title: Gene expression analysis of Wnt+ and Wnt- effector CD8 T cells

status: Public on Dec 16 2013

city: Epalinges

first: Werner

last: Held

address: Chemin des Boveresses 155

department: Ludwig Center for Cancer Research

institute: University of Lausanne

summary:
Wnt signal transduction during an immune response is involved in the establishment of functional CD8 T cell memory
P14 ConductinLacZ CD8 T cells (CD45.2) were transferred in CD45.1+.2+ recipient mice. The day after, recipients were infected with 200pfu LCMV WE. At day 8 after infection, cells from spleen and lymph nodes were harvested, magnetically enriched for CD8 T cells, loaded with the beta-galactosidase substrate (FDG) and sorted as 7AAD-negative CD45.- negative, beta-galactosidase positive versus negative cells.

overall_design: P14 CD8 T cells were sorted at day 8 after LCMV infection according to LacZ activity for RNA extraction and hybridization on Affymetrix microarrays.

first: Caroline

last: Boudousquié


title: Identification of chondrocyte subsets during human development

city: Los Angeles

first: Denis

last: Evseenko

state: CA

address: 1450 Biggy St

department: Orthopaedic Surgery

country: USA

institute: University of Southern  California

summary: Joint injury and osteoarthritis affect millions of people worldwide, but attempts to  generate articular cartilage using adult stem/progenitor cells have been unsuccessful.  We hypothesized that recapitulation of the human developmental chondrogenic  program using pluripotent stem cells (PSCs) may represent a superior approach for  cartilage restoration. Using laser capture microdissection followed by microarray  analysis, we first defined a surface phenotype  (CD146low/negCD166low/negCD73+CD44lowBMPR1B+) distinguishing the earliest  cartilage committed cells (pre-chondrocytes) at 5-6 weeks of development; pellet  assays confirmed these cells as functional, chondrocyte-restricted progenitors. Flow  cytometry, qPCR and immunohistochemistry at 17 weeks revealed that the superficial  layer of peri-articular chondrocytes was enriched in cells with this surface phenotype.  Isolation of cells with a similar immunophenotype from differentiating human PSCs  revealed a population of CD166negBMPR1B+ putative pre-chondrocytes. Functional  characterization confirmed these cells as cartilage-committed, chondrocyte  progenitors. The identification of a specific molecular signature for primary cartilagecommitted  progenitors may provide essential knowledge for the generation of purified,  clinically relevant cartilage cells from PSCs.

overall_design: A total of 15 samples were analyzed.  In the first comparison, there were 6 biological replicates for both the chondrogenic condensations and total limb cells.  In the second comparison, three biological replicates of chondrocytes from the articular region were compared to the 6 replicates of the condensations.


title: Genome-scale methylome profiling of hepatocellular adenomas.

status: Public on Dec 18 2013

city: Paris

first: Eric

last: Letouzé

address: 15 rue de l'école de médecine

country: France

institute: Ligue Contre Le Cancer

type: Methylation profiling by genome tiling array

summary: Genome-scale DNA methylation was analyzed in a cohort of 50 hepatocellular adenomas and 4 normal liver tissues. We performed consensus clustering to identify homogeneous tumor clusters, and we characterized DNA methylation changes in tumor subgroups.

overall_design: Bisulfite converted DNA from 50 fresh frozen hepatocellular adenomas and 4 normal liver samples were hybridized to Illumina HumanMethylation450 BeadChips.

first: Camilla

last: Pilati

first: Sandrine

last: Imbeaud

first: Jessica

last: Zucman-Rossi


title: Gene analysis of flagellin-treated nasal mucosa of Duox2-/- mice

city: Seoul

first: JUNGHEE

last: JOO

address: 134 Shinchon-dong, Seodaemun-gu

department: College of Medicine

country: South Korea

institute: Yonsei University

summary:
To evaluate the roles of DUOX2 in flagellin- induced inflammatory response in mouse nasal mucosa. Wild type (Duox2+/+) and Duox2 knockout (Duox2-/-) mice were stimulated with 1 μg/ml of flagellin for 4h.
422 genes (> 2 fold) were up-regulated in nasal mucosa of Duox2+/+ that was treated with flagellin and the full list of genes is presented in Supplemental Table II. These genes included the following defense- and immune response-related genes : Cytokine/chemokine-related genes (CCL20, CCR2, CCR5, CXCL2, CXCL5, CXCL9, CXCL16, IL18RAP, TNFAIP2, IL1B EAR2, FPR1), Granulocyte-related genes (IL8RB, MPO, PRG2, PPBP, PRG3), interferon-related genes (IFITM6, IFI47), macrophage related genes (IL1B, S100A9), and T-cell mediated immune response related genes (H2-Q6, IL1F9). In addition, signal transduction (PPBP, OLFR60, P2RY10) and cell adhesion (SELL, SELP, ICAM1, DSG1A, DSG3, VCAM1) related genes were also increased by flagellin treatment. These genes were selected based on the biological processes and molecular functions of their gene ontology. However, the increase of inflammation and immune response related genes by flagellin treatment were diminished in the nasal mucosa of the Duox2-/- mice compared with that of Duox2+/+ mice.

overall_design: Wild type (Duox2+/+) and Duox2 knockout (Duox2-/-) mice received either PBS (control) or flagellin (5 ug/ml) intranasally for 4h.

first: Jung-Hee

last: Joo

first: Yun

middle: S

last: Bae

first: Joo-Heon

last: Yoon


title: Contribution of paracrine signalling on dendritic cell activation

status: Public on Dec 15 2013

city: NEW YORK

first: Boris

middle: Michael

last: Hartmann

state: NY

address: One Gustave L Levy Place

department: Neurology

institute: Icahn School of Medicine at Mount Sinai

summary: The physiological function of the immune system and the response to therapeutic immunomodulators may be sensitive to combinatorial cytokine micro-environments that shape the responses of specific immune cells. Previous work shows that paracrine cytokines released by virus-infected human dendritic cells (DC) can dictate the maturation state of naïve DCs. To understand the effects of paracrine signaling, we systematically studied the effects of combinations cytokines in this complex mixture in generating an antiviral state. After naïve DCs were exposed to either IFNβ or to paracrine signaling released by DCs infected by Newcastle Disease Virus (NDV), microarray analysis revealed a large number of genes that were differently regulated by the DC-secreted paracrine signaling. In order to identify the cytokine mechanisms involved, we identified 20 cytokines secreted by NDV infected DCs for which the corresponding receptor gene is expressed in naïve DCs. By exposing cells to all combinations of 19 cytokines (leave-one-out studies) we identified 5 cytokines (IFNβ, TNFα, IL-1, TNFSF15 and IL28) as candidates for regulating DC maturation markers. Subsequent experiments identified IFNβ, TNFα and IL1 as the major synergistic contributors to this antiviral state. This finding was supported by infection studies in vitro, by T cell activation studies and by in vivo infection studies in mouse. Combination of cytokines can cause response states in DCs that differ from those achieved by the individual cytokines alone.  These results suggest that the cytokine microenvironment may act via a combinatorial code to direct the response state of specific immune cells.  Further elucidation of this code may provide insight into responses to infection and neoplasia as well as guide the development of combinatorial cytokine immunomodulation for infectious, autoimmune and immunosurveillance-related diseases.

overall_design: Cells exposed to the supernatant of NDV infected cells were compared to NDV infected cells, IFNβ treated cells and naïve dendritic cells after 8 hours.

middle: M

first: Stuart

middle: C

last: Sealfon


title: Genome-scale methylome and SNP profiling of hepatocellular adenomas and carcinomas

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

overall_design: Refer to individual Series


title: Validation of a histology-independent prognostic gene signature for early stage, non-small cell lung cancer including stage IA patients

status: Public on Dec 22 2013

city: Toronto

first: Ming

last: Tsao

state: Ontario

address: 610 University Avenue

department: Ontario Cancer Institute

country: Canada

institute: University of Toronto

summary:
Background: Patients with early stage non-small cell lung carcinoma (NSCLC) may benefit from treatments based on more accurate prognosis. A 15-gene prognostic classifier for NSCLC was identified from mRNA expression profiling of tumor samples from the NCIC CTG JBR.10 trial. Here, we assessed its value in an independent set of cases.
Methods: Expression profiling was performed on RNA from frozen, resected tumor tissues corresponding to 181 Stage I and II NSCLC cases collected at University Health Network (UHN181). Kaplan-Meier methodology was used to estimate three year overall survival probabilities and the prognostic effect of the classifier was assessed using log-rank testing. Cox proportional hazards model evaluated the signature's effect adjusting for clinical prognostic factors.
Results: Expression data of the 15-gene classifier stratified UHN181 cases into high and low-risk subgroups with significantly different overall survival (HR=1.92, 95% CI: 1.15-3.23, p=0.012). Its strength as a prognostic classifier was superior to stage alone (HR=1.52, 95% CI: 0.90-2.55, p-value=0.11). In subgroup analysis, this classifier predicted survival in 127 Stage I patients (HR=2.17, 95% CI: 1.12-4.20, p=0.018) and the smaller subgroup of 48 Stage IA patients (HR=5.61, 95% CI: 1.19-26.45, p=0.014. The signature was prognostic for both adenocarcinoma and squamous cell carcinoma cases (HR= 1.76, p-value=0.058; HR= 4.19, p-value=0.045, respectively).
Conclusions: The prognostic accuracy of a 15-gene classifier was validated in an independent cohort of 181 early stage NSCLC samples including Stage IA cases and in different NSCLC histologic subtypes.

overall_design: Expression profiling was performed on RNA from frozen, resected tumor tissues corresponding to 181 Stage I and II NSCLC cases collected at University Health Network (UHN181). !Series_contributor = Sandy,D,Der

first: Melania

last: Pintilie

first: Chang-Qi

last: Zhu

first: Dan

last: Strumpf

first: Ni

last: Liu

first: Igor

last: Jurisica

first: Frances

middle: A

last: Shepherd

first: Ming-Sound


title: Regulatory T cells from injured skeletal muscle

city: Boston

first: CBDM

last: Lab

state: MA

address: 77 Avenue Louis Pasteur

department: Microbiology and Immunobiology

institute: Harvard Medical School

summary: A phenotypically and functionally distinct population of CD4+ Foxp3+ T cells (Tregs) rapidly accumulates in acutely injured skeletal muscle of mice, just as invading myeloid-lineage cells switch from a pro-inflammatory to a pro-regenerative state.  Analysis of gene expression of Tregs and CD4+Foxp3- T cells (Tconvs) from injured muscle and spleen revealed that the transcriptome of muscle Treg cells is distinct from that of splenic Tregs. A set of genes is uniquely expressed by muscle Tregs, while another set is over-expressed by the two muscle populations vis-à-vis their two spleen counterparts.

overall_design: 6 wk-old Foxp3-ires-GFP mice were injured in skeletal muscles with cardiotoxin.  Four and fourteen days later, Tregs and Tconvs from spleen and muscle were double-sorted into Trizol. To reduce variability, cells from multiple mice were pooled for sorting, and three replicates were generated for all groups. RNA from 1.5-2.5 x 104 cells was amplified, labeled, and hybridized to Affymetrix Mouse Gene 1.0 ST Arrays.

first: D

last: Burzyn

last: Mathis

first: C

last: Benoist


title: Effects of Treg depletion in dystrophic muscle.

summary: CD4+Foxp3+ regulatory T cells (Tregs) accumulate in skeletal muscle from dystrophin-deficient mdx mice. Analysis of global gene expression in muscles from mdx mice treated with anti-CD25 compared with muscles from mdx mice treated with control antibody revealed that Tregs partially protect mdx mice from muscle pathology and promote muscle repair/regeneration.

overall_design: Mdx mice received 2 ip injections of 100 mg of anti-CD25 mAb (clone PC61) or rat IgG (Jackson Immunoresearch) at days 17 and 20 of age. Muscles were dissected 7 days after the last injection.


title: Gene expression profiling of injured skeletal muscle in the presence or absence of CD4+Foxp3+ regulatory T cells (Tregs).

summary: A comparative analysis of gene expression of injured skeletal muscle from wild-type (Foxp3-DTR-) and Treg-depleted (Foxp3-DTR+) mice showed that Treg cells are critical for effective repair and regeneration of acute injury of skeletal muscle.

overall_design: Foxp3-DTR+ and Foxp3-DTR- mice were injured with cardiotoxin in TA muscle at day 0 and treated with diphtheria toxin every other day from day 0 until dissection on day 4 or 8. TA muscle was flash-frozen and RNA was extracted using Trizol. RNA from whole tissue samples was amplified, labeled, and hybridized to Affymetrix Mouse Gene 1.0 ST Arrays.


title: Comparative study of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in MCL

status: Public on Dec 14 2013

city: BARCELONA

first: DOLORS

last: COLOMER

address: VILLARROEL 170

country: Spain

institute: IDIBAPS-HOSPITAL CLINIC

summary:
Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. However, the use of mTOR inhibitors as single agents have shown limited clinical efficacy in relation with drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we evaluated the antitumor activity of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in primary MCL cells. We found that dual PI3K/mTOR inhibitor modulated angiogenesis, tumor invasiveness and cytokine signaling compared to a mTOR inhibitor and a pan-PI3K inhibitor in MCL.
We used microarrays to compare the effect of these three compounds in MCL and identified distinct classes of down-regulated genes modulated by each compound.

overall_design: Global RNA expression in primary cells from two MCL patients treated with a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor for 8 hours

first: Laia

last: Rosich

first: Dolors

last: Colomer


title: Microarray analysis of WT and L-Myc-deficient DC subsets

city: Saint Louis

first: Kenneth

last: Murphy

state: MO

address: 660 S. Euclid Ave.

department: Pathology and Immunology

institute: Washington University School of Medicine

summary: Analysis of L-Myc-dependent genes in pDCs and classical DC subsets with and without stimulation.

overall_design: Splenocytes were harvested from C57BL/6 wild-type (WT) or 10 generation C57BL/6 backcrossed Mycl1-gfp/gfp (LmycKO) mice and DC subsets sorted to >95% purity on the FACSAriaII.

first: Wumesh

last: KC


title: Effect of Amphiregulin on global gene expression in injured skeletal muscle in the presence or absence of CD4+Foxp3+ regulatory T cells (Tregs).

summary: Global gene expression analysis of injured skeletal muscle showed that amphiregulin (Areg), a growth factor over-expressed by muscle Treg cells, enhances muscle regeneration both in the presence and in the absence of Tregs.

overall_design: Foxp3-DTR+ and Foxp3-DTR- mice were injured with cardiotoxin in TA muscle at day 0 and treated with diphtheria toxin every other day from day 0 until dissection. Amphiregulin or PBS were administered im on day 0 and ip every other day until dissection. TA muscle was flash-frozen and RNA was extracted using Trizol. RNA from whole tissue samples was amplified, labeled, and hybridized to Affymetrix Mouse Gene 1.0 ST Arrays.


title: A special population of regulatory T cells potentiates muscle regeneration


title: All trans-retinoic acid (ATRA) re-differentiate early transformed breast epithelial cells to normal.

status: Public on Dec 13 2013

city: Philadelphia

first: Sandra

middle: Viviana

last: Fernandez

state: PA

address: 233 South 10th Street

department: Medical Oncology

institute: Thomas Jefferson University

summary: Retinoids have been used as potential chemotherapeutic or chemo-preventive agents because of their differentiation, anti-proliferative, pro-apoptotic, and anti-oxidant effects. We investigated the effect of all trans- retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the human normal-like breast epithelial MCF-10F cells with high dose of estradiol and consist of five cell lines which shown a progressive neoplastic transformation: MCF-10F (normal stage), trMCF (premalignant stage), bsMCF (invasive stage) and caMCF (tumorigenic stage).  In 3D-cultures, MCF-10F cells form tubules resembling the normal mammary gland although after treatment with high doses of estradiol, trMCF cells, formed tubules and, spherical masses which are an indication of cell transformation. By ring cloning, trMCF clone 11 which only formed spherical masses in collagen was isolated. Our results showed that the early transformed trMCF clone 11 cells shown a reduction of spherical masses and increased of tubules in collagen after being treated with 10-5M (10µM) and 10-6M (1µM) ATRA; the number of tubules was higher in cells treated with 10-6M ATRA  (43%  vs. 10% tubules). The invasive bsMCF and tumorigenic caMCF cells did not shown any changes in morphology after ATRA treatment. Analysis of expression studies in early transformed cells treated with 10-6M ATRA showed that 271 probes upregulated in trMCF clone 11 cells were downregulated after ATRA treatment and, 316 probes that were downregulated were upregulated after ATRA treatment in these cells to similar levels than the normal breast epithelial cells MCF-10F.  These genes were involved in the aryl hydrocarbon receptor signaling, RAR Activation, xenobiotic metabolisms signaling, molecular mechanisms of cancer and cell morphology. Our results shown that ATRA was able to re-differentiate transformed cells at early stages of the neoplastic process suggesting that ATRA could potentially be used to inhibit the progression of premalignant lesions of the breast such as ductal carcinoma in situ (DCIS).

first: Maria

middle: F

last: Arisi

first: Rebecca

last: Staker

first: Sankar

last: Addya

first: Yong

last: Huang

middle: V


title: DNA methylation in postmortem brain samples from autism cases and controls

status: Public on Dec 12 2013

city: Baltimore

first: Christine

last: Ladd-Acosta

state: MD

address: 615 N. Wolfe Street, E6518

department: Epidemiology

institute: Johns Hopkins University

summary: We used the Illumina 450KMethylation BeadChip to measure DNA methylation at 485,512 loci across the genome for 40 postmortem brain samples. The purpose of our study was to identify differentially methylated regions (DMRs) associated with autism. Samples included 16 temporal cortex brain tissue samples (6 cases and 10 controls), 11 prefrontal cortex brain tissue samples (6 cases and 5 controls), and 13 cerebellum brain tissue samples (7 cases and 6 controls).

overall_design: We bisulfute converted DNA from the 40 brain tissue samples, processed, and hybridized them to the Illumina Infinium 450K HumanMethylation450 BeadChip as specificed by the manufacturer.

first: Andrew

middle: P

last: Feinberg


title: Transcriptomic analysis of carboxylic acid challenge in Escherichia coli: beyond membrane damage

status: Public on Dec 10 2013

city: Ames

first: Laura

last: Jarboe

state: IA

address: 3051 Sweeney Hall

department: Chemical & Biological Engineering

institute: Iowa State university

summary:
Carboxylic acids are an attractive biorenewable chemical. Enormous progress has been made in engineering microbes for production of these compounds though titers remain lower than desired.
Here we used transcriptome analysis of Escherichia coli during exogenous challenge with octanoic acid (C8) at pH 7.0. This analysis suggests that C8 challenge causes intracellular acidification and membrane damage.

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: Escherichia coli MG1655 was grown to midlog (OD550 ~0.8) with or without 10 mM octanoic acid  (pH=7.0) and the RNA was harvested and prepared for Affymetrix Microarray analysis.

first: Liam

last: Royce

first: Erin

last: Boggess

first: Yao

last: Fu

first: Julie

last: Dickerson

middle: R


title: The DNA Double-Strand Break Response Is Abnormal in Myeloblasts From Patients With Therapy-Related Acute Myeloid Leukemia

first: Matt

last: Walter

address: 4940 parkview

department: oncology

institute: washington university in st.louis school of medicine

type: Genome variation profiling by genome tiling array


title: Gene expression in psoriasis lesions and uninvolved skin

first: William

last: Swindell

department: Genetics

institute: Harvard University

summary: Psoriasis is a chronic inflammatory skin disease characterized by marked proliferation of keratinocytes leading to pronounced epidermal hyperplasia, elongation of rete ridges and hyperkeratosis. The most common form of psoriasis, chronic plaque psoriasis (Psoriasis vulgaris), involves relatively stable occurrence and progression of sharply demarcated lesions, usually on the trunk and extremities, which share a combination of trademark histological features, including tortuous and dilated dermal capillaries, loss of the epidermal granular layer, and accumulation of neutrophils beneath parakeratotic scale. In this study, whole-genome transcriptional profiling was used to characterize gene expression in 4 lesional and uninvolved skin samples obtained from patients with stable chronic plaque psoriasis.Skin mRNA expression was analysed by microarray.

overall_design: Four individuals with chronic plaque psoriasis were enrolled. 6 mm punch biopsies were obtained under local anaesthesia (lidocaine) from uninvolved skin and a target plaque.

last: Johnston

first: Johann

middle: E

last: Gudjonsson


title: The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts [methylation profiling]

city: Montreal

first: Stephan

last: Busche

state: Quebec

address: 740 Dr. Penfield Avenue

department: Human Genetics

institute: McGill University

summary:
Background   DNA methylation has long been known to play an essential role in the epigenetic regulation of gene expression and other cellular functions, and has been in some cases linked to genetic variation. While its presence near the transcription start site of a gene has been associated with reduced expression, the variation in methylation levels across individuals, its environmental or genetic causes, and its association with gene expression remain poorly understood.
Results   We report the joint analysis of sequence variants, gene expression and DNA methylation in primary fibroblast samples derived from a set of 62 unrelated individuals. Approximately 2% of the most variable CpG sites are mappable in cis to sequence variation, usually within 5kb. However, only 5% of those mappable CpG sites also have methylation levels that correlate in cis with a gene's expression level. Methylation and gene expression are often correlated but not always in the expected direction (negative for promoter CpGs, positive for gene body CpGs). Population-level correlation between methylation and expression is strongest in a subset of developmentally significant genes, including all four HOX clusters. The presence and sign of this correlation are best predicted using specific histone marks or DNase hypersensitivity rather than position of the CpG site with respect to the gene, showing that other epigenetic markers are necessary to interpret downstream effects of individual methylation variants.
Conclusion  Our results indicate strong relationships between gene expression and DNA methylation in untransformed adult human fibroblasts, with considerable involvement of chromatin features and relatively modest involvement of sequence variation.

overall_design: 62 human skin fibroblast samples obtained from Coriell and McGill Cellbank, bisulfite converted DNA was hybridized to the Illumina Infinium 450K chip.

first: James

last: Wagner

first: Bing

last: Ge

first: Tony

last: Kwan

first: Tomi

last: Pastinen

first: Mathieu

last: Blanchette


title: Development of MLL-rearranged leukemia is dependent on a transcriptional program orchestradt by C/EBPα

city: Copenhagen N

first: Ewa

last: Ohlsson

address: Ole Maaløes vej 5

department: Finsen Laboratory/BRIC/DanStem

country: Denmark

institute: University of Copenhagen

summary:
Translocations involving the MLL genes are frequently found in Acute Myeloid Leukemia (AML) and are associated with poor prognosis. The MLL fusion proteins act as aberrant transcription factor activating a transcriptional program that transforms the cells, potentially through collaboration with other transcription factors. To investigate this we searched gene expression profiles from patients with MLL-rearranged AML compared with normal hematopoietic progenitor cells for transcriptional regulators and found targets of C/EBPα to be up-regulated in the AML samples, suggesting that C/EBPα might collaborate with MLL fusion proteins in the initial transformation process. We could show that transformation by MLL fusion proteins is dependent on C/EBPα activity both in early progenitors as well as in GMPs. In contrast, C/EBPα was found to be indispensable in an already established leukemia. These results suggest that C/EBPα play an important role in the early transforming event of leukemogenesis.
We used microarray to study the early transcriptional changes induced by MLL-ENL expression and we identified a combined C/EBPα / MLL-ENL transcriptional signature.

overall_design: 3 Cebpaflox/flox;Mx1Cre and 3 Cebpaflox/flox;Mx1Cre- mice were sacrificed 14 days after pIpC injection and bone marrow cells were harvested, enriched for cKit-expression and transduced with a pMIG retroviral vector expressing the MLL-ENL fusion protein and GFP. 72 h post first transduction, GFP-positive or negative PreGM cells were sorted.

first: Bo

middle: T

last: Porse


title: Liver adapts mitochondrial function to insulin-resistant and diabetic states in mice

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum Muenchen

summary:
Objective: To study if diabetic and insulin-resistant states lead to mitochondrial dysfunction in the liver, or alternatively, if there is adaption of mitochondrial function to these states in the long-term range.

Results: High-fat diet (HFD) caused insulin resistance and severe hepatic lipid accumulation, but respiratory chain parameters were unchanged. Livers from insulin-resistant IR/IRS-1+/- mice had normal lipid contents and normal respiratory chain parameters, however showed mitochondrial uncoupling. Livers from severely hyperglycemic and hypoinsulimic, streptozotocin (STZ)-treated mice had massively depleted lipid levels, but respiratory chain abundance was unchanged. However, their mitochondria showed increased abundance and activity of the respiratory chain, which was better coupled compared to controls.

Conclusions: Insulin resistance, either induced by obesity or by genetic manipulation, does not cause mitochondrial dysfunction in the liver of mice. However, severe insulin deficiency and high blood glucose levels in mice cause an enhanced performance of the respiratory chain, probably in order to maintain the high energy requirement of the unsuppressed gluconeogenesis.

overall_design: We performed gene expression microarray analysis on liver tissue derived from mice treated with STZ or standard diet (control).

first: Andras

last: Franko

first: Martin

last: Irmler

first: Jürgen

last: vonKleist-Retzow

first: Marlen

last: Böse

first: Alexander

last: Kunze

first: Ursula

last: Hartmann

first: Carmen

last: Sanchez-Lasheras

first: Oliver

last: Stoehr

first: Michael

last: Huntgeburth

first: Susanne

last: Brodesser

last: HrabĕdeAngelis

first: Mats

last: Paulsson

first: Markus

last: Schubert

first: Rudolf

middle: J

last: Wiesner


title: Transcriptomic analysis of human skin Langerhans cell and dermal dendritic cells stimulated in vitro with TNF-alpha and TSLP

status: Public on Dec 08 2013

city: Southampton

first: Marta

middle: Ewa

last: Polak

state: Hampshire

address: Southampton General Hospital, Mailpoint 813, LE59,

department: Clinical and Experimental Sciences

country: United Kingdom

institute: University of Southampton

summary:
Langerhans cells (LCs) are antigen presenting cells residing in the epidermis. Due to the difficulties with obtaining sufficient quantities of LCs for functional studies, many controversies exist about their origin and function. To gain insights into the molecular mechanisms underpinning LC biology and to elucidate how similar they are to a classical tissue resident DCs of myeloid origin, we undertook a whole transcriptome analysis of human skin migratory CD1a+ LCs and CD11c+ DDCs, stimulated with an epidermal pro-inflammatory cytokine, TNF-α and TSLP over a time course of 24h.
RNA was extracted from 250,000 human skin migratory CD1a+ LCs and CD11c+ DDCs stimulated in culture with 25ng/ml of TNF-α or 15ng/ml TSLP for 0, 2, 8 and 24h. RNA concentration and integrity was determined with an Agilent Bioanalyser (RIN of 7.0 or above) and gene expression analysis was carried out using the Human Genome U-219 Affymetrix platform by ARK-Genomics Centre, The Roslin Institute, Edinburgh. Expression data were normalised using the Robust Multichip Average (RMA) package. 2,334 transcripts regulated by exposure of skin DCs to TNF-α were identified with Bayesian Estimation of Temporal Regulation, a cut-off threshold 0.05 , for genes showing ≥ 1.5 fold difference between the maximum gene expression level and time 0 control in log2(x) RMA normalised gene expression.  The interactive 3D diagram presenting the transcriptomic networks in human skin DCs can be viewed at: http://www.macrophages.com/LC_vs_DC. The model of IRF-GRN can be vieved at : http://www.virtuallyimmune.org/irf-grn/

overall_design:
RNA was extracted from 250,000 human skin migratory CD1a+ LCs and DDCs stimulated in culture with 25ng/ml of TNF-α 15ng/ml TSLP for 0, 2, 8 and 24h. RNA concentration and integrity was determined with an Agilent Bioanalyser (RIN of 7.0 or above) and gene expression analysis was carried out using the Human Genome U-219 Affymetrix platform by ARK-Genomics Centre, The Roslin Institute, Edinburgh. Expression data were normalised using the Robust Multichip Average (RMA) package. 2,334 transcripts regulated by exposure of skin DCs to TNF-α were identified with Bayesian Estimation of Temporal Regulation, a cut-off threshold 0.05 , for genes showing ≥ 1.5 fold difference between the maximum gene expression level and time 0 control in log2(x) RMA normalised gene expression.
*submitter cannot locate the CEL files

last: Ardern-Jones

first: Tom

last: Freeman


title: Differential Methylation Of The TRPA1 Promoter In Pain Sensitivity: DNA methylation 450k array

status: Public on Dec 09 2013

city: London

first: Jordana

last: Bell

address: St Thomas' Hospital, Westminster Bridge Rd

department: Department of Twin Research and Genetic Epidemiology

institute: King's College London

summary: Genome wide DNA methylation profiling of normal whole blood samples. The data consist of 43 samples with Illumina HumanMethylation450 BeadChip data.

overall_design: Bisulphite converted DNA from 43 of these samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip.


title: Polyamines are critical for the induction of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli

status: Public on Dec 05 2013

city: Bethesda

first: WeiPing

last: Chen

address: Bldg 8, Room 1A11, NIDDK/NIH

department: GCL

institute: NIDDK/NIH

summary: As part of our studies on the biological functions of polyamines we have used a mutant of Escherichia coli that lacks all the genes for polyamine biosynthesis for a global transcription analysis on the effect of added polyamines. The most striking early response to polyamine addition is the increased expression of the genes for the glutamate dependent acid resistance system (GDAR) that is essential for the survival of bacteria when passing through the acid environment of the stomach. Not only were the two genes for glutamate decarboxylases (gadA and gadB) and the gene for glutamate -γ-aminobutyrate antiporter (gadC) induced by polyamine addition, but also the various genes involved in the regulation of this system were induced. We confirmed the importance of polyamines for the induction of the GDAR system by direct measurement of glutamate decarboxylase activity and acid-survival. Effects of deletions of the regulatory genes in the GDAR system and on the effects of overproduction of two of these genes were also studied. Strikingly, overproductions of the alternate sigma factor rpoS and of the regulatory gene gadE resulted in very high levels of glutamate decarboxylase and almost complete protection against acid stress even in the absence of any polyamines. Thus, these data show that a major function of polyamines in E. coli is protection against acid stress by increasing the synthesis of glutamate decarboxylase, presumably by increasing the levels of the rpoS and gadE regulators.

overall_design: E. coli coltures were treated with PA and PS and its control  with three biological replications

first: Manas

middle: K

last: Chattopadhyay

first: Herbert

last: Tabor

first: Chithra

last: Keembiyehetty

first: Weiping


title: Pivotal role of HMGA1 gene signature in highly metastatic breast cancer

city: Trieste

first: Silvano

last: Piazza

address: localita' Padriciano 99

country: Italy

institute: ICGEB

summary: Analysis of MDA-MB-231 breast cancer cells depleted for High Mobility Group A1 (HMGA1) using siRNA. HMGA1 is involved in invasion and metastasis in breast cancer cells. Results identify the specific transcriptional program induced by HMGA1 in highly metastatic breast cancer cells.

overall_design: MDA-MB-231 cells were transfected with HMGA1-specific siRNA or a control siRNA. Transfections were performed by using Lipofectamin RNAiMAX (Invitrogen) according to the manufacturer's procedure. Seventy-two hours after transfection, samples were processed for total RNA extraction and hybridization on Affymetrix microarrays. Four biological replicas (A, B, C, D) were used for each of the two conditions, for a total of 8 samples.

first: Silvia

last: Pegoraro

first: Gloria

last: Ros

first: Yari

last: Ciani

first: Roberta

last: Sommaggio

first: Antonio

last: Rosato

first: Giannino

last: DelSal

first: Stefano

last: Gustincich

first: Riccardo

last: Sgarra

first: Guidalberto

last: Manfioletti


title: Aspirin Exposure Reveals Novel Genes Associated with Platelet Function and Cardiovascular Events (outpatient cardiology)

status: Public on Dec 06 2013

city: Durham

first: Deepak

last: Voora

state: NC

address: 905 S. Lasalle St, 2004 Snyderman Building, DUMC 3445

department: Institute for Genome Sciences & Policy

institute: Duke University

summary:
Background: Identifying individuals at heightened cardiovascular risk is a priority for reducing the global burden of cardiovascular disease.  Aspirin is widely used to prevent cardiovascular events, though with variable results.  Therefore, we hypothesized that aspirin exposure would reveal novel biological pathways relevant to the development of cardiovascular events.  Methods: We administered aspirin, followed by peripheral blood RNA microarray profiling, in a discovery cohort of healthy volunteers (n = 50, HV1), followed by two validation cohorts of healthy volunteers (n = 53, HV2) or outpatient cardiology (OPC, n = 25) patients, in conjunction with platelet function testing with the platelet functions score (PFS, HV1 and HV2) or the VerifyNow Asprin (VN, OPC) test.  Sets of coexpressed genes, or “Factors” were identified via Bayesian sparse factor analysis and associated with platelet function in HV1 and validated in HV2 and OPC.  Validated factors were associated with death/MI in observational (n = 191) and case:control (n = 447) patient cohorts with available RNA data collected at the time of cardiac catheterization.  Results: Factor analysis yielded 20 Factors, of which one, Factor 14, contained 60 genes and was associated with PFS in HV1 (r = -0.31, p-value = 0.03).  Factor 14 was associated with platelet function with the same strength and direction in HV2 (r = -0.34, p-value = 0.02) and OPC (one-sided p-value for aspirin resistant vs. aspirin sensitive = 0.046), thus validating the association.  Factor 14 was associated with death/MI in the two patient cohorts, odds ratio (OR) = 1.2, 95% CI [1.02-1.4], p-value = 0.01 and hazard ratio = 1.5, [1.2-1.9], p = 0.001, respectively, independent of known cardiovascular risk factors (combined OR = 1.2, CI = [1.02, 1.4], p = 0.03).  Factor 14 and the expression of the Factor 14 transcript most highly correlative of PFS, ITGA2B, improved reclassification compared to traditional risk factors (category-free net reclassification index = 31% and 37%, p ≤ 0.0002 for both).  Conclusions: By challenging humans subjects with aspirin, a medication used for cardiovascular risk reduction, we elucidated genes and pathways that may underlie platelet function and mechanisms responsible for cardiovascular death/MI.
This accession represents the OPC cohort microarray data

overall_design: 26 subjects selected for microarray analysis were divided into three groups: aspirin resistant (AR, n=8, >550 ARU), high normal (HN, n=9, ARU 500-549) and aspirin sensitive (AS, n=9, ARU<500)

first: Timothy

last: McCaffrey


title: Deletion of Cebpa from HSCs

first: Marie

last: Hasemann

address: Ole Maaløes Vej 5

department: Finsen Laboratory

institute: Rigshospitalet

summary: In this study, we use a conditional mouse model for Cebpa to investigate the significance of C/EBPα in HSCs. The frequency of HSCs is unaltered following deletion of C/EBPα, however, upon serial transplantations of either full BM or purified HSCs, the stem cells and stem cell activity is lost. This is not due to increased proliferation, but rather caused by a shift from quiescence to apoptosis with a resultant exhaustion of the stem cell pool. We identify direct C/EBPα target genes by combining genome-wide C/EBPα ChIP-seq analysis in stem and progenitor cells with gene expression data from HSC with and without C/EBPα. Furthermore, we explore the impact of C/EBPα on active and repressive histone modifications by doing functional genome-wide ChIP-seq analysis of H3K4Me3 and H3K27Me3 in stem and progenitor cells with and without C/EBPα.

overall_design: We have sorted HSCs from 3 Cebpaflox/flox and 4 Cebpaflox/flox;Mx1Cre mice 18 days after pIC injection.

first: Bo

last: Porse


title: Expression data from oxaliplatin-treated tumors from mice pre-treated or not with antibiotics cocktail

status: Public on Dec 03 2013

city: Frederick

first: Amiran

last: Dzutsev

address: 1050 Boyles Str

department: CIP

institute: NCI, NIH

summary:
The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression and treatment of cancer, but it remains unclear whether commensal bacteria affect inflammation in the sterile tumor microenvironment. Here we show that disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy. In antibiotic-treated or germ-free mice, tumor-infiltrating myeloid-derived cells responded poorly to therapy, resulting in lower cytokine production and tumor necrosis after CpG-oligonucleotide treatment, and deficient production of reactive oxygen species and cytotoxicity following chemotherapy.  Thus, optimal responses to cancer therapy require an intact commensal microbiota that mediates its effects by modulating myeloid-derived cell functions in the tumor microenvironment. These findings underscore the importance of the microbiota in the outcome of disease treatment.
Oxaliplatin treatment induces expression of pro-inflammatory genes, which are inhibited by antibiotic pretreatment.

overall_design: Our goal was to ascertain the effect of antibiotic on the tumor gene expression profile prior to treatment and early on after the treatment with chemotherapy (oxaliplatin). The time points were selected t

first: Giorgio

last: Trinchieri


title: Expression data after BCLAF1-L knockdown in human RKO cells

city: Tianjin

first: Xuexia

last: Zhou

address: 154 Anshan Road

department: Tianjin Neurological Institute

country: China

institute: Tianjin Medical University General Hospital

summary:
Bcl-2-accociated transcription factor 1(BCLAF1) has been reported to be involved in diverse biological processes. Alternative splicing leads to mutiple transcript virants in human cells and we are interested in functions of its full length isoform(BCLAF1-L) in human colon cancer cells, thus to understanding its role in colon cancer progression.
We used microarray to detail the global programme of gene expression after BCLAF1-L knockdown(sh-BCLAF1-L#1) in RKO cells and identified distinct classes of up-regulated or down-regulated genes impaired by its inhibition, when comparing with the control group(sh-Luci).

overall_design: RKO cells were infected with retroviruses either expressing control (sh-Luci) or BCLAF1-L knockdown (sh-BCLAF1-L#1). Medium was replaced 24h after infection, and infected cells were selected by the addition of puromycin (2ug/ml) for 72-96h. Then cells were havested for RNA extraction and hybridization on Affymetrix microarrays.

first: Xuebing

last: Li

first: Yuanming

last: Cheng

first: Zhiqin

last: Xie

first: Guohao

last: Wu

first: Jing

last: Fang

first: Ying

last: Feng


title: Genome wide DNA methylation changes with age in disease free human skeletal muscle

city: Novato

first: Simon

last: Melov

address: 8001 Redwood Blvd

institute: Buck Institute for Research on Aging

summary:
A decline in skeletal muscle mass and function with aging is well recognized, but remains poorly characterized at the molecular level. Here we report for the first time a genome-wide study of DNA methylation dynamics in skeletal muscle of healthy male individuals during normal human aging. We predominantly observed hypermethylation throughout the genome within the aged group as compared to the young subjects. Differentially methylated CpG (dmCpG) nucleotides tend to arise intragenically, and are underrepresented in promoters and are overrepresented in the middle and 3’ end of genes. The intragenic methylation changes are over represented in genes which guide the formation of the junction of the motor neuron and myofibers.
We report a low level of correlation between previous gene expression studies of aged muscle with our current analysis of DNA methylation status. For those genes that had both changes in methylation and gene expression with age, we observed a reverse correlation, with the exception of intragenic hypermethylated genes, that were correlated with increased gene expression. We argue that a minimal number of dmCpG sites or select sites are required to be altered in order to correlate with gene expression changes. Finally, we identified 500 dmCpG biomarkers that perform well in a prediction of human biological age within our cohorts. Our findings highlight epigenetic links between aging post-mitotic skeletal muscle and DNA methylation.

overall_design: 48 experimental samples (24 young and 24 older individuals) were used overall. There were 4 replicates per group.

first: Artem

last: Zykovich

first: Alan

last: Hubbard

first: James

last: Flynn

first: Mark

last: Tarnopolsky

first: Mario

last: Fraga

first: Chad

last: Kerksick

first: Dan

last: Ogborn

first: Lauren

last: MacNeil

first: Sean

middle: D

last: Mooney


title: Acute venous hypertension induces local release of inflammatory cytokines and endothelial activation in humans

status: Public on Dec 04 2013

city: New York

first: Ryan

last: Demmer

institute: Columbia University

summary: Background: Venous hypertension is often present in advanced and in acute decompensated heart failure (HF). However, it is unclear whether high intravenous pressure can cause alterations in homeostasis by promoting inflammation and endothelial cell (EC) activation. We used an experimental model of acute, local venous hypertension to study the changes in circulating inflammatory mediators and EC phenotype that occur in response to biomechanical stress. Methods and Results: Twenty-four healthy subjects (14 men, age 35±2 years) were studied. Venous arm pressure was increased to ~30 mmHg above baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 minutes of venous hypertension, using angiocatheters and endovascular wires. Magnetic beads coated with EC specific antibodies were used for EC separation; amplified mRNA was analyzed by Affymetrix HG-U133 2.0 Microarray. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. 5,332 probe sets were differentially expressed in venous ECs before vs. after testing. Among the 143 probe sets that exhibited a significant absolute fold change >2, we identified several inflammatory mediators including ET-1, VCAM-1, and CXCL2. Conclusions: Acute experimental venous hypertension is sufficient to cause local increase in circulating inflammatory mediators and to activate venous ECs in healthy human subjects. Additional work is needed to determine the effect of venous hypertension in patients with established HF.

overall_design: 24 samples were analyzed from 12 patients. Each patient contributed 2 samples (1 prior to intervention and 1 after intervention). The pre-intervention sample serves as the control.

first: Paolo

last: Colombo

first: Duygu

last: Onat

first: Ante

last: Harxhi

first: Yacki

last: Hayashi

first: Sanja

last: Jelic

first: Thierry

middle: H

last: LeJemtel

first: Loredana

last: Bucciarelli

first: Moritz

last: Kebschull

first: Panos

middle: N

last: Papapanou

first: Nir

last: Uriel

first: Ann

last: Schmidt

first: Hani

last: Sabbah

first: Ulrich

last: Jorde


title: Expression data from mouse intestine: BALB/c MTHFR+/+ on control diet vs BALB/c MTHFR+/- on folate deficient diet

first: Daniel

last: Leclerc

address: 4060 Ste-Catherine West

department: Medical Genetics, Room 242

institute: Montreal Children's Hospital

summary:
Previous studies in our laboratory have shown that low folate diet (control diet with 2mg folate/kg, low folate diet with 0.3mg folate/kg) can induce intestinal tumors in BALB/c mice.
We used microarrays to compare  MTHFR+/+ BALB/c mice fed control diet and MTHFR+/- BALB/c mice fed low folate diet.

overall_design: After weaning, 4 BALB/c Mthfr +/+ mice were fed with a control diet (CD, 2mg folate/kg)  and 4 BALB/c Mthfr +/- mice were fed a low folate diet (FD, 0.3mg folate/kg) for 1 year. Both diets contain succinylsulfanthiozole (1%) to prevent folate synthesis by intestine microbial biota.

first: YuanHang

last: Cao


title: Expression Data from Mouse Mammary Gland Adipose Stroma

city: Worcester

first: Jessica

last: McCready

address: 500 Salisbury St

institute: Assumption College

summary:
Adipose stroma in the mouse mammary gland undergoes remodeling throughout the 5 stages of development.  These include nulliparous (virgin;never been pregnant), pregnant, lactating, involuting and regressed.
We used a microarry to determine the changes in gene expression during gland development.

overall_design: Mouse mammary glands were selected at three developmental stages for RNA extraction and hybridization on Affymetrix microarrays.

first: Charlotte

last: Kuperwasser


title: Differential gene expression profiles between SUM149 cells transfected with control siRNA and SUM149 cells transfected with siRNA targeting tarzarotene-induced gene 1 (TIG1)

city: Houston

first: Naoto

last: Ueno

state: TX

address: 1515 Holcombe Blvd.

department: Breast Medical Oncology

institute: UT MD Anderson Cancer Center

summary: We identified tazarotene-induced gene 1 (TIG1) as a potential tumorigenic gene in IBC. To investigate the underlying mechanism by which TIG1 promotes tumor growth and invasiveness of IBC cells, we first sought to identify TIG1 functional partners by using DNA microarray analysis to compare gene expression profiles between SUM149 cells transfected with control siRNA and SUM149 cells transfected with siRNA targeting TIG1. We identified receptor tyrosine kinase Axl as a functional partner of TIG1.

overall_design: SUM149 cells transiently transfected with control siRNA or siRNA targeting TIG1 were used. Total RNA was extracted and purified using RNeasy mini kit (Qiagen, Inc.) according to the manufacturer’s instructions. The integrity of the obtained RNA was assessed using an Agilent 2100 BioAnalyzer (Agilent Technologies). The Affymetrix HGU133 plus platform was used for hybridization, staining, and imaging of the arrays by following the manufacturer’s instructions. Gene expression analysis was performed in triplicate.

first: Xiaoping

last: Wang


title: DNA methylation profiles of freshly isolated CD34+ cells and upon expansion on either tissue culture plastic (TCP) or mesenchymal stromal cells (MSCs)

city: Aachen

first: Wolfgang

last: Wagner

address: Pauwelsstrasse 20

department: Helmholtz Institute for Biomedical Engineering

institute: RWTH Aachen University

summary: Hematopoietic stem and progenitor cells (HPCs) can be maintained in vitro, but the vast majority of their progeny loses “stemness” during culture. In this study, we have analyzed DNA methylation (DNAm) profiles of freshly isolated CD34+ cells and upon expansion on either tissue culture plastic (TCP) or mesenchymal stromal cells (MSCs). DNAm profiles of expanded CD34+ versus CD34- subsets reflected hematopoietic differentiation, whereas culture on TCP or MSCs had little impact. Notably, all cultured HPCs - even those which remained CD34 positive - acquired significant DNA-hypermethylation, particularly in up-stream promoter regions, shore-regions of CpG islands, and binding sides for PU.1 and RUNX1. Our results point to a coordinated epigenetic process which needs to be controlled to enhance self-renewal of HPCs in vitro.

overall_design: 12 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: Carola

middle: I

last: Weidner

first: Thomas

last: Walenda

first: Qiong

last: Lin

first: Monika

last: Wölfler

first: Bernd

last: Denecke

first: Martin

last: Zenke


title: In vitro Expansion of Hematopoietic Stem and Progenitor Cells Induces Tightly Regulated DNA-Hypermethylation

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

overall_design: Refer to individual Series


title: Expression data from fibroblast growth factor receptor 4 (FGFR4) knock down ovarian cancer cell lines

first: Tsz-Lun

last: Yeung

address: 1515 Holcombe Blvd. Unit 1362

department: Gynecologic Oncology and Reproductive Medicine

institute: University of Texas MD Anderson Cancer Center

summary: Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Currently patients are treated by surgical cytoreductive surgery with the aim of reducing tumor burden to microscopic disease followed by adjuvant combined treatment with a platinum and taxane containing chemotherapy, which affords 80% of patients an initial complete response. However, Abdominal and pelvic recurrence rates are high and response to further chemotherapy is limited.  Attempts at introducing biologic therapeutic agents to improve outcome in this disease are ongoing, while prognostic or predictive biomarkers that can stratify patients for treatment are still lacking.    Using a 60-mer 22K oligonucleotide-based array comparative genome hybridization (CGH) platform combined with DNA isolated from microdissected tumor tissue samples, Birrer et. al. reported that the amplification of 5q31-35.3 in ovarian cancer cells is a negative prognostic indicator for patients with advanced stage high-grade serous ovarian cancer (HGSC).  Further studies showed that fibroblast growth factor 1 (FGF1) located in the amplicon, may be one of the driving genes for ovarian cancer progression (Birrer et. al., 2007).  Besides FGF1, located on the same amplicon is one of its receptors fibroblast growth factor receptor 4 (FGFR4), suggesting that it may also be amplified and may be another driving gene involved in ovarian cancer pathogenesis.In this study, we used microarrays to explore and compare gene expression profiles between FGFR4 knock down ovarian cancer cell lines and their corresponding parental cell lines.

overall_design: Two high grade serous ovarian cancer cell lines: SKOV3 and OVCA432 were selected for this study. For each of the cell lines, two different siRNA sequences which both target human FGFR4 were used. While a non-target scramble siRNA sequence was used as control. Ovarian cancer cells were transfected with siRNA using lipofectamine (Invitrogen). RNA extraction was performed 72 hours post-transfection, followed by hybridization on Affymetrix microarrays.

first: Tarrik

middle: M

last: Zaid

first: Sze

last: Leung

first: Samuel

last: Mok


title: Gene expression profiling associated with the progression to poorly differentiated thyroid carcinomas

city: Lisboa

first: Branca

middle: Maria

last: Cavaco

address: Rua Prof. Lima Basto

department: Unidade de Investigação de Patobiologia Molecular (UIPM)

country: Portugal

institute: Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG)

summary:
Poorly differentiated thyroid carcinomas (PDTC) represent a heterogeneous, aggressive entity, presenting features that suggest a progression from well-differentiated carcinomas.
To elucidate the mechanisms underlying such progression and identify novel therapeutical targets, we assessed the genome-wide expression in normal thyroid tissues, well-differentiated thyroid carcinomas and PDTC.

overall_design:
RNA were extracted from 2 normal thyroid tissues taken from the opposite lobe of thyroid tumors, and 24 thyroid carcinomas: 5 PDTC, 7 classic papillary thyroid carcinomas (cPTC), 8 follicular variants of PTC (fvPTC) and 4 follicular thyroid carcinomas  (FTC). All samples were obtained at time of surgery and immediately frozen in liquid nitrogen. We also hybridized a commercial pool of human thyroid total RNA (BD Bioscience).
PTC were screened for BRAF mutations and rearrangements of RET/PTC and, in addition, follicular variants were also analyzed for RAS mutations and PAX8-PPARG rearrangements. FTC were screened for RAS and PAX8-PPARG rearrangements. PDTC were analyzed for BRAF, RAS and PAX8-PPARG genes.

first: Jaime

last: Pita

first: Ana

last: Banito

first: Valeriano

last: Leite


title: Expression profiling on HPSE deleted SGC-7901 gastric cancer cells

status: Public on Dec 02 2013

city: Beijing

first: Yan

last: Zhang

state: Not Applicable

address: Dongdajie street

institute: Beijing institute of Biotechnology

summary: HPSE plays important roles in gastric cancer cell proliferation, apoptosis and metastasis.The aim of this study is to explore molecular mechanism underling roles of HPSE in gastric cancer cell proliferation, survival, migration and metastasis.

overall_design: SGC-7901 gastric cancer cells were transfected with HPSE siRNA (10nM) or scramble control siRNA, RNA were extracted 24hours after transfectioin and hybridized to Affymetrix microarrays. 3 biological repeats were used for each condition.

first: Aizhen

last: Cai

first: Shaoquan

last: Chen

first: Canrong

last: Lu

first: Yuan

last: luo

first: Lezhi

first: Zhihu

last: Zhao

first: Lin


title: Gene Expression data from human radioresistant and radiosensitive Nasopharyngeal Carcinoma Cells

city: Changsha

first: Jia-Quan

last: QU

state: Hunan

address: Xiangya street No.87

department: Xiangya Hospital

institute: Central South University

summary: Most of the NPC patients suffer from local recurrences and distant metastases within 1.5 years after radiotherapy due to radioresistance. Distinct patterns of gene expression and signatures were found in NPC, and have been used to associate them with cell proliferation, apoptosis, invasion and metastasis, but few gene expression profiling studies have been focused on the tumor radioresistance.We used gene expression microarray analyses to identify the difference of mRNA in radioresistant NPC CNE2-IR cells and radiosensitive CNE2 cells.

overall_design: Radioresistant subclone of nasopharyngeal carcinoma CNE2-IR cell line was cultured and produced according to the experienment schedule to undergo five rounds of sublethal dose of irradiation (11 Gy), and the parent cell line CNE2 cell line sensitive to radiotherapy as the control

first: Zhiqiang

last: Xiao

first: Xinhui

last: Li

first: Jiaquan

last: Qu


title: Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation [array]

city: Cold Spring Harbor

first: Christopher

last: Vakoc

address: 1 Bungtown Rd

institute: Cold Spring Harbor Lab

summary: Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cancer types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 megabases downstream of Myc that are occupied by SWI/SNF, as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in 3% of acute myeloid leukemia. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs

overall_design: In order to understanding the transcription regulation network downstream of Brg1 in murine AML, we performed microarray in murine MLL-AF9/NrasG12D cell line under the condition that Brg1 was suppressed by three independent shRNAs for 96h.

first: Junwei

last: Shi

last: Johns


title: Transcriptional responses of mantle cell lymphoma (MCL) lines to IKKB inhibition

status: Public on Dec 01 2013

city: Cambridge

first: Joshua

last: Korn

address: 250 Mass Ave

institute: Novartis

summary:
MCL cell lines were treated with DMSO or 5uM AFN700 for 20hrs
This experiment is designed to see if NFKB-target genes are downregulated by inhibition of IKKB in MCL cell lines that are insensitive to ibrutinib (BTK inhibitor) or sotrastaurin (PKC inhibitor)

overall_design: MCL cells were seeded in 6well dishes and treated for 20hrs with DMSO or 5uM AFN700

first: Rami

last: Rahal


title: Expression data from human radioresistant and radiosensitive Nasopharyngeal Carcinoma Cells

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


title: DNA Methylation Changes in Allergic Patients Correlate with Symptom Severity

city: Linkoping

first: Colm

middle: Eamonn

last: Nestor

address: KEF, Hälsuniversitetet

country: Sweden

institute: Linkoping University

type:
Expression profiling by array
Methylation profiling by array


title: Identification of candidate FOXA2-regulated genes in the adult mouse uterus

city: Columbia

first: Thomas

last: Spencer

address: 920 East Campus Drive

department: Animal Sciences

institute: University of Missouri

summary: To identify candidate genes regulated by forkhead  transcription factor box A2 (FOXA2) in the uterus,  control and Foxa2-deleted uteri were collected at day of pseudopregnancy (DOPP) 3.5 (DOPP  0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the Foxa2-deleted as compared to control uteri that are candidiate FOXA2-regulated genes in the uterus.

overall_design: Whole uteri (control wild type  n=4;  Foxa2-deleted  n=4) were analyzed for differences in their transcriptome using a mouse microarray.

first: Justyna

last: Filant

first: John

last: Lydon


title: Bone marrow-derived multipotent mesenchymal stromal cells promote tongue cancer invasion by inducing collagen production

city: Oulu

first: Jussi

last: Vuoristo

address: Aapistie 5

department: Biocenter Oulu

country: Finland

institute: University of Oulu

summary: Tumor microenvironment (TME) is an active player in malignant growth and spread. Changes in the composition and structure of TME and extracellular matrix can result in either suppression or facilitation of malignant tumor growth. Carcinoma‐associated fibroblasts, bone marrow-derived multipotent mesenchymal stromal cells (BMMSCs), tumor associated macrophages and other inflammatory cells all affect the composition of TME, proliferation and survival of cancer cells, angiogenesis, invasion and metastasis. The objective of this work was to investigate the effect of the interaction between bone marrow-derived BMMSCs and human oral tongue squamous cell carcinoma (OTSCC) cells in the processes of invasion and gene expression. Co-cultures of OTSCC cancer cells and BMMSCs in 3D organotypic invasion assay were used in addition to cell culture, immunological, microarray, and RNA interference techniques.

overall_design: Total number of 4 samples were analyzed. 2 replicates of cultured human oral tongue squamous cell carcinoma (OTSCC) cells, and 2 replicates of OTSCC cells co-cultured with bone marrow-derived multipotent mesenchymal stromal cells

first: Sirpa

last: Salo

first: Carolina

last: Bitu

first: Kalle

last: Merkku

first: Pia

last: Nyberg

first: Meeri

last: Sutinen

first: Hannu

last: Vähänikkilä

first: Siri

last: Lehtonen

first: Daniela

last: Costea

first: Joonas

last: Kauppila

first: Petri

last: Lehenkari

first: Tuula


title: DNA Methylation Changes in Allergic Patients Correlate with Symptom Severity [methylation]

summary: Altered DNA methylation patterns in CD4+ T-cells indicate the importance of epigenetic mechanisms in inflammatory diseases. However, the identification of these alterations is complicated by the heterogeneity of most inflammatory diseases. Seasonal allergic rhinitis (SAR) is an optimal disease model for the study of DNA methylation because of its well-defined phenotype and etiology. We generated genome-wide DNA methylation (Npatients = 8, Ncontrols = 8) and gene expression (Npatients= 9, Ncontrols = 10) profiles of CD4+ T-cells from SAR patients and healthy controls using Illumina’s HumanMethylation450 and HT-12 microarrays, respectively. DNA methylation profiles clearly and robustly distinguished SAR patients from controls, during and outside the pollen season. Moreover, we found that this methylation signature correlated with symptom severity. In agreement with previously published studies, gene expression profiles of the same samples failed to separate patients and controls. Separation by methylation (Npatients = 12, Ncontrols = 12), but not by gene expression (Npatients = 21, Ncontrols = 21; GSE50223) was also observed in an in vitro model system in which purified PBMCs from patients and healthy controls were challenged with allergen. We observed changes in the proportions of memory T-cell populations between patients (Npatients = 35) and controls (Ncontrols= 9), which could explain the observed difference in DNA methylation. Our data highlight the potential of epigenomics in the stratification of immune disease and represents the first successful molecular classification of SAR using CD4+ T cells.

overall_design: Genomic DNA was isolated from CD4+ T-cells of patients with seasonal allergic rhinitis and healthy controls both during and outside the pollen season. Genomic DNA was bisulfite converted and hybridized to Illumina  HumanMethylation450 BeadChip (Illumina, San Diego, CA) and scanned using the Illumina iScan.

first: Mikael

last: Benson


title: Gene expression from epidydimal fat pad

first: Timothy

last: Fitzgibbons

address: 55 Lake Avenue North

department: Molecular Medicine

institute: University of Massachusetts Medical School

summary: Gene expression from epidydimal fat pad of wild type C57BL6/J and Apoliprotein E (EKO) mice on C57BL6/J mice

overall_design: Whole tissue of wild type and EKO mice fed with normal and high fat diet (3 and 4 biological replicates)

first: Michael

last: Czech


title: Expression data from C2C12 myotubes infected with adenovirus expressing Gli1

city: Portland

first: Teresa

last: Zimmers

state: OR

address: 3181 S.W. Sam Jackson Park Road

department: Cell, Developmental & Cancer Biology

institute: Oregon Health & Science University

summary:
We sought to determine the effects of over-expression of Gli1 on gene expression in C2C12 myotube cultures.
C2C12 myoblasts were induced to differentiate for 4 days. At that time, when >80% of nuclei were incorporated into multi-nucleated syncitial myotubes, we infected the cultures with recombinant adenovirus expressing GFP alone or GFP and a full length human Gli1. Media was changed 12 hours later. Cultures were lysed 60 hours after the initial infection.
Gli1 over-expression induces de-differentiation of myotubes and proliferation of myoblasts.

overall_design: Results provide insight into the molecular basis of SHH signaling on skeletal muscle cells.

middle: A

first: Rui

last: Zhan


title: DNA methyltransferase inhibitor zebularine inhibits human hepatic carcinoma cells proliferation and induces apoptosis.

city: Setagaya

first: Kazuhiko

last: Nakabayashi

state: Tokyo

department: Department of Maternal-Fetal Biology

country: Japan

institute: National Research Institute for Child Health and Development

summary: Hepatocellular carcinoma is one of the most common cancers in world wide. During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Zebularine [1-(β-ᴅ-ribofuranosyl)-1,2-dihydropyrimidin-2-one] acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. In this study, we explore the effect and possible mechanism of action of zebularine on hepatocellular carcinoma cell line HepG2. Here, we demonstrated that zebularine exhibited antitumor activity on HepG2 cells by inhibiting cell proliferation and inducing apoptosis. Zebularine treatment down-regulated CDK2 and phosphorylation of retinoblastoma protein (RB), and up-regulated p21WAF/CIP1 and p53. We also found that zebularine treatment up-regulated phosphorylation of p44/42 MAPK. These results suggest that p44/42 MAPK pathway play a role in zebularine induced cell cycle arrest by regulating activity of p21WAF/CIP1 and Rb. Furthermore, we found that zebularine induced apoptosis. Although proapoptotic protein Bax levels were not affected, antiapoptotic protein Bcl-2 level was down-regulated with zebularine treatment. The data in the present study suggest that the action of the double-stranded RNA-dependent protein kinase (PKR) is involved in inducing apoptosis with zebularine. These results provide a novel mechanism of zebularine-induced cell growth arrest and apoptosis in hepatocellular carcinoma.

overall_design: Three each independent batches of zebuluarine-treated and control HepG2 cells were subjected to illumina Human methylation 450K Beadchip analysis.

first: Kazuaki

last: Nakamura

first: Akito

last: Tanoue


title: Expression data from paediatric ependymoma short-term cell cultures

city: Wolverhampton

first: Katherine

last: Karakoula

address: Wulfruna Street

department: Brain Tumour Research Centre

institute: University of Wolverhampton

summary:
Promoter hypermethylation and transcriptional silencing is a common epigenetic mechanism of tumour suppressor inactivation in cancer, including malignant brain tumours.
To identify targets of epigenetic silencing mediated by CpG island methylation in paediatric ependymoma, we used a pharmacological unmasking approach through treatment with the demethylating agent 5-Aza-2’-deoxycytidine followed by global expression microarray analysis.

overall_design: Three short-term ependymoma cell cultures were used for whole genome expression analysis following treatment with the demethylating agent 5-Aza-dC (5 µmol/L) or mock-treated with DMSO (≤0.1% v/v) for 96-hrs.


title: Expression data from murine hematopoietic stem cells isolated from mice treated with control oil or estradiol

status: Public on Nov 30 2013

first: Daisuke

last: Nakada

address: One Baylor Plaza

institute: Baylor College of Medicine

summary: The division rate of hematopoietic stem cells (HSCs) are promoted by estradiol. To identify the mechanism by which estradiol regulates HSCs, we performed gene expresssion profiling of HSCs isolated from mice of both sexes treated with either control vehicle (oil) or estradiol for one week.

overall_design: 4 groups were analyzed; 1) HSCs from male mice treated with oil, 2) HSCs from male mice treated with estradiol, 3) HSCs from female mice treated with oil, and 4) HSCs from female mice treated with estradiol. All groups include 3 biological replicates isolated from 3 mice.


title: Interactive effects of arsenic and a high-fat diet on hepatic gene expression

city: Nanjing

first: Bing

last: Wu

state: Jiangsu

address: NO.163 Xianlin Road

department: School of the Environment

institute: Nanjing University

summary:
Chronic exposure to inorganic arsenic (iAs) or a high-fat diet (HFD) can produce liver injury. However, the interactive molecular biological effects and mechanism of iAs and HFD are as of yet unclear.
We used microarrays to detail the interactive effects of arsenic and a high-fat diet on hepatic gene expression.

overall_design: The C57BL/6 Mice fed low-fat diet (LFD) or HFD were exposed to 3 mg/L iAs or deionized water for 10 weeks. Then, hepatic RNA were extraction and hybridization on Affymetrix microarrays. Differentially expressed genes in LFD+As, HFD, and HFD+As groups compared to LFD group were identified, and interactive molecular biological effects and mechanism of iAs and HFD were discussed.

first: Su

last: Liu


title: Differentially expressed cellular genes in non-tumorigenic and tumorigenic HPV18 positive HeLa x fibroblast hybrid cells

status: Public on Nov 27 2013

city: Essen

first: Ludger

last: Klein-Hitpass

address: Virchowstr. 173

department: Universitaetsklinikum

institute: Institut fuer Zellbiologie

summary:
Identification of genes differentially expressed in tumorigenic compared to non-tumorigenic, HPV18 positive cells

Keywords: ordered

overall_design: We used microarrays to identify genes differentially expressed in tumorigenic HeLa x fibroblast hybrid cells (CGL3) and parental HeLa cells compared to non-tumorigenic HeLa x fibroblast hybrid cells (444). Gene expression profiles of proliferating cells under cell culture conditions were compared to identify differential gene expression patterns of upregulated and downregulated mRNA expression patterns of tumorigenic CGL3 and HeLa cells versus non-tumorigenic 444 cells..

first: Kerstin

last: Kleine-Lowinski


title: Expression signatures and cytogenetic aberrations in HPV16 E6, E7 and E6/E7-positive immortalized human epithelial cells

summary:
Identification of genetic/cytogenetic alterations and differentially expressed cellular genes in HPV16 E6, E7 and E6/E7 positive human foreskin keratinocytes

Keywords: ordered

overall_design: We used microarrays to identify differentially expressed genes in human foreskin keratinocytes (HFK) transfected with retroviral vectors harboring the human papillomavirus type 16 oncogenes E6, E7, or E6/E7 in comparison to HFK containing the empty vector control pLXSN.

first: Antje

last: Repenning


title: Gene signature predictive of response to chemotherapy in mCRC [array]

city: Seville

first: Purificacion

last: Estevez-Garcia

state: Seville

address: Manuel Siurot avenue

department: Molecular Oncology

institute: Institute of Biomedicine

summary: The objective is to generate a robust and validated predictor profile for chemotherapy response in patients with mCRC using microarray gene expression profiles of primary colorectal cancer tissue.

overall_design: To define a gene signature of response to chemotherapy in metastatic colorectal cancer, samples were obtained from 40 patients from Marques de Valdecilla Hospital who underwent primary surgery. Gene expression was detected and quantified using the Human Whole Genome U133 Plus 2.0 array (Affymetrix), containing 54675 human gene probes. Adequate RNA and microarray analysis were obtained from only 37 patients.

first: Sonia

last: Molina-Pinelo

first: Marta

last: Benavent-Viñuales

first: Fernando

last: Rivero

first: Javier

last: Gomez

first: Maria

last: Pastor

first: Amancio

last: Carnero

first: Luis

last: Paz-Ares

first: Rocio

last: Garcia-Carbonero


title: Bone marrow gene expression profiling of the response to hemorrhage in mouse

city: Los Angeles

first: Léon

last: Kautz

state: CA

department: Medicine/Pulmonary and critical care

institute: UCLA

summary:
Search for transcripts encoding secreted proteins whose expression are highly induced after phlebotomy.
This analysis allowed the identification of erythroferrone, a new erythroid factor regulating hepcidin expression and body iron requirements

overall_design: We compared gene expression profiles 4-9-12-15 and 48 hours after phlebotomy to baseline control mice using Affymetrix GeneChip® Mouse Gene 1.0 ST Array.

first: Elizabeta

last: Nemeth

first: Tomas

last: Ganz


title: Gene expression profiles in mouse livers depleted of HDAC3 or NCOR1

status: Public on Nov 25 2013

city: Houston

first: Zheng

last: Sun

address: 1 Baylor Plaza

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

overall_design: Refer to individual Series


title: Gene signature predictive of response to chemotherapy in mCRC

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


title: Genome wide analysis of RNA species present in SMN-containing RNPs

status: Public on Nov 29 2013

city: Montpellier

first: johann

last: Soret

address: 1919, route de Mende

department: Institut de Genetique Moleculaire

institute: CNRS

summary: Several studies indicate that SMN-containing mRNP complexes could be involved in the axonal localization of a large number of mRNAs. We have used murine motor neuron-like NSC-34 cells and RNA Immuno-Precipitation experiments coupled to microarray analyses to perform a genome-wide analysis of RNA species present in mRNP complexes containing the full length SMN protein (flSMN). In situ hybridization and immuno-fluorescence experiments performed on several candidates indicate that these mRNAs colocalize with the SMN protein in neurites and axons of differentiated NSC-34 cells. Moreover, they localize in cell processes in a SMN-dependent manner. Thus, low SMN levels might result in localization deficiencies of mRNAs required for axonogenesis.

overall_design: RNA species coimmunoprecipitated with the SMN protein were used for hybridization of Affymetrix microarrays

first: Florence

last: Rage

first: Nawal

last: Boulisfane

first: Henry

last: Neel

first: Thierry

last: Gostan

first: Edouard

last: Bertrand

first: Rémy

last: Bordonné

first: Johann


title: Genes related to allergen avoidance in allergic rhinitis mouse model

status: Public on Nov 28 2013

first: wang

last: min

state: Beijing

address: No. 17, HouGouHuTong, DongCheng District

institute: Beijing Institute of Otolaryngology

summary:
Allergen exposure was thought to play a critical role in the etiology of AR. And allergen avoidance, the practice of avoiding exposure to allergens, has been generally advised as the management of AR. However, the effect is uncertain and the underlying mechanism is far from known.
We used gene expression microarrays to identify genes differentially regulated by allergen avoidance in allergic rhinitis mouse model.

overall_design: Affymetrix Mouse Gene 1.0 ST arrays were used to identify the expression profiling of nasal mucosa in three groups of mice: (1) mice sensitized and challenged with saline (control group); (2) mice sensitized and challenged with ovalbumin (OVA) and sacrificed 2 hours after the last challenge (OVA group); (3) mice sensitized and challenged with OVA and sacrificed 4 weeks after the last challenge (4w-after group).

first: Min

last: Wang

first: Jun

last: Yang

first: Luo

last: Zhang


title: Transcriptional responses of mantle cell lymphoma (MCL) lines to PKC inhibition

first: Joshua

last: Korn

state: MA

summary:
MCL lines (biological replicates) were treated with DMSO or 2.5uM Sotrastaurin for 3hrs
This experiment is designed to see if a common set of genes is affected by Sotrastaurin (STN) treatment in STN-sensitive and STN-insensitive MCL lines.

overall_design: MCL cells were seeded in 6well dishes and treated for 3hrs with DMSO or 2.5uM Sotrastaurin

first: Rami

last: Rahal


title: The miR-126/VEGFR2 axis controls the innate response to pathogen-associated nucleic acids

status: Public on Nov 24 2013

city: New York

first: Brian

last: Brown

state: NY

address: 1470 Madison Avenue

department: Genetics and Genomic Sciences

institute: Icahn School of Medicine at Mount Sinai

summary: microRNA-126 is a microRNA predominately expressed by endothelial cells and controls angiogenesis. Unexpectedly, we found that mice deficient in miR-126 have a major impairment in their innate response to pathogen-associated nucleic acids, as well as HIV, which results in more widespread cell infection. Further examination revealed that this was due to miR-126 control of plasmacytoid DC (pDC) homeostasis and function, and that miR-126 regulates expression of TLR7, TLR9, NFkB1 and other innate response genes, as well as VEGF-receptor 2 (VEGFR2). Deletion of VEGFR2 on DCs resulted in reduced interferon production, supporting a role for VEGFR2 in miR-126 regulation of pDCs. These studies identify the miR-126/VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.

overall_design: Plasmactyoid dendritic cells were FACS-sorted from spleens from wildtype and miR-126 KO mice and their RNA extracted. RNA was amplified, labeled and hybridized to Mouse Gene 1.0 ST arrays with the data generation and quality control pipeline of 19 the Immunological Genome Project (www.immgen.org). Raw data were background-corrected and normalized using the RMA algorithm.


title: Expression data from fibroblasts derived from human normal oral mucosa, oral dysplasia and oral squamous cell carcinoma

city: Sheffield

first: Johanna

last: Thurlow

address: Addison Bldg, Western Bank

institute: University of Sheffield

summary:
Identification of genes that are differentially regulated in fibroblasts derived from dysplastic oral mucosa and oral squamous cell carcinoma compared to fibroblasts derived from normal oral mucosa.
Affymetrix microarrays were used to define differential gene expression.

overall_design: Populations of fibroblasts were isolated from human normal oral mucosa, oral dysplasia and oral squamous cell carcinoma, maintained in 3D collagen I biomatrices, RNA extracted and processed for Affymetrix arrays. Fibroblasts maintained as monolayers were also included as comparators.

first: Max

last: Partridge

first: Daniela

last: Costea

first: Allison

last: Hills

first: Claudia

last: Murillo

first: Gabriella

last: Kalna


title: Ovarian and Breast Cancer Spheres Are Similar in Transcriptomic Features and Sensitive to Fenretinide

city: FuZhou

first: Haiwei

state: FuJian

address: Daoshan road 180

institute: Fujian Maternity and Child Health Hospital

summary: The identification and characterization of subpopulations of cancer stem cells (CSCs) provide new understandings and possible therapeutic implications in cancer biology. We found the ovarian cancer sphere cells possessed CSCs properties maintained self renewal, drug resistance, and tumorigenesis. Using high-throughput microarray system, we identified common GO terms and pathway signatures significantly enriched in ovarian and breast cancer stem cells.

overall_design: Ovarian and breast cancer cells were cultured in sphere formation conditions, and total RNA from those spheres and conresponding adhered cell  was hybridized on Affymetrix microarrays.

first: Ji

first: Yanzhi

last: Du


title: Mucosal biopsies from groups Normal (NOR) and patients who underwent curative large bowel resection for colorectal cancer  (M-CRC)

city: Torino

first: Raffaele

last: Calogero

state: To

address: Via Nizza 52

department: Molecular Biotechnology Center

institute: University of Torino

summary: The challenge of preventing colorectal cancer (CRC) is the early identification of individuals whose apparently normal colorectal mucosa will develop cancer, because of inherited trait or environmental exposure. We sought to use genome-wide expression profiling of endoscopic biopsies to detect a signature of propensity for cancer. We performed oligonucleotide microarray analysis of normal appearing mucosa of the following cases: healthy individuals (NOR), disease-free carriers predisposed to HNPCC (hereditary non-polyposis CRC), disease-free patients who underwent curative large bowel resection for CRC 1 to 15  years earlier and patients with CRC (MCRC) (GSE23011). As test set we run on affymetrix arrays an independent set of mucosal biopsies of MCRC and NOR samples.

overall_design: This profiling is based on the analysis of 5 patients who underwent curative large bowel resection for CRC from 1 to 15 years before (MCRC samples),  and 12 endoscopy-negative, asymptomatic individuals (NOR samples)

first: Martina

last: Olivero

first: Giovanni

last: Galatola

first: Cristiana

last: Laudi

first: Stefania

last: Crispi

last: Cantarella

first: Mario

last: Morino

first: Maria

middle: F

last: Direnzo


title: Gene expression profiling of HDAC3-depleted mouse liver rescued with wild-type exogenous HDAC3

first: Zheng

last: Sun

summary: We have shown that intravenous injection of HDAC3 floxed mice with adeno-associated virus (AAV) expressing Cre depletes hepatic HDAC3, upregulates lipogenic gene expression, and causes fatty liver. When AAV-Flag-HDAC3 wild-type (WT) is co-injected along with AAV-Cre, the exogenous HDAC3 is expressed at endogenous levels and can completely rescue fatty liver phenotype. Here we profile transcriptome of the rescued WT livers in comparison with HDAC3-depleted (KO) livers.

overall_design: 4-months old C57BL/6 male mice were co-injected with AAV-Cre or AAV-Cre plus AAV-Flag-HDAC3. Mice were fed ad libitum and harvested at 5 pm (ZT10) at 2-weeks post-injection. Liver total RNA was extracted and hybridized to Affymetrix Mouse Gene 1.0ST array.

first: Bin

last: Fang

first: Mitchell

last: Lazar


title: Transcriptional responses of mantle cell lymphoma (MCL) after NIK knockdown

city: Cambridge

first: Joshua

last: Korn

address: 250 Mass Ave

institute: Novartis

summary:
MCL lines were treated with or without 100ng/ml doxycycline for 7 days
This experiment is designed to see if shRNA-mediated knockdown of NIK downregulates NFKB signaling in MCL lines with mutations in upstream regulators of the alternative pathway (TRAF2 & TRAF3)

overall_design: MCL cells carrying inducible non-targeting control (NTC) shRNA, NIKshRNA#1 (NIKsh#1), or NIKshRNA#2 (NIKsh#2) were seeded in 6well dishes and treated for 7 days with or without 100ng/ml doxycycline.

first: Rami

last: Rahal


title: Identification of BORIS-bound transcripts in neural progenitor cells and young neurons

city: London

first: Denise

last: Sheer

address: Blizard Institute, 4 Newark Street

department: Neuroscience & Trauma

institute: Barts & The London School of Medicine & Dentistry

summary: This study compares the transcripts bound to BORIS in neural progenitor cells and cells differentiated for 6 days into young neurons

overall_design: We present expression profiles for neural progenitor cells (arrays hybridised in triplicate) and in young neurons (arrays hybridised in duplicate). Immunoprecipitated BORIS-mRNA complexes were used to assess the association of BORIS with target mRNAs in neural progenitor cells and in young neurons (both arrays hybridised in duplicate).


title: DNA methylation differences between multiple sclerosis and controls in frontal lobe white matter

first: Patrizia

last: Casaccia

address: 85 St Nicholas Terrace

department: Neuroscience

institute: ASRC-CUNY

summary: Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis–affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The transcriptional consequences of differential DNA methylation were further defined by genome-wide RNA-sequencing analysis and validated in two independent cohorts. Genes regulating oligodendrocyte survival, such as BCL2L2 and NDRG1, were hypermethylated and expressed at lower levels in multiple sclerosis–affected brains than in controls, while genes related to proteolytic processing (for example, LGMN, CTSZ) were hypomethylated and expressed at higher levels. These results were not due to differences in cellular composition between multiple sclerosis and controls. Thus, epigenomic changes in genes affecting oligodendrocyte susceptibility to damage are detected in pathology-free areas of multiple sclerosis–affected brains.

overall_design: 47 samples analyzed in total: 17 MS females, age 55.5 ± 10.3 years; 11 MS males, age 55.0 ± 9.9 years; 7 control females, 69.1 ± 9.2 years; 12 control males, 64.7 ± 8.0 years. From each individual, white matter was dissected from the frontal lobe and global DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.

first: Jimmy

middle: L

last: Huynh

first: Paras

last: Garg

first: Andrew

last: Sharp


title: IKZF1 in BCR-ABL1 driven pre-B cells

status: Public on Nov 22 2013

first: Markus

last: Müschen

address: 4650 Sunset Blvd

department: Childrens Hospital Los Angeles

institute: University of Southern California

summary: In order to investigate the function of IKZF1 in ALL, we isolated bone marrow cells from C57Bl6 mice and transformed them with BCR-ABL1. In a second transduction the BCR-ABL1 driven pre-B cells were transformed either with IKZF1-GFP or empty vector control (GFP) and subjected to gene expression analysis.

overall_design: Three days post transduction, total RNA of GFP positive sorted cells were extracted and subjected to gene expression analysis.

first: Parham

last: Ramezani-Rad


title: Gene and microRNA transcriptome analysis of Parkinson's related LRRK2 mouse models

city: Quebec

first: Sebastien

last: Hebert

state: QC

address: 2705 Boul Laurier, Centre de recherche du CHU de Quebec

department: Medecine

institute: Lavay University

summary: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of familial and sporadic Parkinson’s disease (PD).  Here, we investigated in parallel gene and microRNA transcriptome profiles of three different LRRK2 mouse models. Striatal tissue was isolated from adult LRRK2 knockout mice, as well as mice expressinghuman LRRK2 wildtype (hLRRK2-WT) or PD-associated R1441G mutation (hLRRK2-R1441G).

platform_organism:
Mus musculus
synthetic construct

overall_design:
We used microarraya to measure gene and microRNA expression levels in various LRRK2 mouse models.
LRRK2 wildtype and knockout mice were bred on a C57BL/6 background. LRRK2 non-transgenic and hLRRK2 transgenic mice were bred on a FVB/N background.

first: Veronique

last: Dorval

middle: S


title: The long non-coding RNA Paupar regulates the expression of both local and distal genes [Pax6 KD]

status: Public on Nov 21 2013

city: Oxford

first: Stephen

last: Sansom

state: Oxfordshire

address: Roosevelt Drive

department: NDORMS

institute: Kennedy Institute of Rheumatology

summary: Although some long noncoding RNAs (lncRNAs) have been shown to regulate gene expression in cis, it remains unclear whether lncRNAs can directly regulate transcription in trans by interacting with chromatin genome-wide independently of their sites of synthesis. Here, we describe the genomically local and more distal functions of Paupar, a vertebrate-conserved and central nervous system-expressed lncRNA transcribed from a locus upstream of the gene encoding the Pax6 transcription factor. Knockdown of Paupar disrupts the normal cell cycle profile of neuroblastoma cells and induces neuronal differentiation. Paupar acts in a transcript-dependent manner both locally, to regulate Pax6, as well as distally by binding and regulating genes on multiple chromosomes, in part through physical association with Pax6 protein. Paupar binding sites are enriched near promoters and can function as transcriptional regulatory elements whose activity is modulated by Paupar transcript levels. Our findings demonstrate that a lncRNA can function in trans at transcriptional regulatory elements distinct from its site of synthesis to control large-scale transcriptional programmes.

overall_design: N2A cells transfected with a non-targeting control vector were compared to N2A cells transfected with a Pax6 knockdown construct. Three biological replicates of each condition were analysed on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.

first: Keith

middle: W

last: Vance

first: Sheena

last: Lee

first: Vladislava

last: Chalei

first: Lesheng

last: Kong

first: Sarah

last: Cooper

first: Peter

last: Oliver

first: Chris

middle: P

last: Ponting


title: Adipocyte XBP1s regulates systemic insulin sensitivity by modulating adiponectin multimerization

city: Wageningen

first: Guido

last: Hooiveld

address: HELIX, Stippeneng 4

department: Div. Human Nutrition & Health

country: Netherlands

institute: Wageningen University

summary: The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. Here we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of HMW adiponectin and indeed, is adiponectin dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription likely through a direct regulation of the expression of several ER-chaperones involved in adiponectin maturation, including Grp78, Pdia6, ERp44 and DsbA-L. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia.

overall_design: Epididymal adipose tissue from wild type and XBP1-overexpressing mice was subjected to gene expression profiling.

first: Haibo

last: Sha

first: Liu

last: Yang

first: Anping

last: Wang

first: Feng

last: Liu

first: Sander

last: Kersten

first: Ling

last: Qi


title: The DNA Double-Strand Break Response Is Abnormal in Myeloblasts From Patients With Therapy-Related Acute Myeloid Leukemia [Affymetrix]

status: Public on Nov 19 2013

first: Matt

last: Walter

address: 4940 parkview

department: oncology

institute: washington university in st.louis school of medicine

summary: In order to examine if the upregulation of DNA repair genes on chromosome 8 was associated with the abnormal DSB phenotype observed in trisomy 8 (defined by array CGH or cytogenetics), we compared the mRNA levels of DNA repair genes on chromosome 8 in trisomy 8 t-AML patients versus normal t-AML gammaH2AX responders using gene expression array data.

overall_design: Bone marrow cells taken directly from patients after written informed consent were cryopreserved, RNA extracted, and microarray analysis was performed using Affymetrix U133plus2 chips.

first: Meagan

last: Jacoby

first: Rigoberto

last: de Jesus Pizarro

first: Jin

last: Shao

first: Daniel

last: Koboldt

first: Robert

last: Fulton

first: Gongfu

last: Zhao

first: Richard

last: Wilson

first: Matthew


title: Expression data from CD4+ Naïve T cells under Treg-inducing condition in the presence or absence of butyrate

status: Public on Nov 20 2013

city: Yokohama

first: Takaho

middle: A.

last: Endo

state: Kanagawa

address: 1-7-22 Suehiro, Tsurumi

department: IMS

institute: RIKEN

summary:
Commensal bacteria shapes gut immune system. Colonization bacteria increase the frequency of regulatory T cells, however, the molecular mechanisms has not yet been unknown.
To reveal the mechanism, we isolated Naïve CD4+ T cells from spleen of C57BL/6 mice and cultured the cells under Treg-inducing condition culture in the presence or absence of butyrate, a metabolite produced by commensal bacteria.

overall_design: Naïve T cells were isolated from spleen and were cultured in the presence of IL-2, TGF-beta and in the presence or absene of Butyrate. RNA was extracted at Day 2

first: Yukihiro

last: Furusawa

first: Koji

last: Hase


title: Genome wide methylation profliling of ETMR tumours.

city: Montrea

first: Simon

last: Papillon-Cavanagh

state: Quebec

address: 740 Dr Penfield

department: Human Genetics

institute: McGill University

summary: Genome wide DNA methylation profiling of normal, ETMR and PNET tumours

overall_design:
Bisulphite converted DNA from 12 ETMR, 28 PNET and 34 control samples hybridised to the Illumina 450k Human Methylation Beadchip
Please note that three of the 12 EMTR samples are tumor, cell line and xenograft sample derived from a single patient. Thus, there are 10 ETMR patients, 12 samples.

first: Claudia

last: Kleinman

first: Noha

last: Gerges

first: Patrick

last: Sin-Chan

first: Albena

last: Pramatarova

first: Dong-Anh

last: Quang

first: Véronique

last: Adoue

first: Stephan

last: Busche

first: Maxime

last: Caron

first: Haig

last: Djambazian

first: Amandine

last: Bemmo

first: Adam

last: Fontebasso

first: Tara

last: Spence

first: Jeremy

last: Schwartzentruber

first: Steffen

last: Albrecht

first: Peter

last: Hauser

first: Miklos

last: Garami

first: Almos

last: Klekner

first: Laszlo

last: Bognar

first: Jose-Luis

last: Montes

first: Alfredo

last: Staffa

first: Alexandre

last: Montpetit

first: Pierre

last: Berube

first: Magdalena

last: Zakrzewska

first: Krzysztof

last: Zakrzewski

first: Pawel

last: Liberski

first: Zhifeng

last: Dong

last: Siegel

first: Thomas

last: Duchaine

first: Christian

last: Perotti

last: Fleming

first: Damien

last: Faury

first: Marc

last: Remke

first: Marco

last: Gallo

last: Dirks

first: Michael

last: Taylor

last: Sladek

first: Tomi

last: Pastinen

first: Jennifer

last: Chan

first: Annie

last: Huang

first: Jacek

last: Majewski

first: Nada

last: Jabado


title: Transcriptional override: a regulatory network model of indirect responses to modulations in microRNA expression

city: Atlanta

first: Christopher

middle: G

last: Hill

state: GA

address: 315 Ferst Dr

department: Biology

institute: Georgia Institute of Technology

type:
Expression profiling by array
Third-party reanalysis
Non-coding RNA profiling by array

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

overall_design: Refer to individual Series


title: Expression data from Uveal Melanoma

status: Public on Nov 18 2013

city: Genoa

first: Adriana

middle: Agnese

last: Amaro

address: Largo Rosanna Benzi 10

department: Molecular Pathology

institute: IRCCS Ospedale Policlinico SAN MARTINO - IST - NATIONAL CANCER RESEARCH INSTITUTE

summary: Despite advances in surgery and radiotherapy of uveal melanoma (UM), many patients develop distant metastases that poorly respond to therapy. Improved therapies for the metastatic disease are therefore urgently needed. Expression of the epidermal growth factor receptor (EGFR), a target of kinase inhibitors and humanized antibodies in use for several cancers, had been reported. 48 human UMs were analyzed by expression profiling. Evidence for signaling in tumors was obtained through the application of a UM-specific EGF signature. The EGFR specific kinase inhibitor, Gefitinib, and the humanized monoclonal antibody, Cetuximab, were tested for their effect on EGFR signaling. Natural killer cell mediated antibody-dependent cellular cytotoxicity (ADCC) and TNF-alpha release was analyzed for Cetuximab. EGFR appears suited as a novel molecular drug target for therapy of uveal melanoma.

overall_design: Gene expression profiles of 19 unique samples from uveal melanoma patients were measured.

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