title: Remodeling of synaptic transmission genomic fabrics in a model of infantile spasms

city: Prairie View

first: Dumitru

middle: Andrei

last: Iacobas

address: Ann Preston St

department: Undergraduate Medical Academy

institute: Prairie View A&M University

summary: We profiled the whole transcriptomes of male rat hypothalamic arcuate nuclei to determine the remodeling of the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in epilepsy and recovery following different treatments. The rats were prenatally exposed (G15) to betamethasone (or just saline for control) followed by repeated adiministration of N-Methyl-D-Aspartic acid on postnatal days 12, 13 and 15 which triggered infantile spasms. Pups were treated with either ATCH, PMX53 (a potent C5ar1 antagonist) or saline to act as a control, on days 13, 14 and 15 prior to NMDA administration to determine what effects each treatment had on transcriptome recovery. Our Genomic Fabric Paradigm (GFP) is proposed as a transformative research approach to enhance the understanding of the brain transcriptomic alterations in epileptic rats and recovery following various treatments. The genomic fabric of a particular synapse is the structured transcriptome associated with the most interconnected and stably expressed gene network responsible for that type of neurotransmission. GFP refines the description of functional pathways by selecting the most prominent genes and determining their networking.  Moreover, it quantifies the remodeling of functional pathways and their interplay in disease and recovery in response to a treatment. We found that priming with betamethasone had substantial consequences on the topology of the genomic fabrics of all kind of synaptic transmission and that NMDA-induced spasms strongly exacerbated the remodeling of these fabrics. However, ACTH treatment, which is effective in significantly improving seizure outcomes, recovered 49% of the normal transcriptome in the hypothalamic arcuate nucleus. Surprisingly, PMX53 treatment recovered 64% of the normal transcriptome despite having no significant effect on behavioural seizure outcomes.

overall_design:
One tissue (hypothalamic arcuate nucleus) x two prenatal exposures (B = betamethasone, S = saline) x two conditions for the betamethasone expossed rats (with (Y) without (N) infantile spasms) x three postnatal treatments (A = ACTH, P = PMX53, S = saline) x one sex (M) . Biological replicates: 4 ASNSM, 4 ABNSM, 4 ABYSM, 4 ABYAM, 4 ABYPM.

We have used the "multiple yellow" design in which differently labeled RNAs from two biological samples are co-hybridized with the array and then CY3 and Cy5-labeled samples are compared separately and the results averaged.

first: Tamar

last: Chachua

first: Sanda

first: Melissa

last: Benson

first: Karin

last: Borges

first: Jana

last: Velíšková

first: Libor

last: Velíšek


title: Renal 0-hour biopsies

status: Public on Apr 25 2016

city: Innsbruck

first: Johannes

last: Leierer

address: Anichstr. 35

department: Internal Medicine IV - Nephrology

country: Austria

institute: Medical University Innsbruck

summary: Profiling of 0-hour wedge biopsies from deceased kidney donors (without signs of AKI) to recognize differences in age groups.

overall_design: mRNA profiling of n=37 samples from from human subjects with no sign of AKI, thus healthy kidney; comparison of three age groups (<40; 40 - 60; >60 years)

first: Michael

last: Rudnicki

first: Paul

last: Perco


title: DMGDH over expression in HCC cell line

status: Public on May 03 2016

city: Shanghai

first: Gang

last: Liu

address: 320 Yueyang Rd, Shanghai

country: China

institute: Shanghai Institutes for Biological Sciences

summary: mRNA levels of MHCCLM3 cell line over expressing DMGDH and GFP were evaluated with Aligent microarray

overall_design: RNA from HCC cell line with over expression of DMGDH and GFP were extracted, and evaluated with Aligent Human 4x44 microaaray

first: Guojun

last: Hou

first: Lei

first: Weiping

last: Zhou


title: Reprogramming lineage committed cells into iMSC-LC, part 2

city: Sydney

first: Ashwin

last: Unnikrishnan

state: NSW

address: Room 217, Level 2, Adult Cancer Program, Lowy Cancer Research Centre, University of New South Wales

department: Lowy Cancer Research Centre

country: Australia

institute: University of New South Wales

summary: Genome-wide gene expression comparison between mesenchymal stem cells, lineage differentiated cells and reprogrammed cells.

overall_design: Total RNA obtained from MSCs, lineage differentiated cells and reprogrammed cells.

first: Vashe

last: Chandrakanthan

first: John

middle: E

last: Pimanda


title: Expression profiling of muscles in NOD-SCID mice bearing RXF and SKR tumors

status: Public on May 01 2016

city: Singapore

first: Shyh-Chang

last: Ng

address: 60 Biopolis St

country: Singapore

institute: Genome Institute of Singapore

summary: Cachexia is a devastating muscle wasting syndrome that occurs in patients suffering from chronic diseases, most commonly observed in 80% of advanced cancer patients. One of the primary causes of cachexia-associated morbidity and mortality is involuntary muscle wasting. And while many cachexia patients show hypermetabolism, its causative role in muscles had remained unclear. To understand the molecular basis of this muscle wasting, accurate models of cachexia are necessary. Using transcriptomics and cytokine profiling of human muscle stem cell-based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors which rapidly led to higher levels of fatty acid metabolism and the activation of a p38 stress response signature, before the cachectic muscle wasting is manifested. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, leading to oxidative stress, p38 activation, and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also significantly improved muscle mass and total weight in cancer cachexia models in vivo. Therefore, fatty acid-induced oxidative stress could be targeted to prevent cancer cachexia.

overall_design: Three NOD-SCID mice were subcutaneously transplanted with RXF393 or SKRC39 cancer cells for 22 d. Quadriceps muscles were harvested and total RNA was extracted with the Trizol reagent (Ambion) for each mouse, processed with the Total Prep RNA for Illumina kit (Ambion), and hybridized to an Illumina MouseWG-6 v2.0 beadchip, then scanned on the Illumina Beadarray Reader. Array normalization was performed with Illumina Genome Studio Gene Expression module 1.9.0 using quantile normalisation. In total 6 RNA samples were prepared on the beadchip.

first: Tomoya

last: Fukawa

first: Jun-Hao

last: Tan


title: Gene expression alterations produced by opioid self-administration in the mouse striatum

city: Krakow

first: Marcin

last: Piechota

address: Smetna 12

department: Molecular Neuropharmacology

country: Poland

institute: Institute of Pharmacology PAS

summary:
Chronic exposure to opioids induces adaptations in brain function that lead to the formation of the behavioral and physiological symptoms of drug dependence and addiction.
Genome wide analysis of molecular effects of protracted morphine or saccharin intake in C57BL/6J mice over a period of 7 months provides an opportunity to observe the alterations in the brain that accompany long-term drug addiction.

overall_design: Microarray experiment was designed to compare chronic and acute effects of protracted morphine or saccharin self-administration. Therefore we have analyzed 4 groups: animals chronically drinking saccharin with a saline or morphine injection, and mice chronically drinking morphine with saline or morphine injection. Animals were sacrificed 4 hours after receiving either a saline (10 ml/kg) or morphine (20 mg/kg, ip) injection.

first: U

last: Skupio

first: M

last: Korostynski

first: R

last: Przewlocki


title: Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Aberrant Calreticulin expression in articular cartilage of Dio2 deficient mice

status: Public on Apr 27 2016

city: Leiden

first: Nils

last: Bomer

state: Zuid-Holland

address: Post zone S-05-P, P.O. box 9600

department: Molecular Epidemiology

country: Netherlands

institute: LUMC

summary: Microarray-data (Illumina MouseWG-6 v2) of knee cartilage of wild-type and Dio2 -/- -mice were re-analyzed to identify differential expressed genes independent of mechanical loading conditions by forced treadmill-running. Differential expression analyses of articular cartilage of Dio2-/- (N = 9) and wild-type-mice (N = 11) while applying a cutoff threshold (P < 0.05 (FDR) and FC > |1,5|) resulted in 1 probe located in Calreticulin (Calr) that was found significantly downregulated in Dio2-/- mice. The beneficial homeostatic state of articular cartilage in Dio2-/- mice is accompanied with significant lower expression of Calr. Functional analyses further showed that upregulation of Calr expression could act as an initiator of cartilage destruction.

overall_design: To identify intrinsic differences in cartilage gene expression profiles between wild-type- and Dio2-/--mice, as a mechanism to investigate factors that contribute to prolonged healthy tissue homeostasis.

first: Frederique

middle: M

last: Cornelis

first: Yolande

middle: F

last: Ramos

first: Wouter

last: den Hollander

first: Nico

last: Lakenberg

first: Ruud

last: van der Breggen

first: Lies

last: Storms

first: P

last: Slagboom

first: Rik

middle: J

last: Lories

first: Ingrid

last: Meulenbelt


title: Expression profile of genes in cord blood (CB)-derived eosinophils

status: Public on Apr 20 2016

city: Ansan

first: Tae Gi

last: Uhm

country: South Korea

institute: hanyang university

summary: To gain inssight into eosinophil development and  finction,  we performed a  global gene expression analysis using developing cord blood (CB) eosinophils.

overall_design: The CB CD34+ cells were cultured for 0, 4, 6, and 12 days. Due to difficulty in obtaining sufficient amounts of total RNA from a small number of freshly isolated CB CD34+ cells, cells pooled from five donors were used for RNA extraction. Additionally, in order to reduce donor-to-donor variation, total RNA isolated from developing cells cultured from three donors’ CB CD34+ cells was pooled in equal amounts.

first: Tae

middle: G

first: Il

middle: Y

last: Chung


title: Genome-wide analysis of differential gene expression after Foxd3 knockdown in colorectal CDCP1+CSCs

status: Public on Apr 22 2016

first: Li

last: Qingquan

address: No.138，Yixueyuan Rd.

institute: fudan university

summary: Analysis of Foxd3-regulation of self-renewal and quiescence in CDCP1+CSCs at gene expression level. The hypothesis tested in the present study was that the Foxd3 global developmental regulator serves a critical role to support the self-renewal of CDCP1+CSCs as one of few known factors involved in maintaining their quiescence. Results provide important information of the response of colorectal CDCP1+CSCs to depletion of Foxd3, such as genes involved in regulation of cell cycle, cell proliferation, and stem-like properties.

overall_design: Total RNA obtained from isolated CDCP1+CSCs subjected to 24 hours in vitro Foxd3 shRNA treatment compared to untreated control cells.

first: Qingquan

last: Li

first: Wenchao

last: Gao


title: Expression analysis of human naïve and memory CD8 T cells at resting stage and following short-term stimulation

status: Public on Apr 01 2016

first: Cheng

last: Yang

address: 227 Chongqing South Road, Luwan District

institute: Shanghai Jiaotong University School of Medicine

summary: Memory T cells (TM) play a prominent role in protection and auto-immunity due to their ability to mount a more effective response than naïve T cells (TN). However, the molecular mechanisms underlying enhanced functionality of TM are not well defined, particularly in human TM. We examined the global gene expression profiles of human CD8+ TN and TM before and after stimulation. There were 1,284, 1,373 and 1,629 differentially expressed genes between TN and TM at 0 hr, 4 hr and 24 hr after stimulation, respectively, with more genes expressed to higher levels in TM. Genes rapidly up-regulated in TN cells were largely involved in nitrogen, nucleoside and amino acid metabolisms. In contrast, those in CD8+ TM were significantly enriched for immune-response-associated processes, including cytokine production, lymphocyte activation and chemotaxis. Multiple cytokines were rapidly up-regulated in TM cells, including effector cytokines known to be produced by CD8+ T cells and important for their functions, as well as regulatory cytokines, both pro- and anti-inflammatory, that are not typically produced by CD8+ T cells. These results provide new insights into molecular mechanisms that contribute to the enhanced functionality of human CD8+ TM and their prominent role in protection and auto-immunity.

overall_design: Naïve and memory phenotype CD8 T cells were purified by FACS from healthy individuals and cultured in vitro with the stimulation of anti-CD3/CD28 mAbs for 0 hr, 4 hr and 24 hr. Total RNA was purified from un-stimulated and stimulated naive and memory CD8 T cells and hybridized to individual single-color arrays.The purification and stimulation protocol was performed two independent times.

first: Hao

last: Shen


title: Gene and microRNA expression predictive of tumour response in patients treated with pCRT for LARC

city: Padova

first: Gerolamo

last: Lanfranchi

address: Via U. Bassi, 58/B

department: CRIBI - Biotechnology Center and Biology Department

country: Italy

institute: University of Padova

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

summary:
The goal of this work is to find robust predictors of tumor response to preoperative chemoradiotherapy in LARC patients.
Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, tumour response to pCRT is not uniform and there are no effective predictive methods. This study investigated whether specific gene and miRNA expression is associated with response to pCRT. Tissue biopsies were obtained from patients before pCRT and resection. Gene and miRNA expression was analyzed using one-color microarrays technique comparing signatures between responders (R) and not responders(NR), as measured by tumour regression grade (TRG). Two groups composed by 38 “exploration cohort” and 21 “validation cohort” LARC patients respectively were considered, for a total of 32 NR and 27 R patients. In the first cohort, SAM Two Class identified 256 genes and 29 miRNAs differentially expressed between NR and R. The anti-correlation analysis showed that the same 8 miRNA interacted with different networks of transcripts. The miR-630 appeared only with NR patients and was anti-correlated with a single transcript: RAB5B. After PAM, resulted as strong predictors of tumour responsen the following 8 transcripts: TMEM188, ITGA2, NRG, TRAM1, BCL2L13, MYO1B, KLF7 and GTSE1. Using this gene set, an unsupervised cluster analysis applied to the second cohort assigned the patients to the NR or R group with 85.7% accuracy with a sensitivity of 90% and a specificity of 82%. All the three parametres reached 100% when the two cohorts were considered together.

overall_design: Tissue biopsies were obtained from patients before pCRT and resection. Two groups composed by 38 and 21 LARC patients respectively were considered, for a total of 32 NR and 27 R patients both for gene and miRNA expression  experiments

first: Caterina

last: Millino

first: Beniamina

last: Pacchioni


title: Essential role of formyl peptide receptor 1 in anthracycline-based anticancer chemotherapy

status: Public on Apr 04 2016

city: Bonn

first: Joachim

last: Schultze

state: NRW

address: Carl-Troll-Strasse 31

department: Genomics and Immunoregulation

country: Germany

institute: LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)

summary: Tumor growth reduction induced by anthracycline-based chemotherapy is largely determined by an anticancer immune response that is ignited by the presentation of dead-cell antigens by intratumoral dendritic cells. In an unbiased screen designed to identify cancer therapy-relevant single nucleotide polymorphisms in genes affecting the interaction between dying tumor cells and immune cells, we identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast cancer patients receiving adjuvant chemotherapy. In mice, the therapeutic effects of anthracyclines were abrogated when the immune system was rendered deficient for FPR1 or when tumor cells lacked the FPR1 ligand Annexin A1 (ANXA1). Defective anticancer immune responses from FPR1 knockout mice could be attributed to the failure of dendritic cells to approach dying tumor cells and hence to present tumor cell antigens to T lymphocytes. Experiments performed in a microfluidic device confirmed the obligatory contribution of ANXA1 and FPR1 to the induction of stable conjugates between dying tumor cells and human or murine leukocytes. Altogether, these results underscore the functional and clinical importance of FPR1 in determining chemotherapy-relevant anticancer immune responses.

overall_design: When the surface of tumor reached 25-45 mm2 after subcutaneous tumor cell innoculation, mice received 2.9 mg/Kg intratumoral doxorubicin (DX) (in 50 μL PBS). Two days after treatment, tumor samples were harvested, rinsed briefly with cold PBS and immediately preserved in RNAlater RNA Stabilization Reagent (Qiagen) overnight at 4°C. Samples were then snap-frozen in liquid nitrogen and stored at -80°C before RNA isolation.

first: Erika

last: Vacchelli

first: Yuting

last: Ma

first: Elisa

last: Baracco

first: Antonella

last: Sistigu

first: David

middle: P

last: Enot

first: Federico

last: Pietrocola

first: Heng

first: Sandy

last: Adjemian

first: Kariman

last: Chaba

first: Michaela

last: Semeraro

first: Fabrizio

last: Mattei

first: Giovanna

last: Schiavoni

first: Valeria

last: Lucarini

first: Francesca

last: Peschiaroli

first: Adele

last: Deninno

first: Luca

last: Businaro

first: Annamaria

last: Gerardino

first: Thomas

last: Ulas

first: Patrick

last: Günther

middle: L

first: Aicha

last: Goubar

first: Gautier

last: Stoll

first: Céline

last: Lefebvre

first: Sylvie

last: Rusakiewicz

first: Peter

last: Van Endert

first: Sylvain

last: Ladoire

first: Monica

last: Lucattelli

first: Fabrice

last: André

first: Ilio

last: Vitale

first: Lorenzo

last: Galluzzi

first: Laurence

last: Zitvogel

first: Guido

last: Kroemer


title: Primary human nasal cells extracted from current smokers treated with kaempferol

city: Chapel Hill

first: Rebecca

middle: Catherine

last: Fry

address: 1213 MHRC

department: Environmental Sciences and Engineering

country: USA

institute: UNC-Chapel Hill

summary:
We are investigating the mRNA expression profiles of human nasal cells from smokers treated with kaempferol
We used microarrays to compare the global mRNA expression profiles upon response to kaempferol treatment

overall_design: Primary nasal epithelial cells were extrated from current smoking volunteers. Cells were cultured, and treated with either DMSO (controls) or 14 uM kaempferol (treated) for 6 hours. RNA was collected after treatment.

first: Julia

last: Rager

first: Luisa

last: Brighton

first: Wenli

last: Zhang

last: Bauer

first: Lisa

last: Smeester

first: Ilona

last: Jaspers

middle: C


title: Expression changes during late stage retinal degeneration in rd1 mice

status: Public on Mar 19 2016

city: Parkville

first: Robb

last: de Iongh

state: VIC

address: Grattan Street

department: Anatomy & Neuroscience

institute: University of Melbourne

summary:
From 3 months of age the retina is known to undergo morphoplogical remodelling. This analysis examines expression in the retina after all the rod photoreceptors are lost (by 1 month) and compares the changes in expression that occur before (2 months) and after (8 months) remodelling.
Total RNA was extracted from central retina regions by punch biopsy at 2 months and 8 months of age from C57Bl6/rd1 mice.

overall_design: Each sample comprised 3-6 retina punch biposies (1.5 mm diameter) of the central retina obtained at dissection in ice-cold PBS. Three independent samples were harvested from rd1/rd1 mice at 2 months of age and three independent samples were isolated from rd1/rd1 mice at 8 months of age.

first: R

last: de Longh

first: E

last: Fletcher

first: U

last: Greferath

first: G

last: Martinez


title: Genome-wide analysis of chronic inflammation-induced gene expression in primary hepatocytes

status: Public on Mar 17 2016

city: Boston

first: Daniel

last: Okin

state: MA

address: 55 Fruit St, BUL148

department: Department of Medicine, Division of Pulmonary and Critical Care

institute: Massachusetts General Hospital

summary: Analysis of whole genome expression changes in primary hepatocytes in response to chronic stimulation with inflammatory cytokines. We hypothesized that chronic treatment of primary hepatocytes with TNFα would result in a reprogramming of the cell's transcriptome to improve adaptation to the presence of a chronic inflammatory stress. Here we provide expression analysis detailing genes upregulated, downregulated, and unchanged after 2 days of TNFα treatment. We have included gene expression profiling of cells treated with TNFα for 2 hours to help isolate the changes unique to chronic TNFα treatment of primary hepatocytes.

overall_design: Total RNA isolated from primary hepatocytes cultured with 2ng/mL TNFα for 2 hours or 2 days, compared to untreated cells

first: Ruslan

last: Medzhitov


title: Analysis of transcriptional signatures in response to Listeria monocytogenes infection reveals temporal and strain dependent changes in interferon signalling

city: London

first: Krzysztof

last: Potempa

address: The Ridgeway

country: United Kingdom

institute: National Institute for Medical Research (NIMR)

summary: Listeriosis is an infectious disease caused by the intracellular bacterium Listeria monocytogenes. To control the infection effectively, the host immune response is directed by intercellular signalling molecules called cytokines that are produced by immune cells following sensing of the bacteria. In this study we used gene expression analysis to examine complex immune signalling networks in the blood and tissues of mice infected with L. monocytogenes. We show that a large set of genes are perturbed in both blood and tissue upon infection and that the transcriptional responses in both are enriched for pathways of the immune response. From these data we also observe an important signalling network emerge from a group of cytokines called interferons (IFNs). Previous findings suggest that different IFN family members can determine the balance between successful and impaired immune responses to L. monocytogenes and several other bacterial infections. Using mice deficient for the detrimental ‘type I’ IFN signalling pathway we show that IFN-inducible genes are differentially regulated at different times upon infection but also present at much lower levels in uninfected mice highlighting how dysregulation of this network in the steady state may determine the outcome of this bacterial infection.

overall_design: Total RNA obtained from isolated blood, liver and spleen of C57BL/6 and B6 IFNAR-/- mice subjected to acute infection by Listeria monocytogenes compared to uninfected controls.

first: Jonathan

last: Pitt

first: Simon

last: Blankley

first: Christine

last: Graham

first: Finlay

middle: W

last: McNab

first: Lucia

last: Moreira-Teixeira

first: Ashleigh

last: Howes

first: Evangelos

last: Stavropoulos

first: Virginia

last: Pascual

first: Jacques

last: Banchereau

first: Damien

last: Chaussabel

first: Anne

last: O'Garra


title: Genomic and functional studies in T-Acute Lymphoblastic Leukemia patients exhibiting clonal T Cell Receptor γ and δ gene rearrangement

city: Kharghar

first: Shubhada

last: Chiplunkar

state: Maharashtra

address: Sector no.22

department: Immunology

country: India

institute: Advanced Centre For Treatment Research And Education in Cancer

summary: T-cell Acute Lymphoblastic Leukemia (T-ALL) is a lymphoid malignancy characterized by clonal proliferation of immature thymocytes arrested at particular stage of differentiation. Earlier studies from our lab have demonstrated that 30% of Indian T-ALL patients exhibited clonal rearrangement of both TCR γ and δ genes. The survival was higher in T-ALL patients showing clonal rearrangements for TCR γ and δ genes. In the present study, we aimed at investigating the gene expression profiles of TCR γδ+ T-ALL patients and correlating it with functional analysis to understand the reasons for increased survival in these patients. Our studies demonstrate differential expression of genes in TCR γδ clonal T-ALL compared to non TCR γδ clonal T-ALL patients. Functional annotation of significantly upregulated genes (p<0.05) in TCR  γδ+ T-ALL patients showed involvement in antigen processing and presentation, cell-cell communication, apoptosis, cell adhesion molecules and immune synapse pathways. Expression of eight selected genes (SMAD3, NFkB1, HLA-DQB1, SOCS2, CISH, FASLG, RXRA,and IFNβ1) was validated in TCRαβ+ and TCRγδ+ subgroups of T-ALL patients using quantitative Real-time PCR. Studies focusing on functional aspects of the gene(s) identified from gene expression profile would aid in developing future therapeutic strategies.

overall_design: Agilent one-color experiment,Organism: Human ,Agilent-014850 Whole Human Genome Microarray 4x44K G4112F  , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)

first: Jaydeep

last: Bhat

first: Gauri

last: Mirji

first: Shripad

last: Banavali


title: Genome-wide analysis of gene expression in TM4 Sertoli cells following siRNA-mediated Gata4 inhibition

city: Helsinki

first: Markku

last: Heikinheimo

address: Tukholmankatu 8

department: Children's Hospital

country: Finland

institute: University of Helsinki

summary: The effects of Gata4 inhibition on global gene expression in TM4 Sertoli cells was analyzed. Using microarray analysis we identified a set of genes that are downregulated or upregulated following siRNA-mediated silencing of Gata4 in the murine Sertoli cell line TM4. Among the downregulated genes were regulators of blood-testtis barrier function and lactate metabolism. TM4 cells were transfected with non-targeting (NT) siRNA and Gata4 siRNA respectively. 72h post transfection cells were lysed and RNA was extracted.

overall_design: n=3 of each sample group; control samples are samples 3-6 (TM4 cells treated with non-targeting siRNA)

first: Anja

last: Schrade

first: Oyediran

last: Akinrinade


title: Identification of genes involved in re-epithelialization

city: Kobe

first: MITSUGU

last: OMATA

address: 6-4-3, Minatojima-MInamimachi, Chuo-ku

country: Japan

institute: ASUBIO PHARMA CO., LTD.

summary: To identify candidate genes involved in re-epithelialization of TGF-b induced dedifferentiated hRPTEC, this experiment was designed.

overall_design: hRPTEC incubated with TGF-b for 48h and hRPTEC incubated with or without TGF-b for additional 24h were collected. Then, they were applied in this experiment.

first: Kei

last: Enomoto

first: Mitsugu

last: Omata


title: MicroRNA-124 and -137 cooperativity controls caspase-3 activity through BCL2L13 in hippocampal neural stem cells. [RNA expression]

status: Public on Mar 12 2016

city: Amsterdam

first: Marijn

last: Schouten

address: Science Park 904

department: Swammerdam Institute for Life Sciences

institute: University of Amsterdam

summary:
Temporal lobe epilepsy (TLE) can develop from alterations in hippocampal structure and circuit characteristics, and can be modeled in mice by administration of kainic acid (KA). Adult neurogenesis in the dentate gyrus (DG) contributes to hippocampal functions and has been reported to contribute to the development of TLE. Some of the phenotypical changes include neural stem and precursor cells (NPSC) apoptosis, shortly after their birth, before they produce hippocampal neurons.
Here we explored these early phenotypical changes in the DG 3 days after systemic KA administration to mice. Our specific aim was to understand the molecular mechanisms underlying altered apoptosis levels in NSPC following KA-induced status epilepticus (KA-SE). Accordingly, we chose a multi-omics experimental setup and analyzed DG tissue samples using proteomics, transcriptomics and microRNA profiling techniques. We here present a description of how these date were obtained and provide them to others for further analysis and validation. This may help to further identify and characterize molecular mechanisms involved in the alterations induced shortly after KA-SE in the mouse DG.

overall_design: Total RNA obtained from dentate gyrus 72h after mice were subjected to repeated low dose kainic acid induced status epilepticus or saline i.p. injections

first: Pascal

last: Bielefeld

first: Silvina

middle: A

last: Fratantoni

first: Chantal

last: Hubens

first: Sander

middle: R

last: Piersma

first: Than

middle: V

last: Pham

first: Rob

last: Voskuyl

first: Paul

last: Lucassen

first: Connie

last: Jimenez

first: Carlos

last: Fitzsimons


title: Molecular function of Prdm1/Blimp1 in trophoblast giant cell differentiation.

status: Public on Mar 14 2016

city: Coventry

first: Andrew

middle: Christopher

last: Nelson

address: Gibbet Hill Campus

department: School of Life Sciences

institute: University of Warwick

summary:
Expression profiling of wild-type and Prdm1 null mouse trophoblast giant cell cultures using Illumina whole genome mouse V2 arrays.
The hypothesis tested was that Prdm1/Blimp1 regulates expression of genes required for spiral artery trophoblast giant cell function.

overall_design: Prdm1 null and littermate control wild-type trophoblast stem cell clones were generated from blastocyst outgrowths.  Total RNA was obtained from multiple replicates of four wild-type TS cell clones and four Prdm1 null TS cell clones differenitated for zero, two, four and six days by growth factor withdrawal and hybridized to Illumina WG6_V2 arrays

first: A

last: Mould

first: E

last: Robertson

last: Bikoff


title: Transcriptome analysis of zinc finger transcription factor CASZ1b in neuroblastoma cells

status: Public on Mar 08 2016

city: Bethesda

first: Zhihui

last: Liu

state: Maryland

address: 9000 rockville pike

institute: National Cancer Institute

summary: Zinc finger transcriptional factor CASZ1b suppresses neuroblastoma growth. We have generated a tetracycline inducible CASZ1b expression neuroblastoma cell line (SY5YtetCASZ1b), in which CASZ1b has been transfected into SY5Y cells and its expression could be induced by treating the cells with tetracycline. Using gene expression profiling assay for the cells treated with tetracycline (Tet+) or without tetracycline (Tet-), we identified CASZ1b target genes and downstream transcriptional pathways in neuroblastoma cells.

overall_design: SY5YtetCASZ1b cells were cultured in 6-well plate overnight, then treated with or without 1 µg/ml tetracyline for 24 hr. Three independent experiments were performed for microarray analysis

first: Carol

last: Thiele


title: TNF dependent induction of inhibitory pathways in CD4+ T cells in HIV and LCMV [acute LCMV]

status: Public on Mar 07 2016

first: Joachim

last: Schultze

summary:
Chronic viral infections caused by HIV in humans or LCMV in mice are characterized by immunodeficiency and chronic inflammation. During chronification, T cells progressively lose effector functions, a process associated with immunoregulatory pathways and known as T-cell exhaustion. A link between ‘exhaustive’ T-cell reprogramming and chronic inflammation has not been established. Using a systems biology approach we demonstrate in HIV and LCMV infection that TNF, a prototypical mediator of chronic inflammation, functions upstream of major immunoregulatory pathways in T cells during chronic viral infection. In vivo blockade of TNFR-signaling interferes with the exhaustive T-cell program during chronic infection and reduces viral loads by several log. Continuous TNFR-signaling during disease progression towards chronic infection seems to be causative for T-cell exhaustion and an important link between immunodeficiency and chronic inflammation. TNF blockade might represent a novel therapeutic option during late stage infections caused by HIV and other virus causing chronic infections.
CD4+ T cells from Infliximab or control treatment of acute LCMV infected animals

overall_design: 4 experimental conditions with 3 biological replicates for each condition

first: Marc

last: Beyer

first: Zeinab

last: Abdullah


title: Assessing gene expression in Rnaseh2b null murine embryonic fibroblasts (MEF)

status: Public on Mar 04 2016

city: Edinburgh

first: Karen

last: Mackenzie

address: Crewe Road

department: IGMM

institute: The University of Edinburgh

summary: Assessing differential gene expression in Rnaseh2b null (p53-/-, Rnaseh2b -/-) murine embryonic fibroblasts (MEF) vs control (p53-/-, Rnaseh2b +/+) .

overall_design: Gene expression was compared between two independent p53-/- Rnaseh2b-/- MEF lines versus four independent p53-/- Rnaseh2b+/+ MEF lines grown under confluent culture conditions and passage matched. MEFs were generated from individual whole E10.5 embryos and were on a C57BL/6J background.


title: Interferon-γ response against C. burnetii of peripheral blood mononuclear cells in the development of chronic Q fever

status: Public on Mar 13 2016

city: Lyon

first: Julien

last: Textoris

address: Hôpital Edouard herriot - Pavillon P; 5 place d'Arsonval

department: Medical Diagnostic Discovery Department (MD3)

country: France

institute: bioMérieux

summary:
Background: Q fever is caused by the Coxiella burnetii, an intracellular bacterium that infects mononuclear cells. In some individuals, it causes a persistent cardiovascular infection (chronic Q fever). The aim of present study was to investigate the C. burnetii-induced IFN-γ response in chronic Q fever patients.
Methods: IFN-γ was measured in supernatants of C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients. Gene-expression profiles of the IFN-γ pathway in PBMCs after incubation with C. burnetii were compared between chronic Q fever patients and control individuals.
Results: IFN-γ production by PBMCs of chronic Q fever patients incubated with C. burnetii in vitro, was significantly higher compared to controls. In transcriptome analysis, genes downstream of IFN-γ were strongly upregulated in patients.
Conclusion: Present study showed that IFN-γ production and the response to IFN-γ seems to be intact in chronic Q fever patients.

overall_design: PBMC were purified from Q fever patients (n=6) or healthy volunteers (n=4), and then stimulated by Coxiella burnetii, LPS or left untreated (NS)

first: Teske

last: Schoffelen

last: Bleeker-Rovers

first: Jos

last: van der Meer

first: Mihai

last: Netea

first: Jean-Louis

last: Mege

first: Esther

last: van de Vosse

first: Marcel

last: van Deuren


title: TNF dependent induction of inhibitory pathways in CD4+ T cells in HIV and LCMV [chronic LCMV]

summary:
Chronic viral infections caused by HIV in humans or LCMV in mice are characterized by immunodeficiency and chronic inflammation. During chronification, T cells progressively lose effector functions, a process associated with immunoregulatory pathways and known as T-cell exhaustion. A link between ‘exhaustive’ T-cell reprogramming and chronic inflammation has not been established. Using a systems biology approach we demonstrate in HIV and LCMV infection that TNF, a prototypical mediator of chronic inflammation, functions upstream of major immunoregulatory pathways in T cells during chronic viral infection. In vivo blockade of TNFR-signaling interferes with the exhaustive T-cell program during chronic infection and reduces viral loads by several log. Continuous TNFR-signaling during disease progression towards chronic infection seems to be causative for T-cell exhaustion and an important link between immunodeficiency and chronic inflammation. TNF blockade might represent a novel therapeutic option during late stage infections caused by HIV and other virus causing chronic infections.
CD4+ T cells from Infliximab or control treatment of chronic LCMV infected animals

overall_design: 4 experimental conditions with 3-5 biological replicates for each condition


title: Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells [Microarray transcriptomic analysis]

status: Public on Mar 24 2016

city: La Tronche

first: Sophie

last: Rousseaux

address: Bd de la Chantourne

department: IAB

institute: INSERM-UGA

summary: Although the conserved AAA ATPase – bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2’s function as a facilitator of general chromatin-templated activities such as transcription.

overall_design: Transcriptomic analyses comparing ES cells stably expressing anti-Atad2 shRNA versus cells expressing control shRNA, in day 3 LIF (-) differentiating ES cells (3 replicates for each condition) were performed using the Illumina MouseWG-6 v2.0 expression beadchip technology

first: Alexandra

last: Debernardi

first: Yuichi

last: Morozumi

first: Faycal

last: Boussouar

first: Philippe

last: Guardiola

first: Matthieu

last: Gerard

first: Davide

last: Gianni

first: Norbert

last: Schweifer

first: Saadi

last: Khochbin


title: MicroRNA-124 and -137 cooperativity controls caspase-3 activity through BCL2L13 in hippocampal neural stem cells.

first: Marijn

last: Schouten

type:
Expression profiling by array
Expression profiling by RT-PCR

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

overall_design: Refer to individual Series


title: TNF dependent induction of inhibitory pathways in CD4+ T cells in HIV and LCMV

first: Joachim

last: Schultze


title: Gene expression profiling of liver from regulatar chow (RC) fed-mice, high fat diet (HFD)-fed mice with vehicle or nobiletin (NOB) treatment

status: Public on Mar 03 2016

city: Houston

first: Zheng

last: Chen

state: Texas

address: 6431 Fannin street, MSB3.135

department: Department of Biochemistry and Molecular Biology

institute: UT health science center at houston

summary: Comparison of liver transcriptome between RC-fed mice, HFD-fed mice with vehicle or nobiletin treatment provides the possibility to identify the effects of nobiletin on gene expression altered by HFD relative to RC.   We used Illumina microarrays to analyze liver transcriptome of different treatment groups following exposure to RC, HFD.Veh (denoted as the HFD group) and  HFD.NOB (denoted as the NOB group).

overall_design: The microarray experiment was performed to investigate effects of HFD and NOB on mouse liver transcriptome. Liver tissues were collected at ZT2 and ZT14 (corresponding to 2 hours after light on and light off, respectively).    The pooled RNA samples, 4 mice each group, were used for the microarray.

first: Baokun

last: He


title: Genome-wide analysis of epidermal gene expression from Presenilin (1&2)-null, RBPjk-null and wild-type litter mates

status: Public on Feb 29 2016

city: Cincinnati

first: Raphael

last: Kopan

state: Ohio

address: 3333 Burnet Avenue

department: Developmental Biology

institute: Cincinnati Children's Hospital

summary:
Analysis of differential gene expression in Psen-null and RBPjk-null epidermal keratinocytes.
The hypothesis tested in the present study was that canonical Notch signals could be present at the beginning of epidermal stratification (E13.5) in the RBPj-null epidermis. If an early signal was preserved by epigenetic memory, E18.5 RBPj-null epidermis would resemble the wild-type at the transcriptional level.

overall_design: Total RNA obtained from 3xRBPj-null and 3xPsen-null epidermis at E18.5 and compared to wild-type (3xRBPjwt & 3xPsenwt) epidermis from littermates.

first: Mustafa

last: Turkoz


title: Nur77-deficiency in bone marrow-derived macrophages modulates inflammatory responses, extracellular matrix homeostasis, phagocytosis and tolerance

status: Public on Mar 01 2016

first: Perry

middle: D

last: Moerland

address: Meibergdreef 9

department: Epidemiology and Data Science

institute: Amsterdam UMC

summary: The nuclear orphan receptor Nur77 (NR4A1, TR3, or NGFI-B) has been shown to exhibit an anti-inflammatory function in macrophages. To further elucidate the role of Nur77 in macrophage physiology, we compared the transcriptome of bone marrow-derived macrophages (BMM) from wild-type (WT) and Nur77-knockout (KO) mice both before and after stimulation with IL4 or LPS.

overall_design: Comparison of gene expression in bone marrow-derived macrophages, isolated from 3 wild-type (control) and 3 Nur77-/- mice (case), left untreated or stimulated in triplicate for 8 hours with LPS or IL-4

first: Anouk

last: Hamers

first: Claudia

last: van Tiel

first: Carlie

last: de Vries


title: Whole genome transcriptional analysis of monocytes/macrophages purified from bone marrow of xeno-transplanted mice

status: Public on Feb 16 2016

city: Milano

first: Michela

last: Riba

address: via Olgettina 60

department: COSR, Center for Omics Sciences

institute: IRCCS, Ospdale San Raffaele

summary: The development and progression of CLL are dependent upon a complex microenvironmental network of cellular and molecular signals. As an example the in vitro survival of CLL cells is supported by nurse-like cells, which have been identified as a CLL-specific tumor-associated macrophage (TAM) population. However little is known regarding the role of TAMs in CLL development and progression. In the CLL xenograft model based on the engraftment of MEC1 human CLL cell line into Rag2-/-γc-/-, we analyzed the whole-genome transcriptome of TAMs isolated from the bone marrow. We found an enrichment of genes involved in inflammation and interaction between TAMs and leukemic cells.

overall_design: Rag2-/-γc-/- were injected intravenously with MEC1 cells and sacrificed at early stage of leukemia with age-matched wt Rag2-/-γc-/- mice (n=3/group). RNA was isolated from bone marrow murine monocytes/macrophages purified by magnetic separation and processed for illumina whole-genome gene expression direct-hybridization assay.

first: Maria

middle: T

last: Bertilaccio

first: Giovanni

last: Galletti

first: Cristina

last: Scielzo

first: Tania

last: Rodriguez

first: Federica

last: Barbaglio

first: Dejan

last: Lazarevic

last: Cittaro

first: Giorgia

last: Simonetti

first: Michele

last: De Palma

first: Paolo

last: Ghia

first: Federico

last: Caligaris-Cappio


title: Comparison of KrasG12D/WT;p53Fx/Fx and KrasG12D/G12D;p53Fx/Fx MEFs

status: Public on Feb 24 2016

city: Belfast

first: Emma

last: Kerr

address: 97 Lisburn Rd

department: PGJCCR

institute: Queen's University Belfast

summary:
Microarray expression data generated to compare the biological impact of KrasG12D allelic duplication in p53null mouse embryonic fibroblasts (MEFs).
The RAS/MAPK-signalling pathway is frequently deregulated in non-small cell lung cancer (NSCLC), often through activating mutations in KRAS. Mouse models demonstrated that activation of a single endogenous mutant Kras allele is sufficient to promote lung tumour formation, but acquisition of other genetic alterations is required for malignant progression. Using a well-established lung cancer mouse model we recently demonstrated that advanced KrasG12D-driven spontaneous tumours frequently exhibit enhanced MAPK signalling and KrasG12D allelic enrichment (KrasG12D/Kraswild-type>1), implying that mutant Kras copy gains are positively selected during lung cancer progression. To compare the oncogenic impact of a single mutant allele versus additional mutant Kras copy gain, we carried out a comprehensive analysis of mutant Kras homozygous and heterozygous MEFs and lung cancer cells and show that these genotypes are phenotypically distinct.    Title: Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities  Authors: Emma M Kerr, Edoardo Gaude, Frances K Turrell, Christian Frezza and Carla P Martins

overall_design: For MEF generation, KrasLSL-G12D/+ ;p53Fx/Fx mixed background (C57Bl/6/129/Sv) animals were interbred and embryos collected at day E12.5 to overcome KrasLSL-G12D/G12D embryonic lethality and Cre-mediated recombination performed immediately after MEF generation. Cells were cultured in DMEM supplemented with 10% FBS, 2 mM L-Glutamine for one passage and then infected with adenovirus-Cre (5 × 107 plaque-forming units/1 x 106 cells). Recombination of LoxP sites was confirmed by PCR analysis. Three independent embryos per genotype were analysed using GPL6887 Illumina MouseWG-6 v2.0 expression beadchip.

first: Carla

last: Martins


title: Gene expression profiling of gastric cells infected by Helicobacter pylori

city: Porto

first: Ceu

last: Figueiredo

address: Rua Dr. Roberto Frias S/N

country: Portugal

institute: IPATIMUP

summary: Helicobacter pylori are gram-negative bacteria that colonize the human stomach and are the major etiological factor in gastric carcinoma development. The aim of this work was to evaluate changes in gene expression in gastric cells induced by H. pylori.

overall_design: The human gastric carcinoma-derived cell line AGS was infected with H. pylori strain 60190 (ATCC 49503) for 24 hours. RNA was extracted from three independent experiments.

first: Rui

last: Ferreira

first: Laura

last: Carreto

first: Manuel

last: Santos


title: Expression data from small intestinal eosinophils and dendritic cells

status: Public on Feb 04 2016

city: Pohang

first: Myoung Ho

last: Jang

address: 77 Cheongam-Ro

institute: Academy of Immunology and Microbiology, Institute for Basic Science

summary: Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. We performed a global gene expression analysis to examine which genes are highly expressed by small intestinal eosinophils (CD11b+CD11c(int)MHCII-SiglecF+) compared with dendritic cells (CD11c+MHCII+).

overall_design: To examine the gene expression profiles of eosinophils and dendritic cells within the small intestinal lamina propria (LP), we isolated eosinophils (CD11b+CD11c(int)MHCII-SiglecF+) and dendritic cells (CD11c+MHCII+) from the small intestinal LP of 8 week-old C57BL/6 mice by FACS, then compared the gene expression profiles between these two populations by microarray analysis.

first: Eun-Jung

last: Lee

first: Bo-Gie

last: Yang

first: Myoung

middle: H


title: Murine embryonic stem cells synthesize retinoic acid to promote their own spontaneous differentiation

status: Public on Feb 10 2016

city: Torino

first: Francesco

last: Neri

state: Italy

address: Via Nizza 52

institute: University of Torino

summary: Embryonic stem cells (ESC) are derived from blastocyst-stage embryos and are thought to be functionally equivalent to the inner cell mass in their developmental potential. ESCs pluripotency is maintained through a complex interplay of different signaling pathways and a network of transcription factors, which is centered around Oct3/4, Sox2 and Nanog. Although, in general, much is known about this pluripotency self-renewal circuitry, the molecular events that lead ESC to exit from pluripotency and begin differentiation are currently less known. Retinoic acid, an active metabolite of the vitamin A (retinol), plays important and pleiotropic roles in vertebrate embryonic development and ESC differentiation. Here we demonstrate that RA promotes early steps of ESC differentiation, and that ESC increase their capacity to synthesize RA during spontaneous differentiation as embryoid bodies, up-regulating the RA biosynthetic pathway components RDH1, RDH10, ADH3, RALDH2, and CRABP2.

overall_design: Microarray derived from total RNA of mESC not treated or treated with all-trans retinoic acid (ATRA) for 2 hours.

last: Galvagni


title: Blockade of interferon-γ normalizes IFN regulated gene expression in subjects with systemic lupus erythematosus (SLE)

city: Thousand Oaks

first: Mara

last: Campbell

state: CA

address: 1 Amgen Center Drive

institute: Amgen

summary: Normal donor blood was incubated with or without IFN-g stimulation to establish an IFN-g gene signature. Systemic lupus erythematosus subjects were treated with placebo or AMG 811, a therapeutic anti-IFN--g antibody, and changes in the IFN--g signature in whole blood of these subjects was measured.

overall_design: Blood from healthy volunteers (n=4) was collected into sodium heparin tubes, and then untreated or treated with 294 pM recombinant human IFN-γ for 0, 24, or 48 hours with incubation at 37oC, 5 % CO2. The blood was then added to PAXgene tubes and processed for RNA purification. Twenty six subjects with stable, mild to moderate SLE were administered placebo or a single dose of AMG 811 ranging from 2 mg to 180 mg SC or 60 mg IV. Whole blood PAXgene tube samples were collected from all cohorts at baseline, day-1 (pre-dose), and at days 15, 56, and end of study (EOS) after treatment Arrays were hybridized in a Loop design.

first: Panteha

last: Kiaei


title: Genome-wide analysis of gonadotropin-dependent gene expression and crosstalk of the regulatory pathways in the female ovaries

status: Public on Feb 03 2016

city: London

first: Ariel

last: Poliandri

state: London

address: WHRI, Charterhouse Sq.

department: Endocrinology

institute: Queen Mary University

summary: Effects of lack of functional LH receptor and/or a constitutively active FSH receptor on gene expression in the ovaries of female mice were studied. The results suggest that transgenic expression of the mouse Fshr in granulosa cells leads to abnormal ovarian structure/function and infertility. This finding indicates that gain-of-function mutations of the Fshr in female mice bring about distinct and clear changes in ovarian function.

overall_design: Total RNA was obtained from ovaries of 12 weeks old mice of different genotypes and extracted using Trizol followed by clean up with Qiage RNeasy MinElute Cleanup Kit

first: Olayiwola

middle: O

last: Oduwole

last: Vengadabady

first: Ilpo

last: Huhtaniemi


title: Analysis of Junctional zone in murine placenta upon loss of Tfap2c

status: Public on Jan 31 2016

city: bonn

first: Neha

last: Sharma

address: sigmund freud str-25

institute: Institute of Pathology

summary: Tfap2c is deleted in Tpbpa positive precursor cells forming the junctional zone of murine placenta. Deregulation in gene expression is analysed compared to the junctional zone in control placenta.

overall_design: TpbpaCre:Tfap2c-/- and wild type junctional zone of murine placenta at E13.5 was punched out using laser microdissection and RNA was isolated to perform Illumina WG6 v2.0 using platform GPL18752

first: Hubert

last: Schorle


title: Genome wide nucleosome specifity and function of chromatin remodellers in embryonic stem cells [Ep400]

status: Public on Jan 26 2016

city: Evry Cedex

first: Robert

last: Olaso

address: 2 rue Gaston Cremieux

department: CNRGH

institute: CEA-DRF

summary: How various ATP-dependent chromatin remodellers bind to nucleosomes to regulate  transcription is not well defined in mammalian cells. Here, we present genome-wide  remodeller-interacting nucleosome profiles for Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1  and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind to nucleosomes at  specific positions, either at one or both nucleosomes that flank each side of nucleosome-free  promoter regions (NFRs), at enhancer elements, or within gene bodies. At promoters,  bidirectional transcription commonly initiates on either side of remodeller-bound  nucleosomes. Transcriptome analysis upon remodeller depletion reveals reciprocal  mechanisms of transcriptional regulation by remodellers. At active genes, certain remodellers  are positive regulators of transcription, whereas others act as repressors. At bivalent genes,  which are bound by repressive Polycomb complexes, the same remodellers act in the opposite  way. Together, these findings reveal how remodellers integrate promoter nucleosomal  architecture to regulate ES cell transcription programs.

overall_design: 6 samples analysed

first: Matthieu

last: Gerard

first: Jean-françois

last: Deleuze


title: Genome wide nucleosome specifity and function of chromatin remodellers in embryonic stem cells [Chd9]


title: Genome wide nucleosome specifity and function of chromatin remodellers in embryonic stem cells [Chd6]


title: Genome wide nucleosome specifity and function of chromatin remodellers in embryonic stem cells [Chd4]


title: Genome wide nucleosome specifity and function of chromatin remodellers in embryonic stem cells [Chd1]

summary: How various ATP-dependent chromatin remodellers bind to nucleosomes to regulate transcription is not well defined in mammalian cells. Here, we present genome-wide remodeller-interacting nucleosome profiles for Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind to nucleosomes at specific positions, either at one or both nucleosomes that flank each side of nucleosome-free promoter regions (NFRs), at enhancer elements, or within gene bodies. At promoters, bidirectional transcription commonly initiates on either side of remodeller-bound nucleosomes. Transcriptome analysis upon remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. At active genes, certain remodellers are positive regulators of transcription, whereas others act as repressors. At bivalent genes, which are bound by repressive Polycomb complexes, the same remodellers act in the opposite way. Together, these findings reveal how remodellers integrate promoter nucleosomal architecture to regulate ES cell transcription programs.


title: Genome wide nucleosome specifity and function of chromatin remodellers in embryonic stem cells [Chd8]


title: Primary and adjacent non-malignant tissue samples of 100 HCC patients (mRNA)

status: Public on Feb 18 2016

city: Singapore

first: Thomas

last: Thurnherr

address: 11 Hospital Drive

institute: NCCS

summary: Genome-wide mRNA expression profiles of 100 primary and matched non-malignant tissues of HCC patients from a Singapore patient cohort. HCC is a hetergenous disease and it is important to understand the underlying molecular mechanisms. Here, we studied the role of microRNAs in HCC by integrating microRNA and gene expression profiles of HCC patients.

overall_design: Profiling of 100 primary and adjacent non-malignant HCC tissue samples on Agilent two-color whole human genome gene expression microarray (design G4112F). All tissues were collected with approvals from the National Cancer Centre, Singapore; the Research Ethics Review Committee; and signed patient informed consent.

first: Steve

last: Rozen

first: Caroline


title: Primary and adjacent non-malignant tissue samples of 100 HCC patients

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

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus


title: Notch-mediated suppression of multiciliate differentiation promotes choroid plexus tumor initiation from progenitors in response to epithelium-derived Sonic Hedgehog

status: Public on Jan 23 2016

city: Sioux Falls

first: Haotian

last: Zhao

state: SD

address: 2301 E. 60th St. North

department: Children's Health Research Center

institute: Sanford Research

summary: Aberrant Notch signaling has been linked to many cancers including choroid plexus (CP) tumors, a group of rare and predominantly pediatric brain neoplasms. We developed animal models of CP tumors by inducing sustained expression of Notch1 that recapitulate properties of human CP tumors with aberrant NOTCH signaling. Whole transcriptome and functional analyses showed that tumor cell proliferation is associated with Sonic Hedgehog (Shh) in the tumor microenvironment. Unlike CP epithelial cells, which have multiple primary cilia, tumor cells possess a solitary primary cilium as a result of Notch-mediated suppression of multiciliate diffferentiation. A Shh-driven signaling cascade in the primary cilium occurs in tumor cells but not in epithelial cells. Lineage studies show that CP tumors arise from mono-ciliated progenitors in the roof plate characterized by elevated Notch signaling. Abnormal SHH signaling and distinct ciliogenesis are detected in human CP tumors, suggesting SHH pathway and cilia differentiation as potential therapeutic avenues.

overall_design: Gene expression profiling was performed on CP tumors in Math1-cre;Rosa26-NICD1 animals and wild type CPs at day P0 and day P21 using a microarray approach. Three sets of tumor specimens from Math1-cre;Rosa26-NICD1 mice and three sets CP specimens from wild type mice were collected at each time point. To ensure that sufficient amount of RNA can be extracted, each set of specimens included tissues pooled from several animals of the same genotype.

first: Erliang

last: Zeng


title: Identification of genes downregulated due to loss at 8p11.22-ter

status: Public on Jan 22 2016

city: Yufu

first: Naoki

last: Hijiya

state: Oita

address: 1-1, Idaigaoka Hasama-machi

department: Medicine

institute: Oita University

summary: In this study, we compared expression profiles between pancreatic cell lines with and without loss at 8p11.22-ter to identify genes downregulated due to loss at 8p11.22-ter.

overall_design: pancreatic carcinoma cell lines with loss at 8p11.22-ter (n = 8) vs pancreatic carcinoma cell lines without loss at 8p11.22-ter (n = 4)

first: Yoshiyuki

last: Tsukamoto

first: Chisato

last: Nakada

first: Nguyen

last: Lam Tung

first: Tomoki

last: Kai

first: Keiko

last: Matsuura

first: Kohei

last: Shibata

first: Masafumi

last: Inomata

first: Tomohisa

last: Uchida

first: Akinori

last: Tokunaga

last: Amada

first: Kuniaki

last: Shirao

first: Yasunari

last: Yamada

first: Hiromu

last: Mori

first: Ichiro

last: Takeuchi

first: Masao

last: Seto

first: Masahiro

last: Aoki

first: Mutsuhiro

last: Takekawa

first: Masatsugu

last: Moriyama


title: Genome-wide analysis of FSH and LH dependent gene expression and the crosstalk between these two pathways in mice testes

status: Public on Jan 20 2016

first: Ariel

last: Poliandri

summary: Effects of the absence of a functional LH receptor and/or expression of a constitutively active FSH receptor on gene expression in the gonads of male mice were studied. The results provide insights into the roles of the hormones LH and FSH in male reproduction. The main conclusion is that constant strong FSH stimulation is able to rescue the impaired spermatogenesis and fertility of male mice in the absence of LH signalling.

overall_design: Total RNA was obtained from testis of 12 weeks old mice of different genotypes and extracted using Trizol followed by clean up with Qiage RNeasy MinElute Cleanup Kit

first: Olayiwola

last: Oduwole

first: Laura

last: Vengadabady

first: Ilpo

last: Huhtaniemi


title: Genome wide nucleosome specifity and function of chromatin remodellers in embryonic stem cells

first: Robert

last: Olaso

type:
Expression profiling by array
Third-party reanalysis

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

Note: The Brg1 transcriptomic data is obtained from GSE27708. We have normalized the data using the RMA method (with default parameters) from the affy rel. 1.42.2 of R/Bioconductor rel. 3.0. Please find the normalized data in GSE64819.txt.gz.

overall_design: Refer to individual Series


title: G-CSF receptor targeting in inflammatory arthritis

status: Public on Jan 19 2016

city: Parkville

first: CSL

last: Research

address: 30 Flemington Rd

institute: CSL Limited / bio21 Institute

summary: G-CSF is a hemopoietic growth factor that has a role in steady state granulopoiesis, as well as in mature neutrophil activation and function. We developed a neutralizing monoclonal antibody to the murine G-CSF receptor (G-CSFR), which antagonizes binding of murine G-CSF and inhibits G-CSFR signalling. Anti-G-CSFR rapidly halts the progression of established disease in collagen antibody-induced arthritis (CAbIA). Neutrophil accumulation in joints is inhibited, without rendering animals neutropenic, suggesting an effect on homing to inflammatory sites. Neutrophils in the blood and arthritic joints of anti-G-CSFR treated mice show alterations in cell adhesion receptors, while anti-G-CSFR suppresses local production of proinflammatory cytokines and chemokines known to drive tissue damage. Our aim in this study was to use differential gene expression analysis of joint and blood neutrophils to more thoroughly understand the effect of G-CSFR blockade on the inflammatory response following anti-G-CSFR therapy in CAbIA.

overall_design: C57BL/6 mice with collagen antibody-induced arthritis were injected intra-peritoneally at day 5 with 50 μg anti-G-CSFR (n = 20 mice) or control mAb (n = 10 mice). At day 7, neutrophils (CD45+ CD11bhi Ly6G+) were sorted (BD FACSAria) from pooled digests of the knee tissues, or peripheral blood, and the RNA was extracted from 3 such experiments, giving a total of 12 samples.

first: Ian

middle: K

last: Campbell

first: David

last: Leong

first: Kirsten

middle: M

last: Edwards

first: Veronika

last: Rayzman

first: Milica

last: Ng

first: Gabrielle

last: Goldberg

first: Nicholas

last: Wilson

first: Kate

middle: E

last: Lawlor

last: Wicks

first: Con

last: Panousis

first: Michael

first: Andrew

last: Nash

first: Brent

middle: S

last: McKenzie

first: Arna

last: Andrews


title: Gene Expression Profiling in PRKCI vs NT-silenced Cells

status: Public on Jan 21 2016

city: Heidelberg

first: Emma

last: Phillips

address: In Neuenheimer Feld 580

department: Brain Tumor Translational Targets

institute: DKFZ

summary: In order to investigate the crucial role of PRKCI in glioblastoma stem-like cell (GSC) survival, gene expression microarray-based transcriptome analysis was conducted on GSCs transduced for 4 days with PRKCI shRNA compared with GSCs transduced with shNT.

overall_design: 3 biological replicates (2 x NCH421k and 1 x NCH644), shNT used as control

first: Verena

last: Lang

first: Violaine

last: Goidts


title: Analysis of gene expression in human Bronchial Alveolar Lavage Cell (BAL) cell pellets

status: Public on Jan 06 2016

city: South San Francisco

first: Mark

last: McCreary

state: California

address: 1 DNA Way, MS 93

department: Bioinformatics

institute: Genentech

summary: Clinical subphenotypes of asthma are characterized by pathological, cellular, and molecular heterogeneity of the airway. Gene expression profiling of airway inflammatory cells in diseased patients by microarray analysis will provide insight into the molecular heterogeneity and support the development of hypotheses of pathological mechanisms.

overall_design: Moderate asthmatic patients and healthy controls were participants in the Study of the Mechanisms of Asthma (MAST, clinicaltrials.gov: NCT00595153). Severe asthmatic patients were participants in the BOBCAT study (as described in Jia G JACI 2012 and Arron JR ERJ 2014). RNA (Qiagen AllPrep with on-column DNase treatment) was isolated from Bronchial Alveolar Lavage cells for gene expression microarray analysis.

middle: F

last: Choy

first: Joseph

last: Arron


title: The role of mRNA decay in p53-induced gene expression

status: Public on Jan 07 2016

city: Ottawa

first: Bruce

last: McKay

state: Ontario

address: 1125 Colonel By Dr.

department: Biology

country: Canada

institute: Carleton University

summary: The p53 tumor suppressor is a DNA damage responsive sequence-specific transcriptional activator.  The sustained activation of the p53 response is incompatible with cell growth and viability.   To circumvent this issue, a variety of negative feedback loops exist to limit the duration of p53 activation.  Despite our understanding of p53-regulation, very little is known about the effect of transient p53 activation on the long term expression of p53 target genes.  Here we used a temperature sensitive variant of p53 and oligonucleotide microarrays to monitor gene expression during and following reversible p53 activation.  The expression of most p53-induced transcripts was rapidly reversible, consistent with active mRNA decay.  Representative 3’UTRs derived from short-lived transcripts (i.e. DDB2 and GDF15) conferred instability on a heterologous mRNA while 3’UTRs derived from more stable transcripts (i.e. CRYAB and TP53I3) did not.  The 3’UTRs derived from unstable p53-induced mRNAs were significantly longer than those derived from stable mRNAs.  These 3’UTRs had high uridine and low cytosine content, leading to a higher density of U-, AU- and GU-rich sequences. Remarkably, short-lived p53 targets were induced faster reaching maximum transcript levels earlier than the stable p53-targets.  Taken together, the p53 transcriptional response has evolved with primarily short-lived target mRNAs and that post-transcription processes play a prominent role in the p53 response.

overall_design: HT29-tsp53 cells expressing a temperature sensitive variant of p53 were used to study the reversal of the p53 response.  Gene expression was assessed using Affymetrix Gene 1.0 ST oligonucleotide microarrays.  Controls were maintained at the restrictive temperature (time 0) and treatments were collected following 16 hours at the permissie temperature (16 hours) and following a subsequent 6 hour recovery period (16 hours at 32 + 6 hour at 37).

first: Brian

last: Melanson

first: Reetesh

last: Bose

first: Jeff

last: Hamill

first: Kristen

last: Marcellus

first: Elysia

last: Pan


title: Hinchcliff 359 microarray dataset

status: Public on Jan 14 2016

city: Lebanon

first: Tammara

last: Wood

state: NH

address: WTRB 674

department: Biomedical Data Science

institute: Dartmouth Medical School

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

overall_design:
Refer to individual Series

Attached to this SuperSeries page is a data matrix of all 359 samples included in this SuperSeries. The values are given as Log(base2) of R/G Lowess Normalized Ratio (Mean) representing reference/test.


title: Human pancreatic adenocarcinoma contains a side population resistant to gemcitabine

status: Public on Jan 04 2016

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary:
BACKGROUND:
Therapy resistance remains one of the major challenges to improve the prognosis of patients with pancreatic cancer. Chemoresistant cells, which potentially also display cancer stem cell (CSC) characteristics, can be isolated using the side population (SP) technique. Our aim was to search for a SP in human pancreatic ductal adenocarcinoma (PDAC) and to examine its chemoresistance and CSC phenotype.

RESULTS:
A SP was identified in all PDAC samples, expanded and analyzed as first-generation xenografts. This SP was more resistant to gemcitabine than the other tumour cells as analyzed in vivo. Whole-genome expression profiling of the SP revealed upregulation of genes related to therapy resistance, apoptotic regulation and epithelial-mesenchymal transition. In addition, the SP displayed higher tumourigenic (CSC) activity than the other main tumour cell population (MP) as analyzed in vitro by sphere-forming capacity.

CONCLUSION:
We identified a SP in human PDAC and uncovered a chemoresistant and CSC-associated phenotype. This SP may represent a new therapeutic target in pancreatic cancer.

overall_design: Micro-array analysis was performed on SP and MP samples of 5 xenografts, grown from 5 different human PDAC samples.

first: Anke

last: Van den broeck

first: Lies

last: Gremeaux

first: Hugo

last: Vankelecom

first: Baki

last: Topal


title: Insights into responses of human astrocytes to H5N1 infection by transcriptional analysis

city: wuhan

first: Lin

last: xian

state: Hubei

address: shizishan street,number 1

department: College of Veterinary Medicine

country: China

institute: Huazhong Agricutural University

summary: Increasing evidence demonstrates influenza virus can not only affect the respiratory system, but also infect CNS and lead to CNS disorder and encephalopathy and encephalitis. Astrocytes are the most abundant cells in the CNS, which are capable of producing cytokines and neurotrophic factors and are essential for brain homeostasis and neuronal function. Previous studies suggested that influenza virus can infect astrocytes and induce proinflammatory cytokines response as well as apoptosis. Nevertheless, very few mechanistic data are available regarding host responses to H5N1 infection in astrocytes. In this study, a functional genomics approach was utilized to investigate comprehensive host responses to H5N1 infection in a human astrocyte cell line, U251 cells.

overall_design: U251 cells were infected by H5N1 at MOI 1 or control . At time points 6, 12, and 24h, total RNA were extracted for microarray experiment. Three replicates were performed at each time point of infection and control infection.

first: Xian

last: Lin

first: Ruifang

last: Wang

first: Xin

last: Sun

first: Jun

last: Zhang

first: Meilin

last: Jin


title: A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells

status: Public on Jan 05 2016

city: Pittsburgh

first: Maria

last: Chikina

state: PA

address: 3501 5th ave

institute: University of Pittsburgh

summary: There is little insight into or agreement about the signals that control differentiation of memory B cells (MBC) and long-lived plasma cells (LLPC). By performing BrdU pulse-labeling studies, we found that MBC formation preceded the formation of LLPC in an adoptive transfer immunization system, which allowed for a synchronized Ag-specific response with homogeneous Ag-receptor, yet at natural precursor frequencies. We confirmed observations in wild type (WT) mice and extended them with germinal center (GC) disruption experiments and variable region gene sequencing. We thus show that the GC response undergo a temporal switch in its output as it matures, revealing that the reaction engenders both MBC subsets with different immune effector function and, ultimately, LLPC at largely separate points in time. These data demonstrate the kinetics of the formation of the cells that provide stable humoral immunity and therefore have implications for autoimmunity, vaccine development, and for understanding long-term pathogen resistance.

overall_design: Adoptive transfer of B1-8i+/- genetically targeted BALB/cJ mice B cells into AM14 Transgenic (Tg) x Vκ8R genetically targeted BALB/cJ mice. Naive, memory, early and late GC B cells.

first: Florian

last: Weisel

first: Mark

middle: J

last: Shlomchik


title: NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers  [microarray]

status: Public on Jan 11 2016

city: St Louis

first: Sabine

last: Dietmann

state: MO

address: 4565 McKinley Avenue

institute: Washington University School of Medicine

summary: Nanog, a core pluripotency factor in the inner cell mass of blastocysts, is also expressed in unipotent primordial germ cells (PGC) in mice1, where its precise role is yet unclear2-4. We investigated this in an in vitro model, where naïve pluripotent embryonic stem cells (ESCs) cultured in bFGF/ActivinA develop as epiblast-like cells (EpiLCs), and gain competence for PGC-like fate5. Consequently, bone morphogenetic protein (BMP4), or ectopic expression of key germline transcription factors Prdm1/ Prdm14/ Tfap2c, directly induce PGC-like cells (PGCLCs) in EpiLCs, but not in ESCs6-8. Here we report an unexpected discovery that Nanog alone can induce PGCLCs in EpiLCs, independently of BMP4. We propose that following the dissolution of the naïve ESC pluripotency network during establishment of EpiLCs9,10, the epigenome is reset for cell fate determination. Indeed, we found genome-wide changes in NANOG binding pattern between ESCs and EpiLCs, indicating epigenetic resetting of regulatory elements. Accordingly, we show that NANOG can bind and activate enhancers of Prdm1 and Prdm14 in EpiLCs in vitro; BLIMP1 (encoded by Prdm1) then directly induces Tfap2c. Furthermore, while SOX2 and NANOG promote the pluripotent state in ESCs, they show contrasting roles in EpiLCs since Sox2 specifically represses PGCLC induction by Nanog. This study demonstrates a broadly applicable mechanistic principle for how cells acquire competence for cell fate determination, resulting in the context-dependent roles of key transcription factors during development.

overall_design: To characterize Nanog-induced Primordial Germ cell-like cells (PGCLCs), we performed expression analysis of Nanog-induced Day4 PGCLCs compared to male mouse Embryonic Stem Cells (mESCs) and male Day4 PGCLCs which were induced by cytokines. mESCs were maintained in N2B27 2i(CHIR99021 3 µM, PD0325901 1 µM) LIF(1000 U/ml) medium and Day4 PGCLCs were induced in GK15 medium with Nanog induction (0.7 µg/ml) or cytokines (BMP4 500 ng/ml, BMP8A 500 ng/ml, SCF 100 ng/ml, EGF 50 ng/ml and LIF 1000U/ml) as previously reported (Hayashi K et al., Cell, 2011).

first: K

last: Murakami

first: U

last: Günesdogan

first: W

last: Tang

first: J

last: Zylicz

first: R

last: Sengupta

first: T

last: Kobayashi

first: S

first: M

last: Surani


title: Gene expression profiling of mouse luminal uterine epithelium with knockout of ALK3

city: Houston

first: Chad

last: Creighton

state: TX

address: One Baylor Plaza, Mail Stop: BCM305

department: Biostatistics, Ducan Cancer Center

institute: Baylor College of Medicine

summary: Bone morphogenetic proteins (BMPs) are transforming growth factor β (TGFβ) family members that regulate the post-implantation and mid-gestation stages of pregnancy. In this study we discovered that signaling via activin-like kinase 3 (ALK3/BMPR1A), a BMP type 1 receptor, is necessary for blastocyst attachment. To understand the role of ALK3 in the luminal uterine epithelium, we obtained the gene expression profiles of isolated luminal uterine epithelium from 3.5dpc control and Alk3 cKO mice.

overall_design:
Gene expression profiling of isolated luminal uterine epithelium from control and Alk3 cKO mice.
two group comparison

first: Diana

last: Monsivais

first: Martin

last: Matzuk


title: Effect of blood sample storage on the study of gene expression in response to ionizing radiation exposure

status: Public on Jan 02 2016

city: Fontenay aux Roses Cedex

first: Gaetan

last: GRUEL

address: BP 17

department: Service de RadioBiologie et d'Epidemiologie

institute: Institut de Radioprotection et de Surete Nucleaire

summary: For around ten years, microarrays have been suggested for the diagnosis of ionizing radiation exposure. We assessed for the first time the relevance of gene expression profiling in a real accidental case. This study was performed on peripheral blood mononuclear cells of 41 potential victims. The different strategies of analysis highlighted a huge effect of the blood sample handling on the gene expression profiles. This effect was so high that it could mask specific modulations as a potential effect of ionizing radiation exposure. Thus, we assessed a new way of blood sampling adapted to gene expression analysis: PAXgene. With this method, more than 70% of the modulations of gene expression induced 3 hours after an ex vivo exposure to 0.5 Gy were preserved even in a 24-hour delayed analysis (as for transportation of blood sample from the accident location to the laboratory). We validated a new methodology in order to propose a new strategy of blood sampling and handling for gene profiling. This system could be used in case of accidental overexposure to study whether gene expression is a relevant biomarker of ionizing radiation exposure.

overall_design: Radiation induced gene expression in human blood was measured at 3 hours after exposure to doses of 0 and 0.5 grays. Following the incubation of 3 hours at 37°C, the RNA extractions were performed either immediately or 24h later (as for transportation of blood sample at room temperature). Two different blood preservation methods were compared: classical anticoagulant and PAXgene Blood RNA System. Venous blood samples of 6 donors were used (3 for anticoagulant study, 3 for Paxgene study). Each sample was hybridized twice.

first: G

first: A

last: VAURIJOUX


title: Alcohol-free fermented berry beverage phenolics attenuate diet-induced obesity and blood glucose in C57BL/6J mice

status: Public on Jan 01 2016

city: Urbana

first: Diego

middle: Armando

last: Luna-Vital

state: ILLINOIS

address: 228 ERML MC 051, 1201 W Gregory Dr

institute: University of Illinois at Urbana-Champaign

summary: The objectives of this study were to understand the effect of phenolic compounds from fermented berry beverages on hyperglycemia and obesity in vivo using mice fed a high fat diet. Our hypothesis was that consumption of a fermented blueberry-blackberry beverage and its phenolic compounds would reduce the development of obesity and hyperglycemia in diet-induced obese mice. Body composition, histomorphological analysis of pancreatic islets and liver, and expression of genes involved in obesity and hyperglycemia were evaluated in order to explain the modulation of diet-induced obesity and hyperglycemia due to treatments.

overall_design: Total RNA was extracted from frozen pancreatic tissue of mice after 12 weeks of high-fat diet, 5 groups treated with sitagliptin, alcohol-free berry beverage (AFFB), 0.1X phenolic extract, 1X phenolic extract and 3X phenolic extract respectively, were compared to the control (water). Four replicates were included for each one of the treatments.

first: Michelle

last: Johnson

first: Matthew

last: Wallig

first: Elvira

middle: G

last: de Mejia


title: Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [hMSC microarray]

status: Public on Dec 31 2015

city: Goettingen

first: Magdalena

last: Wienken

address: Justus-von-Liebig-Weg 11

institute: University Medical Center Goettingen

summary: The Mdm2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that Mdm2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, Mdm2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the Mdm2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. Mdm2 physically associated with EZH2 on chromatin, enhancing the trimethylation of Histone 3 at lysine 27 and the ubiquitination of Histone 2A at lysine 119 (H2AK119) at its target genes. Removing Mdm2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, Mdm2 supports the Polycomb-mediated repression of lineage specific genes independent of p53.

overall_design: microarray analysis in osteoblasts differentiated from human mesenchymal stem cells after siRNA kd

first: Matthias

last: Dobbelstein


title: Essential Role of Sirt2 in Type I Interferon Signaling

city: Berlin

first: Pawel

last: Lisowski

address: Hannoversche Str. 28

institute: Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association

summary: We provide evidence for the essential role of Sirt2 in IFN mediated signaling. Our studies demonstrate that SIRT2 controls expression of key interferon stimulated genes (ISGs) that mediate important biological functions, including anti-viral and antineoplastic responses.

overall_design: Total RNA was isolated from untreated and IFNβ-treated Sirt2+/+ and Sirt2-/- mouse embryonic fibroblasts (MEFs). Cells were treated for 4hours with or without mouse IFNβ (2500 IU/ml).

first: Swarna

last: Mehrotra

first: Leonidas

middle: C

last: Platanias


title: Gene expression profile of gastric cancer stem cells after CD44 knockdown

city: Chengdu

first: Xiao-Long

last: Chen

address: No.37 Guo Xue Xiang Street

institute: West China Hospital

summary: We did the microarray to further compare the changes of gene expression between gastric cancer stem cells with CD44 knockdown by lentivirus and gastric cancer stem cells by scamble short hairpin RNA.

overall_design: Gastric cancer stem cells (Lentivirus) were infected with lentivirus that expressed human CD44-speciﬁc short hairpin RNA (shRNA). Control group of gastric cancer stem cells (Vector group) were only infected with scramble shRNA.


title: BCOR controls maintenance of haematopoietic stem cell quiescence and regulates myeloid cell proliferation and differentiation [Illumina]

city: Singapore

first: Henry

last: Yang

address: 28 Medical Drive

institute: Cancer Science Institute of Singapore

summary: BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1) complex. Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukaemia (AML). However the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine cell models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with reduced protein levels of RING1B, a ubiquitin ligase subunit of PRC1 family complexes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with proliferation and myeloid differentiation and decreased stem cell quiescence. Further, we used a MLL-AF9 murine model of AML and found that loss of Bcor increased serial replating efficiency, enhanced MLL-AF9 in blocking cell differentiation, and increased expression of Evi1 which is associated with leukemic transformation. Our results strongly suggest that BCOR plays an indispensable role in maintaining hematopoietic stem cell (HSC) quiescence by inhibiting myeloid stem cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes.

overall_design: We took advantage of a mouse conditional Bcor allele which has exons 9 and 10 been flanked by LoxP sites to allow their removal via expression of Cre recombinase. Excision of these exons results in a frame shift and a premature stop codon causing nonsense mediated decay and/or carboxy-terminal deletion of the BCOR protein. CD34+ cells were sorted from control or Bcor mutant cells cultured under myeloid stem/progenitor conditions (IL3, 6 and SCF). We used microarrays to detail the global programme of gene expression in Control and Bcor mutant CD34+ cells.

first: Qi

last: Cao

first: Micah

last: Gearhart

first: Sigal

last: Gery

first: Seyedmehdi

last: Shojaee

first: Wenwen

last: Chien

first: Haibo

last: Sun

first: Monica

last: Mead

first: Zhiqiang

last: Zhao

first: Dechen

last: Lin

first: Serhan

last: Alkan

first: Torsten

last: Haferlach

first: Markus

last: Müschen

first: Vivian

last: Bardwell

first: H

middle: P

last: Koeffler


title: Muscle transcriptome analysis of mouse models of partial trisomy and monosomy 21

city: Strasbourg

first: Veronique

last: BRAULT

address: 1 rue Laurent Fries

institute: IGBMC

summary: Aneuploidies of human chromosome 21 (Down syndrome (DS) and monosomy 21 (M21)) lead to variable physiological abnormalities with constant mental retardation, locomotor deficits and altered muscle tone. To search for dosage-sensitive genes involved in DS and M21 phenotypes, we created two new mouse models carrying either tandem duplication (Ts2Yah) or a deletion (Ms3Yah) of the Stch-App interval homologous and syntenic with 21q11.2-q21.3 in humans. Here we report the complex mirror phenotypes of the trisomy and monosomy involving locomotion, muscle strength, mass and energetic balance that vary while ageing. Expression profiling of skeletal muscles revealed global changes in the expression of genes implicated in energetic metabolism, mitochondrial activity and biogenesis with down-regulation in Ts2Yah and up-regulation in Ms3Yah mice.  The shift in skeletal muscle metabolism correlated with a change in mitochondrial proliferation without an alteration of the respiratory function. However ROS production from mitochondrial complex I decreased in Ms3Yah mice while membrane permeability of Ts2Yah mitochondria slightly increased. Our results clearly demonstrate the central versus peripheral impact of the variation of copy number of the Stch-App region on the locomotor activity, muscle biology and mitochondrial biogenesis in models of these aneuploidies.

overall_design: Total RNA isolated from gastrocnemius muscles of mice that are trisomic (Ts2Yah) and monosomic (Ms3Yah) for the Stch-App region on Mmu16 and diploid control mice

first: Véronique

last: Brault

first: Yann

last: Herault

first: Doulaye

last: Dembele

first: Christelle

last: Borel

first: Stylianos

last: Antonarakis


title: the nuclear receptor tailless promotes increase of neurogenesis after stroke

first: Haikun

last: Liu

address: INF 581

summary: Tlx expression is upregulated after stroke, and stroke-induced neurogenesis is blocked when Tlx is inactivated. Tlx overexpression in NSCs leads to massive induction of neurogenesis via stroke,  which leads to an improved motor function recovery.

overall_design: Four Tlx overexpressing mice, and 5 wild type mice as control. Technique repeat is done for one of the wild type mouse c1 to validate the quality of the data.  Stroke are induced to all the mice  by one side stratum ischemia.

first: Sajjad

last: Muhammad

first: Muhammad

middle: A

last: Khan

first: Dagmar

last: Bock

first: Olga

last: Bernhardt

last: Schwaninger

first: Günther

last: Schütz

first: Hai-Kun


title: Gene expression profiling of rudhira null embryo and yolk sac at 9.5 dpc

city: Bangalore

first: madavan

last: vasudevan

state: Karnataka

address: Kasturi Nagar

institute: Theomics International Private Limited

summary:
Rudhira is essential for mouse developmental angiogenesis and tissue morphogenesis. Embryos lacking endothelial rudhira die at mid-gestation with vascular patterning defects. Rudhira mutant yolk sac endothelial cells show slow and random migration. So to identify key signaling pathways perturbed in the absence of rudhira, we undertook whole transcriptome based analysis of gene expression in rudhira null yolk sac and embryo.
Transcriptome analysis shows that key mediators of angiogenesis, cell adhesion, migration and extracellular matrix degradation as well as several components of the TGFβ pathway are perturbed in rudhira null mutant yolk sacs at 9.5 dpc.

overall_design: We used two embryo samples ( 2E- wild type; 5E- rudhira mutant). Repetition was done on each sample. We used 4 yolk sac samples (3Y,4Y- wild type; 7Y,8Y-rudhira mutant) for the analysis. Repetition was done on each sample.

first: Maneesha

last: Inamdar

first: Madavan

last: Vasudevan

first: Ronak

last: Shetty


title: Transcriptome analysis of MCL-treated leukemic cells

status: Public on Dec 30 2015

city: TianJin

first: Ding

last: Yahui

address: Nanjing Road 288

institute: Institute of Hematology & Hospital of Blood Diseases

summary: To analyze the molecular mechanisms by which MCL may induce apoptosis, microarray gene expression profiling of MCL-treated KG1a cells was performed.

overall_design: MCL induced gene expression in KG1a cell was measured at 8 hours after exposure to doses of 10µM. Each sample was performed in triplicate.

first: Yahui

last: Ding

first: Hui-er

last: Gao


title: Gene expression changes in  Apc-mutant mouse intestinal organoids 7 and 20 days after the induction of the Apc deletion

city: Helsinki

first: Zoltan

last: Wiener

address: Haartmaninkatu 8

department: Molecular Cancer Biology Programme

institute: University of Helsinki

summary: We isolated and selected intestinal adenoma organoids from Lgr5-EGFP-IRES-CreER; Apcflox/flox mice and added tamoxifen to induce the deletion of the Apc gene in the intestinal stem cells. Gene expressions on day7 and day20 after the addition of tamoxifen were compared, representing two stages with different colorectal cancer stem cell content.

overall_design: Total RNA obtained from  Lgr5-EGFP-IRES-CreER; Apcflox/flox organoids were compared 7 days and 20 days after the addition of tamoxifen, cultured without the Wnt-agonist R-Spondin1.

first: Jenny

last: Hogstrom

first: Ville

last: Hyvonen

first: Kari

last: Alitalo


title: Immunoregulatory function of placental dendritic cells: tolerance against intracellular bacteria

status: Public on Dec 28 2015

city: Lyon

first: Julien

last: Textoris

address: Hôpital Edouard herriot - Pavillon P; 5 place d'Arsonval

department: Medical Diagnostic Discovery Department (MD3)

institute: bioMérieux

summary: The role of placental dendritic cells (plaDCs) is largely unknown. These cells were isolated using CD14-, CD11c+ selection. PlaDCs, exhibited similar morphology as monocyte-derived DCs (moDCs), and several DCs markers such as DC-SIGN, BDCA-1, ASGPR and Dectin-1. They also express HLA-G and ILT4 two molecules involved in tolerance maintain during pregnancy. At the transcriptomic level, plaDCs showed reduced expression of class II MHC and costimulatory moecules genes, while that of Toll like receptors and MHC class I were increased. PlaDCs also showed an important gene signature dependant on hormon influence. Indeed, Estrogen and Progesterone regulated genes were uprelated in plaDCs compared to moDCs. For example, CSH1 (prolactin), was highly upregulated in plaDCs and was also produced at the protein level, which was not the case in moDCs. PlaDCs remained weakly activable, as TLR agonist such as LPS and peptidoglycan were not able to induce membranous expression of CD80, CD83, CD786 and HLA-DR contrary to moDCs. Strinckinglky, plaDCs were able to produce spontaneously high levels of IL-10, but not IL-6 or IL-12p70, even after stimulation. This was also observable, when plaDCs were infected with bacterial pathigens with placenta tropism, namely C. burnetii and B. abortus, which were not able to induce maturation. However, these pathogens were able to enter plaDCs and to survive in them. These result suggest that plaDCs are rather immunomodulatory cells that participate to the maintaining of tolerance for the fetus during pregnancy.

overall_design: Placental DCs were isolated from at term placenta and RNA was extracted. moDCs were obtained by harvesting monocyte during 7 days with IL-4+GM-CSF cocktail and their RNA was extracted. The transcriptome of plaDCs was compared to the transcriptome of moDCs.

first: Laurent

last: Gorvel

first: Amira

middle: B

last: Amara

first: Mignane

last: Ka

first: Christian

last: Capo

first: Jean-Pierre

first: Eric

last: Ghigo

first: Jean-Louis

last: Mège


title: Tetraspanin-2 promotes glucotoxic apoptosis by regulating JNK/β-catenin signaling pathway in human pancreatic β-cells

status: Public on Dec 21 2015

city: Seoul

first: Jung Min

last: Kim

address: Gangnam-gu Teheran-ro 216

department: Department of Health Genomics

institute: NAR Center, Inc. & Genoplan, Inc.

summary: Diabetes mellitus is a complex and heterogeneous disease that has β cell dysfunction at its core. Glucose toxicity affects pancreatic islets where it leads to β cell apoptosis. However, the role of JNK/β-catenin signaling pathway in glucotoxic β-cell apoptosis is poorly understood. To identify the potential genes whose expression changed in response to high glucose, we performed microarray analysis of gene expression in the RNAKT-15 cells for 48 h. Among the 41,000 genes tested, 1394 and 741 were twofold-upregulated and -downregulated, respectively. Genes involved in carbohydrate metabolism, cell cycle control, apoptotic process, and response to reactive oxygen species were upregulated. In contrast, genes involved in intracellular protein traffic, cell cycle, cell adhesion-mediated signaling, cell cycle control, response to reactive oxygen species, and apoptotic process were downregulated under high glucose-treated RNAKT-15 cells.

overall_design: RNAKT-15 cells were incubated with low glucose (5mM, LC), and high glucose (33mM, HC) for 48 hours. The microarray experiments were performed in triplicate.

first: Jung

first: Ik-Soon

last: Jang


title: Cardiac gene expression after transgenic overexpression or deletion of MeCP2 in cardiomyocytes

status: Public on Dec 22 2015

city: Freiburg

first: Ralf

last: Gilsbach

address: Albertstr. 25

institute: Institute of Pharmacology

summary:
To identify potentially regulated target genes of MeCP2 we used celltype-specific models for transgenic overexpression and ablation of MeCP2. Gene expression was analyzed in cardiac biopsies of adult male mice.
The study contains three different treatment groups: 1. healthy mice (Sham), 2. mice suffering from 4-6 weeks of cardiac pressure overload (TAC) and 3. with a reversible induction of TAC (TAC followed by 2 weeks without TAC)

overall_design: In all experiments we added the corresponding WT for the muted strains. The three different disease conditions were performed individually and thus the results are not directly comparable.

first: R

first: S

last: Mayer

first: F

last: Rühle

first: L

last: Hein


title: Potential biomarkers tah could help to determine the prognosis of azoospermia treatment

city: Bergen

first: Tomasz

last: Stokowy

address: Nygardsgaten 5

department: IT Division

country: Norway

institute: University of Bergen

summary: We analyzed gene expression profiles of human testicular biopsies in men with idiopathic nonobstructive azoospermia who underwent therapy with hCG/rFSH. Using new generation oligonucleotide microarray platform GeneChip® Human Gene 1.0 ST,  we identified genes which could be potential prognostic biomarkers of azoospermia treatment.

overall_design: We analyzed 6 testicular biopsy samples with Affymetrix Human Gene 1.0 ST microarrays. 3 of them were obtained from patients with NOA, who positively responded to hormonal therapy and 3 non-respoders.

first: A

last: Malcher

first: N

last: Rozwadowska

first: T

first: P

last: Jedrzejczak

first: W

last: Zietkowiak

first: M

last: Kurpisz


title: Anti-SLBP RIPchip data

status: Public on Dec 16 2015

city: Hanover

first: Michael

last: Whitfield

address: Geisel School of Medicine; HB 7400

institute: Geisel School of Medicine at Dartmouth

summary: The animal replication-dependent (RD) histone mRNAs are coordinately regulated with chromosome replication. They are the only known cellular mRNAs that are not polyadenylated.  Instead, the mature transcripts end in at a conserved stem-loop (SL) structure. This SL structure interacts stably with the stem-loop binding protein (SLBP), which is involved in all aspects of RD-histone mRNA metabolism. We used several genomic methods, including RNA Binding Protein IP followed by microarray analysis (RIP-ChIP) to analyze the RNA binding landscape of SLBP.

overall_design: Reference based design on two color Agilent DNA microarrays.  Experimental sample is labeled in Ch1 (Cy3), which are mRNA bound by the SLBP RNA-binding protein.  The reference sample is labeled in Ch2 (Cy5) which are the polyribosomal mRNAs from the supernatant that were not bound by anti-SLBP.  Controls included no antibody in the IP (which tends to have non-specific background binding to the beads) and pre-incubation of the SLBP with the antibodies antigenic peptide, which blocks antibody binding to the SLBP.

first: Lionel

last: Brooks

middle: L