confirming the clinical observations that SOX11 may play an important role in the aggressive behavior of MCL (Vegliante et al., 2013). However, the specific mechanisms regulated by SOX11 that promote the oncogenic and rapid tumor growth of aggressive MCL still remain to be elucidated. To further characterize the potential oncogenic mechanisms regulated by SOX11 in MCL, we have analyzed the GEP derived from the xenograft SOX11-positive and knockdown xenograft derived tumors.
Differential gene expression  between SOX11-positive Z138 and SOX11-negative Z138 MCL cell lines xenotransplanted in SCID mices derived tumors.

overall_design: To determine the transcriptional programs regulated by SOX11 we first generated a 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, CB17-severe combined immunodeficient (CB17-SCID) mice (Charles River Laboratory, Wilmington, MA) were subcutaneously inoculated into their lower dorsum with Z138 shSOX11.1, shSOX11.3, shControl in Matrigel basement membrane matrix and compared the GEP of SOX11-positive and SOX11-negative MCL xenotransplant derived tumors using the Affymetrix U133+2.0 microarrays.

first: Jara

last: Palomero

first: Maria

last: Vegliante

last: Cid

first: Elias

last: Campo


title: Diverse phospho-signaling networks mediate RTK dependent growth and survival in childhood ALL

first: Thomas

last: Streichert

type:
Expression profiling by array
Genome variation profiling by SNP array

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

overall_design: Refer to individual Series


title: Human transcripts up-regulated in the human mesenchymal stem cells migrated within the rat synovium; rat transcripts up-regulated in the rat synovium after human mesenchymal stem cells injection

status: Public on Oct 27 2014

city: Tokyo

first: Nobutake

last: Ozeki

address: 1-5-45 Yushima, Bunkyo-ku

department: Department of Joint Surgery and Sports Medicine

institute: Tokyo Medical and Dental University

summary: After the injection of human synovial mesenchymal stem cells into the rat (Lewis strain) knee joint, synovium was investigated using species specific microarray analyses of human and rat transcripts to investigate the gene expression change after injection.

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus

overall_design: Human synovial mesenchymal stem cells were injected into the rat anterior cruciate ligament transected knee. After harvesting the synovium and extraction of RNA, species specific microarray analyses were performed uisng Affymetrix microarrays to investigate the gene expression change of human and rat transcripts after injection.

first: Ichiro

last: Sekiya

first: Kenji

last: Matsumoto


title: Gene Expression Profile of Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) Culutured in Chemical Defined Serum Free Medium

city: Tianjin

first: Youwei

last: Wang

state: --- Select One ---

address: 92 Weijin Road

department: Medical College

institute: Tianjin University

summary:
Human umbilical cord mesenchymal stem cells maintained multipotency and immunosuppressive ability when being cultured in chemical defined serum free medium, but gained different gene expression profile.
We used microarrays to identify the transcriptional difference between human umbilical cord mesenchymal stem cells cultured in serum containing medium and chemical defined serum free medium.

overall_design: human umbilical cord mesenchymal stem cells were cultured in conventional serum containing medium and chemical defined serum free medium separately. Total RNA was extracted and hybridized on Affymetrix microarrays.


title: Affymetrix HG-U133A 2.0 Expression data from 6 human cell lines derived from metastasized melanoma

status: Public on Oct 25 2014

city: Heidelberg

first: Rajiv

last: Kumar

address: Im Neuenheimer Feld 580

department: Division of Molecular Genetic Epidemiology

institute: German Cancer Research Center

summary: Study of global gene expression differences in malignant melanoma cell lines with or without specific abberations in BRAF NRAS or CDKN2A.

overall_design: Expression .CEL files from Affymetrix HG-U133A 2.0 arrays using total RNA from 6 human cell lines derived from metastasized melanoma

first: Sandra

last: Bloethner

first: Andreas

last: Gast

first: Selma

last: Ugurel

first: Sivaramakrishna

last: Rachakonda

first: Antje

last: Sucker

first: Dirk

last: Schadendorf


title: Immune status, strain background, and anatomic site of innoculation affect mouse papillomavirus (MmuPV1) induction of exophytic papillomas or endophytic trichoblastomas

city: Bar Harbor

first: Timothy

middle: Michael

last: Stearns

state: ME

address: 600 Main Street

department: Computational Sciences

institute: The Jackson Laboratory

summary: Papillomaviruses (PVs) are able to induce papillomas, premalignant lesions, and carcinomas in a wide variety of species. PVs are classified first based on their host and tissue tropism and then their genomic diversities. A laboratory mouse papillomavirus, MmuPV1 (formerly MusPV), naturally infects NMRI-Foxn1nu/Foxn1nu (nude; T cell deficient) mice. C57BL/6J wild-type mice were not susceptible to MmuPV1 infection; however, immunocompetent, alopecic, S/RV/Cri-ba/ba (bare) mice developed small papillomas at injection sites that regressed. NMRI-Foxn1nu and B6.Cg-Foxn1nu but not NU/J-Foxn1nu mice were susceptible to MmuPV1 infection. B6 congenic strains, but not other congenic strains carrying the same allelic mutations, that lack B- and T-cells, but not B-cells alone, were susceptible to infection, indicating that mouse strain and T-cell deficiency are critical to tumor formation. Although lesions initially observed were exophytic papillomas around the muzzle, exophytic papillomas on the tail and condylomas of the vaginal lining could be induced by experimental infections. On the dorsal skin, locally invasive, poorly differentiated tumors developed with features similar to human trichoblastomas. Transcriptome analysis revealed significant differences between the normal skin in these anatomic sites and in papillomas versus trichoblastomas. The primarily dysregulated genes involved molecular pathways associated with cancer, cellular development, cellular growth and proliferation, cell morphology, and connective tissue development and function. Surprisingly, few of the genes commonly associated with basal cell carcinoma or squamous cells carcinoma were dramatically dysregulated.

overall_design: To determine if there were transcriptome differences between papillomas on the tail skin compared to invasive trichoblastomas on the dorsal skin, tumors from the tail and dorsal skin from 3 B6.Cg-Foxn1nu/Foxn1nu mice and unaffected skin from the tail or contra-lateral (dorsal skin) were compared using the Affymetrix GeneChip Mouse Genome 1.0 ST Array. Concurrently, a matched study was done at the University of Louisville comparing facial (muzzle) papillomas and dorsal skin trichoblastomas to respective unaffected contralateral skin.

first: John

last: Sundberg

middle: M

first: Joongho

last: Joh

first: Mary

last: Proctor

first: Arvind

last: Ingle

first: Kathleen

last: Silva

first: Soheil

last: Dadras

first: A

middle: B

last: Jenson

first: Shin-je

last: Ghim


title: Diverse phospho-signaling networks mediate RTK dependent growth and survival in childhood ALL [gene expression]

first: Thomas

last: Streichert

summary: Deregulated RTK activity has been implicated as a causal leukemogenic factor in the context of molecular aberrations that perturb differentiation in the hematopoietic lineage such as in childhood ALL. A deeper understanding of RTK signaling processes on a system-wide scale will be key in defining critical components of signaling networks. To link RTK activity with in vivo output in primary ALL we took a functional approach, which combined SH2 domain binding, mass spectrometry, and transcriptome analyses. Structure and composition of evolving networks were highly diverse with few generic features determined by receptor and cell type. A combinatorial assembly of varying context-dependent and few generic signaling components at multiple levels likely generates output specificity. PAK2 was identified as a phosphoregulated FLT3 target, whose allosteric inhibition resulted in apoptosis of ALL cells. Our studies provide evidence that a functional approach to leukemia signaling may yield valuable information for a network-directed intervention.

overall_design:
Three different primary ALL samples expressing FLT3 and/or PDGFRß were stimulated with the corresponding ligands FLT3L and PDGF-BB for five time points. Unstimulated samples served as control.

ALL22089 coexpresses FLT3 and PDGFRß.
ALL109 expresses PDGFRß.
ALL114 expresses FLT3.

first: Kevin

last: Dierck

first: Martin

last: Horstmann

first: Benjamin

last: Otto