title: Genome-wide effect of islet isolation and in vitro culture on gene expression profile of pancreatic beta-cells enriched tissue.

status: Public on Feb 12 2012

city: Montreal

first: Steven

last: Paraskevas

state: Quebec

address: 687 Pine Avenue West

department: Department of Surgery

institute: McGill University

summary: It is known that the stresses encountered during islet isolation have deleterious effects on beta-cell physiology. The nature of these effects, however, is incompletely known, partly due to the heterogeneity of islet preparations. The objective was to assess the genome-wide effect of islet isolation and in-vitro culture on beta-cell transcriptome. Beta cells identified by their intrinsic autofluorescence, were captured from donor pancreas and isolated islets using Laser Capture Microdissection. Beta cells from donor pancreas serve as the control. Our results indicated induction of a strong inflammatory response induced by islet isolation which continues during in vitro culture manifested by upregulation of several cytokines, chemokines and their receptors. IL-8 was induced by 3.6-fold and 56-fold in fresh and 3-days cultured islets respectively. Concordantly, several pancreatic progenitor cell-specific transcription factors like were upregulated in cultured islets, suggesting progressive transformation of mature beta-cell phenotype toward an immature endocrine cell phenotype.

overall_design: There are three sample types in our experiment; 1) beta-cells captured from the frozen sections of donor pancreas n=8, 2) beta cells extracted from islets frozen immediately after isolation (d0 islets) n=8 and, 3) beta cells extracted from isolated islets frozen after culturing for 3 days (d3 islets) n=5. For the analysis, beta cells from pancreas were considered as the reference point.

first: Sarita

last: Negi

first: Arif

last: Jetha

first: Reid

last: Aikin

first: Craig

last: Hasilo

first: Rob

last: Sladek


title: Anti-telomerase therapy provokes ALT and mitochondrial adaptive mechanisms

status: Public on Jan 17 2012

city: Houston

first: Jian

last: Hu

state: TX

address: 1515 Holcombe Blvd

department: Cancer Biology

country: USA

institute: MD Anderson Cancer Center

type:
Expression profiling by array
Genome variation profiling by array

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

overall_design: Refer to individual Series

first: Ron

last: DePinho


title: Genome-wide mapping of Flag-Evi1 in SKOV-3 ovarian carcinoma cells

status: Public on Jan 15 2012

city: Singapore

first: Justin

middle: Jeyakani

last: Joseph Gnanakkan

state: Singapore

address: 60, Biopolis street

department: Computational and Systems Biology

country: Singapore

institute: Genome Institute of Singapore

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Discovery of Evi1 genomic occupancy and target genes

overall_design: ChIP-enriched DNA and input DNA were analyzed by Solexa sequencing.

first: Emilie

middle: A

last: Bard-Chapeau

last: Jeyakani

first: Guillaume

last: Bourque

first: Neal

middle: G

last: Copeland


title: Functional analysis of the cytoprotective transcription factor Nrf2 in skin morphogenesis and disease: Identification of Nrf2 target genes

status: Public on Feb 01 2012

city: Zürich

first: Matthias

last: Schäfer

state: ZH

address: Schafmattstrasse 18

department: Department of Cell Biology

country: Switzerland

institute: ETH Zürich

summary: The Nrf2 transcription factor is a key player in the cellular stress response, which regulates the expression of important antioxidant enzymes and other cytoprotective proteins. We recently generated a novel transgenic mouse model to determine the function of Nrf2 in the skin. These mice revealed interesting phenotypic abnormalities, including hyperkeratosis and acanthosis. To gain insight into the underlying molecular mechanisms, we wanted to identify genes, which are differentially expressed in the skin of wild-type and mutant mice before the onset of phenotypic abnormalities.

overall_design: RNA from whole skin of 3 single P2.5  K5cre-caNrf2 (tg/tg) and 3 single P2.5 K5cre-wt (tg/wt=control) mice were used

first: Sabine

last: Werner

first: Stefan

last: Zoller

first: Catharine

last: Aquino

first: Hubert

last: Rehrauer


title: PKCz-mediated Gaq stimulation of the ERK5 pathway is involved in cardiac hypertrophy

status: Public on Jan 10 2012

city: Madrid

first: Ramon

last: Garcia-Escudero

state: Madrid

address: Avda Complutense 40, Ed 70A

department: Biomedical Innovation

country: Spain

institute: CIEMAT

summary:
Background: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells.  Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent  signaling in cardiac cells.
Methodology/Principal Findings: We have explored the mechanisms involved in Gq-coupled GPCR-mediated stimulation of the ERK5 pathway and its functional consequences in cardiac hypertrophy using both cultured cardiac cells and an animal model of angiotensin- dependent induction of cardiac hypertrophy in wild-type and PKCz knockout mice. We find that PKCζ is required for the activation of the ERK5 pathway by Gq-coupled GPCR in cardiomyocytes and in cardiac fibroblasts. Stimulation of ERK5 by angiotensin II is blocked upon pharmacological inhibition or siRNA-mediated silencing of PKCz in primary cultures of cardiac cells and in cardiomyocytes isolated from PKCz-deficient mice. Moreover, these mice do not develop cardiac hypertrophy upon chronic challenge with angiotensin II, as assessed by morphological, biomarker, electrocardiographic and global gene expression pattern analysis.
Conclusion/Significance: Our data put forward that PKCζ is essential for Gq- dependent ERK5 activation in cardiac cells and indicate a key cardiac physiological role for this recently described Gaq/PKCz/MEK5 signaling axis.

overall_design: Littermate wild-type and PKCz -/- male mice (32 weeks of age) were subjected to continuous infusion of angiotensin II (or PBS as a control) for 14 days, a well established model for the induction of cardiac hypertrohy

first: Carlota

last: García-Hoz

first: Guzmán

last: Sánchez-Fernández

first: Ramón

last: García-Escudero

first: Maria

last: Fernandez-Velasco

first: Julia

last: Palacios-Garcia

first: Marisol

last: Ruiz-Meana

middle: T

last: Diaz-Meco

first: Michael

last: Leitges

first: Jorge

last: Moscat

first: David

last: Garcia-Dorado

first: Lisardo

last: Bosca

first: Federico

last: Mayor Jr

first: Catalina

last: Ribas


title: Notch1-driven transcriptional changes in a mouse model of T-ALL

city: NEW YORK

first: Panagiotis

last: Ntziachristos

address: 522 FIRST AVENUE

department: PATHOLOGY

institute: NYU MEDICAL SCHOOL

summary: T-cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we used a mouse model of T-ALL through the overexpression of the intarcellular transcriptionally active part of Notch1 (N1-IC). This model faithfully recapitulates the major characteristics of the human disease. Comparison of the leukemic cells from peripheral tumors(thymoma) of this mouse model to normal thymic cells Double Positive (DP) for the markers CD4 and CD8 that express very low levels of Notch1 showed major expression changes in pathways controlling the transition from physiology to disease. Further correlation of the data to ChIP-Seq data from the same cell populations led us to identify a hitherto unknown antagonism of the Notch1 oncogenic pathway and the polycomb complex (PRC2) in leukemia. Importantly exome sequencing in primary samples from human patients with T-ALL revealed that the PRC2 complex is frequently mutated and inactivated, further supporting the tumor suppressor role of the complex in this disease.

overall_design: Gene expression profiles from CD4+/8+ Double Positive derived from normal thymus and Notch1-IC over-expressing tumors were compared using genome wide mRNA expression profiling by Affymetrix genechip arrays (Mouse 430 2.0).

first: Aristotelis

last: Tsirigos

first: Pieter

last: Van Vlierberghe

first: Jelena

last: Nedjic

first: Thomas

last: Trimarchi

middle: S

last: Flaherty

first: Dolors

last: Ferres-Marco

first: Vanina

last: da Ros

first: Zuojian

last: Tang

first: Jasmin

last: Siegle

first: Patrik

last: Asp

last: Hadler

first: Isaura

last: Rigo

first: Kim

last: De Keersmaecker

first: Jay

last: Patel

first: Tien

last: Huynh

first: Filippo

last: Utro

first: Sandrine

last: Poglio

first: Jeremy

middle: B

last: Samon

first: Elisabeth

last: Paietta

first: Janis

last: Racevskis

first: Jacob

middle: M

last: Rowe

first: Raul

last: Rabadan

first: Ross

middle: L

last: Levine

first: Stuart

last: Brown

first: Francoise

last: Pflumio

last: Dominguez

first: Adolfo

last: Ferrando

first: Iannis

last: Aifantis


title: Polysome-bound mRNA during oocyte maturation

status: Public on Jan 14 2012

city: San Francisco

first: Jing

last: Chen

state: CA

address: 513 Parnassus Ave. HSW 1456

institute: UCSF

summary: Oocyte maturation, fertilization, and early embryonic development occur in the absence of gene transcription. Therefore, it is critical to understand at a global level the post-transcriptional events that are driving these transitions. Here, we have used a systems approach by combining polysome mRNA profiling and bioinformatics to identify RNA binding motifs in mRNAs that either enter or exit the polysome pool during mouse oocyte maturation. Association of mRNA with the polysomes correlates with active translation.

overall_design: Forty-eight hours (h) after PMSG injection, mice were stimulated with hCG for 0, 4, or 14 h, and GV-, MI- and MII-stage oocytes were collected. Polysome-bound mRNAs were purified, reverse-transcribed and linearly amplified with the WT-Ovation FFPE RNA Amplification System V2 (NuGEN). 5µg cDNA were fragmented and hybridized with Affymetrix Mouse Genome 430.2 array chips. Experiments were done using 3 independent sample sets.

first: Marco

last: Conti


title: Expression Profiling Identifies Novel Gene Targets and Functions for Pdx1 in the Duodenum of Mature Mice

status: Public on Jan 12 2012

city: Stanford

first: Chin

address: 300 Pasteur Drive

department: Pediatric Gastroenterology

institute: Stanford University School of Medicine

summary:
Transcription factor pancreatic and duodenal homeobox 1 (Pdx1) plays an essential role in the pancreas to regulate its development and maintain proper islet function. However, less is known about the function of Pdx1 in the small intestine.
We aim to investigate the role of Pdx1 in mature proximal small intestine by profiling the expression of genes differentially regulated in response to Pdx1 inactivation restricted to the intestinal epithelium in mice.

overall_design: Pdx1 was conditionally inactivated in the intestinal epithelium of Pdx1flox/flox;VilCre mice, by crossing mutant mice homozygous for loxP site-flanked Pdx1 alleles with transgenic mice expressing Cre recombinase under the control of the mouse villin 1 gene promoter. Total RNA was isolated from the first five centimeters of the small intestine from adult Pdx1flox/flox;VilCre and littermate control mice. Microarray analysis was performed to investigate genome-wide transcriptional profiles in the proximal small intestine.

first: Eric

last: Sibley


title: IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid progenitors (Affymetrix).

status: Public on Jan 07 2012

city: St. Louis

first: Amy

middle: M.

last: Becker

state: MO

address: 660 S. Euclide Ave.

department: Pathology and Immunology

institute: Washington University School of Medicine

summary: While most blood lineages are assumed to mature through a single cellular and developmental route downstream of hematopoietic stem cells (HSCs), dendritic cells (DCs) can be derived from both myeloid and lymphoid progenitors in vivo.  To determine how distinct progenitors can generate similar downstream lineages, we examined the transcriptional changes that accompany loss of in vivo myeloid potential as common myeloid progenitors (CMPs) differentiate into common dendritic cell progenitors (CDPs), and as lymphoid-primed multipotent progenitors (LMPPs) differentiate into all lymphoid progenitors (ALPs).  Microarray studies revealed that Interferon regulatory factor 8 (IRF-8) expression increased during each of these transitions.  Competitive reconstitutions using Irf8-/- bone marrow demonstrated cell-intrinsic defects in the formation of CDPs and all splenic dendritic cell subsets.  Irf8-/- CMPs and, unexpectedly, Irf8-/- ALPs produced more neutrophils in vivo than their wild type counterparts at the expense of DCs.  Retroviral expression of IRF-8 in multiple progenitors led to reduced neutrophil production and increased numbers of DCs, even in the granulocyte-macrophage progenitor (GMP), which does not normally possess conventional DC potential.  These data suggest that IRF-8 represses a neutrophil module of development and promotes convergent DC development from multiple lymphoid and myeloid progenitors autonomously of cellular context.

overall_design: CMP (Lineage-c-kithiSca-1-CD11c- CD34+ Flk2+CD16/32-CD115- ) or CDP (Lin-c-kitintSca-1-CD34+Flk2+CD16/32-CD115+) were double sorted from the bone marrow of wild type C57BL/6 mice.  RNA was extracted from 10,000-30,000 sorted cells using Trizol (Invitrogen) and linear acrylamide (Ambion), amplified using Affymetrix Two-Cycle Amplification and IVT kits (Affymetrix), and hybridized to Affymetrix Mouse Genome 430 2.0 chips.

first: Drew

last: Michael

first: Ansuman

last: Satpathy

first: Roger

last: Sciammas

first: Harinder

last: Singh

first: Deepta

last: Bhattacharya


title: FGFR1 target genes in brown adipose tissues

status: Public on Jan 06 2012

city: South San Francisco

first: Li

last: Li

address: 1 DNA Way

institute: Genentech, Inc

summary: We aimed to identify genes that are regulated by FGFR1 in brown adipose tissues of adult male ob/ob mice by injecting 1 mg/kg anti-FGFR1 agonistic antibody.

overall_design: Brown adipose tissues were isolated from adult male ob/ob mice at day 4 after a single intraperitoneal injection of 1 mg/kg anti-FGFR1 agonistic antibody or pair-fed mice injected with control IgG. N=6 mice per each group.

first: Junichiro

last: Sonoda

first: Ai-Luen

last: Wu


title: IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid progenitors


title: Smad4 and Trim33 dependend nodal/activin responsive genes in differentiated mouse ESCs

status: Public on Jan 09 2012

city: New York

first: Qiaoran

last: Xi

state: NY

address: 1275, York ave.

department: Cancer biology and genetics

institute: MSKCC

summary: In differentiated mouse ESCs, most of the nodal/activin responsive genes are dependent on both Smad4 and Trim33, some are solely dependent on Smad4, and some are dependent on Trim33.

overall_design: Ebs at Day2.5 from WT, Smad4 null, and Trim33 knock-down ESCs, were treated with activin or SB 431542 for 2 h.

first: Xiang

middle: H

last: Zhang

first: Joan

last: Massague


title: The metastatic microenvironment. Brain-derived soluble factors alter the malignancy phenotype of cutaneous and brain- metastasizing melanoma cells

status: Public on Jan 11 2012

city: Tel Aviv

first: Metsada

last: Pasmanik-Chor

address: Ramat Aviv

department: Biology

country: Israel

institute: Tel Aviv University

summary:
The present study deals with functional interactions of cutaneous and brain-metastasizing human melanoma cells with brain-derived molecules. In this study we employed the unique melanoma xenograft model developed by Izraely and described in Int J Cancer. 2011 Oct 25. doi: 10.1002/ijc.27324. The present study aims to determine if brain-derived soluble factors regulate malignancy-associated functions of cutaneous and brain-metastasizing melanoma cells and identify which functions are regulated by such factors.
The working hypothesis of this study is that the interactions between the brain microenvironment and melanoma cells determine metastasis formation at this organ site. The aim of the study was to evaluate the contribution of such interactions to the formation of brain metastasis in nude mice xenografted with human melanoma cells. An insight into these interactions is an essential pre-requisite for the development of effective targeted therapy for melanoma brain metastasis.   We assessed the effects of soluble factors present in supernatants of short-term cultures of normal mouse brain (referred here after as brain-derived soluble factors) on several characteristics linked to melanoma brain metastasis. It was found that brain-derived soluble factors affect differentially cutaneous and brain-metastasizing melanoma cells variants in-vitro. Such factors enhanced the viability of cutaneous melanoma cells but caused an S phase arrest followed by apoptosis of brain-metastasizing cells. Brain-derived soluble factors enhanced migration of melanoma cells metastasizing to the brain, but did not affect the migration of the cutaneous variants. Such factors up-regulated the expression of the chemokine receptor CCR4 in both cutaneous and brain metastasizing melanoma cells. It is not unlikely that CCR4 ligands expressed in the brain interact with the CCR4-expressing melanoma cells thereby directing them to the brain.   Brain-derived soluble factors enhanced the transmigration, across human brain endothelial cells of cutaneous but not of brain metastasizing melanoma variants. This activity could promote the capacity of the cutaneous cells to metastasize to the brain.

overall_design: 4 Samples (arrays) were analyzed. There is 1 replicate for each variant and each treatment. We generated pairwise comparisons between cutaneous and brain metastatic variants of the same genetic background, using Partek Genomics Suite, in the three melanoma models. Genes with p≤5% and a fold-change difference of  ≥2 or <-2 were selected.

first: Anat

last: Klein

first: Orit

last: Sagi-Assif

first: Sivan

last: Izraely

first: Tsipi

last: Meshel

first: Clara

last: Nahmias

first: Pierre-Olivier

last: Couraud

first: Neta

last: Erez

first: Dave

last: Hoon

first: Isaac

middle: P

last: Witz


title: AMPK stimulation and PGC-1 alpha suppression in peroxisome deficient hepatocytes favor catabolic over anabolic carbohydrate metabolism

city: Cologne

first: Emiel

last: Ver Loren van Themaat

address: Carl von linneweg

country: Germany

institute: Max Planck Institute

summary: These arrays contain data from the livers of 10 week old L-Pex5 -/- male mice

overall_design: 6 arrays, 3 biological replicates

first: Annelies

last: Peeters

first: Myriam

last: Baes


title: Paracrine TGFß Signaling Counterbalances BMP-Mediated Repression in Hair Follicle Stem Cell Activation

status: Public on Jan 04 2012

first: Naoki

last: Oshimori

state: New York

address: 1230 York Avenue

institute: The Rockefeller University/HHMI

summary:
Hair follicle (HF) regeneration begins when communication between quiescent epithelial stem cells (SCs) and underlying mesenchymal dermal papillae (DP) generates sufficient activating cues to overcome repressive BMP signals from surrounding niche cells. We uncovered a hitherto unrecognized DP transmitter, TGFβ2, which activates Smad2/3 transiently in HFSCs concomitant with entry into tissue regeneration.
We used microarrays to detect the genes specifically affected by TGFß receptor II-deficient mice upon HFSC activation.

overall_design: Hair follicle stem cells (HFSCs) of hair gem (HG) and bulge, and total skin keratinocytes were FACS-purified from the mouse back skin at 2nd telogen-to-anagen transition stages.

first: Elaine

last: Fuchs


title: High Fat Diet Reduces the Expression of Glutathione Peroxidase 3 in Mouse Prostate

status: Public on Jan 02 2012

city: Bethesda

first: Yoshitaka

last: Sekine

state: Maryland

address: 10 Center Dr

institute: NHLBI

summary:
High fat diets are known to be a risk factor for prostate cancer. In this study, we investigated the effect of high fat diet on mouse prostate gene expression.   C57BL/6J mice were fed either a control or high fat diet for 12 weeks. Microarray analyses were performed on mouse ventral prostate (VP) and dorsolateral prostate (DLP), followed by canonical pathway analysis and regulatory network identification. mRNA changes were confirmed by real time PCR.   Approximately 2,125, and 1,194 genes responded significantly to the high fat diet in VP, DLP, respectively. Pathways and networks related to oxidative stress, glutathione metabolism, NRF-mediated oxidative stress response and NF-kappaB were all differentially regulated by high fat diet. GPx3 mRNA levels were decreased by approximately 2-fold by high fat diet in all 3 prostate lobes. In human non-transformed prostate cells (PrSC, PrEC and BPH-1), cholesterol loading decreased GPx3 expression, and increased H2O2 levels of culture medium. Troglitazone increased GPx3 expression in 3 normal prostate cells, and decreased H2O2 levels. In addition, troglitazone attenuated cholesterol-induced H2O2 increase. Tissue from prostate cancer biopsies had decreased GPx3 mRNA and its level was inversely related to the Gleason score.
High fat diet alters pathways related to many genes concerned with oxidative stress. GPx3, a gene identified by this analysis, was found to be down regulated by high fat diet and appears be decreased in human prostate cancers, suggesting that GPx3 may have a possible role in modulating carcinogenesis.

overall_design: Control group:5 C57BL/6J mice (Taconic, Hudson, NY), 8-weeks of age, fed control diet ad libitum for 12 weeks; Experimental group: 5 C57BL/6J mice (Taconic, Hudson, NY), 8-weeks of age, fed ad libitum high fat diet for 12 weeks.

first: Alan

last: Remaley


title: Comparison of global expression profile of bulge and hairshaft of the hair follicle in murine skin

status: Public on Jan 01 2012

city: Lausanne

first: Joerg

last: Huelsken

address: Station 19

institute: EPFL

summary: To assess potential differences in skin stem cells and their associated stromal cells

overall_design: Total RNA of specific substructures of the hair follicle (bulge and hairshaft) were collected by laser-capture micro-dissection and resulting amplified cDNA hybridized to Affymetrix Mouse Genome 430 2.0 arrays.

first: Ilaria

last: Malanchi


title: Effect of 5-azacytidine on gene expression in C2C12 myoblasts

city: Nijmegen

first: Marlinda

last: Hupkes

address: Heyendaalseweg 135

department: Cell and Applied Biology

country: Netherlands

institute: Radboud University Nijmegen

summary: Mesenchymal progenitor cells can be differentiated in vitro into myotubes that exhibit many characteristic features of primary mammalian skeletal muscle fibers. However, in general, they do not show the functional excitation-contraction coupling or the striated sarcomere arrangement typical of mature myofibers. Epigenetic modifications have been shown to play a key role in regulating the progressional changes in transcription necessary for muscle differentiation. In this study, we demonstrate that treatment of murine C2C12 mesenchymal progenitor cells with 10 µM of the DNA methylation inhibitor 5-azacytidine (5AC) promotes myogenesis, resulting in myotubes with enhanced maturity as compared to untreated myotubes. Specifically, 5AC treatment resulted in the upregulation of muscle genes at the myoblast stage while at later stages nearly 50 % of the 5AC-treated myotubes displayed a mature, well-defined sarcomere organization as well as spontaneous contractions that coincided with action potentials and intracellular calcium transients. Both the percentage of striated myotubes and their contractile activity could be inhibited by 20 nM TTX, 10 µM ryanodine and 100 µM nifedipine, suggesting that action potential-induced calcium transients are responsible for these characteristics. Our data suggest that genomic demethylation induced by 5AC overcomes an epigenetic barrier that prevents untreated C2C12 myotubes from reaching full maturity.

overall_design: C2C12 cells were plated at 1500 cells/cm2 (day -1), cultured for 1 day in DMEM 10%NCS, then treated (d0) with or without 10uM 5-azacytidine (5AC) for an additional 3 days. RNA was extracted on day 3 and hybridized to GeneChip Mouse Genome 430 2.0 array (Affymetrix).

first: Ana

last: Sotoca

first: Eugene

last: van Someren

first: Roselinde

middle: I

last: van Ravestein-van Os

first: Susanne

last: Bauerschmidt

first: Everardus

middle: J

last: van Zoelen

first: Koen

last: Dechering


title: Expression profiles of Telomerase+ vs. ALT+ G3 Atm-/-TERT-ER T-cell lymphomas

first: Jian

last: Hu

summary: We used microarray profiling to document the difference between telomerase+ vs. ALT+ T-cell lymphomas developed on G3 Atm-/-TERT-ER genetic background.

overall_design: T-cell lymphomas were developed in G3 Atm-/-TERT-ER mice with 4-OHT treatment. These cells were either maintained on SCID mice treated with 4-OHT or vehicle. Cells maintained on vehicle eventually developed ALT-dependent resistance. We used microarray to profile telomerase+ tumors vs. ALT+ tumors from the same parental lines.

first: Ron

last: DePinho


title: Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation

city: Taipei

first: Yi-Yu

last: Su

department: Graduate Institute of Physiology

country: Taiwan

institute: National Taiwan university

summary: To investigate the transcriptional response of tumor adaptation to reoxygenation, breast cancer cells MCF-7 was cultured under 0.5% of hypoxia for 24h followed by 24h of reoxygenation in normoxia. Cells were harvested respectively at 0, 1, 4, 8, 12, and 24h during reoxygenation.

overall_design: Total RNA obtained from human breast cancer cell line MCF-7 were collected respectively at 0, 1, 4, 8, 12 and 24 hours after reoxygenation.

first: Liang-Chuan

last: Lai


title: Expression profiling of rheumatoid arthritis patients treated with anti-TNF

first: Erik

last: Toonen

address: Geert Grooteplein-zuid 10

department: Medicine

institute: Radboud University Nijmegen Medical Centre

summary: Expression profiles of anti-TNF responders were compared to profiles of anti-TNF non-responders in order to identify an expression signature for anti-TNF response

overall_design: In total 42 patients were treated with anti-TNF. RNA was isoloated from white blood cells and anti-TNF responders (n=18) were compared to nonresponders (n=24) regarding expression profiles

first: Christian

last: Gilissen

first: Barbara

last: Franke

first: Wietske

last: Kievit

first: Agnes

last: Eijsbouts

first: Alfons

last: den Broeder

first: Simon

last: van Reijmersdal

first: Joris

last: Veltman

first: Hans

last: Scheffer

first: Tim

last: Radstake

first: Piet

last: van Riel

first: Pilar

last: Barrera

first: Marieke

last: Coenen


title: Gene level expression profiling of colorectal cancer tissue samples (test sample series)

status: Public on Jan 05 2012

city: Oslo

first: Anita

last: Sveen

address: P.O.Box 4953, Nydalen

department: Department of Molecular Oncology

country: Norway

institute: Institute for Cancer Research, Oslo University Hospital

summary: This series is part of a larger series (GSE24549) of colorectal cancer tissue samples analyzed for global gene expression. The expression measures were used to develope a gene signature for prediction of prognosis in stage II and III colorectal cancer.

overall_design: Gene expression profiling of colorectal cancer tissue samples for prognosis prediction.

first: Trude

last: Ågesen

first: Torleiv

middle: O

last: Rognum

first: Ragnhild

last: Lothe

first: Rolf

last: Skotheim


title: Expression data from postnatal mouse apical and basal organ of Corti from Dicer1 conditional knockout and littermate control cochleae.

city: Omaha

first: Garrett

last: Soukup

state: NE

address: 2500 California Plaza

department: Biomedical Sciences

institute: Creighton University

summary:
Cre recombinase-mediated conditional knockout of floxed Dicer1 alleles causes depletion of small RNAs including microRNAs, which function to repress target mRNA expression by inhibiting translation and/or stimulating mRNA degradation.
We used microarrays to examine gene expression in apical versus basal organ of Corti from the cochleae of control and mutant mice in which Dicer1 was deleted and microRNAs were depleted specifically in sensory hair cells by Atoh1 promoter-driven Cre recombinase expression.

overall_design: Each biological replicate represents the combined apical or combined basal segments of organ of Corti from both cochleae of a single mouse. Two biological replicates for apical and basal organ of Corti from Dicer1 conditonal knockout and littermate controls were collected for RNA extraction and microarray analysis.


title: Genome-wide analysis of gene expression profiles in individuals infected with the Human T-Lymphotropic virus Type 1 (HTLV-1) - test set

city: London

first: Charles

middle: R. M.

last: Bangham

address: Norfolk Place

department: Immunology

country: United Kingdom

institute: Imperial College London

summary: Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In a previous study we identified a 80-gene transcriptional signature of HAM based in the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. In this study we wished to validate the 80-gene signature on an independent cohort comprising 17 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 8 uninfected healthy control subjects.

overall_design: Patients attending the HTLV-1 clinic at St Mary’s hospital in London, UK were classified according to their clinical status as asymptomatic HTLV-1 carriers (ACs, n=17), patients with HTLV-1-associated meylopathy (HAM, n=10) or uninfected control subjects (n=8). Three ml of blood were drawn into a Tempus tube (Applied Biosystems, Foster City, CA, USA). Total RNA was extracted, globin mRNA depleted and following cRNA generation samples were analysed on HUmanWG6 v3 Illumina BeadChip arrays.

first: Sonja

last: Tattermusch

first: Jason

last: Skinner

first: Damien

last: Chaussabel

first: Jacques

last: Banchereau

first: Matthew

last: Berry

first: Finlay

middle: W

last: McNab

first: Anne

last: O'Garra

first: Graham

last: Taylor

middle: R


title: Genome-wide analysis of gene expression profiles in individuals infected with the Human T-Lymphotropic virus Type 1 (HTLV-1)

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

overall_design: Refer to individual Series


title: Transcriptome in 129sv and Crx-/- pineal gland at ZT (Zeitgeber time) 6 and ZT20

city: Copenhagen

first: Louise

last: Rovsing

address: Blegdamsvej 3

department: Neuroscience and Pharmacology

country: Denmark

institute: Copenhagen University

summary:
The cone-rod homeobox gene (Crx) encodes Crx, a transcription factor selectively expressed in two cell types, retinal photoreceptors and the melatonin secreting pinealocytes of the pineal gland. In this report the role of Crx in regulating gene expression in the mammalian pineal gland was extended using Affymetrix GeneChip technology. Deletion of Crx results in broad modulation of the mouse pineal transcriptome, including a >2-fold downregulation of 543 genes and a >2-fold upregulation of 745 genes. In addition to Crx, there was a >10-fold downregulation of 13 other genes. Of special interest was the discovery of a link between Crx and the homeobox gene Hoxc4, which was upregulated ~20-fold in the Crx-/- pineal gland. Analysis of night and day expression of genes indicated that a set of 51 genes exhibited differential expression in control animals.
Of these genes, only eight were also differentially expressed in Crx-/- animals. This group included Aanat, which encodes the enzyme that controls the daily rhythm in melatonin synthesis in the vertebrate pineal gland. Accordingly, Crx appears to be essential for the 24-hour rhythmic component of expression of some genes in the pineal gland. In the Crx-/- mouse pineal gland, 41 genes exhibited differential night/day expression that was not seen in control animals, suggesting that Crx may function to modulate rhythmic expression of these genes as well. Together, the results of this investigation indicate that Crx broadly modulates the pineal transcriptome, perhaps in part through suppressive effects on expression of the homeobox gene Hoxc4.

overall_design:
Pineal glands from control (129sv) mice and Crx-/- mice were collected at ZT6 and ZT20 for RNA extraction and hybridization on Affymetrix mouse 430_2 chip. Each condition were performed as triplicats.

SUPPLEMENTARY FILES:
The GCOS signal intensity data were analyzed using ChipInspector (Genomatix) version 2.1. FDR= 0, p-value <0.05, cut off=1, region size = 300 bp and 4 and 5 significant probes.
Log(2) fold change independently of time of day. Up regulated genes: genes which are up regulated in Crx-/- compared to the control; down regulated genes: genes which are down regulated in Crx-/- compared to the control.

first: Samuel

last: Clokie

first: Diego

last: Bustos

first: Kristian

last: Rohde

first: Steve

last: Coon

first: Martin

middle: F

last: Rath

first: Morten

last: Møller

first: David

middle: C

last: Klein


title: Protective gene expression changes elicited by an inherited defect in photoreceptor structure.

status: Public on Dec 31 2011

city: Rockville

first: Radu

last: Cojocaru

state: MD

address: 5635 Fishers Lane, Suite 510

institute: Elsevier

summary: To investigate pathogenic mechanisms in such instances, we have characterized rod photoreceptor and retinal gene expression changes in response to a defined insult to photoreceptor structure, using the retinal degeneration slow (rds) mouse model.  Global gene expression profiling was performed on flow-sorted rds and wild-type rod photoreceptors immediately prior and subsequent to times at which OSs are normally elaborated.  Dysregulated genes were identified via microarray hybridization, and selected candidates were validated using quantitative PCR analyses. We identified a single key gene, Egr1, that was dysregulated in a sustained fashion in rds rod photoreceptors and in the retina.  Egr1 upregulation was associated with microglial activation and migration, into the outer retina at times subsequent to the major peak of photoreceptor cell death.  Interestingly, this response was accompanied by neurotrophic factor upregulation.  We hypothesize that activation of Egr1 and neurotrophic factors represents a protective immune mechanism, contributing to the characteristically slow retinal degeneration of the rds mouse model.

overall_design: We had two conditions WT and Rds-KO at 4 different time points: postnatal (P) 6, P9, P14 and P21.

first: Yagya

middle: V

last: Sharma

first: Linda

last: Ritter

first: Nidhi

last: Khattree

last: Brooks

first: Alison

last: Scott

first: Anand

last: Swaroop

first: Andrew

last: Goldberg


title: Activation of SREBP in Alveolar Type II Cells Enhances Lipogenesis Causing Pulmonary Lipotoxicity

status: Public on Mar 01 2012

city: Cincinnati

first: Yan

last: Xu

state: OH

address: 3333 Burnet Ave

institute: Cincinnati Children's Hospital Medical Center

summary:
Background:  Lung function is dependent upon the precise regulation of the synthesis, storage, and catabolism of tissue and alveolar lipids.
Results:  Activation of SREBP (Sterol Response Element Binding Protein) induced lipogenesis in alveolar epithelial cells, causing neutral lipid accumulation, lung inflammation, and tissue remodeling.
Conclusions:  The accumulation of neutral lipids in type II epithelial cells and alveolar macrophages caused lung inflammation, consistent with findings in lipid storage disorders.
Significance:  Pulmonary lipotoxicity may contribute to the pathogenesis of lung dysfunction associated with diabetes, obesity, and other metabolic disorders.

overall_design: Genome-wide transcription profiling comparison between doxycycline-exposed SFTPC-rtTAWT/Tg/(tetO)7CMV-CreWT/Tg/Insig1flox/flox/Insig2-/- mice (i.e., Insig1/2∆/∆  ) and Insig1flox/flox/Insig2-/- . Three independent pooled RNA from isolated lung type 2 cells of each genotype were used.

first: Laurent

last: Plantier

first: Valérie

last: Besnard

first: Machiko

last: Ikegami

first: Susan

middle: E

last: Wert

first: Alan

middle: N

last: Hunt

first: Anthony

middle: D

last: Postle

first: Jeffrey

middle: A

last: Whitsett


title: Renal Dysfunction in the Setting of Massive Hepatic Necrosis: A Network-based Analysis in a Mouse

city: Salt Lake City

first: Jason

last: Schwartz

state: UT

address: 30 North 1900 East

department: Surgery

institute: University of Utah

summary: To date, no published reports (human or animal) have examined the impact of acute liver failure on global gene expression profiles in remote organ systems like the kidney.  In this study, we have characterized a model of acute kidney injury (AKI) using two highly-accurate techniques for assessing renal function in a mouse. In this model, mice developed massive hepatocyte necrosis, disordered hepatosplanchnic hemodynamics, and alterations consistent with ALF. Simultaneously, acute renal insufficiency developed, manifesting as oliguria, azotemia, and decreased glomerular filtration.  In this paper, renal function is corroborated using two independent methodologies. These techniques are used in addition to hemodynamic, biochemical, and histologic analyses to demonstrate that acute hepatic injury promulgates renal dysfunction in a mouse. Similar to network-based analyses conducted in other models of human disease, we present a comprehensive, genome-wide assessment of the differentially-regulated, renal transcriptome in the setting of massive hepatic necrosis. Using this approach, mice receiving the select hepatotoxin D-(+)-Galactosamine HCl (GalN) were found to have significant perturbations in renal pathways related to lipid metabolism, small molecule biochemistry, the cell cycle, molecular transport, and amino acid metabolism, despite normal renal histology. By combining data obtained from clinical, physiologic, and molecular investigations, our findings have direct implications for exploring potential pharmacological approaches to the prevention of AKI in this setting.

overall_design:
Male C57BL6 mice weighing 20 grams were given i.p. injections of the select hepatotoxin D-(+)-Galactosamine HCl (GalN).  Animals were divided into 3 groups (n =3 per group):  1)  Saline control injection (necropsy at 24 hours), 2) 4.5 g / kg GalN injection (necropsy at 24 hours), and 3)  4.5 g / kg i.p. injection (necropsy at 48 hours).  At necropsy, liver and kidney were harvested after in situ perfusion with 10 ml of ribonuclease (RNAse)-free PBS and 10 ml of RNA Later reagent (Qiagen, Valencia, CA). Total cellular RNA was isolated from morcellated whole kidneys and liver using a commercial kit (RNA Easy, Qiagen). To extract RNA, 30 mg of tissue was processed according to the manufacturer’s instructions. RNA integrity was monitored using an Agilent Bioanalyzer (Agilent Technologies, Palo Alto, CA). One microgram of denatured RNA was used for cDNA synthesis, with reverse transcription carried out using random hexamer primers (Invitrogen, Carlsbad, CA). For quantitative real-time PCR (RT-PCR), 100 ng of cDNA template, 20 μL of SYBR green master mix and pre-optimized and validated mouse primer sets (Qiagen, Valencia, CA) were used and analyzed in an ABI Prism 7000 Thermocycler or a Roche LightCycler. Relative expression of gene targets was determined by the ΔΔCt method first normalizing to expression of the housekeeping gene, GAPDH, and then to expression in the sham treated control. Expression of RPLP0 was included in the analysis to verify the “housekeeping” status of GAPDH. Efficiencies for each primer pair were determined using the REST program  and verified to be comparable to efficiencies for housekeeping gene primer pairs
           Equal amounts of total RNA from the three individual mice for each treatment condition were prepared for Affymetrix array hybridization according to the Affymetrix GeneChip Expression Analysis Technical Manual (www.affymetrix.com). A total of 18 array measurements were made (sham, 24 hr., and 48 hr. for each animal, liver and kidney, respectively).   These correspond to the various CEL files and are labeled 1-18.  All samples were hybridized to the GeneChip Mouse Genome 430 2.0 Array (Affymetrix, Santa Clara, CA) and preprocessed using R packages affy and gcRMA from the Bioconducter project.
         Greater than 45,000 transcripts and variants on the mouse genome 430 2.0 gene chip array were analyzed. Probe sets significantly perturbed after GalN administration were identified using rank product analysis. False discovery rate was used to control for multiple comparisons using the method of Benjamini and Hochberg. Adjusted p-values <0.05 were considered significant.

first: Matt

last: Firpo

first: Robert

last: Weiss

first: Diane

last: Dunn


title: Expression data from embryoid body with BRCA1 mutation [mRNA]

city: Frederick

first: Suhwan

last: Chang

address: PO Box B, NCI-Frederick

institute: National Cancer Institute

summary: We examined the functional significance of the R1699Q variant of human BRCA1 gene using a mouse ES cell-based assay.

overall_design: The total RNA from the embryoid body of WT, R1699Q and M1652I at day 7 were labeled and used for hybridization against Affymetrix gene expression microarray.

first: Shyam

middle: K

last: Sharan


title: MDS and DNA repair defects in Crebbp+/- mice

city: Plantagenet

first: Madeleine

middle: E.

last: Lemieux

state: ON

address: 275 Main St., Suite 252

country: Canada

institute: Bioinfo

summary: Myelodysplastic syndrome (MDS) is considered a disease of hematopoietic stem cell (HSC) origin.  To begin to unravel the molecular mechanisms underlying the deregulation of HSCs in MDS, we performed comparative gene expression profiling on Crebbp+/- and wild type HSCs.  We chose to isolate HSCs from the fetal liver (FLHSC) because at this stage there were no differences in cell number between Crebbp+/- and wild type fetal livers, suggesting no overt hematopoietic differences.  Thus, any change in gene expression found in Crebbp+/- FLHSCs is likely to reflect the initially compromised genetic program of HSC regulation, as opposed to that of Crebbp+/- HSCs in adult bone marrow, where secondary changes in gene expression may also occur as compensatory mechanisms for a compromised or failing hematopoietic system. We used day 14.5 post coitus FLHSC (Sca-1+,Lin-,AA4.1+,c-Kit++) from wild type (wt) and Crebbp heterozygous (ht) embryos to examine changes in gene expression before overt myelodysplastic disease manifestation.

overall_design: Total RNA from wt and Crebbp+/- FLHSCs was isolated, PCR-amplified using the Ovation RNA amplification system and hybridized to Affymetrix Mouse 430 2.0 expression microarrays.


title: Expression data of murine model of cardiac hypertrophy

city: Sendai

first: Masaharu

last: Nakayama

address: 1-1 Seiryo-machi, Aoba-ku

country: Japan

institute: Tohoku University School of Medicine

summary:
An initial cellular change in the pathogenesis of heart failure is cardiomyocyte hypertrophy, characterized by increased cell size, enhanced protein synthesis and reactivation of fetal genes. In addition to mechanical stresses, several neurohumoral factors have been identified as potent hypertrophic agents, including angiotensin II, endothelin, and catecholamines.
We used microarrays to study the gene expression during cardiac hypertrophy.

overall_design: Balb/c mice (6-8w) were treated with TAC, ATII infusion, and myocardial infarction. TAC model: The transverse aorta (TAC) was constricted at the upper left sternal border by ligation with a 7-silk surgical thread and 27-gauge needle, which was removed thereafter.  Sham-operated controls underwent an identical procedure without TAC. At 1 week and 1month after the procedure, LV was harvested. Ang II model.: Ang II was dissolved in 0.9% NaCl at concentrations sufficient to allow an infusion rate of 2.0 mg/kg/day, known to produce hypertension and cardiac hypertrophy.  Control mice received a vehicle (saline) via an osmotic minipump. At 1 week after the procedure, LV was harvested. MI model: The proximal portion of the left coronary artery was ligated using an 8-0 nylon thread. Myocardial ischemia was confirmed by the discoloration of the heart and typical ECG changes. After 30 min occlusion, the left coronary artery was reperfused by loosening the ligature. In sham-operated mice (SHAM), the pericardium was opened, but the coronary artery was not ligated. At 1 day, 1week, and 1 month after the procedure, LV was harvested.

first: Moriiko

last: Takeda

first: Yasuhide

last: Asaumi

first: Hiroko

last: Tada


title: Expression data of MCK conditional frataxin knock-out mice

city: Sydney

first: Michael

middle: Li-Hsuan

last: Huang

state: NSW

address: Level 5 Blackburn Building D06, University of Sydney

department: Pathology

country: Australia

institute: University of Sydney

summary: Frataxin deficiency in human is the cause of Friedreich's ataxia (FA), a lethal neuro- and cardio-degenerative disease. Knock-out (KO) mice of this mouse model of FA exhibit classical cardiomyopathy of the patients. The onset of FA phenotypes in the KO mice is approximately 6-7 weeks of age. This genearray analysis was conducted to examine the changes in gene expression in the heart of KO mice relative to their wild-type (WT) littermates at 4- and 10-weeks of age. At 10-weeks of age, the KO mice begin to die from severe cardiomyopathy.

overall_design: RNA from the heart of four female 4-week-old MCK littermates (two WT and two KO) and four female 10-week-old MCK littermates (two WT and two KO) was extracted and hybridised to Affymetrix Mouse Genome 430 2.0 Array.

middle: L

first: Des

last: Richardson


title: Expression in IFN-gamma treated control and Atg5-/- macrophages

city: Saint Louis

first: Nicole

last: Maloney

address: 660 South Euclid

department: Pathology/Immunology

institute: Washington University in St Louis School of Medicine

summary: Type-I (α/β) and -II (γ) interferons (IFN), through an incompletely understood combination of redundant and unique mechanisms, are essential for host resistance to viral infection. We report a requirement for the Atg5-Atg12/Atg16L1 autophagosome elongation complex in IFNγ-mediated control of murine norovirus in macrophages. We use microarrays to compare transcriptional changes induced in control and Atg5 deficient macrophages by IFNγ treatment.

overall_design: Bone marrow derived macrophages were generated from Atg5flox/flox and Atg5flox/flox+LysM cre mice and treated with media alone or 100U/ml of IFNγ for 14 hrs. RNA was extracted using Trizol (Invitrogen) and 10 µg of RNA hybridized to Affymetrix microarrays.

first: Seungmin

last: Hwang

middle: S

first: Monique

last: Bruinsma

first: Gautam

last: Goel

first: Ramnik

last: Xavier

first: Larissa

middle: B

last: Thackray

first: Herbert

last: Virgin


title: The Identification of Genetic Factors Influencing Susceptibility to Staphylococcus aureus Infection in mice susceptible and resistant to S. aureus infection

city: Durham

last: Johnson

state: NC

address: 2424 Erwin Rd

institute: Duke University

summary: It has been shown that inbred strains of mice exhibit variable susceptibility to S. aureus infection, but the specific genes responsible for this differential phenotype are unknown. Using ISHM to identify genomic regions associated with the phenotypes, we considered genes within those interval to be candidate genes and used the gene expression patterns of the genes contained in the region to determine whether the genes are differentially expressed between the 2 phenotypically different groups of mice.

overall_design: To identify genes differentially expressed between mice susceptible and resistant to S. aureus infection that could contribute to host susceptibility to S. aureus infection, we compared the gene expression profiles between 2 groups of mice where 3 were susceptible (A/J, BALBcBy/J, AKR/J) and resistant (C57BL/J, C3H/HeJ, NOD/ShiLtJ) to S. aureus. The susceptible group had high bacterial count values in the kidney while the resistant group had low values.

first: SunHee

last: Ahn


title: Cellular response to protein-conjugated nanoparticles

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary:
Interaction of nanomaterials with the mammalian cells remains to be poorly understood at the molecular level. Here we report the first synthesis of hybrid nanomaterial termed phage mimetic nanorods (PMN’s) inspired from filamentous bacteriophage present in nature. We emulate filamentous bacteriophage structure by combining two separate nanoscale entities, one functionalized gold nanorods and the other is coat proteins isolated from filamentous bacteriophage obtained through landscape phage screening. Utilizing biochemical interactions between a phage-derived protein and functionalized gold nanorods, we synthesized novel phage mimetic nanorods. The resulting nanovectors showed excellent multi functional properties including target specificity, imaging and photo destruction ability in a model SKBR-3 breast cancer cells. In addition, to gain insight into the molecular interactions involved during internalization of PMNs by SKBR-3 cells, we performed gene expression profiling of cells exposed to PMNs as compared with naive cells. We identified 70 upregulated and 26 downregulated genes responding to PMNs. Heparin binding internalization was identified as most plausible mechanisms of PMNs entry.  Members of Major Histocompatibility complex I (MHC class I) were activated by PMNs, leading to enhanced lysosome and proteasome activity. Seven members of poorly annotated G antigen family (GAGE) of genes were upregulated, and may represent novel mechanism of PMNs entry recognition by cells. In summary, we present a versatile technique of PMNs production as any protein isolated from phage libraries selected against any in vitro and in vivo cells can be used as a source to synthesize PMN’s. This study also opens new avenues to understand the role of nanomaterials at the molecular level.
Investigate the effect of phage mimetic nanorods onto SKBT-3 cells

overall_design: Two groups were compared, three biological replicates each. One group was control cells and the other was test.

first: Gopal

last: Abbineni

first: Aihua

last: Liu

first: Penghe

last: Qui

first: Sita

last: Modali

first: Barbara

last: Safiejko-Mroczka

first: Chuanbin

last: Mao


title: Genome-wide analysis of matched microRNA-mRNA time-course data after androgen injection to prostate cancer LNCaP cell line

city: Shanghai

first: Wenjuan

last: Mo

address: No. 220 Handan Road

department: Life School

country: China

institute: Fudan University

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

summary: Androgen receptor (AR) signalling pathway plays an important role in carcinogenesis and development of prostate cancer. The involvement of microRNA (miRNA) in this process is still largely unknown. In this study, we performed a matched miRNA-mRNA time-course expression profiling to reveal androgen response in hormone-sensitive prostate cancer cells.We introduced novel statistics Response Score (RS) and Modulation Score (MS) to identify significant androgen-regulated target genes and miRNA-modulated target mRNAs. Based on the analysis, we found several novel androgen-regulated targets, which had significant androgen response in expression pattern, and were highly enriched in predicted androgen responsive elements (AREs). AR-bindings to these AREs were validated with ChIP assay. Furthermore, a set of target mRNAs involved in crucial processes of tumor progression were identified to be significantly regulated by these miRNAs. Therefore, a miRNA-mediated androgen signalling network was inferred, including three novel feedback mechanisms for AR self-modulation. In conclusion, our study provides new approaches to further miRNA regulation research and contributes novel findings into miRNA-mediated pathological effects in prostate cancer.

overall_design: Total RNA obtained from androgen dihydrotestosterone (DHT) subjected to LNCaP cells in vitro at 20min, 40min, 1h, 2h, 4h, 8h, 16h, 24h and 48h, compared to the control at 0h.

first: Jiyuan

last: Zhang


title: Gene expression in CD8α+ SPDCs and CD8α- SPDCs

city: Suita

first: Satoshi

last: Uematsu

state: Osaka

address: 3-1 Yamada-oka

department: Department of Host Defense

institute: Research Institute for Microbial Diseases, Osaka University

summary: Microarray analysis of CD8α+ SPDCs and CD8α- SPDCs from C57BL/6 mice; to elucidate genes specifically expressed in CD8α+ SPDCs

overall_design: CD8α+ DCs and CD8α- DCs were isolated from the spleen of C57BL/6 mice. Total RNA was extracted with an RNeasy kit (Qiagen), and purified using an Oligotex mRNA Kit (Pharmacia). Fragmented and biotin-labeled cDNA was synthesized from 100 ng purified mRNA using the Ovation Biotin System (Nugen), according to the manufacturer’s protocol. cDNA was hybridized to Affymetrix Murine Genome 430 2.0 microarray chips (Affymetrix) according to the manufacturer’s instructions. Hybridized chips were stained, washed and scanned using a GeneArray Scanner (Affymetrix). Data analysis was performed with Microarray Suite software (Version 5.0, Affymetrix) and GeneSpring software (Silicon Genetics).


title: Expression data from squamous cell carcinoma stem cells, epidermal progenitor cells and hair follicle bulge stem cells

status: Public on Dec 30 2011

city: New York

first: Markus

last: Schober

address: 1230 York Ave

institute: Rockefeller University

summary:
We used microarrays to assess the global gene expression profiles of cancer stem cells which were isolated from cutaneous squamous cell carcinomas which developed when WT, TGF beta receptor II ko, FAK KO, and TGF beta receptor II/FAK double KO were subjected to continuous DMBA treatment.
Squamous cell carcinoma stem cells were compared to epidermal progenitor cells (CD49fhighCD34low) and hair follicle bulge stem cells (CD49fhighCD34high).

overall_design: Squamous cell carcinoma was initiated by continuous DMBA treatment (complete carcinogenesis). Cancer cells were sorted based on high CD29 and CD49f expression, infected with a retrovirus expressing a triple modality reporter (luciferase, RFP, thymidine kinase) and grafted onto nude recipient mice. RFP positive lineage was separated into CD29 high, CD49f high and CD34 low; or CD29high, CD49f high and CD34high squamous cell carcinoma initiating cells.

first: Elaine

last: Fuchs


title: Gene expression profiles of 48 normal and 47 prostate tumor tissue samples

city: Heidelberg

first: Ruprecht

last: Kuner

address: Im Neuenheimer Feld 460

department: Molecular Genetics

institute: German Cancer Research Center and National Center of Tumor Diseases

summary: Large-scale gene expression profiles were investigated in 48 normal and 47 prostate tumor tissue samples using Affymetrix GeneChip Exon 1.0 ST microarrays.

overall_design:
Gene expression profiling of human prostate samples using Affymetrix Human Exon 1.0 ST arrays

Two disease subtype analyses were performed:

- Prostate Tumor vs Benign
- TMPRSS2-ERG fusion-positive vs fusion-negative prostate tumors

first: Jan

last: Brase

first: Marc

last: Johannes

first: Maria

last: Faelth

first: Thorsten

last: Schlomm

first: Holger

last: Sueltmann


title: Expression in LT-HSC after in vitro culture in mSCF, mTpo, mFlt3L, hIGFBP2 and Angptl5.

status: Public on Dec 28 2011

city: Leiden

first: Martijn

middle: H

last: Brugman

address: Albinusdreef 2

department: IHB

institute: LUMC

summary: Mouse LT-HSC were sorted and cultured in mScf, mTpo, mFlt3L, hIGFBP2 and Angptl5 for 2 days. These expression values were related to insertions of gamma-retroviral, lentiviral or alpharetroviral vectors carrying GFP which were retrieved after serial murine BM transplantation. The relation between gene expression in the cells responsible for long-term hematopoiesis and location of vector integration was investigated.

overall_design: Biological duplicate measurements of murine sorted and cultured LT-HSC (LSK, CD34-, CD135-)

first: Julia

last: Suerth

first: Christopher

last: Baum


title: Transcriptional Response of Adult Mouse Brain to Hypoxia

city: Sacramento

first: Huichun

last: Xu

address: 2805 50th Street

institute: University of California at Davis

summary:
Since normal brain function depends upon continuous oxygen delivery and short periods of hypoxia can precondition against subsequent ischemia, this study examined the effects of brief hypoxia on the whole genome transcriptional response in adult mouse brain.
Genomic expression profiling was perfromed for individual brain regions of the adult mice following the entire time course of hypoxia preconditioning.

overall_design: Adult C57BL/6 male mice were exposed to systemic preconditioning hypoxia (8% O2 ) for 3 hr and allowed to recover in normoxia for 24 hr. The mouse brains were removed and dissected into individual brain regions at multiple time points during the 3hr hypoxia and subsequent 24hr reoxygenation periods. Total RNA was purified from the human whole blood or individual mouse brain regions. Genomic scale gene expression was then measured with Affymetrix Mouse Expression 430 2.0 arrays.

first: Aigang

last: Lu

first: Frank

last: Sharp


title: Single Cell based genomewide gene expression analysis of murine bone-marrow derived Very Small Embryonic-Like Stem Cells (VSELs)

status: Public on Dec 21 2011

city: Louisville

first: DONG-MYUNG

last: SHIN

state: KY

address: 500 South, Floyd Street

department: Stem Cell Institute at James Graham Brown Cancer Center

institute: University of Louisville

summary:
Recently, we identified a population of Oct4+Sca-1+Lin-CD45- very small embryonic-like stem-cells (VSELs) in adult tissues. Open chromatin structure of pluripotency genes and genomic imprinting-related epigenetic mechanisms maintain pluripotency and quiescence of VSELs, respectively. However, global transcriptome signature of this rare stem-cell population remains elusive. Here, we demonstrate by genomewide gene-expression analysis with a small number of highly purified murine bone-marrow (BM)-derived VSELs, that Oct4+ VSELs i) express a similar, yet nonidentical, transcriptome as embryonic stem-cells (ESCs), ii) up-regulate cell-cycle checkpoint genes, iii) down-regulate genes involved in protein turnover and mitogenic pathways, and iv) highly express Ezh2, a polycomb group protein.
Furthermore, as a result of Ezh2 overexpression, VSELs, like ESCs, exhibit bivalently modified nucleosomes (trimethylated H3K27 and H3K4) at promoters of important homeodomain-containing developmental transcription factors, thus preventing their premature transcription. Notably, spontaneous or RNA interference-enforced down-regulation of Ezh2 during VSEL differentiation removes the bivalent-domain (BD) structure, which leads to de-repression of several BD-regulated genes. Therefore, we suggest that VSELs, like other pluripotent stem-cells, maintain their pluripotent state through an Ezh2-dependent BD-mediated epigenetic mechanism.

overall_design: T7-primed cDNA libraries was synthesized using FACS sorted twenty cells. T7-primed libraries were biotin-labeled using the GeneChip 3’ in vitro transcription (IVT) kit (Affymetrix), starting from ‘‘In vitro Transcription to Synthesize Labeled aRNA. Nine Samples (3 VSELs, 3 HSC, and 3 ESC-D3) are analyzed using GeneChip 3’ Mouse Genome 430 2.0 array (Affymetrix), according to the manufacturer’s instructions.

first: Dong-Myung

last: Shin

first: Sabine

middle: J

last: Waigel

first: Mariusz

middle: Z

last: Ratajczak

first: Magda

last: Kucia


title: Mouse bone marrow-derived macrophages infected with T. gondii (Type I, RH strain) for 6 hr

city: Irvine

first: Melissa

last: Lodoen

address: 3238 McGaugh Hall

institute: UC Irvine

summary:
Toxoplasma gondii is a globally distributed parasite pathogen that infects virtually all warm-blooded animals.  A hallmark of immunity to acute infection is the production of IFN-γ and IL-12, followed by a protective T cell response that is critical for parasite control.  Naïve T cell activation requires both TCR stimulation and the engagement of costimulatory receptors.  Because of their important function in activating T cells, the expression of co-stimulatory ligands is believed to be under tight control.  The molecular mechanisms governing their induction during microbial stimulation, however, are not well understood.  We found that all three strains of T. gondii (Types I, II, and III) up-regulated the expression of B7-2, but not B7-1, on the surface of mouse bone marrow-derived macrophages.  This induction occurred at the transcriptional level, required active parasite invasion, and was not dependent on MyD88 or TRIF.  Genome-wide transcriptional analysis comparing infected and uninfected macrophages revealed the activation of MAPK signaling in infected cells.  Using specific inhibitors against MAPKs, we determined that parasite-induced B7-2 is dependent on JNK, but not ERK or p38 signaling.  We also observed that T. gondii-induced B7-2 expression on human peripheral blood monocytes is dependent on JNK signaling, indicating that a common mechanism of B7-2 regulation by T. gondii may exist in both humans and mice.
We used microarrays to examine genome-wide changes in host cell gene expression during T. gondii infection at an early time point (6 hpi).

overall_design: BMdM were mock-treated or infected with T. gondii (Type I, RH strain) at an MOI of 2 and cultured for 6 hours.  Biological triplicates were performed.  Total RNA was harvested and used for cDNA synthesis, labeling, and hybridization to Affymetrix mouse 430 2.0 expression arrays.


title: Human Mesenchymal Stem Cells Exploit the Immune Response Mediating Chemokines to Impact the Phenotype of Glioblastoma

status: Public on Dec 20 2011

city: Ljubljana

first: Kristina

last: Gruden

address: Vecna pot 111

department: Department of Biotechnology and Systems Biology

country: Slovenia

institute: National Institute of Biology

summary: Four human mesenchymal stem cells (hMSC) clones (MSC-1, MSC-2, MSC-3, MSC-4) and three different glioblastoma multiformae (GBM) cell lines (U87-MG, U251, U373) were used to study their mutual paracrine interactions in the indirect co-cultures compared to their monocultures, which were grown under the same experimental conditions. The effects on cell growth, proliferation and invasion in matrigel were quantified. Further on, bioinformatic tools were used to relate these results to the data obtained from cytokine macroarrays and DNA microarrays that revealed proteins and genes significantly involved in the interaction. We showed that hMSC are responsible for the impairment of GBM cell invasion and growth, possibly via induction of their senescence. On the other hand, U87-MG cells even more strongly inversely affected some of these characteristics in hMSCs. We found several chemokines that may account for changed co-cultured cells’ phenotype, affecting genes associated with proliferation and senescence. CCL2/MCP-1 was collectively identified as the most significantly regulated chemokine during hMSC and U87-MG paracrine signalling. Its role in U87-MG cell invasion was also functionally confirmed. Microarray data deposited here contain gene expression data from three biological replicates of monocultures and indirect co-cultures of MSC-4 and U87-MG cells, representing 12 microarrays.

overall_design: Three biological replicates of four cell set-ups were performed: MSC-4 monoculture, U87-MG monoculture, MSC-4 co-cultured with U87-MG (in Boyden chambers) and U87-MG co-cultured with MSC-4 (in Boyden chambers).

first: Helena

last: Motaln

first: Matjaž

last: Hren

first: Christian

last: Schichor

first: Tamara

last: Lah Turnšek


title: Reduction of dietary glycemic load modifies expression of several miRNAs associated with energy balance and cancer pathways in premenopausal women

status: Public on Dec 19 2011

city: buffalo

first: Dan

last: Wang

address: Elm & Carlton Streets

institute: RPCI

summary: We assessed the effect of dietary glycemic load on miRNA expression in a sample of healthy, premenopausal women participating in a 12 month intervention designed to lower dietary glycemic load.

overall_design: Comparing post-intervention to baseline miRNA expression data of 14 participants receiving the active intervention.

first: Susan

last: McCann

first: Song

last: Liu

first: Hua

last: Zhao


title: Global Gene Expression Analysis of Murine Limb Development

city: Livermore

first: Gabriela

last: Loots

address: 7000 East Avenue

department: BBTD

institute: Lawrence Livermore National Laboratory

summary: Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here, we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature, and nerves are specified and the musculoskeletal system of the limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore-limb and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which tampers off at later time points. Among 3520 genes identified as significantly up-regulated in the limb, we find ~30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that correlate with functional programs during limb development and are likely to provide new insights into specific tissue patterning processes. Here we provide for the first time, a comprehensve analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis.

overall_design: Fifty- one arrays were analyzed, consisting of whole fore-limb and hind-limb bud RNA (experimental) and whole embryo RNA (reference) samples from E9.5 to E13.5 DPC mouse (FVB strain). Embryos were not pooled to generate samples. Each time point has 3 to 5 biological replicates for limb bud samples, duplicates for whole embryos. Comparisons were made between limb bud samples and whole embryo at the same stage, fore-limb samples of different stages, hind-limb samples of different stages, and fore-limb samples compared to hind-limb samples at the same or the next stage.

first: Leila

last: Taher

first: Nicole

last: Collette

first: Deepa

last: Murugesh

first: Evan

last: Maxwell

first: Ivan

last: Ovcharenko


title: Expression data from Estrogen Receptor alpha-positive Progesterone Receptor-positive Mammary Tumors in STAT1-/- Mice.

status: Public on Dec 15 2011

city: St Louis

first: Szeman

middle: Ruby

last: Chan

address: 425 S. Euclid Ave

department: Pathology and Immunology

institute: Washington University School of Medicine

summary:
Aged STAT1-/- female mice spontaneously develop ERa+ PR+ mammary tumors that exhibit strikingly similar hormone-sensitivity and -dependency as human ERa+ luminal breast cancers.
We used microarray data to compare the genetic relationships between the STAT1-/- mammary tumors and human breast cancers.

overall_design: We compared five STAT1-/- mammary tumor datasets with the publicaly available datasets of human breast cancers and those from other mouse mammary tumor models.

first: Robert

last: Schreiber

middle: R


title: Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.

status: Public on Dec 16 2011

city: Basel

first: Jonathan

last: Moggs

address: Fabrikstrasse 2

institute: Novartis

type: Methylation profiling by genome tiling array

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

overall_design: Refer to individual Series

first: Harri

last: Lempiäinen

first: Arne

last: Müller

first: Sarah

last: Brasa

first: Soon-Siong

last: Teo

first: Tim-Christoph

last: Roloff

first: Laurent

last: Morawiec

first: Natasa

last: Zamurovic

first: Axel

last: Vicart

first: Enrico

last: Funhoff

first: Philippe

last: Couttet

first: Dirk

last: Schübeler

first: Olivier

last: Grenet

first: Jennifer

last: Marlowe

first: Rémi

last: Terranova


title: ISR target genes in the liver of either LFD and HFD-treated Alb::GC mice and AP20187-treated TTR::Fv2E-PERK mice

status: Public on Dec 23 2011

city: Tokushima

first: Seiichi

last: Oyadomari

state: Tokushima

address: 3-18-15 Kuramoto

department: Institute for Genome Research

institute: The University of Tokushima

summary:
The molecular mechanisms linking the stress of unfolded proteins in the endoplasmic reticulum (ER stress) to glucose intolerance in obese animals are poorly understood. In this study enforced expression of a translation initiation 2alpha (eIF2a)-specific phosphatase, GADD34, was used to selectively compromise signaling in the eIF2(Î±P)-dependent arm of the ER unfolded protein response in liver of transgenic mice. The transgene resulted in lower liver glycogen levels and susceptibility to fasting hypoglycemia in lean mice and glucose tolerance and diminished hepato-steatosis in animals fed a high fat diet. Attenuated eIF2(aP) correlated with lower expression of the adipogenic nuclear receptor PPARgamma and its upstream regulators, the transcription factors C/EBPalpha and C/EBPbeta, in transgenic mouse liver, whereas eIF2alpha phosphorylation promoted C/EBP translation in cultured cells and primary hepatocytes. These observations suggest that eIF2(aP)-mediated translation
  of key hepatic transcriptional regulators of intermediary metabolism contributes to the detrimental consequences of nutrient excess.
Keywords: genotype comparison

overall_design:
The high expressing Ttr::Fv2E-Perk transgenic mice was injected by either mock or AP20187. Wildtype and Alb::GC transgenic mice were fed by either Low Fat Diet (LFD) or High Fat Diet (HFD) .

bred into the Atf4 knockout strain and the derivative compound heterozygous mice (in the mixed FvB/n; Swiss Webster background) were backcrossed to the Atf4+/- parental stock and Ttr::Fv2E-PERK positive siblings with Atf4+/+ and  Atf4-/- genetypes were analyzed.

first: Heather

middle: P

last: Harding

first: Yuhong

last: Zhang

first: Miho

first: David

last: Ron


title: Global analysis reveals HDAC1 occupies active and inactive genes and core transcription factors in embryonic stem cells and trophoblast stem cells

city: Rockland

first: Benjamin

last: Kidder

state: MA

address: 1 Technology Place

department: Reproductive Health

institute: EMD Serono Research Institute

type: Genome binding/occupancy profiling by genome tiling array

summary: Epigenetic regulation of gene expression is important in maintaining self-renewal of embryonic stem (ES) cells and trophoblast stem (TS) cells. Histone deacetylases (HDACs) negatively control histone acetylation by removing covalent acetylation marks from histone tails.  Because histone acetylation is a known mark for active transcription, HDACs presumably associate with inactive genes.  Here, we used genome-wide chromatin immunoprecipitation to investigate targets of HDAC1 in ES cells and TS cells.  Through evaluation of genes associated with acetylated histone H3 marks, and global expression analysis of Hdac1 knockout ES cells and trichostatin A treated ES cells and TS cells, we found that HDAC1 occupies mainly active genes, including important regulators of ES cell and TS cell self-renewal.  By mapping HDAC1 targets on a global scale, our results describe further insight into epigenetic mechanisms of ES cell and TS cell self-renewal.

overall_design: RNA was harvested from ES cells and TS cells cultured in the presence of 0 nM, 10 nM, 50 nM, or 100 nM Trichostatin A (TSA) for 24 hours for transcriptome analysis.


title: Expression data from osteocytes in virgin,lactating and post lactation mice

city: KANSAS CITY

first: Lynda

middle: F

last: Bonewald

address: 650 E 25th Street

department: Department of Oral Biology

institute: School of dentistry University of Missouri-Kansas City

summary:
We have previously shown that during lactation, osteocytes directly remodel their perilacunar and pericanalicular matrix, thereby mobilizing calcium and contributing to maternal bone loss. To identify genes potentially responsible for perilacunar remodeling, microarray analysis was performed on osteocytes from CD-1 virgin and lactating mice and mice sacrificed on day 7 post weaning.
By comparing how gene expression changes in osteocytes among virgin, lactation and post lactation, the goal is to identify the genes osteocytes use to remodel their perilacunar matrix

overall_design: To identify genes responsible for perilacunar remodeling, microarray analysis was performed on tibiae from CD-1 virgin and lactating mice and mice sacrificed on day 7 post weaning. Periosteum and bone marrow were removed from the tibiae and the bone fragments underwent sequential collagenase/trypsin digestion and were examined histologically to ensure removal of all surface cells and confirm osteocyte enrichment prior to RNA extraction. Microarray Affy M430 arrays, n=3 per group were performed and Genepattern and Bioconductor were used to analyse the microdata.

first: Hai

last: Qing


title: Tumor Suppressor BRCA1 epigenetically controls oncogenic miRNA-155

city: Frederick

first: Suhwan

last: Chang

address: PO Box B, NCI-Frederick

institute: National Cancer Institute

summary:
BRCA1, a well-known breast and ovarian cancer susceptibility gene with multiple interacting partners, is predicted to have diverse biological functions. However, to date its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate risk variant, and found that it does not impair DNA damage repair but abrogates the repression of miR-155, a bona fide oncomir. We further show that in the absence of functional BRCA1, miR-155 is up-regulated in BRCA1-deficient mouse mammary epithelial cells, human and mouse BRCA1-deficienct breast tumor cell lines as well as tumors. Mechanistically, we found that BRCA1 represses miR-155 expression via its association with HDAC2, which deacetylates H2A and H3 on the miR-155 promoter. Finally, we show that over-expression of miR-155 accelerates whereas the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Taken together, our findings demonstrate a new mode of tumor suppression by BRCA1 and reveal miR-155 as a potential therapeutic target for BRCA1-deficient tumors.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series.


title: Sex-specific effects of prenatal stress in 5-Htt deficient mice: towards molecular mechanisms of gene x environment interactions

status: Public on Dec 12 2011

city: Wuerzburg

first: Susanne

middle: Elma

last: Kneitz

address: Biozentrum, Am Hubland

department: Physiologigcal Chemistry

institute: University of Wuerzburg

summary:
prenatal stress response, genetic modification
Background: Prenatal stress (PS) exposure has been shown to increase the risk for emotional disorders in later life. Furthermore, the serotonin transporter (5-HTT) genotype is suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we use a 5-HTT x PS paradigm to investigate whether the effects of PS are dependent upon the 5-HTT genotype.  Methods: The effects of PS on cognition, anxiety- and depression-related behaviour were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous (+/-) 5-HTT knockout mice. Additionally, in the female offspring, a genome-wide hippocampal gene expression screening was performed.  Results: 5-HTT +/- offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. Conversely, exposure of 5-HTT +/- mice to PS was associated with altered stress-responsivity and increased depressive-like behaviour, particularly in female offspring. Further, 5-HTT genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signalling were regulated by both the 5-HTT +/- genotype and PS exposure, whereas cytokine and Wnt signalling were affected in a 5-HTT genotype x PS manner, indicating a gene x environment interaction at the molecular level.  Conclusions: The long-term behavioural effects of PS in C57BL6 mice are partly dependent on the 5-HTT genotype. Further, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioural effects of the 5-HTT genotype, PS exposure, and their interaction.

overall_design: total samples analysed are 12

first: Daniel

last: Van den Hove

first: Sissi

last: Jakob

first: Karla

middle: G

last: Schraut

first: Gunther

last: Kenis

first: Angelika

last: Schmitt

first: Claus-Juergen

last: Scholz

first: Valentina

last: Wiescholleck

first: Gabriela

last: Ortega

first: Jos

last: Prickaerts

first: Harry

middle: M

last: Steinbusch

first: Klaus-Peter

last: Lesch


title: Genome wide analysis of acral melanoma

status: Public on Dec 13 2011

city: London

first: Simon

last: Furney

address: 237 Fulham Road

institute: Institute of Cancer Research

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


title: Effects of Nicotine on the Fetal Mouse Palate Development and Transcriptome

city: Lincoln

first: Ali

last: Nawshad

address: 40th and Holdrege

department: Oral Biology

institute: Unviersity of Nebraska Medical Center

summary: Nonsyndromic cleft palate is a common birth defect (1:700) with a complex etiology involving both genetic and environmental risk factors. Nicotine, a major teratogen present in tobacco products, was shown to cause alterations and delays in the developing fetus. To demonstrate the effect of nicotine on craniofacial development, particularly palatogenesis, we delivered three different doses of nicotine (1.5, 3.0 and 4.5 mg/kg/day) into pregnant BALB/c mice throughout their entire pregnancy using subcutaneous osmotic mini-pump. We assessed the pups for morphological anomalies, as well as genome-wide mRNA (transcriptome) microarray analysis. Consistent administration of nicotine caused developmental retardation, still birth, low birth weight, and significant palatal size and shape abnormality in the pups. However, it did not cause obvious cleft palate. The microarray data analysis using IPA identified differential expression of genes involved in various biological pathways, particularly cancer, genetic diseases, and tissue development in response to consistent nicotine exposure. 6232 up-regulated and 6310 down-regulated genes were detected in nicotine-treated groups compared to the control. Moreover, 45% of the genes associated with cleft palate were found to be affected by nicotine. Alterations of a subset of differentially expressed genes were illustrated with hierarchal clustering and RT-PCR. We concluded that consistent nicotine exposure during pregnancy interferes with normal growth and development of the fetus including palatogenesis; however, this interference does not result in cleft palate, rather smaller palate size with persistent MES. To our knowledge, this is the first experiment revealing the impact of nicotine on the fetal palate transcriptome in mice.

overall_design: Total 8 samples were analyzed. Using an osmotic minipump, duplicate samples from palates of  either sterile physiological saline or nicotine (1.5 mg/kg/day, 3.0 mg/kg/day, or 4.5 mg/kg/day)-treated newborn pups.

first: Ferhat

last: Ozturk

first: Elizabeth

last: Sheldon

first: Serkan

last: Aydemir

first: Hasan

last: Out

first: Eric

last: Fung


title: Expression data from the liver of wild-type and Cnot3+/- mice

status: Public on Dec 09 2011

city: San Antonio

first: Masahiro

last: Morita

state: Texas

address: 4939 Charles Katz Drive

department: Department of Molecular Medicine

institute: University of Texas Health Science Center at San Antonio


title: CD8+ T cell mediated lung inflammation

city: Braunschweig

first: Robert

last: Geffers

address: Inhoffenstr. 7

department: Dep. Molecular Bacteriology

institute: HCI - Helmholtz Centre for Infection Research

summary: Role for naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) in counterbalancing this process. Using a transgenic murine model for autoimmune-mediated lung disease, we demonstrated that, despite pulmonary inflammation, lung-specific CD8+ T cells can reside quiescently in close proximity to self-antigen. Whereas self-reactive CD8+ T cells in the inflamed lung and lung-draining lymph nodes down-regulated the expression of effector molecules, those located in the spleen appeared to be partly antigen-experienced and displayed a memory-like phenotype. Since ex vivo-reisolated self-reactive CD8+ T cells were very well capable to respond to the antigen in vitro, we investigated a possible contribution of nTregs to the immune control over autoaggressive CD8+ T cells in the lung.

overall_design:
We isolated antigen-specifc CD8+ T-cells from lungs and bronchial lymphnodes derived from chronic diseased mice (SPC-HAxCL4), healthy control mice (CL4) and acute influenza infected control mice (CL4+IAV) and perormed mRNA expression profiling of isolated CD8+ T cells. Each group represents a pool of at least n=4 animals.
CD8+ T cell type comparison; lung disease state analysis

first: R

first: M

last: Gereke

first: D

last: Bruder

last: Tosiek


title: Candidate Genes for Panhypopituitarism identified by gene expression profile

status: Public on Dec 14 2011

city: Ann Arbor

first: Amanda

last: Mortensen

state: MI

address: 4909 Buhl Bld. 1241 E. Catherine St.

department: Human Genetics

institute: University of Michigan

summary:
Prop1 controls the expression of genes besides Pit1 that are important for cell mgration, survival and differentiation in the mouse and human pituitary gland.
Microarray analysis was used to compare pituitary RNA from newborn Prop1 and Pit1 mutants and their wild type littermates.

overall_design: Total RNA was collected and pooled  from Prop1df/df, Porp1+/+, Pit1dw/dw, and Pit+/+ at the age of P1. 5 pools per genotype were hybridized to the Affymetrix Mouse Genome 430 2.0 array.

first: Sally

middle: A

last: Camper


title: Expression data from ESC and in vitro derived somatic cells and germ cells

city: Los Angeles

first: John

last: Vincent

address: 621 Charles E Young Dr. S

department: MCDB

institute: UCLA

summary: We performed gene expression profiling on in vitro derived PGCs, undifferentiated ESCs, and somatic cells from the EB to examine germ cell expression in ESC-derived cells

overall_design: All cells were collected using fluorescence activated cell sorting to isolate SSEA1+/cKit+ ESCs, SSEA1+/cKitbright PGCs, Oct4-gfp+/cKitbright PGCs, and SSEA1-/cKit- somatic cells and Oct4-gfp-/cKit- somatic cells.

first: Amander

middle: T

last: Clark


title: Expression data from the liver of wild-type and Cnot3+/- mice: Fasted

summary:
Decay of mRNAs initiates with shortening of the poly(A) tail. Although the CCR4-NOT complex participates in deadenylation, how it becomes activates remain obscure. We show that complete deficiency in CNOT3, subunit 3 of this complex, is lethal in mice, but that heterozygotes survive as lean mice with hepatic and adipose tissues containing reduced lipid levels. Cnot3+/- mice have enhanced metabolic rates and remain lean on high-fat diets.
To examine the underlying mechanisms by which CNOT3 is involved in the control of metabolic balance, we compared the gene expression profiles of wild-type and Cnot3+/- mice using Affymetrix microarray technology. We chose to analyze the liver because the CNOT3 level in the liver was affected by the feeding condition and because the liver plays a major role in glucose and lipid metabolism.

overall_design: The livers were isolated from 12-week-old wild-type and Cnot3+/- mice (n = 2 for each genotype).

first: Takeshi

last: Nagashima


title: In vivo Gene Expression Profiling of Retina Post-Intravitreal Injections of Dexamethasone and Triamcinolone at Clinically Relevant Time Points for Patient Care

status: Public on Dec 08 2011

city: Davis

first: Zeljka

last: Smit-McBride

state: CA

address: One Shields Ave, Tupper Hall #2403

department: Ophthalmology & Vision Science

institute: University of California, Davis Eye Center

summary:
PURPOSE   To identify retinal genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care.
METHODS   Differential gene expression of over 34,000 well-characterized mouse genes, in the retinas of 6 weeks old C57BL/6J mice were analyzed after intravitreal steroid injections at 1 week and 1 month time points, using Affymetrix Mouse Genome 430 2.0 microarrays.  The data were analyzed using GeneSpringGX11 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes.
RESULTS   A common gene pathway, with differentially activated genes for both steroids and time points was ‘Semaphorin Signaling in Neurons’, a member of ‘Axonal Guidance Signaling System’.  At 1 week post-injections a common theme was activation of genes expressed in retinal glial cells, TNF alpha and TGF beta signaling pathways and upregulation of stress response proteins (Serpina3n, Cebpd), as well as neuropeptide signaling somatostatin receptor (Sstr2). Unique for Dex was the upregulation of acute phase proteins (Gfap, Cp, Edn2) as well as Plexna2, a semaphorin signaling receptor,  while EphrinB receptor ephexin1 (Argef15) was downregulated. Folate signaling appears to be unique for TAA at 1 week (Folh1, Cubn), while aryl-hydrocarbon receptor (AhR) signaling might be important for both steroids at 1 month.
CONCLUSIONS  Understanding the molecular and genetic effects of intraocular steroid treatments is of clinical relevance.  This in vivo study has elucidated several genes and pathways that are potentially altering the neuroprotective/neurodegenerative balance between glial and retinal ganglion cells during intravitreal steroid treatment.

overall_design: Total of 18 retinal samples were analysed. There were two time points, day7 and day30. Each time point had three groups: BSS control, DEX treatment and TAA treatment. Each group had three biological replicas.


title: Expression data from livers of F2 mice (C57BL/6 X DBA/2) deficient in leptin receptor (db/db)

status: Public on Dec 29 2011

first: Calvin

last: Pan

address: 675 Charles Young Dr South

summary:
In several models of obesity-induced diabetes, increased lipid accumulation in the liver has been associated with decreased diabetes susceptibility. For instance, deficiency in leptin receptor (db/db) leads to hyperphagia and obesity in both C57BL/6 and C57BLKS mice but, only on the C57BLKS background do the mice develop beta-cell loss leading to severe diabetes while C57BL/6 mice are relatively resistant. Liver triglyceride levels in the resistant C57BL/6 mice are 3 to 4 fold higher than in C57BLKS.
To better understand the mechanisms contributing to metabolic dysfunction in obesity-induced diabetes, we used microarrays to comprehensively profile gene expression livers of F2 mice (B57BL/6 X DBA/2) deficient in leptin receptor (db/db)

overall_design: DBA/2J females were mated to C57BL/6 males carrying leptin receptor deficiency (db/+) and, F1 (db/+) offspring were interbred to produce F2 mice. Offspring deficient in leptin receptor (db/db) were fed on a chow diet until 5 weeks or 12 weeks of age and then euthanized for collection of liver tissue for RNA profiling along with other diabetes-related phenotypes.

first: Richard

middle: C

last: Davis

first: Aldons

last: Lusis


title: Expression data from BMDC cells with or without Sendai virus infection

city: Shanghai

first: Yuan

last: Zhang

address: Yueyang St. 320#

institute: Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences

summary: Innate immunity is the first line of defense against viral and microbial pathogens. BMDC is critical for innate immunity. To investigate the complicated net signaling after virus invasion, we did a cDNA microarray analysis of BMDC with or without Sendai Virus infection. We used microarrays to find proteins that upregulated by Sendai Virus infection and investigated if these proteins had functions in regulating Sendai Virus induced signaling pathway.

overall_design: BMDC cells are seperated from C57BL6 mice, infected with Sendai Virus or not,cultured and harveseted for RNA extraction and hybridization on Affymetrix microarrays

first: Bo

last: Yang

last: Wang


title: Expression data of mouse ENCCs and mouse embryonic Gut E14.5

status: Public on Dec 07 2011

city: Groningen

first: Duco

last: Schriemer

address: Hanzeplein 1

department: Genetics

institute: University Medical Center Groningen

summary:
Signaling of the RET receptor is crucial for the migration, proliferation, differentiation and survival of enteric neural crest cells (ENCCs) that form the enteric nervous system (ENS). Disturbances in RET signaling are associated with ENS defects, as is seen in patients with Hirschsprung disease. However, the downstream effectors of RET signalling in ENCCs is largely unknown. This study aims to gain new insight into the pathways involved in or triggered by RET in ENCCs.
We used microarrays to detect the gene expression of mouse embryonic ENCCs when we stimulated with GDNF compare to control without GDNF and also compare to the gene expression of mouse embryonic gut (all are isolated from mouse embryonic day 14.5). Our aim is to gain insight of RET-GDNF downstream effectors and also all signalling pathways that regulate by RET-GDNF in ENCCs during development.

overall_design: We performed gene expression profiling with RNA isolated from GDNF- (the RET ligand) stimulated and non-stimulated mouse ENCCs and also from mouse embryonic gut E14.5. We compare these three set of microarray data to each other and analyzed single-gene analysis methods. by this analysis we could detect genes that regulate by RET-GDNF signalling in ENCCs and by comparing data of ENCCs with and without GDNF to the expression data of mouse embryonic gut in the same stage of development, we could also detect gene that specifically express in ENCCs dependent and independently of RET-GDNF signalling. We analyzed the gene expression data of ENCCs with and without GDNF by gene set enrichment analysis (GSEA) to detect which pathways are down- and up-regulated by RET-GDNF signalling.

first: Yunia

last: Sribudiani

first: Ellen

last: Binder

first: Wanda

last: Douwenga

first: Evelyn

last: Wesseling

first: Uli

last: Eisel

first: Alan

last: Burns

first: Bart

last: Eggen

first: Nikhil

last: Thapar

last: Hofstra

first: Rudolf

last: Fehrmann

first: Marco

last: Metzger


title: Neural invasion induces cachexia via astrocytic activation of neural route in pancreatic cancer

city: Takatsuki

first: Akira

last: Imoto

institute: Osaka Medical College

summary: Pancreatic cancer is characterized by a high frequency of cachexia, pain and neural invasion (N-inv). Neural damage is occurred by N-inv and modulates pain and muscle atrophy via the activation of astrocyte in the connected spine. The activated astrocyte by N-inv, thus, may affect cachexia in pancreatic cancer. Clinical studies in patients and autopsy cases with pancreatic cancer have revealed that N-inv is related to cachexia and astrocytic activation. We established a novel murine model of cancer cachexia using N-inv of human pancreatic cancer cells. Mice with N-inv showed a loss of body weight, skeletal muscle, and fat mass without appetite loss, which are compatible with an animal model of cancer cachexia. Activation of astrocytes in the spinal cord connected with N-inv was observed in our model. Experimental cachexia was suppressed by disrupting neural routes or inhibiting the activation of astrocytes. These data provide the first evidence that N-inv induces cachexia via astrocytic activation of neural route in pancreatic cancer.

overall_design: We produced neural invasion (N-inv) model using intraneural injection of Capan-1 cells to left sciatic nerve of male SCID mouse. For controls, subcutaneous model (SC) and PBS model were produced. Microarray analysis was performed using the first lumbar cord (L1) from PBS, SC, and N-inv mice at 6 w (n = 2 each).

first: Akir


title: Functional Plasticity of Regulatory T Cell Function

city: Memphis

first: David

last: Finkelstein

state: TN

address: 332 N. Lauderdale St.

department: Computational Biology

institute: St Jude Children's Research Hospital

summary: Regulatory T cells (Tregs) can suppress a wide variety of cell types, in diverse organ sites and inflammatory conditions.  While Tregs possess multiple suppressive mechanisms, the number required for maximal function is unclear.  Furthermore, whether any inter-relationship orcross-regulatory mechanisms exist that areused to orchestrate and control their utilization is unknown.  Here we assessed the functional capacity of Tregs lacking the ability to secrete both interleukin-10 (IL-10) and IL-35, which individually are required for maximal Treg activity.  Surprisingly, IL-10/IL-35-double deficient Tregswere fully functionalin vitro and in vivo. Loss of IL-10 and IL-35 was compensated for by a concurrent increase in cathepsin E (CTSE) expression, enhanced TRAIL (Tnfsf10)expression and soluble TRAIL release, rendering IL-10/IL-35-double deficient Tregsfunctionally dependent on TRAIL in vitro and in vivo.  Lastly, while C57BL/6 Tregs are IL-10/IL-35-dependent, Balb/c Tregs, which express high levels of CTSE and enhanced TRAIL expression, are TRAIL-dependent.These data reveal that cross-regulatory pathways exist, which control the utilization of suppressive mechanisms,thereby providing Tregfunctional plasticity.

overall_design: Isolate natural Tregs from the different knockout mouse

first: Meenu

last: Pillai

first: Lauren

middle: W

last: Collison

first: Xiaohua

first: Jerold

middle: E

last: Rehg

first: Kelli

last: Boyd

first: Andrea

last: Szymczak-Workman

first: Teresa

last: Doggett

first: Thomas

last: Griffith

last: Ferguson

first: Dario

last: Vignali


title: mRNA composition of IRP2 mRNPs in mouse tissues

city: Heidelberg

first: Mayka

last: Sanchez

address: Meyerhofstrasse 1

institute: EMBL

summary: Affymetrix microarrays were used to determine the mRNA composition of mRNPs obtained by immunoprecipitation with IRP2 (iron regulatory protein 2).

overall_design:
Reference Sanchez at al., 2007 Nat. Protoc. Affymetrix microarrays were used to determine the mRNA composition of mRNPs obtained by immunoprecipitation with IRPs (iron regulatory proteins). In brief, total RNA was extracted from the reported tissue of four to six C57BL6/J mice using Trizol reagent. mRNA from duodenum, liver and spleen were extracted from mice fed with an iron poor diet (<10mg/kg, Altromin Spezialfutter GmbH & Co, Lage, Germany) for 21 days starting from weaning age. mRNAs from bone marrow and brian were extracted from mice (8-10 weeks old) fed with an iron-normal diet. For each tissue, the RNA samples were pooled and the immunoprecipitations were carried out combining 50 µg of total RNA with purified recombinant His-tagged IRP2  produced in E.coli and a mouse monoclonal anti-His tag antibody.  A control reaction in which the recombinant IRP2 was omitted was performed in parallel (referred with the word “control” in the title).
All the microarray procedures were conducted at  the EMBL Genomics Core Facility using standard Affymetrix protocols.  In brief, approximately 120ng of immunoprecipitated RNA was used as input to a two-step amplification procedure to generate biotin-labeled RNA fragments for hybridization to the Affymetrix GeneChip Mouse Genome 430 2.0 array (Eukaryotic Sample and Array Processing manual 701024 Rev.3). Intensity values for the hybridizations were obtained either using RMA, calculations done in bioconductor  (www.bioconductor.org) or MAS5, calculated using Affymetrix GCOS package. MAS5 calculated intensities were further quantile normalized using bioconductor.

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