title: TGF-beta/atRA induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation

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

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

overall_design: Refer to individual Series


title: Transcriptome profile of HBV-specific CD8 cells from acute, resolved and chronic patients

status: Public on Jan 11 2017

city: PARMA

first: Barbara

last: Montanini

state: PR

address: Parco Area delle Scienze 23/A

department: Life Sciences

country: Italy

institute: University of Parma

summary: HBV-specific CD8 cells are deeply exhausted in chronic hepatitis B and their function can only be partially corrected by modulation of up-regulated inhibitory pathways, suggesting a more complex molecular interplay. With the aim of identifying more suitable molecular targets to correct T cell dysfunction, we compared the transcriptome profile of HBV-specific CD8 cells of acute and chronic patients with the reference profile of HBV- and Flu-specific CD8 cells from patients able to resolve HBV infection spontaneously and from healthy subjects. The results indicate that exhausted HBV-specific CD8 cells are deeply impaired at a metabolic and energetic level with a prevalent down-regulation of different key cellular processes centered on an extensive alteration of mitocondrial functions. Mitochondrial modulation by antioxidant compounds could improve significantly the HBV-specific T cell function with minimal effect on T cells of different specificity. The results identify mitochondria as ideal targets for functional T cell reconstitution strategies to cure HBV infection

overall_design: Virus-specific CD8+ T cells were isolated and sorted from four (chronic, resolved), five (acute) different patients and from five healthy donors. RNA from sorted CD8+ T cells was processed, amplified, labeled, and hybridized to Agilent microarrays.

first: Paola

last: Fisicaro

first: Valeria

last: Barili

first: Simone

last: Ottonello

first: Carlo

last: Ferrari


title: Gene expression profiling of cancer cells with genetic disruption of DNA methyltransferases [Agilent-014850]

status: Public on Jan 13 2017

city: Baltimore

first: Stephen

middle: B

last: Baylin

state: MD

address: 1650 Orleans St. Suite 541

country: USA

institute: Johns Hopkins University

summary: Maximizing DNA methyltransferase (DNMT’s) inhibition for cancer therapy requires defining the roles and interactions between these enzymes for maintaining the widespread DNA methylation abnormalities in cancer.  Combining genetic  and shRNA depletion  in colon and other cancer cells reveals that DNMT1 is extremely dominant in this maintenance, with DNMT’s 3A and 3B playing minor roles,  at all genomic loci including promoters and enhancers.  Reducing DNMT1 below a deep threshold level, especially at promoters, is required for reversing abnormal DNA methylation and re-expressing key tumor suppressor genes.  Current DNMT inhibitors (DNMTis) are challenged, at tolerable patient doses, for achieving such reductions.  We introduce a new approach in which reducing levels of the DNMT targeting protein, UHRF1, complements low DNMTi doses to DNA demethylate and reactivate expression of such genes.

overall_design: To understand precisely how the three DNMT’s, 1, 3A, and 3B, interact for maintaining DNA methylation abnormalities in cancer. We perfomed genome-wide DNA methylation and gene expression anaylses in colon cancer and other cancer cell lines following  a series of genetic and shRNA depletions of each enzyme. Our data revealed that DNMT1 overwhelmingly plays the essential maintenance role.  Even with combined deletions of the proteins, lowering DNMT1 below a threshold level is required for maximal loss of  DNA methylation at all genomic regions and is required for maximally reversing promoter DNA promoter DNA hypermethylation with associated re-expression of key tumor suppressor genes.

first: Hsing-Chen

last: Tsai

first: Yi

last: Cai


title: Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer’s disease mouse model.

status: Public on Jan 09 2017

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: Several studies have indicated that the cannabinoid receptor 2(CB2) plays an important role in neuroinflammation associated with Alzheimer’s disease (AD) progression. The present study examined the role of CB2 in microglia activation in vitro as well as characterizing the neuroinflammatory process in a transgenic mouse model ofAD (APP/PS1mice). We demonstrate that microglia harvested from CB2-/- mice were less responsive to pro-inflammatory stimuli than CB2+/+ microglia based on the cell surface expression of ICAM and CD40 and the release of chemokines and cytokines CCL2, IL-6, and TNFα. Transgenic APP/PS1 mice lacking CB2showed reduced percentages of microglia and infiltrating macrophages. Furthermore, they showed lowered expression levels of pro-inflammatory chemokines and cytokine in the brain, as well as diminished concentrations of soluble Aβ 40/42.The reduction in neuroinflammation did not affect spatial learning and memory in APP/PS1*CB2-/- mice. These data suggest a role for the CB2 in Alzheimer’s disease-associated neuroinflammation independent of influencing Aβ mediated pathology and cognitive impairment.

overall_design: Primary microglia generated from 1-5 days old C57BL/6J (CB2+/+) pups were treated for 16h with LPS (100n/ml) and IFNγ (20 ng/ml)) or for 48 h with Interleukin-4 (IL-4) (100 U/ml). After harvesting, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.

first: A

middle: C

last: Schmöle

first: R

last: Lundt

first: S

last: Ternes

first: Ö

last: Albayram

first: T

last: Ulas

first: J

middle: L

first: D

last: Bano

first: P

last: Nicotera

last: Alferink

last: Zimmer


title: Transcriptomes regulated by NFAT5 in RAW264.7 macrophages

status: Public on Jan 05 2017

city: LA

first: Sungyong

last: You

state: CA

address: Beverly Blvd 8400

department: Surgery

institute: Cedars-Sinai Medical Center

summary: To explore the function of NFAT5 in macrophage, we performed transcriptome analysis in raw cells.

overall_design: In order to identify reliable transcriptional targets of NFAT5, we introduced two strategies Including 1) stable knock-down of NFAT5 transcript using shRNA (shNFAT5) and 2) a decoy system that inhibits the NFAT5 binding to its promoter by stably transfecting of the cells with oligonucleotides harboring the consensus sequence for NFAT5 target genes (NFAT5-decoy).

first: Wan-Uk

last: Kim


title: Cell-of-origin links lung tumor histotype spectrum to immune microenvironment diversity

status: Public on Jan 17 2017

city: Helsinki

first: Jenni

last: Lahtela

address: Tukholmankatu 8

country: Finland

institute: Institute for Molecular Medicine Finland

summary: Lung cancers exhibit pronounced functional heterogeneity, confounding precision medicine. We studied how the cell-of-origin contributes to phenotypic heterogeneity following conditional expression of KrasG12D and loss of Lkb1 (Kras;Lkb1). Using progenitor cell type-restricted adenoviral-Cre to target cells expressing Surfactant Protein C (SPC) or club cell antigen 10 (CC10), we show that Ad5-CC10-Cre infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts. We further demonstrate that CC10+ cells are the predominant progenitors of adenosquamous carcinoma (ASC) tumors, and give rise to a wider spectrum of histotypes that includes mucinous and acinar adenocarcinomas. Transcriptome analysis shows ASC histotype-specific upregulation of proinflammatory and immunomodulatory genes. This is accompanied with an ASC-specific immunosuppressive environment, consisting of downregulated MHC genes, recruitment of CD11b+ Gr-1+ tumor-associated neutrophils (TANs) and decreased T-cell numbers. We conclude that progenitor cell-specific etiology influences the Kras;Lkb1-driven tumor histopathology spectrum and histotype-specific immune microenvironment.

overall_design: Two tumors per mouse from three Kras;Lkb1 mice infected with Ad5-CC10-Cre, two tumors per mouse from three Kras;Lkb1 mice infected with Ad5-SPC-Cre,  one tumour per mouse from two Kras;p53 mice infected with Ad5-CC10-Cre, and one tumour per mouse from three Kras;p53 mice infected with Ad5-SPC-Cre were analysed.

first: Ashwini

middle: S

last: Nagaraj


title: Upregulation of Interferon-inducible and damage response pathways in chronic graft-versus-host disease

status: Public on Jan 04 2017

city: BETHESDA

first: PING

last: JIN

address: 9000 ROCKVILLE PIKE

department: DTM

institute: CC/DTM/NIH

summary:
To identify systemic cytokine patterns in Chronic Graft-versus-Host-Disease (CGVHD), we  profiled the gene expression of circulating monocytes. Pathway analysis identified two gene sets  that were significantly upregulated across a broad range of patients with inflammatory and  sclerotic presentations: (1) genes induced by Type I and Type II IFN, and (2) receptor genes for  innate immune responses to cellular damage. Multiple IFN-inducible genes involved in signal  transduction, anti-viral function, lymphocyte homeostasis, trafficking, and antigen presentation  were increased. Furthermore, upregulation of TLR/NLR/CLR receptor genes for nucleic acids,  ribonucleoproteins and annexin implicated response to damaged cells as a source of activation of  inflammasomes and induction of Type I IFN.
Serial time courses substantiated a pattern of  upregulation of multiple IFN-inducible genes at CGVHD onset, and of decline upon therapy and  resolution. Corticosteroid effects could be discriminated from CGVHD gene profiles by  assessment of glucocorticoid-inducible genes. Elevated expression of IFN-inducible proteins in  plasma and tissue substantiated a role for IFN in lymphocyte trafficking and, through  upregulation of BAFF, an involvement of IFN in B cell activation in CGVHD. These results  support a unifying hypothesis of induction of IFN by innate response to cellular damage as a  mechanism for initiation and persistence of CGVHD.

first: Frances

middle: T

last: Hakim

first: Sarfraz

last: Memon

first: Ping

last: Jin

first: Matin

last: Imanguli

first: Heidi

last: Wang

first: Najibah

last: Rehman

first: Xiao-Yi

last: Yan

first: Jeremy

last: Rose

first: Jacqueline

middle: W

last: Mays

first: Susan

last: Dhamala

first: David

last: Stroncek

first: Ronald

middle: E

last: Gress


title: Intestinal FXR controls transintestinal cholesterol excretion in mice

status: Public on Jan 10 2017

city: Groningen

first: vincent

last: bloks

department: Pediatrics

country: Netherlands

institute: UMCG

summary:
ABSTRACT
Background & aims: The role of the intestine in the maintenance of cholesterol homeostasis is increasingly recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport (RCT) pathway, to which both biliary and transintestinal cholesterol excretion (TICE) contribute. The mechanisms controlling the flux of cholesterol through the TICE pathway are,however, poorly understood. In the current study we aimed to identify treatment modalities that stimulate TICE and to uncover underlying driving mechanisms.

Methods: TICE was assessed in a panel of knock-out and transgenic mice as well as in mice treated with the FXR agonist PX20606 either or not combined with the cholesterol absorption inhibitor ezetimibe.

Results: We show that TICE is regulated by intestinal farnesoid X receptor (FXR) via its target fibroblast growth factor 15/19 (FGF15/19) and that the pathway can be stimulated to such an extent that mice excrete ~60% of their total cholesterol content each day. Both PX20606 and FGF19 increased the muricholate/cholate ratio in bile, inducing a more hydrophilic bile salt pool. The altered bile salt pool robustly stimulated secretion of cholesterol into the intestinal lumen via the sterol exporting heterodimer ATP binding cassette subfamily G member 5/8 (ABCG5/G8). Of note, we demonstrate that the increase in TICE induced by PX20206 is independent of changes in cholesterol absorption.

Conclusions: Hydrophilicity of the bile salt pool, controlled by FXR and FGF15/19, is an important determinant of cholesterol removal via TICE. Translation of these results to humans may offer new treatment modalities for prevention of cardiovascular disease.

overall_design: 4 WT mice on chow and 4 WT mice on chow supplemented with FXR agonist PX20606 (PX) compound 10mg/kg/day for 2 weeks. Liver and intestine (s1=proximal, s3=distal) were collected from all 8 mice.

first: Marleen

last: Schonewille

first: Jan

middle: F

last: de Boer

first: Marije

last: Boesjes

first: Trijnie

last: Bos

first: Theo

middle: H

last: van Dijk

first: Henk

last: Wolters

first: Angelika

last: Jurdzinski

first: Vincent

last: Bloks

first: Renze

last: Boverhof

first: Claus

last: Kremoser

last: van Deursen

middle: P

last: Oude Elferink

first: Antonio

last: Moschetta

first: Henkjan

last: Verkade

first: Folkert

last: Kuipers

first: Albert

middle: K

last: Groen


title: Systemic sclerosis skin disease trajectory during mycophenolate mofetil treatment

status: Public on Jan 01 2017

city: Lebanon

first: Tammara

last: Wood

state: NH

address: WTRB 674

department: Biomedical Data Science

institute: Dartmouth Medical School

summary:
Background: Only a subset of patients with systemic sclerosis (SSc) demonstrate improvement in modified Rodnan skin score (mRSS) during mycophenolate mofetil (MMF) treatment. Here we investigated the molecular and cellular effects in skin associated with MMF therapy in subjects who demonstrated or lacked clinical improvement.
Methods: Clinical and skin gene expression data were obtained genome-wide from baseline and longitudinal (6-, 12-, 24-, and 36-mo) biopsies in 33 MMF-treated subjects with SSc. Clinical improvement was defined as mRSS reduction ≥ 25%. An inflammatory signature score was calculated for each patient sample using single-sample gene set enrichment analysis (ssGSEA). Cell type specific changes during treatment were characterized.
Results: Eleven subjects with SSc completed at least 24 months of MMF therapy and were termed ‘completers’. Two distinct gene expression patterns were observed that corresponded to MMF treatment status. Three subjects showed attenuation of the inflammatory signature by 24 months, paralleling reductions in activated dendritic cells. MMF cessation at 24 months resulted in an inflammatory signature rebound paralleling mRSS increase. Three subjects that remained on MMF showed persistent inflammatory signature reductions with decreasing or stable mRSS. The remaining six completers either did not fulfill minimum mRSS (n=5), and/or lacked a baseline inflammatory signature (n=4).
Conclusions: An elevated inflammatory skin gene expression signature is associated with clinical improvement during MMF therapy. Inflammation returned upon MMF discontinuation with concomitant mRSS increase. These data summarize MMF’s molecular effects in skin and support MMF therapy for longer than 24 months in patients who demonstrate clinical response.

overall_design: Gene expression was measured (longitudinally if available) in SSc patients receiving treatment with mycophenolate mofeti, registry patients, and healthy controls

first: Monique

last: Hinchcliff

first: Michael

last: Whitfield


title: Aberrant splicing of cdkn1a/p21 through micro-RNA mediated downregulation of JMJD6

city: Leiden

first: Annemarie

middle: H.

last: Meijer

address: Einsteinweg 55

department: Animal Sciences and Health

institute: Institute of Biology, Leiden University

summary: Post-transcriptional modifications of tumor suppressors, including microRNA-mediated downregulation, are important events in tumor progression. To identify microRNAs involved in oncogenic transformation, we examined global microRNA profiles of three ras transgenic zebrafish models.  Four microRNAs are upregulated in all transgenic systems. Analysis of the predicted targets shows that three of them target Jmjd6, and overexpression of Jmjd6 in ras transformed melanocytes blocks proliferation and melanoma development. We found that Jmjd6 functions to regulate splicing of the tumor suppressor cdkn1a/p21. Truncated cdkn1a/p21 transcripts, lacking the PCNA binding domain, accumulate in ras-expressing melanocytes during melanoma development. These findings implicate Jmjd6 in a novel mechanism for inactivation of a major tumor suppressor pathway in melanoma.

overall_design: A custom-designed Agilent zebrafish 8x15k miRNA platform was used to profile miRNA  expression in transgenic zebrafish overexpressing the oncogene HRAS in melanocytes (kita:HRAS transgenic zebrafish (= Et(kita:Gal4TA, UAS:mCherry)hmz1;Tg(UAS:eGFP-HRASV12)io006, Santoriello et al., 2010) and in the telencephalon (zic:HRAS (= Et(zic4:Gal4TA4, UAS:mCherry)hzm5; Tg(UAS:eGFP-HRASV12)io006, Marina Mione, manuscript in preparation). The 15k design contained a duplicate of 7604 probes of 60-oligonucleotide length. The probes consisted of 2x22 nucleotide sequences antisense to mature miRNAs separated by a spacer of 8 nucleotides (CGATCTTT) and with a second spacer with the same sequence at the end. From 7604 probes 546 were designed for left (5') and right (3') arms of the hairpins of zebrafish miRNAs  known in miRBase, while the remainder 7058 probes corresponded to predicted hairpin structures in the zebrafish genome that might include additional miRNAs but were not considered in this study. miRNA profiles of kita:HRAS transgenic zebrafish larvae were compared to control larvae at 3, 7, and 14 days post fertilization (dpf; 3 or 4 replicates per time point), miRNA profiles of zic:HRAS transgenic zebrafish larvae were compared to control larvae at 3 days post fertilization, and miRNA profiles of a heat-shock inducible RAS line (hsp70:HRAS = Tg(hsp70l:EGFP-HRASV12)i03, Santoriello et al., 2009) were analyzed at 6 hours after a 30 min 37 °C  heat-shock induction at 3 dpf. In addition, miRNA profiles were determined of tumors in the tail fin of adult  kita:HRAS fish and compared to tail fin tissue from control fish (3 replicates). For dual color hybridization of the Agilent chips miRNA samples from HRAS transgenics were labeled with Hy3 and samples from control fish were labeled with Hy5.

first: Viviana

last: Anelli

first: Cristina

last: Santoriello

first: Anita

last: Ordas

first: Elisa

last: Alghisi

first: Luisa

last: Lanfrancone

first: Giulio

last: Tosti

first: Kyuson

last: Yun

first: Marina

last: Mione


title: Inactivation of KLF4 in T cell acute lymphoblastic leukemia promotes the expansion of leukemia cells by activating the Map2k7/Jnk pathway. [array]

status: Public on Jan 03 2017

city: Houston

first: Toni-Ann

last: Mistretta

state: TX

address: 1 Baylor Plaza, BCM 315

department: Pathology

institute: Baylor College of Medicine

summary:
Gene expression analysis of bone marrow cells from control and Klf4 deficient T-ALL mice
Deletion of Klf4 accelerates NOTCH1-induced leukemia. Analysis provides insight into function of KLF4 in leukemia.

overall_design: GFP+CD4+CD8+bone marrow cells were sorted from control and Klf4 deficient T-ALL mice induced by NOTCH1 at 4 weeks after transplantation. Sorted cells were subjected to gene expression analysis.

first: Ye

last: Shen

first: Koramit

last: Suppipat

first: Chun

last: Park

first: Terzah

last: Horton

first: Karen

last: Rabin

first: Daniel

last: Lacorazza


title: A genome-wide RNAi screen identifies genes and networks governing hematopoietic stem cell development [Illumina_Expression]

status: Public on Dec 31 2016

city: La Jolla

first: Tianxu

last: Han

address: 9500 Gilman Dr

institute: UCSD

summary: We report a genome-wide microarray analysis of gene expression in mouse embryonic stem cell (ESC) and in vitro ES-derived cells. iHoxB4 ESCs were transduced with a library of shRNAs targeting >15,000 genes, and were differentiated towards hematopoietic stem and progenitor cells by forcing HoxB4 expression in the cells. Five cell populations were isolated on differentiation days 6 and 20. Differentiated mesodermal/endothelium cell population D6F (Ssea1-Flkl+Cxcr4-), endodermal cell population D6C (Ssea1-Flkl-Cxcr4+), D20LS (Lin-Sca1+c-Kit–), D20LK (Lin–Sca1–c-Kit+), and D20LSK (Lin–Sca1+c-Kit+) cells were purified by FACS. Transduced iHoxB4 cells were analyzed as undifferentiated control cells. The experiment was performed three times independently.

overall_design: A total of 18 samples from three replicates were analyzed for microarray. Sample ESC serves as control.

first: Tariq

middle: M

last: Rana


title: PfAP2-I-GFP-msp5MUT vs PfAP2-I-GFP 3D7 [timecourse 2]

city: University Park

first: Manuel

last: Llinas

state: Pennsylvania

address: Millennium Science Complex, Pollock Rd

department: Biochemistry and Molecular Biology

institute: Penn State University

summary: Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor belonging to the Apicomplexan Apetala 2 (ApiAP2) family that is responsible for regulating the expression of a subset of merozoite genes involved in RBC invasion (PfAP2-I). Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of these genes. msp5 transcription levels decrease when the PfAP2-I DNA-binding motif is mutated in PfAP2-I-GFP parasites, showing that PfAP2-I must bind the DNA motif in order for msp5 to be transcribed.

overall_design: Plasmodium falciparum strains AP2-I-GFP and AP2-I-GFP were highly synchronized and two parallel timecourses resulting in a total of 8 samples (4 wildtype PfAP2-I-GFP, 4 msp5 mutant) were hybridized against a Cy3-labeled reference pool of 3D7 mixed stage parasites on a two-color array. Starting at 18 hours post-invasion, samples were harvested in Trizol for total RNA extraction every 6 hours until 36h post-invasion and then every 3h until the end of the IDC (48h post-invasion).

first: Joana

last: Santos

first: Philipp

last: Ross

first: Preeti

last: Joshi

first: Lindsey

last: Altenhofen

first: Tracey

last: Campbell

first: Ariel

last: Schieler

first: Ileana

last: Cristea

last: Llinás


title: Dnmt3a restrains mast cell inflammatory responses

status: Public on Feb 06 2017

city: Bellinzona

first: Francesco

last: Bertoni

state: Ticino

address: Via V. Vela 6

department: Lymphoma & Genomics Research Program

country: Switzerland

institute: IOR

summary: By utilizing mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to stimuli, both in vitro and in vivo.

overall_design: GEP analysis of WT and KO mast cells, either resting or stimulated with IgE and antigen for 4 hr and 24 hr

first: Cristina

last: Leoni

first: Andrea

last: Rinaldi

first: Silvia

last: Monticelli


title: PfAP2-I-GFP-msp5MUT vs PfAP2-I-GFP 3D7


title: Exosomal miRNA in liver disease

city: Kamakura

first: Satoshi

last: Kondo

state: Kanagawa

address: 10-1 tebiro 6-chome

country: Japan

institute: Toray Industries,Inc.

summary:
Aiming to develop novel biomarker for cancer prediction after successful treatment of interferon therapy
SVR-HCC is HCC appearance after IFN treatment. Each sample was collected 3 times; before IFN treatment, after IFN treatment, and appearance of HCC in SVR-HCC group. HCV-CHC is not HCC appearance after interferon treatment. Each sample was collected three times, before IFN treatment, after IFN treatment, and observation period after IFN treatment. For example, the sample which is SVR-HCC002-1 is the patient who suffered from HCC after IFN treatment, was collected before IFN treatment. SVR-HCC001-3 is missing.

overall_design: 42 HCC related patients

first: Yoshiki

last: Murakami

first: Saori

last: Itami


title: Expression of Idh1R132H in the murine subventricular zone stem cell niche recapitulates features of early gliomagenesis

status: Public on Jan 30 2017

city: Oxford

first: Ian

last: Tomlinson

address: Roosevelt Drive

country: United Kingdom

institute: Wellcome Trust Centre for Human Genetics, University of Oxford

summary: Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1R132H in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced -ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased.Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells over-expressed Wnt, cell cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.   Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1R132H in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced -ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells over-expressed Wnt, cell cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.

overall_design: 9 RNA  samples extracted from SVZ of Tam-Idh1-KI, and 9 RNA samples extracted from SVZ of control mice

first: Chiara

last: Bardella

first: Osama

last: Al-Dalahmah

first: Daniel

last: Krell

first: Pijus

last: Brazauskas

first: Khalid

last: Al-Qahtani

first: Marketa

last: Tomkova

first: Julie

last: Adam

first: Sébastien

last: Serres

first: Helen

last: Lockstone

first: Luke

last: Freeman-Mills

first: Inga

last: Pfeffer

first: Nicola

last: Sibson

first: Robert

last: Goldin

first: Benjamin

last: Schuster-Böeckler

first: Patrick

middle: J

last: Pollard

first: Tomoyoshi

last: Soga

first: James

last: McCullagh

first: Christopher

last: Schofield

first: Paul

last: Mulholland

first: Olaf

last: Ansorge

first: Skirmantas

last: Kriaucionis

first: Peter

last: Ratcliffe

first: Francis

middle: G

last: Szele


title: Gene expression profiling of transgenic d16HER2- and WT HER2-positive transgenic mammary tumor cell lines

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

institute: IRCSS Istituto Nazionale Tumori

summary: d16HER2 is a splice variant of HER2 receptor characterized by a significant tumor aggressiveness. We derived primary tumor cell lines from spontaneous tumors grown in mice transgenic respectively for human d16 (MI6 and MI7 cell lines) and WT HER2 isoforms (WTHER2_1 and WTHER2_2). To analyze the molecular mechanisms underlying the higher tumorigenicity of d16HER2 than that of WTHER2, we conducted gene expression profiling analysis of these cell lines.

overall_design: Gene expression profiling was performed using RNA from two transgenic d16HER2-positive (named MI6 and MI7) and two transgenic WT HER2-positive (named WTHER2_1 and WTHER2_2) mammary tumor cell lines.


title: Effect of sodium butyrate on colorectal cancer cell line HT-29

city: Kolkata

first: Santasabuj

last: Das

state: West Bengal

address: P-33,CIT Road

department: Clinical Medicine

country: India

institute: National Institute of cholera & Enteric Diseases

summary: Analysis of colorectal cancer (CRC) cell line HT-29 treated with Sodium Butyrate. Sodium Butyrate, a HDAC inhibitor present in gut, can differentiate the undifferentiated HT-29 to enterocytes by the induction of brush border enzyme alkaline phosphatase.  Results provide the transcriptional profiling underlying the butyrate-induced differentiation of CRC.

overall_design: Two-condition experiment, Butyrate treated vs. untreated HT-29 cells. Two Time points: 24 hours and 48 hours. Biological replicates: 2 control replicates, two 24 hours butyrate treated replicates  and two 48 hours butyrate treated replicates.

first: Nirmalya

last: Dasgupta


title: The Impact of Influenza Infection on the Lung Transcriptome During Repair

status: Public on Dec 28 2016

city: Pittsburgh

first: John

last: Alcorn

state: PA

address: 4401 Penn Ave

institute: Children's Hospital of Pittsburgh

summary:
Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild to moderate disease phenotypes and recover within a few weeks.
Influenza is known to cause persistent alveolitis in animal models, however little is known about the molecular pathways involved in this phenotype.
We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathology and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days post-infection.
Influenza induced persistent parenchymal lung inflammation, alveolar epithelial metaplasia, and epithelial endoplasmic reticulum stress that were evident following the clearance of virus and resolution of morbidity.
Influenza infection induced robust changes in the lung transcriptome including a significant impact on inflammatory and extracellular matrix protein expression.

overall_design: We analyzed 16 samples of whole lung RNA from mice infected with influenza (FLU, A/PR/8/34) or with vehicle control (PBS). Samples were collected at 21 and 35 days post-infection. All samples were run twice, thus producing technical replicates for each sample.


title: Assessment of embryonic vascular toxicity by pluripotent stem cell-derived arterial endothelial cells on a microfluidic system

city: Cantanhede

first: Helena

last: Vazão

address: Nucleo 4, Lote 4

department: Tissue Engeneering

country: Portugal

institute: Biocant

summary: To further understand the similaries and differences between 3 types of arterial cells (adult cells, fetal cells, and arterial cells derived from pluripotent stem cells, we analyzed the gene expression. We were able to confirm the specific gene expression hallmark of arterial endothelial cells and also to identify which are the genes that make the difference between fetal and derived endothelial cells.

overall_design: The 3 populations of cells were tripsinized and compared between them, without any treatment. All the populations were studied at the same passage number (p4) and cultured at the same densities and using the same culture media.

first: H

first: L

last: Ferreira


title: Gene expression profiles in livers with conditional knock out of autophagy related protein 7 (Atg7)

city: New York

first: Kemal

middle: Marc

last: Akat

state: NY

address: 1230 York Avenue

institute: The Rockefeller University

summary: Expression array analysis of mice livers with conditional deletion of autophagy related protein 7 (Atg7). Whole RNA from mice livers of 2 month old control (Atg7 FF), Olig1-CRE:Atg7 FF (conditional deletion in hepatocytes) and Alb-CRE:Atg7 FF (conditional deletion in hepatocytes/cholangiocytes) were analyzed. The results provide insight into the gene expression profile and role of autophagy in hepatocytes or hepatocytes/cholangiocytes in hepatic growth regulation and hepatocarcinogenesis.

overall_design: total RNA isolated from whole livers of 2 month old mice (Atg7 FF, Olig1-CRE:Atg7 FF, Alb-CRE:Atg7 FF mice).

first: Youngmin

middle: A

last: Lee

first: Scott

last: Friedman


title: Genome-wide mapping of expression in WT and p63 mutant mouse mandibular prominences at E10-E13

status: Public on Dec 23 2016

city: Saskatoon

first: Julia

last: Boughner

state: Saskatchewan

address: 107 Wiggins Road

country: Canada

institute: University of Saskatchewan

summary: Despite even large phenotypic differences among vertebrate groups, dentitions and jaws fit and function together, yet the genetic processes that orchestrate cranial and dental morphogenesis remain poorly understood. In the p63-/- mouse mutant, teeth but not jaws fail to form. This edentate mouse is a model with which to tease out genes important for odontogenesis but not jaw morphogenesis, and which may thus allow dentitions to change during development and evolution without necessarily affecting the jaw skeleton. With the working hypothesis that tooth and jaw development are autonomously controlled by discreet gene regulatory networks, we probed for genes crucial for tooth development only. Using gene expression microarray assays validated by quantitative reverse-transcription PCR, we contrasted expression in mandibular prominences at embryonic days (E) 10-13 among mice with normal lower jaw development and either normal (p63+/-, p63+/+) or arrested (p63-/-) tooth development. We predicted that expression of a suite of genes specific to odontogenesis would differ in the edentate mice. The p63-/- mice showed significantly different expression (fold change ≥1.5, ≤-1.5; p≤0.05) of several genes, some of which are already reported to help regulate odontogenesis (e.g., p63, Osr2, Cldn3/4) and/or to be targets of p63 (e.g., Jag1/2, Fgfr2), others of which have no previously reported roles in odontogenesis or the p63 pathway (e.g, Fermt1, Cbln1, Pltp, Cxcl14, Krt8, and additional keratin and claudin family members). As expected, from E10-E13 few genes known to regulate mandible morphogenesis differed in expression between mouse strains. Thus this study links for the first time several genes to odontogenesis and/or the p63 signaling network. We propose that these genes act in a novel odontogenic network that is exclusive of lower jaw morphogenesis, and posit that this network evolved in oral, not pharyngeal, teeth.

overall_design:
All experiments used mouse tissues from the B6.129S7-Trp63tm2Brd/J (generated by Mills et al., (1999)) and C57BL6/J strains (The Jackson Laboratory/JAX). We refer to mice with both copies of the mutant p63 allele as homozygote or p63-/-.  The p63+/- samples represent B6.129S7-Trp63tm2Brd/J and p63-/- represent embryos from crosses of B6.129S7-Trp63tm2Brd/J x B6.129S7-Trp63tm2Brd/J mice.
For each stage, p63-/- and p63+/- littermates were collected to minimize between-litter variation within each genotype. Also for each stage, three biological replicates (i.e., three embryos, each from a different litter) were assayed per genotype. Samples were not pooled between litters.

first: Muhammad

last: Raj


title: Crim1 regulates integrin signaling in murine lens development

status: Public on Dec 21 2016

city: Darlinghurst

first: Joshua

last: Ho

state: NSW

address: Lowy Packer Building

country: Australia

institute: Victor Chang Cardiac Research Institute

summary:
The developing lens is a powerful system for investigating the molecular basis of inductive tissue interactions and for studying cataract, the leading cause of blindness. The formation of tightly controlled cell-cell adhesions and cell-matrix junctions between lens epithelial (LE) cells, between lens fiber (LF) cells, and between these two cell populations enables the vertebrate lens to adopt a highly ordered structure and acquire optical transparency. Adhesion molecules are thought to maintain this ordered structure, but little is known about their identity or interactions. Cysteine-rich motor neuron 1 (Crim1), a type I transmembrane protein, is strongly expressed in the developing lens and its mutation causes ocular disease in both mice and humans. How Crim1 regulates lens morphogenesis is not understood. We identified a novel ENU-induced hypomorphic allele of Crim1, Crim1-glcr11, which in the homozygous state causes cataract and microphthalmia. Using this and two other mutant alleles, Crim1-null and Crim1-cko, we show that the lens defects in Crim1 mouse mutants originate from defective LE cell polarity, proliferation and cell adhesion. Crim1 adhesive function is likely to be required for interactions both between LE cells and between LE and LF cells. We show that Crim1 acts in LE cells, where it colocalizes with and regulates the levels of active β1 integrin and of phosphorylated FAK and ERK. The RGD and transmembrane motifs of Crim1 are required for regulating FAK phosphorylation. These results identify an important function for Crim1 in the regulation of integrin- and FAK-mediated
LE cell adhesion during lens development.

overall_design: This study surveys the gene expression profiles of Crim1 mutant mice (Crim1-glcr11) at P60 compared to heterozygote controls.

first: Salil

last: Lachke

first: Richard

last: Maas


title: Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells

summary: To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs), we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs) using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs) was verified by demonstrating embryonic stem cell (ESC) antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs) and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs) revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2) than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4) and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha) as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1) more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory.

overall_design: The goal of the microarray gene expression analysis is to explore and compare the gene expression profiles of mouse ES cells, iPSC derived from granulosa cells, P2 ovary and adult ovary

first: Raymond

last: Anchan


title: Development of gene expression signatures for cord blood (CB)-derived MDSCs

status: Public on Dec 19 2016

city: Zhuhai

first: Hong-Wei

last: Sun

address: 79 Kangning Road

department: The Affiliated Hospital of Beijing Institute of Technology (Zhuhai People's Hospital)

country: China

institute: Beijing Institute of Technology

summary: We have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish CB-MDSCs treated with or without combined cytokines, and CB-MDSCs cultured in complete or glucose-deprived medium.

overall_design: Purified CD34+ cells from cord blood were cultured in HSC expansion media for 7-8 d. The expanded cells were then incubated with (GM+G) or without (Med) combined GM-CSF and G-CSF for 3 d. Cytokine-treated CB-MDSCs were cultured in comoplete or glucose-deprived medium (-Glc). Two or three independent experiments were performed at each group (Med, GM+G, -Glc) using different donors for each experiment.

first: Wen-Chao

last: Wu

first: Limin

last: Zheng


title: Transcriptional profiling of CFBE41o-ΔF508 cells and CFBE41o−CFTR cells.

status: Public on Dec 12 2016

city: Napoli

first: Annamaria

last: Carissimo

address: via Castellino

institute: Tigem

summary: Cystic fibrosis bronchial epithelial (CFBE41o-ΔF508) cells subjected to 23 bio-active small molecules including vehicle controls, at low temperature and untreated cells. Untreated Cystic fibrosis bronchial epithelial cells (CFBE41o−CFTR) are also included.

overall_design: Two-colors Dye-swap, two or three biological replicates with two technical replicates each and DMSO (vehicle control) were included in each hybridization batch.

first: Fabiana

last: Ciciriello

first: Suzana

last: Anjos

first: David

middle: Y

last: Thomas


title: VEGF blockade enhances the antitumor effect of BRAFV600E inhibition (mouse)

city: Candiolo

first: Davide

last: Cora'

state: TO

department: Dept. of Oncology

institute: Piemonte Orientale University and IRCCS Candiolo Cancer Institute

summary: In this work we investigated the combined effects  of the BRAF inhibition and of the VEGF blockade in a preclinical model of melanoma. The purpose of this dataset was to examine the transcriptional responses of a A375 xenograft model to PLX472 and bevacizumab, either as single agents or as combination therapy. We performed species-specific analysis of gene expression to discriminate the effects of the different therapeutic regimens on tumor cells (human) and stromal microenvironment (mouse). Here, Illumina Mouse BeadChips were used to profile the transcriptome after 12 days treatment. We reported that dispensing the dual treatment is more efficient than the single compounds and the occurrence of resistance by modifying the tumor genetic programs regulating myeloid cells recruitment and extracellular matrix remodeling.

overall_design: A375 melanoma cell line xenografts treated with vehicle, PLX4720, bevacizumab or COMBO for 12 days

first: V

last: Comunanza

first: D

last: Corà


title: Transcriptomic profiling of microglia from a model of Experimental Cerebral Malaria Transcriptomic profiling of microglia from a model of Experimental Cerebral Malaria

city: London

first: Jean

last: Langhorne

address: The Ridgeway

institute: The Francis Crick institute

summary: Cerebral malaria is a pathology involving inflammation in the brain. There are many immune cell types activated during this process, but there is little information on the contribution of microglia, the brain resident macrophages, to this severe complication. We have examined the responses of microglia in a model of experimental cerebral malaria (ECM), in which C57BL/6 mice are infected with Plasmodium berghei ANKA. Genome wide transcriptomic analysis of these cells revealed that thousands of transcripts were differentially expressed at two different time points during the infection. The analysis indicated that proliferation of microglia was a dominant feature before the onset of ECM, and supporting this, we observed an increase in numbers of these cells in the brain. When cerebral malaria symptoms were manifest, genes involved in immune responses and chemokine production were upregulated, which were possibly driven by Type I Interferon. Together, our data offer a unique insight into the responses of microglia in the brain during ECM.

overall_design: Total RNA obtained from isolated microlgia from brains of Plasmodium berghei ANKA infected mice, 5 and 7 days post infection, compared to their uninfected controls

first: Barbara

last: Capuccini

first: Jingwen

last: Lin

first: Jan

last: Sodenkamp

first: Roberta

last: Spaccapelo

first: Carlos

last: Talavera-López

first: Shahid

last: Khan


title: VEGF blockade enhances the antitumor effect of BRAFV600E inhibition

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: Gene expression profiling of CD4+ T cell line due to presence of Nef during HIV-1 infection.

status: Public on Dec 06 2016

city: Pune

first: Debashis

last: Mitra

state: Maharashtra

address: Pune university

institute: National Centre For Cell Science

summary: We have utilized microarray technology to compare gene expression profile in presence or absence of Nef during HIV-1 infection in T cell-line. We found several genes significantly differentially regulated due to ∆nef HIV-1 infection and WT HIV-1 infection when compared to Uninfected cells and also several genes significantly dergulated due to WT HIV-1 infection as compared to ∆nef HIV-1 infection. We redistributed genes belonging to several gene ontology into broad categories like “signaling”, “apoptosis”, “transcription” and “lipid metabolism”. We selected some lipid metabolism genes to validate the Nef directed differential expression using quantitative real-time RT-PCR. Thus the present work highlights the importance of Nef directed differential gene expression in milieu of other viral proteins present during infection.

overall_design: Gene expression profiling of Uninfected CEMGFP, 0.5 MOI (Multiplicity of Infection) of ∆nef HIV-1 or Wild Type HIV-1 infected CEM-GFP after 72 hours of infection. Three independent infection experiments were set up to be used as replicates.

first: Surya

last: Shrivastava


title: mRNA profiling in gastric cancer cell line AGS upon miR-25-3p silencing

status: Public on Dec 07 2016

city: Madurai

first: Kumaresan

last: Ganesan

state: Tamil Nadu

address: School of Biological Sciences,

department: Genetics

institute: Madurai Kamaraj University

summary: Genome-wide mRNA expression profiling was performed in AGS, gastric cancer cell line, upon miR-25 silencing. At 48 hours upon anti-miR-25-3p (miRNA inhibitor) and non-targeting control RNA transfection, the whole transcriptome profiling was performed in triplicates. The miR-25 silencing elevates the diffuse gastric cancer features like expression of COL1A2, expression of COL1A2 co-expressed genes, Epithelial to Mesenchymal Transition (EMT) and angiogenesis associated genes.

overall_design: AGS cells were transfected with anti-miR-25-3p (miRNA inhibitor) and non-targeting control RNA in triplicates.  miRNA inhibitor transfection was performed twice with 24 hrs interval. Total RNA was isolated from the samples after 48 hrs of initial transfection. The RNA samples were processed and hybridized in Human Gene 1.0 ST Array and the differentially expressed probe sets were taken for Gene Set Enrichment Analysis.

first: Sembulingam

last: Tamilzhalagan


title: Integrative analysis of disease signatures shows inflammation disrupts juvenile experience-dependent cortical plasticity

status: Public on Dec 15 2016

first: Milo

middle: Robert

last: Smith

address: 1 Gustave L Levy Place

department: Neuroscience

institute: Icahn School of Medicine at Mount Sinai

summary: Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicates that treating inflammation may reduce the burden of neurodevelopmental disorders.

overall_design: Comparative RNA expression profiles from juvenile wild-type, adult Lynx1-KO, and adult wild-type bilateral primary visual cortex (n=3 biological replicates per group)

middle: R

first: Poromendro

last: Burman

first: Masato

last: Sadahiro

first: Brian

last: Kidd

first: Joel

last: Dudley

first: Hirofumi

last: Morishita


title: Differential transcriptional networks regulated by high sugar consumption in normal and high-fat-fed mice

city: Seoul

first: Jooyoung

last: Lee

address: 1 Gwanak-ro, Gwanak-gu

country: South Korea

institute: Seoul National University

summary: High sugar consumption, as well as high-fat diet, is a known cause of obesity and metabolic syndrome. However, the synergistic effect of high-sugar and high-fat consumption rarely has been evaluated, especially in terms of transcriptional regulation. Therefore, we focused on the effect of high sugar consumption on hepatic transcriptional networks in normal and high fat-fed mice. C57BL/6J mice were divided into four groups and were provided either 23%(w/v) sugar solution or plain water with either high-fat or normal-fat diet for 10 weeks. As a result, high sugar consumption significantly altered lipid metabolism-related genes in normal fat-fed mice; however, in high fat-fed mice, high sugar consumption altered inflammation-responsive genes rather than lipid metabolism. After all, these modulations eventually increased lipid accumulation in the liver and caused systemic metabolic disturbances. These observations for the first time suggested that high sugar consumption along with high-fat diet could lead to the development of severe metabolic syndrome via altering hepatic transcriptional networks.

overall_design: Total RNA was obtained from liver tissues in C57BL/6J mice supplied either plain water or 23% (w/v) sugar drink with either normal- or high-fat diet for 10 weeks.

first: Dong-Mi

last: Shin


title: PfAP2-I-GFP-msp5MUT vs PfAP2-I-GFP 3D7 [timecourse 1]

city: University Park

first: Manuel

last: Llinas

address: Millennium Science Complex, Pollock Rd

institute: Penn State University

summary: Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor belonging to the Apicomplexan Apetala 2 (ApiAP2) family that is responsible for regulating the expression of a subset of merozoite genes involved in RBC invasion (PfAP2-I). Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of these genes. msp5 transcription levels decrease when the PfAP2-I DNA-binding motif is mutated in PfAP2-I-GFP parasites, showing that PfAP2-I must bind the DNA motif in order for msp5 to be transcribed.

overall_design: Plasmodium falciparum strains AP2-I-GFP and AP2-I-GFP were highly synchronized and two parallel timecourses resulting in a total of 8 samples (4 wildtype PfAP2-I-GFP, 4 msp5 mutant) were hybridized against a Cy3-labeled reference pool of 3D7 mixed stage parasites on a two-color array. Starting at 18 hours post-invasion, samples were harvested in Trizol for total RNA extraction every 6 hours until 36h post-invasion and then every 3h until the end of the IDC (48h post-invasion).

first: Joana

last: Santos

first: Philipp

last: Ross

first: Preeti

last: Joshi

first: Lindsey

last: Altenhofen

first: Tracey

last: Campbell

first: Ariel

last: Schieler

first: Ileana

last: Cristea

last: Llinás


title: α7β1 Integrin Regulation of Gene Transcription in Skeletal Muscle Following an Acute Bout of Eccentric Exercise

status: Public on Dec 01 2016

city: Urbana

first: Marni

last: Boppart

address: 405 N Matthews

department: Kinesiology

institute: University of Illinois at Champaign-Urbana

summary: The objective of this study was to understand the mechanisms behind the contribution of the alpha7BX2 integrin to improvements and growth in skeletal muscle post exercise.  We utilized global gene profiling to identify novel signaling pathways and patterns of gene expression involved in this adaptation process, and found the alpha7BX2 integrin initiates transcription of genes that allow for protection from stress and modulation of protein synthesis.

overall_design: RNA was extracted from frozen gastrocnemius muscles of female mice 3 hours post an acute 40 minute bout of downhill running. Mice that had transgenic overexpression of the alpha7BX2 integrin were compared to wild type mice, and half of each were exercised or left as sedentary controls.  Mice were equally distributed among the four groups, and genes of interest were validated via qPCR using remaining RNA from the female mice, and RNA from equal numbers of male mice.

first: Ziad

middle: S

last: Mahmassani

first: Yair

last: Pincu

first: Michael

last: Munroe

first: Jenny

last: Drnevich

middle: D


title: Rac1-mediated DNA damage and inflammation promote Nf2 tumorigenesis but also limit cell cycle progression by inducing p53 checkpoint and cellular senescence

city: Washington

first: Garrett

middle: Thomas

last: Graham

state: DC

address: 3970 Reservoir Rd NW

department: Oncology

institute: Georgetown University Medical Center

summary: Neurofibromatosis type 2 (NF2) is caused by mutations of the tumor suppressor MERLIN/NF2. Prior studies established Yap as the driver of proliferation and tumorigenesis upon Nf2 inactivation in a well defined, genetically engineered murine liver model. Here, we report that in this model system Nf2 tumorigenesis also involves DNA damage and inflammation via Rac1-mediated production of ROS. Ablation of Rac1 blocks Nf2 tumorigenesis in spite of hyperactivation of the cyclinD1-pRb-E2F1 pathway and profound increase in liver size associated with the loss of Rac1-dependent p53 checkpoint and senescence programs. Surprisingly, Erk, Akt and Stat3 signaling does not correlate with proliferation or tumorigenesis despite being activated in Nf2 deficient livers, indicating a lesser role of these pathways for Nf2 tumorigenesis. Because a senescence gene signature is associated with benign NF2 tumors but not with malignant NF2 mutant mesotheliomas, we conclude that senescence may underlie the benign nature of NF2.

overall_design: A total of 15 independent liver samples from 5 genetic cohorts of 3-month-old mice were included in this analysis. Three independent wild-type samples were used as controls and one was replicated so as to include a reference sample across two independent plates. Within each genetic cohort, three independent mouse samples were tested in order to achieve statistical significance from the analysis. The Alb-cre;Nf2flox/flox genetic cohort presents with frank tumors on the liver, which were separated from the tumor associated region upon dissection and separately included for analysis, denoted as Nf2KO_TA. All other samples were isolated from representative liver tissue chunks.

first: Yuhao

last: Shi

first: Saumya

last: Bollam

first: Sean

middle: Z

last: Laughlin

middle: T

first: Chunling

last: Yi


title: Exosomal or serum miRNA in liver disease

city: Kamakura

first: Satoshi

last: Kondo

address: 10-1 tebiro 6-chome

institute: Toray Industries,Inc.


title: Apple peel polyphenolic content as a key player for the prevention and treatment of experimental inflammatory bowel disease.

city: Sherbrooke

first: Jean-François

last: Beaulieu

state: Québec

address: 3001, 12ème avenue nord

department: Anatomie & biologie cellulaire

institute: Université de Sherbrooke

summary:
Colonic gene expression profiles of mice with DSS-induced colitis treated with apple peel polyphenolic extract
Four-condition experiment: control, DSS-induced colitis, and mice treated with DAPP (two different doses (200 and 400 mg/kg/day) before or during induction and development of DSS-induced colitis.

overall_design: Differential gene expression

first: Marie-Claude

last: Denis

first: Denis

last: Roy

first: Pantea

last: Yeganeh

first: Yves

last: Desjardins

first: Thibault

last: Varin

first: Nour

last: Haddad

first: Devendra

last: Amre

first: Alain

last: Sané

first: Carole

last: Garofalo

first: alexandra

last: Furtos

first: Natalie

last: Patey

first: Edgar

last: Delvin

first: Eric

last: Tremblay

first: André

last: Marette

first: Jean-françois

first: Emile

last: Levy


title: Gene expression profiling in human glioma stem cell

status: Public on Nov 23 2016

city: Nagoya

first: Keisuke

last: Katsushima

address: 1 Kawasumi, Mizuho-cho, Mizuho-ku

department: Department of Epigenomics

institute: Nagoya City University Graduate School of Medical Sciences

summary: Glioblastomas show heterogeneous histological features. These distinct phenotypic states are thought to be associated with the presence of glioma stem cells (GSCs), which are highly tumorigenic and self-renewing sub-population of tumor cells that have different functional characteristics. To investigate gene expression profiling in GSC, we have performed microarray experiment using Agilent Whole Human Genome Oligo Microarrays (G4112F).

overall_design: Microarray experiment was performed as single-color hybridization on Agilent human whole genome catalog 4x44k array.

first: Atsushi

last: Natsume

first: Fumiharu

last: Ohka

first: Keiko

last: Shinjo

first: Akira

last: Hatanaka

first: Norihisa

last: Ichimura

first: Yutaka

last: Kondo


title: Genomic maps of TUG1 and gene expression profiling in human glioma stem cell

type: Genome binding/occupancy profiling by genome tiling array


title: Abrogation Of Gap Junctional Communication In ES Cells Results In A Disruption Of Primitive Endoderm Formation In Embryoid Bodies

status: Public on Nov 22 2016

city: Würzburg

first: Philipp

last: Wörsdörfer

state: Bavaria

address: Koellikerstr. 6

department: Institute of Anatomy and Cell Biology

institute: University of Würzburg

type: Expression profiling by high throughput sequencing

summary: Gap junctional intercellular communication (GJIC) has been suggested to be involved in early embryonic development but the actual functional role remained elusive. Connexin (Cx) 43 and Cx45 are co-expressed in embryonic stem (ES) cells, form gap junctions and are considered to exhibit adhesive function and/or to contribute to the establishment of defined communication compartments. Here we describe the generation of Cx43/Cx45-double deficient mouse ES cells to achieve almost complete breakdown of GJIC. Cre-loxP induced deletion of both, Cx43 and Cx45, results in a block of differentiation in embryoid bodies without affecting pluripotency marker expression and proliferation in ES cells. We demonstrate that GJIC-incompetent ES cells fail to form primitive endoderm in embryoid body cultures, representing the inductive key step of further differentiation events in this system. Lentiviral overexpression of either Cx43 or Cx45 in Cx43/45 mutants rescued the observed phenotype, confirming the specificity and indicating a partially redundant function of both connexins. Upon differentiation GJIC-incompetent ES cells exhibit a strikingly altered subcellular localization pattern of the transcription factor NFATc3. Control EBs exhibit significantly more activated NFATc3 in cellular nuclei than mutant EBs suggesting that Cx-mediated communication is needed for synchronized NFAT activation to induce orchestrated primitive endoderm formation. Moreover, pharmacological inhibition of NFATc3 activation by Cyclosporin A, a well-described inhibitor of calcineurin, phenocopies the loss of GJIC in control cells.

overall_design: For this study we analyzed embryonic stem (ES) cells double deficient for connexin43 and connexin45 (Cx43/45 del ESC) as well as control ESCs (Cx43/45 flox ESC) and embryoid bodies at day 6 of differentiation derived thereof (Cx43/45 flox EB and Cx43/45 del EB). For the ESC samples 2 biological replicates were included. For the Cx43/45 flox EBs 3 biological replicates and for the Cx43/45 del EBs 4 biological replicates were used. RNA was isolated using the RNeasy-Kit (Qiagen, Hilden, Germany). Expression analysis had been performed following the Illumina (Illumina Inc., San Diego, CA, USA) Whole-Genome Gene Expression Direct Hybridization Assay analysis pipeline. mRNA transcription levels were evaluated using the MouseWG-6 (version 2, revision 3) array which queries 45281 probes in 30854 genes and described mRNA features. Data processing was performed using the GenomeStudio suite version 2011.1 and the Gene Expression module version 1.9.0 (both Illumina Inc., San Diego, CA, USA). The downstream analyses were performed using R/Bioconductor packages and Chipster, a graphical user interface for gene expression profiling (Kalio et al., 2011). The raw intensities were quantile normalized.

first: Thileepan

last: Sekaran

first: Frank

last: Edenhofer


title: Combined transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions

status: Public on Nov 18 2016

city: Jena

first: Ilse

middle: Denise

last: Jacobsen

address: Beutenbergstr. 11a

institute: Leibniz Institute for Natural Product Research and Infection Biology

sample_organism:
Candida albicans
Mus musculus

platform_organism:
Candida albicans
Mus musculus


title: Transcriptomic, (phospho)proteomic, and metabolomic analysis of tumor-comprising cells treated by photodynamic therapy [mouse]

status: Public on Nov 25 2016

city: Amsterdam

first: Perry

last: Moerland

address: Meibergdreef 9

department: Epidemiology and Data Science

institute: Amsterdam UMC

summary: Photodynamic therapy (PDT) is a tumor treatment strategy that relies on the production of reactive oxygen species (ROS) in the tumor following local illumination. Although PDT has shown promising results in the treatment of non-resectable perihilar cholangiocarcinoma, it is still employed palliatively. In this study, tumor-comprising cells (i.e., cancer cells, endothelial cells, macrophages) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). Post-PDT survival pathways were studied following sublethal (50% lethal concentration (LC50)) and supralethal (LC90) PDT using a multi-omics approach.     ZPCLs did not exhibit toxicity in any of the cells as assessed by toxicogenomics. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly hypoxia-inducible factor 1 (HIF-1)-, nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-кB)-, activator protein 1 (AP-1)-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. (Phospho)proteomic and metabolomic analysis showed that PDT-subjected SK-ChA-1 cells downregulated proteins associated with epidermal growth factor receptor (EGFR) signaling, particularly at LC50. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling.  In conclusion, sublethal PDT activates multiple pathways in tumor parenchymal and non-parenchymal cells that, in tumor cells, transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, sublethally afflicted tumor cells are a major therapeutic culprit. Our multi-omics analysis unveiled multiple druggable targets for pharmacological intervention.

overall_design: RAW 264.7 murine macrophages as a model for tumor-resident macrophages were analyzed by whole genome expression analysis following photodynamic therapy (PDT). Cells were incubated with buffer (control group) or received a sublethal (vehicle group, 50% lethal concentration (LC50) group) or superlethal concentration (LC90 group) of zinc phthalocyanine (ZnPC)-encapsulating cationic liposomes (ZPCLs). After 60 minutes, cells were either maintained in the dark (control group, vehicle (dark toxicity (DT)) group) or were treated with 500-mW laser light (LC50 and LC90 groups) using a cumulative light dose of 15 J/cm2 (n = 3 per group). Ninety minutes after photodynamic therapy, total cellular RNA was isolated and gene expression levels were analyzed by using the Illumina WG-6 v2.0 platform. The data was analyzed in the context of survival signalling and comparisons were made with the control group.

first: Ruud

last: Weijer

first: Michal

last: Heger


title: Genome wide analysis of HDL and cyclodextrin induced gene expression in LPS-stimulated bone marrow derived macrophages

status: Public on Nov 17 2016

city: Maastricht

first: Emiel

last: van der Vorst

address: Universiteitssingel 50

institute: Maastricht University

summary: While LPS as expected induced a strongly upregulatedion of pro-inflammatory genes and signaling pathways, HDL and cyclodextrin clearly enhanced LPS-induced signaling, especially of Interferon Regulatory Factor (IRF)1 and Nuclear Factor-κB (NF-κB)-p65 dependent genes

overall_design: Total RNA obtained from bone marrow derived macrophages incubated for 24h with 300ug/ml HDL or 4h with 4% cyclodextrin, compared to PBS treated control cells.

middle: C

first: Marjo

last: Donners


title: Combined transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions [mouse tissues 8 h]

summary: The opportunistic fungal pathogen Candida albicans is a common cause of life-threatening nosocomial bloodstream infections. In the murine model of systemic candidiasis the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To get a better understanding of the organ-specific differences in host-pathogen interaction during systemic murine candidiasis, we performed a time-course gene expression profiling to investigate the differential responses of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We clearly demonstrate a delayed immune response on the transcriptional level in kidney accompanied by late induction of fungal stress response genes in this organ. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptional profile resembling that of phagocytosed cells, suggesting that the resident phagocytic system contributes significantly to fungal control in the liver. Although no visible filamentation occurred in the liver, C. albicans hypha-associated genes were upregulated, indicating an uncoupling of gene expression and morphology during infection of this organ. In vitro the induction of hypha-associated gene expression in yeast cells led to altered interaction with macrophages, suggesting that the observed transcriptional changes affect host-pathogen interaction in vivo. Consistently, the combination of host and pathogen transcriptional data in an inference network model implied that C. albicans cell wall remodeling and metabolism were connected to the immune responses in kidney and liver. Furthermore, the network suggested links between fungal iron acquisition and amino acid metabolism in the kidney and host organ homeostasis. Thus, this work provides novel insights into the organ-specific host-pathogen interactions during systemic C. albicans infection.

overall_design: 66 mouse samples, 9 arrays, time points: 8h post infection with Candida albicans

first: Betty

last: Hebecker

first: Sebastian

last: Vlaic

first: Michael

last: Bauer

first: Sascha

middle: O

last: Brunke

first: Theresia

last: Conrad

first: Jörg

last: Linde

first: Bernhard

last: Hube


title: Transcriptomic, (phospho)proteomic, and metabolomic analysis of tumor-comprising cells treated by photodynamic therapy


title: The gene expression profile of non-cultured, highly purified human adipose tissue pericytes: transcriptomic evidence that pericytes are stem cells in human adipose tissue

status: Public on Oct 31 2016

city: Canoas

first: Lindolfo

last: da Silva Meirelles

state: RS

address: Av. Farroupilha 8001

department: PPGBioSaúde

country: Brazil

institute: Lutheran University of Brazil

summary: Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs (e.g., PDGFRB, NGFR, CSPG4, ACTA2, ALPL, NESTIN, LEPR, CXCL12, SEPT4, and GLI1), but also of AT stem/progenitor cells previously described in mice (BHLHE22, ZNF423, CYP7B1, FABP4, PPARG, and CD34). Additional analyses defined a gene expression signature for AT PCs, and revealed putative novel AT PC markers (e.g., APOD, ARC, SPARCL1, OMD, IGF1, EDNRB, and TNMD). Various transcripts, including NGFR, LEPR, and almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded PCs. Genes expressed by ATMSCs but not by ATPCs (e.g., CDH2, SSTR1, and FGF1) were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology.

overall_design: Highly purified human adipose-tissue pericytes (AT3G5Cs) were isolated based on the expression of the antigen detected by the 3G5 antibody, lack of expression of CD31, and ability to adhere to tissue-cultured plastic whithin a short time.  Gene expression profiles of freshly isolated AT3G5Cs (n = 2 different biological samples) were compared to published expression profiles of other cell types, including adipose tissue-derived mesenchymal stromal cells, in order to further dissect the hypothesis that pericytes give rise to cultured mesenchymal stromal cells, determine characteristics of the pericytic gene expression profile, and find an adipose tissue pericyte gene expression signature.

first: Virgínia

last: de Deus Wagatsuma

first: Tathiane

last: Malta

first: Patrícia

middle: V

last: Bonini Palma

first: Amélia

last: Araújo

first: Rodrigo

last: Panepucci

first: Wilson

last: Silva Jr

first: Simone

last: Kashima

first: Dimas

last: Covas


title: High-Throughput Screening of Tyrosine Kinase Inhibitor Cardiotoxicity using Human Induced Pluripotent Stem Cells

status: Public on Nov 02 2016

city: Stanford

first: Jared

last: Churko

state: CA

address: 265 Campus Dr G1105 SIM1

department: Radiology

institute: Stanford

summary: Tyrosine kinase inhibitors (TKIs), despite efficacy as anti-cancer therapies, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We have utilized patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen FDA-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling. With these data, we generated a “cardiac safety index” to assess cardiotoxicities of existing TKIs. Many TKIs with a low cardiac safety index exhibit cardiotoxicity in patients. We also derived endothelial cells (hiPSC-ECs) and cardiac fibroblasts (hiPSC-CFs) to examine cell type-specific cardiotoxicities. Using high-throughput screening, we determined that VEGFR2/PDGFR-inhibiting TKIs caused cardiotoxicity in hiPSC-CMs, hiPSC-ECs, and hiPSC-CFs. Using phosphoprotein analysis, we determined that VEGFR2/PDGFR-inhibiting TKIs led to a compensatory increase in cardioprotective insulin and insulin-like growth factor (IGF) signaling in hiPSC-CMs. Activating cardioprotective signaling with exogenous insulin or IGF1 improved hiPSC-CM viability during co-treatment with cardiotoxic VEGFR2/PDGFR-inhibiting TKIs. Thus, hiPSC-CMs can be used to screen for cardiovascular toxicities associated with anti-cancer TKIs, correlating with clinical phenotypes. This approach provides unexpected insights, as illustrated by our finding that toxicity can be alleviated via cardioprotective insulin/IGF signaling.

overall_design: 8 samples, 4 conditions, 2 replicates for each condition.

first: Arun

last: Sharma


title: FOXP3 regulates ARHGAP15 expression and affects migration of glioma cells via the Rac1 signaling pathway

status: Public on Nov 03 2016

city: Tianjin

first: Jinhuan

last: wang

address: Room 6  Jizhao Road, Tianjin City

institute: Tianjin Huanhu Hospital

summary: FOXP3 plays a crucial role in the development and function of regulatory T cells and was recently identified as a tumor suppressor in different cancer types. FOXP3 is expressed in normal brain tissues, but is strongly downregulated or absent in glioblastomas. In order to understand the FOXP3 adjustment mechanisms in glioma cell,  We do a set of DNA microarray in U87 overexpressing FOXP3 and test by Quantitative real-time PCR，Western blot analysis and immunohistochemistry in vitro and vivo. So we focus on ARHGAP15. We found FOXP3 can regulate the expression of ARHGAP15. Meanwhile，FOXP3 expression was correlated with ARHGAP15 in glioma samples.FOXP3 overexpression inhibited glioma cell migration via ARHGAP15 upregulation and Rac1 inactivation. Silencing FOXP3 promoted migration via ARHGAP15 downregulation and Rac1 activation. ARHGAP15, a GTPase activating protein for Rac1, inhibits small GTPase signaling in a dual negative manner. We found there is also a correlation between expression of ARHGAP15 and Glioma level. The small GTPase Rac1 plays an important role in cell migration. In addition to this, We also found that FOXP3 regulates expression of epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin), which is important given that EMT is critically involved in tumor spreading and dissemination. Thus, FOXP3 or ARHGAP15 may serve as a new molecular target for anti-metastatic therapies in treating glioma.

overall_design: Control  vs FOXP3

last: Wang

first: Biao

last: Zhang

first: Zhen

last: Sun


title: Transcriptome dynamics and potential roles of Sox6 in the postnatal heart

status: Public on Nov 10 2016

city: Davis

first: Chung-Il

last: An

address: One Shields Ave.

institute: University of California, Davis

summary: To gain an integrated view of the dynamic changes in gene expression during postnatal heart development at the organ level, time-series transcriptome analyses of the postnatal hearts of neonatal through adult mice (P1, P7, P14, P30, and P60) were performed using a newly developed bioinformatics pipeline. Additionally, the role of the transcription factor Sox6 in the postnatal maturation of cardiac muscle was investigated by differential transcriptome analyses between Sox6 knockout (KO) and control hearts.

overall_design: Total RNA was extracted from cardiac ventricles of control (MCK-Cre) and Sox6 KO (Sox6loxp/loxp; MCK-Cre) mice at postnatal day 1 (P1), day 7 (P7), day 14 (P14), 1 month (P30), and 2 months (P60). Three biological replicates were prepared for each time point.

first: Yasunori

last: Ichihashi

first: Jie

last: Peng

first: Neelima

last: Sinha

first: Nobuko

last: Hagiwara


title: Preferential Epigenetic Programming of Estrogen Response after in utero xenoestrogen (bisphenol-A) exposure

status: Public on Oct 24 2016

city: New Haven

first: Myles

middle: H

last: Alderman III

state: Ct

address: 10 Amistad St

department: Cell Biology

institute: Yale University School of Medicine

type: Methylation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Transcriptional respose at 18hrs in Interferon treated lungs from C57BL/6 wt mice

city: London

first: Stefania

last: Crotta

address: The Ridgeway

department: IR

institute: The Crick- Mill Hill Laboratories

summary: We used microarrays to analyse the global programme of gene expression in response to intranasal interferon treatment (IFNa4 and IFNl2) in lungs from C57BL/6 wt mice

overall_design: IFNa4, IFNl2 or Vehcile Control treated lungs from C57BL/6 mice taken at 18hr post treatment (intranasal). Whole lungs collected and processed for expression profiling

first: S

last: Davidson

first: T

last: McCabe

first: A

last: Wack


title: Gene expression in the mouse brain following early pregnancy exposure to ethanol [Hippocampus_Males_P21]

status: Public on Oct 20 2016

city: Woolloongabba

first: Suyinn

last: Chong

state: QLD

address: 37 Kent St

institute: Mater Research Institute - The University of Queensland

summary: Exposure to alcohol during early embryonic or fetal development has been linked with a variety of adverse outcomes, the most common of which are structural and functional abnormalities of the central nervous system. Behavioral and cognitive deficits reported in individuals exposed to alcohol in utero include intellectual impairment, learning and memory difficulties, diminished executive functioning, attention problems, poor motor function and hyperactivity. The economic and social costs of these outcomes are substantial and profound. Improvement of neurobehavioural outcomes following prenatal alcohol exposure requires greater understanding of the mechanisms of alcohol-induced damage to the brain. Here we use a mouse model of relatively moderate ethanol exposure early in pregnancy and profile gene expression in the hippocampus and caudate putamen of adult male offspring. The effects of offspring sex and age on ethanol-sensitive hippocampal gene expression were also examined.

overall_design:
Hippocampus, male, 3 weeks old
Two groups, ethanol-exposed (EtOH) and Control, with 6 replicates per group.

first: Christine


title: Gene expression in the mouse brain following early pregnancy exposure to ethanol [Hippocampus_Females_P87]

overall_design:
Hippocampus, female, 12 weeks old
Two groups, ethanol-exposed (EtOH) and Control, with 6 replicates per group.


title: Gene expression in the mouse brain following early pregnancy exposure to ethanol [CaudatePutamen_Males_P87]

overall_design:
Caudate putamen, male, 12 weeks old
Two groups, ethanol-exposed (EtOH) and Control, with 6 replicates per group.


title: MicroRNA-29 Impairs the Early Phase of Reprogramming Process by Targeting Active DNA Demethylation and Wnt Signaling

status: Public on Oct 05 2016

city: Ribeirao Preto

first: Rodrigo

middle: Alexandre

last: Panepucci

state: São Paulo

address: R. Tenente Catao Roxo, 2501

institute: Regional Blood Center of Ribeirâo Preto (FUNDHERP, HC-FMRP-USP)

summary: Somatic cell reprogramming by transcription factors and other modifiers such as small molecules or miRNAs has opened broad avenues for the study of developmental processes, cell fate determination, and interplay of molecular mechanisms in signaling pathways. However, many of the mechanisms that drive nuclear reprogramming itself remain yet to be elucidated. Here, we analyzed the role of miR-29 during reprogramming in more detail. Therefore, we evaluated miR-29 expression during reprogramming of fibroblasts transduced with lentiviral OKS and OKSM vectors and we show that addition of c-MYC to the reprogramming factor cocktail decreases miR-29 expression levels. Moreover, we found that transfection of pre-miR-29a strongly decreased OKS-induced formation of GFP+- colonies in MEF-cells from Oct4-eGFP reporter mouse, whereas anti-miR-29a showed the opposite effect. Furthermore, we studied two pathways which are important for reprogramming and which involve miR-29 targets: active DNA-demethylation and Wntsignaling. We show that inhibition of active DNA-demethylation as well as activation of Wnt-signaling leads to decreased reprogramming efficiency. Moreover, transfection of premiR-29 resulted in elevated expression of β-Catenin transcriptional target sFRP2 and increased TCF/LEF-reporter activity. Finally, we report that Gsk3-β is a direct target of miR-29 in MEF-cells. Together, our findings contribute to the understanding of the molecular mechanisms by which miR29 influences reprogramming.

overall_design: In order to identify potential miR-29a targets, human BJ1 fibroblasts were transfected with 50 nM of synthetic miR-29a mimics (n=3) or control miR-Ctr molecules (n=3) in 12-well plates, using Lipofectamine RNAiMax (Invitrogen), according to the manufacturer's instructions. Total RNA was extracted 72 hours post-transfection and analyzed.

first: Mariane

last: Fráguas

first: Reto

last: Eggenschwiler

first: Jeannine

last: Hoepfner

first: Josiane

last: Santos

last: Haddad

first: Lucila

middle: B

last: Oliveira

first: Amélia

last: Araújo

first: João

last: Baiochi

first: Marco

last: Zago

first: Tobias

last: Cantz


title: Recipient and donor expression differences in children treated with HSCT

status: Public on Oct 19 2016

city: Krakow

first: Miroslaw

last: Bik-Multanowski

address: ul. Wielicka 265

department: Dept. of Medical Genetics

country: Poland

institute: Jagiellonian University

summary: Reconstitution of cell lines and occurrence of complications following hematopoietic stem cell transplantation (HSCT) are regulated by genome expression. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare whole genome expression in children before and after HSCT. A total of 44 children treated with HSCT were enrolled in the study. Gene expression was measured before HSCT (pre-HSCT group; n=44) and after a median of 6 months after allogenic HSCT (post-HSCT group; n=27; all children were included in the pre-HSCT group). Neoplasms were the indication for HSCT in 73% of the patients. Whole genome expression was assessed in leukocytes using GeneChip® HumanGene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed 18 significantly different genes with defined function. These genes are responsible for proliferation and differentiation of cells (14 genes), apoptosis (8 genes), migration of cells (3 genes) and fluid/electrolyte homeostasis (2 genes). Our findings allow us to conclude that activation of genes involved in reconstitution of donor cell lines, and those related to immune reactions observed after HSCT, form the genetic background for physiological and pathological processes following HSCT.

overall_design: Comparison of genome expression before and after HSCT (hematopoietic stem cell transplantation)

first: Symon

last: Skoczen


title: Expression data from 7 cell lines in early and late stages and their corresponding tumor

status: Public on Oct 01 2016

city: Toulouse

first: Frédéric

last: Chibon

address: 2 avenue Hubert Curien

department: Team 19 - INSERM UMR1037

country: France

institute: Cancer Research Center of Toulouse

summary:
Background: Sarcoma oncogenesis is still poorly understood and there is a pressing need to generate cell lines representative of diverse sarcoma types.
Methods: We submitted to culture all sarcoma from patients receiving surgery in a large tertiary referral centre in France. Of the 32 established cell lines we report the genomic and transcriptomic study of 7 which were extensively tested for the representativeness to the original tumor and the evolution over passages.
Results: Pleomorphic sarcomas are genetically heterogeneous. As a consequence, cell lines derived from that kind of tumor developed from selected clones roughly representing the initial tumor. More importantly our results show that there are no genetic imbalances and transcription modifications along passages.
Conclusions: This likely means that even if pleomorphic sarcomas are genetically unstable at the cellular level, they appear to be genetically stable at the multicellular one and therefore remain representative of the initial tumor even after passages. We established a sarcoma cell line panel gathering 32 cell lines with genomic, transcriptomic and clinical data, which will be very powerful to go further in the understanding of genomic alterations, sarcoma biology and to manage preclinical studies and clinical trials.

first: Frederic


title: Overexpression of histone demethylase Fbxl10 leads to enhanced migration in mouse embryonic fibroblasts

city: Bonn

first: Jutta

last: Kirfel

state: NRW

department: Institute of Pathology

institute: University Hospital

summary: Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, immune responses and invasive tumors all require the orchestrated movement of cells to specific locations.  Histone demethylase proteins alter transcription by regulating the chromatin state at specific gene loci. FBXL10 is a conserved and ubiquitously expressed member of the JmjC domain-containing histone demethylase family and is implicated in the demethylation of H3K4me3 and H3K36me2 and thereby removing active chromatin marks. However, the physiological role of FBXL10 in vivo remains largely unknown. Therefore, we established an inducible gain of function model to analyze the role of Fbxl10 and compared wild-type with Fbxl10 overexpressing mouse embryonic fibroblasts (MEFs). Our study shows that overexpression of Fbxl10 in MEFs doesn`t influence the proliferation capability but leads to an enhanced migration capacity in comparison to wild-type MEFs. Transcriptome and ChIP-seq experiments demonstrated that Fbxl10 binds to genes involved in migration like Areg, Mdk, Lmnb1, Thbs1, Mgp and Cxcl12.  Taken together, our results strongly suggest that Fbxl10 plays a critical role in migration by binding to the promoter region of migration-associated genes and thereby might influences cell behaviour to a possibly more aggressive phenotype.

overall_design: To analyse the role of histone demethylase Fbxl10 we generated gain of function model overexpressing HA-tagged Fbxl10 and identified target genes by expression analysis. We isolated MEFs from our gain of function model and three independent RNA samples were generated from non-induced and induced MEFs.

first: Magdalena

last: Rohde


title: Norrin-dependent gene expression in cerebellar granule neuron progenitors

status: Public on Oct 12 2016

city: Toronto

first: Valerie

middle: Anne

last: Wallace

state: ON

address: 60 Leonard St

department: Vision

institute: Krembil Research Institute

summary: Medulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor in children. One third of all human MB exhibits a gene expression signature of Sonic hedgehog (Shh) signaling. Hedgehog (Hh) pathway inhibitors have shown efficacy in clinical trials for MB, however, tumors develop resistance to these compounds, highlighting the need to identify additional therapeutic targets for treatment.      We have identified a role for Norrin signaling in tumor initiation in the Patched (Ptch) mouse model of MB.   Norrin is a secreted factor that functions as an atypical Wnt by binding to the Frizzled4 (Fzd4) receptor on endothelial cells to activate canonical beta-catenin-mediated Wnt signaling pathway.   In the cerebellum, activation of Norrin/Fzd4 signaling is required for the establishment and maintenance of the blood brain barrier (BBB).  We have identified a role for Norrin signaling in the stroma as a potent tumor inhibitory signal.  Inactivation of Norrin in Ptch+/- mice significantly shortens latency and increases MB incidence.  This phenotype is associated with an increased frequency of pre-tumor lesions and their conversion to malignancy. In this context, loss of Norrin signalling in endothelial cells is associated with an accelerated transition to a pro-tumor stroma characterized by vascular permeability, inflammation and angiogenic remodelling. Accordingly, loss of Ndp significantly alters the stromal gene expression signature of established Ptch MB.

overall_design: Ptch+/- mice were maintained on a C57Bl/6 background. NdpKO mice, generated by disruption of the Ndp locus by a lacZ-containing cassette were obtained from Lexicon Pharmaceuticals (Junge et al., 2009) and maintained by interbreeding on a mixed background. Ndp is an X-linked gene and Ndp+/- females were crossed with Ptch+/- males, to generate male (Ndp-/y;Ptch+/-) NdpKO;Ptch+/- compound mutants. All compound mutants were compared to single Ptch+/- or wild-type controls from the same breeding cohort to ensure matched backgrounds. Granule neuron progenitors (GNPs) were isolated from postnatal day 6 (P6) cerebella of WT, Ptch+/- and Ndp-/y;Ptch+/- mice.  MB tumors were dissected from the cerebella of symptomatic Ptch and Ndp-/y;Ptch+/- mice.  To identify an NDP-dependent gene signature in tumors we compare gene expression in GNPs and MB from mice of the indicated genotypes.


title: Ectopic TLX expression skews lineage commitment toward a myeloid fate and promotes an inflammatory phenotype

status: Public on Sep 21 2016

city: Philadelphia

first: daniel

last: beiting

state: PA

address: 380 S. University Ave

department: Pathobiology

institute: University of Pennsylvania

summary: We previously showed that the orphan nuclear hormone receptor, TLX (also known as NR2E1), selectively modifies the output of IFN-gamma-driven, STAT1-dependent gene expression.  Since IFN-gamma and STAT1 are also known to regulate myeloid cell development and function, we tested whether ectopic expression of TLX or COUPTF2 (a closely related orphan nuclear receptor) might influence hematopoietic differentiation.  Indeed, TLX promotes lineage commitment toward myeloid development and suppresses erythropoiesis, phenocopying IFN-gamma treatment. Moreover, TLX expression in our assay is sufficient to activate a proinflammatory transcriptional program with two hallmarks: differential regulation of STAT1-dependent genes, and suppression of an anti-inflammatory program in favor of a fatty acid signature – a process known to be essential for cellular remodeling during macrophage maturation and phagocytosis. These results demonstrate an important role for a new nuclear hormone receptor in STAT1 signaling, and link TLX to myeloid lineage commitment and function.

overall_design: Cells purified from three different experiments were analyzed as biological triplicates for four different treatments.

first: Daniel

last: Beiting

first: Sara

last: Cherry

first: David

last: Roos


title: Gene expression in the mouse brain following early pregnancy exposure to ethanol

status: Public on Oct 07 2016

first: Suyinn

last: Chong


title: Norrin-dependent gene expression in Patched mouse medulloblastoma

middle: A


title: Norrin-dependent gene expression in murine cerebellar granule neuron progenitors and Patched medulloblastoma


title: Human lung cancer Cells: Control vs. FENDRR stably over-expressed lung cancer cells

status: Public on Nov 15 2016

city: Guangzhou

first: Lei

last: Yang

address: Xinzao, Panyu District,

institute: Guangzhou medical university

summary: Transcriptional profiling of human lung cancer cell lines A549 comparing control cells transfected with an empty lentiviral expression vector pEZ-Lv201 and A549 cells transfected with a pEZ-Lv201-FENDRR. The latter forms a FENDRR stably over-expressed cell lines. Goal was to to assess the alteration of gene expression profiles caused by FENDRR upregulation.

overall_design: Two-condition experiment, A549 vs. FENDRR stably over-expressed A549 cells. No replicate.

first: Jiachun

last: Lu


title: Lipids reprogram metabolism to become a major carbon source for histone acetylation

status: Public on Sep 22 2016

city: Durham

first: Matthew

last: Hirschey

state: NC

address: 300 N. Duke Street

department: Department of Medicine

institute: Duke University Medical Center

summary: We found that lipid-derived acetyl-CoA is a major source of carbon for histone acetylation. Gene expression profiling of octanoate-treated hepatocytes identified a pattern of upregulated lipid metabolic genes, demonstrating a specific transcriptional response to lipid. These studies expand the landscape of nutrient sensing and uncover how lipids and metabolism are integrated by epigenetic events that control gene expression.

overall_design: Cells were plated at 350,000 cells per well in 6-well plates and seeded overnight; the following day cells were treated with PBS, 1 mM, 2 mM or 5 mM octanoate for 24 hours added to complete DMEM media with 10% FBS.

first: Eoin

last: McDonnell


title: Gene expression of Ovarian Tumor Samples measured by Agilent microarray

status: Public on Sep 30 2016

city: Santa Monica

first: Habib

last: Hamidi

address: 2825 Santa Monica Blvd., Suite 200

institute: UCLA

summary: The goal of the study was to collect ovarian cancer samples for gene expression profiling (n = 529). The data will be used in several publications, the first of which described molecular signatures associated with high-grade serous ovarian cancer subtype

overall_design: Ovarian tumors (n=529) were compared to a reference pool of 106 ovarian samples. Mixed reference includes normal, benign, borderline, and malignant sample of various histolgies.

first: G

last: Konecny

first: D

last: Slamon

first: C

last: Wang

first: E

last: Goode

first: L

last: Hartmann

last: Ginther

first: H

last: Chen

first: J

last: Dering

first: Gregory

last: Way

first: James

last: Rudd

first: Casey

last: Greene

first: Jennifer

last: Doherty


title: Gene expression analysis in the kidney following disseminated candididiasis

status: Public on Oct 18 2016

city: Pittsburgh

first: Partha

middle: Sarathi

last: Biswas

address: 203 Lothrop Street

department: Medicine

institute: University of Pittsburgh

summary:
Comparative analysis of renal gene expression between wild type and mice deficient in IL-17 receptor signaling following disseminated candidiasis. The hypothesis to be tested in the present study was that there should be a differential renal gene expresion in the absence of IL-17 receptor signaling following disseminated candidiasis.
Wild type and IL-17RA-/- mice were systemically infected with Candida albicans and 48 hour post infection renal gene expression was analyzed.

overall_design: Total RNA was isolated from the kidney of wild type and IL-17RA-/- kidney and analyzed for renal gene expression.


title: Effects of VEGF-B on doxorubicin-induced cardiotoxicity

city: Helsinki

first: Riikka

last: Kivelä

address: Haartmaninkatu 8

institute: University of Helsinki and Wihuri Research Institute

summary: Doxorubicin is a widely used and effective anthracycline chemotherapy drug, which use is limited due to its cardiotoxic side effects. We show that gene therapy with AAV-VEGF-B can inhibit the doxorubicin-induced cardiac atrophy and whole body cachexia.

overall_design: Total RNA obtained from myocardium of mice in 3 groups: 1) control (injected with PBS, n= 5), 2) doxorubicin injected alone (Dox, n=5 ), 3) AAV9-VEGF-B administration 7 days before doxorubicin injection (n=5 ). Mice were euthanized 20 hours after doxorubicin or PBS injection.

first: Kari

last: Alitalo


title: Tubular epithelial NF-κB activity regulates acute ischemic kideny injury [130402-EV-EmxdN]

status: Public on Sep 17 2016

city: Hannover

first: Christian

last: Hinze

address: Carl-Neuberg-Str. 1

department: Department of Nephrology and Hypertension

institute: Hannover Medical School

summary: NF-κB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of acute kidney injury (AKI). The cell type-specific functions of NF-κB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue-parenchymal cells. We analyzed tubular epithelial-specific NF-κB signaling in a mouse model of ischemia-reperfusion injury (IRI)-induced AKI. NF-κB reporter activity and nuclear localization of phosphorylated NF-κB subunit p65 analyses in mice revealed widespread NF-κB activation in renal tubular epithelia and in interstitial cells following IRI that peaked at 2-3 days after injury. To genetically antagonize tubular epithelial NF-κB activity, we generated mice expressing the human NF-κB super-repressor IκBα∆N in renal proximal, distal, and collecting duct epithelial cells. These mice were protected from IRI-induced AKI, as indicated by improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration. Tubular NF-κB-dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IκBα∆N-expressing mice exposed to hypoxia-mimetic agent cobalt chloride were protected from apoptosis and expressed reduced levels of chemokines. Our results indicate that postischemic NF-κB activation in renal-tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response.

overall_design: Expression profiling was performed by Illumina Mouse WG6 v2.0 Expression Bead Chip microarray analysis. Differentially expressed genes of ischemic wild-type vs. Emx1-ΔN kidneys were analyzed at 24 hours following ischemia reperfusion injury, compare to Sham control kidneys. 6 biological replicates were used per group.

first: Lajos

last: Markó

first: Emilia

last: Vigolo

first: Joon-Keun

last: Park

first: Giulietta

last: Röel

first: András

last: Balogh

first: Mira

last: Choi

first: Anne

last: Wübken

first: Jimmi

last: Cording

first: Ingolf

middle: E

last: Blasig

first: Friedrich

last: Luft

first: Claus

last: Scheidereir

first: Kai

middle: M

last: Schmidt-Ott

first: Ruth

last: Schmidt-Ullrich

first: Dominik

middle: N

last: Müller