title: Evaluating the effects of cardiac telomerase re-activation after myocardial infarction in adult mice

status: Public on Dec 15 2014

city: Madrid

first: Christian

last: Baer

state: Madrid

address: Calle Melchor Fernandez Almagro 3

department: Molecular Oncology

institute: CNIO

summary: Coronary heart disease is a main cause of death in the developed world and treatment success remains modest with high mortality rates within one year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases including heart disease. Here, we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression in a mouse model of MI. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared to controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work highlights telomerase activation as a novel therapeutic strategy to prevent heart failure after MI.

overall_design: Mice of one year of age were left untreated (control) or injected with 5*10^11 adeno associated viruses particles of serotype 9 (AAV9) that carry either en empty expression cassette or express telomerase under control of the CMV promoter. Virus injected mice then underwent myocardial infarction induced through permenant left anterior descending artery  (LAD) ligation. Mice that survived for six weeks after LAD ligation were sacrificed and 4 hearts per group (AAV9-empty or AAV9-Tert) and 3 control hearts (no virus treatment, no ligation) were subjected to total RNA isolation for micro array analysis.

last: Bär

first: Bruno

last: Bernardes de Jesus

first: Rosa

last: Serrano

first: Gonzalo

last: Gomez-Lopez

first: David

last: Pisano

first: Ivan

last: Formentini

first: Agueda

last: Tejea

first: Eduard

last: Ayuso

first: Veronica

last: Jimenez

first: Maria

last: Bobadilla

first: Jacques

last: Mizrahi

first: Alba

last: de Martino

first: Francisca

last: Mulero

first: Kai

middle: C

last: Wollert

first: Fatima

last: Bosch

last: Blasco


title: Effect of AZD1208 on gene expression in recurrent resistant Myc-CaP tumors grown in castrated mice.

status: Public on Dec 24 2014

city: Salisbury

first: Philip

middle: D

last: Anderson

state: Maryland

address: 1101 Camden Avenue

department: Biological Sciences

country: USA

institute: Salisbury University

summary: AZD1208 is a novel PIM kinase inhibitor that we have shown inhibits tumorigenesis in tissue recombination models, Myc-CaP allograft models, and human prostate cancer xenografts. We sought to determine the intracellular pathways that are responsible for the anti-tumor effect. To this end we used the tissue recombination protocol to implant MYCCaP cells into castrated mice. MYCCaP cells are an androgen-dependent mouse cell line that overexpresses the oncogene MYC. The mice used for implantation were castrated, so any tumors that result from the grafting procedure are androgen-independent. The grafted mice were divided into a control population receiving vehicle, and a test population receiving AZD1208. The tumors were harvested and in vitro cell lines were made. The new cell lines have been perpetuated in androgen-depleted media.

overall_design: RNA was harvested from three cell lines from mice receiving vehicle, three cell lines from mice receiving AZD1208, and from the parental MYCCaP cell line which was raised in media containing androgen. The RNA was hybridized to nine Affymetrix Mouse Gene 2.0 ST Arrays in the Vanderbilt University microarray processing core.

first: Austin

middle: N

last: Kirschner

first: Sarki

middle: A

last: Abdulkadir


title: Placental growth factor as potential target against hepatocellular carcinoma in an orthotopic mouse model.

status: Public on Dec 23 2014

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary: The placental growth factor (PlGF) is member of the vascular endothelial growth factor (VEGF)-family known to stimulate endothelial cell growth, migration and survival, attract angiocompetent macrophages and bone marrow progenitor cells and determine the metastatic niche. Unlike VEGF, genetic studies have shown that PlGF is specifically involved in the pathologic angiogenesis, thus its inhibition would not affect healthy blood vessels, providing an attractive drug candidate with a good safety profile. In this study, we assess whether inhibition of PlGF could be used as a potential therapy against hepatocellular carcinoma (HCC), by using PlGF-knock out mice and monoclonal antibodies targeting PlGF in an orthotopic model for HCC. In addition, the effect of PlGF-antibodies is compared to that of Sorafenib, as well as the combination of both therapies. In our study we have found that both in a transgenic knock out model as in a treatment model, silencing or inhibition of PlGF significantly decreased tumour burden, not only by inhibiting the vascularisation, but also by decreasing hepatic macrophage recruitment and by normalizing the remaining blood vessels, thereby decreasing hypoxia and thus, reducing the pro-metastatic potential of HCC. Conclusion: considering its favourable safety profile and its pleiotropic effect on vascularisation, metastasis and inflammation, targeting PlGF could become a valuable therapeutic strategy against HCC.

overall_design: Hybridisation on the Mouse Gene Expression Microarray (Agilent) was performed in a single sample per chip and in a monocolore mode, using cyanine-3 (Cy3) labeling.  Following conditions were assessed: 25W DEN + 5W αPlGF tumour tissue (n = 5), 25W DEN + 5W αPlGF surrounding tissue (n = 4), 25W DEN + 5W IgG tumour tissue (n = 5), 25W DEN + 5W IgG surrounding tissue (n = 4), 25W saline + 5W αPlGF (n = 3) and 25W saline + 5W IgG (n = 3).

first: Femke

last: Heindryckx

first: Stephanie

last: Coulon

first: Ellen

last: Terrie

first: Christophe

last: Casteleyn

first: Jean-Marie

last: Stassen

first: Anja

last: Geerts

first: Louis

last: Libbrecht

first: Peter

last: Carmeliet

first: Isabelle

last: Colle

first: Hans

last: Van Vlierberghe


title: Expression profiling of WI38 normal lung fibroblasts following overexpression of p53 and/or Retinoblastoma

status: Public on Nov 30 2014

city: Huntington

first: James

last: Denvir

state: WV

address: One John Marshall Drive

department: Biochemistry and Microbiology

institute: Marshall University School of Medicine

summary: RNA expression profiling was performed on normal human lung fibroblast WI38 cells following overexpression of p53 and pRb, in order to identify genes co-regulated and involved in mediating p53 and pRb tumor suppressor processes.

overall_design: Four condition experiment with four biologicial replicates of each condition in a two-color reference design. The four conditions were Adenovirus with Cytomegalovirus (CMV) promotor (control); Adenovirus with p53 gene under control of CMV; Adenovirus containing RB1 gene under control of CMV; Adenovirus containing p53 and RB1 gene under CMV.

first: Miranda

middle: B

last: Carper

first: Goran

last: Boskovic

first: Donald

last: Primerano

first: Pier-Paulo

last: Claudio


title: Alterations in hepatic gene expression induced by chromic exposure to high levels of the SV40 LT/st oncoproteins (4P)

status: Public on Dec 22 2014

city: New York

first: Nikolaus

last: Schultz

state: NY

address: 1275 York Ave, Box 460

department: Computational Biology Center

institute: Memorial Sloan-Kettering Cancer Center

summary: Hepatic gene expression induced by chromic exposure to high levels of the SV40 LT/st oncoproteins (4P)

overall_design: Affymetrix mouse genome U74Av2 platform was used, duplicate measurements for wild-type and transgenic animals

first: Sarah

last: Comerford

first: Sharon

middle: L

last: Milgram

first: Robert

middle: E

last: Hammer


title: Gene epxression profiling in murine Flt3+ granulocyte progenitors (Flt3+ GPs) and Flt3- granulocyte progenitors (Flt3- GPs)

status: Public on Nov 17 2014

city: Yokohama

first: Tomohiko

last: Tamura

address: 3-9 Fukuura, Kanazawa-ku

department: Department of Immunology

country: Japan

institute: Yokohama City University

summary: To understand the mechanism by which IRF8 promotes basophil differentiation

overall_design: Murine bone marrow Flt3+ GPs and Flt3- GPs were isolated by cell sorting from wild-type or Irf8 deficient mice. Two independent experiments were performed.

first: Daisuke

last: Kurotaki

first: Haruka

last: Sasaki

first: Akira

last: Nishiyama


title: Estrogen-Related Receptor-a Coordinates Transcriptional Programs Essential for Exercise Tolerance and Muscle Fitness

status: Public on Dec 08 2014

city: Montréal

first: Vincent

last: Giguère

state: QC

address: 1160 Pine Ave West, McIntyre Bldg Room 710

department: Goodman Cancer Centre

country: Canada

institute: McGill University

summary:
The molecular mechanisms involved in the coordinate regulation of the metabolic and structural determinants of muscle endurance are still poorly characterized.
To help elucidate the role of ERRa in this process, gene expression arrays were employed resulting in the identification of ERRa-dependent genes involved in metabolic processes, oxidative stress response, maintenance of muscle fiber integrity and neovascularization.

overall_design: Gastrocnemius (n=3) isolated from 2-3 month old WT and ERRa-null mice under pre-exercise (sedentary) and post-exercise (2 h following acute exhaustion on a treadmill) were used for gene expression studies using Affymetrix mouse 2.0 gene ST arrays.

first: Marie-Claude

last: Perry

first: Catherine

middle: R

last: Dufour

first: Ingrid

middle: S

last: Tam

first: Wafa

last: B'Chir

last: Giguere


title: AKT network of genes and impaired myocardial contractility during murine acute chagasic myocarditis

status: Public on Dec 05 2014

city: Aurora

first: Andrés

middle: F.

last: Henao-Martínez

state: Colorado

address: 12700 E. 19th Avenue.

department: Medicine

institute: University of Colorado Denver

summary:
Rationale: Chagasic disease is associated with high morbidity in Latin America. Acute Chagasic myocarditis is consistently found in acute infections but little is known about its contribution to chronic cardiomyopathy. The aim of the study was to phenotypically characterize two strains of mice with differential Chagas infection susceptibility and correlate strain myocarditis phenotypes with heart tissue gene expression.
Methods: C57BL/6J and Balb/c mice were injected intraperitoneally with 0 or 150-200 tissue-derived trypomastigotes (Tulahuen strain). Echocardiograms, brain natriuretic peptide and troponin were measured. Heart tissue was harvested for histopathological analysis and gene expression profiling on microarrays. Genes differently expressed between infected Balb/c and C57BL/6J were identified
Results: Echocardiograms demonstrated differences in heart rate in Balb/c vs. C57BL/6J infected mice: 413 vs. 476 bpm, (p=0.0001), stroke volume: 31.9 ± 9.3 vs. 39.2 ± 5.5 µl (p=0.03); and cardiac output: 13.1 ± 3.5 vs. 18.7 ± 3.2 µl/min (p=0.002). Gene expression at 4 weeks analysis demonstrated 32 statistically significant (q-value < 0.05) differentially expressed genes between infected Balb/c and C57BL/6J which were enriched for genes related to protein kinase B (AKT) pathway

overall_design: 8 Balb/c mice and 8 C57BL/6J mice were infected and 8 Balb/c and 8 C57BL/6J were used as controls. 6 mice per group were used for gene expression analysis.

middle: F

first: Anne

middle: H

last: Agler

first: Alan

middle: M

last: Watson

first: Corinne

last: Hennessy

first: Elizabeth

last: Davidson

first: Kim

last: Demos-Davies

first: Timothy

last: McKinsey

first: Michael

last: Wilson

first: David

last: Schwartz

first: Ivana

middle: V

last: Yang


title: BRCA1 Haploinsufficiency Leads to Altered Expression of Genes Involved in Cellular Proliferation and Development

status: Public on Dec 12 2014

city: Kingston

first: Scott

last: Davey

state: Ontario

address: Botterell Hall, Room 364

institute: Queen's University

summary: Background: The BRCA1 protein has been shown to play critical roles in several molecular pathways, but the specific defect(s) that promote breast and ovarian carcinogenesis remain a mystery. Furthermore, while mutations that result in a truncated protein can unequivocally be called disease-causing, many other variants mutations have poorly defined clinical significance. Given these factors, development of a functional assay for BRCA1 is a significant clinical priority, but presents significant biological challenges. Methodology and Significant Findings: We have developed a novel function-based assay for BRCA1 carrier identification by examining the effect of loss of a single copy of BRCA1 on global gene expression levels. Comparison of the gene expression profiles of undamaged, actively cycling EBV-transformed lymphocytes allowed accurate discrimination between BRCA1+/+ and BRCA1+/- cells. The best predictor was 100% (16/16) accurate in predicting BRCA1 status in an independent test set; the overall sensitivity and specificity of the test are 84% and 92%, respectively, when the training set data (53 samples) is also included. A set of 22 genes was identified by two distinct analytical approaches, including a set of 11 genes (TBX21, MX2, IFIT1, IFIT2, IFIT3, GLDC, F13A1, SOX4, LCK, HERC5, USP18) that could be linked in a single   pathway encompassing cellular proliferation and development. By contrast, analysis of the same samples for global gene expression level changes following irradiation did not support the development of an accurate class predictor. Conclusions and Significance: Our results support the idea that the fundamental defect resulting from BRCA1 mutation is a reduction in cellular differentiation, and that changes in the DNA damage response require inactivation of the second BRCA1 allele. Given that the class predictor we have developed was based on unperturbed cells, this work could ultimately lead to the development of a rapid and accurate test for identification of BRCA1 mutation carriers.

overall_design: 69 cell lines consist of 38 control (BRCA1+/+) and 31 BRCA1 mutation carriers (BRCA1+/-), two color arrays, non radiated vs. radiated for each cell line. Although the experiment was done to allow for analysis of radiation-dependent effects (Cy5/Cy3 ratio), the results reported in Sample Data Tables are from unperturbed cells (Cy3 one color data only).

first: Claire

last: Michel

first: Larbi

last: Benhabib

first: Harriet

last: Feilotter


title: BEAS2B cells and A549 cells: control versus nanoparticle exposure

status: Public on Dec 01 2014

city: Mol

first: Sylvie

last: Remy

state: Antwerp

address: Boeretang 200

institute: VITO

summary: Fragmentary knowledge exists on the adverse health effects of CoO- and CeO2-nanoparticles (NP)s. We analyzed toxicogenomic profiles of BEAS-2B versus A549 cells using genome-wide transcriptomics to identify molecules and cellular processes that are triggered by monodispersed noncytotoxic suspensions of 7-nm CoO- and 4-nm CeO2-NPs for 3, 6, 10, and 24 hours. We aimed to investigate 1) whether a cell type responds similarly to two different NPs exposure, 2) whether alveolar versus bronchial epithelial cells respond differently to the same NP, and 3) whether immune processes are influenced. The kinetics of the cell responses induced by the two NPs were different between the two lung epithelial cell models. Both CoO- and CeO2-NP exposure induced mainly downregulation of gene transcription. BEAS-2B cells were found to be more sensitive towards NP exposure, as they showed a higher total number of differentially expressed transcripts (DET) at a 10-fold lower NP-concentration than A549 cells. Hierarchical clustering of all DET indicated that the transcriptional responses were quite heterogeneous among the two cell types and two NPs. Between 1% and 14% DET encoding markers involved in immune system processes were observed in the BEAS-2B and A549 cell lines, with the highest fractions observed in BEAS-2B cells. Most of these genes, i.e. ITGB2, TLR6, PAG1, HLA-DRB3, TIRAP, and HLA-A, are involved in immune signalling. The AKT1 gene, which showed persistently decreased expression levels, was identified as a possible generic marker of lung epithelial cell-NP interaction. Our data suggest that CoO- and CeO2-NPs give rise to distinct responses.

overall_design: Replicates: 3 biological replicates; Exposure: 2 different cell types, 2 different nanoparticles versus solvent, 1 exposure concentration; Exposure time: 4 different exposure time points;

first: Sandra

last: Verstraelen

first: Eudald

last: Casals

first: Patrick

last: De Boever

first: Hilda

last: Witters

first: Antonietta

last: Gatti

first: Victor

last: Puntes

first: Inge

last: Nelissen


title: Addiction and Reward-related Genes Show Altered Expression in the Postpartum Nucleus Accumbens

city: Madison

first: Stephen

middle: Coull

last: Gammie

state: WI

address: 430 Lincoln Drive

department: Zoology

institute: University of Wisconsin

summary: Motherhood involves a switch in natural rewards, whereby offspring become highly rewarding. Nucleus accumbens (NAC) is a key CNS region for natural rewards and addictions, but to date no study has evaluated on a large scale the events in NAC that underlie the maternal change in natural rewards. In this study we utilized microarray and bioinformatics approaches to evaluate postpartum NAC gene expression changes in mice. Modular Single-set Enrichment Test (MSET) indicated that postpartum (relative to virgin) NAC gene expression profile was significantly enriched for genes related to addiction and reward in 5 of 5 independently curated databases (e.g., Malacards, Phenopedia). Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, Gabrb3, Adra2a, Ntrk2, Cry1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder, and schizophrenia. Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions.

overall_design: In total, 12 total RNA samples derived from micropunched nucleus accumbens were used for microarray analysis: 6 samples from lactating maternal mice (maternal) and 6 samples from age-matched virgin mice (virgin). All samples are biological replicates.

first: C

last: Zhao

first: B

last: Eisinger

first: T

last: Driessen

first: S


title: Human endometrial cancer cell gene expression profiles of the estrogen receptor α (ERα) hinge region mutants (H1 and H2NES)

status: Public on Nov 24 2014

city: RTP

first: NIEHS

last: Microarray Core

state: NC

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary:
ERa negative Ishikawa cells were stably infected with Era: Wild type ERa, H1 ERa, H2NES ERa
the design was to determine if rapid action non-genomic mediated signals would lead to gene expression changs.

overall_design: Four stable cell lines, vector, WT, H1 and H2NES ERa were treated for 4hr or 24 hr with 10nM Estradiol or vehicle, n=3 for each treatment group

first: Kenneth

last: Korach

first: Katherine

last: Burns


title: Expression profiling of stroma cells from prostate cancer co-cultures, with or without TGF-beta signaling

status: Public on Nov 12 2014

city: Houston

first: Chad

last: Creighton

state: TX

address: One Baylor Plaza, Mail Stop: BCM305

department: Biostatistics, Ducan Cancer Center

institute: Baylor College of Medicine

summary: Prostate stroma-specific TGF-beta signaling induces morphological changes in LNCaP cells. We have previously shown that stromal TGF-beta signaling regulates prostate tumor growth.  To further delineate the underlying mechanisms, we generated LNCaP cells overexpressing an HA-tagged constitutively activate TGF-beta1 ligand (LNCaP-HA-TGF-β1(a)) and control LNCaP cells  (LNCaP-Ctrl), and performed in vitro co-cultures of LNCaP-HA-TGF-β1(a) and LNCaP-Ctrl cells on top of the confluent HPS-19I cells, a human prostate stromal cell line.   Since LNCaP cells are defective in TGF-beta receptor I (TbetaRI / ALK-5) that is essential for mediating TGF-beta signaling, only HPS19I cells are able to respond to TGF-beta ligand in these co-cultures.  This provides a unique opportunity to study how prostate stromal cell-specific TGF-beta signaling regulates PCa biology. To identify the prostate epithelia-specific gene that was regulated by prostate stromal TGF-beta signaling, we also treated HPS19I cells using conditioned media collected from LNCaP- HA-TGF-β1(a) cells and LNCaP-Ctrl cells cultured in RPMI1640 supplemented with 0.2% FBS.  After 6 days of treatment, we extracted total RNA from these HPS19I cells and performed microarray.

overall_design:
HPS-19I prostate stroma cells from LNCaP+HPS-19I co-culture, with or without TGF-beta
KEYWORDS: two group comparison

first: David

last: Rowley

first: Feng

last: Yang


title: A Novel Human Gastric Primary Cell Culture System for Modeling Helicobacter Pylori Infection In Vitro

status: Public on Dec 10 2014

city: Berlin

first: Hans-Joachim

last: Mollenkopf

address: Charitéplatz 1

country: Germany

institute: Max-Planck-Institute for Infection Biology

summary: We identified specific long-term culture conditions that allow the formation of 3-dimensional human gastric spheroids, which can be differentiated by withdrawal of Wnt3A and R-spondin1 to human gastric organoids. These cultures can expand indefinitely and exhibit important characteristics of human stomach tissue. Furthermore, these 3-dimensional cultures can be transferred into 2-dimensional primary epithelial cell layers, which can be successfully infected with H. pylori and thereby provide ideal conditions to study infections in vitro.

overall_design: Microarray experiments were performed as dual-color hybridizations on Agilent human whole genome catalog 44K arrays. To compensate for dye-specific effects, a dye-reversal color-swap was applied.

first: Philipp

last: Schlaermann

first: Thomas

last: Meyer


title: NCoR1 and SMRT play unique roles in thyroid hormone signaling in the liver

status: Public on Nov 21 2014

city: Vienna

first: Markus

last: Jeitler

address: Lazarettgasse 14

country: Austria

institute: Medical University Vienna

summary: NCoR1 (Nuclear receptor Co-Repressor) and SMRT (Silencing Mediator of Retinoid and Thyroid hormone receptor) are well-recognized coregulators of nuclear receptor (NR) action. However, their unique roles in the regulation of thyroid hormone (TH) signaling in specific cell types have not been determined. To accomplish this we generated a mouse model that lacked function of either NCoR1 or SMRT or both in the liver only.  Despite both corepressors being present in the liver, SMRT had no ability to regulate TH signaling when deleted in either euthyroid or hypothyroid animals. In contrast, disruption of NCoR1 action confirmed that it is the principal mediator of TH sensitivity in vivo. While SMRT played little role in TH signaling alone, when disrupted in combination with NCoR1 it greatly accentuated the activation of hepatic lipogenesis regulated by NCoR1.  Thus, corepressor specificity exists in vivo and NCoR1 is the principal regulator of TH action in the liver. However, both NCoR1 and SMRT collaborate to control hepatic lipogenesis and lipid storage, which likely reflects their cooperative activity in regulating the action of multiple NRs including the thyroid hormone receptor (TR).

overall_design: RNA was extracted from livers from 3 individual mice for each group (Double-floxed, Liver specific-SMRT knock out, and Liver specific-double knock out); all were euthyroid, female mice

first: Hiroaki

last: Shimizu

first: Tony

last: Hollenberg


title: Transcriptome of human odontoblast, pre-secretory ameloblast and secretory ameloblast

status: Public on Nov 14 2014

city: Chapel Hill

first: Shijia

last: Hu

address: 228 Brauer Hall Campus Box 7450

department: Pediatric Dentistry

institute: University of North Carolina

summary: The goal of the study was to characterize the whole genome transcriptome profiles of human ameloblasts and odontoblasts, evaluate molecular pathways and advance our knowledge of the human tooth development. We found that during primary tooth formation, odontoblasts expressed 14,802 genes, presecretory ameloblasts 15,179 genes and secretory ameloblasts 14,526 genes.

overall_design: Four human fetuses were obtained at ages 15-20 weeks gestation, immediately placed on ice and the tooth buds dissected from the jaws, placed in RNAlater and refrigerated at 4C for 1-4 weeks to allow decalcification by EDTA. The tissue was then frozen and stored at -80C. The tissue was sectioned at -35C at a thickness of 7 microns. These sections were used for laser capture microdissection (LCM) to isolate the human odontoblasts and ameloblasts in different stages of enamel formation, using static image settings.  In total, 4 odontoblast, 4 pre-secretory ameloblast and 4 secretory ameloblast pooled samples were used for RNA extraction and microarray analysis.

first: J

middle: T

last: Wright


title: Expression analysis of blastocysts in Kdm4b-PEs

status: Public on Nov 15 2014

city: Setagaya-ku

first: Atsushi

last: Fukuda

state: Tokyo

department: Reproductive biology

institute: National Center for Child Health and Development

summary: To identify the genes that are controled by H3K9me3 modification in PEs, we conducted transcriptome analysis using Egfp-, Kdm4b-PEs, and IVF embryos at blastocyst stages.

overall_design: Kdm4b or Egfp mRNA injected oocytes were parthenogenetically activated.  IVF embryos were generated according to standard protcol. All embryos were cultured in KSOM medium for 120 hours after activation or sperm insemination. Five blastocysts per one biological replicate were pooled and analyzed.


title: Expression data from Ankrd11Yod/+ and WT embryonic cortical neurospheres

city: Toronto

first: Freda

last: Miller

address: 686 Bay Street

department: Neurosciences and Mental Health

institute: Hospital for Sick Children

summary:
Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin, colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial epigenetic regulator of neural development that controls histone acetylation and gene expression, thereby providing a likely explanation for its association with cognitive dysfunction and ASD.
We used microarrays to compare the gene expression profile in embryonic neurospheres prepared from neocortices of WT and Ankrd11Yod/+ mice

overall_design: E14.5 cortical secondary neurosheres 5 days post-passage were collected and total RNA extracted. cDNA was hybridized on Affymetrix Mouse Gene 2.0 ST Array and gene expression was analyzed using Parterk software. In total, 6 Ankrd11Yod/+ and 5 WT embryos were used.

last: Kaplan


title: Liver expression data from 1 week old mouse portal tracts

status: Public on Nov 05 2014

city: Philadelphia

first: Matthew

middle: Joseph

last: Ryan

state: PA

address: 34th and Civic Center Blvd

department: Pediatrics

institute: The Children's Hospital of Philadelphia

summary:
Intrahepatic biliary and arterial development proceed with complex orchestrations involving Notch, TgfB, Wnt and Vegf signaling within the portal tracts of the liver.  These pathways
coordinate morphogenesis and remodeling temporally and spatially from mid-gestation through early postnatal life.

overall_design: We used microarrays to examine changes in remodeling/differentiation programs in portal tracts at 1 week postanally, comparing Jag1+/-Rfng+/- and controls.

first: Lara

last: Underkoffler

first: Emily

last: McComb

first: John

last: Dutton

first: Anthony

last: Nelson

first: Kathleen

last: Loomes

middle: J


title: Identification of TRIML2, a Novel p53 Target, that Enhances p53-SUMolylation and Regulates the Transactivation of Pro-apoptotic Genes

city: 3601 Spruce Street

first: Yan

last: Zhou

address: 333 Cottman Ave

department: Bioinformatics

institute: Fox Chase Cancer Center

summary:
The tumor suppressor protein p53, encoded by TP53, inhibits tumorigenesis by inducing cell cycle arrest, senescence and apoptosis. Several genetic polymorphisms exist in TP53, including a proline to arginine variant at amino acid 72 (P72 and R72, respectively); this polymorphism alters p53 function. In general, the P72 variant shows increased ability to induce cell cycle arrest, while the R72 variant
possesses increased ability to induce apoptosis, relative to P72. At present, the underlying mechanisms for these functional differences are not fully understood. Toward elucidating the molecular basis for these differences a gene expression microarray analysis was conducted on normal human fibroblast cells that are homozygous for P72 and R72 variants, along with subclones of these lines that express a p53 short hairpin (shp53). Approximately three dozen genes were identified whose transactivation is affected by the codon 72 polymorphism. One of these is the tripartite motif family-like 2 (TRIML2) gene, which is preferentially induced by the R72 variant. Importantly, the accumulated data indicate that TRIML2 interacts with p53, and facilitates the modification of p53 with SUMO2. TRIML2 also enhances the ability of p53 to transactivate a subset of pro-apoptotic target genes associated with prolonged oxidative stress, including PIDD, PIG3 (TP53I3) and PIG6 (PRODH). These data indicate that TRIML2 is part of a feed-forward loop that activates p53 in cells expressing the R72 variant, particularly after prolonged stress.

overall_design: Normal human fibroblast cells were untreated (0 hour) or following 2 or 4 hours of exposure to 5 Gray of gamma radiation. 3 independent experiments were performed at each time point for each cell line and at each timepoint 2 cell lines were used.

first: Che-Pei

last: Kung

first: Sakina

last: Khaku

last: Jennis

first: Maureen

last: Murphy


title: Regulation of LbetaT2 gonadotrope gene expression by GnRH pulses

city: La Jolla

first: Nick

last: Webster

state: CA

address: 9500 Gilman Drive

institute: UCSD

summary:
LbetaT2 cells exposed to different number and concentration of GnRH pulses over 4 hours during in vitro perfusion culture
We used MU74Av2 arrays to profile gene expression in response to different pulse frequency and pulse amplitude

overall_design: RNA extracted at end of 4 h of perfusion

first: Nicholas

first: Mark

last: Lawson


title: Gene expression profiles of MCF-7-derived models of endocrine-resistant breast cancer

city: Dunedin

first: Heather

middle: E.

last: Cunliffe

state: Otago

address: P O Box 913

department: Department of Pathology

country: New Zealand

institute: University of Otago, Dunedin School of Medicine

summary:
MCF-7:5C and MCF-7:2A are two in vitro models of Estrogen Receptor alpha positive (ER+) estrogen deprivation-resistant breast cancer. Both cell lines grow robustly in the absence of estrogen [PMID:1301400, PMID:7780972].  MCF-7:PF is an in vitro model of antihormone resistant breast cancer that exhibits the characteristics of acquired tamoxifen resistance [PMID:24183378]
The goal of this study was to compare basal levels of gene expression during exponential phase of growth in MCF-7-derived models of endocrine resistance, relative to their isogenic parental cells

overall_design: All cell lines were cultured in their respective replete medium. During exponential phase of growth, cells were harvested and total RNA prepared. To compare basal levels of gene expression in MCF-7-derivative cell lines, Cy3-labeled cRNA probes were prepared from each individual isolate harvested from MCF-7:5C, MCF-7:2A, MCF-7:PF and MCF-7:WS8 (including biological replicates where indicated) and co-hybridized with Cy5-labeled cRNA reference probe prepared from untreated MCF-7 parental cells,  to Agilent 4x44K dual colour oligonucleotide microarrays.

first: Ping

last: Fan

first: Pilar

last: Ramos

first: Megan

last: Russell

first: Eric

last: Ariazi

first: Joan

last: Lewis-Wambi

first: Surojeet

last: Sengupta

first: V

middle: C

last: Jordan


title: Gene expression profiling of 1205Lu human melanoma cells after reversible shifting between monolayer and stem cell-like growth

status: Public on Oct 31 2014

city: Rehovot

first: Yuval

last: Levy Peretz

state: Israel

address: pob 12

country: Israel

institute: Hebrew Un

summary: RNA samples were prepared from a 1205Lu original cell monolayer (OM), melanoma stem cell-like bodies (MB), and a new cell monolayer derived from stem cell-like bodies (NM).

overall_design: Experiment included 3 samples: a reference sample (OM) and two experimental samples (MB,NM).

first: Richard

last: Katz

last: Peretz


title: Expression data from adult mouse cortex harvested at two different zeitgeber (ZT) timepoints of the 24h cycle

city: Munich

first: Moritz

last: Rossner

address: Nussbaumstr. 7

department: Psychiatry

summary:
Gene expression in forebrain structures change during day and night depending on circadian and rest-activity cycles. Clock genes have been shown to be involved in the control of circadian and sleep-wake control.
In this study, we aimed at studying the consequences of loss of SHARP1 (DEC2/BHLHE40) and SHARP2 (DEC1/BHLHE41) on cortical gene expression at rest (ZT4) and activity (ZT16) phases.

overall_design: We harvested cortex tissue from individual mice from WT and SHARP1/2 double null mutant mice at ZT4 and ZT16, prepared total RNA and subjected the corresponding samples (n=2 biological replicates per timepoint and genotype) to Affymetrix genechip analysis to assay the changes of gene expression.


title: Toxicity Evaluation of Manufactured CeO2 Nanoparticles Before and After Alteration: Combined Physicochemical and Whole-Genome Expression Analysis in Caco-2 Cells.

status: Public on Oct 01 2014

city: Bagnols sur Cèze

first: Odette

last: Prat

address: Site de Marcoule

department: Life Science

country: France

institute: CEA

summary: We have employed whole genome microarray expression to distinguish the effect of environmental aging on the toxicity of several cerium oxide nanoparticles (NPs) in human intestinal cells compared  .  Cells were exposed in vitro, and datasets of differentially expressed genes were identified for each type of NPs versus control samples.

overall_design: NPs induced gene expression in Caco-2 cells was measured at 24 hours after exposure .  Six independent experiments were performed  using different NPs and controls for each experiment.

first: Prat

last: Odette

first: Fisichella

last: Matthieu


title: ADAR2 reproducibly changes abundance and sequence of mature microRNAs in the mouse brain [gene expression]

status: Public on Oct 02 2014

first: Fritz

last: Sedlazeck

state: Vienna

address: Dr. Bohr-Gasse 9

department: CIBIV

institute: MFPL

summary:
Background: Adenosine deaminases that act on RNA (ADARs) bind to double-stranded and structured RNAs and deaminate adenosines to inosines. This A to I editing is widespread and required for normal life and development. Besides mRNAs and repetitive elements, ADARs can target miRNA precursors. Editing of miRNA precursors can affect processing efficiency and alter target specificity. Interestingly, ADARs can also influence miRNA abundance independent of RNA-editing. In mouse embryos where editing levels are low, ADAR2 was found to be the major ADAR protein that affects miRNA abundance. Here we extend our analysis to adult mouse brains where high editing levels are observed.
Results: Using Illumina deep sequencing we compare the abundances of mature miRNAs and editing events within them, between wild-type and ADAR2 knockout mice in the adult mouse brain. Reproducible changes in abundance of specific miRNAs are observed in ADAR2 deficient mice. Most of these quantitative changes seem unrelated to A to I editing events. However, many A to G transitions in cDNAs prepared from mature miRNA sequences, reflecting A to I editing events in the RNA, are observed with frequencies reaching up to 80%. About half of these editing events are primarily caused by ADAR2 while a few miRNAs show increased editing in the absence of ADAR2, suggesting preferential editing by ADAR1. Moreover, novel, previously unknown editing events were identified in several miRNAs. In general 64% of all editing events are located within the seed region of mature miRNAs. In one of these cases retargeting of the edited miRNA could be verified in reporter assays. Also, altered processing efficiency upon editing near a processing site could be experimentally verified.
Conclusions: ADAR2 can significantly influence the abundance of certain miRNAs in the brain. Only in a few cases changes in miRNA abundance can be explained by miRNA editing. Thus, ADAR2 binding to miRNA precursors, without editing them, may influence their processing and thereby abundance. ADAR1 and ADAR2 have both overlapping and distinct specificities for editing of miRNA editing sites. Over 60% of editing occurs in the seed region possibly changing target specificities for many edited miRNAs.

overall_design: Examination of the effect of ADAR2 on gene expression in mature mouse wildtype and ADAR2 knockout brain using Affymetrix® GeneChip® Whole Transcript (WT) Expression Arrays (Analysis by KFB Regensburg, Germany)

first: Cornelia

last: Vesely

first: Stefanie

last: Tauber

first: Mansoureh

last: Tajaddod

first: Arndt

last: von Haeseler

first: Michael

last: Jantsch


title: Mapping of a QTL for airway hyperresponsiveness on mouse chromosome 12

status: Public on Nov 11 2014

city: Montreal

first: Cynthia

last: Kanagaratham

state: Quebec

address: 1650 Cedar Ave.

department: Human Genetics

institute: McGill University

summary: The BcA86 strain is a unique recombinant congenic strain created from parental strains A/J and C57BL/6J. Naive mice from the BcA86 strain have a lung responsiveness phenotype resembling mice from airway hyperresponsive strain A/J. However, majority of the BcA86 genome is from the hyporesponsive strain C57BL/6J. Our goal was to identify the genomic regions that are associated with this BcA86 phenotype. Using F2 mice generated from BcA86 backcrossed to C57BL/6J, we identified a QTL for airway hyperresponsiveness on mouse chromosome 12. We validated the importance of mouse chromosome 12 in airway responsiveness using a chromosome 12 substitution strain (CSS12) which contains A/J chromosome 12 on a C57BL/6J background. The CSS12 strain also had a lung responsiveness phenotype similar to A/J. We selected genes within our QTL as candidates for airway hyperresponsiveness if they contained a deleterious coding variant (based on PROVEAN analysis) or if they were differently expressed between hyperresponsive (A/J, BcA86, CSS12) and hyporesponsive (C57BL/6J) strains.

overall_design: Based on microarray analysis followed by validation with RT-QPCR, genes within the QTL that are differently expressed between hyperresponsive strains (CSS12 and BcA86) and hyporesponsive strain (C57Bl/6J) were selected as candidates for airway hyperresponsiveness.

first: Robert

last: Sladek

first: Silvia

last: Vidal

first: Danuta

last: Radzioch


title: Whole genome microarray analysis in myxoid liposarcoma

status: Public on Oct 28 2014

city: Cologne

first: Helen

last: Künstlinger

address: Kerpener Str. 62

department: Institute of Pathology

institute: University Hospital Cologne

summary: In order to identify new key molecules in the pathogenesis of myxoid liposarcoma, we performed comparative gene expression profiling in myxoid liposarcoma and fat tissue samples.

overall_design: Whole genome microarray analysis was performed on eight primary myxoid liposarcoma samples and an RNA pool of eight healthy fat tissue samples.

first: Sabine

last: Merkelbach-Bruse


title: Expression data from fasted macroH2A1/2 double knockout adult mouse liver

status: Public on Oct 15 2014

first: John

last: Pehrson

address: 3800 Spruce Street

institute: University of Pennsylvania

summary:
MacroH2As core histone variants have a unique structure that includes C-terminal nonhistone domain. MacroH2As are highly conserved in vertebrates, and are thought to regulate gene expression. However the nature of genes regulated by macroH2As and the biological significance of macroH2As for the organism remain unclear. Here we examine macroH2A function in vivo by knocking out both macroH2A1 and macroH2A2 in the mouse.
We used microarrays to examine how the absence of macroH2A.1 and macroH2A.2 histone variants affect gene expression fasted adult mouse liver.

overall_design: Two month old male mice were fasted overnight (~16 hours). Mice were sacrificed between 9:00 and 10:00 AM, livers were collected and snap frozen with liquid nitrogen. Total RNA was extract with Trizol (life technologies) following standard protocol.


title: The long noncoding RNA PCAT-1 promotes prostate cancer cell proliferation through post-transcriptional stabilization of the cMyc oncogene

city: Ann Arbor

last: Prensner

state: MI

address: 1400 E. Medical Center Drive, Room 7431 CCGC

department: Michigan Center for Translational Pathology

institute: University of Michigan

summary: Transcriptional profiling of Du145-PCAT1 and RWPE-PCAT1 cells treated with either non-targeting siRNA or two independent siRNAs targeting cMyc. The goal was to determine the role of cMyc in mediating PCAT-1 transcriptional regulation.

overall_design: Three-condition experiment, PCAT1 cells with non-targeting siRNA vs cMyc siRNA #3 or cMyc siRNA #4. Performed on two cell lines, Du145 and RWPE. Biological replicates: 2 control replicates per cell line, 2 transfected replicates per siRNA per cell line.

first: Felix

last: Feng


title: Transcriptional profile of genes affected by the loss of Brd4 in the embryonic stem cells

first: Jianxin

last: You

address: 3610 Hamilton Walk

department: Department of Microbiology

institute: University of Pennsylvania Perelman School of Medicine

summary:
BRD4 is an important epigenetic reader implicated in the pathogenesis of a number of different cancers and other diseases.  Brd4-null mouse embryos die shortly after implantation and are compromised in their ability to maintain the inner cell mass (ICM), which gives rise to embryonic stem cells (ESCs). We investigated the functions of Brd4 in the ESCs in the present study.
To determine the Brd4 target genes in embryonic stem cells.

overall_design: TL1 ESCs were transfected with control siRNA, or Brd4 siRNA.  At 48 h post-transfection, total RNAs were isolated using the RNeasy minikit (Qiagen). Expression microarray analyses were performed on mRNA samples isolated from three independent experiments using a mouse Gene 2.0ST array (Affymetrix) at the University of Pennsylvania Microarray Core Facility. RMA from Affymetrix package  was applied to the data for preprocessing and normalization. Limma was used for detection of differentially expressed genes. Benjamini & Hochberg correction was applied for the multiple comparisons.

first: Wei

last: Liu


title: Gene expression profile in human cancer BG-1 and MCF-7 cells

city: RTP

first: NIEHS

last: Microarray Core

address: 111 T.W. Alexander Drive

institute: NIEHS

summary: We have evidence to believe that the BG-1 cells (named as BG-1 NIEHS here) we had obtained some years ago and provided to some laboratories are actually a clonal variation of MCF-7 cells. This only became evident from a recent Short Tandem Repeats (STR) analysis. We also have obtained another source of BG-1 cells from an investigator in France which we have named BG-1 FR. In this study, we compared gene expression profile in the two BG-1 lines (BG-1 FR or BG-1 NIEHS) and MCF-7 cells to identify differential genes set. We then will compare within each cell line and determine gene expression changes in response to E2 treatment that are specific for mechanism of ER’s actions in each cell type.

overall_design: The total RNA was isolated from the cells tretaed with vehicle (75% EtOH) or Estrodiol (10 nM E2) for 18 hrs. In each treatment group, we included the 3 biological replicates.The microarray analysis was perfomed using Agilent whole human 4x44K multiplex oligo arrays (014868).

first: Yin

last: Li

first: Ken

last: Korach


title: Expression data from loss-of-TET2 and/or JAK2V617F mutant Lineage-c-Kit+Sca-1+ (LSK) bone marrow cells

status: Public on Oct 16 2014

city: Miyazaki

first: Takuro

last: Kameda

address: 5200, Kihara, Kiyotake

department: Division of Gastroenterology and hematology, Department of Internal medicine

institute: University of Miyazaki

summary: Recent studies have shown that both TET2 mutation and JAK2V617F mutation are frequent in myeloproliferative neoplasms patients. The pathophysiological roles of each mutation have been elucidated in murine models, but the cooperative effect of the two mutations has not been elucidated yet. In this study, we examined the function of the cooperative effect of loss-of-TET2 function and JAK2V617F mutation in murine hematopoiesis.

overall_design: In this study, we utilized wild type (WT) mice, TET2 knock down (TET2KD) mice, JAK2V617F transgenic mice, double mutant mice. We transplanted 4 types of E14.5 fetal liver cells (WT, TET2KD, JAK2V617F, double mutant) into lethally irradiated mice. At 10-16 weeks post-transplantation, LSK cells from the BM of the recipients were collected, and gene expression analysis was performed. (WT,5 mice at 16 weeks; TET2KD, 5 mice at 10 weeks; JAK2V617F, 5 mice at 16 weeks; double mutant, 5 mice at 13 weeks)

first: Kazuya

last: Shimoda


title: Targeted disruption of BMAL1 in the peripheral reproductive axis results in infertility in female mice

city: Madison

first: Brian

middle: P

last: Johnson

address: 1400 University Ave

department: Oncology

institute: UW-Madison

summary: The product of the Bmal1 locus is an essential component of the circadian clock that plays important roles in various aspects of reproductive biology,and when disrupted results in infertility. In an effort to establish the identity of the tissue specific clock that is responsible for this infertility, we used the steroidogenic factor-1 (Sf1) promoter to drive Cre-mediated recombination and genetically delete Bmal1 within cells of the reproductive axis. We show that Bmal1 within the reproductive axis of females is essential for normal fertility through its role in maintaining implantation, but is not required for normal estrous cycling. At the root of this biology appears to be a defect in the ovaries, including regulation of ovarian lipid biosynthetic or metabolic processes  and their roles in maintaining progesterone synthesis.  This conclusion is based upon three observations.  First, that deletion of Bmal1 within the reproductive axis reducesleads to affected transcripts in steroidogenic pathways for the LH receptor  , and lowers progesterone levels.  Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants rescues fertility.  Our study demonstrates the significance of ovarian Bmal1 as an overriding influence in experimental models of infertility.

overall_design:
A time series was performed in time-mated C57Bl/6J mice to identiy oscillating transcripts.
During the peak and trough of the majority of transcripts (ZT0 and ZT12) samples from Bmal1fx/fx  Sf1Cre mice and control litermates as well and global Bmal1 nulls were also analyzed.
The tissue types (ovary, pituitary) are not comparable.

first: Yan

first: Christopher

middle: A

last: Bradfield


title: Expression profiling of co-cultures of prostate cancer cells and stroma cells, with or without TGF-beta signaling

city: Houston

first: Chad

last: Creighton

address: One Baylor Plaza, Mail Stop: BCM305

institute: Baylor College of Medicine

summary: Prostate stroma-specific TGF-beta signaling induces morphological changes in LNCaP cells. We have previously shown that stromal TGF-beta signaling regulates prostate tumor growth.  To further delineate the underlying mechanisms, we generated LNCaP cells overexpressing an HA-tagged constitutively activate TGF-beta1 ligand (LNCaP-HA-TGF-β1(a)) and control LNCaP cells  (LNCaP-Ctrl), and performed in vitro co-cultures of LNCaP-HA-TGF-β1(a) and LNCaP-Ctrl cells on top of the confluent HPS-19I cells, a human prostate stromal cell line.   Since LNCaP cells are defective in TGF-beta receptor I (TbetaRI / ALK-5) that is essential for mediating TGF-beta signaling, only HPS19I cells are able to respond to TGF-beta ligand in these co-cultures.  This provides a unique opportunity to study how prostate stromal cell-specific TGF-beta signaling regulates PCa biology.

overall_design:
LNCaP + HPS19I co-cultures, with or without TGF-beta and with or without SD208 (a TBetaRI (ALK-5) protein kinase-specific inhibitor)
KEYWORDS: multiple group comparison

first: David

last: Rowley

first: Feng

last: Yang


title: Co-cultures of prostate cancer cells and stroma cells, with or without TGF-beta signaling

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

overall_design: Refer to individual Series


title: Comparison of gene expression in control and BRG1-knockdown H358 cell lines

status: Public on Sep 23 2014

city: Chapel Hill

first: Vonn

last: Walter

address: CB#7295, School of Medicine

institute: Lineberger Comprehensive Cancer Center

summary: Transcription was assessed in the human H358 NSCLC cell line after knockdown of BRG1, one of the mutually exclusive subunits of the SWI/SNF chromatin remodeling complex, by 2 different shRNAs.

overall_design: One biolgical replicate of each treatment; 4 technical replicates of each treatment.

first: Bernard

last: Weissman

first: Tess

last: Orvis


title: Influence of SB431542 on J1 mouse embryonic stem cells growth

status: Public on Oct 29 2014

city: Yangling

first: Juan

last: Du

state: China/Shaanxi

address: 3 Taicheng Road

country: China

institute: College of Life Sciences

summary: To know exactly how SB431542 contribute to mouse embryonic stem cells (mESCs) undifferentiated state maintenance, microarray experiment for DMSO mock treated and SB431542 treated J1 mESCs was performed

overall_design: J1 mESCs maintained in  medium containing 1000 U/mL LIF and supplemented without or with SB431542 for 24 hours, then total RNA was extracted for analysis.

first: Yongyan

last: Wu

first: Zhiying

last: Ai

first: Xiaoyan

last: Shi

first: Zekun

last: Guo


title: Small molecules facilitate rapid and synchronous iPSC generation

city: Boston

first: Ori

last: Bar-Nur

state: MA

address: 185 Cambridge st.

department: Center of Regenerative medicine

institute: Harvard University

summary: The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) upon overexpression of OCT4, KLF4, SOX2 and c-MYC (OKSM) provides a powerful system to interrogate basic mechanisms of cell fate change. However, iPSC formation with standard methods is typically protracted and inefficient, resulting in heterogeneous cell populations. We show that exposure of OKSM-expressing cells to both ascorbic acid and a GSK3-β inhibitor (AGi) facilitates more synchronous and rapid iPSC formation from several mouse cell types. AGi treatment restored the ability of refractory cell populations to yield iPSC colonies, and it attenuated the activation of developmental regulators commonly observed during the reprogramming process. Moreover, AGi supplementation gave rise to chimera-competent iPSCs after as little as 48 h of OKSM expression. Our results offer a simple modification to the reprogramming protocol, facilitating iPSC induction at unparalleled efficiencies and enabling dissection of the underlying mechanisms in more homogeneous cell populations.

overall_design:
18 samples were analyzed in total, samples represent bulk cultures of reprogrammable-MEFs (Rep-MEFs) that express OKSM and were supplemented with ascorbic acid and GSK3i during iPS cell induction. Control samples represent similar bulk cultures of reprogrammable-MEFs that express OKSM but were not supplemented with ascorbic acid and GSK3i during iPS cell induction.
GMP-iPSCs were generated using 48 hours of OKSM+AGi induction. Fibroblast-iPSCs were generated using 96 hours of OKSM+AGi induction.

first: Justin

last: Brumbaugh

first: Konrad

last: Hochedlinger


title: Ebf2 is a selective marker of brown and beige adipogenic precursor cells (Microarray)

status: Public on Sep 16 2014

city: Cincinnati

first: Hee-Woong

last: Lim

state: Ohio

address: 3333 Burnet Ave. MLC 7024

department: Division of Biomedical Informatics

institute: Cincinnati Children's Hospital Medical Center

summary: Brown adipocytes, muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to Pdgfrα+, Myf5Cre-lineage-marked cells. RNAseq analysis identified Early B Cell Factor-2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2-GFP embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2-expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells.

overall_design: Embryonic fibroblasts, isolated from dorsal body wall of E14.5 Ebf2(GFP)/+ embryos, were further fractionated based on the expression of PDGFRα and Ebf2 (GFP).  Affymetrix microarray analysis was prefromed,to compare the gene expression between PDGFRα+ Ebf2(GFP)- and PDGFRα+ Ebf2(GFP)+ cells.

first: Wenshan

last: Wang

first: Megan

last: Kissig

first: Sona

last: Rajakumari

first: Li

last: Huang

first: Kyoung-Jae

last: Won

first: Patrick

last: Seale


title: Human renal clear-cell carcinoma cells : control vs MUC1 overexpressing cells

status: Public on Aug 25 2014

city: lille

first: frédéric

last: leprêtre

address: Boulevard du Pr Leclercq

department: CHU of Lille, CBP

institute: Lille University

summary: Transcriptional profiling of human renal clear-cell carcinoma cells comparing control unexpressing MUC1 cells (82-F7 and 82-65 samples) with MUC1 overexpressing cells (83-2 and 83-5 samples)

overall_design: Goal was to determine the effect of MUC1 expression on global gene expression

first: Michaël

last: Perrais


title: An eIF4E1/4E-T complex determines the genesis of neurons from precursors by translationally repressing a proneurogenic transcription program

status: Public on Sep 25 2014

city: Toronto

first: Freda

middle: D

last: Miller

address: 686 Bay Street

institute: Hospital for Sick Children

summary: Here, we have addressed the mechanisms that determine genesis of the correct numbers of neurons during development, focusing upon the embryonic cortex. We identify in neural precursors a repressive complex involving eIF4E1 and its binding partner 4E-T that coordinately represses translation of proteins that determine neurogenesis. This eIF4E1/4E-T complex is present in granules with the processing body proteins Lsm1 and Rck, and disruption of this complex causes premature and enhanced neurogenesis and neural precursor depletion. Analysis of the 4E-T complex shows that it is highly enriched in mRNAs encoding transcription factors and differentiation-related proteins. These include the proneurogenic bHLH mRNAs, which colocalize with 4E-T in granules, and whose protein products are aberrantly upregulated following knockdown of eIF4E, 4E-T, or processing body proteins. Thus, neural precursors are transcriptionally primed to generate neurons, but an eIF4E/4E-T complex sequesters and represses translation of proneurogenic proteins to determine appropriate neurogenesis.

overall_design: We obtained 3 biological replicates of IgG-bound RNA, 4E-T-bound RNA, and cooresponding total RNA input from mouse E12-13 cortices. RNA samples were analyzed on the Affymetrix Mouse Gene 2.0 ST Arrays.

first: Guang

last: Yang

first: Craig

last: Smibert

first: David

last: Kaplan


title: Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster at P1

status: Public on Aug 22 2014

city: Villenave d'Ornon

first: Pascal

middle: GP

last: Martin

address: 71 avenue Edouard Bourlaux

department: UMR1332 BFP

institute: INRAE

summary: In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the mother’s milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions.

overall_design: Liver gene expression at P1 was measured in neonates with a maternally-inherited deletion of the miR-379/miR-410 cluster (KO) and compared to that of wild-type littermates (n=5). KO_normoglycemic and KO_hypoglycemic individuals correspond to mutant pups wild mild hypoglycemia (n=3) and with severe hypoglycemia (n =7), respectively.

first: Yannick

last: Lippi

middle: G

first: Stephane

last: Labialle

first: Virginie

last: Marty

first: Magalie

last: Hoareau-Hossman

first: Marie-Line

last: Bortolin-Cavaillé

first: Jérôme

last: Cavaillé


title: Gene expression data of Kas-/- mouse emobryonic fibroblasts transfected with KRAS siRNAs

status: Public on Sep 01 2014

city: Bethesda

first: Ji

last: Luo

state: MD

address: 10 Center Drive, 10/3B43c

institute: National Cancer Institute

summary:
We used Kras/Hras/Nras-triple knockout MEFs expressing recombinant Nras to test the off-target effect of 2 Kras siRNAs at different transfection concentrations.
Gene expression profiles were generated using Affimymetrix Mouse Gene ST 2.0 microarrays.

overall_design: Cells were transfected with Kras siRNAs and gene expression profiles were generated to identify genes up or down regulated by each siRNA at different transfection concentrations.

first: Tina

last: Yuan

first: Chih-Shia

last: Lee

first: Frank

last: McCormick


title: Transcriptomic characterization of C57BL/6 mouse embryonic stem cell differentiation and its modulation by developmental toxicants

status: Public on Sep 09 2014

city: Laurel

first: Xiugong

last: Gao

address: 8301 Muirkirk Rd

department: HFP/OLOAS/OCT/DT

institute: US FDA

summary:
To develop an in vitro model for developmental toxicity testing, we characterized gene expression changes during mouse embryonic stem cell (mESC) differentiation and their modulation by developmental toxicants.
C57BL/6 mESCs were allowed to differentiate spontaneously and global gene expression changes were studied using microarrays at at different time points after embryoid body (EB) formation.
Develpmental toxicants tested include 2.0 mM monobutyl phthalate (MBP), 0.25 mM thalidomide (THD), and 1.0 mM valproic acid (VPA).

overall_design: RNA of control samples (unexposed) was collected at 0, 24, 48, 72, 96, 120 and 168 h after EB formation; RNA of compound-exposed samples were collected at 24 h after EB formation. Three replicates were included for each experimental condition.

first: Jeffrey

last: Yourick

first: Robert

middle: L

last: Sprando


title: Up-regulated aldo-ketoreductase1B10 in chronic hepatitis C: Association with serum alpha-fetoprotein and hepatocellular carcinoma

status: Public on Sep 15 2014

city: Izunokuni

first: Shunsuke

last: Sato

state: Shizuoka

address: 1129 Nagaoka

department: Department of Internal Medicine

institute: Juntendo University Shizuoka Hospital

summary:
We attempted to identify a specific gene expression signature by performing microarray analysis on the livers of patients with chronic hepatitis C and AFP elevation. Distinct hepatic gene expression patterns were demonstrated between patients with elevated AFP (≥10ng/mL) and normal AFP (<10ng/mL). Among the 30,150 valid genes, 627 were identified as differentially expressed genes with a minimal fold change of 2.0. Using these 627 genes, PCA and HCA were used to successfully distinguish samples according to their AFP status.
Of the 627 differently expressed genes, AKR1B10 was most abundantly expressed in patients with elevated AFP. AKR1B10 expression was validated by Real-time RT-PCR and immunohistochemical study. Furthermore, a proportional correlation between AKR1B10 expression and serum AFP was demonstrated by regression analysis.  A matched case-control study indicated that AKR1B10 up-regulation was an independent risk factor for HCC development.

overall_design: Liver tissues samples from 48 chronic hepatitis C patients were stratified by their serum AFP levels and analyzed for gene expression profiles. AKR1B10 was up-regulated in patients with chronic hepatitis C in association with serum AFP, and was an independent risk factor for HCC development.

first: Takuya

last: Genda

first: Katsuharu

last: Hirano

first: Hironori

last: Tuzura

first: Yutaka

last: Narita

first: Yoshio

last: Kanemitsu

first: Tetsu

last: Kikuchi

first: Katsuyori

last: Iijima

first: Ryo

last: Wada

first: Takafumi

last: Ichida


title: Gene expression in Bone marrow derived macrophages (BMDM) in the presence or absence of Necrotic cells.

status: Public on Aug 08 2014

city: Gifu

first: Takashi

last: MaruYama

address: 1-1 Yanagido

institute: Gifu University

summary: We have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish danger signal induced inflammatory response.   BMDM from C57/BL6 mice cultred in the presence or absence of heat shock necrotic A20 cells for 1hr.

overall_design: Control sample (Non_4) is  'BMDM in the absence of necrotic A20 cells' and reference sample (Dead_4) is 'BMDM in the presence of necrotic A20 cells'


title: Opposing Effects of HIF1α and HIF2α on Chromaffin Cell Phenotypic Features and Tumor Cell Proliferation: Insights from MAX

status: Public on Sep 18 2014

city: Madrid

first: Mercedes

last: Robledo

state: Madrid

address: C/ Melchor Fernández Almagro, 3

department: Human Cancer Genetics Program

country: Spain

institute: Spanish National Cancer Research Centre (CNIO)

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus


title: Gene expression regulating the onset of heat-induced intratesticular calcification.

status: Public on Aug 01 2014

city: Sapporo

first: Masataka

last: Chihara

state: Hokkaido

address: Kita 18, Nishi 9, Kita-ku

department: Department of Biomedical Sciences

institute: Graduate School of Veterinary Medicine, Hokkaido University

summary: We compared gene expression profiles between testes from C57BL/6 and C57BL/6-background congenic mouse strain B6.MRLc1-(D1Mit202–D1Mit403) carrying the telomeric region of MRL-type Chr 1 (67.97–81.63 cM) at 10 days after a single scrotal heat stress of 43°C for 20 min.

overall_design: Heat-induced gene expression in mouse testis was measured at 10 days after a single heat exposure. The testes were isolated from 3 C57BL/6 and 3 B6.MRLc1-(D1Mit202–D1Mit403). C57BL/6 versus B6.MRLc1-(D1Mit202–D1Mit403) analysis was performed.


title: Gene expression analysis of B16-F1 melanoma tumors established in WT and Stat2KO mice

status: Public on Aug 17 2014

city: Philadelphia

first: Ana

middle: Maria

last: Gamero

address: 3440 N. Broad St.

department: Biochemistry

institute: Temple University

summary:
STAT2 is an essential transcription factor in type I interferon (IFN) signaling. STAT2 mediates the antigrowth and apoptotic effects of IFN as demonstrated in cell lines thus leading to the hypothesis that STAT2 has tumor suppressor function.
We used microarrays to identify genes in the tumors that are STAT2 dependent and important in anti-tumor immunity.

overall_design: B16-F1 melanoma tumor cells were implanted on the dorsal flank of either wild type (WT) or Stat2KO (S2KO). Tumor growth was monitored during the course of 3 weeks. S2KO mice developed larger tumors when compared to WT mice.


title: SIRT6 and SIRT1 contribute to circadian gene expression

status: Public on Aug 05 2014

city: Irvine

first: Paolo

last: Sassone-Corsi

state: CALIFORNIA

address: Sprague Hall

institute: University of California, Irvine

summary: Comparison of the hepatic circadian transcriptomes reveals that SIRT6 and SIRT1 separately control transcriptional specificity, and therefore, define distinctly partitioned classes of circadian genes.

overall_design: Livers from WT and SIRT6 KO mice, and livers from WT and SIRT1 KO mice, were harvested over the circadian cycle at ZT 0, 4, 8, 12, 16 and 20 for gene expression analysis.

first: Selma

last: Masri


title: Transcriptomes of the Cochlear Inner and Outer Hair Cells

status: Public on Aug 12 2014

city: Omaha

first: David

last: He

state: Nebraska

address: 2500 California Plaza

institute: Creighton University

summary:
The transcriptome is the complete set of all RNA transcripts produced by the genome in a cell and reflects the genes that are being actively expressed. Transcriptome analysis is essential for understanding the genetic mechanism controlling the phenotype of a cell.
Using DNA microarray technique we examined transcriptomes of 2,000 individually collected inner (IHCs) and outer hair cells (OHCs), two types of auditory sensory cells critical for hearing.  Among approximately 16,645 and 17,711 transcripts considered to be expressed, 1,296 and 256 genes showed significant differential expression in IHCs and OHCs, respectively.  The top ten differentially expressed genes include Slc17a8, Dnajc5b, Slc1a3, Atp2a3, Osbpl6, Slc7a14, Bcl2, Bin1, Prkd1, Map4k4 in IHCs, and Slc26a5, C1ql1, Strc, Dnm3, Plbd1, Lbh, Olfm1, Plce1, Tectb, Ankrd22 in OHCs. Many unknown sequences and non-coding RNAs were also expressed in hair cells. The differentially expressed genes underlie the genetic mechanism for unique functions of IHCs and OHCs.

overall_design: The total RNA was extracted from the collected pools of single outer hair cells (OHCs) and inner hair cells (IHCs). Their whole-genome transcriptome expression was detected using GeneChip microarray analysis. The analysis and comparison between OHC and IHC allow us to determine what genes are expressed and what genes are uniquely or differential expressed in each population.

first: Huizhan

middle: Z

last: Liu

first: Jason

last: Pecka

first: Qian

last: Zhang

first: Garrett

last: Soukup

first: Kirk

middle: W

last: Beisel


title: Global expression profiling of newly derived EpiSC lines

city: Tsukuba

first: Kuniya

last: Abe

state: Ibaraki

address: 3-1-1 Koyadai

department: BioResource Center

institute: RIKEN

summary: To characterize molecular features of new EpiSC lines established by the Wnt inhibition method, global gene expression profiles of the EpiSC lines were determined by microarray, and compared to those of EpiSC lines established by other group using the conventional method. Epiblasts, the source of the EpiSCs, and mESCs were also analyzed.

overall_design: EpiSCs and mESC were maintained as undifferentiated state on feeder layers. The stem cells were then separated from feeders, and RNAs were extracted from the stem cell lines. Embryonic tissues were manually dissected out from mouse embryos of E5.5, E6.5 or E7.5, from which RNAs were extracted.


title: Gene expression signatures in Tif1b, Hp1a or Hp1g knockdown hematopoietic progenitors

city: Chiba

first: Satoru

last: Miyagi

state: Chiba

department: Graduate school of Medicine

institute: Chiba university

summary: Gene expression analyses of Tif1b, Hp1a or Hp1g knockdown hematopoietic progenitors. Growth of hematopoietic stem cells (HSCs) are significantly impaired upon knockdown of Hp1a and Hp1g. Results provide insight into the role of these factors in hematopoiesis.

overall_design: HSCs (CD34- c-Kit+ Sca1+  Lineage- )  were transduced with lentivirus expressing shRNA against Tif1b, Hp1a or Hp1g, and cultured for 14 days. Then, GFP+ c-Kit+ Lineage- hematopoietic progenitors were sorted and subjected into microarray analysis

first: Atsushi

last: Iwama

first: Syuhei

last: Koide


title: Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster obtained 4h following a caesarean at embryonic day E19.5

first: Pascal

last: Martin

overall_design: Liver gene expression was measured in mice with a maternally-inherited deletion of the miR-379/miR-410 cluster and in wild-type littermates at embryonic day E19.5, 4h following the caesarean delivery (n=4 biological replicates per genotype)

first: Yannick

last: Lippi

first: Stéphane

last: Labialle

first: Virginie

last: Marty

first: Magali

last: Hoareau-Osman

first: Marie-Line

last: Bortolin-Cavaillé

first: Jérôme

last: Cavaillé


title: Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster at E19.5 and P0

overall_design: Liver gene expression was measured in mice with a maternally-inherited deletion of the miR-379/miR-410 cluster (KO) and in wild-type littermates (WT) at embryonic day E19.5 (n=3 per genotype) and on the day of birth (P0, n=4 WT and 5 KO).

first: Stephane

first: Magalie

last: Hoareau-Hossman


title: Expression data from vehicle and adrenomedullin treated human lymphatic endothelial cells

status: Public on Jul 31 2014

city: Chapel Hill

first: Kathleen

last: Caron

state: NC

address: 111 Mason Farm Drive

institute: UNC-Chapel HIll

summary: Human dermal lymphatic endothelial cells were cultured and treated with either vehicle or 10 nM AM for 15 minutes, 1 hour, or 24 hours to assess gene expression changes across the human genome with AM treatment.

overall_design: Two variable experiment, time (0.25, 1, 24 hours) and treament (vehicle vs adrenomedullin) of gene expression in human lymphatic endothelial cells. Biological replicates: 3-4 per condition.

first: Klara

last: Klein

first: Dunworth

last: William


title: Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster

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

overall_design: Refer to individual Series


title: The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy

city: Cambridge

first: Marc

last: Mendillo

address: 9 Cambridge Center

institute: Whitehead Institute for Biomedical Research

summary:
Stromal cells within the tumor microenvironment are essential for tumor progression and metastasis. Yet surprisingly little is known about the factors that drive the transcriptional reprogramming of stromal cells within tumors. We report that the transcriptional regulator Heat-Shock Factor 1 (HSF1) is activated in cancer-associated fibroblasts (CAFs) and is a potent enabler of malignancy.  In CAFs, HSF1 drives a transcriptional program that complements, yet is completely different from, the program it drives in adjacent cancer cells. This CAF program is uniquely structured to support the malignant potential of cancer cells in a non-cell-autonomous way and involves two central stromal signaling molecules—TGFβ and stromal-derived factor 1 (SDF1). As clinical confirmation, in early stage breast and lung cancer high stromal HSF1 activation is strongly associated with poor patient outcome. Thus, cancers co-opt the ancient, multifaceted survival functions of HSF1 to orchestrate malignant progression in unexpected ways that have far-reaching therapeutic implications.
Gene expression data

overall_design: We used microarrays to examine the HSF1-dependent effect of co-culture on gene expression in cancer cells and fibroblasts. D2A1 mouse breast cancer cells were co-cultured with WT or Hsf1 null MEFs for 72h, afterwhich the two cell types were separated from each other by FACS and analyzed. Each cell type was also grown separately, as control.

first: Ruth

last: Scherz-Shouval

first: Sandro

last: Santagata

first: Lynette

middle: M

last: Sholl

first: Irit

last: Ben-Aharon

first: Andrew

middle: H

last: Beck

first: Dora

last: Dias-Santagata

first: Laleh

last: Montaser-Kouhsari

first: Martina

last: Koeva

first: Salomon

last: Stemmer

first: Luke

last: Whitesell

first: Susan

last: Lindquist


title: SIRT1 deficiency enhances RA induced mESC differentiation

status: Public on Aug 21 2014

city: RTP

first: NIEHS

last: Microarray Core

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary: Retinoid homeostasis is critical for normal embryonic development, and both the deficiency and excess of these compounds are associated with congenital malformations. Here we found that SIRT1, the most conserved mammalian NAD+-dependent deacetylase, contributes to the maintenance of homeostatic retinoic acid (RA) signaling and modulates mouse embryonic stem cell (mESC) differentiation. Our data show that SIRT1 deficiency enhances RA signaling, thereby accelerating mES cell differentiation in response to RA. Our findings highlight the importance of SIRT1 in transcriptional regulation of ESC pluripotency and embryogenesis.

overall_design: Three pairs of sh-Control and sh-SIRT1 E14 mESC cells (with dulpicate for each sample) were treated with vehicle ethanol or with 20 nM of RA for 2 days. Total RNA was isolated using a Qiagen RNA easy mini kit with on-column DNAseI treatment. RNA quality was validated with the Agilent 2100 Bioanalyzer in the microarray facility.  Three-pairs of ethanol treated samples, and 4 RA treated sh-Control, and 6 RA treated sh-SIRT1 samples were analyzed by Agilent Whole Mouse Genome 4x44 formate oligo arrays (014868) (Agilent Technologies) following the Agilent 1-color microarray-based gene expression analysis protocol.

first: Xiaoling

last: Li


title: Expression data for Lck-Cre, Med23flox/flox and Med23flox/flox;Lck-Cre thymocytes +/- 3hr exposure to plate bound anti-CD3 antibody

status: Public on Jul 30 2014

city: Memphis

first: Suzanne

last: Baker

state: TN

address: 262 Danny Thomas Place

department: Developmental Neurobiology

institute: St Jude Children's Research Hospital

summary: MED23, a subunit of the Mediator coactivator complex, is important for the expression of a subset of MAPK/ERK pathway-dependent target genes; however, the genes in this subset varies between cell types.  MAPK/ERK pathway-dependent processes are essential for T-cell development and function, but whether MED23 has a role in this context is unknown.  We generated Med23 conditional knockout mice and induced Med23 deletion in early T cell development using the lineage specific Lck-Cre transgene.  While the total cell number and distribution of cell populations in the thymuses of Med23flox/flox;Lck-Cre mice were essentially normal, MED23 null T-cells failed to efficiently populate the peripheral lymphoid organs.  MED23 null thymocytes displayed decreased expression of the MAPK/ERK-responsive genes Egr1, Egr2, as well as of the membrane glycoprotein Cd52 (CAMPATH-1).  MED23 null CD4 single-positive thymocytes also showed decreased expression of KLF2 (LKLF), a T cell master regulatory transcription factor.  Indeed, similarities between the phenotypes of mice lacking MED23 or KLF2 in T-cells suggest that KLF2 deficiency in MED23 null T-cells is one of their key defects.  Mechanistic experiments using MED23 null MEFs further suggest that MED23 is required for full activity of the MAPK-responsive transcription factor MEF2, which has previously been shown to mediate Klf2 expression.  In summary, our data indicate that MED23 has critical roles in enabling T-cells to populate the peripheral lymphoid organs, possibly by potentiating MEF2-dependent expression of the T-cell transcription factor KLF2.

overall_design: 12 samples, 2 of each genotype (Lck-Cre, Med23flox/flox and Med23flox/flox;Lck-Cre) both with mock and anti-CD3 treatment

first: Paul

middle: K

last: Brindle

first: Lawryn

last: Kasper


title: SIRT6 regulates glucose metabolism and glutamatergic synapse in the mouse retina

city: Boston

first: Kenneth

middle: N

last: Ross

address: 450 Brookline Ave., Rm M640

department: Pediatric Oncology

institute: Dana-Farber Cancer Institute

summary:
Microarray analysis on total retinal RNA from 15 day old Sirt6 wild-type (WT) and knock-out (KO) mice.
The retina is one of the major energy consuming tissues within the body. In this context, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is a highly demanding energy consuming process. Sirtuin 6 (SIRT6), a NAD-dependent deacylase, plays a key role in regulating glucose metabolism. In this study, we demonstrate that SIRT6 is highly expressed in the retina, controlling levels of histone H3K9 and H3K56 acetylation. Notably, despite apparent normal histology, SIRT6 deficiency caused major retinal transmission defects concomitant to changes in expression of glycolytic genes and glutamate receptors, as well as elevated levels of apoptosis in inner retina cells. Our results identify SIRT6 as a critical modulator of retinal function, likely through its effects on chromatin.

overall_design: Microarray analysis of total retinal RNA from 15 day old Sirt6 wild-type (WT) and knock-out (KO) mice with 3 replicates in each condition using the Affymetrix Mouse Gene 2.1 ST array (transcript (gene) version).

first: Dafne

last: Silberman

first: Raul

last: Mostoslavsky


title: Development of gene expression signatures for Mmp19 regulation of fibroblast phenotype in mouse lungs

city: Mexico

first: Annie

last: Pardo

state: Mexico DF

address: 200n lothrop st

department: Facultad de Ciencias

country: Mexico

institute: Universidad Nacional Autónoma de México

summary: We have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish Mmp19 regulation of fibroblast phenotype changes in mouse lungs. Pulmonary fibrosis was induced by bleomycin at 0.08 u in 50ul of saline. At 21st day the mice were sacrificed and mouse lung fibroblasts were isolated and cultured in FBM plus additives following Lonza's portocol. RNA was extracted with miRNA mini kit from Qiagen. Gene expression microarray was performed with Agilent. A 834-gene consensus signature was identified that distinguished between Mmp19 knockout mice from wildtype. Some gene expression in the same RNA samples were validtaed by real-time PCR.

overall_design: The established bleomycin induced fibrosis was used in this experiment. At day 21 the fibrosis would be the situation of stable fibrosis. We administrated 0.08u of bleomycin intratracheally into wildtype and Mmp19 knockout mice, sacrificed the mice at 21st day and isolated the lung fibroblasts and culturing. Five independent experiments were performed and 3 for gene expression experiment.

first: Guoying

last: Yu


title: Comparison of H460 derived CSCs and cisplatin-resistant cells

city: Cantoblanco

first: Juan

middle: Carlos

last: Oliveros

address: Darwin 3

institute: CNB, CSIC

summary: Transcription profile of cancer stem cells isolated from human non-small cells lung cancer (NSCLC) H460 cells. The profile of H460 cells that were made resistant to cisplatin after a single treatment with the drug was also determined. Both profiles were finally compared.

overall_design: Each microarray contained one of these comparative experiments (two-channels): H460C (H460 derived CSCs) vs H460 and H460R (cisplatin-resistant H460 cells) vs H460. Technical replicates were made with dye-swap-based design. Total biological replicates per cell type (H460C and H460R): 2.

first: Blanca

last: Lopez-Ayllon

first: Veronica

last: Moncho-Amor

first: Ander

last: Abarrategi

first: Inmaculada

last: Ibañez-de-Cáceres

first: Javier

last: Castro-Carpeño

first: Cristobal

last: Belda-Iniesta

first: Rosario

last: Perona

first: Leandro

last: Sastre


title: Prostate cancer specific gene expression

city: Kanazawa

first: Atsushi

last: Mizokami

state: Ishikawa

address: 13-1 Takara-machi

department: School of Medicine

institute: Kanazawa University

summary:
To identify prostate cancer-specific gene expression, we have employed whole cDNA microarray expression profiling between benign prostate hypertrophy and prostate cancer. We performed needle biopsy of patients with prostatic hyperplasia who were suspected as prostate cancer for minor high level (4.0-10 ng/ml). As a result of needle biopsy, we used the tissue of patients with prostatic hyperplasia that prostate cancer was denied for cDNA microarry analysis. Furthermore, we also performed needle biopsy of patients that prostate cancer should have been strongly suspected because of high PSA.
Needle biopsies were performed after we obtained informed consent from patients with the document approved from the Graduate School of Medical Science, Kanazawa University.

overall_design: Gene expression profile was determied in each of normal prostate samples and prostate cancer samples. Then the profiles were compared between normal prostate samples and prostate cancer samples.


title: Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development

status: Public on Jul 22 2014

first: Michael

middle: Patrick

last: Morley

state: PA

address: 3400 Civic Center Blvd, Bldg 421

department: Penn Cardiovascular Institute

institute: Perelman School of Medicine at the University of Pennsylvania

summary: To identify potential biological functions for three lncRNAs (NANCI, LL12, and LL34) we used shRNAs to knockdown expression of lncRNAs in MLE12 cells, a cell resembling type two lung epithelial cells. This data set contains the microarrays looking at gene expression.

overall_design: We used biological triplicate for each shRNA treatment and each treatment group was compared to a biological triplicate of MLE12 cells treated with a scrambled shRNA.

last: Herriges

first: Daniel

last: Swarr

first: Kathleen

last: Stewart

first: Edward

middle: E

last: Morrisey

first: Komal

middle: S

last: Rathi

first: Tian

last: Peng


title: Role of Fzd2 in lung epithelium development

status: Public on Jul 29 2014

first: Rachel

last: Kadzik

address: Translational Research Center, 11th Flr.; Room 179, 3400 Civic Center Boulevard, Bldg 421

department: Molecular Cardiology

institute: University of Pennsylvania

summary: Fzd2 is a Wnt receptor expressed in the embryonic lung.  We made a conditional knockout of Fzd2 to specifically address the role of signaling through Fzd2 in lung epithelial development.

overall_design: To explore the genes that are regulated by signaling through the Fzd2 receptor in the lung epithelium, we performed microarray analysis of Shhcre control and Fzd2CKO lungs at E12.5

first: Ethan

last: Cohen

first: Min

last: Lu

middle: P


title: Expression data from E18 mouse dorsal telencephalon

first: William

last: Snider

address: Mason Farm Road

department: Neuroscience Center

institute: UNC Chapel Hill

summary:
Neurons deficient in both GSK-3 alpha and beta isoforms fail to migrate properly and develop abnormal morphology.  In exploring mechanisms, we found no change in Wnt transcriptional target genes.
Verified decrease in GSK-3B exon 2

overall_design: RNA was extracted from presumptive somatosensory cortices of E18 GSK-3 alpha -/- beta loxp/loxp (control) and GSK-3:Nex conditional mutant embryos.  There were totally 6 samples: 3 control and 3 mutants.

first: Meghan

last: Morgan-Smith


title: Effects of (-)-cannabidiol on human sebocytes

city: Debrecen

first: Attila

last: Oláh

address: Nagyerdei krt. 98.

department: Department of Physiology

country: Hungary

institute: University of Debrecen

summary: In the current study, we aimed at exploring the effects of the major non-psychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland functions. We found that CBD behaved as a highly effective anti-acne agent, targeting all the three key, sebocyte-specific steps of the pathogenesis (i.e. without compromising viability or basal sebaceous lipid production, CBD normalized pro-acne agents-induced excessive lipid synthesis, reduced proliferation and exerted anti-inflammatory actions). The goal of the present microarray analyses was to identify signaling pathways and target genes being involved in mediating the above beneficial effects of CBD.

overall_design: Microarray analyses were performed by using three independent sets of control (vehicle-treated) and CBD-treated (10 μM, 24-hr) human, immortalized SZ95 sebocytes. The first two sets of the samples were analyzed by two-color microarrays (“rep1” and “rep2”). Later on, the RNA from the second sample set was used for the “rep2-1” hybridization (techical repeat). Finally, we analyzed the third (biological) sample set by using one-color microarray (“rep3”).

first: Balázs

middle: I

last: Tóth

first: István

last: Borbíró

first: Koji

last: Sugawara

last: Szöllősi

first: Gabriella

last: Czifra

last: Pál

first: Lídia

last: Ambrus

first: Jennifer

last: Kloepper

first: Emanuela

last: Camera

first: Matteo

last: Ludovici

first: Mauro

last: Picardo

first: Thomas

last: Voets

first: Christos

middle: C

last: Zouboulis

first: Ralf

last: Paus

first: Tamás

last: Bíró

first: András

last: Gézsi


title: Transcriptional changes taking place during differentiation of H460-derived CSCs

first: Juan

last: Oliveros

summary: Cancer Stem Cells derived from human non-small cells lung cancer (NSCLC) H460 cells were differentiated by culturing them in the presence of Foetal Bovine Serum under adherent conditions. Changes in gene expression profiles were determined at 3, 9 and 24 hours of differentiation

overall_design: Expression profiles were determined for H460C cells undifferentiated of after 3, 9 and 24 hours of differentiation. Each sample type was hybridized to in-situ oligonucleotide microarrays (Agilent-014850 Whole Human Genome Microarray 4x44K). One channel per slide.  Each differentiated population was compared to undifferentiated cells. Biological replicates: 2

first: Blanca

middle: D

last: Lopez-Ayllon

first: Veronica

last: Moncho-Amor

first: Ander

last: Abarrategi

first: Inmaculada

last: Ibañez-de-Cáceres

first: Javier

last: Castro-Carpeño

first: Cristobal

last: Belda-Iniesta

first: Rosario

last: Perona

first: Leandro

last: Sastre


title: Genes regulated by estrogen and 4-hydroxytamoxifen in MCF-7:PF cells

status: Public on Jul 14 2014

city: Dunedin

first: Heather

middle: E.

last: Cunliffe

state: Otago

address: P O Box 913

department: Department of Pathology

institute: University of Otago, Dunedin School of Medicine

summary:
MCF-7:PF is a a new in vitro model of antihormone resistant breast cancer that exhibits the characteristics of acquired tamoxifen resistance in vivo.
It is well known that estrogen (E2) induces apoptosis in long-term estrogen-deprived breast cancer cells, MCF-7:5C (PubMed References PMID:15862958, PMID:16333030). MCF-7:PF was derived from MCF-7:5C through inhibition of c-Src, which blocks E2-induced apoptosis, coverts E2 responses from apoptosis to proliferation. MCF-7:PF cell growth is stimulated by E2 and SERMS in an  ERα-dependent manner.
Abstract: A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to stimulating growth in E2-deprived breast cancer cells. A resulting cell line, MCF-7:PF, is reprogrammed with features of functional estrogen receptor (ER) and over-expression of insulin-like growth factor-1 receptor beta (IGF-1Rβ). We addressed the question of whether the antiestrogenic selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Unexpectedly, 4-OHT stimulated cell growth in an ER-dependent manner. However, unlike E2, 4-OHT suppressed classic ER-target genes as does the pure antiestrogen ICI 182,780, even during growth stimulation. Chromatin-immunoprecipitation (ChIP) assay indicated that 4-OHT did not recruit ER or nuclear receptor coactivator 3 (SRC3) to the promoter of ER-target gene, pS2. Paradoxically, 4-OHT reduced total IGF-1Rβ but increased phosphorylation of IGF-1Rβ, which was responsible for the activation of the phosphatidylinositol-3 kinases (PI3K)/Akt signaling pathway. Mechanistic studies revealed that 4-OHT rapidly activated the non-genomic pathway through ER, but other membrane-associated proteins such as IGF-1Rβ and c-Src participated. Furthermore, 4-OHT was more potent than E2 to up-regulate membrane remodeling molecules and activated focal adhesion molecules to promote cell growth. Therefore, disruption of membrane-associated signaling completely abolished 4-OHT-stimulated cell growth, but not E2-stimulated cell growth. Despite continued suppression of classic ER-target genes, 4-OHT activated the complex network of cytoskeleton remodeling and extracellular matrix-related signaling which facilitated 4-OHT-stimulated cell growth. This study is the first to recapitulate a cellular model in vitro of acquired tamoxifen (TAM) resistance developed in athymic mice in vivo.

overall_design: MCF-7:PF cells were treated with E2, 4-OHT, ICI 182,780, and combinations of E2 or 4-OHT with ICI 182,780 to examine ER-dependent and independent gene regulation patterns by E2 and 4-OHT

first: Ping

last: Fan

first: Pilar

last: Ramos

first: V

last: Jordan


title: Gene expression profiling of intracranial aneurysms

city: Mishima

first: Hirofumi

last: Nakaoka

address: Yata 1111

department: Department of Human Genetics

institute: National Institute of Genetics

summary: The rupture of intracranial aneurysm (IA) causes subarachnoid hemorrhage associated with high morbidity and mortality. We compared gene expression profiles in aneurysmal domes between unruptured IAs (UIAs) and ruptured IAs (RIAs) to elucidate biological mechanisms predisposing to the rupture of IA. We determined gene expression levels of eight RIAs, five UIAs, and 10 superficial temporal arteries (STAs) with the Agilent microarrays. To explore biological heterogeneity of IAs, we classified the samples into subgroups showing similar gene expression patterns by using clustering methods. The clustering analysis identified four groups: STAs and UIAs were aggregated their own clusters, whereas RIAs segregated into two distinct subgroups (early and late RIAs). By comparing gene expression levels between early RIAs and UIAs, we identified 430 up-regulated and 617 down-regulated genes in early RIAs. The up-regulated genes were associated with inflammatory and immune responses and phagocytosis including S100/calgranulin genes (S100A8, S100A9, and S100A12). The down-regulated genes suggest mechanical weakness of aneurysm walls. The expressions of Krüppel-like family of transcription factors (KLF2, KLF12, and KLF15), which were anti-inflammatory regulators, and CDKN2A, which was located on chromosome 9p21 that was the most consistently replicated locus in genome-wide association studies of IA, were also down-regulated. We demonstrate that gene expression patterns of RIAs were different according to age of the patients. The results suggest that macrophage-mediated inflammation is a key biological pathway for IA rupture. The identified genes can be good candidates for molecular markers of rupture-prone IAs and therapeutic targets.

overall_design: We determined gene expression levels of 8 ruptured intracranial aneurysms (RIAs) (5 early and 3 late RIAs), 5 unruptured intracranial aneurysms (UIAs), and 10 superficial temporal arteries (STAs).

first: Ituro

last: Inoue

first: Atsushi

last: Tajima


title: Telomeric ORFs (TLOs) in pathogenic Candida spp. encode Mediator subunits that regulate the transcription of distinct subsets of genes

status: Public on Jul 11 2014

city: Dublin

first: Gary

middle: P.

last: Moran

address: Lincoln Place

department: Dental Science

country: Ireland

institute: Trinity College Dublin

summary:
Analysis of the role of the Candida dubliniensis Telomeric (TLO) genes and MED3, encoding subunits of Mediator, in regulating transcription
The transcriptional response of a Candida dubliniensis TLO1/TLO2 double (null) mutant was analysed. Reintegrant strains harboring TLO1 or TLO2 were compared to this null mutant to elucidate the individual role of each ORF. The role of MED3 was compared also.

overall_design: 9 experiemental parameters were analysed, each carried out in triplicate or quadruplicate


title: The effect of BrdU on gene expression profiles of B6C3F1 mice treated with furan

status: Public on Jul 01 2014

city: Ottawa

first: Anna

middle: Francina

last: Jackson

state: Ontario

address: 50 Colombine Drive, Tunney's Pasture

department: Environmental Health Center

institute: Health Canada

summary: Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action.

overall_design:
In this study we examined the transcriptional response in liver tissue of female B6C3F1 mice to BrdU treatment (in drinking water for 5 days before sacrifice). This was a toxicogenomic study in which mice were also exposed to 0, 1 or 8 mg/kg bw furan (by oral gavage) for 3 weeks. Mice were sacrificed four hours after the final furan exposure.  Each dose group had 4-5 biological replicates. We used a two-colour reference design and SurePrint G3 Mouse GE 8x60K microarrays (Agilent).

Please note that data for all non-BrdU treated animals was previously reported in GEO [GSE48644]. All samples (with or without BrdU) were part of the same randomized block design for the microarrays.

first: A

middle: F

first: Andrew

last: Williams

first: Leslie

last: Recio

first: Carole

middle: L

last: Yauk


title: Expression data from  livers from Sco1 liver-specific KO and WT adult mice

status: Public on Jul 02 2014

city: Saskatoon

first: Scot

last: Leary

state: SK

address: 107 Wiggins Road

institute: University of Saskatchewan

summary:
Sco1 is a gene required for cytochrome c oxidase biogenesis and the regulation of copper homeostasis.  We characterized the transcriptional changes that occur as a result of liver-specific deletion of Sco1 in mice at 27 days of age
In this dataset, we include the expression data obtained from dissected wild-type mouse livers and mouse livers in which Sco1 has been specifically deleted.

overall_design: 8 samples: 4 Sco1 liver knockouts (Alb-Cre Sco1fl/fl), 4 wild-type (Sco1fl/fl)

first: S

first: F

last: Lefebvre