title: Transcriptome alteration by ZIC5 knockdown in melanoma cell lines, A375 and SK-MEL-28.

city: Hachioji-city

first: Reiko

last: Satow

state: Tokyo

address: 1432-1 Horinouchi

institute: Tokyo University of Pharmacy and Life Science

summary: To examine the transcriptome alteration caused by ZIC5 knockdown in melanoma, we performed gene expression microarray analysis.

overall_design: Human melanoma cell lines, A375 or SK-MEL-28, were transfected with siRNA for ZIC5 or negative control siRNA. After 48h,  total RNA was extracted and microarray analysis was performed.

first: Kiyoko

last: Fukami


title: DNA methylation profiling of pediatric B lymphoblastic leukemia with KMT2A rearrangement identifies hypomethylation at enhancer sites

status: Public on Nov 04 2016

city: Kiel

first: Anke

middle: Katharina

last: Bergmann

address: Arnold-Heller Str.

country: Germany

institute: University Hospital Schleswig-Holstein

type:
Methylation profiling by array
Third-party reanalysis

summary: Genome wide DNA methylation profiling of 26 pediatric KMT2Ar rearranged ALLs in comparison to 22 previously profiled samples of different non-neoplastic human B-cell precursor populations (GSE45459). The Illumina Infinium 450k Human DNA methylation Beadchip was used.

overall_design: Bisulphite converted DNA from 26 pediatric KMT2Ar rearranged ALLs were hybridized to the Illumina Infinium 450k Human Methylation Beadchip in comparison to 22 previously profiled samples of different non-neoplastic (benign) human B-cell precursor populations (GSE45459). The Illumina Infinium 450k Human DNA methylation Beadchip was used.


title: KLHL23 Regulates a Novel Positive-Feedback Signaling Loop of EMT Maintaining the Mesenchymal State of Cancer Cells during Metastasis

status: Public on Nov 01 2016

city: TauYau

first: Yun-Shien

last: Lee

state: Taiwan

address: TauYau

department: Dept. Biotechnology

country: Taiwan

institute: Ming Chuan Univ

summary: Epithelial-mesenchymal transition (EMT) is initiated and regulated by a transcriptional reprogramming in response to microenvironmental cues. How cancer cells overcome the lack of such cues during the metastatic journey remains unclear. Here we report a novel positive-feedback loop of EMT that maintains the mesenchymal traits of cancer cells during metastasis. Using subgenome-wide screening, we identified KLHL23 as a tumor invasion suppressor, which binds to actin and suppresses actin-filament formation. Silencing or ectopic expression of KLHL23 induces EMT or MET (mesenchymal-epithelial transition), respectively, through its action on actin dynamics. Increased actin-dynamics by silencing KLHL23 or treatment with F-actin disruptors or inducers enhances the EMT transcriptional reprogramming via the induction of ROS, HIF-1a, HIF-2a and NOTCH signalling pathways in cancer cells under stress or ongoing EMT. Downregulation of KLHL23 is found in human liver and pancreatic cancers and associated with tumor metastasis and poor prognosis.

overall_design: Hep-3B and Huh7 cells were transduced with shLuc or shKLHL23 virus.Stable cells were selected for RNA extraction and hybridization on Affymetrix microarrays. The differential expression gene between shLuc and shKLHL23 were selected and validated with qPCR method.

first: Jei-Ming

last: Peng

first: Rabindranath

last: Bera

first: Chih-Yung

last: Chiou

first: Ming-Chin

last: Yu

first: Tse-Chin

last: Chen

first: Chia-Wei

first: Tsung-Rei

last: Wang

first: Mien-Chie

last: Hung

first: Sen-Yung

last: Hsieh


title: Disruption of Estrogen Signaling Enhances Invasiveness of Breast Cancer Cells by Attenuating a HER2-independent Gene Repression Program

city: Toledo

first: Robert

middle: J

last: Trumbly

state: OH

address: 3000 Arlington Avenue

department: Biochemistry and Cancer Biology

country: USA

institute: University of Toledo

overall_design: In ER+ breast cancer cells, genes that were directly or indirectly repressed by E2, but not E2-activated genes, overlapped the gene overexpression signature of clinical progression of ductal carcinoma in situ to invasive ductal carcinoma. They also showed a strong collective functional bias toward tumor progression. In MCF-7 (ER+/PR+), ZR-75-1 (ER+/PR+) and BT474 (ER+/PR+/HER2 amplified) cells hormone depletion or tamoxifen treatment restored gene expression and invasiveness that were inhibited by E2.

first: Mugdha

last: Patki

first: Marcela

last: d'alincourt Salazar

first: Manohar

last: Ratnam


title: Identification of miR-210 target genes in T20 patient-derived sphere culture

status: Public on Oct 27 2016

city: Belvaux

first: Elisabeth

last: Letellier

address: 6, Avenue du Swing

department: Life Sciences Research Unit

country: Luxembourg

institute: University of Luxembourg

summary:
Hypoxia is known to regulate tumor-initiating cells and to have an effect on miRNA expression. We were interested in studying the role of hypoxia-induced miR-210 in colorectal cancer patient-derived sphere cultures.
Downregulated genes after overexpression of miR-210 were retained as potential miR-210 target genes for further validation sudies.

overall_design: Colorectal cancer patient-derived (patient name: T20) sphere cultures were stably transduced with miR-210 lentiviral particles (Biosettia) or control vectors, respectively. Three technical replicates were used for both conditions.


title: Gene expression profiling of three human prostate epithelial subpopulations

status: Public on Oct 22 2016

city: Los Angeles

first: Andrew

middle: Scott

last: Goldstein

state: CA

address: 610 Charles E Young Dr East

department: Urology

institute: University of California, Los Angeles

summary:
The human prostate epithelium is predominantly comprised of two cell-types: basal and luminal. While basal cells exhibit significant progenitor activity in a variety of functional assays, luminal cells are depleted of this activity. Recent studies indicate that approximately 1% of luminal cells exhibit progenitor activity. We have discovered that differential expression of the glycoprotein CD38 can fractionate the luminal population into two subsets: CD38+ and CD38-low. In functional assays, the CD38-low luminal cells exhibit roughly 5-fold increased progenitor activity compared to the remaining CD38+ population. Therefore, we propose that CD38-low luminal cells represent an enriched luminal progenitor population while the CD38+ subset is predominantly comprised of mature non-progenitor luminal cells.
In this microarray experiment, we have performed expression profiling of three epithelial subsets (basal, CD38-low luminal progenitor, and CD38+ mature luminal) purified by Fluorescence Activated Cell Sorting from the benign prostate of four different patients.

overall_design: Benign human prostate from four different patients, provided to researchers in a de-identified manner, were enzymatically and mechanically digested to single cells using a combination of collagenase, dispase and trypsin as described in Goldstein et al (Nature Protocols, 2011). Single cells were stained for antibodies against CD45, EpCAM, CD49f and CD38. CD45-EpCAM+ epithelial cells were further sorted into basal (CD49f-hi), luminal progenitor (CD49f-lo CD38-lo) and mature luminal (CD49f-lo CD38+). Cell pellets were frozen and later lysed in buffer RLT to isolate RNA using the Qiagen RNEasy micro kit. Samples were subjected to microarray analysis on the Affymetrix platform at the UCLA Clinical Microarray Core.

middle: S


title: Increased Wnt and Notch signaling: A clue to the renal disease in Schimke immuno-osseous dysplasia? [array]

status: Public on Oct 31 2016

city: Vancouver

first: Cornelius

middle: F.

last: Boerkoel

state: British Columbia

address: 950 West 28th Avenue

department: Medical Genetics

country: Canada

institute: University of British Columbia

summary: Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in SWI/SNF-related matrix associated actin-dependent regulator of chromatin, subfamily A-like protein 1 (SMARCAL1). Changes in gene expression appear to underlie the immunodeficiency and arteriosclerosis of SIOD; therefore, we hypothesized that SMARCAL1 deficiency alters renal gene expression to cause the focal segmental glomerulosclerosis (FSGS) of SIOD, and that these gene expression alterations would be comparable to those observed in isolated FSGS. We tested this hypothesis by gene expression microarray analysis.

overall_design: Comparison of gene expression between the cultured primary renal proximal tubular cells of a Schimke immuno-osseous dysplasia (SIOD) patient and of a patient with non-SIOD-associated FSGS

first: Marie

last: Morimoto

middle: F


title: Epipolymorphisms associated with the clinical outcome of autoimmune arthritis affect CD4+ T cell activation pathways (methylation)

status: Public on Oct 28 2016

first: Maura

last: Rossetti

address: 1000 Veteran Avenue

institute: UCLA

summary: Multifactorial diseases, including autoimmune juvenile idiopathic arthritis (JIA), result from a complex interplay between genetics and environment. Epigenetic mechanisms are believed to integrate such gene-environment interactions, fine-tuning gene expression and possibly contributing to immune system dysregulation. Although anti-TNF therapy has strongly increased JIA remission rates, it is not curative and up to 80% of patients flare upon treatment withdrawal. Thus, a crucial unmet medical and scientific need is to understand the immunological mechanisms associated with remission or flare to inform clinical decisions. Here, we explored the CD4+ T cell DNA methylome of 68 poly-articular and extended oligo-articular JIA patients, before and after anti-TNF therapy withdrawal, to identify features associated with maintenance of inactive disease (ID). Individual CpG sites were clustered in coherent modules without a priori knowledge of their function through network analysis. The methylation level of several CpG modules, specifically those enriched in CpG sites belonging to genes that mediate T cell activation, uniquely correlated with clinical activity. Differences in DNA methylation were already detectable at the time of therapy discontinuation, suggesting epigenetic predisposition. RNA profiling also detected differences in T cell activation markers, including HLA-DR, but, overall, its sensitivity was lower than epigenetic profiling. Changes to the T cell activation signature at the protein level were detectable by flow cytometry, confirming the biological relevance of the observed alterations in methylation. Our work proposes, for the first time, epigenetic discrimination between clinical activity states, and reveals T cell-related biological functions tied to, and possibly predicting and/or causing, clinical outcome.

overall_design: We measured DNA methylation (single replicates) in 136 CD4+ T cell samples form 63 randomly selected patients recruited in the trial “Determining Predictors of Safe Discontinuation of Anti-TNF Treatment in JIA” (ID: NCT00792233). At baseline (T0), patients were in clinical remission on medication, i.e., they maintained ID, for at least 6 months under treatment (anti-TNF). Therapy was withdrawn for eight months, after which (Tend) patients were stratified by clinical activity in patients maintaining ID or not (NO ID). Flares were tested at the time of flare (Tend), and therapy was then reintroduced.

first: Roberto

last: Spreafico

first: John

middle: W

last: Whitaker

first: Wei

first: Daniel

last: Lovell

first: Salvatore

last: Albani


title: DNA methylome analysis of human peripheral blood samples in cancer discordant monozygotic twin-pairs

status: Public on Oct 25 2016

city: London

first: Tim

last: Spector

address: Westminster Bridge road

department: Twin Research and Genetic Epidemiology

country: United Kingdom

institute: King's College London

summary: Genome wide DNA methylation profiling with the HumanMethylation450 BeadChip (450k) of peripheral blood samples of 46 adult female monozygotic twin-pairs obtained at the same time point. Samples included 41 healthy females (not diagnosed with cancer to date) paired with their co-twin diagnosed with cancer within a 5 year window around the time of sampling as well as 5 extra pairs with a co-twin diagnosed with cancer within 11 to 5 years prior to blood sampling.

overall_design: Bisulphite converted DNA from the 92 samples were hybridised to the Illumina HumanMethylation450 BeadChip

first: Leonie

last: Roos

first: Jordana

last: Bell


title: BLUEPRINT hematopoietic progenitors

status: Public on Nov 06 2016

city: Vienna

first: Christoph

last: Bock

address: Lazarettgasse 14

country: Austria

institute: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences

type: Expression profiling by high throughput sequencing

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to the individual SubSeries listed below.


title: Epipolymorphisms associated with the clinical outcome of autoimmune arthritis affect CD4+ T cell activation pathways

type:
Methylation profiling by array
Expression profiling by array

overall_design: Refer to individual Series


title: Gene expression profiles of mouse monocytes deficient in the CCL2/CCR2 chemokine signaling

status: Public on Oct 21 2016

city: Boston

first: Barrett

last: Rollins

state: MA

address: 450 Brookline Ave

institute: Dana-Farber Cancer Institute

summary:
Gene-level transcriptome analysis of monocyte mRNA derived from mice that are genetically deficient of the Ccl2 gene or Ccr2 gene
The CCL2/CCR2 chemokine axis is critical in monocytes mobilization and innate immunity. Although mice deficient in either gene manifest similar phenotype, such as reduced atherosclerosis, some biologic processes are disrupted in starkly different ways in these mice. We found in a Her2/neu driven mammary carcinoma model, the absence of Ccl2 inhibits tumor growth and prolongs survival, while genetic deletion of Ccr2 has the opposite effect. One of the postulated mechanisms is that Ccl2 and Ccr2 affect monocyte development in different manners. This experiment was designed to compare the whole transcriptome of monocytes that are deficient in either Ccl2 or Ccr2, with the hypothesis that differential development of these monocytes will manifest as differential gene expression profiles.

overall_design: We purified monocytes from peripheral blood of mice by MACS (magnetic activated cell sorting) technique. Given the relative scarcity of mouse monocytes in the peripheral blood, we pooled the white blood cells from 5 mice in each sample, and compared 3 replicate samples from wild type Balb/cJ mice, and Ccl2-/- and Ccr2-/- mice on the same genetic background. We analyze each sample using the Affymetrix GeneChip Mouse Gene 1.0 ST Array. Array data was processed using the dChip software.

first: Xuguang

last: Chen


title: Functional enterospheres derived in vitro from human pluripotent stem cells

city: Hamilton

first: Jon

last: Draper

state: On

address: 1200 Main Street West

department: Pathology and Molecular Medicine

institute: McMaster University

summary: Comparison of gene expression signatures in hESC-derived gastrointestinal precursors, enterospheres and primary human tissues to determine lineage and cell type identity.

overall_design: Comparison of gene expression using microarray analysis (Affymetrix Human Gene 2.0 ST).

first: Rohan

middle: R

last: Nadkarni

first: Soumeya

last: Abed

first: Brian

last: Cox

first: Sonam

last: Bhatia

first: Jennifer

middle: T

last: Lau

first: Michael

middle: G

last: Surette

first: Jonathan


title: Gene expression analysis of mouse E9.5 presomitic mesoderm wt vs TCre/+;Taf10flox/flox

city: Illkirch

first: Stephane

middle: D

last: VINCENT

address: 1 rue Laurent Fries

department: Development and Stem Cells

country: France

institute: IGBMC

summary: Presomitic mesoderm (PSM) were microdissected from E9.5 mouse embryos (WT and TCre/+;Taf10flox/flox). 3 PSM (17-19 somites stage) were pooled per microarray, in triplicates, per genotypes

first: Stéphane

last: Vincent

first: Olivier

last: Pourquié


title: DNA methylation profile for BL2 and BL2 AID-/- cell lines

city: New Haven

first: Yang

last: Xi

address: 300 George St

department: Cancer Center

institute: Yale University

type: Methylation profiling by genome tiling array

summary: AID (activation-induced cytidine deaminase) is expressed at low levels in many tissue types but is most highly expressed in germinal center B cells where it deaminates cytidine to uracil during somatic hypermutation and class switch recombination of the immunoglobulin genes. In addition to this critical role in immune diversification, aberrant targeting of AID contributes to oncogenic point mutations and chromosome translocations associated with B cell malignancies. Thus, to explore a role for AID in DNA demethylation in B cell lymphoma, we performed genome-wide methylation profiling in BL2 and AID-deficient (AID-/-) BL2 cell lines (Burkitt lymphoma that can be induced to express high levels of AID).

overall_design: Using Illumina's Infinium II DNA Methylation assay combined with the Infinium Human Methylation 450 BeadChip, we analyzed over 450,000 methylation (CpG) sites in two samples, BL2 and BL2 AID-/- cell lines, at single nucleotide resolution.

first: Velizar

last: Shivarov

first: Matthew

last: Strout


title: In vivo gene expression profiling of mouse tumor progenitor cells with differences in EGFRvIII activation

status: Public on Oct 17 2016

city: San Francisco

first: Joanna

last: Phillips

state: California

address: 1450 3rd Street

department: Neurosurgery

institute: UCSF

summary:
Murine gliomblastoma tumor progenitor cells TPCs with high and low EGFRvIII activity, pEGFR-Hi and pEGFR-Lo, showed differences in proliferation, differentiation, and invasion. Zs-Green-expressing
TPCs were injected intracranially into immune-competent FVB mouse and tumor cells isolated at median survival +/-1 day by FACS followed by RNA isolation.

overall_design: Expression analysis of FACS-isolated Green-expressing tumor cell from in vivo tumors

first: Olle

last: Lindberg

first: Andrew

last: McKinney

first: Jane

last: Engler

first: Gayane

last: Koshkakaryan

first: Henry

last: Gong

first: Aaron

middle: E

last: Robinson

last: Ewald

first: Emmanuelle

last: Huillard

first: C

last: James

first: Annette

middle: M

last: Molinaro

first: Joseph

last: Shieh


title: Human intervention study to assess the effects of supplementation with olive leaf extract on peripheral blood mononuclear cell gene expression

status: Public on Oct 18 2016

city: Auckland

first: Anna

last: Boss

address: 85 Park Rd

country: New Zealand

institute: University of Auckland

summary:
Olive oil is correlated to long life and low rates of cancers and cardiovascular disease. The health benefits of the oil is contributed to the polyphenols. The polyphenols in olive leaf are simialr bit in high concentrations. We wanted to uncover whether measurable changes would occur with supplementation in human participants.
we used affymetrix arrays to measure the gene expression changes with olive leaf extract compared to placebo control.

overall_design: Intervention trial- parallel 8 week

first: Lynnette

last: Ferguson


title: Lysophosphatidylcholines activate PPARδ and protect human skeletal muscle cells from lipotoxicity

status: Public on Oct 14 2016

city: Tuebingen

first: Christian

last: Klingler

address: Otfried-Mueller Street 10

department: Medical Clinic IV

institute: IDM at the University Hospital Tuebingen

summary: Metabolomics studies of human plasma demonstrate a correlation of lower plasma lysophosphatidylcholines (LPC) concentrations with insulin resistance, obesity, and inflammation. This relationship is not unraveled on a molecular level. Here we investigated the effects of the abundant LPC(16:0) and LPC(18:1) on human skeletal muscle cells differentiated to myotubes. Transcriptome analysis of human myotubes treated with 10 µM LPC for 24 h revealed enrichment of up-regulated peroxisome proliferator-activated receptor (PPAR) target transcripts, including ANGPTL4, PDK4, PLIN2, and CPT1A. The increase in both PDK4 and ANGPTL4 RNA expression was abolished in the presence of either PPARδ antagonist GSK0660 or GSK3787. The induction of PDK4 by LPCs was blocked with siRNA against PPARD. The activation of PPARδ transcriptional activity by LPC was shown as PPARδ-dependent luciferase reporter gene expression and enhanced DNA binding of the PPARδ/RXR dimer. On a functional level, further results show that the LPC-mediated activation of PPARδ can reduce fatty acid-induced inflammation and ER stress in human skeletal muscle cells. The protective effect of LPC was prevented in the presence of the PPARδ antagonist GSK0660. Taking together, LPCs can activate PPARδ, which is consistent with the association of high plasma LPC levels and PPARδ-dependent anti-diabetic and anti-inflammatory effects.

overall_design: Human myotubes from four different donors were treated with 10 µM LPC(16:0) or LPC(18:1) or solvent for 24 h

first: Xinjie

last: Zhao

first: Till

last: Adhikary

first: Jia

last: Li

first: Guowang

last: Xu

first: Hans-Ulrich

last: Häring

first: Erwin

last: Schleicher

first: Rainer

last: Lehmann

first: Cora

last: Weigert


title: Gene expression data of trial drug Dehydroabietylamine derivative-2 (DAAD-2) for Sensitive (HEP3B) and resistant (SNU449) hepatocellular carcinoma (HCC) cell lines with controls

city: Karachi

first: Muhammad

middle: Ayaz

last: Mustufa

state: Sindh

address: Rafeequee Shaheed road

department: SRCCH

country: Pakistan

institute: PHRC

summary:
Hepatocellular carcinoma (HCC) is a highly prevalent and deadly disease world-wide. The survival of HCC patients is usually very poor due to the lack of efficient anti-cancer drugs
acting against HCC cells. Structural modification is one of the important routes in chemical field for finding novel drugs with more potential bioactivities and broad bioactive spectra. Hence, a dehydroabietylamine derivative (DAAD-2) is prepared and subjected for cytotoxic activities on HCC cell lines.

overall_design: Qualitative, analytical study for gene expression profiling by array

first: M

last: Ozturk

last: Ozen

middle: A

first: G

last: Yildiz


title: A commonly inactivated tumor suppressor silences endogenous retroelements in somatic cells [Affymetrix expression]

first: Fred

last: Dick

state: ON

address: Cancer Research Labs 790 Commissioners Road East

institute: Western University

summary: Upon G1-S transition, cyclin-dependent kinases (CDKs) phosphorylate the retinoblastoma tumor suppressor protein (pRB) to release E2F transcription factors, which activate transcriptional programs, required for S-phase entry. Beyond the G1-S transition, pRB activity remains poorly understood. Our lab has discovered that pRB retains exclusive binding to E2F1 through an alternate E2F1-‘specific’ binding site at the pRB c-terminus independent of CDK phosphorylation. We have developed a gene-targeted mouse model that is defective for the E2F1-‘specific’ interaction. We are exploring the function of this complex through genome-wide binding and expression profiling. Overall, this work suggests an alternate pRB-E2F1 complex persists independent of CDK phosphorylation to establish regions of constitutive heterochromatin

overall_design: Total RNA was extracted from wild-type and mutant MEFs following 72h of serum deprivation. Expression levels were determined using the Affymetrix GeneChip Mouse Gene 1.0ST Array followed by analysis using Partek genomics suite to generate RMA values.

first: Frederick

first: Charles

last: Ishak

first: Aren

last: Marshall


title: Expression data from human osteosarcoma cells after transfected miR-206

status: Public on Oct 24 2016

first: Zhenfeng

last: Duan

state: Massachusetts

address: 55 Fruit Street Jackson Building

institute: Massachusetts General Hospital

summary: The U-2OS and KHOS osteosarcoma cell lines were seeded into the 100mm cell culture plate respectively, then transfected miRSelect pEP-miR-206 or miRSelect pEP-miR-Null into the two cell lines with Lipofectamine LTX and Plus Reagent (Invitrogen) for 48 hours. After that, total RNA was collected from these cells using TRIzol® Reagent (GIBCO Grand Island, NY) according to the manufacturer’s instructions. To account for and eliminate biologic noise, RNA was isolated from three distinct flasks of each cell line and pooled together. RNA quality was determined via ethidium bromide staining following agarose/formaldehyde gel electrophoresis. Total RNA was processed and hybridized to Affymetrix Genechip HG-U95Av2 arrays (Affymetrix, Santa Clara, CA) by the Gene Array Technology Center at Harvard Medical School (http://genome.med.harvard.edu). Affymetrix Gene Chip U133 Plus 2.0 in the first and most comprehensive whole human genome expression array. This array completes coverage of the whole human Genome with over 47,000 transcripts. The expression level of each mRNA is quantified by measuring its hybridization to these 23-mers in comparison to its hybridization to a one-base mismatch oligonucleotide. Qlucore were used to analyze the microarray data (http://www.qlucore.com). Fold change in expression between miR-206 treated cell lines and control cell lines were evaluated using the Mann-Whitney test. A 1.2 foldchange or greater change in intensity combined with a Mann-Whitney associated P value less than 0.05 was used as the criterion for inclusion in our filtered data set.

overall_design: Evalutate the effect of miR-206 regulated gene expression in osteosarcoma cells

first: Chao

last: Han


title: Expression data from invasive lobular carcinoma

status: Public on Oct 15 2016

city: Brussel

first: Yacine

last: Bareche

address: Rue Héger-Bordetstraat 1

country: Belgium

institute: Jules Bordet Institute

summary:
Background: The prognostic value of histologic grade (HG) in invasive lobular carcinoma (ILC) remains uncertain, and most ILC tumors are graded as HG2. Genomic grade (GG) is a 97-gene signature that improves the prognostic value of HG. This study evaluates whether GG may overcome the limitations of HG in ILC.

Methods: Gene expression data were generated from frozen tumor samples, and GG calculated according to the expression of 97 genes. The prognostic value of GG was assessed in a stratified Cox regression model for invasive disease-free survival (IDFS) and overall survival (OS).

overall_design: Gene expression data were generated from frozen tumor samples of patients with ILC.

first: O

last: Metzger-Filho

first: S

last: Michiels

first: F

last: Bertucci

first: A

last: Catteau

first: R

last: Salgado

first: C

last: Galant

first: D

last: Fumagalli

middle: K

last: Singhal

last: Desmedt

last: Ignatiadis

last: Haussy

first: P

last: Finetti

last: Birnbaum

first: K

last: Saini

last: Berlière

first: I

last: Veys

first: E

last: de Azambuja

last: Bozovic

first: H

last: Peyro-Saint-Paul

last: Larsimont

last: Piccart

last: Sotiriou


title: Integrative Epigenome-Wide Analysis Shows That DNA Methylation May Mediate Genetic Risk In Inflammatory Bowel Disease [Cells, Methylation profiling]

status: Public on Nov 13 2016

city: Edinburgh

first: Nichols

last: Ventham

address: Western General Hospital

department: CGEM

institute: Univerisity of Edinburgh

summary:
Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe  epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two genetic polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data highlight the cell type of origin of epigenetic signals seen in whole blood; IBD-associated hypermethylation within the TXK gene transcription start-sitepromoter region negatively correlates with gene expression in whole blood and CD8+ T-cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD are relatedrelate to underlying genotype and associate with cell-specific alteration in gene expression.

overall_design:
DNA methylation profiling using the Illumina450K array in whole blood and separated cells (CD14+ monocytes, CD4+ and CD8+ T-cells, naive CD4+ T Cells) in inflammatory bowel disease cases and controls

Several samples were excluded during sample processing (e.g. sex mismatches, mislabelled samples, technical replicates). The following samples were excluded in the final analysis (P009034-16122013-TD8-01, P009034-16122013-TDM-01,  P009034-16122013-TD4-01, P008985-09102013-TDM-01, P007821-10102013-TDM-01, P007821-10102013-TD8-01,  P008946-28082013-TDM-01). The following technical replicates were also excluded from final analysis (P009050-10012014-TB-01_R2, P009050-10012014-TB-01_R3, P009050-10012014-TB-01_R4)
Simplified_Diagnosis: CD=Crohn's disease, UC=Ulcerative colitis, HC=Control
Full_Diagnosis: CD=Crohn's disease, UC=Ulcerative colitis, HL=Healthy Lab Control, IB = Symptomatic Control
Cell Type: wh blood = whole blood, monocytes = CD14+ monocytes, CD4= CD4+ T-Cell, CD8 = CD8+ T-Cell

first: Nicholas

first: Jack

last: Satsangi


title: Genome-wide methylation profiling of ovarian cancer patient-derived xenograft (PDXs) treated with the demethylating agent decitabine identifies novel epigenetically regulated genes and pathways

status: Public on Oct 10 2016

city: Groningen

first: G. Bea

middle: A.

last: Wisman

state: Groningen

address: Hanzeplein 1

department: Department of Gynecologic Oncology

country: Netherlands

institute: University of Groningen, University Medical Centre Groningen

summary:
Background: In high-grade serous ovarian cancer (HGSOC) intrinsic and/or acquired resistance against platinum-containing chemotherapy is a major obstacle for successful treatment. A low frequency of somatic mutations, but frequent epigenetic alterations including DNA methylation in HGSOC tumors, presents the cancer epigenome as a relevant target for innovative therapy. Patient-derived xenografts (PDXs) supposedly are good preclinical models for identifying novel drug targets. However, the representativeness of global methylation status of HGSOC PDXs compared to their original tumors has not been evaluated. Aims of this study were to explore how representative HGSOC PDXs are for their corresponding patient tumors methylome and to evaluate the effect of epigenetic therapy and cisplatin on putative epigenetically regulated genes and their related pathways in PDXs.
Methods: Genome-wide analysis of the DNA methylome of HGSOC patients with their corresponding PDXs, from different generations, was performed using Infinium 450K. Further, we analyzed global methylome changes after treatment of HGSOC PDXs with the FDA approved demethylating agent decitabine and cisplatin. Findings were validated by bisulfite pyrosequencing with subsequent pathway analysis. Publicly available datasets comprising HGSOC patients were used to analyze the predictive/prognostic value of the identified genes.
Results: Only 0.6-1.0% of all analyzed CpGs (388,696 CpGs) changed significantly (p<0.01) during propagation showing that HGSOC PDXs are epigenetically stable. Treatment of F3 PDXs with decitabine caused a significant reduction in methylation in 10.6% of CpG sites in comparison to untreated PDXs (p<0.01, FDR<10%). Cisplatin treatment had a marginal effect on the PDX methylome. Pathway analysis of decitabine-treated PDX tumors revealed several putative epigenetically regulated pathways (e.g. Src family kinase pathway). Particularly, C-terminal Src kinase (CSK) gene was successfully validated for epigenetic regulation in different PDX models and ovarian cancer cell lines. Low CSK methylation and high CSK expression were both significantly associated (p<0.05) with improved progression free survival and overall survival in HGSOC patients.
Conclusion: HGSOC PDXs resemble the global epigenome of patients over many generations, which can be modulated by epigenetic drugs. Novel epigenetically regulated genes such as CSK and related pathways were identified in HGSOC. Our results encourage future application of PDXs for cancer epigenome studies.

overall_design: DNA was isolated from frozen tumors of three different ovarian PDXs models up to 3 generations (F0, F1, F2 and F3) (n=12), one PDX model with treatment of vehicle, cisplatin and Decitabine (DAC) with 3 mice in each group and SKOV3 cell line with and without DAC treatment. Bisulphite converted DNA from each sample (n=22) was hybridized to the Illumina Infinium 450k Human Methylation BeadChip.

first: Tushar

last: Tomar

first: Steven

last: de Jong

first: G

middle: B


title: Expression data of siFAM210B and control A549 cells

status: Public on Oct 12 2016

city: Wuhan

first: Shujuan

last: Sun

address: Cancer Biology Research Center, Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology, 1095 JiefangAnv, Wuhan,China

country: China

institute: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

summary:
Our previous study screened a novel cancer progression suppressor gene, FAM210B, which encodes an outer mitochondrial membrane protein, by the suppression of mortality by antisense rescue technique (SMART). We demonstrated that FAM210B loss was significantly associated with cancer metastasis and decreased survival in a clinical setting.
We used microarrays to find diffrenet gene expression between siFAM210B and control A549 cells

overall_design: A549 cells were transfected with siRNA for 72h  for RNA extraction and hybridization on Affymetrix microarrays, and Realtime PCR were used to verified the effect of siRNA knockdown. We used  mixed siRNA, tirplicated per sample and designed the control to increase the resolution of expression profiles.

first: Jia

last: Liu


title: The Somatic Landscape of Schwannoma

city: PITTSBURGH

first: SAMEER

last: AGNIHOTRI

state: Pennsylvania

address: Rangos Research Center, 7th Floor, ROOM 7126, 530, 45th Street

department: MacFeeters-Hamilton Brain Tumour Centre

institute: University of Pittsburgh

summary: To identify the role of the SH3PXD2A-HTRA1 fusion on gene expression in Schwann cells

overall_design: Immortailzed Schwann cells expressing empty vector control were compared to immortalized Schwann cells expressing a Fusion protein. Three biological replicates per condition were used.

first: Gelareh

last: Zadeh


title: Differential gene expression data from MCF7 and MCF7_ADR

status: Public on Oct 13 2016

city: Daegu

first: Sarala

last: Manandhar

address: 80 Daehakro, Bukgu

department: College of Pharmacy

country: South Korea

institute: Kyungpook National University

summary:
To identify differentially up or downregulated genes in MCF7_ADR cell compare to MCF7, we have employed whole genome microarray expression profiling.
We used microarray to evaluate the up or down regulated genes in doxorubicin resistant MCF7_ADR cells compare to MCF7

overall_design: Healthy MCF7 and MCF7_ADR cells were used for extraction of RNA and  hybridization on Affymetrix microarray

first: You-Mie

last: Lee

first: Chan-Gu

last: Kim


title: Expression data from human-derived oligodendrocytes, astrocytes and fibroblasts

city: Sheffield

first: Laura

last: Ferraiuolo

address: 385a Glossop Road

institute: University of Sheffield

summary: Oligodendrocytes have recently been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). Here we differentiated fibroblasts into induced neural progenitors and subsequently into oligodendrocytes and astrocytes. To confirm that the cells obtained with this protocol express the gene signature of oligodendrocytes, we performed a small gene expression study limited to four iOligodendrocyte lines from two controls (nos. 155 and 170) and two patients (nos. 12 and 17), four iAstrocyte lines from the same samples, and four fibroblast lines from one of our previously published studies

overall_design: We performed a small gene expression study limited to four iOligodendrocyte lines from two controls (nos. 155 and 170) and two patients (nos. 12 and 17), four iAstrocyte lines from the same samples, and four fibroblast lines from one of our previously published studies

first: Paul

middle: H

last: Heath


title: Genomic Landscape of Schwannoma

summary: Epigenome analysis of schwannoma tumor samples

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

first: Kenneth

last: Aldape


title: mRNA, miRNA and SNP profiles of 50 HB tumors

city: Houston

first: Toni-Ann

last: Mistretta

state: TX

address: 1 Baylor Plaza, BCM 315

department: Pathology

institute: Baylor College of Medicine

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

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

overall_design: Refer to individual Series


title: Implication of an Immune Score in Molecular Subtypes and Distant Metastasis of Breast Cancer: Comparison between Western and Chinese Han Patients

city: Winston-Salem

first: Jeff

last: Chou

state: NC

address: Medical Center Blvd

institute: Atrium Health Wake Forest Baptist

summary: Seventy-one breast cancer patients with stages II and III breast cancer were included. They received four preoperative cycles of a weekly PCb (paclitaxel plus carboplatin) regimen. The purpose of this study was to examine the predictive value of the ER pathway for a response to chemotherapy using a gene microarray method. In addition, this study aimed to identify novel ER-related genes, which, combined with ER levels, would provide a robust multi-variable prediction of patient outcome to chemotherapy.

overall_design: Biopsy tissue was taken from patients received neoadjuvant chemotherapy. They received four preoperative cycles of a weekly PCb (paclitaxel plus carboplatin) regimen. The arrays were washed and stained according to the Affymetrix protocol (EukGE-WS2v4) using a GeneChip Fluidics Station 450 (Affymetrix). The arrays were scanned with the GeneChip Scanner 3000 (Affymetrix).

first: Zhiyuan

last: Hu

first: Benlong

last: Yang

first: Chunxiao

last: Wang

first: Naim

last: Rashid

first: Yiwei

last: Chu

first: Tong

last: Zhou

first: William

last: Kaufmann

first: Jiong

last: Wu


title: Transcriptional response of terminal ileum to bacterial monocolonization

status: Public on Oct 07 2016

city: Boston

first: CBDM

last: Lab

address: 77 Avenue Louis Pasteur

department: Microbiology and Immunobiology

institute: Harvard Medical School

summary: Here we analyzed the transcriptional profile of the terminal ileum of GF mice or mice monocolonized with three different bacterial species (C. histolyticum, B. adolescentis, or SFB) for 2 weeks.

overall_design: A small 3-5 mm segment of the terminal ileum of mice was placed directly into TRIzol.

first: Tze

last: Tan

first: Naama

last: Geva-Zatorsky

first: Esen

last: Sefik

first: Lindsay

last: Kua

first: Debdut

last: Naskar

first: Fei

last: Teng

first: Lesley

last: Pasman

first: Adriana

last: Ortiz-Lopez

first: Ray

last: Jupp

first: Hsin-Jung

middle: J

first: Dennis

middle: L

last: Kasper

first: Christophe

last: Benoist

first: Diane

last: Mathis


title: Integrative Epigenome-Wide Analysis Shows That DNA Methylation May Mediate Genetic Risk In Inflammatory Bowel Disease

first: Nichols

last: Ventham


title: mRNA profiles of 50 HB tumors

first: Toni-Ann

last: Mistretta

summary: Hepatoblastoma (HB) is the most common liver cancer in children, but few pre-treatment tumors have been molecularly profiled. Consequently, there are no validated prognostic or therapeutic biomarkers for HB patients. We report on molecular analysis of 88 clinically-annotated HB tumors. This analysis pointed to three risk-stratifying molecular subtypes—low, intermediate and high risk—that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways. High-risk tumors are characterized by high NFE2L2 activity and LIN28B, HMGA2, SALL4 and AFP expression, low let-7 expression and HNF1A activity, and high coordinated expression of oncofetal proteins and stem cell markers. Tests on a 35 HB validation set supported these genes as prognostic biomarkers.

overall_design: 88 clinically-annotated frozen pre-clinical HB specimens with corresponding surgical pathology reports were included in the study (Table S1) following histological review. Specimens and clinical annotation were obtained from the COG Tumor Biospecimen Bank in Columbus, Ohio, the Pediatric Oncology Group Hepatoblastoma Biology Study P9346, and Texas-based institutions, under IRB-approved protocols. Whole exome sequencing (WES) was performed on 35 tumors for which matching normal DNA – either a blood sample or tumor-adjacent normal liver – was available (Table S2). Targeted sequencing of the CTNNB1 and NFE2L2 genes and the TERT promoter was completed on all 88 tumors. DNA from 47 HBs, including all 35 samples subjected to WES, was also analyzed by SNP array. RNA and miRNA expression profiling were performed on 50 and 57 tumors, respectively.

first: Pavel

last: Sumazin

first: Yidong

last: Chen

first: Lisa

last: Treviño

first: Stephen

last: Sarabia

first: Oliver

last: Hampton

first: Kayuri

last: Patel

first: Barry

last: Zorman

first: Patrick

last: Thompson

first: Andras

last: Heczey

first: Sarah

last: Comerford

first: David

last: Wheeler

first: Murali

last: Chintagumpala

first: Rebecka

last: Meyers

first: Dinesh

last: Rakheja

first: Milton

last: Finegold

first: Gail

last: Tomlinson

first: D

last: Parsons

first: Dolores

last: López-Terrada


title: Mafb lineage tracing marks macrophages

status: Public on Oct 01 2016

city: St. Louis

first: Xiaodi

last: Wu

state: Missouri

address: 4940 Parkview Pl

institute: Washington University/HHMI

summary: Current systems for conditional gene deletion within mouse macrophage lineages are limited by ectopic activity or low efficiency; we generated a Mafb-driven Cre strain to determine whether any dendritic cells (DCs) identified by Zbtb46-GFP expression originate from a Mafb-expressing population

overall_design: Ly-6C(hi) monocytes, Ly-6C(lo) YFP(-) monocytes, and Ly-6C(lo) YFP(+) monocytes were isolated by FACS from blood samples harvested from MafB-mCherry-Cre x R26-stop-YFP x Zbtb46-GFP lineage-tracing mice

first: Kenneth

last: Murphy


title: Comparative DNA methylation profiling reveals an immunoepigenetic signature of HIV-related cognitive impairment

status: Public on Oct 05 2016

city: New York

first: Michael

last: Corley

state: NY

address: 413 East 69th Street

department: Medicine, Division of Infectious Diseases

institute: Weill Cornell Medicine

summary: Genome wide DNA methylation profiling of isolated human CD14+16+ monocyte and CD8+ T cell samples from HIV-infected individuals with cognitive impairment and without.

overall_design: Bisulphite converted DNA from the 21 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: Alika

last: Maunakea


title: Epigenome analysis for spina bifida

status: Public on Oct 03 2016

city: Leuven

first: Anne

last: Rochtus

state: Vlaams-Brabant

address: Herestraat 49, Box 911

department: Cardiovascular Sciences

institute: University of Leuven

summary: Genome wide DNA methylation profiling of 10 patients with myelomeningocele (MMC) and 6 healthy controls

overall_design: Bisulphite converted DNA from the samples were hybridised to the Illumina HumanMethylation 450k BeadChip

first: Kathleen

last: Freson


title: Transcriptional profile of pancreatic and splenic Treg cells

first: CBDM

last: Lab

summary: Here we analyzed the transcriptional profile of pancreatic and splenic Treg cells from prediabetic NOD mice.

overall_design: Treg cells were double-sorted from the pancreata and spleens of 10-week-old prediabetic female NOD.Foxp3-ires-gfp mice directly into TRIzol. RNA was prepared in Trizol for gene expression profiling by  Affymetrix Mouse Gene 1.0 ST Arrays.

first: Tze

last: Tan

first: Diane

last: Mathis

first: Christophe

last: Benoist


title: Gene expression data from head and neck cancer patient derived xenografts

city: Berlin

first: Raik

last: Otto

state: Berlin

address: Rudower Chaussee 25

department: Computer Science

institute: Humboldt-Universität zu Berlin

summary:
Head and neck cancer is a hetergeneous disease. Based on previoulsy defined molecular subtypes we associated gene expression with response to different compounds. We used microarry gene expression for molecular subtyping
Cetuximab is the single targeted therapy approved for the treatment of head and neck cancer (SCCHN). Predictive biomarkers have not been established in the clinical setting and patient stratification based on molecular tumor profiles has not been possible. Since EGFR pathway activation is pronounced in basal subtype, we hypothesized this activation could be a predictive signature for an EGFR directed treatment. From our patient derived xenograft platform of head and neck cancer, 28 models were subjected to Affymetrix gene expression studies on HG U133+ 2.0. Based on the expression of 821 genes, the subtype of each of the 28 models was determined by integrating gene expression profiles through centroid-clustering with previously published gene expression data by Keck et al.,CCR 2015. Response was evaluated by comparing tumor volume at treatment initiation and after three weeks of treatment (RTV).

overall_design:
Untreated control tumors of 3rd passage were harvested and subjected to gene expression studies.
basal (BA), mesenchymal (MS), atypical (AT), and classical (CL)

first: Konrad

last: Klinghammer


title: Effect of timed sleep restriction on transcriptome rhythms in the MBH of mice

city: Lübeck

first: Henrik

last: Oster

address: Marie Curie Street

department: CBBM

institute: University of Lübeck

summary:
Timed sleep restriction designed to mimic human shift work was performed over a 2 week period in mice. On the final day, MBH biopsies were collected at 6 hour intervals to exmaine the effects of sleep restriction on circadian gene expression.
(MBH = mediobasal hypothalamus)

overall_design: 3 mice were used at each time point, for both controls and sleep restricted (TSR) groups

first: J

last: Husse

last: Kiehn

last: Barclay

first: B

last: Bode

first: N

last: Naujokat

last: Meyer-Kovac

first: H

last: Lehnert


title: The NCI60 DNA methylome

status: Public on Oct 08 2016

city: L'Hospitalet de Llobregat

first: Manel

last: Esteller

state: Barcelona

address: Hospital Duran i Reynals Av. Gran Via s/n km, 2.7

department: PEBC

country: Spain

institute: IDIBELL

summary: Comprehensive characterization of the DNA methylome in the NCI60 cancer cell line panel

overall_design: Array-based profiling of DNA methylation in 60 cancer cell lines.

first: Holger

last: Heyn


title: Expression data from 20-day-old mouse Sertoli cells and 20-day-old Sertoli cell treated with 500 nm Microcystin-Leucine Arginine (MC-LR)

status: Public on Sep 30 2016

city: Nanjing

first: Yabing

last: Chen

address: No. 22 Hankou Rd., Gulou District, Nanjing, Jiangsu

institute: Nanjing University

summary:
Microcystin-Leucine Arginine causes cytotoxic effects in Sertoli Cells
We used microarrays to analyze up-regulated and down-regulated genes to investigate the molecular mechanism associated with cytotoxic effects in Sertoli cells treated with MC-LR

overall_design: Primary mouse Sertoli cells were isolated and cultured for 48 h, cells were then treated with MC-LR. Microarray technique was used to analyze differently expressed genes to understand the molecular mechanism associated with cytotoxicty induced with MC-LR.

first: Xiaodong

last: Han

first: Yuan

last: Zhou


title: Expression data for iPSC-derived hepatocyte-like cells (HLCs) treated with 100 µM pazopanib for 24 hours

city: Singapore

first: Yukti

last: Choudhury

address: 31 Biopolis Way

country: Singapore

institute: Institute of Bioengineering and Nanotechnology, A*STAR

summary: Pazopanib is a drug with idiosyncratic hepatotoxicity risk. Analysis of gene expression changes after exposing hepatocytes can indicate effects on specific biological pathways and  potential mechanisms of hepatotoxicity. HLCs derived from patient-specific iPSCs were treated with pazopanib to identify both drug-related global effects and patient-specific effects

overall_design: HLCs (200,000) differentiated from iPSCs from HT1, HT2 and HT3 (patients with clinical hepatotoxicity) and NHT1 and NHT2 (patients without clinical hepatotoxity) were each treated with pazopanib or DMSO for 24 hours. RNA was isolated. Primary analysis was differential gene expression analysis for each sample compared to vehicle control. Secondary analysis compared HT to  NHT samples, after data normalization to respective controls. Gene set enrichment analysis to measure enrichment of custom gene sets in pazopanib treatment and and to identify differential enrichment of gene sets between HT and NHT cases.


title: Amygdalar microRNA-15a is essential for coping with chronic stress

city: Rehovot

first: Alon

address: 234 Herzel St.

department: Neurobiology

country: Israel

institute: The Weizmann Institute of Science

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

platform_organism:
Mus musculus
synthetic construct


title: Gene expression data from iPSC-derived astrocytes, comparison

city: Kyoto

first: Haruhisa

last: Inoue

state: Kyoto

address: 53 Kawahara-cho, Shogoin, Sakyo-ku

country: Japan

institute: Kyoto University

summary: Alexander disease (AxD) is a fatal neurological illness characterized by white-matter degeneration and formation of Rosenthal fibers, which contain glial fibrillary acidic protein (GFAP) as astrocytic inclusion. AxD is mainly caused by a gene mutation encoding GFAP, although the underlying pathomechanism remains unclear.

overall_design: We differentiated human iPSCs into astrocytes and analyzed gene expression profiles of control and the AxD astrocytes. Comparison between control (n=3) and AxD (n=1)

first: Takayuki

last: Kondo


title: Transcriptional response of small intestinal epithelial cells (S-IECs) to bacterial monocolonization

first: CBDM

last: Lab

summary: Here we analyzed the transcriptional profile of S-IECs sorted from GF and monocolonized mice (C. histolyticum and B. adolescentis), as well as SPF mice colonized with SFB or not.

overall_design: S-IECs were double-sorted from mice colonized with the respective bacterial species directly into TRIzol.

first: Tze

last: Tan

first: Naama

last: Geva-Zatorsky

first: Esen

last: Sefik

first: Lindsay

last: Kua

first: Debdut

last: Naskar

first: Fei

last: Teng

first: Lesley

last: Pasman

first: Adriana

last: Ortiz-Lopez

first: Ray

last: Jupp

first: Hsin-Jung

last: Wu

first: Dennis

last: Kasper

first: Christophe

last: Benoist

first: Diane

last: Mathis


title: Purified CD123+BDCA4+ plasmacytoid dendritic sorted cell-population derived from IFN signature positive primary Sjögren’s syndrome  patients and IFN signature negative primary Sjögren’s syndrome patients compared to Healthy Control individuals

status: Public on Sep 28 2016

city: Rotterdam

first: Arne

last: IJpma

address: Dr. Molewaterplein 50

department: Bioinformatics

institute: Erasmus MC

summary:
The IFN type I signature is present in over half of primary Sjögren’s syndrome (pSS) patients and associated with higher disease-activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered to be the source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of pSS patients.
We used microarray gene expression analysis to detail the programme of gene expression underlying IFN type I bioactivity in  pDCs of primary Sjogrens' Syndrome patients.

overall_design:
Microarray expression data from purified CD123+BDCA4+ plasmacytoid dendritic sorted cell-population derived from IFN signature positive primary Sjögren’s syndrome  patients and IFN signature negative primary Sjögren’s syndrome patients, compared to Healthy Control individuals
We isolated RNA from FACS sorted CD123+BDCA4+ plasmacytoid dentritic cells (pDCs) and compared gene expression of IFN signature positive primary Sjögren’s syndrome  patients (pSS), IFN signature negative pSS patients and Healthy Control (HC) individuals. pDCs obtained from 4 HC, 3 IFNneg and 3 IFNpos pSS patients were analyzed. After quality control analysis of the gene chip arrays, 2 HC, 2 IFNneg and 3 IFNpos pSS samples remained for further analysis.

first: N

middle: I

last: Maria

first: A

first: W

last: Beumer


title: Neuronal Kmt2a/Mll1 histone methyltransferase is essential for prefrontal synaptic plasticity and working memory

status: Public on Oct 06 2016

city: Munich

first: Mira

middle: Alexandra

last: Jakovcevski

state: Bavaria

address: Kraepelin Str. 2-10

department: Stress Neurobiology and Neurogentics

country: Germany

institute: Max Planck Institute of Psychiatry

summary: Neuronal histone H3-lysine 4 methylation landscapes are defined by sharp peaks at gene promoters and other cis-regulatory sequences, but molecular and cellular phenotypes after neuron-specific deletion of H3K4 methyl-regulators remain largely unexplored. We report that neuronal ablation of the H3K4-specific methyltransferase, Kmt2a/Mixed-lineage leukemia 1 (Mll1), in mouse postnatal forebrain and adult prefrontal cortex (PFC) is associated with increased anxiety and robust cognitive deficits without locomotor dysfunction. In contrast, only mild behavioral phenotypes were observed after ablation of the Mll1 ortholog Kmt2b/Mll2 in PFC. Impaired working memory after Kmt2a/Mll1 ablation in PFC neurons was associated with loss of training-induced transient waves of Arc immediate early gene expression critical for synaptic plasticity. Medial prefrontal layer V pyramidal neurons, a major output relay of the cortex, demonstrated severely impaired synaptic facilitation and temporal summation, two forms of short-term plasticity essential for working memory. Chromatin immunoprecipitation followed by deep sequencing in Mll1-deficient cortical neurons revealed downregulated expression and loss of the transcriptional mark, trimethyl-H3K4, at <50 loci, including the homeodomain transcription factor Meis2. Small RNA-mediated Meis2 knockdown in PFC was associated with working memory defects similar to those elicited by Mll1 deletion. Therefore, mature prefrontal neurons critically depend on maintenance of Mll1-regulated H3K4 methylation at a subset of genes with an essential role in cognition and emotion.

overall_design:
This array was used to chararacterize transcription in the Mll1 mutant mouse PFC
N=4 mouse PFCs / genotype @ basal, resting condtions

first: M

first: H

last: Ruan

first: E

middle: Y

last: Shen

last: Dincer

first: B

last: Javidfar

first: Q

last: Ma

first: CJ

last: Peter

first: I

last: Cheung

middle: C

last: Mitchell

first: Y

last: Jiang

first: C

last: Lin

first: V

last: Pothula

middle: F

last: Stewart

first: P

last: Ernst

last: Yao

first: S

last: Akbarian


title: Expression data from human CD34-positive hematopoietic stem cells

status: Public on Sep 26 2016

city: Braunschweig

first: Claudia

last: Pommerenke

address: Inhoffenstraße 7B

institute: Leibniz Institute DSMZ

summary: We used microarrays to detail the global program of gene expression underlying stemness of hematopoietic cells.

overall_design: CD34+ hematopoietic stem cells (HSCs).

first: Stefan

last: Nagel


title: Effect of lenalidomide on alloresponses of adult perpheral blood

city: London

first: Caroline

last: Besley

state: - None -

address: John Vane Centre, Charterhouse Sq

department: Haemato-Oncology

institute: Barts Cancer Institute

summary: Immunomodulatory drugs (IMiDs), such as lenalidomide provide a tool to enhance both direct anti-tumor and graft-versus-tumor effects after allogeneic haematopoietic stem-cell transplantation (AHCT). However, early clinical experience with IMiDs after AHCT using adult peripheral blood (APB) as a stem cell source has been limited by induction of graft-versus-host disease. Characterization of the mechanisms by which IMIDs can modulate alloresponses of T-cells from different cell sources could facilitate more effective use of these drugs in the setting of AHCT. In this study we have used in vitro modelling to identify changes in alloresponses of APB and umbilical cord blood (UCB) T-cells after exposure to the widely used IMiD lenalidomide. We demonstrate that lenalidomide increases net alloproliferation of APB T-cells by selectively enhancing allospecific proliferation of CD8+ T-cells. These CD8+ T-cells have enhanced effector memory differentiation, are enriched for polyfunctional effectors, and have a distinct gene expression profile with altered expression of key immunoregulatory genes. In contrast, although lenalidomide treatment of UCB T-cells results in a similar increase in alloreactive effector CD8+ T-cells, it also reduces allospecific proliferation of CD4+ T-cells and selectively expands frequencies of CD4+ regulatory T-cells, resulting in a net reduction in UCB T-cell alloproliferation. Our findings show that lenalidomide has a qualitatively different impact on alloresponses of T-cells from different cell sources, with a potentially tolerogenic effect on UCB T-cells. These findings have important implications for the future use of IMiDs in the setting of AHCT.

overall_design: CFSE labelled responder CD8+ T cells were isolated by negative magnetic selection on day 7 of allogeneic co-cultures that had been exposed to 1micromolar lenalidomide or vehicle control. These were further FACS sorted into alloproliferative and non-proliferative fractions by their CFSE fluorescence.  RNA was extracted and used to perform gene expression analysis using the GeneChip 3’IVT Express Kit and Human Genome U133 plus 2.0 GeneChips (Affymetrix).

first: Jeff

last: Davies


title: Evidence of two distinct functionally specialized fibroblast lineages in breast stroma

city: Copenhagen

first: Mikkel

last: Morsing

state: Nørrebro

address: Blegdamsvej 3b

department: Department of Cellular and Molecular Medicine and Danish Stem Cell Center

country: Denmark

institute: University of Copenhagen

summary: Background: The terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma. Methods: The two lineages are prospectively isolated by FACS based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271low/MUC1high normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase stained cultures. Results: Lobular fibroblasts are CD105high/CD26low while interlobular fibroblasts are CD105low/CD26high. Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors. Conclusions: Two distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that lobular fibroblasts constitute a specialized microenvironment for human breast luminal epithelial progenitors, i.e. the putative precursors of breast cancer.

overall_design: CD105high and CD26high fibroblasts in technical triplicates were analyzed.

first: Marie

last: Klitgaard

first: Abbas

last: Jafari

first: René

last: Villadsen

first: Moustapha

last: Kassem

first: Ole

middle: W

last: Petersen

first: Lone

last: Rønnov-Jessen


title: A Methylation Assay Predicts Response to Radiation Therapy in Patients with Glioblastoma

city: Houston

first: Erik

middle: P.

last: Sulman

address: 1515 Holcombe Blvd

department: Radiation Oncology

country: USA

institute: The University of Texas M. D. Anderson Cancer Center

summary: Genome wide DNA methylation profiling of glioma sphere-forming cells (GSC) derived from surgery specimens of glioblastoma patients.The Illumina Infinium 450K Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 450,000 CpGs in 12 GSC samples. Clonogeneic assays were used to detemine the radiation response of these 12 GSCs.

overall_design: Bisulphite converted DNA from the 12 GSCs were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2

middle: P

first: Qianghu

last: Wang


title: Carbon monoxide metabolism is essential for circadian transcription and dynamics

first: Karsten

last: Jürchott

address: Luisenstraße

department: Rahel Hirsch Center

institute: BIH at Charité

summary:
Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Conversely, metabolic signals such as redox state, NAD+/NADH and AMP/ADP ratios or heme feed back to and modulate circadian mechanisms to optimize energy utilization across the 24-hour cycle. We show that the signaling molecule carbon monoxide (CO) generated by rhythmic heme degradation is required for normal circadian rhythms as well as circadian metabolic outputs.
CO suppresses circadian transcription by attenuating CLOCK/BMAL1 binding to target promoters. Pharmacological inhibition or genetic depletion of CO-producing heme oxygenases abrogate normal daily cycles in mammalian cells and Drosophila. In mouse hepatocytes, suppression of CO production leads to a global upregulation of CLOCK/BMAL1-dependent circadian gene expression and thereby misregulation of many metabolic processes including gluconeogenesis.

overall_design: Overall, 8 samples of HO1 knock-out mice and their wildtype littermates (BALB/c), untreated or treated with HO2-shRNA, were analyzed. Two replicates were used for each knock-out/knock-down group and for the normal controls.

first: Roman

last: Klemz

first: Achim

last: Kramer


title: White Blood Cell Differentials Enrich Whole Blood Expression Data in the Context of Acute Cardiac Allograft Rejection

status: Public on Sep 24 2016

city: Vancouver

first: Scott

last: Tebbutt

state: BC

address: 1190 Hornby Street

country: Canada

institute: PROOF Centre of Excellence

summary: Acute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.

overall_design: A single treatable acute rejection (International Society for Heart & Lung Transplantation, ISHLT grade >=2R) sample from each of 10 subjects and one non-rejection sample (ISHLT grade = 0R) from 16 subjects who did not have treatable acute rejection at any time within the first six months post-transplant were selected for analysis. Groups had similar mean age (48 ± 14 and 50 ± 16 in ARs and NRs, respectively) and were mainly composed of Caucasian subjects. NRs were more predominantly male (14/16 subjects) compared to ARs (6/10 subjects).

first: Bruce

middle: M

last: McManus


title: Expression data from hematopoietic stem cells from Zeb2-KO (Zeb2Δ/ΔMx1-Cre) mice versus WT mice

city: Bonn

first: Viktor

last: Janzen

address: Sigmund-Freud-Str. 25

institute: University of Bonn

summary:
Zeb2 has been shown to influence hematopoietic differentiation and loss thereof leads to complex differentiation defects in multiple hematopoietic lineages.
We used microarrays to compare the expresssion profile of Zeb2-defective with WT hematopoietic stem cells and identified several dinstict classes of up-regulated genes during this process.

overall_design: A population of cells highly enriched for hematopoietic stem cells (LKS-Slam marker positive cells) was sorted by flow cytometry from bone marrow of (Zeb2Δ/ΔMx1-Cre) mice and WT mice eight weeks after induction with pIC.  Total RNA was RNA extracted and hybridised on Affymetrix microarrays. We used three distict biological replicates from each the Zeb2Δ/ΔMx1-Cre cells versus WT (control) cells.


title: Expression data from the CD8 T cells of healthy donors and dengue patients from Thailand

city: Atlanta

first: Jaturong

last: Sewatanon

state: GA

address: 1462 Clifton Rd. NE, Room 412

department: Microbiology and Immunology

institute: Emory University School of Medicine

summary:
CD8 T cells play roles in eliminating virus infected targets through cytotoxic effector function and are of great interest from vaccination prespective.  Previous studies suggest that the cytokines produced by the CD8 T cells may contribute to the pathological  consequences. Because the dengue specific memory T cells strongly secrete cytokines upon in vitro stimulation with heterologous viral antigen, the ‘cytokine storm’ induced by activated T cells may contribute to the immunopathology of dengue infection.  Moreover, the CD8 T cell expansion peaks before or around the time of the peak of clinical symptoms, and the frequency of activated CD8 T cells and cytokine producing cells was somewhat higher in patients with severe forms of dengue disease.
To gain further insight into the characteristics of activated CD8 T cells, we performed microarray analysis of the HLA-DR+CD38+ CD8 T cells that were sorted from the PBMCs of seven dengue patients from Siriraj Hospital in Bangkok, Thailand and compare with the sorted naive (CCR7+CD45RA+) CD8 T cells from five Thai healthy donors.

overall_design: The HLA-DR+CD38+ CD8 T cells that were sorted from the PBMCs of seven dengue patients from Siriraj Hospital in Bangkok, Thailand and compare with the sorted naive (CCR7+CD45RA+) CD8 T cells from five Thai healthy donors.

first: Anmol

last: Chandele

first: Haydn

middle: T

last: Kissick

first: Rafi

last: Ahmed

first: Murali-Krishna

last: Kaja


title: miR-125b controls mitochondrial metabolism and dynamics by targeting BIK and MTP18

first: Pawel

last: Durek

address: Charitéplatz 1

institute: Deutsches Rheuma-Forschungszentrum

summary: Abnormal mitochondria metabolism and innate immune responses participate in the pathogenesis of many inflammatory disorders. The molecular events regulating mitochondrial activity to control survival and cell death in monocytes/macrophages are poorly understood. Here we show that miR-125b attenuates the activity of the mitochondrial respiratory chain through BIK silencing, and promotes the elongation of mitochondrial network through MTP18 targeting, without impacting autophagy, in the human monocytes. Proinflammatory activation is associated with a concomitant increase in miR-125b expression, decrease in BIK and MTP-18 expression, reduced oxidative phosphorylation, and enhanced mitochondrial fusion. Furthermore, expression of M1-associated transcripts as well as mitochondrial dynamics and energy metabolism are induced upon ectopic expression of miR-125b. In turn, by repressing miR-125b, mitochondrial dynamics was preserved, LPS-induced repression of BIK expression and of mitochondrial respiration were prevented, and M1 polarization of macrophages was inhibited. Altogether, our data reveal a novel role for miR-125b in controlling mitochondrial metabolism and dynamics by targeting BIK and MTP18, respectively, two novel cellular target proteins involved in maintaining the mitochondrial integrity in human monocytes. These findings not only suggest a novel function for miR-125b in regulating metabolic adaptation of monocytes to inflammation but also unravel new molecular mechanisms for its pro-apoptotic role and identify potential targets for interfering with inflammatory activation of monocytes.

overall_design: To identify specific targets of miR-125b, we over- and down-expressed miR-125b as well as a control miRNA in THP-1 cells. Chemically synthesized miRNA duplexes, called pre-miR-125b and pre-miRCTRL, as well as anti-miR-125b were purchased from lifetechnology. Cells were transfected with pre-miRNA, anti-miR and pre-miR control at a final concentration of 50 nM using Lipofectamin 2000 (Invitrogen) according to the manufacturer’s instructions. RNA samples were harvested at 48 hours post-transfection. 2 independent experiments (biological duplicates) were carried out for a total of 6 samples. Total RNA was isolated using an RNeasy mini kit (Qiagen). Quality control was ensured with Bioanalyzer (Agilent Technologies) and RNA quantification with NanoDrop ND-1000 spectrophotometer (NanoDrop Technologies). The generation of cRNA, sample hybridization (using Affymetrix HG U133 plus 2.0 arrays) and scanning with a GeneChip Scanner 3000 (Affymetrix) were performed according to the manufacturer’s instructions. Data were analyzed with High Performance Chip Data Analysis (HPCDA) with BioRetis database.

first: Isabelle

last: Duroux-Richard

first: Christine

last: Roubert

first: Meryem

last: Ammari

first: Jessy

last: Présumey

first: Joachim

middle: R

last: Grün

first: Thomas

last: Häupl

first: Andreas

last: Grützkau

first: Charles-Henri

last: Lecellier

first: Patrice

last: Codogno

first: Christian

last: Jorgensen

first: Florence

last: Apparailly


title: Genome-wide methylation profile of Lymphocytes and induced pluripotent stem cells

status: Public on Oct 04 2016

first: Akira

last: Watanabe

address: Rm504, Miyako Bldg, 233, Isa-cho, kamigyo-ku

institute: CyberomiX Inc

summary: Vα24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer, represent promising therapeutic target. However, reduced iNKT-cell numbers and function have been observed in many patients with cancer. To overcome this obstacle, we reprogramed human iNKT cells to pluripotency and then redifferentiated into regenerated iNKT cells in vitro through IL-7/IL-15-based optimized cytokine combination. They showed proliferation and IFN-γ production in response to α-galactosylceramide, induced dendritic cell maturation and downstream activation of cancer antigen-specific cytotoxic T lymphocytes in vitro, and exhibited NKG2D- and DNAM-1-mediated natural killer celllike cytotoxicity against cancer cell lines. Their immunological features and availability in an unlimited supply from induced pluripotent stem cells offer the potential to develop effective immunotherapies against cancer.

overall_design: Bisulphite converted DNA from the lymphocytes (n = 6) and undifferentiated induced pluripotent stem cells (n = 3) were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.

first: Shuichi

last: Kitayama

first: Yasutaka

last: Mizoro

first: Shin

last: Kaneko


title: Deciphering KRAS and NRAS mutated clones dynamics in MLL-AF4 pediatric leukemia by ultra deep sequencing analysis

city: Padova

first: Luca

last: Trentin

address: Via Giustiniani, 3

department: Department of Women's and Children's Health

country: Italy

institute: University of Padova

summary: We studied the KRAS and NRAS mutational status in pediatric MLL-AF4+ leukemia patients by means of ultra deep amplicon sequencing. The gene expression profiles of RAS wild type and RAS mutated patients were investigated by gene expression analysis. We showed that mutated patients were characterized by a RAS related expression signature.

overall_design: Gene expression was measured using Affymetrix platform in 9 BCP-ALL MLL-AF4+ patients at diagnosis with avaible information on their KRAS and NRAS mutational status


title: Interferon ε protects primary macrophages against HIV infection

city: Newark

first: Selvakumar

last: Subbian

state: NJ

address: 225 Warren Street

department: Medicine

institute: PHRI, NJMS, Rutgers the State University of NJ

summary:
Interferon ε (IFNε) is a unique type I IFN that is not induced by pattern-recognition  response elements. IFNε is constitutively expressed in mucosal tissues including the  female genital mucosa. We show here that IFNε  induces an antiviral state in human macrophages that blocks HIV-1 replication.
In this work, we examined effects and underlying mechanisms of IFNε in HIV infection  of monocyte-derived macrophages (MDMs). We found that IFNε blocked HIV replication  in macrophages. It acted on early stages of the HIV life cycle including entry and  reverse transcription. It did not appear to operate through known IFN-induced HIV host  restriction factors. IFNε induced immune responses in primary macrophages distinct  from those induced by IFNα. Importantly, we discovered a novel protective effect of  IFNε in primary macrophages against HIV by surging reactive oxygen species (ROS).

overall_design: Gene expression profiling was performed using the Affymetrix GeneChip® Human Gene 2.0 ST Array (Affymetrix Inc., Santa Clara, CA). Total RNA was isolated from untreated or IFNe or IFNa treated-PBMC (n=4 per group)using miRNeasy Mini Kit (Qiagen), and was converted to cDNA following the GeneChip® WT Plus Reagent Kit protocol. Briefly, total RNA (300 ng) was used for 1st and 2nd strand cDNA synthesis. cRNA was obtained by an in vitro transcription reaction, and was then used as the template for generating 1st strand cDNA. The cDNA was fragmented and end-labeled with biotin. The biotin labeled cDNA was hybridized to the array for 16 hours at 45°C using the GeneChip® Hybridization Oven 640. Washing and staining with streptavidin-phycoerythrin was performed using the GeneChip® Hybridization, Wash and Stain Kit, and the GeneChip® Fluidics Station 450. Images were acquired using the GeneChip® Scanner 3000 7G and the GeneChip® Command Console® Software. Normalized and background-corrected, raw probe intensity values were uploaded to Partek Genomics Suite ver 6.5 (PARTEK Inc, St. Louis, MO) for further analysis as described

first: Theresa

last: Cheng


title: Gene expression data from mice Ago2-amygdala

first: Alon

last: Chen

summary:
In this study we aimed to uncover which mRNAs are changed in the Ago2-amygdala complex following chronic social defeat in mice
We used microarrays to determine which mRNAs are changed in the Ago2-amygdala complexof mice following chronic social defeat compared to control

overall_design: Mice were subjected to chronic social defeat. 8 days following the end of the protocol, mice were sacrificed and amygdala was collected. The amygdala was immunoprecipitated using Ago2 beads and RNA was extracted to microarray.

first: Naama

last: Volk


title: Enterohemorrhagic Escherichia coli (EHEC) deletion of phage cro gene

status: Public on Sep 29 2016

city: Dallas

first: Juan

middle: D

last: Hernandez

state: Texas

address: 5349 Amesbury Drive, 2314

department: Microbiology

institute: University of Texas Southwestern medical centre

summary: Global regulation of the effects of deletion of phage cro gene in EHEC

overall_design: WT EHEC and ∆cro strains were grown for 6 hours in low glucose DMEM anaerobically. Total RNA bacterial strains was extracted and hybridized according the manufacturer's specifications.

last: Hernandez-Doria

first: Vanessa

last: Sperandio


title: Comparative expression analysis of carfilzomib-resistant and parental LP-1 human multiple myeloma cells

status: Public on Sep 13 2016

city: Washington

first: Robert

last: Hawley

state: DC

address: 2300 I Street NW, Suite 431

department: Anatomy and Regenerative Biology

institute: George Washington University

summary: LP-1 cells were exposed to stepwise increasing concentrations of carfilzomib over a period of 18 weeks: cells adapted to growth in 4 nM carfilzomib by 4 weeks, in 6 nM in another 6 weeks and in 12 nM after a further 8 weeks. The resulting cell culture, denoted LP-1/Cfz, retained resistance to carfilzomib even when tested after removal of selective pressure for approximately 8 weeks.

overall_design: LP-1/Cfz cells were profiled for gene expression after 1 week of growth in the absence of carfilzomib together with parental LP-1 cells which had not been selected in the drug (triplicate samples).

first: Irene

last: Riz

first: Teresa

middle: S

middle: G


title: Expression data of mucociliated human airway epithelia on-chip with or without exposure to whole cigarette smoke under physiological breathing

status: Public on Sep 20 2016

city: Boston

first: Kambez

last: Hajipouran Benam

state: MA

address: Center for Life Science Boston, 3 Blackfan Circle

institute: Wyss Insstitute, Harvard Medical School

summary: Smoking represents a major risk factor for chronic obstructive pulmonary disease (COPD), but it is difficult to characterize smoke-induced injury responses under physiological breathing conditions in humans. Here we generated small airway-on-a-chip microdevices lined by living human bronchiolar epithelium from normal or COPD patients and connected them to an instrument that 'breathes' whole cigarette smoke in and out of the chips to study smoke-induced pathophysiology in vitro. We used microarrays to detail the global program of gene expression in well-differentiated epithelial cells following smoke exposure to recapitulate clinical pathologies and identify disease-specific responses.

overall_design: Epithelial cells on-chip were challenged with whole cigarette smoke for 75 min (9 x research-grade 3R4F cigarettes), and 24 hours later were lysed and their RNA extracted for Affymetrix microarray analysis.

middle: H

last: Benam

first: Richard

last: Novak

first: Donald

middle: E

last: Ingber


title: The BET bromodomain inhibitor CPI203 improves lenalidomide activity in in vitro and in vivo models of multiple myeloma by synergistic blockade of Ikaros and c-Myc signaling

city: Barcelona

first: Patricia

last: Pérez-Galán

address: Centre Esther Koplowitz, Hemato-oncology dept, Rosello 149-153, 2nd floor

department: Hemato-oncology

institute: IDIBAPS

summary:
Multiple myeloma (MM) cells were treated with the BET inhibitor CPI203 alone and in combination with lenalidomide plus dexamethasone in vitro and in vivo (mouse xenograft).
We used microarrays to uncover the mechanisms underlying CPI-203 activity in MM, alone and in combination with lenalidomide plus dexamethasone (combo).

overall_design: Global RNA expression was done in three MM cell lines treated in vitro with the BET inhibitor alone or with the combo for 6h.

first: Tania

last: Diaz

first: Gaël

last: Roué

first: Carlos

last: Fernandez de Larrea


title: Epigenomic Profiling of Primary Gastric Adenocarcinoma Reveals Super-enhancer Heterogeneity [methylation]

city: Singapore

first: Aditi

last: Qamra

address: 60 Biopolis Street, Genome, #02-01

institute: GIS

summary: Regulatory elements in cancer remain poorly characterized in primary solid tumors. Here we applied microscale histone modification profiling to delineate the landscape of somatic promoters and super-enhancers in primary gastric adenocarcinoma, analyzing 94 epigenomic  profiles of primary tumors, normal tissues, and cell lines

overall_design: DNA methylation profiles of 19 T/N pairs

first: Ooi

last: Fong

first: Patrick

last: Tan


title: Molecular Characterization of Down Syndrome Embryonic Stem Cells Reveals a Role for RUNX1 in Neural Differentiation

city: Jerusalem

first: Nissim

last: Benvenisty

state: Israel

address: Edmond Safra Campus Givat Ram

department: Genetics

institute: Hebrew University

summary: Down syndrome (DS) is the leading genetic cause of mental retardation and is caused by a third copy of human chromosome 21. The different pathologies of DS involve many tissues with a distinct array of neural phenotypes. Here we characterize new embryonic stem cell lines with DS (DS-ESCs), and focus on the neural aspects of the diease. Our results show that neural progenitor cells (NPCs) differentiated from five independent DS-ESC lines display increased apoptosis and down-regulation of forehead developmental genes. Analysis of differentially expressed genes suggested RUNX1 as a key transcription regulator in DS-NPCs. Using genome editing we were able to disrupt all three copies of RUNX1 in DS-ESCs, leading to down-regulation of several RUNX1 target developmental genes accompanied by reduced apoptosis and neuron migration. Our work sheds new light on the role of RUNX1 and the importance of dosage balance in the development of neural phenotypes in DS.

overall_design: Gene expression analysis was performed on a total of 3 human cell lines, including Down syndrome neural progenitor cells and genome edited Down syndrome neural progenitor cells

first: Tomer

last: Halevy

first: Juan-Carlso

last: Biancotti

first: Ofra

last: Yanuka

first: Tamar

last: Golan-Lev


title: Expression data from lung CD11b+ conventional dendritic cells in the steady-state and following exposure to house dust mite allergens

city: Liège

first: Thibaut

last: Janss

address: Avenue de l'hopital 1

department: GIGA-R

institute: Ulg

summary:
Using mouse lung resident conventional CD11b+ dendritic cells (CD11b+ cDCs) in the context of house-dust mite (HDM)-driven allergic airway sensitization as a model, we aimed here to identify transcriptional events regulating the pro-Th2 activity of cDCs.
We used microarray analyses to identify genes differentially expressed by lung CD11b+ conventional dendritic cells in response to house dust mite allergens in wild-type and Irf3-deficient mice

overall_design: Lung Cd11b+ conventional dendritic cells were isolated from either wild type or Irf3-deficient mice 12 hours after a treatment with house dust mite extract or saline excipient

first: Claire

last: Mesnil

first: Dimitri

last: Pirottin

first: Pierre

last: Lemaitre

first: Thomas

last: Marichal

first: Fabrice

last: Bureau

first: Christohe

middle: J

last: Desmet


title: Global Gene Expression Analyses of Three BCC Subsets, Based on the Relative Level of Oct4A

status: Public on Sep 14 2016

first: Pranela

last: Rameshwar

address: 150 Bergen Street

department: Department of Medicine

institute: New Jersey Medical School, Rutgers School of Biomedical Health Science

summary: Despite education and aggressive treatment, breast cancer (BC) remains a clinical problem. BC cells (BCCs) can migrate early to metastatic sites where they may exist in cellular dormancy for decades. Presently, there are no consensus markers for cancer stem cells (CSCs) that are involved in tumor initiation and progression, and drug resistance. The current designation of CSCs might comprise similar tumor initiating cells, but at different developmental phase. In order to understand these differences, we developed a working hierarchy of BCCs. We initiated the studies in which three BCC subsets were selected based on the relative expressions of the stem cell-linked genes, Octamer4A (Oct4A). The sorted BCCs were subjected to array analyses using Affymetrix gene chip. Hierarchical clustering indicated distinct gene expression among the three subsets. Differential gene expressions of membrane proteins validated three novel genes, TMEM-98, GPR64 and FAT4. These three genes, in combination of known markers for CSCs, CD44, CD24, aldehyde dehydrogenase 1 (ALDH1) and Oct4A, were used to stratify BCCs led to a working hierarchy of BCCs. The validity of the hierarchical BCCs was applied to blood samples from patients, during relapse, and before and after treatment. These studies resulted in the patients grouped with distinct BCCs in the circulation. The relevance of the latter findings are discussed with regards to prediction of treatment response and time of BC relapse. The findings require a larger cohort of patients in a prospective multi-center study. The stratification could be important to understand treatment response, strategies for alternative approaches, and an understanding of the interaction between particular BCC subsets and the tissue microenvironment.

overall_design: MDA-MB-231 cells were transfected with pEGFP1-Oct3/4 and then selected with neomycin. Three groups of cells were isolated with the FACSDiva cell sorter. The top and lowest 5% of cells according to GFP expression were designated as Oct4hi and Oct4low while the Oct4med cells were in the middle of the two extreme subsets.  Cells were counted and processed in quadruplicate in a random order.  Due to limited reagents only duplicates of the Oct4med cells were processed.

first: Sarah

middle: A

last: Bliss

first: Sunirmal

last: Paul

first: Piotr

last: Pobiarzyn

first: Neha

last: Sharma

first: Daniel

last: Engelberth

first: Saumya

last: Pant

first: Holly

last: Hilton

first: Margarette

last: Bryan


title: Single and double knock-down of ETV6 and NFKB1 in U251 glioblastoma cell line.

city: Seattle

first: Christopher

middle: L

last: Plaisier

state: Washington

address: 401 Terry Avenue North

institute: Institute for Systems Biology

summary: To elucidate the mechanism(s) underlying the synergistic interaction between ETV6 and NFKB1, we analyzed the genome-wide transcriptional consequences of single and double knock-downs of the two TFs in U251 cells.

overall_design: The glioblastoma U251 cell line was transiently transfected with ETV6 and NFKB1 siRNA alone and then in combination, and were compared against control siRNA that doesn't target any known human transcript.

first: Sofie

last: O'Brien

first: Brady

last: Bernard

first: Sheila

last: Reynolds

first: Zac

last: Simon

first: Chad

last: Toledo

first: Yu

last: Ding

first: David

last: Reiss

first: Patrick

last: Paddison

first: Ilya

last: Shmulevich

first: Nitin

last: Baliga


title: Neuroprotection by a novel immunomodulatory peptide [adult mice]

status: Public on Sep 17 2016

last: Fjell

address: Room 166 - 1081 Burrard Street

institute: University of British Columbia

summary:
Perinatal brain injury is a major clinical problem associated with high neonatal mortality and morbidity and an increased risk of life-long chronic disabilities. Despite improved survival rates, the absolute numbers of neurological handicaps of perinatal origin have not decreased. There is currently no pharmacological treatment providing neuroprotction in neonates. As activation of the innate immune response is a key contributing factor to brain injury in both term and preterm infants we investigated the therapeutic potential of novel immunomodulatory innate defence regulator peptides (IDRs) in perinatal brain injury. IDR-1018 significantly reduced the production of inflammatory mediators by LPS-stimulated microglia cells in vitro.
IDR-1018 was also neuroprotective in a clinically-relevant animal model of neonatal brain injury, exerting effects on regulatory molecules of TLR-, Ca2+- and p53-signaling. Of utmost importance, IDR-1018 markedly protected both white and grey brain matter when administered after the injury, thus has tremendous applicability to the clinical setting. Here we demonstrate for the first time that peripheral administration of an immunomodulatory peptide is neuroprotective in vivo in a clinically relevant model of perinatal brain damage.
In this second data set, adult mice were used for comparison.

overall_design: 5 samples each for 4 groups were used for a total of 20 samples. Groups were: LPS-sensitized hypoxic-ischemic (LPS+HI) with injured (left) and uninjured (right) brain hemispheres, in the presence or absence of peptide IDR1018. The groups are therefore: 1) LPS + HI, left hemisphere, 2) LPS + HI with IDR1018, left hemisphere,  3) LPS + HI, right hemisphere, 4) LPS + HI with IDR1018, right hemisphere.

first: Hayde

last: Bolouri

first: Karin

last: Sävman

first: Wei

last: Wang

first: Anitha

last: Thomas

first: Norbert

last: Maurer

first: Edie

last: Dullaghan

first: Joakim

last: Ek

first: Henrik

last: Hagberg

first: Robert

last: Hancock

first: Kelly

last: Brown

first: Carina

last: Mallard


title: Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling [HumanMethylation450]

status: Public on Sep 12 2016

city: Darlinghurst

first: Ruth

last: Pidsley

state: NSW

address: 384 Victoria Street

country: Australia

institute: Garvan Institute of Medical Research

summary: We performed a critical evaluation of the new Infinium MethylationEPIC BeadChip microarray. EPIC covers over 850,000 CpG sites, including >90% of the CpGs from the HumanMethylation450 (HM450) BeadChip and an additional 413,743 CpGs. Even though the additional probes improve the coverage of regulatory elements, including 58% of FANTOM5 enhancers, only 7% distal and 27% proximal ENCODE regulatory elements are represented.  Detailed comparisons of regulatory elements from EPIC and whole-genome bisulphite sequencing data (WGBS) show that a single EPIC probe is not always informative for those distal regulatory elements showing variable methylation across the region.  However, overall data from the EPIC array at single loci are highly reproducible across technical and biological replicates and demonstrate high correlation with HM450 and WGBS data. We show that the HM450 and EPIC arrays distinguish differentially methylated probes, but the absolute agreement depends on the threshold set for each platform.

overall_design: To assess the performance of the EPIC array we ran a series of technical analyses using DNA from different samples types (cell lines, clinical samples and blood) commonly profiled in array-based methylation studies: a transformed prostate cancer cell line (LNCaP); primary cell cultures of prostate epithelial cells (PrEC); patient-matched cancer associated fibroblasts (CAF) and non-malignant tissue associated fibroblasts (NAF); and infant blood from archival Guthrie cards. We first profiled the DNA on both the HM450 and EPIC arrays. LNCaP and PrEC samples were also profiled with WGBS.

first: Elena

last: Zotenko

first: Timothy

last: Peters

first: Susan

last: Clark


title: Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase

city: Manhasset

first: Peder

last: Olofsson

state: NY

address: 350 Community Drive

institute: Feinstein Institute

summary:
Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4+ T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals.
Here we show that these CD4 +CD44hiCD62L lo T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 TChAT). Mice lacking ChAT expression in CD4+ cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JTChAT) decreased blood pressure when infused into mice. Co-incubation of JTChAT and endothelial cells increased endothelial cell levels of phosphorylated endothelial nitric oxide synthase, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasorelaxant nitric oxide.

overall_design: 3 samples of CD4+ CD44hiCD62LloChAT-eGFP− are compared to 3 samples of CD4+ CD44hiCD62LloChAT-eGFP+

first: Michaela

last: Oswald


title: Neuroprotection by a novel immunomodulatory peptide

first: Christopher

last: Fjell

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

overall_design: Refer to individual Series


title: Expression data from sentinel lymph node RNA of stage III melanoma patients

city: Louisville

first: Hongying

last: Hao

state: KY

address: 505 South Hancock Street

department: Surgery

institute: University of Louisville

summary: To identify a panel of Seninel Lymph Node (SLN) genes to aid in risk stratification of patients with tumor-positive SLN, total SLN RNA from 97 SLN-positive melanoma patients were chosen from the Sunbelt Melanoma Trial. Microarray experiments were performed to screen SLN genes in recurrence (=39) versus non-recurrence (=58) group. We identified 20 differentially expressed SLN genes in the recurrence vs. the non-recurrence group.

overall_design: Total RNA from sentinel lymph nodes were isolated using TRIREAGENT according to the manufacturer’s guidelines. RNA was quantified using Nanodrop ND-1000. The integrity of these total RNAs was assessed using Agilent 2100 Bioanalyzer. Total high-quality RNA was converted to cDNA, transcribed and labelled, and then hybridized to human HG-U133 plus 2 arrays (Affymetrix) then scanned according to the standard protocol recommended by Affymetrix.

first: Deyi

last: Xiao

first: Jianmin

last: Pan

first: J

last: Qu

first: Michael

last: Egger

first: Sabine

last: Waigel

first: M

last: Sanders

first: Wolfgang

last: Zacharias

first: Shesh

middle: N

last: Rai

last: McMasters


title: Expression data for nuclear actin regulated genes in keratinocytes

status: Public on Sep 22 2016

city: London

first: John

last: Connelly

address: 4 Newark Street

department: Centre for Cell Biology and Cutaneous Research

country: United Kingdom

institute: Queen Mary University of London

summary:
Actin dynamically shuttles between the nucleus and cytosplasm and regulates a wide range of transcriptional processes within the nucleus
We used gene expression profiling of keratinocytes overexpressing wild type actin or actin tagged with a nuclear localisation sequence to identify genes specifically regulated by nuclear actin

overall_design: Total RNA was isolated from HaCaT keratinocytes expressing WT-actin or NLS-actin and analysed using Affymetrix 2.0 plus microarrays

first: David

last: Chambers