title: Effect of Prox1 in tibialis anterior skeletal muscle

first: Riikka

last: Kivelä

summary: We show that Prox1 overexpression induces slow muscle fiber type gene program in fast muscle and activates calcineurin signaling

overall_design: Three AAV8-Prox1 overexpressing TA muscles were compared to three AAV8-mCherry controls


title: Tubular epithelial NF-κB activity regulates acute ischemic kideny injury

status: Public on Sep 17 2016

city: Hannover

first: Christian

last: Hinze

address: Carl-Neuberg-Str. 1

department: Department of Nephrology and Hypertension

country: Germany

institute: Hannover Medical School

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

overall_design: Refer to individual Series


title: Gene expression in a 3D skin tissue subjected to bystander alpha-particle irradiation

status: Public on Sep 10 2016

city: New York

first: Sally

last: Amundson

state: NY

department: Center for Radiological Research

country: USA

institute: Columbia University

summary: The radiation bystander effect has been documented with multiple endpoints in various models.  While many of the factors regulating this response are known, the mechanisms are still not well understood, and even less is known about signaling of bystander responses in 3-dimensional (3D) tissues.  We have used the EPI-200 3D epidermal tissue model to measure global gene expression changes in bystander tissue in order to gain insight into the molecular pathways involved.  We identified 187 genes with significantly altered expression in the region between 250 μm and 1 mm from the site of irradiation four hours after exposure.  Gene expression at 250-500 μm and 500-750 μm was similar to that within the first 250 μm, the region that also included the directly irradiated tissue. Gene expression, although still significantly altered, began to return toward control levels in the region between 750 μm and 1 mm, however, suggesting a spatial limit to the bystander signal.  The 3D bystander genes were concentrated in gene ontology classifications associated with direct irradiation, such as regulation of cell cycle progression and cell death, as well as categories previously associated with bystander responses, such as extracellular signaling, inflammatory processes, and terminal differentiation.

overall_design: A 25-micron wide strip across the center of a 3D skin tissue model was exposed to either 0 or 0.5 Gy alpha particles, and gene expression was analyzed in slices of tissue located at various distances away from the site of irradiation 16 hours after exposure.  Three biological repeats were performed for each condition

middle: A

first: Alexandre

last: Mezentsev


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

status: Public on Sep 15 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

summary: Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure  toBPAin utero hasbeen linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and  estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression  microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation,  which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-a (ERa)–binding genes. The majority of genes that demonstrated both altered expression and ERa binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERa. Gene–  environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen related disease in adults.—Jorgensen, E. M.,Alderman,M.H., III,Taylor, H. S. Preferential epigenetic programmingof  estrogen response after in utero xenoestrogen (bisphenol-A) exposure.

overall_design: Dams were exposed to 5mg/kg/day of BPA or DMSO (CTL) for day 9-21 of gestation. Offspring were oopherectomized at 6 weeks. At 8 weeks mice were given 300ng E2 or DMSO and uteri were harvested 6h later. Total RNA was analyzed. Samples were pooled by litter.

first: Elisa

middle: M

last: Jorgensen

first: Hugh

middle: S

last: Taylor


title: Transcriptional profiling of E14.5 control and Tbr2 fl/fl;Foxg1::Cre cortices

status: Public on Sep 08 2016

city: Milano

first: Luca

last: Massimino

state: MI

address: Via Olgettina, 58

department: Gastroenterology

country: Italy

institute: Ospedale San Raffaele

summary: The abscence of TBR2 gene in human leads to microcephaly. This condition is mimicked by the specific ablation of the murine gene in developing cerebral cortex. Herein we compared gene expression in control and Tbr2 cKO in E14.5 cerebral cortices. This approach represents a useful tool to identify the molecular mechanisms at the basis of the phenotype.

overall_design: 6 samples, 3x Tbr2 +/+;Foxg1::Cre (control) and 3x Tbr2 fl/fl;Foxg1::Cre

first: Alessandro

last: Sessa

first: Vania

last: Broccoli


title: Tubular epithelial NF-κB activity regulates acute ischemic kideny injury [OTT-211009]

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. Gene expression was analyzed at time points 6 hours, 48 hours, and 7 days after IRI-induced AKI in C57Bl/6J mice compare to healthy control. 3 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

middle: C

last: Luft

first: Claus

last: Scheidereir

first: Kai

last: Schmidt-Ott

first: Ruth

last: Schmidt-Ullrich

first: Dominik

middle: N

last: Müller


title: Microarray analysis of IL-17 gene transfer in murine dorsal skin.

city: Davis

first: Matt

middle: L

last: Settles

state: CA

address: 451 Health Sciences Sr

department: Genome Center

institute: University of California, Davis

summary: Comparison of dorsal skin gene expression between GFP and IL-17 gene transfer in C57BL/6J mice

overall_design: 4 samples with 6 mice per sample.

first: I

last: Adamopoulos

first: Erika

last: Suzuki


title: ROSA26Foxf1; Tie2-cre lung gene expression analysis.

status: Public on Sep 01 2016

city: Houston

first: Pawel

last: Stankiewicz

state: Texas

address: One Baylor Plaza

department: Molecular and Human Genetics

institute: Baylor College of Medicine

summary: Analysis of genes deregulated due to heterozygous overexpression of Foxf1 in endothelial and hematopoietic cells using Tie2-cre in embryonic day 18.5 mouse lungs.

overall_design: Total RNA obtained from three ROSA26Foxf1; Tie2-cre mouse lungs compared to three control ROSA26-lox-stop-lox (LSL) -Foxf1 mouse lungs.

first: Avinash

last: Dharmadhikari

first: Tadeusz

last: Majewski

first: Krzysztof

last: Gogolewski

first: Anna

last: Gambin


title: Identification of Death-promoting transcription factor Btf down stream targets by microarray.

status: Public on Aug 31 2016

city: Shanghai

first: Hanshao

last: Liu

address: No.1239 Siping Rd.

country: China

institute: Tongji University

summary: Death-promoting transcription factor Btf has been reportedly implicated in the apoptotic signal triggered by ionizing radiation, DNA damage-inducing agents, and cyclic stretch. However, mechanisms for the regulation of Btf-mediated apoptosis remain largely unknown. In the present study, we performed genome-wide mRNA expression profiling from Btf-depleted Hela cells and identified SMAD3 as a potential downstream target of Btf. Btf interacted with the SMAD3 promoter and this interaction was associated with the activation of SMAD3 gene transcription. Furthermore, we provided evidence that SMAD3 is involved in the induction of apoptosis, and that the disruption of Btf-mediated SMAD3 expression leads to resistance to DNA damage-induced apoptosis

overall_design: Twelve samples are analysed.Three replicates are included. Hela cells are transfected with scrambled siRNA or Btf siRNA, and then left either untreated or treated with ADR for 8 hours.

first: Chuanchuan

last: Ma

first: Jiajing

last: Zhou

first: Kiyotsugu

last: Yoshida

first: Libo

last: Lin

first: Liang

last: Wang

first: Huasheng

last: Xiao


title: Eicosapentaenoic acid and docosahexaenoic acid - enriched high fat diet reduces adiposity related genes in different adipose tissues transcriptome of C57BL/6J mice

city: Gothenburg

first: Nikulkumar

middle: Kirtilal

last: Soni

state: Vastra Gotaland

address: Kemivagen 10

department: Department of Biology and Biological Engineering

country: Sweden

institute: Chalmers University of Technology

summary: Effects of EPA/DHA enriched high fat diets (HFD) compared to HFD-Corn oil after 8 weeks intervention on different adipose depots of C57BL/6J mice.

overall_design: Four mice representing each diet group on the basis of body weight, plasma triglyceride and plasma cholesterol levels were selected for RNA isolation and microarray analysis. Total RNA from skeletal muscle of these selected animals was purified using the RNeasy® Plus Universal Mini kit (Qiagen Nordic, Sollentuna, Sweden) by following the manufacturer's instruction carefully. The extracted RNA was quantified by NanoDrop 2000c UV-Vis Spectrophotometer (Thermo Scientific, USA) and the quality of the RNA was estimated by RNA 6000 Nano LabChip for Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, California, USA).


title: Systems analysis of B16-WT, B16-shTGFb and B16-shVEGF tumor microenvironment 4 or 14 days after tumor inoculation

city: Farmington

first: Djamel

last: Nehar-Belaid

state: CONNECTICUT

address: 10 discovery drive

institute: THE JACKSON LABORATORY

summary: Analysis of B16 tumor microenvironments at gene expression level. The hypothesis tested in the present study was that Tregs orchastrated the immune reponse triggered in presence of tumors

overall_design: Total RNA obtained from tumor microenvironment tissues (at Day 4 and Day 14 after tumor inoculation) compared to control tissues.

first: Tristan

last: Courau

first: Béatrice

last: Levacher

first: Bertrand

last: Bellier

first: Faustine

last: Brimaud

first: Laura

last: Florez

first: David

last: Klatzmann


title: Different genotypes of Trypanosoma cruzi produce distinctive placental environment genetic response in chronic experimental infection

status: Public on Aug 25 2016

city: Buenos Aires

first: Natalia

middle: Anahí

last: Juiz

address: 2490, Vuelta de Obligado

country: Argentina

institute: INGEBI-CONICET

summary: Congenital infection of Trypanosoma cruzi allows transmission of this parasite through generations. Despite the problematic that this entails, little is known about the placenta environment genetic response produced against infection. We performed functional genomics by microarray analysis in C57Bl/6J mice comparing placentas from uninfected animals and from animals infected with two different T. cruzi strains: K98, a clone of the non-lethal myotropic CA-I strain (TcI), and VD (TcVI), isolated from a human case of congenital infection. Analysis of networks by GeneMANIA of differentially expressed genes showed that “Secretory Granule” was a pathway down-regulated in both infected groups, whereas “Innate Immune Response” and “Response to Interferon-gamma” were pathways up-regulated in VD infection but not in K98. Applying another approach, the GSEA algorithm that detects small changes in predetermined gene sets, we found that metabolic processes, transcription and macromolecular transport were down-regulated in infected placentas environment and some pathways related to cascade signaling had opposite regulation: over-represented in VD and down-regulated in K98 group. We also have found a stronger placental tropism by VD strain, by detection of parasite DNA and RNA, suggesting living parasites in that tissue. Our study is the first one to describe in a murine model the genetic response of placental environment to T. cruzi infection and suggests the development of a strong immune response, parasite genotype-dependent, to the detriment of cellular metabolism.

overall_design: Total RNA obtained from isolated placentas from mice with chronic T. cruzi infection (K98 or VD strains) at 18.5 days of gestation compared to uninfected control mice.

first: María

last: Solana

first: Alejandro

middle: G

last: Schijman


title: Identification of TWIST1 transcriptoinal targets in the cranial mesoderm [WNT1 vs. MESP1]

status: Public on Aug 23 2016

city: WESTMEAD

first: PIERRE

last: OSTEIL

state: NSW

address: 214 Hawkesbury Road

department: Embryology

country: Australia

institute: CMRI

summary: TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. Our previous work showed that, in the absence of TWIST1, some cells within the cranial mesoderm adopt an abnormal epithelial configuration. Here, we show by transcriptome analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics. By comparing the transcriptional profiles of cranial mesoderm-specific Twist1 loss-of-function mutant and control mouse embryos, we identified a set of genes that are both TWIST1-dependent and predominantly expressed in the mesoderm. By ChIP-seq in a cell line model of a TWIST1-dependent mesenchymal state, we identified, among the downstream genes, three direct transcriptional targets of TWIST1: Ddr2, Pcolce and Tgfbi.  Our findings show that the mesenchymal properties of the cranial mesoderm is likely to be regulated by a network of TWIST1 targets genes that influence the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures.

overall_design: Cranial neural crest and cranial mesoderm cells were isolated by flow sorting of GFP reporter-labelled cells collected from heads of E9.5 mouse embryos. Three replicates were independently isolated and hybridized to Illumina mouse WG v 2.0 chips

first: Patrick

last: Tam


title: Identification of TWIST1 transcriptional targets in the cranial mesoderm [E9_5]

overall_design:
For microarray analysis of CM-CKO embryos, embryo heads of four genotypes were collected at E8.5 (5-7 somites) and E9.5 (18- 20 somites):  CM-CKO (Twist1flox/del; Mesp1Cre/+), CM-Het (Twist1flox/wt; Mesp1Cre/+), Het (Twist1flox/del; Mesp1+/+) and Control (Twist1flox/wt; Mesp1+/+).
Sample sizes for E9.5 were as follows: Control, n=3; CM-CKO, n=4; Het, n=4; CM-Het, n=4). RNA was extracted using the RNeasy Micro kit (Qiagen) and samples sent to the Australian Genome Research Foundation for labelling and hybridization.


title: Identification of TWIST1 transcriptional targets in the cranial mesoderm [E8_5]

overall_design:
For microarray analysis of CM-CKO embryos, embryo heads of four genotypes were collected at E8.5 (5-7 somites) and E9.5 (18- 20 somites):  CM-CKO (Twist1flox/del; Mesp1Cre/+), CM-Het (Twist1flox/wt; Mesp1Cre/+), Het (Twist1flox/del; Mesp1+/+) and Control (Twist1flox/wt; Mesp1+/+).
Sample sizes for E8.5 embryos were as follows: Control, n=4 CM-CKO, n=4; Het, n=3; CM-Hets, n=3).


title: Gene expression signatures for miR-26a over-expression and negative control in hela cells

status: Public on Aug 17 2016

city: Xi'an

first: Xiang

last: Zhang

address: Changle west road #169

institute: the Fourth Military Medical University

summary: To further development of our gene expression approach to microRNA-26a over-expression, we have employed whole mRNA microarray expression profiling as a discovery platform. Hela cells at 70–80% confluence in 6-well plates were transfected using Lipofectamine 2000 (Invitrogen). Negative control mimics or miR-26a mimics (100nM) were transfected in each well. Cell extracts were prepared 48 h after transfection, total RNA was checked for a RIN number to inspect RNA integration by an Agilent Bioanalyzer 2100 (Agilent technologies, Santa Clara, CA, US).

overall_design: Hela cells at 70–80% confluence in 6-well plates were transfected using Lipofectamine 2000 (Invitrogen). Negative control mimics or miR-26a mimics (100nM) were transfected in each well. Total RNA was prepared 48 h after transfection.

first: Lintao

last: Jia


title: Integrated molecular pathway analysis informs a synergistic combination therapy targeting PTEN/PI3K and EGFR pathways for basal-like breast cancer.

status: Public on Aug 21 2016

city: Lund

first: Lao

last: Saal

address: Scheelevägen 2, MV404B2

department: Department of Oncology and Pathology

institute: Lund University

summary:
Abstract
BACKGROUND: The basal-like breast cancer (BLBC) subtype is characterized by positive staining for basal mammary epithelial cytokeratin markers, lack of hormone receptor and HER2 expression, and poor prognosis with currently no approved molecularly-targeted therapies. The oncogenic signaling pathways driving basal-like tumorigenesis are not fully elucidated.

METHODS: One hundred sixteen unselected breast tumors were subjected to integrated analysis of phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations by immunohistochemistry, mutation analysis, and gene expression profiling. Incidence and relationships between molecular biomarkers were characterized. Findings for select biomarkers were validated in an independent series. Synergistic cell killing in vitro and in vivo tumor therapy was investigated in breast cancer cell lines and mouse xenograft models, respectively.

RESULTS: Sixty-four % of cases had an oncogenic alteration to PIK3CA, PTEN, or INPP4B; when including upstream kinases HER2 and EGFR, 75 % of cases had one or more aberration including 97 % of estrogen receptor (ER)-negative tumors. PTEN-loss was significantly associated to stathmin and EGFR overexpression, positivity for the BLBC markers cytokeratin 5/14, and the BLBC molecular subtype by gene expression profiling, informing a potential therapeutic combination targeting these pathways in BLBC. Combination treatment of BLBC cell lines with the EGFR-inhibitor gefitinib plus the PI3K pathway inhibitor LY294002 was synergistic, and correspondingly, in an in vivo BLBC xenograft mouse model, gefitinib plus PI3K-inhibitor PWT-458 was more effective than either monotherapy and caused tumor regression.

CONCLUSIONS: Our study emphasizes the importance of PI3K/PTEN pathway activity in ER-negative and basal-like breast cancer and supports the future clinical evaluation of combining EGFR and PI3K pathway inhibitors for the treatment of BLBC.

overall_design: Gene expression profiles were generated for 95 breast tumors using Agilent Human 44K v5 microarrays following the manufacturer protocol. Stratagene Universal Human Reference RNA was used as the common control sample.

first: Qing-Bai

last: She

first: Sofia

middle: K

last: Gruvberger-Saal

first: Matthew

last: Maurer

first: Yilun

last: Chen

first: Mervi

last: Jumppanen

first: Tao

last: Su

first: Meaghan

last: Dendy

first: Ying-Ka

middle: I

last: Lau

first: Lorenzo

last: Memeo

first: Hugo

last: Horlings

first: Marc

middle: J

last: van de Vijver

first: Jorma

last: Isola

first: Hanina

last: Hibshoosh

first: Neal

last: Rosen

first: Ramon

last: Parsons


title: Gene expression of developed cancer stem cells [all]

city: Okayama

first: Akimasa

last: Seno

state: Okayama

address: 1-1, Tsushima-Naka, 1-chome, Kita-Ku

department: Applied Chemistry and Biotechnology

country: Japan

institute: Okayama University

summary: RNA expression of human induced cancer stem cells and human induced pluripotent stem cells were analyzed.

overall_design: mRNA expression analysis of cancer stem cells which are induced from human cancer patient tissue cells with defined factors or human iPS cells with a cancer cell culture medium

first: Tetsuya

last: Ishikawa

first: Tomonori

last: Kasai


title: Gene expression of developed cancer stem cells [iPS-CC1]

overall_design: We compared mRNA expression between cancer stem cells (that were induced from human cancer tissue-derived cells with defined factors or that were developed from human iPS cells with a cancer cell-conditioned medium) and human iPS cells.


title: Downregulation of WDR20 due to loss of 14q is involved in the malignant transformation of clear cell renal cell carcinoma

status: Public on Aug 09 2016

city: Yufu

first: Mika

last: Takahashi

address: Idaigaoka 1-1

institute: Oita University

summary: Previously, we have reported that genomic loss of 14q occurs more frequently in high grade clear cell renal cell carcinomas (ccRCCs) than low grade ones and shows a significant impact on the expression levels of genes located on this region, suggesting that the genes located on the region and downregulated by the loss may be involved in the malignant transformation of ccRCCs. Here, among the genes located on the minimal common region of 14q loss, we found that 6 were significantly downregulated in high grade ccRCCs due to copy number loss. Using the data set from The Cancer Genome Atlas (TCGA) Research Network, downregulation of one out of the 6 genes, WDR20, was significantly associated with poorer prognosis for the patients with ccRCC, suggesting that downregulation of WDR20 may be involved in the malignant transformation of ccRCC. In functional assays, exogeneous WDR20 significantly inhibited growth and induced apoptosis in RCC cell lines. Interestingly, the phosphorylation levels of ERK and AKT, which reportedly contribute to the malignant phenotype of RCC cells, were clearly reduced by the exogeneous expression of WDR20. Thus, our data suggest that downregulation of WDR20 due to 14q loss may be involved in the malignant transformation of ccRCCs in part through the activation of ERK and AKT pathways.

overall_design: Downregulated expression levels of genes in minimal common region due to 14q loss. Expression levels of 6 genes were determined by microarray analysis and compared between normal kidney tissues (normal, n=16), low grade (low, n=16) and high grade (high, n=16) ccRCCs. The expression level (log2) normalized by the median expression level for the 16 normal samples.

first: Yoshiyuki

last: Tsukamoto

first: Tomoki

last: Kai

first: Akinori

last: Tokunaga

first: Chisato

last: Nakada

first: Naoki

last: Hijiya

first: Tomohisa

last: Uchida

first: Tsutomu

last: Daa

first: Takeo

last: Nomura

first: Fuminori

last: Sato

first: Hiromitsu

last: Mimata

first: Keiko

last: Matsuura

first: Masatsugu

last: Moriyama


title: Mannose receptor-induced T cell tolerance via interaction with CD45 and up-regulation of CTLA-4

city: Bonn

first: Joachim

last: Schultze

state: NRW

address: Carl-Troll-Strasse 31

department: Genomics and Immunoregulation

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

summary: The MR is an endocytic receptor, which plays an important role in serum homeostasis and antigen presentation. In this study, we firstly describe an important role of the MR as a direct regulator of CD8+ T cell activity. We could demonstrate that the presence of the MR on DCs impaired the cytotoxicity of activated CD8+ T cells both in vitro and in vivo. This regulatory effect was mediated by a direct interaction of the MR with CD45 on the T cells surface, which abolished CD45 activity. MR-mediated suppression of CD45 resulted in the up-regulation of the inhibitory molecule CTLA-4, which in turn was responsible for the reduced T cell activity. MR-mediated inactivation of CD45, up-regulation of CTLA-4 and T cell inactivation could be circumvented by increased signaling via CD28, which was achieved by DC maturation. These implications point out an important role of the MR in maintaining the balance between tolerance and immunity and might have pivotal implications for the development of vaccination strategies aimed at dampening adaptive immunity.

overall_design: DesTCR T cells were incubated with MR-deficient DCs in the presence of FcMR or isotype controls for the indicated time points. Afterwards, CD8+ T cells were isolated by cell sorting (FACSAria), and immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.

first: Verena

last: Schütte

first: Astrid

last: Draffehn

first: Thomas

last: Ulas

first: Sven

last: Burgdorf


title: Heparin promotes cardiac differentiation of human pluripotent stem cells in chemically defined albumin-free medium enabling consistent manufacture of cardiomyocytes

status: Public on Jul 28 2016

city: Bethesda

first: Kory

middle: R

last: Johnson

state: MD

address: 10/3B01, 9000 Rockville Pike

department: DIR IT & Bioinformatics

institute: NINDS/NIH

summary: Cardiomyocytes can be differentiated from human pluripotent stem cells (hPSCs) in defined conditions, but efficient and consistent cardiomyocyte differentiation often requires expensive reagents such as B27 supplement or recombinant albumin. Using a chemically defined albumin-free (E8 basal) medium, we identified heparin as a novel factor that significantly promotes cardiomyocyte differentiation efficiency, and developed an efficient method to differentiate hPSCs into cardiomyocytes. The treatment of heparin helped cardiomyocyte differentiation consistently reach at least 80% purity (up to 95%) from more than 10 different hPSC lines in chemically defined DMEM/F-12 based medium on either Matrigel or defined matrices like Vitronectin and Synthemax. One of heparin’s main functions was to act as a WNT modulator that helped promote robust and consistent cardiomyocyte production. Our study provides an efficient, reliable, and cost-effective method for cardiomyocyte derivation from hPSCs that can be used for potential large-scale drug screening, disease modeling, and future cellular therapies.

overall_design: 12 human pluripotent stem cells (hPSCs) at three different cardiac differentiation times (0 Days, 3 Days, 6 Days, 10 Days) under different culture conditions (+/- Heparin, +/- IWP2).

first: Yongshun

last: Lin

first: Kaari

last: Linask

first: Barbara

last: Mallon

first: Michael

last: Klein

first: Jeanette

last: Beers

first: Wen

last: Xie

first: Yubin

last: Du

first: Chengyu

last: Liu

first: Yinzhi

last: Lai

first: Jizhong

last: Zou

first: Mark

last: Haigney

first: Hushan

last: Yang

first: Mahendra

last: Rao

first: Guokai

last: Chen


title: Oncostatin M (OSM) and Leukemia Inhibitory factor (LIF) treatment of osteoblasts via LIF and OSM receptors

city: Parkville

first: Gordon

last: Smyth

state: Vic

address: 1G Royal Pde

department: Bioinformatics

institute: Walter and Eliza Hall Institute of Medical Research

summary: Oncostatin M (OSM) and Leukemia Inhibitory Factor (LIF) signal within cells via the gp130 (Il6st) coreceptor bound either to the LIF receptor (LIFR) or the oncostatin M receptor (OSMR), but whether murine OSM can act through both receptors is controversial. Both LIF and OSM stimulate bone formation, inhibit adipocyte differentiation, and promote osteoclast differentiation, but our earlier work suggested this may depend on the receptor subtype used. This project aimed to identify those gene targets regulated by murine OSM via OSMR and LIFR by using wild type and OSMR null primary osteoblasts. Cells were differentiated to their most mature state (i.e. osteocytes) because the only prior target gene known to be regulated by murine OSM via the LIFR was an osteocyte-specific gene, sclerostin.

overall_design: Primary calvarial osteoblasts were generated from wild type and OSMR null mice, both on C57BL/6 background (cousin-bred litters), and frozen down for later treatment. On three occasions, WT and OSMR null cells were defrosted, expanded, and differentiated for 17 days in osteoblast differentiation media. At 17 days, when the cells have reached a stage of expressing osteocyte-specific genes, they were treated with human OSM (which acts only through LIFR in mouse cells), mouse LIF (which acts only through LIFR in mouse cells) or murine OSM (which can act through both OSMR and LIFR). RNA was analysed at 1 and 6 hours after commencement of treatment.

first: Natalie

last: Sims

first: Yifang

last: Hu


title: Functional dissection of Bmi1 independence of MN1 leukemia

status: Public on Aug 12 2016

city: London

first: Venu

middle: Madhav

last: Pullabhatla

address: Great Maze Pond

department: Guy's Hospital

country: United Kingdom

institute: Biomedical Research Centre

summary: MN1 leukemia is a poor prognosis leukemia occuring as MN1 overexpression or fusion with TEL (MN1-TEL), MN1 and MN1-TEL show different biology in terms of dependence of known self-renewal associated genes in leukemia, c-kit positive murine primary bone marrow cells were retrovirally transduced with MN1, MN1-TEL or MN1-TEL mutant MN1-TELdelDBD showing biological similarity with MN1, after retroviral transformation of cells and 10 d culture RNA was extracted and gene expression profiling was assessed

overall_design: 3 samples with 3 replicates each sample: gene expression array comparing expression profiles of MN1, MN1-TEL and MN1-TEL del DBD trasformed murine c-kit+ bone marrow cells

first: Jan

last: Mikesch


title: Gene expression of developed cancer stem cells

status: Public on Aug 16 2016

first: Akimasa

last: Seno

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

overall_design: Refer to individual Series


title: YY1 Controls Em-3’RR DNA Loop Formation and Immunoglobulin Heavy Chain Class Switch Recombination.

status: Public on Aug 06 2016

city: Philadelphia

first: daniel

last: beiting

state: PA

address: 380 S. University Ave

department: Pathobiology

institute: University of Pennsylvania

summary: Activation of splenic B cells induces formation of a 220kb DNA loop between Em and 3’RR enhancers in the immunoglobulin heavy chain locus (IgH).  This DNA loop has been proposed to be necessary for the crucial immune diversification mechanism of IgH class switch recombination, but the factors that control its formation are unknown.  We show that conditional deletion of transcription factor YY1 in primary splenic B cells results in a dramatic drop in formation of this DNA loop, as well as immunoglobulin class switch recombination. Reconstitution of YY1-deleted splenic B cells with various YY1 mutants showed that the C-terminal half of YY1 lacking the transactivation domain restored both Em-3’RR DNA loop formation as well as class switch recombination.  RNA transcript analyses of YY1 conditional deleted splenic B cells suggest that YY1 does not regulate genes needed for DNA looping or CSR.  Our results argue for a direct physical mechanism of YY1 mediating long-distance DNA loops and provide strong evidence of the importance of this DNA loop for class switching.  Our results provide foundational mechanistic insight into a crucial immune function.

overall_design: Follicular B cells were isolated from the spleens of three C57Bl/6 yy1 fl/fl mice. For each spleen, half the cells received mock treatment and half received TATCRE. The 6 samples were then grown in RPMI medium along with LPS, Il4, OPI, and 20% FBS for 72 hours. The 6 groups of cells were lysed and RNA was isolated for library preparation. Expression differences between Mock and TATCRE treated cells were determined to understand the role of yy1 in B cell class switching.

first: Daniel

last: Beiting

first: Michael

last: Atchison

first: Corbett

last: Berry

first: Arindam

last: Basu


title: Gene expression of developed cancer stem cells [iPS-GC1]

first: Tetsuya

last: Ishikawa


title: Gene expression in peripheral blood mononuclear cells from healthy control and autistic infants

status: Public on Aug 01 2016

city: Kyoto

first: Ryo

last: Inoue

address: 1-5, Hangi-cho, shimogamo

institute: Kyoto Prefectural University

summary: Whole blood was collected from healthy and autistic infants and peripheral blood mononuclear cells (PBMC) were isolated. Transcriptional profile in PBMCs was compared between healthy and autistic infants.

overall_design: Comparison: healty control infants vs autistic infants. Biological replicates; 4 control infants and 4 autistic infants.

first: R

first: T

last: Tsukahara


title: Genome-wide analysis of gene expression changes in mouse subcutaneous adipose tissue in cold compared to thermal neutrality

status: Public on Jul 27 2016

city: Dallas

first: Yi

last: Zhu

address: 5323 Harry Hines Boulevard, L5.210

department: Internal Medicine

institute: UT Southwestern

summary: Comparison of gene expression pattern of subcutaneous adipose tissue from mice housed in cold (6-degree Celsius) or in thermal neutrality (30-degree celsius).Verify canonical white adipose tissue beiging pathways and genes that are regulated by cold-exposure as well as identify gap junction genes that are regulated by cold in white adipoes tissue.

overall_design: Total RNA obtained from mouse subcutaneous tissue from mice house at two different temperature; RNA extracted from 3-4 mice was pooled into one sample.

first: Philipp

last: Scherer


title: Suppression of antitumor immunity by the oncometabolite 2-hydroxyglutarate

city: Heidelberg

first: Lukas

last: Bunse

address: Im Neuenheimer Feld 280

institute: DKFZ

summary: Isocitrate dehydrogenase (IDH) mutations, a hallmark of gliomagenesis, result in the production of the oncometabolite R-2-hydroxyglutarate (R-2-HG) which is thought to promote tumorigenesis via DNA methylation. Here we identify an additional immunosuppressive activity of R-2-HG: Tumor cell-derived R-2-HG is taken up by T-cells where it induces a strong and immediate perturbation of calcium- and ATP-dependent signaling events, and polyamine biosynthesis. This results in a profound suppression of antigen-specific T-cell activation and effector cytokine production in experimental mouse and human systems. In a large cohort of WHO grade II and III gliomas, IDH1 mutant tumors display reduced infiltration by T-cells compared to IDH1 wildtype tumors. Spontaneous and induced mutation-specific antitumor immunity to syngeneic IDH1-mutant tumors in MHC-humanized mice is improved by isolated genetic ablation of the neomorphic enzymatic function of mutant IDH1. Taken together, these data attribute a novel, fundamentally non-tumor-cell-autonomous role of an oncometabolite in shaping the tumor immune microenvironment.

overall_design: We investigated the effects of exogenous R-2-HG on primary human T cells.

first: Theresa

first: Stefan

last: Pusch

first: Felix

last: Sahm

first: Khwab

last: Sanghvi

first: Dalia

last: Alansary

first: Mirco

last: Friedrich

first: Anna

last: Berghoff

first: Kelly

last: Marsh

first: Mya

last: Steadman

first: Dongwei

first: Benedikt

last: Wiestler

first: Edward

last: Green

first: Simone

last: Karcher-Bausch

first: Iris

last: Oezen

first: Katrin

last: Deumelandt

first: Jana

last: Sonner

first: Gernot

last: Poschet

last: Weller

first: Matthias

last: Preusser

first: Minou

last: Nadji-Ohl

first: Axel

last: Benner

first: Jürgen

last: Okun

first: Barbara

last: Niemeyer

first: Marion

last: Dorsch

first: Andreas

last: von Deimling

first: Wolfgang

last: Wick

last: Platten


title: Gene expression in mouse thyrotrope adenoma: transcription elongation factor stimulates proliferation

status: Public on Aug 05 2016

city: Ann Arbor

first: Sally

middle: Ann

last: Camper

address: 1241 Catherine St

department: Human Genetics

institute: University of Michigan

summary: Differential gene expression study comparing choriogonadotropin alpha (Cga) gene deficient and wild type adult mouse pituitary. Thyrotrope hyperplasia and hypertrophy are common responses to primary hypothyroidism.  To understand the genetic regulation of these processes, we studied gene expression changes in the pituitaries of Cga-/- mice, which are deficient in the common alpha subunit of TSH, LH and FSH.  These mice have thyrotrope hypertrophy and hyperplasia and develop thyrotrope adenoma.  We report that cell proliferation is increased, but the expression of most stem cell markers is unchanged.  The alpha subunit is required for secretion of the glycoprotein hormone beta subunits, and mutants exhibit elevated expression of many genes involved in the unfolded protein response, consistent with dilation and stress of the endoplasmic reticulum.  Mutants have elevated expression of transcription factors that are important in thyrotrope function, such as Gata2 and Isl1, and those that stimulate proliferation, including Nupr1, E2f1 and Etv5.  We characterized the expression and function of a novel, over-expressed gene, transcription elongation factor A (SII)-like 5 (Tceal5).  Stable expression of Tceal5 in a pituitary progenitor cell line is sufficient to increase cell proliferation.  Thus, Tceal5 may act as a proto-oncogene.  This study provides a rich resource for comparing pituitary transcriptomes and an analysis of gene expression networks.

overall_design: Total RNA was obtained from 8 week old Cga-deficient and littermate wild type mouse pituitary tissue. Total sample number was 24 as follows: 6 male and 6 female wild types, 6 male and 6 female mutants. Each sample was applied to an individual microarray.

first: Peter

last: Gergics

first: Helen

last: Christian

first: Monica

last: Choo

first: Adnan

last: Ajmal


title: Gene expression profiles of livers and liver tumors from mice fed high-fat diet and high fructose-glucose solution for 52 weeks

status: Public on Jul 25 2016

first: Yujin

last: Hoshida

state: TX

address: 5323 Harry Hines Blvd

institute: University of Texas Southwestern Medical Center

summary: The lack of a preclinical model of nonalcoholic steatohepatitis (NASH) and hepatocellular cancer (HCC) that recapitulates human disease is a major barrier to therapeutic development. We report a high fat-high sugar diet-induced NASH and HCC in a stable isogenic 129S1/SvImJ crossed with C57Bl/6J mice. Following diet initiation, there was sequential development of steatosis (4-8 weeks), steatohepatitis with ballooning and Mallory-Denk bodies (12-16 weeks), progressive fibrosis (16 week onwards) and spontaneous HCC (32-52 weeks). The mice developed obesity, insulin resistance and dyslipidemia. There was concordance with the human NASH transcriptome (FDR 0.001) with activation of lipogenic, inflammatory and apoptotic pathways relevant in humans. The HCC gene signature resembled S1 and S2 human HCC subclass (FDR 0.01 for both). This simple model of NASH and HCC that resembles human disease in terms of its triggers, physiological and biochemical parameters, histology, transcriptomic profile, and outcomes can facilitate preclinical development for these conditions.

overall_design: 129S1/SvImJ;C57Bl/6J (129/B6) mice were fed with high-fat diet (Western Diet) and high fructose-glucose solution (Sugar Water) (WD SW) or chow diet (CD) for 52 weeks, and total RNA samples were isolated from liver and tumor tissues for genome-wide expression profiling.

first: Amon

last: Asgharpour

first: Sophie

last: Cazanave

first: Arun

last: Sanyal


title: Gene expression profiles of livers from mice fed high-fat diet and high fructose-glucose solution for 8 weeks

overall_design: 129S1/SvImJ;C57Bl/6J (129/B6) mice were fed with high-fat diet (Western Diet) and high fructose-glucose solution (Sugar Water) (WD SW) or chow diet (CD) for 8 weeks, and total RNA samples were isolated from liver tissues for genome-wide expression profiling.


title: Therapeutic properties of Scutellaria baicalensis measured in genome-wide expression

status: Public on Jul 26 2016

city: Daejeon

first: Bu-Yeo

last: Kim

address: 1672 Yuseongdae-ro, Yuseong-gu

department: Herbal Medicine Research Division

country: South Korea

institute: Korea Institute of Oriental Medicine

summary: This study was designed to measure expressional profile induced by temporal treatment with Scutellaria baicalensis in HepG2 cells.

overall_design: Time-dependent expression of genes by treatment of Scutellaria baicalensis was measured on HepG2 cells. Total RNA  was isolated and was subject to single channnel microarray.


title: Identification of baseline gene expression signatures predicting therapeutic responses to three biologic agents in rheumatoid arthritis: a retrospective observational study

status: Public on Jul 21 2016

city: Minato-ku

first: Seiji

last: Nakamura

state: Tokyo

address: 1-15-1, Kaigan, Suzuebaydium 5F

institute: DNA Chip Research Inc.

summary: The aim of this study was to identify the specific molecular biological features predicting the therapeutic outcomes of three bDMARDs, infliximab (IFX), tocilizumab (TCZ), and abatacept (ABT) by studying blood gene expression signature of patients prior to biologic treatment in a unified test platform. GSEA analyses showed that inflammasome genes were significantly upregulated in IFX’s NON-REM compared with its REM. In TCZ’s REM, B cell-specifically expressed genes were upregulated. RNA elongation, apoptosis-related, and NK cell-specifically expressed genes were upregulated in ABT’s NON-REM.

overall_design: RA patients who responded inadequately to methotrexate and were later commenced with any one of IFX (n=140), TCZ (n=38), and ABT (n=31) as their first biologic between May 2007 and November 2011 were enrolled. Whole blood gene expression data were obtained prior to their biologic administration. They were defined as remission and non-remission groups, according to CDAI at 6 months of biologic therapy.

first: Katsuya

last: Suzuki

first: Hiroshi

last: Iijima

first: Yuko

last: Hata

first: Chun

last: Lim

first: Yohei

last: Ishizawa

first: Hideto

last: Kameda

first: Koichi

last: Amano

first: Kenichi

last: Matsubara

first: Ryo

last: Matoba

first: Tsutomu

last: Takeuchi


title: Gene array data of tumour draining lymph node fibroblastic reticular cells (FRCs)

status: Public on Jul 11 2016

city: Cambridge

first: Angela

last: Riedel

address: Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus

department: MRC Cancer Unit

institute: University of Cambridge

summary:
Lymph node (LN) stromal cells, particularly fibroblastic reticular cells (FRCs), provide critical structural support and regulate immunity, tolerance and transport properties of LNs. In many tumors, LN metastasis is predictive of poor prognosis, however, stromal contribution to the evolving microenvironment of tumor draining LNs (TDLN) remains poorly understood. Here we present comparative transcriptional data of resting and TDLN FRCs after different time points of tumor drainage.
FRCs were isolated from lymph nodes and FACS sorted based on the expression of CD45-, CD31- and PDPN+

overall_design: FRCs were pooled per animal of 2 brachial LNs and gene array analysis was performed on triplicates

first: Jacqui

last: Shields


title: Remodeling of synaptic transmission genomic fabrics in the hypothalamic arcuate nucleus of a rat female model of infantile spasms

status: Public on Jul 20 2016

city: Prairie View

first: Dumitru

middle: Andrei

last: Iacobas

address: Ann Preston St

department: Undergraduate Medical Academy

institute: Prairie View A&M University

summary: We profiled the whole transcriptomes of female rat hypothalamic arcuate nuclei to determine the remodeling of the genomic fabrics responsible for the glutamatergic, GABAergic, dopaminergic, cholinergic and serotonergic transmission in epilepsy and recovery following different treatments. The rats were prenatally exposed (G15) to betamethasone (or just saline for control) followed by repeated adiministration of N-Methyl-D-Aspartic acid (NMDA) on postnatal days 12, 13 and 15 which triggered infantile spasms. Pups were treated with either ATCH, PMX53 (a potent C5ar1 antagonist) or saline to act as a control, on days 13, 14 and 15 prior to NMDA administration to determine what effects each treatment had on transcriptome recovery. Our Genomic Fabric Paradigm (GFP) is proposed as a transformative research approach to enhance the understanding of the brain transcriptomic alterations in epileptic rats and recovery following various treatments. The genomic fabric of a particular synapse is the structured transcriptome associated with the most interconnected and stably expressed gene network responsible for that type of neurotransmission. GFP refines the description of functional pathways by selecting the most prominent genes and determining their networking.  Moreover, it quantifies the remodeling of functional pathways and their interplay in disease and recovery in response to a treatment. We found that priming with betamethasone had substantial consequences on the topology of the genomic fabrics of all kind of synaptic transmission and that NMDA-induced spasms strongly exacerbated the remodeling of these fabrics. Contrary to our findings in male rats, neither ACTH or PMX53 treatment recovered the normal synaptic transcriptomes.

overall_design:
One tissue (hypothalamic arcuate nucleus) x two prenatal exposures (B = betamethasone, S = saline) x two conditions for the betamethasone expossed rats (with (Y) without (N) infantile spasms) x three postnatal treatments (A = ACTH, P = PMX53, S = saline) x one sex (F) . Biological replicates: 4 ASNSF, 4 ABNSF, 4 ABYSF, 4 ABYAF, 4 ABYPF.
Please note that a the multiple yellow strategy has been adopted, in which differently labeled biological replicas are cohybridized, similarly labeled samples of distinct conditions are compared and the results of the green and red comparisons are averaged.

middle: A

first: Tamar

last: Chachua

first: Sanda

first: Melissa

last: Benson

first: Karin

last: Borges

first: Jana

last: Velíšková

first: Libor

last: Velíšek


title: Haemopedia: An Expression Atlas of Murine Haematopoietic Cells

status: Public on Jul 17 2016

city: Melbourne

first: Jarny

last: Choi

state: Victoria

address: The University of Melbourne

department: Anatomy and Neuroscience

institute: Centre for Stem Cell Systems

summary: Haematopoiesis is a multi-stage process that involves the differentiation of multipotent stem cells and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, a comprehensive atlas of murine gene expression data that covers all the mature lineages in haematopoiesis, including rare cell populations such as eosinophils, mast cells, basophils and megakaryocytes and a large collection of progenitor and stem cells. We have used this dataset to identify gene sets with specifically enriched expression in each of the mature blood cell lineages. Many of the genes in these sets show conserved lineage-enriched expression patterns in human haematopoiesis. We also identify some genes with divergent expression patterns between mouse and human, highlighting species specific differences in blood cell production. To make analyses of Haemopedia and other blood cell transcriptional datasets easier, we have created an online web portal, Haemosphere, which provides simple tools to interrogate gene expression-based relationships between haematopoietic cell types and genes of interest.

overall_design: Total RNA was obtained from 54 haematopoetic cells types and 8 non-haematopoietic out groups.

first: Carolyn

last: de Graaf

first: Tracey

middle: M

last: Baldwin

first: Douglas

last: Hilton


title: IL-4 and IL-13 treatment of murine hepatic progenitor cells

status: Public on Jul 08 2016

first: Richard

middle: Lee

last: Gieseck

address: 4 Memorial Drive

department: NIAID

institute: NIH

summary: The goal of this study was to determine the response of murine hepatic progenitor cells to the type 2 cytokines IL-4 and IL-13.

overall_design: 12 samples were analyzed. 4 controls samples, 4 IL-4 samples, and 4 IL-13 samples.

first: Thirumalai

last: Ramalingam

first: Kevin

last: Hart

last: Vannella

first: David

last: Cantu

first: Wei-Yu

last: Lu

first: Sofia

last: Ferreira-Gonzalez

first: Stuart

last: Forbes

first: Ludovic

last: Vallier

first: Thomas

last: Wynn


title: A preclinical mouse model of nonalcoholic steatohepatitis and hepatocellular cancer that mimics human disease

first: Yujin

last: Hoshida


title: Plasmodium falciparum blood stage parasites: control vs PfTRF-depleted parasites

status: Public on Jul 14 2016

city: Basel

first: Till

middle: Steffen

last: Voss

address: Socinstrasse 59

department: Medical Parasitology and Infection Biology

country: Switzerland

institute: Swiss Tropical and Public Health Institute

summary: Transcriptional profiling of transgenic Plasmodium falciparum blood stage parasites expressing the telomere repeat-binding factor PfTRF as a C-terminal GFP-DD fusion (3D7/TRFGFP-ON). The DD (FKBP destabilisation domain) allows for the conditional depletion of fusion proteins in absence of the stabilising ligand Shield-1 (Banaszynski LA, Chen LC, Maynard-Smith LA, Ooi AG, Wandless TJ. A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules.Cell. 2006 Sep 8;126(5):995-1004). The goal of this experiment was to identify genes differentially expressed in response to PfTRF depletion.

overall_design: P. falciparum strain 3D7 parasites expressing endogenous PfTRF-GFP-DD were grown in presence of 4nM WR/625nM Shield-1 (3D7/TRFGFP-ON) or 4nM WR (3D7/TRFGFP-OFF). RNA extracted from these samples at four (3D7/TRFGFP-ON) and five (3D7/TRFGFP-OFF) consecutive time points each was processed for microarray analysis.

first: Nicole

last: Bertschi

first: Christa

last: Toenhake

first: Angela

last: Zou

first: Igor

last: Niederwieser

first: Rob

last: Henderson

first: Suzette

last: Moes

first: Paul

last: Jenoe

first: John

last: Parkinson

last: Bartfai

middle: S


title: FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation

status: Public on Jun 23 2016

city: Cardiff

first: Anne

last: Rosser

state: SOUTH GLAMORGAN

address: Museum Ave

institute: Cardiff University

summary: To understand the developing striatum, key genes during development were identified using microarray analsyis tha could be considered as marker of medium spiny neurons.  The ages studied is at peak striatal neurogenesis.

overall_design: 3 different gestational ages of CD1 mice were used with triplicate repeats

first: Sophie

middle: V

last: Precious

first: Claire

last: Kelly

first: Ngoc-Nga

last: Vinh

first: Amy

middle: E

last: Evans

first: Vladamir

last: Pekarik

first: Caroline

last: Scherf

first: Ragavan

last: Jeysingham

first: James

last: Glasbey

first: Monika

last: Holeiter

first: Lesley

last: Jones

first: Micheal

last: Taylor


title: Differential production of Type I IFN determines the reciprocal levels of IL-10 and proinflammatory cytokines produced by C57BL/6 and BALB/c macrophages

status: Public on Sep 07 2016

first: Christina

last: Taubert

address: The Ridgeway

institute: The Francis Crick Institute, MH

summary: Pattern recognition receptors (PRR) detect microbial products and induce cytokines which shape the immunological response. Interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-α) and IL-1β are proinflammatory cytokines which can be essential for resistance against infection, but if produced at high levels, may contribute to immunopathology. In contrast, IL-10 is an immunosuppressive cytokine which dampens proinflammatory responses, but can also lead to defective pathogen clearance. The regulation of these cytokines is therefore central to the generation of an effective but balanced immune response. Here, we show that macrophages derived from C57BL/6 mice produce low levels of IL-12, TNF-α and IL-1β, but high levels of IL-10 in response to TLR4 and TLR2 ligands LPS and PamCSK4, and Burkholderia pseudomallei a Gram-negative bacterium which activates TLR 2/4. In contrast, macrophages derived from BALB/c mice show a reciprocal pattern of cytokine production. Differential production of IL-10 in B. pseudomallei and LPS stimulated C57BL/6 and BALB/c macrophages was due to a type I IFN dependent, but IL-27 independent mechanism. Further, type I IFN contributed to differential IL-1β and IL-12 production in B. pseudomallei and LPS stimulated C57BL/6 and BALB/c macrophages, via both IL-10-dependent and independent mechanisms. These findings highlight key pathways responsible for the regulation of pro- and anti-inflammatory cytokines in macrophages and reveal how they may differ according to the genetic background of the host.

overall_design: Total RNA obtained from bone-marrow derived macrophages of C57BL/6 WT, C57BL/6 Ifnar1-/- and BALB/c mice stimulated with heat-killed Burkholderia pseudomallei or media as controls.

first: Ashleigh

last: Howes

first: Simon

last: Blankley

first: Natasha

last: Spink

first: Xuemei

last: Wu

first: Christine

last: Graham

first: Jiawen

last: Zhao

first: Margarida

last: Saraiva

first: Paola

last: Ricciardi-Castagnoli

first: Gregory

last: Bancroft

last: O'Garra


title: Genome-wide analysis of gene expression of mouse ovarian cancer cell lines generated in vivo and in vitro

status: Public on Jun 30 2016

city: Pittsburgh

first: Anda

last: Vlad

address: 204 Craft Ave

department: Ob-Gyn

institute: University of Pittsburgh

summary: Mouse ovarian cancer cells lines were generated from primary tumor tissues, metastatic tumor tissues and in vitro cultured ovarian bursa cells. Gene transcripts from the whole genome were tested using WG6 microarray to compare gene expression level of cells lines with and without Epithelial to Mesenchymal Transition(EMT).

overall_design: Total RNAs were isolated from different cell lines with two time points for each cell line and compare the differentially expressed genes in cell lines with different biological characteristics.

first: Lixin

last: Zhang

first: Tianzhou

last: Ma


title: Genoma-wide analysis of pro- and anti-inflammatory activation states in primary microglia.

status: Public on Jun 19 2016

city: Bonn

first: Joachim

last: Schultze

address: Carl-Troll-Strasse 31

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

summary:
Murine primary microglia were treated with different inflammatory stimulants to induce different activation states and analyze the associated transcriptional changes.
Abstract: Microglia, the immune cells of the CNS, are highly adaptive cells that can acquire different pro- and anti-inflammatory activation states with distinct functions in CNS homeostasis and pathologies. To study microglial function in vitro, primary microglia or immortalized cell lines are commonly used. An alternative to these cells are embryonic stem cell-derived microglia (ESdM). ESdM have previously been shown to be very similar to primary microglia in terms of expression profiles and surface molecules. In this study, ESdM and primary microglia were treated with different inflammatory stimulants to analyze their ability to adopt different activation states. Using quantitative real time PCR, comparative transcriptomics, ELISA, and flow cytometry, we found that different activation states can be induced in ESdM, which are similar to those found in primary microglia. These states are characterized by specific sets of inflammatory marker molecules and differential transcriptome signatures. Our results show that ESdM are a valuable alternative cell model to study microglial functions and neuroinflammatory mechanisms.

overall_design: Primary microglia were treated with either IL-4, TGFb, LPS/IFNg, or left untreated. Each stimulation was analyzed in duplicates or triplicates.

first: Eva

middle: C

last: Beins

first: Svenja

last: Ternes

first: Thomas

last: Ulas

first: Harald

last: Neumann

middle: L

first: Andreas

last: Zimmer


title: Genome-wide analysis of LPS-responsive gene expression by microglia cells in Ntg and LRRK2KO mouse brain

status: Public on Jun 22 2016

city: Bethesda

last: Sun

address: 35 Convent Drive

institute: NIH/NIA

summary: Analysis of LRRK2-regulation of microglia responce to the LPS at gene expression level. The hypothesis tested in the present study was whether LRRK2 influence the microglial phagocytosis- and neuroinflammation- related gene expression at mRNA level.

overall_design: Total RNA obtained from microglia cells isolated from Ntg or LRRK2KO mouse brain subjected to  6 or 24 hours of LPS treatment in vitro

first: Cai

last: Huaibin

first: Ma

last: Bo

first: Sun

last: Lixin

first: Ding

last: Jinhui


title: Gene expression in macrophages in response to Acetylated-LDL (Ac-LDL)

status: Public on Jun 21 2016

city: New Haven

first: Yajaira

last: Suarez

state: Connecticut

address: 10 Amistad Street

department: Comparative Medicine

institute: Yale University School of Medicine

summary:
Analysis of mouse thioglycollate-elicited peritoneal macrophages incubated in presence of acetylated low density lipoprotein (Ac-LDL) (120 μg/ml) for 24 h vs. mock-treated controls.
Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Angiopoietin-like protein 4 (ANGPTL4) is the most up-regulated gene in foamy macrophages and its absence in hematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis.

overall_design: Total RNA isolated from mouse thioglycollate-elicited peritoneal macrophages incubated in presence of Acetylated-LDL (120 μg/ml) for 24 h vs. mock-treated controls.


title: Genome-wide analysis of ex vivo gene expression of tumour pericytes and tumour endothelial cells obtained from 67NR mouse primary tumors

status: Public on Jul 06 2016

city: London

first: Clare

last: Isacke

address: 237 Fulham Road

department: Breast Cancer Now

institute: Institute of Cancer Research

summary: Pericytes are integral components of the tissue vasculature and have essential functions in tumour angiogenesis. Endosialin (CD248) is a type I transmembrane glycoprotein highly expressed on pericytes in the tumour vasculature of most solid tumours, however it is low or negligibly expressed on normal tissue pericytes. Experiments using wild-type and endosialin-knockout mice has revealed that stromal endosialin expression facilitates intravasation of tumor cells from the primary tumor into the circulation, thereby promoting metastatic dissemination.

overall_design: BALB/c Ub-GFP wild-type and endosialin-knockout mice were inoculated with 67NR tumor cells. Tumor pericytes and tumor endothelial cells were isolated from primary tumors by FACSorting and total RNA was extracted from freshly isolated (i.e. without in vitro culture) cell populations.

first: Carmen

last: Viski


title: Genoma-wide analysis of pro- and anti-inflammatory activation states in embryonic stem cell-derived microglia

summary:
Embryonic stem cell derived microglia (ESdM) were treated with different inflammatory stimulants to analyze their ability to adopt different activation states.
Abstract: Microglia, the immune cells of the CNS, are highly adaptive cells that can acquire different pro- and anti-inflammatory activation states with distinct functions in CNS homeostasis and pathologies. To study microglial function in vitro, primary microglia or immortalized cell lines are commonly used. An alternative to these cells are embryonic stem cell-derived microglia (ESdM). ESdM have previously been shown to be very similar to primary microglia in terms of expression profiles and surface molecules. In this study, ESdM and primary microglia were treated with different inflammatory stimulants to analyze their ability to adopt different activation states. Using quantitative real time PCR, comparative transcriptomics, ELISA, and flow cytometry, we found that different activation states can be induced in ESdM, which are similar to those found in primary microglia. These states are characterized by specific sets of inflammatory marker molecules and differential transcriptome signatures. Our results show that ESdM are a valuable alternative cell model to study microglial functions and neuroinflammatory mechanisms.

overall_design: Embryonic stem cell-derived microglia were treated with either IL-4, TGFb, LPS/IFNg, or left untreated. Each stimulation was analyzed in triplicates.


title: Effect of H2O2 treatment on gene expression of islet derived hybrid cell of 1.1B4

status: Public on Jun 16 2016

first: Yuzuru

last: Otsuka

department: Department of Nutrition

institute: Toita Women's College

summary:
We analyzed the comprehensive gene expression changes by H2O2 in pancreatic beta-cell derived 1.1B4 cells using Agilent microarray. The genes of 2903 H2O2 treated were up-regulated and 2283 genes were down-regulated compared with control sample.
HMOX1, EGR1, IGF, IL8 and NR4A3 were strongly up-regulated

overall_design: Gene regulation associated with antioxidant defense system in pancreatic beta cells still needs to be elucidated, we analyzed the genes expression with Agilent micro-array after 4 hours of 100mM H2O2 treatment by one color method, and found 2903 genes were up-regulated and 2283 genes were down regulated. Changes of some genes expressions were confirmed by real time PCR.

first: Mitsuru

last: Takahashi


title: Aging and atherosclerosis

status: Public on Jun 07 2016

first: Hailong

last: Meng

state: CT

address: 300 George Str

institute: Yale University

summary: To examine gene expression in young and aged aortas with and without atherosclerosis

overall_design: Comparison of the aortas of young (2-4 months of age) and aged (12-13 months of age) mice. WT= wild type, KO = LDLr deficient. HDF= high fat diet. CHOW= chow diet

first: Daniel

last: Goldstein

first: Steven

last: Kleinstein


title: Genome-wide analysis of PPARg regulated gene expression in adipose progenitor cells

status: Public on Jun 08 2016

city: dallas

first: Jonathan

middle: m

last: graff

state: tx

address: 6000 harry hines blvd

institute: ut southwestern medical center

summary: Analysis of PPARg targets in adipose progenitor cells at gene expression level. The hypothesis tested in the present study was that PPARg control adipose nichenenesis and niche occupancy through regulating downstream targets in adipose progenitors. Results provide important information of the response of PPARg deletion in adipose progenitor cells, such as specific up- or down-regulated genes involved in cellular adhesion, chemotaxis and mural cell to endothelial interactions.

overall_design: Total RNA obtained from flow sorted GFP+ cells and GFP- cells of pparg null adipose tissue compared to pparg het adipose tissue.

first: Yuwei

last: Jiang

last: Berry

last: Graff


title: Transcriptome analysis of differentiating C2C12 mouse myoblasts (ATCC, Lot 59501261) with knock-down of NET39, TMEM38A, TMEM214 and WFS1.

status: Public on Jun 17 2016

city: Edinburgh

first: Jose

middle: Ignacio

last: de las Heras

address: Max Born Crescent

department: Wellcome Trust Centre

institute: University of Edinburgh

summary: The nuclear envelope transmembrane proteins (NETs) NET39/PPAPDC3, TMEM38A, TMEM214 and WFS1 are expressed or localise preferentially to the nuclear envelope in muscle cells. We knocked these proteins down using specific shRNAs and studied their effect in the diffentiation of the mouse C2C12 myoblast cell line.

overall_design: Total RNA was isolated from C2C12 myoblasts at d0 and d6 post induction of differentiation by the addition of medium with 2% horse serum 48h post-confluency, replacing the medium every 48h up to 144h (6 days) post-induction. 1 µM Tetrodotoxin was added to media 72 h post-induction. Control and NET knockdown myoblast cell lines were generated by transduction of shRNA-encoding lentiviruses targetting  the four NETs studied or a non-target shRNA. An additional 'untransduced' control was used to monitor for possible effects of the transduction protocol.

first: Michael

last: Robson

first: Eric

last: Schirmer


title: Feasibility of unbiased RNA profiling of colorectal tumors: a proof of principle.

status: Public on Jun 15 2016

city: Jerusalem

first: Vardit

last: Moshayoff

address: Hadassaah Medical Center, Ein Kerem

country: Israel

institute: BioMarCare technology

summary:
Liquid biopsy profile which can screen for early CRC. We aimed to depict the profile of early stage CRC as well as for advanced adenomas by combination of current molecular knowledge with microarray technology, using efficient circulating free RNA purification from blood and RNA amplification technologies.
Circulating free RNA profile of plasma from colorectal cancer patients, advanced adenomas and healthy colonoscopia subjects.

overall_design:
Plasma was drawn from 3 healthy colonoscopia subjects, 4 adanced adenomas subjects and 3 colorectal cancer patients. Circulating free RNA was purified from plasma samples and applied on GeneChip human 1.0 ST Arrays.
The 'HuGene_1_0_green_yelow_red_DATASET.xlsx' and 'probe_level_expression_matrix.txt' files contain the primary data that was used to draw the conclusions of the current study.  Please note that exon-level' analysis was performed but NO probe summarization to probeset was performed, therefore both data matrices contains non-unique identifiers.

first: Ouriel

last: Faktor

first: Giuseppe

last: Celesti

first: Luigi

last: Laghi

first: Dan

last: Keret

first: Dana

last: Cohen

first: Eran

last: Israeli


title: CX3CR1/Fractalkine receptor expression separates memory CD8+ T cells with distinct functional profiles (expression)

status: Public on Jun 10 2016

first: Joachim

last: Schultze

department: Genomics and Immunoregulation

summary: Memory T cells are important for protective immunity against infectious microorganisms. Such protection is achieved by cooperative action of memory T cell populations that differ in their tissue localization and functionality. We report on the identification of the fractalkine receptor CX3CR1 as marker for stratification of memory T cells with cytotoxic effector function from those with proliferative function in both, mice and man. Based on CX3CR1 and CD62L expression levels four distinct memory T cell populations can be distinguished based on their functional properties. Transcriptome and proteome profiling revealed that CX3CR1 expression was superior to CD62L to resolve memory T cell functionality and allowed determination of a core signature of memory T cells with cytotoxic effector function. This identifies a CD62Lhi CX3CR1+ memory T cell population with an identical gene signature to CD62LlowCX3CR1+ effector memory T cells. In lymph nodes, this so far unrecognized CD62LhiCX3CR1+ T cell population shows a distinct migration pattern and anatomic positioning compared to CD62LhiCX3CR1neg TCM. Furthermore, CX3CR1+ memory T cells were scarce or absent during chronic HBV, HCV and HIV infection in man and chronic LCMV infection in mice confirming the value of CX3CR1+ in understanding principles of protective immune memory.

overall_design: CD8+ T cells were isolated and directly assessed or incubated with DC or LSEC. After harvesting, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.

first: J

middle: P

last: Böttcher

first: M

last: Beyer

last: Sander

first: P

last: Knolle


title: Downregulation of miR-15b is associated with increased SIRT4 expression in premature senescence and photoaging of the skin

city: Duesseldorf

first: Antje

last: Lindecke

address: Universitaetsstr. 1

department: BMFZ

institute: Universitaet Duesseldorf

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

summary:
Sirtuins are deacetylases or ADP-ribosyltransferases which are implicated in multiple pathways involved in metabolism and life-span regulation. Here, we link the mitochondrial sirtuin SIRT4, which overexpression negatively impacts on mitochondrial oxidative capacity, with premature senescence and skin aging. Accordingly, SIRT4 mRNA levels were significantly increased in vitro in human dermal fibroblasts after repetitive UVB exposure or in senescence triggered by mitotic spindle stress or ionizing radiation. Similarly, analysis of SIRT4 expression in vivo in human skin revealed upregulation of SIRT4 mRNA levels in the dermal compartment of photaged skin as compared with the dermis of intrinsically aged skin. In all our in vitro models, upregulation of SIRT4 expression was associated with decreased levels of miR-15b.
Also, in human skin, highest copy numbers of miR-15b mRNA were detected in the epidermis, and epidermal expression was significantly reduced in photoaged skin as compared with intrinsically aged skin. Reduced miR-15b expression is most likely causally linked to increased SIRT4 expression because we found that (i) miR-15b displays a conserved and direct binding site within the 3'-untranslated region of the SIRT4 gene as demonstrated by luciferase reporter assays and (ii) transfection of oligonucleotides mimicking miR-15b function was sufficient to prevent SIRT4 upregulation in senescent cells in vitro. Thus, we propose that miR-15b acts as a negative regulator of SIRT4 expression to antagonize mitochondrial dysfunction and hence cellular senescence as well as tissue aging, in particular photoaging of the skin.

overall_design:
MCF7 cells were transfected with a control shRNA or Tacc3 shRNA, respectively. The expression of the shRNA were controled via DOX treatment. All experiments were done in 4 independent replicates [GSM1113279-GSM1113290]

The effect of Tacc3 depletion on the expression level of miRNA's were measured [GSM1129017-GSM1129023].

MCF7 breast carcinoma cells were exposed to gammaIR (20 Gy). After irradiation, cells were cultured for 4 and 6 days. The effect of irradiation on the gene expression were measured [GSM1129024-GSM1129031].

first: Fabian

last: Kuck

first: Karl

last: Köhrer

first: Roland

last: Piekorz


title: Molecular subtypes in pancreatic adenocarcinoma [pancreatic cancer cell lines]

status: Public on Jun 01 2016

city: Santa Monica

first: Habib

last: Hamidi

state: CA

address: 2825 Santa Monica Blvd., Suite 200

institute: UCLA

summary: The goal of the study was to examine the transcriptional profile of pancreatic cancer cell lines and assess if the molecular subtypes observed in tumor samples were represented in existing cell line models.  Cell line models allow us to investigate if the molecular subtype observed in tumor have unique sensitivity profiles to anticancer drugs.

overall_design: 29 pancreatic cancer cell lines were compared to a mixed reference pool of 30 pancreatic cancer cell lines to identify cell line specific gene expression.

first: Charles

last: Ginther

first: Lee

last: Anderson

first: Eddie

last: Garon

first: Peter

last: Schirmacher

first: Frank

last: Bergmann

first: Hsiao-Wang

last: Chen

first: Sarah

last: Dry

first: Ann

last: Mongan

first: Kim

last: Quon

first: Steve

last: Pandol

first: Dennis

middle: J

last: Slamon

first: Richard

last: Finn


title: Cross-talk between 4-1BB and TLR1-TLR2 signaling in CD8+ T cells regulates TLR2’s costimulatory effects

status: Public on Jun 14 2016

city: New Orleans

first: Jovanny

last: Zabaleta

state: LA

address: 1700 Tulane Ave

department: Interdisciplinary Oncology

institute: LSUHSC

summary: The activation of TLR-MyD88 (Toll like receptor- Myeloid differentiation factor 88) signaling within T cells functions as a potent costimulatory signal that boosts antitumor and antiviral responses. However, the molecular mechanisms underlying the costimulatory processes are poorly understood. We compared microarray gene analysis data between TLR1-TLR2 stimulated and unstimulated T cell receptor transgenic ‘pmel’ and MyD88-/-pmel CD8+ T cells and identified changes in the expression levels of several TNF family members. In particular, TLR-stimulation increased 4-1BB levels in pmel but not in MyD88-/-pmel T cells. A link between 4-1BB and TLR1-TLR2 signaling in CD8+ T cells was highlighted by in fact that 4-1BB-/- T cells exhibited suboptimal responses to TLR1-TLR2 agonist, but responded normally to CD28 or OX40 costimulation. Moreover, blocking 4-1BB signaling with antibodies also hindered the costimulatory effects of the TLR1-TLR2 agonist. The elevated levels of 4-1BB transcripts in TLR1-TLR2–stimulated cells were not due to increased mRNA stability nor increased histone activation but instead were associated with increased binding of p65 and c-Jun to two distinct 4-1BB promoter sites. Combining TLR1-TLR2 ligand with an agonistic anti-4-1BB antibody enhanced the antitumor activity in mice with established melanoma tumors. These studies reveal that the costimulatory effects of TLR1-TLR2 signaling in CD8+ T cells are in part mediated by 4-1BB and are important for mounting an effective antitumor immune response.

overall_design: CD8+ T cells from the B6.Cg-Thy1/Cy Tg(TcraTcrb)8Rest/J mice, referred to as ‘pmel’ T cells or from MyD88 knockout pmel mice (MyD88–/–pmel) were sorted. pmel and MyD88–/–pmel T cells were activated using MyD88–/– CD8 T cell-depleted splenocytes pulsed with 10ng/ml of mgp100. This was with or without 10µg/ml of Pam3CSK4. pmel or MyD88–/–pmel CD8 T cells were enriched  and used for the extraction of RNA used for genomic analysis.

last: Joseph

first: Ratika

last: Srivastava

first: Eduardo

last: Davila


title: Expression profiling Hawaiian Drosophila species, tissues, and sexes

first: Brian

last: Oliver

address: 50 South Drive

department: LBG

institute: NIDDK, NIH

type: Expression profiling by high throughput sequencing

summary:
This is a prepublication dataset that should change as updates are made to the underling genomes and annotations.  Additional samples may be deposited and some samples may fail quality control. Please contact Haiwang Yang <haiwang.yang@nih.gov> for details.

The RNA-seq data set contains the transcriptional profiling of eight sexed tissue types (head, thorax, carcass, abdomen w/o gonad, gonad, other reproductive tract, genitalia, and digestive system) and/or whole adult flies from five strains of Drosophila grimshawi, two strains of D. silvestris, and one strain each of D. hemipeza, D. heteroneura, and D. hawaiiensis.

sample_organism:
Drosophila grimshawi
Drosophila heteroneura
synthetic construct
Drosophila hawaiiensis
Drosophila hemipeza
Drosophila silvestris

overall_design: Samples were collected in duplicate to quadruplicate from sexually mature sexed adults (4-5 weeks post eclosion), which had been allowed to freely mate.  Single-end stranded 76bp PolyA+ RNA-seq was performed on all samples.  Libraries were multiplexed with indexed adaptors, and some were also prepared as mixed libraries with RNA from genetically distant species: Drosophila melanogaster (GSE81142) and Anopheles stephensi (GEO entry in preparation). All whole adult samples were prepared from single flies.  Tissues were pooled from 3-5 individuals depending on the size of both the tissue and the species.  For the G1 strain (reference assembly strain) of D. grimshawi, we profiled seven adult tissues for each sex in addition to whole flies. Samples were whole fly (one fly per sample), head (5 flies), thorax (5 flies), abdomen w/o gonad (5 flies), gonad (testes or ovaries) (5 flies), other reproductive tract (accessory gland and male reproductive duct or female spermatheca and oviduct; 10 flies per sample), genitalia (10 flies), and digestive system (proventriculus, crop, salivary gland, gut, and renal tubule; 5 flies).  We prepared sexed single fly whole body samples in quadruplicate for ZA27Z2, ZA27Z3, and Mo010 strains of D. grimshawi.  We also prepared sex-specific head, carcass, gonad, other reproductive tract with genitalia with duplicate for Wm1041 strain of D. grimshawi and other species - D. silvestris (Y11R6 and U26B9 strains), D. hemipeza (W40B14 strain), D. heteroneura (W48B6 strain), and D. hawaiiensis (Y17P5 strain).  We used reduced number of flies for the non-grimshawi species (i.e., 3 heads, gonads or carcasses per sample, and 6 reproductive tracts plus genitalia per sample).

first: Haiwang

last: Yang

first: Maria

last: Jaime

first: Klvin

last: Kanegawa

first: Kenneth

last: Kaneshiro


title: Transcriptome and translatome profiling of CPX 24h effects in neuroblastoma cells CHP134

city: Povo

first: Toma

last: Tebaldi

state: Trento

address: via Sommarive n. 9

department: Centre for Integrative Biology

institute: University of Trento

summary:
Neuroblastoma (NB) is the most frequent extracranial solid tumour of childhood. Clinical courses are highly variable, ranging from spontaneous regression/maturation to rapid progression despite intensive multimodal therapy. The estimation of 5-year event free survival in high-risk patients of only about 40 % stresses an importance of novel therapeutic strategies. A number of iron chelators have demonstrated marked in vitro and in vivo anti-tumor activity and are currently being developed as novel anti-cancer agents. Therefore, the potential antitumor effect of iron chelators in NB cancer was investigated. Among the compounds tested, ciclopirox olamine (CPX) was shown to be one of the most effective intracellular iron chelators in NB cells. To unveil the molecular mechanisms underlying the effects of CPX on viability of NB cells, microarray analysis was performed in CHP134 control cells and cells treated with 5 µM CPX for 24 hours. Inclusion of both total RNA (reflecting transcriptional status of the cells) and polysomal RNA (approximating the proteomic representation of the cells) provided us with a deeper understanding of changes in the cells upon CPX treatment.
Keywords: ciclopirox olamine, iron chelator, neuroblastoma, translatome profiling, transcriptome profiling, polysomal profiling, polysomal RNA, translational control, translational profiling, polysome profiling

overall_design: Microarray analysis was performed to enable a comprehensive view of the changes in the transcriptional and translational status of the cells in response to the treatment with an iron chelator CPX. Polysomal RNA and total RNA were isolated from vehicle-treated CHP134 cells and CHP134 cells treated with 5 µM CPX for 24 hours. Each condition is represented by three biological replicates, i.e. the experiment was repeated starting each time from cells seeding yielding an independent RNA sample. In total, 12 samples corresponding to 4 conditions were subjected to microarray analysis.

first: Viktoryia

last: Sidarovich

first: Valentina

last: Adami

last: Greco

first: Alessandro

last: Quattrone


title: Gene expression analysis in lung fibroblasts from p38+/+ (wt) and p38ki/ki (ki) mice

city: Singapore

first: Anna

last: Brichkina

address: 61 Biopolis Drive

country: Singapore

institute: Institute of Molecular and Cell Biology

summary: To assess differently expressed genes beween wt and ki fibroblasts

overall_design: Total RNA was purified from fibroblasts of 3 different mice for wt and 3 different mice for ki

first: Hui

last: Loh

first: Dmitry

last: Bulavin


title: Transcriptional response to mouse and human AIM2-like receptor activation

status: Public on May 31 2016

city: Seattle

first: Daniel

middle: B

last: Stetson

state: WA

address: 750 Republican St

department: Immunology

institute: University of Washington

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: Molecular subtypes in pancreatic adenocarcinoma

first: Habib

last: Hamidi


title: Transcriptional response to intracellular DNA in cells lacking AIM2-like receptors

summary:
Analysis of ALR-deficient cells indicates that ALRs are not required for the IFN response to intracellular DNA. To explore whether AIM2-like receptors activated another innate signaling pathway upon
DNA detection, we performed microarray analysis comparing ALR+/+, ALR-/-, and AIM2-/- macrophages and fibroblasts 4 or 8 hours after transfection with calf-thymus DNA.

overall_design: Total RNA was isolated from ALR+/+, ALR-/-, and AIM2-/- bone marrow-derived macrophages (BMMs) or fibroblasts (MEFs) mock-treated (lipofectamine alone) or transfected with 5ug CT-DNA for 4 or 8 hours.

first: Elizabeth

last: Gray


title: Overlapping and distinct roles of LIN28 paralogs

status: Public on May 24 2016

city: Boston

first: JIN

last: ZHANG

state: Massachusetts

address: 1 Blackfan Circle

department: Hematology/Oncology

institute: Harvard Medical School/Boston Children's Hospital

summary:
Lin28a or Lin28b single knockout or double knockout MEF cells reprogrammed to iPS cells
Lin28a or Lin28b single knockout or double knockout MEF cells reprogrammed to iPS cells

overall_design: 12 samples in total were analyzed. 3 replicates for each phenotypes. Controls are the wild type iPS without lin28a/b loss of function.

first: Jin

last: Zhang

first: George

middle: Q

last: Daley


title: Unbiased transcriptome profiling of mNS-5 (mouse embryonic stem cell-derived neural stem cells) following RNAi-mediated MED12 depletion.

status: Public on May 19 2016

city: San Antonio

first: NAM HEE

last: KIM

address: 7703 Floyd Curl Dr.

department: Molecular Medicine/IBT

institute: UTHSCSA

summary: The RNA polymerase II transcriptional Mediator subunit MED12 is broadly implicated in vertebrate brain development, and genetic variation in human MED12 is associated with X-linked intellectual disability and neuropsychiatric disorders. Although prior studies have begun to elaborate the functional contribution of MED12 within key neurodevelopmental pathways, a more complete description of MED12 function in the developing nervous system, including the specific biological networks and cellular processes under its regulatory influence, remains to be established. Herein, we sought to clarify the global contribution of MED12 to neural stem cell (NSC) biology through unbiased transcriptome profiling of mouse embryonic stem (ES) cell-derived NSCs following RNAi-mediated MED12 depletion. A total of 240 genes (177 up, 73 down) were differentially expressed in MED12-knockdown versus control mouse NS-5 (mNS-5) NSCs. Gene set enrichment analysis revealed MED12 to be prominently linked with “cell-to-cell interaction” and “cell cycle” networks, and subsequent functional studies confirmed these associations. Targeted depletion of MED12 led to enhanced NSC adhesion and upregulation of cell adhesion genes, including Syndecan 2 (SDC2). Concomitant depletion of both SDC2 and MED12 reversed enhanced cell adhesion triggered by MED12 knockdown alone, confirming that MED12 negatively regulates NSC cell adhesion by suppressing the expression of cell adhesion molecules. MED12-mediated suppression of NSC adhesion is a dynamically regulated process in vitro, enforced in self-renewing NSCs and alleviated during the course of neuronal differentiation. Accordingly, MED12 depletion enhanced adhesion and prolonged survival of mNS-5 NSCs induced to differentiate on gelatin, effects that were bypassed completely by growth on laminin. On the other hand, MED12 depletion in mNS-5 NSCs led to reduced expression of G1/S phase cell cycle regulators and a concordant G1/S phase cell cycle block without evidence of apoptosis, resulting in a severe proliferation defect. These findings suggest that MED12 contributes to the maintenance of NSC identity through a functionally bipartite role in suppression and activation of gene expression programs dedicated to cell adhesion and G1/S phase cell cycle progression, respectively. MED12 may thus contribute to the regulatory apparatus that controls the balance between NSC self-renewal and differentiation, with important implications for MED12-linked neurodevelopmental disorders.

overall_design: To investigate the global contribution of MED12 to NSC biology, we profiled the transcriptomes of mouse NS-5 (mNS-5) NSCs following RNAi-mediated MED12 depletion. Parallel cultures of mNS-5 NSCs were infected with lentiviruses expressing either nonsilencing control (n=3) or MED12-specific (n=6) shRNAs. Gene expression data from the MED12 depletion was compared to non-silencing control to identify differentially expressed genes.

first: Nam Hee

last: Kim

first: Carolina

last: Livi

first: P.

middle: R

last: Yew

first: Dong Hyun

first: Thomas

middle: G

last: Boyer


title: Search for a novel therapeutic target in myeloid leukemia

status: Public on May 14 2016

city: Hefei

first: Xiaohu

last: Zheng

state: Anhui

address: Huang Shan Road

department: School of Life Sciences

institute: University of Science and Technology of China

summary:
Antibody-based therapy for cancer is now one of the most successful and important strategies for treating patients with hematological malignancies. However, the lack of efficient tumor-associated antigens restricts the targeting therapy of myeloid leukemia.
Analysis of the gene expression proﬁles of primary bone marrow samples from human acute myeloid leukemia (AML) patients or healthy donors was to identify and expand novel targets for the treatment of myeloid leukemias. we found that epithelial cell adhesion molecule (EpCAM) is overexpressed in patients with AML.

overall_design: we analyzed the gene expression proﬁles of bone marrow mononuclear cells from 2 human acute myeloid leukemia (AML) patients and 2 healthy donors using an oligonucleotide microarray, to identify up-regulated genes in AML samples comparing with healthy tissues.

first: Haiming

last: Wei


title: Serotonin effect on Bxpc-3 pancreatic adenocarcinoma cell line.

status: Public on May 12 2016

city: Shanghai

first: Shuheng

last: Jiang

address: #800, Dongchuan Road

institute: Shanghai Cancer Institute

summary: Analysis of Bxpc-3 cells treated with serotonin under metabolic stress induced by serum deprivation. Serotonin (5-HT), a well-known neuromodulator with both neurotransmitter and neuroendocrine functions, is also involved in tumorigenesis. Results provide insight into molecular basis of serotonin in pancreatic cancer.

overall_design: Three serotonin treated Bxpc-3 cells, three untreated controls.

first: Z

first: S


title: Notch1 - WISP1 Axis Determines Tumor-Regulating Role of Melanoma Stromal Fibroblasts

status: Public on May 29 2016

city: Silver Spring

first: BIJU

last: ISSAC

address: 503 Robert Grant Ave, Rm 2W123

department: Military HIV Research Program

institute: Walter Reed Army Institute of Research

summary: Cancer-associated fibroblasts (CAF) are crucial in regulating cancer progression, yet  the molecular mechanisms that determine the tumor-regulating function of CAF are  poorly understood. Here, we uncover the Notch1 pathway as a molecular determinant  that controls the regulatory role of CAF in melanoma growth, invasion and metastasis,  and can be manipulated to reprogram and convert CAF to act as tumor suppressors.  The Notch1-determined tumor-regulating function is in part mediated by Wnt-induced  secreted protein 1 (WISP1). These findings reveal the Notch1—WISP1 axis as a crucial  molecular determinant in governing stromal regulation of tumor progression, and  establish this axis as a potential therapeutic target

overall_design: Total RNA obtained from MSCD-SF transduced with Cre-GFP/lentivirus in vitro compared to MSCD-SF transduced with GFP/lentivirus. Samples are duplicates.

first: Hongwei

last: Shao

first: Long

last: Cai

first: Mecker

last: Moller

first: Massimiliano

last: Ferrari

first: Ranran

last: Kong

first: Biju

last: Issac

first: Freddy

last: Radtke

first: Anthony

last: Capobianco

first: Zhao-Jun

last: Liu


title: Mesenchymal stromal cells perturb human monocyte in vitro differentiation into dendritic cells

status: Public on May 09 2016

city: Montreal

first: Panojot

last: Bifsha

state: QC

address: 3175 Chemin de la Côte Ste-Catherine

department: Pediatrics

country: Canada

institute: CHU Sainte-Justine

summary: Monocytes cultured in media containing GM-CSF and IL4 for 5 days normally differentiate into immature dendritic cells which, upon further stimulation with LPS for an additional 2 days, acquire a mature phenotype. In the present study, we evaluated the effect of human cord-blood mesenchymal stem cells (MSC) on human monocyte differentiation into immature and mature DCs by examining the trancriptional profile of the cells that were obtained after both the differentiation and maturation stages.

overall_design: This is a six condition experiment (iDC, iDC-MSC, mDC, mDC-MSCd, mDC-MSCm, mDC-MSCdm) where each condition is in biological triplicates, that is 3 donors (A, B, C) per condition. iDC are cells obtained after 5-day differentiation of monocytes, otherwise known as immature DCs. iDC-MSC are the cells obtained at the end of the 5-day differentiation phase of monocytes, during which MSC were also present. mDC are cells obtained after a 2-day maturation of  iDC with LPS, also known as mature DCs. mDC-MSC are cells obtained after MSC have been present during only the differentiation (mDC-MSCd) phase, only the maturation (mDC-MSCm) phase or during both the differentiation and maturation phases (mDC-MSCdm).

first: Silvia

last: Selleri

first: Elie

last: Haddad


title: Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR

status: Public on May 11 2016

city: Aurora

first: Jill

last: Slansky

address: 12800 East 19th Ave

institute: Univ Colorado Som

summary: We report the discovery of T cell receptors that are present and shared in multiple HLA-matched breast cancer patient tumors using a single cell emulsion based RT-PCR technique that pairs the alpha and beta TCR chains for high throughput analysis

overall_design: Analysis of TCR sequences from 20 breast cancer patient tumors and blood, as well as 6 control HLA matched individuals

first: Daniel

last: Munson

first: Colt

middle: A

last: Egelston

first: Kami

last: Chiotti

first: Zuly

last: Parra

first: Tullia

last: Bruno

first: Brandon

last: Moore

first: Taizo

last: Nakano

first: Diana

last: Simons

first: Grecia

last: Jimenez

first: Dmitri

last: Rozanov

first: Michael

middle: T

last: Falta

first: Andrew

last: Fontenot

first: Paul

last: Reynolds

first: Sonia

last: Leach

first: Virginia

middle: F

last: Borges

first: John

middle: W

last: Kappler

last: Spellman

first: Peter

last: Lee


title: Cyclodextrin promotes atherosclerosis regression via LXR activation (I)

status: Public on May 06 2016

city: Bonn

first: Joachim

last: Schultze

state: NRW

address: Carl-Troll-Strasse 31

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

summary: Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol levels. Despite ongoing advances in the prevention and treatment of atherosclerosis 1, cardiovascular disease remains the leading cause of death worldwide 2. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Since cholesterol accumulation and deposition of cholesterol crystals (CCs) triggers a complex inflammatory response 3  4, we tested the therapeutic potential of increasing cholesterol solubility in experimental atherogenesis. Here we show that treatment of murine atherosclerosis with the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that solubilizes lipophilic substances, reduced atherosclerotic plaque size, cholesterol crystal load and promoted plaque regression even under continuing Western diet. CD solubilized CCs and promoted cholesterylester and oxysterol production in macrophages leading to liver X receptor (LXR)-mediated transcriptional reprogramming. CD increased cholesterol efflux from macrophages and substantially augmented reverse cholesterol transport in vivo. Furthermore, CD reduced proinflammatory cytokines in vivo and decreased macrophage responsiveness towards TLR and inflammasome activation. Since CD treatment in humans is safe and CD beneficially affects key pathogenetic factors in atherogenesis it may thus be used clinically to prevent or treat human atherosclerosis .

overall_design: We hypothesize that cyclodextrin (CD) treatment of mice results in activation of LXR transcription factors, which is described to be antiatherogenic. To test whether LXR activation by CD contributes to the anti-atherogenic effects of CD, LDLR knockout mice were transplanted with bone-marrow of wt or LXRa/LXRb dko mice. The mice were put on a high-fat diet for 8 weeks and subcutaneously treated with cyclodextrin (CD) or a vehicle control as described in the methods part of the paper. Snap-frozen descending aortas of these mice were used for gene expression analysis.

first: S

last: Zimmer

first: A

last: Grebe

middle: S

last: Bakke

first: N

last: Bode

first: B

last: Halvorsen

first: M

last: Skjelland

first: D

last: De Nardo

first: L

middle: I

last: Labzin

last: Kerksiek

first: C

last: Hempel

first: T

last: Heneka

last: Fitzgerald

first: J

last: Gustafsson

last: Tall

middle: D

last: Wright

last: Espevic

last: Ulas

first: G

last: Nickenig

last: Lütjohann

first: E

last: Latz


title: Cyclodextrin promotes atherosclerosis regression via LXR activation (II)

last: Schultze

overall_design: We hypothesize that cyclodextrin (CD) reprograms macrophage gene expression by activating LXR transcription factors. Therefore, we used M-CSF derived bone-marrow macrophages from wt and LXRa/LXRb dko mice, which were loaded with cholesterol crystals for 3h or left untreated. Excess cholesterol crystals were washed aways and the BMDMs were treated for 4h with 10 mM of CD prior to gene expression analysis.

last: Zimmer

last: Grebe

last: Bakke

last: Bode


title: Cyclodextrin promotes atherosclerosis regression via LXR activation


title: Gene expression in groups of sympathetic neurons from an NPY reporter mouse

status: Public on May 04 2016

city: PITTSBURGH

middle: P.

last: Horn

address: 3500 Terrace Street

department: Neurobiology

institute: University of Pittsburgh

summary:
In paravertebral sympathetic ganglia, 50 to 70% of the neurons selectively express neuropeptide Y (NPY). We sought to identify other genes that are differentially expressed by NPY-positive and NPY-negative neurons.
This study used NPY reporter mice (B6.FVB-Tg(Npy-hrGFP)1Lowl/J) (Jackson Laboratory #006417) that were bred as hemizygotes with C57BL/6 mice.

overall_design: Superior cervical ganglia (SCG) from 4- and 7-month-old male mice were dissociated and manually sorted into groups of 10 cells by Renilla Green Fluorescent Protein expression. RNA was amplified and run on Illumina BeadChips.

first: Kristine

middle: M

last: Sikora

first: Paul

last: Kullmann


title: Different gene expression between CDK5 knocking down and control colorectal cancer cell line HCT116

status: Public on May 05 2016

city: Guangzhou

first: Kangmin

last: Zhuang

address: No.1838, North of Guangzhou Avenue, Guangzhou City, Guangdong Province, China

institute: Nanfang Hospital Southern Medical University

summary: We sought to find out the molecular mechanism of CDK5 displayed in colorectal cancer. Microarray experiments were carried out to identify different gene expression between CDK5-knockdown HCT116 cell lines and Scramble HCT116 cell lines.

overall_design: Lentiviral expression vector of CDK5 short hairpin RNA and the control group of scramble sequence was both used to infect the HCT116 cell line. Total RNA was  extracted and analyzed by the Agilent 4x44K whole human genome oligo microarray with triple replication.

first: Side

last: Liu