title: Cish inhibits CD8+ T cell immunity and disrupts proximal T cell receptor signaling

first: Shashank

last: Patel

address: 10 Center Drive; Bldg10-CRC, Room 3-5816W

institute: NCI, NIH

summary: T cell receptor (TCR) signaling is a critical process in immunity to infectious disease and cancer. Recently, a genome-wide association study has implicated polymorphisms in the CISH locus with susceptibility to infectious diseases. However, the role of Cish in the immune responses and its molecular underpinnings remains unclear. Here we demonstrate that Cish deletion resulted in protection against viral infection and enhanced CD8+ T cell tumor immunity. Transcriptome profiling revealed a hyper-TCR activation signature in Cish-deficient CD8+ T cells. Subsequent analysis revealed an inhibitory role for Cish in PLCγ1 activation, ensuing Ca2+ release and downstream signaling. In the steady-state Cish was found to physically interact with PLCγ1, however, PLCγ1 was only found to be ubiquitinated after acute TCR stimulation in the presence of Cish. These data implicate Cish as a potent negative regulator of TCR signaling and T cell immunity to infection and cancer and may have significant clinical applications.

overall_design: 4 biological replicates from wild-type mice and 3 biological replicates from Cish knock-out (-/-) mice were analyzed.

first: Douglas

last: Palmer

first: Nicholas

last: Restifo


title: PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.

status: Public on Apr 30 2015

city: Paris

first: Andre

last: Bortolini Silveira

address: 26 rue d'Ulm

country: France

institute: Institut Curie

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

overall_design: Refer to individual Series

first: André

middle: B

last: Silveira

first: Angelo

last: Laranjeira

first: Paulo

last: Leal

first: Bruno

middle: A

last: Cardoso

first: João

middle: P

last: Barata

first: Rosendo

last: Yunes

first: Nilson

middle: I

last: Zanchin

first: Sílvia

middle: R

last: Brandalise

first: José

first: Gisele

middle: O

last: Rodrigues


title: Gene expression signature of T-ALL cell lines treated with the PI3K inhibitor AS605240

summary: The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.

overall_design: Seven T-ALL cell lines (CCRF-CEM, HPB-ALL, Molt-4, ALL-SIL, P12-ICHIKAWA, TALL-1 and Jurkat) were cultured for 6h with the respective IC50 concentration of AS605240 or vehicle.


title: Expression data from MCF7 cells: control or tuberin-depleted

status: Public on Apr 28 2015

city: Barcelona

first: Miguel Angel

last: Pujana

address: Gran Via 199

country: Spain

institute: Institut Catala d'Oncologia IDIBELL

summary: Analysis of the expression profiles of MCF7 cells transduced with a control shRNA and an TSC2-targeted shRNA (leading to tuberin depletion).

overall_design: MCF7 cells were cultured in standard conditions, transduced, selected with puromycin (pLKO.1 shRNA vectors) and processed for expression profiling.

first: M


title: CD8 CDKN2A-/- lymphocytes expressing an active form of the transcription factor Stat5

status: Public on May 04 2015

city: MARSEILLE

first: Nathalie

last: AUPHAN-ANEZIN

address: Parc Scientifique de Luminy

institute: CIML

summary: Transcriptome analyses of  memory CDKN2A-/- CD8  T lymphocytes expressing an active form of the transcription factor Stat5.

overall_design:
CDKN2A-/- CD8 T lymphocytes were activated by anti-CD3/CD28. After 40h, an active form of Stat5 was introduced in activated cells. Culture was continued for another 48h to induce their differentiation in effector T cells. These 88h activated T cells were injected in congeneic hosts and recovered 15 days later from the host spleen and lymph nodes: CDKN2A-/- Stat5ca -d15: 2 replicates– S46, S47.
This study is a complement of the samples previously deposited under accession number GSE41819.  Those two new samples are compared to previously deposited:  - activated CD8 T lymphocytes transduced to express Stat5ca and transferred in congenic hosts:   o S11 (GSM663446);   o S12 (GSM663445);   o S13 (GSM663444);  o S14 (GSM663439).  and  - naive peripheral CD8 T lymphocytes :  o S33 (GSM663441);  o S34 (GSM663435);  o S35 (GSM663449);  o S36 (GSM663447).

first: N

last: Auphan-Anezin

first: A

last: Schmitt-Verhuls

first: P

last: Barbry

first: K

last: Lebrigand


title: Human IFNG+/- Treg and Tconv transcriptome

status: Public on May 01 2015

city: SAN FRANCISCO

first: GAURAV

last: CHOPRA

state: CA

address: 513 PARNASSUS AVE, HSW 1102

department: DIABETES CENTER

country: USA

institute: UNIVERSITY OF CALIFORNIA - SAN FRANCISCO (UCSF)

summary: Microarray used to detail the global gene transcription underlying sorted IFNg+ and IFNg- Tregs (CD4+CD25+CD127lo) and Tconv (CD4+CD25-CD127+) for fresh (unexpanded) and 14 day expanded cells from human blood.

overall_design: Treg and Tconv were FACS isolated from five healthy subjects (median age of 26, range 22-30).  Sorted cells were separated into two groups: the first group was stimulated for 4 hours with PMA/ionomycin and labeled with the IFNg cytokine capture kit (Miltenyi Biotech) followed by FACS isolation of IFNg- and IFNg+ populations. The second set was expanded to day 14 prior to reactivation and cytokine cell capture.  For each IFNg sorted population, cells were pelleted and flash frozen before RNA isolation and processing.

first: Gaurav

last: Chopra

first: Stephanie

last: McClymont

first: Mahesh

last: Yadav

first: Ying

last: Zhang

first: David

middle: V

last: Schack

first: Yizheng

last: Li

first: Maryann

last: Whitley

first: Jeffrey

last: Bluestone


title: Assessment of the Osteoblast Transcriptome in a Model of Markedly Enhanced Intramembranous Bone Formation Due to Constitutive Gs-G Protein Signaling in Osteoblasts

status: Public on Apr 25 2015

city: San Francisco

first: Lalita

last: Wattanachanya

address: 1700 Owens St.

institute: San Francisco VA Medical Center

summary: G protein coupled receptor (GPCR) signaling in osteoblasts (OBs) is an important regulator of bone formation. We previously described a mouse model expressing Rs1, an engineered constitutively active Gs-coupled GPCR, under the control of the 2.3 kb-Col I promoter. These mice showed a dramatic age-dependent increase in trabecular bone which were accompanied by an increase in OB lineage cells, especially immature OBs, indicated by an expansion of cells expressing Osterix and Runx2 in the whole femur. In this study, we further evaluated how Gs signaling in OBs affects intramembranous bone formation by examining calvariae of one-and nine-week-old Col1(2.3)/Rs1 mice. Rs1 calvariae displayed a dramatic increase in total volume and trabecular bone volume with partial loss of cortical structure. By immunohistochemistry, Osterix was detected in cells throughout the inter-trabecular space in Rs1 expressing mice while Osteocalcin was expressed predominantly in cells along bone surfaces. These findings resembled that previously seen in Rs1 femoral bones, suggesting the role of paracrine mediators secreted from OBs driven by 2.3 kb-Col I promoter could influence early OB commitment, differentiation, and/or proliferation. However, it is still unclear how G protein signaling in mature OBs leads to the observed alterations in bone mass. In this study, we investigated the cellular basis of the skeletal changes by assessing the effect of Rs1 expression in vivo on the transcriptome of mature OBs. We identified the complete set of Gs-GPCRs and other GPCRs that are expressed on OBs which may contribute to the observed skeletal phenotype. Candidate paracrine mediators of the effect of Gs signaling in OBs were determined. Genes affected by Rs1 signaling include those encoding proteins important for cell differentiation, cytokines and growth factors, angiogenesis, coagulation, and energy metabolism. Our results identify novel candidate mediators of the anabolic response to the skeleton to Gs signaling in mature OBs.

overall_design: We utilized a microarray approach to examine Rs1-induced alterations in the OB transcriptome. The approach used to identify an approximate snapshot of the OB transcriptome at the time of sacrifice by isolating the OB population that expresses Rs1 by GFP labeling, without the use of cell culture. We compared gene expression between control OBs and OBs-expressing Rs1 in triplicates.

first: Liping

last: Wang

first: Susan

middle: M

last: Millard

first: Wei-Dar

last: Lu

first: Dylan

last: O’Carroll

first: Edward

middle: C

last: Hsiao

first: Bruce

last: Conklin

first: Robert

last: Nissenson


title: Natural killer cell sensing of infected cells compensates deficient Toll-like receptor but not IFN-I activity for mouse resistance to cytomegalovirus

status: Public on Apr 24 2015

city: Marseille

first: Marc

last: DALOD

address: Parc scientifique de Luminy, Case 906

department: Dendritic cells and antiviral defense

institute: Center of Immunology of Marseille Luminy (CIML)

summary:
Plasmacytoid dendritic cells (pDC) are the major source of type I IFN (IFN-I) in vivo during Murine Cytomegalovirus (MCMV) infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll Like Receptors 7/9. Provided that they express appropriate recognition receptors such as Ly49H, Natural Killer (NK) cells can directly sense and kill MCMV-infected cells. While MyD88- and Ly49H-dependent responses can contribute to MCMV control, the objective is to understand the relative importance of these 3 mechanisms.
In order to decipher the relative impact of MyD88- and Ly49H-dependent mechanisms during MCMV infection, we performed a genome-wide expression analysis on total spleen of Ly49H-/-MyD88+/+, Ly49H-/-MyD88-/-, Ly49H+/+MyD88+/+ and Ly49H+/+MyD88-/- BALB/c mice at different time points after MCMV infection (d0, d1,5, d2, d3 and d6).

overall_design: This study includes data from the spleen BALB/c mice, under steady-state or MCMV condition at different time points. 2 to 5 mice for each mouse strain for each time point were used, and were hybridized on 5 separate batches of gene chips.

first: C

last: COCITA

first: R

last: CHELBI

first: M


title: An Immune and Inflammation Signature in Prostate Tumors of Smokers (part 3)

status: Public on Apr 22 2015

city: bethesda

first: Stefan

last: Ambs

state: md

address: 37 convent cir

institute: NIH

summary: Current smokers develop metastatic prostate cancer more frequently than nonsmokers, suggesting that a tobacco-derived factor induces metastasis. To identify smoking-induced alterations in human prostate tumors, we analyzed gene and protein expression of tumors from current, past, and never smokers and observed distinct molecular alterations in current smokers. Specifically, an immune and inflammation signature was identified in prostate tumors of current smokers that was either attenuated or absent in past and never smokers. Key characteristics of this signature included augmented immunoglobulin expression by tumor-infiltrating B cells, NF-kB activation, and increased interleukin-8 in tumor and blood. In an alternate approach to characterize smoking-induced oncogenic alterations, we explored the effects of nicotine in prostate cancer cells and prostate cancer-prone TRAMP mice. These experiments showed that nicotine increases both invasiveness of human prostate cancer cells and metastasis in tumor-bearing TRAMP mice, indicating that nicotine can induce a phenotype that resembles the epidemiology of smoking-associated prostate cancer progression. In summary, we describe distinct oncogenic alterations in prostate tumors from current smokers and show that nicotine can enhance prostate cancer metastasis.

overall_design: TRAMP mice in five replicates received either tap water or a solution of 250 µg/ml of nicotine [nicotine tartrate salt (Sigma-Aldrich, St. Louis, MO)] in tap water

first: Wei

last: Tang


title: Expression data from WT and TREM2 deficient microglia in response to cuprizone mediated demyelination

city: Saint Louis

first: Marco

last: Colonna

state: MO

address: 660 S Euclid Ave.

department: Pathology and Immunology

institute: Washinton University School of Medicine

summary: We examined the role of TREM2 on microglia responses to demyelination

overall_design: Microglia were FACS-purified from WT or Trem2-/- mice fed with 0.2% cuprizone diet.

first: Yaming


title: An Immune and Inflammation Signature in Prostate Tumors of Smokers

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Gene expression profile of cell lines 2106T, H1975 and MeWo after knockdown of PAEP.

city: Heidelberg

middle: Andre

last: Schneider

address: Amalienstraße 5

department: Translational Research Unit

country: Germany

institute: Thoraxklinik am Universitätsklinikum Heidelberg

summary:
Gene expression profile was analyzed after knockdown of PAEP in lung cancer cell lines 2106T and H1975 as well as in skin cancer cell line MeWo.
The aim of the study was to investigate the role of PAEP and its protein product glycodelin in lung cancer cell lines.

overall_design: Cells were treated with a control siRNA or a siRNA pool of 4 siRNAs targeting PAEP. RNA of three biological replicates each was extracted and used for Affymetrix analyses.

first: Liz

last: Meister

first: Martin

last: Granzow

first: Meister

last: Michael

first: Muley

last: Thomas


title: Methylation data from presentation and relapsed medulloblastoma tumour samples

status: Public on Apr 23 2015

city: Newcastle upon Tyne

first: Ed

last: Schwalbe

address: Ellison Place

department: Applied Sciences

country: United Kingdom

institute: Northumbria University

type: Methylation profiling by genome tiling array

summary: We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of Trp53 function in this model produced aggressive tumors that mimicked the characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity, genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53–MYC interactions which emerge at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Using this dataset, assignation of medulloblastoma molecular subgroup by Illumina 450k microarray was performed for diagnostic and relapsed medulloblastoma samples to compare subgroup membership at diagnosis and relapse.

overall_design: We investigated the DNA methylation profiles of 18 diagnostic and  22 relapsing samples (including 15 diagnostic / relapse pairs) using the Illumina 450k methylation microarray

first: E

last: Hill

first: S

last: Clifford


title: Expression data from AT/RTs, AT/RT-like tumors and medulloblastomas

status: Public on Apr 15 2015

city: Taipei

first: Tsung-Han

last: Hsieh

address: No.250, Wusing St., Xinyi Dist., Taipei City 112, Taiwan (R.O.C.)

department: Institute of Microbiology and Immunology

country: Taiwan

institute: Taipei Medical University


title: Expression data from malignant human B-cell cell lines

status: Public on Apr 19 2015

city: Aalborg

first: Steffen

middle: Falgreen

last: Larsen

address: Sdr Skovvej 15

department: Department of Haematology

country: Denmark

institute: Aalborg University Hospital

summary: We used global gene expression profiles from human B-cell cell lines to generate gene expression signatures for prediction of response to the drugs cyclophosphamide, doxorubicin or vincristine. The signatures were validated in two publicly available clinical cohorts.

overall_design: Global gene expression data combined with dose response experiments for prediction of chemoresistance


title: Transcriptome analysis in medulloblastoma groups

summary: Embryonal tumors of the central nervous system (CNS) represent a highly malignant tumor group of medulloblastoma (MB), atypical teratoid/rhabdoid tumor (AT/RT), and primitive neuroectodermal tumor (PNET) that frequently afflict children. In this study, we report transcriptome traits in MB by using gene expression microarray analyses. We also compare MB dataset with AT/RT cases and AT/RT-like cases.

overall_design: 22 MB cases are subjected to transcriptome analysis

first: Hsei-Wei

last: Wang


title: Gene expression study of MCF7/tet-off clones expressing different HER2 isoforms

first: Kim

last: Pedersen

address: Psg. Vall d'Hebron 119-129

institute: Vall d'Hebron Institute of Oncology (V.H.I.O.)

summary:
HER2 is a tyrosine kinase receptor causally involved in cancer. A subgroup of breast cancer patients with particularly poor clinical outcome expresses a heterogeneous collection of HER2 carboxy-terminal fragments (CTFs). However, since the CTFs lack the extracellular domain that drives dimerization and subsequent activation of full-length HER2, they are in principle expected to be inactive. Here we present evidence that at low expression levels one of these fragments, 611-CTF, activated multiple signaling pathways because of its unanticipated ability to constitutively homodimerize. A transcriptomic analysis revealed that 611-CTF specifically controlled the expression of genes that we found correlated with poor prognosis in breast cancer. Among the 611-CTF-regulated genes were several that previously have been linked to metastasis, including MET, EPHA2, MMP1, IL11, ANGPTL4 and different Integrins. Transgenic mice overexpressing HER2 in the mammary gland develop tumors only after acquisition of activating mutations in the transgene. In contrast, we show that expression of 611-CTF led to development of aggressive and invasive mammary tumors without the need for mutations. These results demonstrate that 611-CTF is a potent oncogene capable of promoting mammary tumor progression and metastasis.
Affymetrix Gene Array expression study, using MCF7/tet-off clones stably transfected with vectors encoding HER2 and different truncated forms of the receptor, were used to elucidate the activity of the various protein isoforms.

overall_design: MCF7 clones were selected, maintain and expanded in the presence of doxycycline to avoid expression of the HER2 receptor isoforms. The experiments were started by seeding equal numbers of cells in two dishes, one with and one without doxycycline. 15 or 60 hours later total RNA was isolated in parallel from the two dishes. In the dishes without doxycycline the cloned HER2 isoforms were expressed from a CMV promoter. In total 50 arrays were included in the analysis. For key clones and time points biological replicates were included.

first: Joaquín

last: Arribas


title: Epigenome analysis of tumor adjacent normal tissue from breast cancer patients

city: Chapel Hill

first: Melissa

last: Troester

state: NC

address: 2104H McGavran-Greenberg 135 Dauer Drive Campus Box 7435 27599-7435

department: Center for Environmental Health Sciences Integrated Sciences Facility Corencer Center

institute: University of North Carolina at Chapel Hill

summary: Genome wide DNA methylation profiling of tumor adjacent normal tissue from patients with invasive breast cancer, as well as tissue from women undergoing reduction mammoplasty or prophylactic surgery.  The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in snap frozen breast tissue. Samples included 70 tumor-adjacent normal breast tissue with invasive disease, 8 tissues from breast prophylactic patients, and 18 tissues from breast reduction patients.

overall_design: Bisulphite converted DNA from the 96 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip.

first: Brionna

last: Hair

first: Erin

last: Kirk


title: Gene expression in the GWAT of ob/ob and ob/ob/Fsp27-/- mice

status: Public on Apr 17 2015

city: Beijing

first: Linkang

last: Zhou

state: Beijing

address: Haidian District

country: China

institute: Tsinghua Unversity

summary:
GWAT store most of the TAG in mice, ob/ob mice is an obese mice. Ob/ob/Fsp27-/- mice are lean when compared with ob/ob mice. The GWAT weight was dramatically reduced in ob/ob/Fsp27-/- mice.
We next extract the total RNA from the GWAT of ob/ob and ob/ob/Fsp27-/- mice, to perform microaary analysis using Mouse Genome 430 2.0 arrays, Affymetrix. We then analysised the up-regulated and down regulated pathways.

overall_design: We extract the RNA of GWAT from 4 month old mice and hybridization on Affymetrix microarrays. We then analysis the data.

first: Xiayu

last: Xia


title: Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells [HumanMethylation450]

city: Boston

first: Adam

last: Gower

state: MA

address: 72 East Concord Street, E632

department: Department of Medicine

institute: Boston University School of Medicine

summary: We monitored 9 pluripotent stem cell lines across three time points of hepatic directed differentiation, representing 3 developmental stages: undifferentiated (T0), definitive endoderm (T5), and early hepatocyte (T24). ESCs (n=3) and patient-derived normal (n=3) or PiZZ (n=3) iPSCs were analyzed in the undifferentiated state (T0), after differentiation to definitive endoderm (T5), and upon reaching hepatic stage (T24) for a total of 27 samples.  We sought to test the hypothesis that a single transgene-free iPSC clone from each donor could be used to detect disease-specific differences between the normal cohort and the PiZZ cohort, anticipating that this difference would emerge only at a developmental stage in which the mutant AAT gene is expressed. Cells were sorted before analysis at T0 and T5 after antibody staining for TRA1-80+/SSEA3+ (T0) or C-kit+/CXCR4+ (T5) cells.

overall_design: ESCs (n=3) and patient-derived normal (n=3) or PiZZ (n=3) iPSCs were analyzed in the undifferentiated state (T0), after differentiation to definitive endoderm (T5), and upon reaching hepatic stage (T24) for a total of 27 samples.  Cells were sorted before analysis at T0 and T5 after antibody staining for TRA1-80+/SSEA3+ (T0) or C-kit+/CXCR4+ (T5) cells. RNA was extracted at each stage, biotin labeled, and hybridized to either Affymetrix GeneChip Human Gene 1.0 ST or miRNA 2.0 arrays. For methylation analysis, gDNA was sorted from the same 27 samples before undergoing bisulfite conversion. Bisulfite converted DNA was then amplified and purified prior to overnight hybridization to Illumina’s Infinium HumanMethylation 450 BeadChips.  Next day staining of hybridized arrays produced methylation-dependent differential fluorescence that was detected via an Illumina iScan array scanner.

first: Andrew

last: Wilson

first: Darrell

middle: N

last: Kotton


title: Epigenome-wide analysis of monozygotic twin pairs discordant for body mass index

status: Public on Apr 20 2015

city: Helsinki

first: Khadeeja

last: Ismail

state: Helsinki

address: Mannerheimintie 172

department: Department of Public Health

country: Finland

institute: University of Helsinki

summary: Genome wide DNA methylation profiling of MZ twins discordant and concordant for BMI. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,000 CpGs. Samples included 30 MZ twin pairs discordant for BMI and 10 pairs concordant for BMI.

overall_design: Bisulphite converted DNA from the 80 samples were hybridised to the Illumina Infinium HumanMethylation450 BeadChip

first: Miina

last: Ollikainen

first: Jaakko

last: Kaprio


title: Testing gene expression changes in VCaP cells following PRMT5 knockdown

city: Cambridge

first: Joshua

last: Korn

address: 250 Mass Ave

institute: Novartis

summary:
VCaP cells expressing either NTC shRNA or PRMT5 shRNA 1 or shRNA 2 were treated with 100ng/ml doxycycline for 5 days
This experiment is designed to see which genes and pathways are modulated by PRMT5 knockdown in VCaP cells

overall_design: VCaP cells  were treated with 100ng/ml doxyxycline for 3 days.

first: Zineb

last: Mounir

first: Ray

last: Pagliarini


title: Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells

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

platform_organism:
Homo sapiens
synthetic construct

overall_design: Refer to individual Series


title: Molecular signaling distinguishes early from late recurrences in ER positive breast cancer

city: Washington

first: Lu

last: Jin

address: 3970 Reservoir Rd NW

department: Oncology

institute: Georgetown University

summary: Unlike many other cancers, estrogen receptor-alpha (ER+) breast cancers are associated with cumulative risks of recurrence and death that persist for decades. We show that molecular differences between breast cancers that recur at distant sites early (² 3 years) or late (³ 5 years) support a robust molecular predictor of recurrence with Tamoxifen therapy and provide novel insights into the signaling features that differ between these recurrent cancers. We applied a support vector machine with recursive feature elimination to gene expression microarray data using a training-internal crossvalidation workflow that minimizes the gene selection bias problem. The resulting predictor was validated in an independent data set. Performance of the predictor suggests that it is possible to identify patients at increased risk of experiencing an early recurrence who require other treatments to prevent early metastasis. We implemented a Metropolis Sampling algorithm as a random walk to identify the protein-protein interactions (PPI) most closely associated with ER in 8 PPI databases. We then walked the gene expression data for the top PPIs to discover a signaling network driving early and late recurrent breast cancers. Consensus features between the training and validation datasets define a complex and highly connected network with major interactions among nodes including AR, CALD1, CALM(1,2,3), CDK1, EGFR, ESR1, ESR2, MAPK1, and SRC. The complexity illustrates the challenges in directing single agent or simple combination therapies to improve overall survival in ER+ breast cancers that will recur but also suggests potentially novel interventions to address this challenge.

overall_design: 49 independent samples (breast tumors) were arrayed

first: Younsook

last: Cho

first: Rebecca

last: Riggins

first: Jason

last: Xuan

first: Minetta

last: Liu

first: Robert

last: Clarke


title: Combined MYC and TP53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease

first: Ed

last: Schwalbe

type: Genome variation profiling by genome tiling array


title: Defining the microglia transcriptome in multifunctional protein-2 deficient mice

status: Public on Apr 14 2015

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary: Purpose: We purified whole brain microglia of MFP2 knockout mice and control mice utilizing percoll gradient and FACS sorting, followed by microarray analysis to define the molecular changes in MFP2 knockout mice at the endstage of the disease. We compared the microglia transcriptome of Mfp2-/- microglia to that of SOD1-G93A microglia isolated from spinal cord to define the microglia signature associated with a non-neurodegenerative environment. Results and conclusions: Mfp2-/- microglia acquire an activation state characterized by activation of mammalian target of rapamycin (mTOR).  In addition, activated microglia display reduced expression of genes that are normally highly expressed by surveillant microglia in steady-state conditions. The immunological profile of is heterogeneous and encompasses upregulation of both pro- and anti-inflammatory genes. In contrast to the neurodegeneration-specific microglia profile in SOD1-G93A mice, Mfp2-/- microglia do not induce genes associated with phagocytosis, lysosomal activation and neurotoxicity.

overall_design: 4 MFP2 knockout and 4 control samples were subjected to microarray analysis.

first: Simon

last: Verheijden

first: Lien

last: Beckers

first: Myriam

last: Baes


title: Activation of Notch1 and Notch3 Skews Human Airway Basal Cell Differentiation Toward a Secretory Pathway

status: Public on Apr 13 2015

city: New York

first: Yael

last: Strulovici-Barel

state: NY

address: 1300 York Avenue

department: Department of Genetic Medicine

institute: Weill Cornell Medical College

summary: Airway basal cells (BC) function as progenitor cells capable of differentiating into ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. The objective of this study was to define the role of Notch signaling in regulating human airway BC differentiation into a pseudostratified mucociliated epithelium. Notch inhibition with γ-secretase inhibitors demonstrated Notch activation is essential for BC differentiation into secre-tory cells and ciliated cells, but more so for the secretory lineage. Sustained Notch activation via lentivirus expression of the intracellular domain of each Notch receptor (NICD1-4) demonstrated that the Notch 2 and 4 pathways have little effect on BC differentiation, while activation of the Notch1 or 3 pathways has a major influence, with persistent expression of NICD1 or 3 resulting in a skewing toward secretory cell differentiation with a parallel decrease in ciliated cell differentiation. These observations provide insights into the control of the balance of BC differentiation into the secretory vs ciliated cell lineage, a balance that is critical for maintaining the normal function of the airway epithelium in barrier defense against the inhaled environment.

overall_design: Array-based expression profiling of the Notch signaling pathway genes specifically in human airway basal cells.

first: Kazunori

last: Gomi

first: Ronald

middle: G

last: Crystal

first: Matthew

middle: S

last: Walters


title: Novel targets for the transcription factors MEF2 in MA-10 Leydig cells

status: Public on Apr 12 2015

city: Quebec

first: Caroline

last: Daems

state: Qc

address: 2705, boulevard Laurier

department: Obstetrics, Gynecology, and Reproduction

country: Canada

institute: CRCHUQ-ULAVAL

summary: Testosterone production by Leydig cells is a tightly regulated process requiring synchronized expression of several steroidogenic genes by numerous transcription factors. Myocyte enhancer factor 2 (MEF2) is a transcription factor recently identified in somatic cells of the male gonad. In other tissues, MEF2 is an essential regulator of organogenesis and cell differentiation. So far in the testis, MEF2 was found to regulate Leydig cell steroidogenesis by controlling Nr4a1 and Star gene expression. To expand our understanding of the role of MEF2 in Leydig cells, we performed microarray analyses of MA-10 Leydig cells depleted in MEF2 and results were analyzed using the Partek and IPA softwares. Several genes were differentially expressed in MEF2-depleted Leydig cells and 15 were validated by qPCR. A large number of these genes are known to be involved in fertility, gonad morphology and steroidogenesis and include Pde8a, Por, Ahr, Bmal1, Cyp1a1, Cyp1b1, Map2k1, Tsc22d3, Nr0b2, Smad4, and Star, which were all downregulated in the absence of MEF2. In silico analyses revealed the presence of MEF2 binding sites within the first 2 kb upstream the transcription start site of the Por, Bmal1, and Nr0b2 promoters, which suggests a direct regulation by MEF2. Using transient transfections in MA-10 Leydig cells, siRNA knockdown, and a MEF2-Engrailed dominant negative, we found that MEF2 activates the Por, Bmal1 and Nr0b2 promoters and that this requires an intact MEF2 element. Our results identify novel target genes for MEF2 and define MEF2 as an important regulator of Leydig cell function and male reproduction.

overall_design: MA-10 Leydig cells were treated with siRNA MEF2A/2D (siRNA MEF2) or scrambled siRNA as control (siRNA Ctrl) 48h before total RNA extraction.

first: Mickael

last: Di-Luoffo

first: Francis

last: Bergeron

first: Jacques

middle: J

last: Tremblay


title: Regulation of T cell cytokine expression by Tet2-mediated DNA demethylation [gene expression]

city: Seattle

first: Raymond

last: Doty

state: WA

department: Division of Hematology

institute: University of Washington

summary: T cell function is regulated by epigenetic mechanisms. 5-methylcytosine (5mC) conversion to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) proteins was identified to mediate DNA demethylation. Here, we characterize the genome-wide distribution of 5hmC in T cells using DNA immunoprecipitation coupled with high-throughput DNA sequencing. 5hmC marks signature genes associated with effector cell differentiation in the putative regulatory elements. Moreover, Tet2 protein is recruited to 5hmC-containing regions, dependent on lineage-specific transcription factors. Deletion of the Tet2 gene in T cells decreased their cytokine expression, associated with reduced p300 recruitment. In vivo, Tet2 plays a critical role in the expression of cytokine genes. Collectively, our findings for the first time demonstrate a key role of Tet-mediated active DNA demethylation in T cells.

overall_design: A total of 8 samples were analyzed. The expression patterns in Tet2 wild-type and deficient Th1 and Th17 cells were analyzed.

first: Kenji

last: Ichiyama

first: Lai

last: Wei

first: Chen

last: Dong


title: Global Analysis of Post-transcriptional Gene Expression in Arsenite-treated Human BJ Fibroblasts

city: RTP

first: NIEHS

last: Microarray Core

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary:
Arsenic is a potent environmental toxin and a cause of numerous health problems.  Most studies have assumed that arsenic-induced changes in mRNA levels result from effects on gene transcription.  The influence of arsenic on post-transcriptional regulation, another important locus of gene expression control, has remained largely unexplored.
To evaluate the prevalence of changes in mRNA stability in response to arsenic in human fibroblasts, we used microarray analyses to determine changes in steady state mRNA levels, and their decay rates, following 24 hour exposure to non-cytotoxic concentrations of sodium arsenite (1 µM).  We conclude that arsenite modification of mRNA stability is relatively uncommon, but in some instances can result in significant changes in gene expression.

overall_design: Human BJ diploid foreskin fibroblasts were used in the study.  The decay rates of transcripts were determined using actinomycin D to stop transcription after sodium arsenite or water treatment for 24 h.  Actinomycin D was added into the culture medium at a final concentration of 5 µg/ml, and treated cells were then harvested at 0, 1, 2, 3 and 4 h for RNA extraction.

first: Perry

last: Blackshear

first: Lianqun

last: Qiu

first: Sarah

last: Abey

first: Shawn

last: Harris

first: Ruchir

last: Shah

first: Kevin

last: Gerrish


title: LRP8-Reelin-regulated Neuronal (LRN) Enhancer signature underlying learning and memory formation (RNA-Seq 2)

status: Public on Apr 29 2015

city: San Diego

first: Qi

last: Ma

address: 9500 Gilman Dr,

institute: UCSD

type: Expression profiling by high throughput sequencing

summary: A comprehensive landscape of epigenomic events regulated by the Reelin signaling through activation of specific cohort of cis-regulatory enhancer elements (LRN-enhancers), which involves the proteolytical processing of the LRP8 receptor by the gamma-secretase activity and is required for learning and memory behavior

overall_design: All RNA-Seq experiments were designed to evaluate the transcriptional program regulated by the Reelin-LRP8 signaling pathway in neuronal cells

first: Francesca

last: Telese


title: Tet2-mediated DNA demethylation controls T cell cytokine expression [array]

summary:
The conversion of 5-methylcytosine (5mC) into 5-Hydroxymethylcytosine (5hmC) by ten-eleven translocation (Tet) family has recently been identified as a key process for active DNA demethylation, whose effects in the immune response is currently unknown.
We used microarrays to characterize the regulation of Tet2 in T cells. We found that deletion of the Tet2 gene in T cells decreased expression of effector cytokines such as IFN-γ, IL-17, and IL-10.

overall_design: To analyze the regulation of Tet2 in Th subset differentation, CD2(Cre)Tet2(f/f) mice were used to derive Tet2-deficient Th1 and Th17 cells, and Tet2(f/f) mice were used for Tet2-enriched Th1 and Th17 cells.

first: Xiaowei

last: Yan


title: Melanomas enhance metastasis and resist BRAF-therapy through regulation of the scaffold protein FHL2 after loss of differentiation markers

status: Public on Apr 11 2015

city: BETHESDA

first: Vincent

middle: J.

last: Hearing

state: MD

address: BG 37 RM 2132B 37 CONVENT DR

institute: National Cancer Institute

summary: To test whether or not the stable restoration of PMEL and FHL2 knockdown affects the oncogenic ability of into amelanotic melanoma cells. Global gene expression analysis performed to identify what different mechanisms and/or factors might be involved in cell motility and cell aggressiveness.

overall_design: A375M2 were stable transduced with lentivirus containing an empty vector expressing eGFP, full length PMEL or shRNA specific sequence against FHL2. Cells were FACS selected and grown in selective medium for 15 days before testing. Total RNA was extracted from cells after being seeded at equal numbers and reached 80% confluence. Samples were obtained from three separate experiments and send together for processing.

first: Julio

last: Valencia

first: Sergio

last: Coelho

first: Zack

last: Howard

first: Lanlan

last: Yin

first: Jin-Qiu

last: Chen

first: Suneet

last: Shukla

first: Michael

last: Lizardo

first: King

middle: L

last: Fung

first: Michelle

last: Herrmann

first: Tie-Chi

last: Lei

first: Jingce

first: Rebecca

middle: K

last: Valaske

first: Mones

last: Abu-Asab

first: Mannan

last: Poonam

last: Pickart

first: Susan

last: Garfield


title: Expression data from prostate cancer cell lines C4-2B (enzalutamide sensitive) and  C4-2B-MDVR (enzalutamide resistant) cells

status: Public on Apr 09 2015

city: Sacramento

first: allen

last: Gao

state: California

address: 4645 2nd Ave Research 3

institute: UC Davis

summary:
Prostate cancer C4-2B cells were cultured in enzalutamide in a dose-escalation manner. After sixty passages cells were resistant to enzalutamide, with a specific sets of genes been deregulated.
We performed global gene expression analysis by cDNA microarrays to identify genes responsible for enzalutamide resistance in C4-2B-MDVR cells.

overall_design: Enzalutamide resistant C4-2B-MDVR cells were selected from C4-2B cells during long time enzalutamide treatment. Genes responsible for enzalutamide resistance were identified using C4-2B vs. C4-2B-MDVR RNA extraction and hybridization on Affymetrix microarrays.

first: Chengfei

last: Liu

first: Allen


title: HDAC inhibition imparts beneficial transgenerational effects in Huntington's disease mice via altered DNA and histone methylation

status: Public on Apr 10 2015

city: La Jolla

first: Roy

last: Williams

address: 3030 Science Park Road

department: Regenerative Medicine

institute: The Scripps Research Institute

summary: Increasing evidence has demonstrated that epigenetic factors can profoundly influence gene expression and, in turn, influence resistance or susceptibility to disease. Epigenetic drugs, such as histone deacetylase (HDAC) inhibitors, are finding their way into clinical practice, although their exact mechanisms of action are unclear. To identify mechanisms associated with HDAC inhibition, we performed microarray analysis on brain and muscle samples treated with the HDAC1/3-targeting inhibitor, HDACi 4b. Pathways analyses of microarray datasets implicate DNA methylation as significantly associated with HDAC inhibition. Further assessment of DNA methylation changes elicited by HDACi 4b in human fibroblasts from normal controls and patients with Huntington's disease (HD) using the Infinium HumanMethylation450 BeadChip revealed a limited, but overlapping, subset of methylated CpG sites that were altered by HDAC inhibition in both normal and HD cells. Among the altered loci of Y chromosome-linked genes, KDM5D, which encodes Lys (K)-specific demethylase 5D, showed increased methylation at several CpG sites in both normal and HD cells, as well as in DNA isolated from sperm from drug-treated male mice. Further, we demonstrate that first filial generation (F1) offspring from drug-treated male HD transgenic mice show significantly improved HD disease phenotypes compared with F1 offspring from vehicle-treated male HD transgenic mice, in association with increased Kdm5d expression, and decreased histone H3 Lys4 (K4) (H3K4) methylation in the CNS of male offspring. Additionally, we show that overexpression of Kdm5d in mutant HD striatal cells significantly improves metabolic deficits. These findings indicate that HDAC inhibitors can elicit transgenerational effects, via cross-talk between different epigenetic mechanisms, to have an impact on disease phenotypes in a beneficial manner.

overall_design: Bisulphite converted DNA from the 12 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2.  We demonstrate that histone deacetylase (HDAC) inhibition can elicit changes in DNA methylation in Huntington’s disease (HD) human fibroblasts, as well as in sperm from HD transgenic mice, in association with DNA methylation-related gene expression changes. We suggest that alterations in sperm DNA methylation lead to transgenerational effects, and, accordingly, we show that first filial generation (F1) offspring of HDAC inhibitor-treated male HD transgenic mice show improved HD disease phenotypes compared with F1 offspring from vehicle-treated male HD transgenic mice. These findings have significant implications for human health because they enforce the concept that ancestral drug exposure may be a major molecular factor that can affect disease phenotypes, yet in a positive manner. Further, we implicate Lys (K)-specific demethylase 5d expression in this phenomenon.

first: Elizabeth

last: Thomas

first: Haiqun

last: Jia


title: Cellular function of a novel human peptide that binds to P-bodies

status: Public on Apr 08 2015

city: West Haven

first: Sarah

middle: A

last: Slavoff

state: CT

address: 600 West Campus Drive, MIC 319A

department: Chemistry

institute: Yale University

summary:
Mass spectrometry peptidomics coupled with RNA deep sequencing has revealed a large number of translated eukaryotic short open reading frames that produce genomically encoded peptides. The human LOC550643 gene, previously annotated as non-coding, encodes such a peptide (referred to as NoBody). NoBody peptide binds to EDC4 (enhancer of decapping 4) site-specifically, enriches complexes of proteins involved in 5'-3' mRNA degradation, and localizes to P-bodies, which are cellular RNA-protein granules associated with RNA degradation. Furthermore, modulating NoBody expression levels inversely regulates P-body numbers. This peptide has the potential to reveal new insights into the P-body structure-function relationship and cellular regulation of mRNA degradation.
We used siRNA-mediated gene silencing coupled with biological pathway analysis to determine the cellular functions of NoBody (LOC550643), and whether it has similar cellular functions to related (Dcp2) and unrelated (DcpS) mRNA degradation proteins.

overall_design: HEK293T cells were silenced for NoBody/LOC550643 expression by transfection with a pool of 4 commercially designed siRNAs (Qiagen). The negative control/reference sample consisted of HEK293T cells transfected with a non-targeting siRNA. Comparison samples were silenced for Dcp2 expression (expected to be functionally related in mRNA decapping and degradation, positive control), DcpS (another mRNA degradation protein from a different pathway, expected to be unrelated, negative control) or GAPDH (unrelated protein, negative control), so that the specificity of cellular responses to NoBody/LOC550643 silencing could be assessed. 48 hours after transfection with siRNA, cells were treated with actinomycin D for 4 hours (expected to blunt transcriptional responses to assay mRNA degradation phenotypes), then harvested and total RNA was extracted and subjected to Affymetrix GeneChip analysis. We note that the mRNA degradation phenotype was apparently overwhelmed by transcriptional responses despite the actinomycin D treatment, so the most meaningful analyses of the data involved gene ontology/biological pathway analysis.

first: Alan

last: Saghatelian

first: Arthur

last: Liberzon

first: Lauren

last: Winkler

first: Jiao

last: Ma

first: Qian

last: Chu

first: Bogdan

last: Budnik

first: Aravind

last: Subramanian

first: Rajiv

last: Narayan


title: Expression data from Chimeric Antigen Receptor (CAR) Expressing T cells

city: Bethesda

first: Adrienne

last: Long

state: Maryland

address: 10 Center Dr.

department: POB

institute: NIH/NCI

summary: Human T cells isolated from healthy donors were transduced with non-tonically signaling CARs or tonically signaling CARs, each with CD28z or 4-1BB costimulatory domains

middle: H

first: Jack

middle: F

last: Shern

first: Crystal

last: Mackall


title: Bcl6 controlled gene expression in naïve CD4 T cells

city: Indianapolis

first: Alexander

last: Dent

state: IN

address: 950 W. Walnut St. R2 302, Walther Oncology Center

institute: Alexander Dent


title: Bcl6 controlled gene expression in naïve CD4 T cells (Tf0)

summary:
Gene expression data from wild-type and Bcl6-/- naive CD4 T cells
In order to find genes regulated by Bcl6 in follicular helper T cells

overall_design: Naïve CD4 T cells were sorted from wild-type (WT) and T cell-specific conditional Bcl6-/- (KO) mice-- 8 samples, 4 WT and 4 KO

first: Kristin

last: Hollister


title: Bcl6 controlled gene expression in naïve CD4 T cells (Tfh)

summary:
Gene expression data from wild-type and Bcl6-/- naive CD4 T cells
In order to find genes regulated by Bcl6 in follicular helper T  cells

first: Deepali

last: Sawant


title: Untreated and iron-treated ARPE-19 cell gene expression

status: Public on Apr 07 2015

city: Philadelphia

first: Joshua

middle: L.

last: Dunaief

state: PA

address: 422 Curie Blvd, 305 Stellar Chance labs

department: Ophthalmology

institute: University of Pennsylvania

summary: To characterize the potential molecular pathway(s) affected by iron treatment and identify the one(s) responsible for C3 induction, we performed a whole genome microarray on untreated ARPE-19 cells and cells treated with 250 μM FAC for 48h/2d.

overall_design: Gene expression was compared between untreated and FAC-treated ARPE-19 cells, with three biological replicates in each.

first: Yafeng

last: Li

first: John

middle: W

last: Tobias


title: Common Immunologic Pathways Between Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis

city: Buffalo

first: kaiyu

last: Jiang

address: 875 Ellicott Street

department: Pediatrics

institute: University at Buffalo

summary: The polyarticular and oligoarticular forms of juvenile idiopathic arthritis are classified as distinct entities. At the same time, many children who present with an oligoarticular phenotype eventually evolve to a polyarticular disease pattern, suggesting that the phenotypes might share with overlapping molecular mechanisms. Using gene expression microarrays, we found that 14 genes in neutrophils and 55 genes in PBMC shows common patterns of differential expression when children with active oligoarticular and polyarticular JIA were compared with healthy controls. These results demonstrate that there are commonalities between oligoarticular and polyarticular JIA that suggest overlapping immune mechanisms.

overall_design: Total RNA was extracted from isolated PBMC and neutrophils from 14 patients with polyarticular JIA and 8 patients with pauciarticular JIA. Total RNA was extracted from neutrophils from 13 healthy controls and from PBMC from 15 healthy controls. Insufficient RNA for microarrays was obtained from neutrophils from two of the healthy controls.

first: Kaiyu

first: Mark

middle: B

last: Frank

first: Jeanette

last: Osban

first: Yanmin

last: Chen

first: Chelsea

last: Hartman

first: James

last: Jarvis


title: Genome-wide DNA methylation identifies trophoblast invasion-related genes: Claudin-4 and Fucosyltransferase IV control mobility via altering matrix metalloproteinase activity

city: Vancouver

first: Wendy

last: Robinson

state: BC

address: 950 W 28th Ave

department: Medical Genetics

institute: University of British Columbia

summary: Previously we have shown that extravillous cytotrophoblast (EVT) outgrowth and migration on a collagen gel explant model were restricted by exposure to decidual natural killer cells (dNK). This study investigates the molecular causes behind this phenomenon. Genome wide DNA methylation of exposed and unexposed EVT was assessed using the Illumina Infinium HumanMethylation450 BeadChip array (450K array). The array identified 444 differentially methylated CpG loci in dNK-treated EVT compared to medium control (P<0.05). The represented genes from these loci had critical biological roles in cellular development, cellular organization and maintenance by Ingenuity Pathway Analysis (IPA). Furthermore, 23 mobility-related genes were identified by IPA from dNK-treated EVT. Among these genes, CLDN4 (encoding claudin-4) and FUT4 (encoding fucosyltranferase IV) were chosen for follow-up studies because of the biological relevance found in the research on tumor cells. The results showed that the mRNA and protein expressions of both CLDN4 and FUT4 in dNK-treated EVT were significantly reduced, and were inversely correlated with DNA methylation. Knocking down CLDN4 and FUT4 by siRNA reduced trophoblast invasion, possibly through the altered MMP-2 and/or MMP-9 expression and activity. Taken together, dNK alter EVT mobility at least partially in association with an alteration of DNA methylation profile. Hypermethylation of CLDN4 and FUT4 reduce protein expressions. CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility.

overall_design: This studied analyzed 17 samples of placental villous explant cultre exposed to different growth conditions. 6 Control samples (biological replicates) were cultured and unexposed to any other cells. 5 samples (biological replicates and from the same placentas as the controls) were cultured and exposed to conditions containing decidua natural killer cells trapped inside hollow fibres (thus only the factors secreted by the cells could interact with the explant culture and not the cells themselves. 6 samples (biological replicates and from the same placentas as the controls) were cultured and exposed to media containing IL-15. The DNA from the villous explants was isolated, bisulfite converted and run on the array.

first: Yuxiang

last: Hu

last: Blair

first: Ryan

last: Yuen

middle: P

first: Peter

last: von Dadelszen


title: Expression data from the commensal bacteria Escherchia coli strain HB101 interacting with Caenorhabditis elegans and/or Giardia duodenalis

status: Public on Apr 02 2015

city: Calgary

first: Teklu

middle: Kuru

last: Gerbaba

address: 2500 University Drive NW

department: Biological Sciences

institute: University of Calgary

summary:
Homeostatic interactions between the host and its resident microbiota is important for normal physiological functions and if altered, it could lead to dysbiosis, a change in the structure and function of the microbiota, and as a result to various pathophysiologies. Altered structure in bacterial community is associated with various pathophysiologies, but we are just beginning to understand how these structural changes translate into functional changes. Environmental factors including pathogenic infections can lead to altered interactions between the host and its resident microbiota.
We used microarray analysis and a C. elegans model system to gain insights on the mechanisms of functional changes in host-commensal bacteria interaction in the presence or absence of G. duodenalis and identified expression pattern in commensal bacteria that are characteristic of homeostatic and dysbiotic interactions.

overall_design: E. coli HB101 exposed to C. elegans in the presence or absence of G. duodenalis conditioned S-basal complete media for 24 hours were used for RNA extraction and hybridization on Affymetrix microarrays. We collected expression data for E. coli HB101, E. coli HB101 exposed to C. elegans, E. coli HB101 exposed to Giardia conditioned media, and E. coli HB101 exposed to both C. elegans and Giardia conditioned media.

first: Andre

last: Buret


title: A Sleeping Beauty Forward Genetic Screen Identifies Genes Promoting Osteosarcoma Development and Metastasis

city: Memphis

first: Chunxu

last: Qu

state: TN

address: 262 Danny Thomas Pl

department: Pathology

institute: St Jude Children's Research Institute

summary: A Sleeping Beauty (SB) transposon forward genetic screen was performed to identify the genes that promote osteosarcoma (OS) development and metastasis.  Mutagenesis induced OS in wild type mice and accelerated it on a Trp53 deficient background. Analysis of tumors demonstrated that Trp53 deficiency is correlated with genomic instability, which was virtually absent in tumors induced by SB mutagenesis alone.  Metastases developed in a subset of animals and in nearly all cases were clonal related to primary tumors. Over 200 candidate genes were identified, many of which are altered in human cancers including OS.  Signaling pathways enriched for candidate genes were also identified and a subset of these pathways and genes were functionally validated and represent new targets for OS treatment.

overall_design: Bisulphite converted DNA from the 21 diagnosis osteosarcoma patients and 3 hOB cell line replicates were hybridised to the Illumina Infinium 450K Human Methylation Beadchip.

first: Branden

last: Moriarity

first: George

middle: M

last: Otto

first: Eric

last: Rahrmann

first: Sue

last: Rathe

first: Natalie

last: Wolf

first: Luke

last: Manlove

first: Rebecca

last: LaRue

first: Nuri

last: Temiz

first: Sam

last: Molyneux

first: Kwangmin

last: Choi

first: Kevin

last: Holly

first: Aaron

last: Sarver

first: Milcah

middle: C

last: Scott

first: Colleen

last: Forster

first: Jaime

last: Modiano

first: Chand

last: Khanna

first: Stephen

last: Hewitt

first: Rama

last: Khokha

first: Yi

last: Yang

first: Richard

last: Gorlick

first: Michael

last: Dyer

first: David

last: Largaespada


title: Expression data from Human Umbilical Vein Endothelial Cell after influenza virus infection

status: Public on Apr 06 2015

city: Beijing

first: Wei

last: Wang

address: HaiDian District, Mingyuanxilu No.2

institute: College of Veterinary Medicine

summary:
This research focus primarily on the interaction between influenza virus and endothelial cell, then we used microarrays to observe global patterns of gene expression in Human Umbilical Vein Endothelial Cells after influenza virus infection and offer further insight into the interaction between endothelial cells and influenza viruses.
We used microarrays to detail the global programme of gene expression and identified distinct classes of up-regulated genes during this process.

overall_design: Human Umbilical Vein Endothelial Cells were selected at an early stage for RNA extraction and hybridization on Affymetrix microarrays. Then, we analysed the selected genes at expression level.


title: TGF-beta stimulation in ovarian cancer cells

first: Horacio

last: Cardenas

address: 980 West Walnut Street

institute: Indiana University

summary: Genome-wide DNA methylation profiles of TGF-beta ovarian cancer cells were obtained using next generation Illumina Infinium 450k assay which includes over 450,000 GpG sites.

overall_design: DNA from 12 samples were hybridized to the Illumina's Infinium HumanMethylation 450 BeadChip

first: Daniela

last: Matei

first: Yunlong

last: Liu

first: Matthew

last: Segar


title: Narrow-band UVB phototherapy reverses DNA methylation changes in psoriatic epidermis

city: Umeå

first: Xiaolian

last: Gu

state: västerbotton

address: Building 6M, 2nd floor, Umeå University

department: Medical Biosciences

country: Sweden

institute: Umeå University

summary: To obtain a comprehensive DNA methylation signature specific for the epidermal component of psoriasis and to analyze methylation changes during therapy, we performed genome-wide DNA methylation profiling of epidermal cells from 12 patients undergoing narrow-band UVB phototherapy and 12 corresponding healthy controls. A distinct DNA methylation pattern was seen in psoriasis compared to controls. An overall hypomethylation was found in psoriasis and 3665 methylation variable positions were identified. The DNA methylation pattern was reversed at the end of phototherapy in patients with clinical response.

overall_design: Bisulphite converted DNA from the 47 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.

first: Elisabet

last: Nylander

first: Philip

last: Coates

first: Robin

last: Fahraeus

first: Karin


title: Blood transcriptomes of chronic HCV patients four years after therapy-induced viral clearance

city: Rotterdam

first: Andre

last: Boonstra

address: Dr. Molewaterplein 40

department: Dept. of Gastroenterology and Hepatology

country: Netherlands

institute: Erasmus MC

summary: Little is known on the immune status in liver and blood of chronic HCV patients long after therapy-induced viral clearance. In this study, we demonstrate that 4 years after clearance, regulation of HCV-specific immunity in blood by regulatory T-cells (Treg) and the immunosuppressive cytokines IL-10 and TGF-β is still ongoing. Importantly, sampling of the liver 4 years after clearance shows that intrahepatic Treg are still present in all patients, suggesting that liver T-cells remain regulated. Identifying mechanisms that regulate HCV-specific memory T-cell responses after clearance is highly relevant for the development of protective vaccines, especially in patients at high-risk of reinfection.

overall_design: A genome-wide gene expression analysis was performed on a blood cohort of 5 chronic HCV patients. For each patient, blood was collected at 4 years after ending of HCV therapy, and blood transcriptomes was compared to the paired transcriptomes at baseline and 24 weeks after ending HCV therapy (GSE59312).

first: Michelle

last: Spaan

first: Mark

last: Claassen

first: Jun

last: Hou

first: Harry

last: Janssen

first: Robert

last: de Knegt


title: DNA methylation of matched primary-metastases medulloblastomas

status: Public on Apr 01 2015

city: Toronto

first: Xin

state: Ontario

address: 686 Bay Street

department: Laboratory Medicine and Pathobiology

institute: Hospital for Sick Children

summary: DNA methylation was generated from 11 pairs of matched primary-metastases medulloblastoma samples using the Illumina Infinium HumanMethylation450 BeadChip array

overall_design: Total DNA was extracted from primary and metastases medulloblastoma samples, bisulfite converted and hybridized to Illumina Infinium HumanMethylation450 BeadChip according to the manufacturer's instructions.

first: Adrian

last: Dubuc

first: Vijay

last: Ramaswamy

first: Marc

last: Remke

first: Michael

middle: D

last: Taylor


title: Whole genome expression of matched primary-metastases medulloblastomas

last: Wang

summary: Affymetrix Human Gene 2.0 ST Array profiling of 9 pairs of matched primary-metastases medulloblastoma samples.

overall_design: Total RNA was extracted from primary and metastases medulloblastoma samples and hybridized to Affymetrix Human Gene 2.0 ST Arrays (24-Array Plates) according to the manufacturer's instructions.


title: Whole genome expression and DNA methylation analysis of matched primary-metastases medulloblastomas

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

overall_design: Refer to individual Series


title: Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren

city: Detroit

first: Douglas

last: Ruden

state: Michigan

address: 275 E. Hancock Ave., Room  291.1

department: Department of Obstetrics and Gynecology

institute: Wayne State University

summary: We report that the DNA methylation profile of a child’s neonatal whole blood can be significantly influenced by his or her mother’s neonatal blood lead levels (BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from current blood and neonatal blood from both the mother and the child. We found that mothers with high neonatal BLL correlate with altered DNA methylation at 564 loci in their children’s neonatal blood. Our results suggest that Pb exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren’s neonatal dried blood spots. This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren.

overall_design: For the study, we selected 35 dried blood spots (DBS) collected from mother-infant pairs from Health Fairs ran in three Detroit communities, because they have a high prevalence (8-11%) of high BLL in children. The sample set consisted of 25 male children and 18 female children. We also collected the neonatal DBS and mother neonatal DBS for these mother-infant pairs from the Michigan Neonatal Biobank. Then we measured a blood lead levels in dried blood spots using using atomic absorbtion spectrophotometry. Finally we measured the DNA methylation levels using human methylation 450K array from Illumina. Then we normalized the data for technical biases and tried to infer the the locus specific DNA methylation changes due to Pb exposure which was carried over from the grandmothers to the grandchildren by the Pb –exposed fetal germ cells of the mother using  statistical model proposed by Sofer et al, 2012.

first: Arko

last: Sen

first: Nicole

last: Heredia

first: Marie-Claude

last: Senut

first: Susan

last: Land

first: Mary

middle: O

last: Dereski


title: Specific Genomic and Transcriptomic Aberrations in Tumors Induced by Partial Hepatectomy of a Chronically Inflamed Murine Liver

city: Jerusalem

first: Daniel

last: Goldenberg

address: Ein Kerem

department: Gene therapy

country: Israel

institute: Hadassah medical center

type:
Expression profiling by array
Genome variation profiling by array


title: Specific Genomic and Transcriptomic Aberrations in Tumors Induced by Partial Hepatectomy of a Chronically Inflamed Murine Liver [expression]

summary: Background & Aims. Resection of hepatocellular carcinoma (HCC) tumors by partial hepatectomy (PHx) is associated with promoting hepatocarcinogenesis. We have previously reported that PHx promotes hepatocarcinogenesis in the Mdr2-knockout (Mdr2-KO) mouse, a model for inflammation-mediated HCC. Now, we explored the molecular mechanisms underlying the tumor-promoting effect of PHx in these mice. Methods. Using microarrays-based techniques, we compared genomic and transcriptomic profiles of HCC tumors developing in the Mdr2-KO mice either spontaneously or following PHx. Results. PHx accelerated HCC development in these mice by four months. PHx-induced tumors had only amplifications affecting multiple chromosomes and locating mainly near the acrocentric centromeres of murine chromosomes. Four different chromosomal regions were amplified each in at least three tumors. All tumors of untreated mice had chromosomal aberrations, including both deletions and amplifications. Comparison of gene expression profiles revealed a significantly enriched expression of oncogenes, chromosomal instability markers and E2F1 targets in the post-PHx compared to spontaneous tumors. Both tumor groups shared the same frequent amplification at chromosome 18. Here, we demonstrated that one of the regulatory genes encoded by this amplified region, Crem, was over-expressed in the nuclei of murine and human HCC cells in vivo, and that it stimulated proliferation of human HCC cells in vitro. Conclusions:  PHx of a chronically inflamed liver directed tumor development to a discrete pathway characterized by amplification of specific chromosomal regions and expression of specific tumor-promoting genes. Crem is a new candidate HCC oncogene frequently amplified in this model and frequently over-expressed in human HCC.

overall_design: To explore the mechanisms of the accelerated HCC development by PHx, we compared liver tumors and their matched non-tumor liver tissues between 9-month-old hepatectomized and 13-14-month-old untreated Mdr2-KO mice. RNA was isolated from frozen liver tissues and subjected to gene expression profiling using GeneChip Mouse Gene 1.0 ST Array

first: Ezra

last: Ella

first: Denise

last: Heim

first: Evgeniy

last: Stoyanov

first: Rona

last: Harari-Steinfeld

first: Israel

last: Steinfeld

first: Orit

last: Pappo

first: Temima

last: Schnitzer Perlman

first: Natalie

last: Nachmansson

first: Ludmila

last: Rivkin

first: Devorah

last: Olam

first: Rinat

last: Abramovitch

first: Henning

last: Wege

first: Eithan

last: Galun


status: Public on Mar 31 2015

city: Miami

first: John

last: Gilbert

state: FL

address: 1535 NW 10th Ave

department: John P. Hussman Institute for Human Genomics

institute: University of Miami

summary:
Epigenome Analysis of Post-Mortem Human Temporal Pole Brain Tissue
For more information, please refer to DOI: 10.3233/JAD-141989

overall_design: Temporal Pole regions from 24 age-matched causcasian males: 8 samples which died of normal causes, 8 samples with Alzheimer's disease (stage 3/4) and 8 samples with dementia with lewy bodies

first: Margaret

last: Pericak-Vance


title: Age-associated DNA methylation changes within 5 years after birth in human blood leukocytes

city: Huddinge

first: Lovisa

middle: E

last: Reinius

address: Novum, Halsovagen 7-9

department: Department of Biosciences and Nutrition

institute: Karolinska Institutet

summary: Age-related changes in DNA methylation occurring in blood leukocytes during early childhood may reflect epigenetic maturation. We hypothesized that some of these changes involve gene networks of critical relevance in leukocyte biology and conducted a prospective study to elucidate the dynamics of DNA methylation. Serial blood samples were collected at 3, 6, 12, 24, 36, 48 and 60 months after birth in 10 healthy girls born in Finland and participating in the Type 1 Diabetes Prediction and Prevention Study. DNA methylation was measured using the HumanMethylation450 BeadChip. After filtering for the presence of polymorphisms and cell-lineage-specific signatures, 794 CpGs showed significant DNA methylation differences as a function of age in all children (41.5% age-methylated and 58.4% age-demethylated, bonferroni corrected p-value <0.001). Age-methylated CpGs were more frequently located in gene bodies and within +5 to +50 kilobases (kb) of transcription start sites (TSS), and enriched in developmental, neuronal and plasma membrane genes. Age-demethylated CpGs were associated to promoters and DNAse-I hypersensitivity sites, located within -5 to +5 kb of the nearest TSS, and enriched in genes related to immunity, antigen presentation, the polycomb-group protein complex and cytoplasm. This study reveals that susceptibility loci for complex inflammatory diseases (e.g. IRF5, NOD2, PTGER4) and genes encoding histone modifiers and chromatin remodeling factors (e.g. HDAC4, KDM2A, KDM2B, JARID2, ARID3A, SMARCD3) undergo DNA methylation changes in leukocytes during early childhood. These results open new perspectives to understand leukocyte maturation and provide a catalog of CpGs that may need to be corrected for age effects when performing DNA methylation studies in children.

overall_design: We analysed the longitudinal changes in DNA methylation in a total of 60 samples at 3, 6, 12, 24, 36, 48, and 60 months after birth, using serial DNA samples extracted from peripheral blood leukocytes of 10 healthy girls of the Diabetes Prediction and Prevention Study (DIPP).

first: Nathalie

last: Acevedo

first: Morana

last: Vitezic

first: Vittorio

last: Fortino

first: Cilla

last: Söderhäll

first: Hanna

last: Honkanen

first: Riitta

last: Veijola

first: Olli

last: Simell

first: Jorma

last: Toppari

last: Ilonen

first: Mikael

last: Knip

first: Annika

last: Scheynius

first: Heikki

last: Hyöty

first: Dario

last: Greco

first: Juha

last: Kere


title: Expression data in the Cap Stage of the Human Embryonic Tooth Germ

city: Fuzhou

first: Zhen

last: Huang

address: Fujian Key Laboratory of Developmental and Neuro Biology, College of Life Science, Fujian Normal University, Fuzhou, Fujian, P.R. China.

institute: Fujian Normal University

summary:
Numerous genes that play important regulative roles during tooth development in mice have been identified. However, very little is known about gene expression and function in human odontogenesis.
We used microarrays to detail the global programme of gene expression underlying tooth development and identified distinct classes of up-regulated genes during in the tooth germs.

overall_design: Tooth germs of molar, incisor, and canine at the cap stage were dissected, respectively, from 12-week-old human embryonic oral cavity for RNA extraction and hybridization on Affymetrix microarrays. We sought to screen for the genes that are strongly expressed in the dental tissues and analysis if these genes related to mammalian tooth development and tooth abnormalities.

first: Xuefeng

last: Hu

first: Yading

last: Zhang


title: Expression data of LoVo cells treated by 10mM metformin for eigher 8 or 24h

city: Shanghai

first: houkai

last: li

state: Shanghai

address: 1200 Cailun Road, Building 1, Room 1531, Pudong New District

institute: Shanghai University of Traditional Chinese Medicine

summary:
Metformin is effective for prevention or treatment of various tumors. There are a lot of studies on the underlying mechanisms of metformin as respect to its anti-tumor action.
We used microarrays to detail the global programme of gene expression underlying the anti-tumor effects of metformin on LoVo cells.

overall_design: Human derived LoVo cells were treated with metformin (10mM) for 8 and 24h, and the control and treated cells were harvested for RNA extraction and hybridization on Affymetrix microarrays.The samples were grouped as Met8h, Met24h, Con8h, and Con24h, respectively.

first: Houkai

last: Li

first: Wei

last: Jia


title: Expression data from adult NSCs/neural progenitors with and without active SIRT1

city: Stanford

first: Victoria

last: Rafalski

state: CA

address: 300 Pasteur Drive Alway M314

department: Genetics

institute: Stanford University

summary: We used microarrays to assess gene expression differences between proliferating adult NSCs/neural progenitors with and without active SIRT1.

overall_design: Adult NSCs/neural progenitors were isolated from 8 week old Sirt1lox/lox and NestinCre;Sirt1lox/lox mice (129SV strain), cultured for one passage in growth factors (EGF and bFGF) before isolation at early passage 2 for RNA extraction and hybridization on Affymetrix microarrays. Gene expression data were adjusted for background and normalized using RMA.

first: Jamie

last: Brett

first: Duygu

last: Ucar

first: Jason

last: Dugas

first: Elizabeth

last: Pollina

first: Lionel

last: Chow

first: Adiljan

last: Ibrahim

first: Suzanne

middle: J

last: Baker

first: Ben

last: Barres

first: Anne

last: Brunet


title: Differential epigenetic effect of cold plasma on MCF-7 and MDA-MB-231 breast cancer cells

city: Seoul

first: Sung-bin

last: Park

address: Dongguk university, Pil-dong, Joong-gu

department: Life Science

country: South Korea

institute: Dongguk Univ.


title: Genome-wide analysis of gene methylation by effect of cold plasma on breast cell line MCF-7.

summary: Genome wide DNA methylation profiling of estrogene receptor postive breast cancer cell line MCF-7, treating atmospheric cold plasma (plasma). The Illumina Infinium Human Methylation 450k Bead chip was used to obtain DNA methylation profiles across approximately 450,000 CpGs. This profiling indicates that plasma induces epigenetic and cellular changes.

overall_design: Genomic DNA obtained from  MCF-7 where effected by cold plasma.

first: Sung-Bin

first: Sun

last: Kim


title: Genome-wide analysis of gene methylation by effect of cold plasma on breast cell line MDA-MB-231.

summary: Genome wide DNA methylation profiling of estrogene receptor negative breast cancer cell line MDA-MB-231, treating atmospheric cold plasma (plasma). The Illumina Infinium Human Methylation 450k Bead chip was used to obtain DNA methylation profiles across approximately 450,000 CpGs. This profiling indicates that plasma induces epigenetic and cellular changes.

overall_design: Genomic DNA obtained from  MDA-MB-231 where effected by cold plasma.


title: RelA Nuclear factor-kappaB (NF-kB) Subunit binding Loci in Promoter Regions of PHM1-31 Myometrial Smooth Muscle Cells (expression)

city: Sheffield

first: Neil

middle: Robert

last: Chapman

state: South Yorkshire

address: Tree Root Walk

department: Oncology and Metabolism

institute: University of Sheffield

summary: A study to define the binding loci of RelA-containing NF-kappaB dimers and subsequent correlation with gene expression in a human myometrial smooth muscle cell line after exposure to TNF.

overall_design: Monolayers of PHM1-31 cells were exposed to TNF (10ng/ml) for 1 hour or left unstimulated. Total RNA was isolated, prepared and used to probe AffymetrixU133Plus2 expression arrays. Both datasets were subsequently analysed in Partek Genomics Suite V6.6 and correlations between promoter occupancy (promoter arrays) and gene expression (expression arrays) were made.

first: Sarah

last: Waite

last: Cookson

first: Paul

middle: R

last: Heath

first: Saurabh

middle: V

last: Gandhi


title: RelA Nuclear factor-kappaB (NF-kB) Subunit binding Loci in Promoter Regions of PHM1-31 Myometrial Smooth Muscle Cells

type: Genome binding/occupancy profiling by genome tiling array


title: Induction of ER stress in HCT116 colon cancer cells

city: Galway

first: Sharon

last: Glynn

address: Biosciences, NUI Galway

country: Ireland

institute: National University of Ireland Galway

summary:
To investigate the role of p53 and DICER in the induction of ER stress, wildtype, p53 knockout or DICER mutant HCT116 colon cancer cells were treated with the ER stress inducers tunicamycin or brefeldin A for 24 hours.
Microarray analysis was used to determine changes in gene expression associated with the induction of ER stress, and to compare this induction in wildtype, p53 knockout or DICER mutant HCT116 colon cancer cells

overall_design: Triplicate samples of HCT116 wildtype, HCT116 p53 knockout and HCT116 DICEREX5/EX5 cells were treated with with 0.5 mg/ml of BFA or 2 mg/ml of Tm for 24 h. Following treatment, cells were harvested and lysed in TRIzol reagent and RNA was extracted. Microarray analysis was carried out using Affymetrix HG-U133_Plus-2 arrays.

first: Afshin

last: Samali

first: Sanjeev

last: Gupta

first: Adrienne

last: Gorman

middle: A


title: Pregnane X receptor knockout mice display aging-dependent wearing of articular cartilage

city: Tokyo

first: Kotaro

last: Azuma

address: 7-3-1, Hongo, Bunkyo-ku

country: Japan

institute: University of Tokyo

summary: Steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and the intestine. They function as xenobiotic sensors by inducing genes involved in detoxification and drug excretion. Recent evidence showed that SXR and PXR are also expressed in bone tissue where they mediate bone metabolism. Here we report that systemic deletion of PXR results in aging-dependent wearing of articular cartilage of knee joints. Histomorphometrical analysis showed remarkable reduction of width and an enlarged gap between femoral and tibial articular cartilage in PXR knockout mice. We hypothesized that genes induced by SXR in chondrocytes have a protective effect on articular cartilage and identified Fam20a (family with sequence similarity 20a) as an SXR-dependent gene induced by the known SXR ligands, rifampicin and vitamin K2. Lastly, we demonstrated the biological significance of Fam20a expression in chondrocytes by evaluating osteoarthritis-related gene expression of primary articular chondrocytes. Consistent with epidemiological findings, our findings indicate that SXR/PXR protects against aging-dependent wearing of articular cartilage and that ligands for SXR/PXR have potential role in preventing osteoarthritis caused by aging.

overall_design: ADC5 cells were infected with adeno-SXR or adeno-DsRed and cultured in phenol red-free DMEM with charcoal/dextran-treated FCS (5%) containing rifampicin (10 μM), vitamin K2 (10 μM), or ethanol. Total RNA was extracted from the cells using the ToTALLY RNA Kit (Ambion, Austin, TX). Profiling of mRNA was performed on Affymetrix Mouse Gene 1.0 ST arrays (Affymetrix Inc., Santa Clara, USA) according to the Gene Chip labeling assay manual version 4.


title: Aurora kinase A is upregulated in cutaneous T-cell lymphoma and represents a potential therapeutic target

city: New York

first: Mayte

last: Suarez-Farinas

state: NY

address: 1425 Madison Ave, L2-70C, Box 1077,

institute: Mount SinaiSchool of Medicine

summary: Cutaneous T-cell lymphomas form a heterogeneous group of non-Hodgkin lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. Here, we demonstrate by gene expression arrays that aurora kinase A is one of highly overexpressed genes of the serine/threonine kinase in CTCL. The finding was confirmed by qualitative RT-PCR, Western blotting and immunohistochemistry in CTCL cell lines and primary patient samples. Moreover, treatment with a specific aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest in G2 phase as well as apoptosis in CTCL cell lines. These new data provide a promising rationale for using aurora kinase A inhibition as a therapeutic modality of CTCL.

overall_design:
14 lesional skin biopsies of different MF patients (patch=3, plaque=6, tumor=4) and 9 healthy controls.
Comparison between Cutaneus Tcell Lymphoma Samples and Healthy Control Tissue

first: Daniel

last: Humme

first: Chalid

last: Assaf

first: James

middle: G

last: Krueger

last: Suárez-Fariñas


title: Expression data from human monocyte-derived dendritic cells treated or not with interleukin 17A (IL-17A)

city: Oullins

first: Karene

last: Mahtouk

address: 165 Chemin du Grand Revoyet : BP12

department: LBMC

country: France

institute: CNRS UMR5239

summary:
IL-17A is a pro-inflammatory cytokine that promotes host defense against infections and contributes to the pathogenesis of chronic inflammatory diseases. Dendritic cells (DC) are antigen-presenting cells responsible for adaptive immune responses. Here, we report that IL-17A induces intense remodeling of lipid metabolism in human monocyte-derived DC, as revealed by microarrays analysis. In particular NR1H3/LXR-a and its target genes were significantly upregulated in response to IL-17A. IL-17A induced accumulation of Oil Red O-positive lipid droplets in DC leading to the generation of lipid-laden DC. A lipidomic study established that all the analyzed lipid species, i.e phospholipids, cholesterol, triglycerides, cholesteryl esters were elevated in IL-17A-treated DC. The increased expression of membrane lipid transporters in IL-17A-treated DC as well as their enhanced ability to uptake the fatty acid Bodipy-FL-C16 suggested that lipid uptake was the main mechanism responsible for lipid accumulation in response to IL-17A. IL-17A-induced lipid laden DC were able to stimulate allogeneic T cell proliferation in vitro as efficiently as untreated DC, indicating that IL-17A-treated DC are potently immunogenic. This study, encompassed in the field of immunometabolism, points out for the first time IL-17A as a modulator of lipid metabolism in DC and provides a rationale to delineate the importance of lipid-laden DC in IL-17A-related inflammatory diseases.
We used microarrays analysis to understand the impact of IL-17A on human monocyte-derived human dendritic cells. We found overexpression of many genes involved in lipid metabolism in IL-17A-treated dendritic cells compared to untreated dendritic cells. In particular NR1H3/LXR-a and its target genes were significantly upregulated in response to IL-17A. IL-17A induced accumulation of Oil Red O-positive lipid droplets in DC leading to the generation of lipid-laden DC. A lipidomic study established that all the analyzed lipid species, i.e phospholipids, cholesterol, triglycerides, cholesteryl esters were elevated in IL-17A-treated DC. The increased expression of membrane lipid transporters in IL-17A-treated DC as well as their enhanced ability to uptake the fatty acid Bodipy-FL-C16 suggested that lipid uptake was the main mechanism responsible for lipid accumulation in response to IL-17A. IL-17A-induced lipid laden DC were able to stimulate allogeneic T cell proliferation in vitro as efficiently as untreated DC, indicating that IL-17A-treated DC are potently immunogenic. This study, encompassed in the field of immunometabolism, points out for the first time IL-17A as a modulator of lipid metabolism in DC and provides a rationale to delineate the importance of lipid-laden DC in IL-17A-related inflammatory diseases.

overall_design: RNA was extracted from untreated in vitro-generated DC at day 0 (DC, 4 biological replicates ) or DC cultured for 12 days with IL-17A, in the absence or presence of IFN-g  (DC-17 and DC-G17, 5 biological replicates)

first: Christine

last: Delprat


title: Expression data from normal and transplanted islets in non-pregnant and pregnant condition

city: Leuven

first: Leentje

last: Van Lommel

address: Herestraat 49 bus 901

department: Molecular cell biology

institute: KULeuven

summary:
ABSTRACT:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by using islet tissue culture with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice.  Additionally, the islet mRNA expression of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or transplanted in female recipients that became pregnant (day 12.5), male islets induced the ‘islet pregnancy gene signature’, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in male and female beta cells.
The data obtained from the normal islets of pregnant mice (day12.5) was already described in Schraenen et al. 2010 (PMID: 20886204 and PMID: 20938637).

overall_design: Islets and islet grafts were isolated from non-prengant and pregnant mice for RNA extraction and hybridization on Affymetrix microarrays. For every condition, at least 3 biological replicates were used.

first: Anica

last: Schraenen

first: Katleen

last: Lemaire

first: Frans

last: Schuit

first: Ingrid

last: Arijs


title: Expression data from 76N human mammary epithelial cells (hMECs)

city: Omaha

first: Vimla

last: Band

state: NE

address: Room 6011, DRC, 985805 Nebraska Medical Center

department: Genetics, Cell Biology and Anatomy

institute: University of Nebraska Medical Center

summary: We used microarrays to detail the global programme of gene expression after knockdown of Ecdysoneless in hMECs

overall_design: 76N cells were treated with control or Ecd siRNA for  for RNA extraction and hybridization on Affymetrix microarrays.

first: Simon

last: Lin

first: Ying

last: Zhang

first: Jun

last: Kim


title: Differential gene expression in neuroblastoma cells after transfection with control siRNA, N-Myc siRNA-1, N-Myc siRNA-2, lncMycN siRNA-1 or lncMycN siRNA-2

city: Randwick

first: Tao

last: Liu

state: NSW

address: Lowy Cancer Research Centre

country: Australia

institute: Children's Cancer Institute Australia

summary:
N-Myc oncoprotein induces neuroblastoma by modulating gene transcription, and long noncoding RNAs exert biological effects by regulating gene expression.
We analysed whether N-Myc and the long noncoding RNA lncMycN mediate the expression of common subsets of genes.

overall_design: Neuroblastoma Kelly cells were transfected with control siRNA, N-Myc siRNA-1, N-Myc siRNA-2, lncMycN siRNA-1 or lncMycN siRNA-2. RNA was extracted from the cells 48 hours after siRNA transfections, and subjected to differential gene expression studies with Affymetrix microarrays.

first: Liu

last: Tao


title: Expression data in PBMCs from SLE patients and controls

city: South San Francisco

first: Michael

last: Townsend

address: 1 DNA Way

department: ITGR Diagnostics Discovery

country: USA

institute: Genentech

summary:
Peripheral blood mononuclear cells were collected from SLE patients in an observational study performed at the University of Michigan
Blood microarray expression data were used to confirm the presence of an Interferon signature and identify additional surrogate genes

overall_design: RNA from PBMCs of SLE patients and normal donor controls were obtained for one time point and were profiled on Affymetrix arrays

first: William

last: Kennedy

first: Romeo

last: Maciuca

first: Kristen

last: Wolslegel

first: Alexander

last: Abbas

first: Christina

last: Chaivorapol

first: Alyssa

last: Morimoto

first: Jacqueline

last: McBride

first: Paul

last: Brunetta

first: Bruce

last: Richardson

first: Jorn

last: Drappa

first: John

last: Davis

first: Timothy

last: Behrens


title: Low- and middle-dose of radiation on hNPC and HUVEC

first: Mari

last: Katsura

address: 2-11-16 Yayoi, Bunkyo-ku

department: Isotope Science Center

institute: The University of Tokyo

summary:
Many neural progenitor cells present in the fetus, but also in adult brain, which play a major role for the reproduction for healingin regeneration of neuronal cells, when differentiated cells are damaged. However, effects of radiation effect on undifferentiated neural progenitor cells remained unclear. The radiation doses of medical exposure, pollution by nuclear power plant accidents, and other exposure of workers; medical workers, airline crews, and astronaut have been focused. In this study, we report the effects of low- to middle- dose doses of radiation on cultured human neural progenitor cells (hNPC) differentiated derived from embryonic stem (ES) cells, which are partially compared with those of human umbilical vein endothelial cell (HUVEC).
Gene expression was changed by continuous exposure of 31mGy; 0.0072 mGy/ minute, 124mGy; 0.029 mGy/ minute and 496mGy; 0.085 mGy/ minute for seventy-two hours. While shortening in neurite length by 124mGy was not significant, its decrease was observed by 496 mGy of radiation. Number of altered pathways increased dose-dependently. By thirty-one mGy per 72 hours of radiation, gene expression of inflammatory pathways involving interferon and cell junction were changed. By 124 mGy of radiation, DNA double strand break repair pathways and cell adhesion molecules were affected. Then, 496 mGy of radiation for 72 hours altered translational DNA synthesis pathway, apoptotic pathway, various metabolic pathways and neural differentiation pathways. Dose-dependent transcriptional changes by low- to middle- radiation are consistent with gradual axonal shortening, growth arrest and neural cell death.

overall_design: Undifferentiated hNPC derived from embryonic stem (ES) cells and HUVECs synchronized in G1 cell cycle phase were irradiated from sealed cesium-137 for 72 h.

first: M

first: H

last: Cyou-Nakamine

first: T

last: Inoue

first: K

last: Kaneki

first: A

last: Taguchi

last: Kobayashi

first: S

last: Amagasa

last: Kaji

last: Sone

last: Kodama

last: Miyagawa

first: Y

last: Wada

first: N

last: Akimitsu


title: Robust enumeration of cell subsets from tissue expression profiles (HGU133Plus2)

status: Public on Mar 29 2015

first: Aaron

last: Newman

address: 265 Campus Drive

department: Institute for Stem Cell Biology and Regenerative Medicine & Division of Oncology, Stanford School of Medicine

summary: We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles. When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen, and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content, and closely related cell types. CIBERSORT should enable large-scale analysis of RNA specimens for cellular biomarkers and therapeutic targets (http://cibersort.stanford.edu).

overall_design: To evaluate the performance of CIBERSORT, RNA was extracted from the following primary human samples: (i) 14 disaggregated lymph node biopsies from patients with follicular lymphoma (FL), (ii) pre- and/or post-immunotherapy PBMC samples from 3 patients with extranodal marginal zone lymphoma (EMZL) or diffuse large B cell lymphoma (DLBCL), and (iii) B or T cells purified from the tonsils of 5 healthy normal controls.

first: Chih-Long

last: Liu

first: Michael

last: Green

first: Andrew

last: Gentles

first: Weiguo

last: Feng

first: Yue

last: Xu

first: Chuong

last: Hoang

first: Maximilian

last: Diehn

first: Ash

last: Alizadeh


title: Robust enumeration of cell subsets from tissue expression profiles

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

overall_design: Refer to individual Series


title: Effect of embryo in vitro culture on mESC transcriptome.

city: San Francisco

first: Rhodel

last: Simbulan

address: 513 Parnassus Ave

department: Obstetrics, Gynecology & Reproductive Sciences

institute: University of California San Francisco

summary:
Transcriptome analysis of mouse embryonic stem cell lines derived from embryos cultured in optimal and suboptimal conditions compared to cell lines derived from control embryos.
The use of assisted reproductive technologies (ART) such as in vitro fertilization (IVF) has resulted in the birth of more than 5 million children. While children conceived by these technologies are generally healthy, there is conflicting evidence suggesting an increase in adult-onset complications like glucose intolerance and high blood pressure in IVF children. Animal models indicate similar potential risks. It remains unclear what molecular mechanisms may be operating during in vitro culture to predispose the embryo to these diseases. One of the limitations faced by investigators is the paucity of the material in the preimplantation embryo to test for molecular analysis. To address this problem, we generated mouse embryonic stem cells (mESC) from blastocysts conceived after natural mating  (mESCFB) or after IVF, using optimal (KSOM + 5% O2; mESCKAA) and suboptimal (Whitten’s Medium, + 20% O2, mESCWM) conditions.

overall_design: We analyzed three female cell lines per group for a total of nine mouse embryonic stem cells on Affymetrix MoGene 1.0 ST Arrays.

first: Marlea

last: DiSanto

first: Xiaowei

first: Wingka

last: Lin

first: Emin

last: Maltepe

first: Archana

last: Shenoy

first: Annemarie

last: Donjacour

first: Andrea

last: Borini

first: Paolo

middle: F

last: Rinaudo


title: Effects of Aging and Anatomic Location on Gene Expression in Human Retina

status: Public on May 27 2015

city: New Haven

first: Hui

middle: Cong

last: Cai

address: 300 George St, Suite 8100

institute: Yale University

summary:
Objective: To determine the effects of age and topographic location on gene expression in human neural retina.
Methods: Macular and peripheral neural retina RNA were isolated from human donor eyes for DNA microarray and quantitative RTPCR analyses.
Results: Total RNA from human donor retina preserved integrity. Hierarchic clustering analysis demonstrates the gene expression profiles of young, old, macula and peripheral retina cluster into four distinct groups. Genes which are highly expressed in macular, peripheral, young or old retina are identified, including inhibitors of Wnt Signaling Pathway  (DKK1, FZD10 and SFRP2) shown preferably expressed in the periphery.
Conclusions: The transcriptome of the human retina is affected by age and topographic location. Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related eye diseases.

overall_design: Twleve youang and older retinal macular or prepheral RNA samples are used for DNA microarray study to compare the effects of aging and anatomic location on gene expression in human retina.

first: Lucian

last: Del Priore