title: Discovery of Gene Expression Signature in the Overexpression of miR-145 in U87 glioma cell.

status: Public on Mar 25 2011

city: Goyang

first: Sang-Jin

last: Lee

state: Gyunggi-Do

address: 323 Ilsan-Ro

department: genitourinary cancer branch

country: South Korea

institute: national cacner center

summary: We have employed whole RNA microarray expression profiling as a discovery platform to identify  genes regulated by overexpression of miR-145 in U87 glioma cell. Lentivirus containing miR-145 coding sequence was infected to U87 cell to make U87 overexpressing miR-145. We did genome microarray between U87 and U87 overexpressing miR-145.

overall_design: Total RNAs from U87 cell or U87 overexpressing miR-145 were extracted. Whole RNA microarray expression profiling was performed between them.


title: Aldosterone-inducible genes in mineralocorticoid receptor expressed human endothelial cell lines

status: Public on Mar 18 2011

city: Tokyo

first: Takanobu

last: Yoshimoto

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

department: Department of Clinical and Molecular Endocrinology

country: Japan

institute: Tokyo Medical and Dental University Graduate School

summary: To elucidate the aldosterone-regulated genes in vascular endothelial cells, we developed human endothelial cell line (EAhy926) stably expressing human mineralocorticoid receptor by retroviral system (MR-EAhy). Then gene expression profile of MR-EAhy stimulated with or without aldosterone was compared using DNA microarray analysis.

overall_design: MR-EAhy were serum-deprived for 24h with 0.2% dextran-coated charcoal-treated FBS, and then stimulated with or without aldosterone (10-9 M) for 6 hr. Then cells were harvested for RNA extraction.

first: Naoko

last: Sekizawa


title: in vivo and in vitro study of asthma

status: Public on Mar 11 2011

city: Seoul

first: Yoosik

last: Yoon

address: 221 HeukSeok-Dong, DongJak-Gu

institute: Chung-Ang University

summary: To further development of our gene expression approach to biodosimetry, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish asthma and normal subjects. We analyzed gene expression patterns of the peripheral blood cells from asthma patients compared with those from normal subjects using microarray analyses. In addition, we analyzed gene expression patterns of the LPS or HDM-treated THP1 cells compared with those from non-treated THP1 cells. And we analyzed the microarray data through clustering analysis, signaling pathway analysis and others.

overall_design: Ten milliliters of peripheral blood of five mild asthma, five severe asthma and five normal subjects were centrifuged at 4000 rpm for 20 min to collect 0.4 mL of the buffy coat fraction for in vivo study. To induce an inflammatory response, for in vitro study, the THP1 cells were seeded in 12-well plates at a density of 1 × 106 cells/well in RPMI 1640 medium containing 0.5% fetal bovine serum and stimulated for 24 hrs with LPS or HDM extract. After stimulation the THP1 cells were harvested using a cell scraper and lysed for total RNA extraction. Total RNA was extracted from the buffy coat fractions and RNA was reverse transcribed into cDNA for microarray analysis

first: Haeyong

first: Sungmin

last: Bae


title: Genomic alterations of chromosome 11 induce transcriptomic dysregulation in aggressive and malignant prolactin tumours

status: Public on Mar 16 2011

city: BRON

first: Joël

last: LACHUER

address: 16 avenue du Doyen Lépine

country: France

institute: INSERM

summary: Pituitary tumors are generally considered as benign. However, many are invasive (45 to 55%) and some are described as aggressive with a high proliferation rate and short post-operative time to recurrence and 0.2% metastasize. The molecular events associated to the progression of the pituitary tumor toward an aggressive and malignant phenotype is still unresolved. To bring new hypothesis on signaling pathways associated to the tumor progression, we applied a wide genome analysis approach combining transcriptome analysis and CGH analysis on the same 13 prolactin tumours classified as non-invasive (n=5), invasive (n=2) and agressive-invasive tumors (n=6). In 5/6 agressive-invasive tumours a loss of a common region in the p arm of the chromosome 11 was detected. This region extending from position 14.9 to position 46.5 Mb harbours the cytobands 11p15.2, 11p15.1, 11p14.3, 11p14.2, 11p14.1, 11p13, 11p12 and 11p11.2.  In 3 of these 5 tumours considered as carcinomas because of the presence of metastasis, an allelic loss is also observed in the 11q arm. The combination of data coming from genome structure exploration and transcriptomic analysis showed that allelic loss impact the expression of genes harbored in the imbalanced region. Data filtering strategy allowed us to highlight among the 139 genes harbored in the 11p region loss, 5 genes (DGKZ, CD44, TSG101, GTF2H1 and HTATIP2) that could be candidate gene for triggering the progression of prolactin tumour toward an aggressive and malignant phenotype. Finally, specific DNA alterations give one molecular argument more to consider agressive-invasive tumour and carcinomas as a distinct step in progression of the pituitary tumours.

overall_design: Copy number analysis of Affymetrix Genome-Wide Human SNP Array 6.0 was performed for 13 prolactin tumors, 6 aggressive-invasive, 2 invasive, 5 non-invasive. The same analysis was performed for one normal pituitary and one genomic DNA called "reference 103" from Affymetrix.

first: Anne

last: WIERINCKX

first: Magali

last: ROCHE

first: Catherine

last: LEGRAS-LACHUER

first: Nicolas

last: NAZARET

first: Séverine

last: CROZE

first: Gérald

last: RAVEROT

last: REY

first: Carole

last: AUGER

first: Emmanuel

last: JOUANNEAU

first: Philippe

last: CHANSON

first: Jacqueline

last: TROUILLAS


title: Combined miRNA and mRNA analysis of CD133(+) and CD34(+) cells

status: Public on Mar 14 2011

city: Bergisch Gladbach

first: Ute

last: Bissels

state: NRW

address: Friedrich-Ebert-Str. 68

department: R&D

country: Germany

institute: Miltenyi Biotec GmbH

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

summary:
Microarray and miRNA analysis of CD133(+), CD34(+)CD133(-) and CD133(-)CD34(-) cells
The goal of the experiment was the comparison of expression levels of mRNA and miRNA in CD133(+) and CD34(+)CD133(-) cells

sample_organism:
Homo sapiens
synthetic construct

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus

overall_design: The RNA of CD133(+), CD34(+)CD133(-) and CD133(-)CD34(-) bone marrow cells was amplified by using the µMACSTM SuperAmpTM Kit (Miltenyi Biotec).


title: Preactivation of the interferon signaling in liver is correlated with non-response to interferon alpha therapy in patients chronically infected with hepatitis B virus

status: Public on Mar 01 2011

city: Chongqing

first: chunyan

last: Xiao

address: No.1 Youyi Road, Yuzhong District

department: Department of Infectious Diseases

country: China

institute: The First Affiliated Hospital, Chongqing Medical University

summary: To screen the differentially expressed genes between responders(Rs) and nonresponders(NRs) in CHB patients treated with IFN-α, and to explore the molecular basis for treatment failure.Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy.Gene expression levels were compared between 7 NRs and 6 Rs,Gene Ontology category and KEGG pathway were analyzed for differentially expressed genes, and the selected differentially expressed genes were confirmed using real-time polymerase chain reaction.NRs and Rs have different liver gene expression profiles before IFN-α treatment. Preactivation of the IFN signaling pathway leading to the increased expression of inhibitory ISGs and inhibition of immune response in the pretreatment livers were associated with NRs.

overall_design: Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy.Gene expression levels were compared between 7 NRs and 6 Rs.

first: Chunyan

first: Bo

last: Qin

first: Limin

last: Chen

first: Lin

last: Gong

first: Hongwei

last: Liu

first: Yanling

last: Zhu

first: Xi

last: Lu


title: Gene expression in human umbilical cord endothelial cells following premiR-100 overexpression

status: Public on Mar 08 2011

city: Freiburg

first: Sebastian

last: Grundmann

address: Hugstetter Str. 55

institute: University Hospital Freiburg

summary: To search for genes regulated by microRNA-100 in endothelial cells, we transfected human umbilical cord endothelial cells (HUVECs) with miR-100 precursor oligonucelotides. Human umbilical vein endothelial cells (HUVECs) were isolated from donated umbilical cords, pooled from two donors and cultivated up to passage 5. For transfection with pre-miR microRNA precursor molecules cells were cultured to 70% confluence and transfected with 8nM pre-miR-100 or an irrelevant control oligonucleotide (both from Ambion) using Lipofectamin RNAiMax (Invitrogen) according to the manufacturers instructions. Total RNA was isolated 48h after transfection.

overall_design: Two individual samples per condition were analyzed.

first: Martin

last: Moser


title: Genome-wide analysis of mechanosensitive genes using in vivo model of mouse carotid artery endothelium exposed to disturbed flow

status: Public on Mar 10 2011

city: Atlanta

first: Hanjoong

last: Jo

state: GA

department: Biomedical Engineering

country: USA

institute: Emory University

summary: Recently, we have shown that disturbed flow caused by partial ligation of mouse carotid artery rapidly induces endothelial dysfunction and atherosclerosis within two weeks.  To understand the molecular mechanisms by which disturbed flow induces atherosclerosis, we carried out genome-wide microarray study using endothelial RNAs isolated from the flow-disturbed left and the contralateral right common carotid artery (LCA and RCA) in C57BL/6 mice.

overall_design: Total intimal RNAs were obtained from LCA and RCA at 12hr  and at 48hr post-ligation. Intimal RNAs from three LCAs or RCAs were pooled to obtain ~30ng total RNA.

first: Chih-Wen

last: Ni


title: Inhibition of BCL6-dependent gene expression in Philadelphia chromosome positive acute lymphoblastic leukemia

city: San Francisco

first: Huimin

last: Geng

state: CA

address: 513 Parnassus Ave., MSB HSW 1201

department: Department of Laboratory Medicine

institute: UCSF

summary: The Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. Tyrosine kinase inhibitors (TKI) are widely used to treat patients with leukemia driven by BCR-ABL1 and other oncogenic tyrosine kinases. In response to TKI-treatment, BCR-ABL1 ALL cells upregulate BCL6 protein levels by ~90-fold, i.e. to similar levels as in diffuse large B cell lymphoma (DLBCL) with BCL6 translocations. In this study, we analyzed the gene expression changes after treatment with Imatinib or Imatinib + RI-BPI.

overall_design: Three Ph+ ALL cell lines (BV-173, SUP-B15 and TOM-1) were treated in the presence or absence of 10 μM STI571 (Imatinib) or in the presence of both 10 μM STI571 and 20 μM RI-BPI for 24 hours.

first: Cihangir

last: Duy

first: Christian

last: Hurtz

first: Seyedmehdi

last: Shojaee

first: Leandro

last: Cerchietti

first: Srividya

last: Swaminathan

first: Lars

last: Klemm

first: Soo-mi

last: Kweon

first: Rahul

last: Nahar

first: Melanie

last: Braig

first: Eugene

last: Park

first: Yong-mi

last: Kim

first: Wolf-Karsten

last: Hofmann

last: Herzog

first: Hassan

last: Jumaa

first: Phillip

last: Koeffler

first: Jessica

last: Yu

first: Nora

last: Heisterkamp

first: Thomas

middle: G

last: Graeber

first: Hong

last: Wu

first: Hilda

last: Ye

first: Ari

last: Melnick

first: Markus

last: Müschen


title: Caco-2 cells:  21-days differentiated cells maintained with the low density protocol (LD cells) vs 21-days differentiated cells maintained with the high density protocol (HD cells)

status: Public on Apr 25 2011

city: Roma

first: Ivan

last: Arisi

address: viale Regina Elena 295

department: Bioinformatics Facility

country: Italy

institute: European Brain Research Institute

summary: Transcriptional profile of 21-days differentiated LD Caco-2 cells compared to 21-days differentiated HD Caco-2 cells. Goal was to find some differences in the genome profile of the LD and HD Caco-2 cells that could be addressed to the different protocols used for the line maintenance.

overall_design: Two-condition experiment: 21-days differentiated Caco-2 cells maintained with the LD protocol and 21-days differentiated Caco-2 cells maintained with the HD protocol. Dye-swap technical replicates.

first: Rossella

last: Brandi

first: Mara

last: D'Onofrio

first: Armando

last: Felsani

first: Manuela

last: Natoli


title: Comparison of gene expression data between control and tissue specific epicardial PDGF receptor (a and b) knockout embryonic hearts

status: Public on Feb 28 2011

city: Dallas

first: Michelle

last: Tallquist

state: TX

address: 5323 Harry Hines BLVD MC9148

department: Molecular Biology

institute: University of Texas Southwestern Medical Center

summary: Epicardial cells undergo an epithelial-to-mesenchymal transtion (EMT) to generate coronary vascular smooth muscle cells (VSMC) and cardiac fibroblasts.  Little is known about the mechanisms regulating EMT or the in vivo signals directing epicardial-derived cell (EPDC) fate.  Here, we show that loss of PDGF signaling leads to a disruption in Sox9 expression, and when Sox9 expression was restored in mutant hearts, the EMT defect was rescued.  Interestingly, mutants lacking only one of the PDGF genes exhibited a lineage specific requirement for the individual receptors.  Loss of PDGFRα resulted in a deficit in cardiac fibroblast formation, while cVSMC development was unperturbed.  Conversely, PDGFRβ was required for cVSMC development but not cardiac fibroblast development.  Combined, our data demonstrate a novel role for PDGF receptors in epicardial EMT and EPDC development.

overall_design:
GSM671723-GSM671724: Total RNA was isolated from E12.5 control and PDGF receptor epicardial knockout hearts using the Trizol reagent.  RNA was processed as per manufacturer's instructions (Illumina Gene expression array, Illumina, inc.   San Diego, CA, USA)
GSM671877-GSM671882: Total RNA was isolated from E12.5 control and PDGF receptor epicardial knockout primary epicardial cultures using the Trizol reagent.  RNA was processed as per manufacturer's instructions (Illumina Gene expression array, Illumina, inc.   San Diego, CA, USA)

first: Christopher

last: Smith


title: Homo sapiens MSCs: Normoxia vs. Hypoxia

status: Public on Feb 19 2011

city: Taipei

first: Chih

middle: Chien

last: Tsai

address: No. 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan

country: Taiwan

institute: Taipei Vaterans General Hospital

summary: Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.

overall_design: Two-condition experiment, Normoxic MSCs vs. Hypoxic MSCs.

first: Chih-Chien

first: Shih-Chieh

last: Hung


title: Influence of alkyl-phospholipids on the gene expression profile of immortalized keratinocytes HaCaT

city: Berlin

first: Geo

last: Semini

address: Oudenarderstrasse 16

department: Institute for Biochemie

institute: Charité - Universitätmedizin

summary: New alkyl-phospholipids (APLs) that are structurally derived from the platelet-activating factor are promising candidates for anticancer treatment. After the incorporation into cell membranes, APLs are able to interfere with a wide variety of key enzymes implicated in cell growth, motility, invasion and apoptosis. Besides the prototype edelfosine, we presented a novel group of APLs, glycosidated phospholipids that efficiently inhibit cell proliferation. Two members of this group, Ino-C2-PAF and Glc-PAF, display high efficacy and low cytotoxicity in immortalized non-tumorigenic skin keratinocyte cell line HaCaT. However, the influence of APLs on the transcription of the whole genome is still unknown. Here, using Agilent cDNA microarray technology, we compared global gene expression profiles of HaCaT cells treated with edelfosine, Ino-C2-PAF or Glc-PAF with the profile of control cells.

overall_design: The influence of APLs on the transcriptional profile of immortalized keratinocytes (HaCaT) was analyzed treating HaCaT cells with respectively 5 µM Ino-C2-PAF, Glc-PAF and edelfosine for 24 h. Control cells were left untreated. Three independent experiments were performed for each condition.

first: Kerstin

last: Danker

first: Andreas

last: Klein


title: Genome-wide Analysis of Transcriptional Reprogramming in Mouse Models of Acute Myeloid Leukaemia

status: Public on Feb 17 2011

city: Cambridge

first: Nicolas

last: Bonadies

address: Hills Road

department: Haematology

country: United Kingdom

institute: Cambridge Institute for Medical Research

summary: Acute leukaemias are commonly caused by mutations that corrupt the transcriptional circuitry of haematopoietic stem/progenitor cells. However, the mechanisms underlying large-scale transcriptional reprogramming remain largely unknown. Here we investigated transcriptional reprogramming at genome-scale in mouse retroviral transplant models of acute myeloid leukaemia (AML) using both gene-expression profiling and ChIP-sequencing. We identified several thousand candidate regulatory regions with altered levels of histone acetylation which were characterised by differential distribution of consensus motifs for key haematopoietic transcription factors. The integrated genome-scale analysis applied in this study represents a valuable and widely applicable approach to study the transcriptional control of both normal and aberrant haematopoiesis and to identify critical factors responsible for transcriptional reprogramming in human cancer.

overall_design: To monitor global expression changes during leukaemia progression for both MLL-ENL and MOZ-TIF1, we performed gene expression profiling for three biological replicates each of the lin-/kit+ bone marrow (WT), Factor-Dependent Cells Patterson-Mix cells (FDCP), MLL-ENL initiation (ME-I), MOZ-TIF2 initiation (MT-I), MLL-ENL progression (ME-L) and MOZ-TIF2 progression (MT-L) samples. Biotin-labelled cRNA from three biological replicates was generated from 250ng of total RNA and hybridized onto MouseWG-6 version 2 Expression Bead Chips.

first: Bertie

last: Göttgens


title: Dose-dependent immunomodulation of human dendritic cells by the probiotic Lactobacillus rhamnosus Lcr35

city: Clermont Ferrand

first: Christiane

last: Forestier

address: 28 place H Dunant

department: Pharmacie

institute: Universite d'Auvergne Clermont 1

summary: Gene expression changes in human dendritic cells after contact with either 10e4 or 10e7 CFU of Lactobacillus rhamnosus Lcr35

overall_design: Bacterial cells were incubated for 3 hours with dendritic cells. Total RNA was extracted, quantified, and labeled with Cy3 or Cy5 (control, dendritic cells without bacteria). Hybridization was performed using Agilent Whole Human Genome microarray 4x44K (Agilent).

first: Bertrand

last: Evrard

first: Sophie

last: Coudeyras

first: Annie

last: Dosgilbert

last: Charbonnel

first: Josette

last: Alamé

first: Arlette

last: Tridon


title: BCL6 enables leukemia cells to cope with inhibition of oncogenic tyrosine kinases

status: Public on Feb 15 2011

first: Huimin

last: Geng

type: Genome binding/occupancy profiling by genome tiling array

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

overall_design: Refer to individual Series

first: Cihangir

last: Duy

first: Christian

last: Hurtz

first: Seyedmehdi

last: Shojaee

first: Leandro

last: Cerchietti

first: Srividya

last: Swaminathan

first: Lars

last: Klemm

first: Soo-mi

last: Kweon

first: Rahul

last: Nahar

first: Melanie

last: Braig

first: Eugene

last: Park

first: Yong-mi

last: Kim

first: Wolf-Karsten

last: Hofmann

first: Sebastian

last: Herzog

first: Hassan

last: Jumaa

first: Phillip

last: Koeffler

first: Jessica

last: Yu

first: Nora

last: Heisterkamp

first: Thomas

last: Graeber

first: Hong

last: Wu

first: Hilda

last: Ye

first: Ari

last: Melnick

first: Markus

last: Müschen


title: Effect of Tet1-knockdown on gene expression in mouse ES cells cultured in ES and TS cell culture conditions

status: Public on Feb 07 2011

city: Turku

first: Kian Peng

last: Koh

address: Tykistökatu 5

country: Finland

institute: Btk

summary: TET-family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA.  Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem (ES) cells.  ES cells depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1, and display hyperactive Nodal signalling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro.  In Fgf4- and heparin-supplemented culture conditions that favor derivation of trophoblast stem (TS) cells, Tet1-depleted ES cells activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in mid-gestation embryo chimeras.  Consistent with these findings, Tet1-depleted ES cells form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm and ectopic appearance of trophoblastic giant cells. Thus Tet1 functions to regulate the lineage differentiation potential of ES cells. Here, we performed whole-genome transcriptome profiling of ES cells stably depleted of Tet1 by shRNA knockdown (Tet1-kd) cultured in either standard ES cell or in TS cell culture conditions. Gene expression changes in Tet1-kd ES cells were fairly modest compared to control (GFP-kd) cells, although gene ontology (GO) analysis of differentially expressed genes yielded many terms related to embryonic development and cell cycle regulation. In TS cell culture conditions, a core set of genes defining trophectodermal cell differentiation, including Cdx2, Eomes and Tead4, was enriched in Tet1-kd compared to GFP-kd cells.

overall_design: A total of 27 samples were analysed with at least 3 replicates in each group. Control/reference samples comprise ES cells cultured in standard ES cell media (true ES cells) and TS cells cultured in Fgf4/heparin-supplemented (TS) media (true TS cells). We compared Tet1-kd ES cells with GFP-kd ES cells cultured in either ES or TS cell media. In addition, we included a set of Tet1-kd subclones (Tet1-kd-sc) cultured in TS cell condition and a set of untransfected ES cells (parental control) cultured in TS cell condition.

first: Kian

middle: P

first: Asta

last: Laiho


title: Molecular Characterization of Tannerella forsythia infection-induced bone and soft tissue transcriptional profiles

city: Gainesville

first: Kesavalu

middle: Naidu

last: Lakshmyya

state: FL

address: 1600 SW Archer road, D11-24

department: Periodontology

institute: University of Florida, College of Dentistry

summary:
The objectives of this investigation were to examine changes in the host transcriptional profiles during a Tannerella forsythia infection using a murine calvarial model of inflammation and bone resorption.  T. forsythia ATCC 43037 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised.  RNA was isolated from infected soft tissues and calvarial bones and analyzed for transcript profiles using Murine GeneChip® MG-MOE430A Affymetrix arrays to provide a molecular profile of the events that occur following infection of these tissues.
We used mouse microarrays to detail the molecular profile of the events that occur following infection of calvarial and bone tissues and identified distinct classes of up- and down-regulated genes during this process.

overall_design: T. forsythia was injected at 1.5 x 109 (N = 10) into the soft tissues overlying the calvaria of the mice for 3 days. A control group (N = 9) was injected with vehicle once daily for 3 days. Mice were euthanized 8 h after the last injection.  The calvarial bones and overlying soft tissues from 5 mice in each group were excised, snap frozen in liquid nitrogen, and stored at –80°C until RNA isolation. Total RNA was isolated from the frozen calvarial tissue and calvarial bone from each mouse (T. forsythia infected and control animals, N = 3-5 in each group) with Trizol reagent (Invitrogen, CA).  Equal amounts of RNA from samples were labeled and hybridized on a mouse GeneChip following the protocol described in the GeneChip Expression Analysis Technical manual (Affymetrix, Santa Clara, CA). After hybridization, the GeneChip arrays were stained and scanned in an Affymetrix GCS 3000 7G Scanner.

first: Lakshmyya

middle: N

last: Kesavalu

first: Vasudevan

last: Bakthavatchalu

first: Archana

last: Meka

first: Sabapathi

last: Sathishkumar

first: Cecilia

middle: M

last: Lopez

first: Raj

middle: K

last: Verma

first: Shannon

last: Wallet

first: Indraneel

last: Bhattacharyya

first: Brendan

middle: F

last: Boyce

first: Jeffrey

middle: J

last: Mans

first: Richard

last: Lamont

first: Henry

middle: V

last: Baker

middle: L

last: Ebersole


title: The kinases MEKK2 and MEKK3 regulate Transforming Growth Factor-β-mediated helper T cell differentiation

status: Public on Feb 02 2011

city: new haven

first: xing

last: chang

address: 10 Amistad street, RM414

institute: Yale University

summary: Mitogen-activated protein kinases (MAPKs) are key mediators of the T cell receptor (TCR) signals but their roles in T helper (Th) cell differentiation are unclear. Here we showed that the MAPK kinase kinases MEKK2 (encoded by Map3k2) and MEKK3 (encoded by Map3k3),negatively regulated transforming growth factor-beta (TGF-beta)-mediated Th cell differentiation.Map3k2-/-Map3k3Lck-Cre/- mice showed an abnormal accumulation of regulatory T (Treg) and Th17 cells in the periphery, consistent with Map3k2-/-Map3k3Lck-Cre/- naïve CD4+ T cells' differentiation into Treg and Th17 cells with a higher frequency than wild-type (WT) cells after TGF-beta stimulation in vitro. In addition, Map3k2-/-Map3k3Lck-Cre/- mice developed more severe experimental autoimmune encephalomyelitis. Map3k2-/-Map3k3Lck-Cre/- T cells exhibited impaired phosphorylation of the SMAD2 and SMAD3 proteins at their linker regions, which negatively regulated the TGF-beta responses in T cells. Thus, the crosstalk between TCR-induced MAPK and the TGF-beta signaling pathways is important in regulating Th cell differentiation.

overall_design: CD4+CD62L-CD44+ cells were FACS sorted from C57BL/6 Lck-Cre MEKK2 KO MEKK3F/-(dKO) or C57BL/6 WT mice

first: Xing

last: Chang

first: Bing

last: Su


title: Genome-wide analysis of gene expression by ileum enterocytes following treatment with probiotic Lactobacillus reuteri

status: Public on Feb 01 2011

city: Houston

first: Jame

last: Versalovic

address: 1 Baylor Plaza, BCM 315

department: Pathology

institute: Baylor College of Medicine

summary: Analysis of changes in gene expression when probiotics are in the neonatal mouse gut (4 hrs) and after they had been excreted (24 hrs post-gavage)

overall_design: Total RNA obtained from mouse ileum epithelial cells isolated by laser capture microdissection 4 or 24 hours after a single orogastric gavage with probiotic or vehicle (PBS)

first: Geoffrey

middle: A

last: Preidis

first: James


title: Gfi1 regulates survival and lineage commitment of hematopoietic precursors and prevents myeloproliferative diseases

city: Essen

first: Ludger

last: Klein-Hitpass

address: Virchowstr. 173

department: Universitaetsklinikum

institute: Institut fuer Zellbiologie

summary:
Hematopoietic stem cells (HSCs) and lymphoid-primed multi-potential progenitors (LMPPs) are able to initiate both lymphoid and myeloid differentiation. We show here that the transcriptional repressor Gfi1 (growth factor independence 1) implements a specific gene expression program in HSCs and LMPPs that is critical for their survival and lymphoid differentiation potential. We present evidence that Gfi1 is required to maintain expression of genes involved in lymphoid development such as Flt-3, IL7R, Ebf1, Rag1, CCR9 and Notch1 and controls myeloid lineage commitment  by regulating expression of genes such as Hoxa9 or M-CSFR. Gfi1 also inhibits apoptosis in HSCs by repressing pro-apoptotic genes such as Bax or Bak. As a consequence, Gfi1-/- mice show defects in self renewal, survival and both myeloid and lymphoid development of HSCs and LMPPs. Co-expression of a Bcl-2 transgene can partially restore the function of HSCs in Gfi1-/- mice, but not the defects in early lymphoid development. Of interest, Gfi1-/- x Bcl-2 transgenic mice show an accelerated expansion of myeloid cells and succumb to a fatal myeloproliferative disease resembling chronic myelomonocytic leukemia (CMML). Our data show that Gfi1 protects HSCs against apoptosis, ensures the proper development of LMPPs and plays a role in the development of myeloid leukemia.
We used microarrays to detail the global gene expression changes following knockout of Gfi1 in mouse LSK cells

overall_design: We compared LSK cells isolated from Gfi1 knockout mice with wildtype cells to determine global gene expression changes by microarray analysis

first: L

last: Vassen


title: Genes regulated by SOX2 overexpression in gastric cancer cells

city: Tokyo

first: Takeshi

last: Otsubo

address: 1-5-45 Yushima Bunkyo-ku

department: Molecular Oncology

institute: Tokyo Medical and Dental University

summary: To identify candidate downstream target genes of SOX2 in gastric cancer cells, we transiently expressed exogenous SOX2 in a gastric cancer cell line NUGC3 and analyzed significant changes of gene expression.

overall_design: NUGC3 cells were infected with the optimum 20 MOI (infectious units/cell) of SOX2- or control GFP-expressing adenoviral vectors. At 72 h after infection, the cells were harvested for cDNA microarray analysis.

first: Yoshimitsu

last: Akiyama

first: Yutaka

last: Hashimoto

first: Shu

last: Shimada

first: Kentaro

last: Goto

first: Yasuhito

last: Yuasa


title: S100A8/A9 activate key genes and pathways in colon tumor progression

city: La Jolla

first: Roy

last: Williams

address: 3030 Science Park Road

department: Regenerative Medicine

institute: The Scripps Research Institute

summary: Studies using bone marrow chimeric mice revealed that S100A8/A9 expression on myeloid cells is essential for development of colon tumors. Our results thus reveal a novel role for myeloid-derived S100A8/A9 in activating specific downstream genes associated with tumorigenesis and in promoting tumor growth and metastasis.

overall_design: Subconfluent cultures of MC38 cells were serum-starved for 16 hrs and activated with 10ug/mL S100A8/A9 for 6 hrs. Total RNA was extracted from unactivated or activated cells. 2 replicates each per stimulated cells, unstimulated cells, and control cells.


title: Transcription levels in human colon biopsies in IBS and IBD patients before and after participating in a high red-meat dietary intervention

city: Maastricht

first: Dennie

last: Hebels

address: Universiteitssingel 50

department: Health Risk Analysis and Toxicology

country: Netherlands

institute: Maastricht University

summary:
Study 1: Transcriptomic profiles in colon tissue from inflammatory bowel diseases patients in relation to N-nitroso compound exposure and colorectal cancer risk

Study 1: N-nitroso compounds (NOC) have been suggested to play a role in human cancer development but definitive evidence is still lacking. In this study we investigated gene expression modifications induced in human colon tissue in relation to NOC exposure to gain insight in the relevance of these compounds in human colorectal cancer (CRC) development. Since there are indications that inflammation stimulates endogenous NOC formation, the study population consisted of patients with inflammatory bowel disease (IBD) and irritable bowel syndrome patients as controls without inflammation. Strong transcriptomic differences were identified in colonic biopsies from IBD patients and compared to controls that enhance the understanding of IBD pathophysiology. However, fecal NOC levels were not increased in IBD patients, suggesting that inflammation did not stimulate NOC formation. By relating gene expression changes of all subjects to fecal NOC levels, we did, however, identify a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending the molecular basis of NOC-induced carcinogenesis. We conclude that NOC exposure is associated with gene expression modifications in the colon that may increase CRC risk in humans.

Study 2: Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon

Study 2: Red meat consumption is associated with an increased colorectal cancer (CRC) risk, which may be due to an increased endogenous formation of genotoxic N-nitroso compounds (NOCs). To assess the impact of red meat intake on potential risk factors of CRC, we investigated the effect of a 7-day dietary red meat intervention in human subjects on endogenous NOC formation and fecal water genotoxicity in relation to transcriptomic changes induced in colonic tissue. In order to evaluate the potential effect of an inflamed colon on endogenous nitrosation, the study population consisted of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) control subjects without inflammation. The intervention had no effect on fecal NOC formation but fecal water genotoxicity significantly increased in response to red meat intake. Since IBD patients showed no difference in fecal NOC formation or fecal water genotoxicity levels as compared to IBS controls, for transcriptomic analyses, all subjects were grouped together. Genes significantly correlating with the increase in fecal water genotoxicity were involved in biological pathways indicative of genotoxic effects, including modifications in DNA damage, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated that are known to play a part in the carcinogenic process in the human colon. These results are in line with a possible oxidative effect of dietary heme. We conclude that the gene expression changes identified in this study corroborate the genotoxic potential of diets high in red meat and point towards a possible risk of CRC development in humans.

overall_design: The study investigated transcription levels in human colon biopsies obtained during a colonoscopic exam in 32 subjects suffering from either inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS). IBS patients served as control patients for comparison with IBD patients (see Study 1). 12 of these patients (6 IBD and 6 IBS) also followed a 7-day diet high in red meat (300 grams/day) after which a second colonscopic exam was performed to obtain colon biopsies to investigate the effect of the red meat intervention (Study 2). For each subject, cRNA copies of mRNA isolated from the colon biopsies were labeled with one dye (Cy3) and each sample was hybridized on a separate array. One replicate per subject or before/after red meat intervention (so 44 arrays in total, i.e. 20 before patients and 12 before and after patients).

first: Kirstine

last: Sveje

first: Marloes

middle: C

last: de Kok

first: Marcel

middle: H

last: van Herwijnen

first: Gunter

last: Kuhnle

first: Leopold

last: Engels

first: Carla

middle: B

last: Vleugels-Simon

first: Wout

last: Mares

first: Marieke

last: Pierik

first: Ad

last: Masclee

first: Jos

last: Kleinjans

first: Theo


title: Prediction of in vivo radiation dose in radiotherapy patients using ex vivo and in vivo gene expression signatures

status: Public on Jan 31 2011

city: New York

first: Sally

last: Amundson

state: NY

department: Center for Radiological Research

institute: Columbia University

summary: After defining a gene expression signature that predicted radiation exposure dose with high accuracy in human peripheral white blood cells irradiated ex vivo, we now demonstrate the predictive power of gene expression signatures in blood from patients undergoing total body irradiation.  Using whole genome microarray analysis, we have identified genes that respond to radiation exposure in cancer patients in vivo.  A 3-nearest neighbor classifier built from these genes correctly predicted samples as exposed to 0, 1.25 or 3.75 Gy with 94% accuracy even when samples from healthy donor controls were included.  The same samples were classified with 98% accuracy using a signature previously defined from ex vivo irradiation data.  The samples could also be classified as exposed or not exposed with 100% accuracy using multiple methods.  The demonstration that ex vivo irradiation is an appropriate model that can provide meaningful prediction of in vivo exposure, and that the signatures are robust across diverse disease states, is an important advance in the application of gene expression for biodosimetry.  Translation of these signatures to a fully automated “lab-on-a-chip” device will enable high-throughput screening for large-scale radiological emergencies, as well as making such tests practical for clinical uses.

overall_design: Radiation induced gene expression was measured in vivo in TBI patients at 4 hours after 1.25Gy exposure or at 24 hours after 3.75Gy exposure with three 1.25Gy split doses (approximately 4 hours apart).  A total of 18 TBI patients, diagnosed with a variety of cancers were used in this study. Blood from 14 healthy control individuals was also used for comparison.

first: Sunirmal

last: Paul

first: Christopher

last: Barker

first: Suzanne

last: Wolden


title: Effects of Tdg deficiency on overall transcription in mouse embryonic fibroblasts and during cell differentiation

city: Bern

first: Fredy

last: Siegrist

address: Freiburgstrasse 15

department: Department of Nephrology

country: Switzerland

institute: University Hospital Bern

summary: Because it excises thymine from G•T mismatches, TDG was proposed to counter mutagenesis by 5-methylcytosine deamination. Yet, TDG was also observed to attack 5-methycytosine itself, making it a candidate DNA demethylase, and interactions with transcription factors implicated additional functions in gene regulation. Unlike other DNA glycosylases, TDG is essential for embryonic development. Fibroblasts from Tdg null embryos show massively impaired gene regulation, and this correlates with imbalanced histone modification and CpG methylation. TDG associates with the promoters of affected genes in MEFs and in embryonic stem cells, but epigenetic aberrations appear only in differentiated cells. TDG also contributes to the maintenance of active and bivalent chromatin during cell differentiation, using its DNA glycosylase activity to counter aberrant de novo methylation. Thus, TDG dependent DNA repair stabilizes epigenetic states during cell differentiation.

overall_design: Comparison of 3 Tdg+/- MEF replicates with 3 Tdg-/- MEF replicates. Comparison of Tdg+/- and Tdg-/- ES cells and respective in vitro differentiated neuronal progenitors. Each condition is represented by 3 replicas.

first: Christophe

last: Kunz

first: Yusuke

last: Saito

first: Daniel

last: Cortazar

first: Primo

last: Schär


title: Transcriptional analysis of time course in response to HY-PDT on human nasopharyngeal carcinoma cell line CNE-2

status: Public on Jan 28 2011

city: shanghai

first: shu

last: yang

address: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science

institute: Fudan University

summary: Analysis of photodynamic therapy with hypericin of nasopharyngeal carcinoma cells CNE-2 in different time-points at gene expression level. The hypothesis tested in the present study was that HY-PDT could induce apoptosis on CNE-2 cells via intrinsic pathways. Results provide important information of the response of apoptosis, such as specific oxidative stress genes, mitochondrial related genes, cell cycle related genes, etc.

overall_design: Total RNAs were isolated from the cultured cells treatment with 20 μg/ml HY and irradiation then cultured in dark for 0, 2, 6, 12, 20 h respectively compared to cells treatment with 20 μg/ml HY only then cultured in dark for 20 h.

first: Xiaoli

last: Wang

first: Yi

last: Guo

first: Shu

last: Yang

first: Caihong

first: Xuping

last: Fu

first: Jinling

first: Yumin

last: Mao

first: Junsong

last: Zhang

first: Yao

last: Li


title: Expression changes following siRNA knockdown of ADRM1 in ovarian cell line OAW42

status: Public on Jan 14 2011

city: Santa Monica

first: Charles

last: Ginther

address: 2825 Santa Monica Blvd, #200

department: Hem-Onc

institute: UCLA

summary:
Knock-down of ovarian cancer amplification target ADRM1 leads to down regulation of GIPC1 and up-regulation of RECK.

Among 20q13-amplified genes in ovarian cancer, ADRM1 overexpression was the most highly correlated with amplification, and was significantly upregulated with respect to stage, recurrence and metastasis. In addition, overexpression of ADRM1 correlated significantly with shorter time to recurrence and overall survival.  Herein, array-CGH and microarray expression of ovarian cancer cell lines, provides evidence consistent with the primary tumor data that ADRM1 is a 20q13 amplification target. Knock-down of ADRM1 in amplified ovarian cell line OAW42 results in down-regulation of growth factor GIPC1 and up-regulation of tumor-suppressor RECK RNA and protein.  In our dataset of 141 ovarian primary tumors, ADRM1 overexpression significantly correlates with GIPC1 overexpression.  In addition, there is a significant anticorrelation between ADRM1 overexpression and RECK expression.  Further research is necessary to determine whether targeting knock-down of ADRM1 in 20q13-amplified ovarian cancers results in growth inhibition and tumor suppression via downstream targets GIPC1 and RECK.

overall_design: ADRM1 siRNA treated OAW42 compared directly to untreated or nonspecific RNA treated OAW42

first: Marlena

middle: S

last: Fejzo

first: Judy

last: Dering

first: Lee

last: Anderson

first: Natarajan

last: Venkatesan

first: Beth

last: Karlan

first: Dennis

last: Slamon


title: Expression of p16 and Retinoblastoma Determines Response to CDK 4/6 Inhibition in Ovarian Cancer: Ovarian cancer cell line expression data.

status: Public on Jan 22 2011

summary: PD-0332991 is a selective inhibitor of the CDK4/6 kinases with the ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. Here we investigate the role of CDK4/6 inhibition in human ovarian cancer.  We examined the effects of PD-0332991 on proliferation, cell-cycle, apoptosis, and Rb phosphorylation using a panel of 40 established human ovarian cancer cell lines. Molecular markers for response prediction, including p16 and Rb, were studied using gene expression profiling, Western blot, and arrayCGH. Multiple drug effect analysis was used to study interactions with chemotherapeutic drugs. Expression of p16 and Rb was studied using immunohistochemistry in a large clinical cohort ovarian cancer patients. Concentration-dependent anti-proliferative effects of PD-0332991were seen in all ovarian cancer cell lines, but varied significantly between individual lines. Rb proficient cell lines with low p16 expression were most responsive to CDK4/6 inhibition. Copy number variations of CDKN2A, Rb, CCNE1,  and CCND1 were associated with response to PD-0332991.  CDK4/6 inhibition induced G0/G1 cell cycle arrest, blocked Rb phosphorylation in a concentration and time dependent manner, and enhanced the effects of chemotherapy.  Rb proficiency with low p16 expression was seen in 97/262 (37%) of ovarian cancer patients and associated with adverse clinical outcome (progression free survival, adjusted relative risk 1.49, 95%CI 0.99-2.22, p =0.054).    PD-0332991 shows promising biologic activity in ovarian cancer cell lines. Assessment of Rb and p16 expression may help select patients most likely to benefit from CDK4/6 inhibition in ovarian cancer.

overall_design: Gene expression of 40 individual ovarian cell lines relative to an ovarian cell line reference mix containing equal amounts of 41 ovarian cell lines (including OCC-1 which was later identified as originating from mouse).  The expression data was correllated with cell line growth response to CDK 4/6  inhibitor PD-0332991 to identify genes associated with drug sensitivity and resistance.

first: Gottfried

last: Konecny

first: Kanthinh

last: Manwong

first: Meenal

last: Chalukya


title: Gene expression analysis of dendritic cells from normal or tumor sections of human prostates

status: Public on Jan 21 2011

city: Frederick

first: Stephanie

middle: Kaye

last: Watkins

state: MD

address: 1050 Boyles St.

department: CIP/LMI

institute: NCI-Frederick

summary:
Tumors cause the induction or repression of many genes associated with inflammation. To investigate the up and down regulation of genes associated with immune stimulation or immune tolerance RNA was isolated from dendritic cells from normal or tumor bearing prostate for microarray analysis.
Using normal or tumorogenic sections of human prostates as determined by Pathology experts (UMD).
Keywords: Comparative gene expression, prostate cancer, dendritic cells

overall_design: Prostatic dendritic cells were isolated from 5 patients for comparison of gene expression.

first: S

first: A

last: Hurwitz


title: IMR90 radiation bystander time-course experiment 0.5Gy alpha particle

first: Shanaz

middle: Adi

last: Ghandhi

address: 630, W 168th street

institute: Columbia University Medical Center

summary: The radiation bystander effect is an important component of the overall biological response of tissues and organisms to ionizing radiation. Little is known about the contribution of genome level changes in neighboring bystander cells to tissue and organ stress after irradiation. The timing of these changes is critical in the physiological context and these questions can only be answered by studying signaling and global transcriptomics in a chronological way. Here, we present a strategy to identify different biologically important signaling modules that act in concert in the radiation and bystander responses. We used time series gene expression analysis of normal human fibroblast cells measured at 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours and 24 hours after exposure to radiation coupled with a novel clustering method targeted to short time series, Feature Based Partitioning around medoids Algorithm (FBPA), to look for genes that were potentially co-regulated. This method uses biologically meaningful features of the expression profile and dimension augmentation to address the analysis of sparse data sets such as ours. We applied FBPA and Short Time series Expression Miner (STEM) to the same datasets and present the results of our comparisons using computational metrics as well as biological enrichment.  Enrichment showed that gene expression in irradiated cells fell into broad categories of signal transduction, cell cycle/cell death and inflammation/immunity; but only FBPA clustered functions well. In bystander cells, the gene expression response was also broadly categorized into functions associated with cell communication and motility, signal transduction and inflammation; but neither STEM nor FBPA separated biological functions as well as in irradiated samples. Network analysis revealed that p53 and NF-kappaB were central players in gene expression in both irradiated and bystander gene clusters. Analysis of individual clusters also suggested new regulators of gene expression in the radiation and bystander response that may act at the epigenetic level such as histone deacetylases (HDAC1 and HDAC2) and methylases (KDM5B) that can act as strong transcription repressors.  Based on these results, we propose a novel time series clustering method, FBPA, as a powerful approach that can be applied to sparse data sets (including genomic profiling data), where the choice of features selected for clustering and stringent statistical outcome analysis can augment our knowledge of the underlying cellular mechanisms in biological processes.

overall_design: There are 72 total samples, 4 corresponding biological replicates of IMR90 cells that were not irradiated (control=C), irradiated (alpha=A) and bystander (B), cells were harvested at 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours and 24 hours after treatment

first: Sally

last: Amundson


title: Identifying estrogen regulated gene expression profile of pre-implantation mouse embryos

status: Public on Jan 27 2011

city: Montreal

first: yuefei

last: lou

state: QC

address: 687Pine Avenue

country: Canada

institute: Mcgill University

summary: Comparison of the gene expression profiles of pre-implantation embryos at day 3.5 post coitum from normal pregnant mice (control); embryos from mice treated with ICI (specific estrogen receptor inhibitor); and embryos in the oviduct that were blocked from entering the uterus by ligation. Results provide insight into the function of estrogen regulated genes and uterine factors involved in the early implantation process.

overall_design: RNA were extracted from 3 groups of 100-120 embryos (a) embryos at d3.5 from uterus of normal pregnant mice; (b) embryos at d3.5 from uterus of ICI treated mice; and (c) embryos at d3.5 from the ligated oviduct.


title: Heparins treated human breast cancer MCF-7 cell

status: Public on Jan 11 2011

city: London

first: Yunliang Chen

last: Chen

address: Manresa Road

institute: Thrombosis Research Institute

summary: To inquire the a possible mechanism for heparin treatment improved cancer survival, three type of heparins: one standard heparin (unfractionated heparin (UFH), and two of  low molecular weight heparin (LMWH) Fragmin and Clexane were used to treat cell for 24 hours. Total RNA was used for cDNA Microarray assay.

overall_design: Untreated cells were used as controls. Cell were treated by three type of heparins one standard heparin (unfractionated heparin (UFH), and two of  low molecular weight heparin (LMWH) Fragmin and Clexane (40 IU/ml for each) were used to treat cell for 24 hours.  Triplicate samples were prepared.


title: Autism-associated gene expression signatures in peripheral blood leucocytes

status: Public on Jan 13 2011

city: Toskushima

first: Yuki

last: Kuwano

address: Kuramoto-cho

department: Pathophysiology

institute: The University of Tokushima Graduate School

summary: Using DNA microarray as a global approach to understanding the molecular basis of autism, we examined gene expression profiling in peripheral blood from 21 young adults with autism spectrum disorder (ASD) and healthy mothers having children with ASD, between whom there was no blood relationship. Several genes which were significantly changed in the ASD group comparing with their age- and gender-matched healthy subjects were mainly involved in cell morphology, cellular assembly and organization, and nerve system development and function. In addition, mothers having children with ASD possessed a unique gene expression signature shown as significant alterations of protein synthesis despite of their nonautistic diagnostic status.  Moreover, an ASD-associated gene expression signature was commonly observed in both individuals with ASD and healthy mothers having children with ASD.

overall_design: Total RNA was prepared from venous blood which was taken from each subject. Gene expression profiling of venous blood from subjects with ASD (21), the healthy women who had children with ASD (21) and their age- and gender-matched healthy subjects (42) were obtained using a whole human genome oligonucleotide microarray (Agilent 44K Human whole genome array G4112F, GPL6480) to measure gene expression in these samples according to the manufacture’s protocol. The one GSM sample of microarray analysis was made by individual subject. Differentially expressed genes were determined across all rationed expression values for age- and gender-matched pairs (ASD vs. control, asdMO vs. ctrlMO) using Genespling analysis.

first: Yoko

last: Kamio

first: Tomoko

last: Kawai

first: Sakurako

last: Katsuura

first: Naoko

last: Inada

first: Akiko

last: Takaki

first: Kazuhito

last: Rokutan


title: Gene expression profiling of Golabi-Ito-Hall derived lymphoblast cells compared to a matched healthy person

status: Public on Jan 01 2011

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary: A point mutation in the WW domain of PQBP1 that mediates its interaction with SIPP1 causes the Golabi-Ito-Hall (GIH) syndrome, which is associated with severe mental retardation and physical deformations. In this project we compared lymphoblast cell lines from a healthy person and a patient with the GIH syndrome and we found that the interaction between SIPP1 and the PQBP1-Y65C mutant is strongly impaired and is associated with significant differences in the expression of numerous genes. Furthermore, our data show that the Y65C mutation in PQBP1 results in a deficiency of (alternative) splicing and in major effects on several epigenetic markers. Thus, we suggest that GIH syndrome is a splicing disease€™ and that both PQBP1 and SIPP1 play an important role in its etiology.

overall_design: Four replicates were obtained from one lymphoblast cell line derived from a patient with Golabi-Ito-Hall syndrome, labeled as GIH. Four replicates were obtained from one lymphoblast cell line derived from a matched healthy person and is indicated as control.

first: Emilia

last: Nicolaescu

first: Monique

last: Beullens

first: Maria

last: Andries

first: Aleyde

last: Van Eynde

first: Guy

last: Froyen

first: Charles

last: Schwartz

first: Stefan

last: Stamm

first: Mathieu

last: Bollen


title: Comparison of genes differentially expressed among effectors with high and low memory potential

city: Columbia

first: Betul

middle: Fatma

last: Guloglu

state: MO

address: 1 Hospital Drive, M616 Medical Sciences Building

department: Microbiology and Immunology

institute: University of Missouri

summary: The events controlling transition of T cells from effector to memory remain poorly understood. Herein, we defined two types of effectors on the basis of cell division, expression of activation markers and production of effector cytokines and investigated their potential for memory generation. The results indicated that the moderately activated early effectors readily transit to memory while highly activated late effectors develop minimal memory. Boosting with antigen-free adjuvant, however, rescues the late effectors from cell death and sustains both survival and cytokine responses through toll-like receptor function. Also, the genome-wide microarray analysis among early and late effectors pointed to a set og defined as well as less known genes that may play a role in transition to memory.

overall_design: CFSE-labeled DO11.10 CD4 naïve T cells were transferred into Balb/c mice and the hosts were immunized with OVA peptide in CFA. Within 3 days, the lymph node cells were harvested and each effector division (from division 2 to 8) was sorted based on CFSE dilution and then they were either transferred into naive hosts to generate memory cells or their RNAs were extracted to perform genome-wide microarray analysis. To correlate gene expression with memory potential, division 4 (D4), which readily transit to memory, and divisions 3 (D3), 6 (D6) and 8 (D8), which display reduced potential for memory transition, were included. The data were derived from 3 independent experiments (3 samples per division, 12 samples total).

first: Habib

last: Zaghouani


title: Integrated genome, transcriptome and translatome profiling of neuroblastoma cells

status: Public on Dec 31 2010

city: Genova

first: PAOLA

last: SCARUFFI

state: GE

address: LARGO R. BENZI, 10

institute: "San Martino" Hospital

type: Genome variation profiling by genome tiling array

summary: Microarray-based genome-wide measurements of copy number alterations and of transcriptome variations are proposed for neuroblastoma prognosis and possible treatment choice. Nonetheless, they lack to provide clues on a neglected layer of systems-level changes, the translatome, whose variations are defined by the activity of the translational regulatory machinery.   Our study extends the conventional genome-wide approaches to translatome profiling in neuroblastoma, by means of polysomal sucrose gradient separation followed by microarray analysis.   The panel of fourteen parental (not subcloned) neuroblastoma cell lines used in the study includes: CHP-134, SIMA, NB-69, LAN-1, KELLY, CHP-126, CHP-212, SK-N-BE(2), IMR-32, SK-N-AS, SK-N-SH, STA-NB-7, STA-NB-1, STA-NB-10 cells. Each cell line has been profiled with high resolution array CGH analysis for copy number changes, and for transcriptome and translatome variations.   The integration of these three types of data sets obtained from the same cells can  provide information on the impact in neuroblastoma of a defined pattern of genomic lesions on both transcriptional and translational alterations of gene expression.

overall_design: We analyzed the following human neuroblastoma cell lines: STA-NB-1, SK-N-AS, NB-69, KELLY, LAN-1, CHP-134, SK-N-SH, SK-N-BE(2), STA-NB-7, CHP-126, CHP-212, IMR-32, SIMA, STA-NB-10.

first: Paola

last: Scaruffi

first: Sara

last: Stigliani

first: GianPaolo

last: Tonini

first: Alessandro

last: Quattrone

first: Angela

last: Re

first: Natalia

last: Arseni

first: Erik

last: Dassi


title: Hepatic induction of cholesterol biosynthesis reflects a remote adaptive response to pneumococcal pneumonia

status: Public on Jan 10 2011

city: Jena

first: S.

last: Lambeck

address: Erlanger Allee 101

institute: JUH

summary:
Transcriptional effects in liver, lung and blood samples from mice after intratracheal challenge with either Streptococcus pneumoniae serotype 19 (lobar-pneumonia) or serotype 2 (sepsis) were monitored after 6 and 24 hours and compared to sham (vehicle control).
We gratefully acknowledge the BMBF grant within the “Promoting global research excellence in severe sepsis” (PROGRESS) study (01KI07111).

overall_design: Three tissues x two serotypes x two time resolved treatment groups x four replicates, three tissues x Sham Control x three replicates.

first: M

last: Weber

first: S


title: Gene expression profiling of pheochromocytoma (PCC)/paraganglioma (PGL) tumors

city: Madrid

first: Elena

middle: López

last: Jiménez

address: Melchor Fernandez Almagro nº3

department: Human Cancer Genetics

country: Spain

institute: Spanish National Cancer Centre

summary: Transcriptional analysis of 84 primary pheochromocytoma (PCC)/paraganglioma tumors.

overall_design: 84 samples (primary pheochromocytoma (PCC)/paraganglioma tumors) were hybridized onto a cDNA microarray in order to investigate possible heterogeneity within these tumors

last: López-Jiménez

first: Alberto

last: Cascón


title: Human NTERA2 (NT2/D1) cells lines

status: Public on Dec 24 2010

city: Barcelona

first: Luciano

last: Di Croce

address: Dr. Aiguader, 88

institute: Centre for Genomic Regulation

type: Genome binding/occupancy profiling by array

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

overall_design: Refer to individual Series


title: Human Breast Cells: Control vs. TRIM29 cDNA- or TRIM29 shRNA-transfected

status: Public on Dec 23 2010

city: Salt Lake City

first: Jin

last: Liu

state: UT

address: 2000 Circle of Hope

institute: Huntsman Cancer Institute

summary:
Transcriptional profiling of human normal-like breast cells MCF10A comparing control MCF10A cells transfected with a pLenti6/BLOCK-iT™-DEST vector with MCF10A cells transfected with a pLenti6/BLOCK-iT™-DEST vector containing TRIM29 shRNA targeting nucleotides 1265–1285 of the TRIM29 open reading frame (ORF, NM_012101).
Transcriptional profiling of human breast cancer cells MCF7 comparing control MCF7 cells transfected with a pLenti6.2/N-LumioTM/V5-DEST vector with MCF7 cells transfected with a pLenti6.2/N-LumioTM/V5-DEST vector containing TRIM29 full-length cDNA (ORF, NM_012101).

overall_design: Two-condition experiment, MCF10A-vector control vs. MCF10A-TRIM29 shRNA cells; MCF7-vector control vs. MCF7-TRIM29 cells.

first: Philip

last: Bernard


title: Translatome and transcriptome profiling of estradiol response in MCF7 cells

city: Povo

first: Toma

last: Tebaldi

state: Trento

address: via Sommarive n. 9

department: Centre for Integrative Biology

institute: University of Trento

summary:
We subjected MCF7 cells to starvation with 0.5% charcoal treated serum for 48h and then we added 17-beta estradiol (E2) at final concentration of 10 nM, profiling before and after 60 minutes of treatment the transcriptome and the translatome, coming from the polysomal pool of mRNAs after sucrose gradient separation. Comparison of translatome profile changes with corresponding transcriptome profile changes represents a way of studying translational control networks and the degree of concordance between cellular controls affecting mRNA abundance and cellular controls affecting mRNA availability to translation. It is well known that E2 is a strong transcriptional regulator, while its translational control activity is less characterized. To provide a direct experimental evaluation of E2 induced translational regulation, we compared translatome and transcriptome profiles of E2 treated cells.

Keywords: polysomal profiling, translatome profiling, polysomal RNA, translational control, translational profiling, polysome profiling, post-transcriptional regulation, estradiol stimulation, estrogen receptor.

overall_design: The comparison between transcriptional and polysomal profiling was used for the discovery of general and mRNA-specific changes in the translation state of the serum starved MCF7 cells transcriptome in response to E2 stimulus. To identify translationally regulated mRNA molecules, gene expression signals derived from the polysomal populations were compared by microarrays analysis to those obtained from unfractionated total RNAs. Polysomal RNA and total RNA were isolated from MCF7 cells serum starved and treated with E2. Cells lysates were collected before (t = 0 min) and after (t = 60 min) E2 treatment. All experiments were run in quadruplicates.

first: Marina

last: Alamanou

first: Valentina

last: Adami

last: Provenzani


title: Effects of ionomycin (final concentration of 2 µM) and BAPTA/AM (final concentration of 6 µM) on the RO82 W-1 human thyroid cell line

status: Public on Dec 22 2010

city: angers

first: frederique

last: savagner

address: 4 rue larrey

institute: Inserm

summary:
The goal of this study was to identifiy cellular pathways modified by calcium storing in cells presenting a glycolytic metabolism and a poor mitochondrial biogenesis.

Keywords: calcium stress response in RO82 W-1 cells

overall_design: In duplicate, cells treated with ionomycin or BAPTA/AM during 96h compared to equivalent DMSO treated cells

last: Le Pennec

first: D

last: Guillotin

first: F

last: Savagner


title: Gene expression data from undifferentiated mouse embryonal carcinoma cell strains (MOE430A and MOE430B)

status: Public on Jan 26 2011

city: Setagaya

first: Yoji

last: Sato

state: Tokyo

address: 1-18-1 Kami-yoga

department: Cell. Gene Thpy. Prod.

institute: NIHS

summary:
Gene expression profiles of undifferentiated mouse embryonal carcinoma cell strains (P19, P19CL6, and 4 P19CL6 sublines) were obtained, using Affymetrix GeneChip Mouse Genome 430A and 430B.
Heart diseases such as cardiac infarction damage cardiomyocytes and consequently lead to significant loss of the contractile capacity of the heart. To repair functions of the injured heart, a great deal of research has attempted to develop regenerative medicine using pluripotent stem cell-based cardiomyocytes as cell therapy products. However, the efficiency of the current methods available for the cardiac differentiation of stem cells is insufficient for clinical settings. A comprehensive understanding of the mechanism involved in the cardiac differentiation of stem cells is necessary to improve the differentiation efficiency. To identify genes assosiated with cardiomyogenic potential, we isolated P19CL6 cell sublines possessing distinct properties in cardiomyogenesis and comprared their transcriptome profiles with those of mouse embryonal carcinoma P19 and P19CL6 cells.

overall_design:
Total RNA isolated from undifferentiated EC cell strains (P19 cells, P19CL6 cells, and 4 P19CL6 sublines)  using Affymetrix chips MOE430A and MOE430AB.

CEL files unavailable.

first: Tetsuya

last: Hasegawa

first: Satoshi

last: Yasuda

first: Tetsuji

last: Hosono

first: Mitsutoshi

last: Satoh

first: Kei

last: Watanabe

first: Kageyoshi

last: Ono

first: Shunichi

last: Shimizu

first: Takao

last: Hayakawa

first: Teruhide

last: Yamaguchi

first: Kazuhiro

last: Suzuki


title: Cytoplasmic Accumulation of Incompletely Glycosylated Sex Hormone-binding Globulin (SHBG) Enhances Androgen Action in Proximal Convoluted Tubule Epithelial Cells

status: Public on Dec 15 2010

city: Vancouver

first: Geoffrey

last: Hammond

state: British Columbia

address: 950 West 28th Ave

department: OB/Gyn

institute: University of British Columbia

summary: Identification of androgen-responsive genes that are influenced by the presence of a functional SHBG versus a steroid-binding-deficient SHBG mutant (SHBG S42L) in the cytoplasm of PCT cells. The hypothesis tested in the study was that SHBG enhances androgen action. Results provide important information that intracellular SHBG enhances androgen-dependent stimulation or repression in PCT cells.

overall_design: RNA was extracted for gene expression profiling from PCT cells expressing wild-type human SHBG or the human SHBG S42L mutant after treatment with testosterone or DHT, and hybridized to Illumina Mouse WG-6 v2.0 expression bead chips. Three replicates each.

first: Eui-Ju

last: Hong

first: Biswajyoti

last: Sahu

first: Olli

last: Jänne


title: Migrating Schistosoma japonicum schistosomula induce type-2 inflammation in the murine lung

status: Public on Feb 10 2011

city: Herston

first: Melissa

middle: Louise

last: Burke

state: QLD

address: 300 Herston Road

department: Division of Infectious Diseases and Immunology

country: Australia

institute: Queensland Institute of Medical Research

summary: Migrating schistosomula are an important stage of the schistosome lifecycle and represent a key target for elimination of infection by natural and vaccine induced host immune responses. To gain a better understanding of how these parasites initiate a primary host immune response we have characterised the host lung response to migrating Schistosoma japonicum schistosomula using a combination of histochemistry, microarrays and quantitative cytokine analysis. Our data suggest that, during a S. japonicum infection, actively migrating schistosomula induce a Type-2 cytokine response in the lung that may support the subsequent development of a CD4+ T helper 2 (Th2) response against egg antigens. This hypothesis is supported by the fact that schistosomula and schistosome eggs are known to express important Th2-inducing antigens such as omega-1, peroxiredoxin, kappa-5 and IPSE/alpha1. The host lung response to migrating schistosomula was associated with increased numbers of macrophages and expression of markers for alternatively activated macrophages (AAMφ) in the lung. Activation of AAMφ in the lung and at the systemic level could lead to the modulation of the host immune response to favour parasite survival. Induction of these cells could also contribute to diminished inflammatory responses to, for example, allergy and asthma that are known to be associated with helminth infections. These data enhance our understanding of the mechanisms whereby schistosomes may evade the immune response and the mechanisms by which schistosome infection can help influence the host response following exposure to allergenic stimuli.

overall_design: The gene expression profile of the murine lung was examined at 3 days weeks post infection with 500 Schistosoma japonicum cercariae in comparison to that of uninfected controls. Microarray analysis was performed on cRNA synthesised from total RNA derived from the lungs of 3 individual mice per group.

first: Laken

last: McGarvey

first: Henry

last: McSorley

first: Helle

last: Bielefeldt-Ohmann

first: Donald

middle: P

last: McManus

last: Gobert


title: Splenic CD4 T cells in naïve C57BL/6 mice or during Plasmodium berghei ANKA infection in C57BL/6 and B6.GzmB-/- mice.

status: Public on Dec 10 2010

first: Ashraful

last: Haque

state: Brisbane

department: Immunology

summary:
Infection of C57BL/6 mice with Plasmodium berghei ANKA (PbA) is a well-established experimental model of cerebral malaria (ECM). ECM is characterised by high levels of parasite sequestration and recruitment of pathogenic CD8+ T cells to the brain. The role of CD4+ T cells in this model has not yet been fully elucidated, although our laboratory has recently shown that CD4+ T cell depletion prior to infection results in significantly lower parasite burdens and protection from ECM. These data highlight a pathogenic role for CD4+ T cells in ECM.
Our unpublished observations indicate that mice lacking the CD8+ T cell cytolytic effector molecule, Granzyme B, (GzmB), are resistant to ECM, showing markedly reduced parasite burdens. Late depletion of CD4+ T cells from PbA-infected GzmB-deficient mice results in enhanced parasite burdens, indicating that these cells may play an anti-parasitic role. In the present study, we have analysed splenic CD4+ T cell gene expression profiles in naïve C57BL/6 mice, and PbA-infected wild-type and GzmB-deficent mice to further our understanding of the CD4+ T cell response in ECM.

overall_design: Splenic CD4 T cells isolated by cell sorting from either uninfected C57BL/6 or PbA-infected C57BL/6 or B6.GzmB-/- mice at day 4 post-infection. Total RNA obtained from four mice per group.

first: Laure

last: Desbarrieres

first: Shannon

middle: E

last: Best

first: Glen

middle: M

last: Boyle

first: Christian

middle: R

last: Engwerda


title: C-terminal splice variants of Gprc5b are expressed in maturing neurons and influence neurite outgrowth

status: Public on Dec 12 2010

city: Seattle

first: James

middle: William

last: MacDonald

state: WA

address: 4225 Roosevelt Way NE

department: Environmental and Occupational Health Sciences

institute: University of Washington

summary: Gprc5b, a retinoic acid-inducible orphan G protein–coupled receptor, is a member of the group C metabotropic glutamate receptor family.  Its function is unknown.  However, recent evidence suggests that it binds Frizzled Wnt receptors and may activate noncanonical Wnt signaling pathways.  Here we report the discovery of a brain-enriched C-terminal splice variant of Gprc5b, Gprc5b_v2, by cDNA microarray and RT-PCR analyses.  The variant appeared to have been downregulated in the brains of learning/memory-deficient p97FE65 null mice.  Despite the fact that the mice had been backcrossed with the C57Bl/6J strain for more than ten generations, Gprc5b and other genes surrounding the FE65 locus on mouse chromosome 7 were retained from the 129-derived ES cells used to generate the knockout line.  The differential splicing is unlikely due to FE65 function, as originally suspected, as Gprc5b_v2 expression is also downregulated in the brains of 129/Sv substrains in comparison to C57Bl/6J mice.  Further characterization revealed the expression of both Gprc5b_v2 and the previously described variant, Gprc5b_v1, in neurons.  Interestingly, Gprc5b_v2 mRNA levels increase with neuronal maturation, paralleling the expression of synaptic proteins involved in the regulation of synaptic plasticity.  Finally, we report evidence that both Gprc5b_v2 and Gprc5b_v1 regulate neurite outgrowth.  These results are consistent with a putative function of Gprc5b in noncanonical Wnt signaling, which play roles in the regulation of neuronal morphology, and the formation and modulation of neuronal circuitry.

overall_design: Cerebral cortex tissues were dissected from five FE65 wild-type and p97FE65 null littermate pairs (6 months of age)

first: Richard

last: Beyer

first: Bethany

last: Cool

first: Guy

last: Chan

first: Lin

last: Lee

first: Junko

last: Oshima

first: George

last: Martin

first: Qubai

last: Hu


title: Human NTERA2 (NT2/D1) cells lines: shZRF1 vs. shRandom during Retinoic Acid (RA) administration

first: Luciano

last: Di Croce

summary:
Transcriptional profiling of human NT2 cell lines comparing control cells (shRandom) with ZRF1 knockdown cells (shZRF1) both either untreated (0 h) or treated with Retinoic Acid (3 h) at 0.01 µM. The cell lines were established by retroviral infection allowing for the transcription of either a random shRNA (shRandom) or a shRNA specific for ZRF1 (shZRF1).
The goal was to determine the effect of ZRF1 on transcriptional activation at the onset of differentiation.

overall_design: Four-condition experiment, shRandom vs. shZRF1 cells either uninduced (0 h) or RA induced (3 h). Biological replicates: 6 replicates (shRandom) taken on 3 different days without or with RA administration. 6 shZRF1 replicates taken on three different days with or without RA administration.

first: Holger

last: Richly

first: Nuria

last: Lopez-Bigas


title: Identification and functional analysis of novel genes expressed in the Anterior Visceral Endoderm

status: Public on Nov 30 2010

city: Faro

first: Lisa

last: Goncalves

address: Campus de Gambelas, Ed8, Lab 1.17

country: Portugal

institute: CBME UALG

summary: During early development, the correct establishment of the body axes is a critical step. The anterior pole of the mouse embryo is established when Distal Visceral Endoderm (DVE) cells migrate to form the Anterior Visceral Endoderm (AVE). Asymmetrical expression of Lefty1, Cerl and Dkk determines the direction of DVE migration and the future anterior side. Besides being implicated in the establishment of Anterior-Posterior axis the AVE has also been correlated with anterior neural specification.  In order to better understand the role of the AVE in these processes, this cell population was isolated using a cerlP-EGFP transgenic mouse line, and a differential screening was performed using Affymetrix GeneChip technology. From this differential screening, 175 genes were found to be upregulated in the AVE, whereas 35 genes were upregulated in the Proximal-posterior sample. Using DAVID, here we characterize the AVE cell population regarding cellular component, molecular function and biological processes. Among the genes that were found to be upregulated in the AVE, several novel genes with expression in the AVE were identified. Four of the identified transcripts displaying high-fold change were further characterized by in situ hybridization in early stages of development in order to validate the screening. From those four selected genes, ADTK1 was chosen to be functionally characterized by targeted inactivation in ES cells. ADTK1 encodes for an unknown serine/threonine kinase. ADTK null mutants present short limbs and defects in the eye and ear. Taken together, these data point to the importance of reporting novel genes present in the AVE.

overall_design: Anterior distal and Posterior proximal portions of an E5.5 mouse embryo were microdissected. RNA was extracted from this portions and hybridized on Affymetrix microarrays in order to identify genes upregulated in the Anterior distal sample. Whole E5.5 embryo RNA was also extracted and hybridized for normalization.

first: Mario

last: Filipe

first: Jorg

middle: D

last: Becker

first: Jose

last: Belo


title: Expression in prospectively purified human prostate orthotopic xenograft tumor cells with varying S/TFE

status: Public on Dec 06 2010

city: New York

first: Nicholas

last: Socci

address: 1275 York Ave

department: Computational & Systems Biology Program

institute: Memorial Sloan Kettering Cancer Center


title: Illumina microarray experiment on LSD1 deletion ES cell with Lsd1Lox/Δ3 and Lsd1Δ3/Δ3

city: Leicester

first: Jinli

last: Luo

address: Lancaster Road

department: University of Leicester

institute: Department of Biochemistry,

summary: Lysine specific demethylase 1 (LSD1), which demethylates mono- and di- methylated histone H3-Lys4 as part of a complex including CoREST and histone deacetylases (HDAC), is essential for embryonic development in the mouse beyond e6.5 days. Here, we demonstrate that LSD1 expression and therefore function, is restricted to the epiblast of the post- implantation embryo. Conditional deletion of LSD1 in mouse embryonic stem (ES) cells, in vitro counterpart of the epiblast, revealed a reduction in CoREST protein, a subsequent decrease in associated HDAC  activity and a global increase in Histone H3 Lys56 acetylation.  Despite this biochemical perturbation, LSD1 deleted ES cells proliferate normally and retain stem cell characteristics. Loss of LSD1 causes the aberrant expression of 588 genes, including a number of transcription factors with roles in tissue development such as brachyury, Hoxb7, Hoxd8 and RARγ. Brachyury, a key-regulator of mesodermal differentiation, is a direct target gene of LSD1 and is over-expressed in e6.5 day Lsd1 genetrap embryos. Thus, LSD1 is required for the appropriate expression of key developmental regulators, via the stabilization of the LSD1/CoREST/HDAC complex, during early embryonic development.

overall_design: RNA samples from Lsd1Lox/Δ3 and Lsd1Δ3/Δ3 cells were compared, three biological replicates were performed.


title: Global analysis of mRNA expression in prospectively purified human prostate orthotopic xenograft tumor cells with varying S/TFE

summary:
Human prostate CWR22 OT-tumor cells were prospectively purified for expression of various stem cell markers (TRA-1-60/CD151/CD166/EpCAM/CD44/α2-Integrin). Unsorted total tumor cells or the additional marker positive cells that do not manifest stem-like characteristics were used as control. All these cells were subjected to molecular profiling of total RNA expression and the fold change data are tabulated according to S/TFE of the purified cells in relation to their control.
Notes: Low S/TFE   = Low sphere and tumor forming efficiency; Moderate S/TFE  = Moderate sphere and tumor forming efficiency;  High S/TFE   = High sphere and tumor forming efficiency; FDR*    = False Discovery Rate;  FC    = Fold Change;  Signal    = Average Expression Signal Level.

overall_design: Low-S/TFE, Moderate S/TFE, High S/TFE data sets were compared to No S/TFE control sets

first: Vinagolu

middle: K

last: Rajasekhar

first: Lorenz

last: Studer

first: William

last: Gerald

first: Howard

middle: I

last: Scher


title: Bcl6 mediates innate immune response

status: Public on Nov 24 2010

city: La Jolla

first: Ruth

middle: T

last: Yu

address: 10010 N Torrey Pines Rd

department: Gene Expression Lab

institute: Salk Institute

summary: Using microarrays, we compared the changes in levels of gene expression between wildtype and Bcl6 KO macrophages in the absence or presence of LPS.

overall_design: Total RNA was obtained from WT and Bcl6 KO unstimulated and LPS-stimulated primary bone marrow-derived macrophages

first: Grant

last: Barish

first: Ronald

last: Evans


title: Polymicrobial sepsis-induced Myocardial Depression Transcriptional Profile

status: Public on Nov 17 2010

city: Toronto

first: Claudia

middle: Chimisso

last: dos Santos

state: ON

address: 30, Bond Street, room 4-011

department: University of Toronto

institute: Saint Michaels Hospital

summary:
To describe the transcriptional changes associated with polymicrobial-sepsis induced myocardial depression in wild type and iNOS deficient mice.
Keywords: myocardium, contractility, differential gene expression, nitric oxide synthase, infection

overall_design: We compared the transcriptional profile of C57/BL6 WT mice and congenic B6 129P2-Nos2tm1Lau/J mice after 48 hrs of polymicrobial sepsis induced by caecal ligation and perforation. 48 hours after surgery, mice were anaesthetised (intraperitoneal 100 mg/kg ketamine and 10 mg/kg xylazine). The right common carotid artery was cannulated (Millar Mikro-Tip pressure transducing catheter: 1.4F sensor, 2F catheter; Houston TX). Pressure tracings from the aorta and left ventricle were recorded (SonoLAB software; Sonometrics Corp., London Ontario Canada) and analysed using Cardiosoft and Origin 6.0 (Sonometrics Corp., and Microcal Software, Northampton MA). The heart was removed, emptied of blood, and snap frozen.

middle: C

first: David

middle: J

last: Gattas

first: James

middle: N

last: Tsoporis

first: Golam

last: Kabir

first: Arthur

last: Slutsky

first: Mansoor

last: Husain

last: Sibbald

first: Thomas

middle: G

last: Parker


title: Gp130-dependent release of acute phase proteins is linked to the activation of innate immune signaling pathways

status: Public on Nov 13 2010

city: Münster

first: Frank

last: Ruehle

address: Domagkstr. 3

institute: Leibniz - Institut für Arterioskleroseforschung

summary: Gp130 dependent gene expression was analyzed in a previously established hepatocyte-specific gp130-knockout mouse model. Whole transcriptome analysis for isolated hepatocytes was performed to measure tissue specific responses after proinflammatory stimulus with IL-6 across different time points. We observed differences in the hepatocyte-specific transcriptional gp130 dependent response for genes associated with different aspects of the innate immune system. Our findings suggest a complex network of tightly-linked genes involved in the early activation of different parts of the innate immune response including acute phase proteins, complement and coagulation cascade.

overall_design: Total RNA obtained from a total number of 61 samples of isolated hepatocytes of hepatocyte-specific gp130-knockout and gp130flox mice, which were subjected to Il-6 treatment for 0, 1, 3, 6 or 12 hours, respectively.

first: Maren

last: Luchtefeld

first: Christoph

last: Preuss

last: Rühle

first: Eskendir

last: Bogalle

first: Anika

last: Sietmann

first: Stefanie

last: Figura

first: Werner

last: Müller

first: Bernhard

last: Schieffer

first: Monika

last: Stoll


title: Genome-wide gene expression comparison (primary central nervous system lymphoma (PCNSL) vs normal lymph node)

city: Seoul

first: Chang Ohk

last: Sung

address: Song-Pa gu,Pung-nap dong

department: Pathology

country: South Korea

institute: Asan Medical Center

summary: A genome-wide gene expression comparison between primary central nervous system lymphoma (PCNSL) and normal lymph node was performed to identify a differential exprssion and specific pathway.

overall_design: Experiment design: 7 PCNSL and 7 normal lymph node tissues were used for comparison.

first: Young-Hyeh

last: Ko

first: Chang-Ohk

first: Sang-Cheol

last: Kim

first: Sivasundaram

last: Karnan

first: Kennosuke

last: Karube

first: Hyung-Jin

last: Shin

first: Do-Hyun

last: Nam

first: Yeon-Lim

last: Suh

first: Seok-Hyung

first: Ji-Yeon

first: Soek-Jin

first: Won-Seog

first: Masao

last: Seto


title: Interleukin-4 and interleukin-13 cytokines effect on epidermal keratinocytes

status: Public on Oct 31 2010

city: Yokohama

first: Satoshi

last: Hirakawa

address: 560 Kashio-cho, Totsuka-ku,

country: Japan

institute: POLA CHEMICAL INDUSTRIES, INC.

summary: Analysis of cultured epidermal keratinocytes treated with interleukin-4 (IL-4) and interleukin-13 (IL-13). IL-4 and IL-13 are up-regulated in atopic dermatitis. Results provide insight into the role of IL-4 and IL-13 cytokines in the pathogenesis of atopic dermatitis.  Analysis of epidermal keratinocytes transfected with dual oxidase 1 (DUOX1) siRNA knockdown before treatment with IL-4 and IL-13. DUOX1 is one of the NOX family members of NADPH oxidases whose primary function is ROS generation. Results provide insight into the role of the incraesed expression of DUOX1 in IL-4/IL-13-treated NHEK for IL4/IL13 signaling.

overall_design: IL-4 and IL-13 induced gene expression in human epidermal keratinocytes (NHEK) was measured at 48 hours. Gene expression in NHEK tranfected with 10 nM DUOX1 siRNA followed by treatment with 100 ng/ml IL-4 and 100 ng/ml IL-13 was measured at 48 hours. Three independent experiments were performed using different strains for each experiment.

first: Rumiko

last: Saito

first: Hiroshi

last: Ohara

first: Ryuhei

last: Okuyama

first: Setsuya

last: Aiba


title: Suppression of insulin like3 receptor reveals the role of β-catenin and Notch signaling in gubernaculum development

status: Public on Nov 10 2010

city: Miami

first: Alexander

last: Agoulnik

address: 11200 SW 8th Street, HLSI 419B

department: Herbert Wertheim College of Medicine

institute: Florida International University

summary: During male development, the testes move from a high intraabdominal position and descend into the scrotum. The gubernaculum, an inguinoscrotal ligament connecting the testis to the lower abdomen, is believed to play a critical role in this process. The first stage of testicular descent is controlled by INSL3, insulin like3 hormone, produced in testicular Leydig cells. Deletion of Insl3 or its receptor, Rxfp2, in mice causes cryptorchidism. We produced Cre/loxP regulated shRNA transgenic mice targeting RXFP2 expression. We have shown that the transgene was able to reduce Rxfp2 gene expression and thus behaved as a hypomorphic allele of Rxfp2. Variable degrees of uni-and bilateral cryptorchidism was detected in males with the activated shRNA transgene on an Rxfp2+/- background. Conditional suppression of Rxfp2 in the gubernaculum led to cryptorchidism. Gene expression analysis of a mutant cremasteric sac using Illumina microarrays indicated abnormal expression of a significant number of genes in Wnt/β-catenin and Notch pathways. We have demonstrated profound changes in the expression pattern of β-catenin, Notch1, desmin, and androgen receptor (AR) in Rxfp2-/- male embryos, indicating the role of INSL3 in proliferation, differentiation, and survival of specific cellular components of the gubernaculum. We have shown that INSL3/RXFP2 signaling is essential for myogenic differentiation and maintenance of AR-positive cells in the gubernaculum. Males with the deletion of β-catenin or Notch1 in the gubernacular ligament demonstrated abnormal development. Our data indicates that β-catenin and Notch pathways are potential targets of INSL3 signaling during gubernacular development.

overall_design: Total RNA obtained from the cremasteric sac of cryptorchid Tg(shRxfp1) males compared to the wild-type control cremasteric sac.


title: Differential Expression of Chemokine and Matrix Re-Modelling Genes Explains Contrasting Schistosoma japonicum-induced Hepatopathology in Murine Models

first: Melissa

last: Burke

summary: The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we demonstrate the variation of host gene expression which underlies the contrasting hepatic pathology observed between two inbred mouse strains following schistosome infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in BALB/c and CBA mice during an active Schistosoma japonicum infection. Here, we show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. Generally, up-regulated genes were largely associated with immune and inflammatory responses, antigen processing and cytokine/chemokine activity. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with significantly greater accumulation of neutrophils at granulomatous regions, compared to CBA mice. In contrast, up-regulated expression of eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the greater degree of liver damage in these mice. Genes involved in fibrosis showed similar levels of expression in both mouse strains. Genes associated with Th1 and Th2 responses showed no significant differences in expression between strains. These results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. Furthermore, this improved understanding of schistosome immunopathogenesis in the murine model will provide the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

overall_design: The gene expression profile of  murine livers (BALB/c and CBA strains) were examined at 4, 7 and 9 weeks post infection with Schistosoma japonicum in comparison to that of uninfected controls. Three mice were utilised per group (Uninfected, 4, 7 and 9 weeks), totalling 24 samples. Microarray analysis was performed on individual RNA samples from each mouse.

first: Carly

last: Perry

middle: L

first: Deborah

last: Stenzel

first: Donald

last: McManus

first: Grant

middle: A

last: Ramm

first: Geoffrey

last: Gobert


title: Transcriptomic fingerprints in human peripheral blood mononuclear cells indicative of genotoxic and non-genotoxic carcinogenic exposure

status: Public on Oct 22 2010

city: Maastricht

first: Kevin

last: Hochstenbach

address: Universiteitssingel 50

department: Health Risk Analysis and Toxicology

institute: Maastricht University

summary:
For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effects markers provide limited mechanistic insight, and are unable to detect exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure. Whole genome gene expression changes were investigated in human blood cells following ex vivo exposure to a range of genotoxic and non-genotoxic carcinogenic compounds using whole genome microarrays. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic genes sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomakers of genotoxic exposure, and possibly even more importantly biomarkers of exposure to non-genotoxic carcinogens since presently no biomarkers are available.

Keywords: Genome wide gene expression analysis, Transcriptomic profile indicative of immunotoxic exposure

overall_design: For analysis of whole genome gene expression by microarray, PBMC from five independent donors per compound were exposed for 20 hours to three concentrations, i.e. the 100% and two serial ten-fold dilutions (10% and 1%), and a DMSO or PBS vehicle control. Exposed samples were always labelled with Cy5, whereas the vehicle control samples were labelled with Cy3, and were competetively hybridized on 4x44K Agilent microarrays.

first: Danitsja

last: van Leeuwen

first: Hans

last: Gmuender

first: Solvor

middle: B

last: Stølevik

first: Unni

last: Nygaard

first: Martinus

last: Løvik

first: Berit

last: Granum

first: Ellen

last: Namork

first: Henk

last: van Loveren

first: Joost

middle: H

last: van Delft


title: Limited systemic sclerosis patients with PAH show biomarkers of inflammation and vascular injury

status: Public on Oct 27 2010

city: Hanover

first: sarah

middle: a

last: pendergrass

state: NH

address: 7400 Remsen

department: Genetics

institute: Dartmouth College

summary:
Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury

Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients.  The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation.

overall_design: Sample vs reference, total RNA isolated from peripheral blood mononuclear cells (PBMC), 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls

first: Sarah

last: Pendergrass

first: Everett

last: Hayes

first: Giuseppina

last: Farina

first: Raphael

last: Lemaire

first: Harrison

middle: W

last: Farber

first: Michael

last: Whitfield

first: Robert

last: Lafyatis


title: Whole genome gene expression modifications associated with micronucleus formation in blood cells from nitrosamine-exposed humans

status: Public on Dec 01 2010

first: Dennie

last: Hebels

summary: N-nitroso compounds (NOCs) can be formed through endogenous nitrosation in the human body and are known to induce micronuclei (MN) formation in vitro. Since lymphocytic MN represent a well-validated biomarker of effect with regard to carcinogenic risk in multiple target organs, establishing a link between NOCs and MN in humans could provide evidence for a carcinogenic risk. Investigating gene expression modulations in relation to NOC exposure could provide further crucial information on underlying molecular mechanisms-of-action. The purpose of this study is therefore to establish the relationship between human NOC exposure under daily life conditions and MN formation in relation to associated transcriptomic changes, using lymphocytes as a surrogate tissue for analyzing carcinogenic events in target organs. We analyzed gene expression levels and MN frequency in lymphocytes from adults participating in a European cohort from the multidisciplinary research project NewGeneris. For assessing exposure to NOCs, urinary samples were analyzed for marker nitrosamines by GC-MS. NOC exposure was subsequently linked to peripheral blood transcriptomics. We found an association between MN frequency and urinary NOCs, indicating that NOC exposure under daily life circumstances may play an important role in human cancer development. Furthermore, we have identified modifications in pathways which indicate a molecular response to NOC-induced genotoxicity. From this, we derived a small group of genes which could be suitable as mechanistic-based transcriptomic biomarkers of NOC exposure-related cancer risk. The modified genetic processes and genes found in this study may be of interest for future investigations into NOC-associated carcinogenicity in humans.

overall_design: The study investigated transcription levels in human whole blood from 30 pregnant mothers in a Danish NewGeneris cohort. For each subject, cRNA copies of isolated mRNA were labeled with one dye (Cy3) and each sample was hybridized on separate arrays. One replicate per subject (so 30 arrays in total).

first: Danyel

last: Jennen

first: Marcel

last: van Herwijnen

first: Edwin

last: Moonen

first: Marie

last: Pedersen

first: Lisbeth

middle: E

last: Knudsen

first: Jos

last: Kleinjans

first: Theo

middle: M

last: de Kok