title: Gene expression changes in HEK293T cells upon overexpression of ING1b and GADD45a

status: Public on Feb 04 2013

city: Mainz

first: Emil

last: Karaulanov

address: Ackermannweg 4

country: Germany

institute: Institute of Molecular Biology

summary: ING1b and GADD45a are nuclear proteins involved in the regulation of cell growth, apoptosis and DNA repair. We found that ING1b and GADD45a physically and functionally interact in the epigenetic regulation of specific target genes. In order to characterise the functional ING1b-GADD45a interaction, we performed a gain-of-function experiment in HEK293T cells by individual and combinatorial plasmid transfections and then analysed the transcriptional response via expression microarray profiling.

overall_design: HEK293T cells were transiently transfected with expression plasmids encoding human GADD45a and/or human ING1b (full-length or without its PHD-domain) and harvested 48h post-transfection for Illumina microarray profiling. Two independently transfected replicate samples of each condition were analysed. Empty vector (control) transfections served as reference samples.

first: Andrea

last: Schäfer

first: Ulrike

last: Stapf

first: Gabi

last: Döderlein

first: Chrsitof

last: Niehrs


title: Time course analysis of colon cancer samples

status: Public on Feb 01 2013

city: Milan

first: Maurizio

last: Callari

address: Via Amadeo, 42

country: Italy

institute: Fondazione IRCCS Istituto Nazionale dei Tumori

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

overall_design: Refer to individual Series


title: Time course analysis of colon cancer samples (part 2)

summary: The study outcome was to evaluate the effect of the time on tumor samples and possibly select specific genes whose expression is time-related, that could be used as detectors of tissue degradation.

overall_design: RNA extracted from specimens of 14 patients at four time points after surgery was analyzed for gene expression on high-density oligonucleotide microarrays. A mixed-effects model implemented by considering the factor time (T0, T1, T2, T3) as fixed and the factor patient as random was used to identify probes with different expression means across the four different time points. The p-values of the model were adjusted with the Bonferroni method (p<0. 05).

first: M

middle: A

last: Pierotti

middle: G

last: Daidone


title: Time course analysis of colon cancer samples (part 1)

summary: The study outcome was to evaluate the effect of the time on normal colon mucosa samples and possibly select specific genes whose expression is time-related, that could be used as detectors of tissue degradation.

overall_design: RNA extracted from specimens of 15 patients at four time points after surgery was analyzed for gene expression on high-density oligonucleotide microarrays. A mixed-effects model implemented by considering the factor time (T0, T1, T2, T3) as fixed and the factor patient as random was used to identify probes with different expression means across the four different time points. The p-values of the model were adjusted with the Bonferroni method (p<0. 05).


title: SNP and expression data from human induced Pluripotent Stem cells derived from normal human dermal fibroblasts

status: Public on Jan 31 2013

city: Oxford

first: Sally

last: Cowley

address: South Parks Road

department: Sir William Dunn School of Pathology

country: United Kingdom

institute: University of Oxford

type:
SNP genotyping by SNP array
Expression profiling by array

first: E

middle: M

last: Hartfield

last: Yamasaki-Mann

first: H

middle: J

last: Fernandes

first: J

last: Vowles

first: W

middle: S

last: James

first: R

last: Wade-Martins


title: Gene expression data from human induced Pluripotent Stem cells

summary:
Human induced Pluripotent Stem cells (hiPSc) and their differentiated progeny have great potential for modelling disease. To realise this potential, robust protocols need to be developed for deriving authentic differentiated cell lineages and these lineages need to be rigorously characterised. We have generated hiPSc using retrovirus-mediated delivery of reprogramming factors, and have used them for characterising mid-brain dopaminergic neurons. hiPSc lines have been screened using SNP array to assess chromosomal stability, and validation of the pluripotency of the hiPSc lines is provided by Pluritest assessment of transcriptome datasets.
A mature physiological cellular model of human dopaminergic neurons.

overall_design: human iPSc lines were derived from normal human dermal fibroblasts.


title: Effect of rBTNL2.Fc co-stimulation on murine CD4+ cells

city: Seattle

first: Jeannette

last: Bigler

state: WA

address: 3200 NE 92nd Street

country: USA

institute: BJ Group, LLC

summary: Naïve T cell activation involves at least two signals from an antigen presenting cell (APC), one through the T cell receptor via interaction with APC peptide-MHC complexes and a second through interaction of CD28 with APC B7 ligands.  Following activation, T cells up-regulate a host of other membrane-bound costimulatory molecules which can either promote or inhibit further T cell maturation and proliferation.  In some cases, it is necessary to attenuate T cell activation to prevent deleterious inflammation, and inhibitory members of the B7/Butyrophilin family of ligands have evolved to balance the strong stimuli the activating B7 ligands confer.  Human genetic association and in vitro studies have implicated one such ligand, BTNL2, in controlling inflammation at mucosal surfaces.  Here we show that  recombinant mouse BTNL2 modifies B7/CD28 signaling to promote expression of Foxp3, a transcription factor necessary for murine Treg development and function.  BTNL2 blocks Akt-mediated inactivation of Foxo1, a transcription factor necessary for Foxp3 expression.  Immunophenotyping and gene profiling reveal that BTNL2-induced Treg share many properties with natural Treg, and in vivo they suppress enteritis induced by mouse  effector T cells.  These findings describe a mechanism by which environmental antigen-driven formation of Treg may be orchestrated by APC expressing specific modulators of costimulatory signals.

overall_design: CD4+CD25- cells isolated from spleen were stimulated on plates coated with anti-mouse CD3 and human IgG (negative control), anti-mouse CD3, rB7-2, and IgG (positive control), and anti-mouse CD3, rB7-2, and rBTNL2 (experimental). Culturing was performed in duplicate for each condition.

first: Ryan

last: Swanson

first: Marc

last: Gavin

first: Sabine

last: Escobar

first: Shishir

last: Dube

first: Heather

last: Arnett


title: PML regulates PPAR signaling and fatty acid oxidation in breast cancer

status: Public on Jan 29 2013

city: Boston

first: Manoj

last: Bhasin

state: MA

address: 330 Brookline Avenue  RN 380E

institute: Beth Israel Deaconess Medical Center

summary: Cancer cells exhibit an aberrant metabolism which facilitates more efficient production of biomass, and hence tumor growth and progression. The genetic cues modulating this metabolic switch remain largely undetermined, however. Here we identify a metabolic function for PML which reveals an unexpected role for this bona-fide tumor suppressor in pro-survival activity in breast cancer. We find that PML acts as both a negative regulator of PGC1A acetylation and as a potent activator of peroxisome proliferator-activated receptor (PPAR) signaling and fatty acid oxidation (FAO). We further show that as FAO PML promotes ATP production, inhibits anoikis, and allows luminal filling in 3D basement membrane breast culture models. Furthermore, analysis of breast cancer biopsies reveals that PML is over-expressed in a subset of breast cancers, and is enriched in triple-negative cases. Indeed, PML expression in breast cancer correlates strikingly with reduced time to recurrence, a gene signature of poor prognosis and activated PPAR signaling. These findings have important therapeutic implications, as PML and its key role in FAO metabolism are amenable to pharmacological suppression as a mode of cancer prevention and treatment.

overall_design: Mouse livers from Pml-WT and Pml-KO mice were harvested after 20 week diet with high fat diet (60% Cal from fat; Harlan 06414) or control diet (10% Cal from fat; Harlan 08806). Mice were fasted for 8h prior to tissue harvesting in order to avoid the effect of immediate food intake. 3 tissue extracts per genotype and condition were analyzed (out of a total of 8 mice per group).

first: Arkaitz

last: Carracedo

middle: K


title: Arabidopsis transcription factor ANAC017 is a necessary and central control point for normal transcriptome changes in response to reactive oxygen signals, such as H2O2, and specific mitochondrial retrograde stress signals

status: Public on Jan 30 2013

city: Perth

first: Estelle

last: Giraud

address: UWA 35 Stirling Highway Crawley

department: ARC CoE Plant Energy Biology

country: Australia

institute: University of Western Australia

summary:
Stresses that target mitochondrial function lead to altered transcriptional responses for 100-1000s of genes genome wide, and are signalled via retrograde communication pathways within the cell. rao2 mutants contain a mutation in the NAC family transcription factor ANAC017 and cannot induce stress responsive genes (such as the mitochondrial alternative oxidase 1a) in response to mitochondrial dysfunction. We sought to define the global gene network regulated through RAO2 function in response to mitochondrial stress (mimicked through treatment of plants with antimycin A - a specific inhibitor of complex III in the mitochondrial electron transfer chain), and non-specific stress signals such as hydrogen peroxide. We have defined global stress responses that are positively and negatively mediated by RAO2 function, and show that greater than 80% of transcripts that are differentially regulated under H2O2 stress require proper functioning of ANAC017 for a normal stress responses.
We used Affymetrix microarray to characterise global gene expression profiles for mutant plants with compromised mitochondrial retrograde signalling (rao2 mutants), to define the genome wide transcriptional network regulated through RAO1 function under mitochondrial stress and hydrogen peroxide stress.

overall_design: rao2 EMS lines, independent T-DNA knock-out lines for ANAC017 (anac017-1), ANAC017 gain of function mutants (anac017-2) and wild type seedlings were grown for 14 days, the optimal stage as defined by forward genetic screens that identifed rao2 mutants. Seedlings were grown on GamborgB5 plates and treated by spraying plants with 50 µM antimycin A (an elicitor of mitochondrial retrograde signalling) or 20mM hydrogen peroxide while mock control samples were sprayed with deionised water. Samples were collected after 3hr of treatment for global expression profiling.

first: Sophia

last: Ng


title: Changes in the transcriptome of circulating neutrophils and skeletal muscle in response to endurance exercise

city: Vienna

first: Oliver

last: Neubauer

address: Althanstraße 14

country: Austria

institute: University of Vienna

summary: Analysis of the changes in the transcriptome of circulating neutrophils and skeletal muscle from standardized resting conditions (baseline; pre-EXTRI) to 3, 48 and 96 hours after an experimental exercise trial (EXTRI; 1 hour of cycling followed by 1 hours of running) in 8 healthy, endurance-trained, male subjects. It was hypothesized that the time-course dependent transcriptomic changes would reflect the molecular and signalling mechanisms by which neutrophils regulate and counter-regulate inflammation, and by which skeletal muscle responds, regenerates, and phenotypically adapts to intense, prolonged exercise involving muscle damage. Results provide an important insight in the signalling pathways underlying the transcriptional activation and priming of circulatory neutrophils in response to physiological stress, in particular muscle-derived damage-associated molecular patterns. Furthermore, the study provides novel data on the skeletal muscle transcriptome beyond 48 hours after strenuous endurance exercise, and indicates important muscular remodelling processes at 96 hours post-EXTRI.

overall_design: Blood and muscle samples were taken under standardized conditions at baseline (pre-EXTRI), and 3, 48 and 96 hours post-EXTRI. Total mRNA was extracted from isolated neutrophils, and from skeletal muscle tissue.

first: Surendran

last: Sabapathy

first: Ross

last: Lazarus

first: Jeremy

middle: B

last: Jowett

first: Kevin

last: Asthon

first: Ben

last: Desbrow

first: Jonathan

last: Peake

first: David

last: Cameron-Smith

first: Luke

last: Haseler

first: Karl-Heinz

last: Wagner

first: Andrew

middle: C

last: Bulmer


title: Differentially expressed genes in human hippocampus and Tera-1 cell line versus HepG2, A549, NT2/D1 and NGP127 cells.

status: Public on Jan 26 2013

city: Moscow

first: Maria

middle: Vladimirovna

last: Suntsova

address: Miklukho-Maklaya, 16/10

department: Department of Genetics and Postgenomic Technologies

country: Russia

institute: M.M. Shemyakin and Yu.A. Ovchinnikov  Institute of  bioorganic chemistry of the Russian Academy of Sciences

summary: We discovered a new tissue specific enhancer originated from the human spesific endogenous retrovirus (hsERV). This enhancer displayed its activity in hippocampus and Tera-1 cell line as opposed to HepG2, A549, NT2/D1 and NGP127 cells. The aim of this study was to find transcription factors responsible for the hsERV enhancer activity. So we attempted to identify a fraction of transcription factor genes that were upregulated in enhancer-positive cells.

overall_design: Total RNA obtained from human hippocampus and Tera-1, HepG2, A549, NT2/D1 and NGP127 cell lines.

middle: V

first: Anton

last: Buzdin


status: Public on Feb 07 2013

city: Baltimore

first: Mirte

middle: Mayke

last: Streppel

state: Maryland

address: 1550 Orleans street, CRBII rm341

department: Pathology

institute: Johns Hopkins Hospital

summary: miR-223 is step-wise increasingly up-regulated in the normal esophagus - Barrett's esophagus -esophageal adenocarcinoma carcinoma sequence. In this study, we aimed to determine the function of miR-223 in esophageal adenocarcinoma carcinogenesis.

overall_design: miR-223 was transfected in OE33 cells using 10nM pre-miR hsa-miR-223 miRNA precursor (Ambion, Life Technologies, Grand Island, NY) and lipofectamin 2000 (OE33_223_1 and OE33_223_2). Mock control OE33 cells were transfected with a negative control pre-miR miRNA (OE33_NEG_1 and OE33_NEG_2). HumanHT-12 v4 Expression BeadChip arrays (Illumina, San Diego, CA) were used for microarray hybridizations to examine the global gene expression of two biological replicated experiments (four samples in total). The array targets more than 25,000 annotated genes with 47,323 unique probes derived from the National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) Release 38 and UniGene (Build 199) databases.

first: Anirban

last: Maitra


title: Cyclin-dependent protein kinase E;1 (CDKE;1) is an essential component for mitochondrial retrograde signalling in Arabidopsis thaliana

status: Public on Jan 28 2013

city: Crawley

middle: Jinq Tyan

address: 35, Stirling Hwy

institute: ARC CoE PEB, UWA

summary:
Stresses that target mitochondrial function lead to altered transcriptional responses for 100-1000s of genes genome wide, and are signalled via retrograde signalling pathways within the cell. rao1 mutants contain a mutation in a gene encoding a Cyclin-Dependant Kinase E;1 and cannot induce stress responsive genes (such as the mitochondrial alternative oxidase 1a) in response to mitochondrial dysfunction. We sought to define the global gene network regulated through RAO1 function in response to mitochondrial stress (mimicked through treatment of plants with antimycin A - a specific inhibitor of complex III in the mitochondrial electron transfer chain). We have defined global stress responses that are positively and negatively mediated by RAO1 function, as well as global stress responses to antimycin A treatment that are regulated independently of RAO1.
We used Affymetrix microarray to characterise global gene expression profiles for mutant plants with compromised mitochondrial retrograde signalling under stress (rao1 mutants), to define the genome wide transcriptional network regulated through RAO1 function.

overall_design: rao1 and wild type 14-day-old seedlings (the optimal stage as defined by forward genetic screens that identifed rao1 mutants) grown on GamborgB5 plates were treated by spraying plants with 50 µM antimycin A  (an elicitor of mitochondrial retrograde signalling) while mock control samples were sprayed with deionised water. Samples were collected after 3hr of treatment for global expression profiling.

first: Estelle

last: Giraud


title: Cultured Cyto and Syncytio-trophoblast samples exposed to varying degrees of hypoxia (expression)

status: Public on Jan 18 2013

city: Vancouver

first: Wendy

last: Robinson

state: BC

address: 950 W 28th Ave

department: Medical Genetics

country: Canada

institute: University of British Columbia

summary: The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast.

overall_design: RNA from cytotrophoblast from 2 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were run on the Illumina HT-12v4 Expression Array

first: Ryan

last: Yuen

first: Baosheng

last: Chen

first: John

middle: D

last: Blair

middle: P

first: D

last: Nelson


title: Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia

city: Memphis

first: Satya

last: Vemula

state: TN

address: 855 Monroe Avenue, Suite 415 Link Building

department: Neurology

institute: University of Tennessee Health Science Center

summary:
Gene expression studies were performed to identify pathways possibly dysregulated by mutant in the gene Gα(olf). These experiments employed RNA derived from lymphoblastoid cell lines established for 4 affected carriers and 4 non-carriers.
In comparison to endogenous control and other dystonia-associated genes, GNAL was expressed at relatively low levels in lymphoblastoid cell lines.

overall_design: Comparison of whole blood expression profiles of mutation carrying dystonia patients with normal controls

middle: R

first: Mark

last: LeDoux


title: Human s.c adipose tissue gene expression during diet-induced weight loss

status: Public on Jan 22 2013

city: Little Rock

first: Intawat

last: Nookaew

address: 4301 W Markham St

department: Department of Biomedical Informatics

institute: University of Arkansas for Medical Sciences

summary:
Obesity has considerable effects on morbidity and mortality and the prevalence of obesity has been increasing rapidly worldwide during the past two decades. Even if obesity affects the entire individual, adipose tissue play a central role in the development of obesity. Expression profiling of adipose tissue may give insights into mechanisms contributing to obesity and obesity-related disorders.
24 obese subjects (6 women and 18 men, BMI 37.6 ± 4.9) received a very low calorie diet (450 kcal/d, Cambridge diet or Modifast) for 16 weeks. On average, patients lost 27.7 kg during the diet.

overall_design: Microarray expression analysis (Affymetrix U133A) in subcutaneous adipose tissue was performed before diet and after 16 weeks of diet.

first: Anders

last: Gummesson

first: Peter

last: Jacobson

first: Margareta

last: Jernås

first: Kajsa

last: Sjöholm

first: Per-Arne

last: Svensson

first: Lars

last: Sjöström

first: Lena

last: Carlsson


title: Unexpected roles of ATP11B in platinum resistance

status: Public on Jan 23 2013

city: Houston

first: Sangbae

last: Kim

state: TX

address: 1 Baylor plaza

department: HGSC

institute: Baylor Colleage of Medicine

summary: Platinum compounds display clinical activity against a wide variety of solid tumors. However, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux-kinetics indicated that ATP11B enhances the export of cisplatin from cells. The co-localization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins such as syntaxin-6 (STX6) and vesicular associated membrane protein 4 (VAMP4) strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, silencing ATP11B expression might be a therapeutic strategy to overcome cisplatin resistance.

overall_design: We performed the transfection of control-siRNA and ATP11B-siRNA to both cisplatin-sensitive A2780-PAR and cisplatin-resistant A2780-CP20 cells respectively.

first: Myrthala

last: Moreno-Smith

first: Anil

last: Sood

first: Ju-Seog

last: Lee


title: Expression analysis of 13 squamous cell carcinomas arising in the vulva

status: Public on Jan 16 2013

city: oslo

first: Francesca

last: Micci

address: Ullernchausseen 70

department: Institute for medical informatics

country: Norway

institute: Oslo Universitetssykehus

summary: The genome of 14 vulvar SCC was analyzed by aCGH and microarray to identify common imbalances present in the tumors as well as which genes were deregulated. Overall there was a good concordance between the imbalances scored by aCGH and the level of gene expression found by microarray, i.e., the genes located in gained regions were overexpressed while those located in lost regions were found down-regulated.

overall_design:
The whole-gene expression profile of 14 SCC of the vulva was compared to 5 normal vulvar samples to identify genes that were deregulated in the tumors genome.
Vulvar hyperplasia 03-48 not further analyzed and not included in the normalized data but included in the non-normalized data

first: Sverre

last: Heim


title: SCC of the vulva

type: Genome variation profiling by genome tiling array


title: Gene expression changes in adipose tissue with diet- and/or exercise-induced weight loss

status: Public on Jan 15 2013

first: Karen

middle: Weber

last: Makar

address: 1100 Fairview Ave N Po box 19024

institute: Fred Hutchinson Cancer Research Center

summary: An ancillary study within a randomized trial of diet, exercise, or combined diet+exercise vs. control among overweight/obese postmenopausal women. Subcutaneous adipose-tissue biopsies were performed at baseline and after 6 months and changes in adipose-tissue gene expression were determined by microarray with an emphasis on pre-specified candidate pathways, as well as by unsupervised clustering. Analyses were conducted first by randomization group, and then by degree of weight change at 6-months in all women combined.

overall_design: Total RNA was obtained from subcutaneous adipose tissue biopsies at baseline and 6 months. A total of 47 women were biopsied and one replicate participant was included for a total of 96 samples.

first: Kristen

middle: L

last: Campbell

middle: E

last: Foster-Schubert

middle: W

first: Mario

last: Kratz

first: Derek

last: Hagman

first: Ellen

last: Schur

first: Nina

last: Habermann

first: Marc

last: Horton

first: Clare

last: Abbenhardt

first: Ling-Yu

last: Kuan

first: Liren

last: Xiao

first: Jerry

last: Davison

first: Martin

last: Morgan

first: Ching-Yun

last: Wang

first: Catherine

last: Duggan

first: Anne

last: McTiernan

first: Cornelia

last: Ulrich


title: Evaluation of subsequent passaging on whole genome expression

city: Tehran

first: SeyedAhmad

last: Mousavi

state: Tehran

address: Bani hashem st - Resalat hw

department: Molecular systems biology

country: Iran

institute: Royan institute

summary: Heart diseases are as most leading causes of morbidity and mortality in the world. One of the promising approaches to cure these diseases is cell therapy using endogenous cardiac precursor cells resident in heart tissues. These cells are isolated from heart biopsies, cultured and passaged to reach to the desirable cell count necessary for transplantation. The process of cell propagation and subsequent passages may cause gene expression alteration unsuitable and dangerous for cell therapy; so in our study, we analyzed whole genome expression using microarray technology to compare expressed transcripts in 4 passages 6, 9, 12 and 15.

overall_design: There were 4 different passage samples (6, 9, 12, and 15) each stage with three replicates. Replicates for passage 6 were determied as control group and the data was analyzed compaired to this passage.

first: Sadaf

last: Vahdat

first: Seyed

middle: A

first: Vahid

last: Hajhosseini

first: Mina

last: Abrari

first: Javad

last: Gharechahi

first: Nasser

last: Aghdami

first: Ghasem

last: Hosseinisalekdeh


title: Gene expression profiling of human telomerase fibroblasts stimulated with dsDNA90

city: Miami

first: Tianli

last: Xia

state: FL

address: 1550 NW 10th Ave

institute: University of Miami

summary: Gene expression analysis of dsDNA90 stimulated human telomerase fibroblasts (hTERT-BJ1) after STING siRNA treatment. Genes whose expression that are affected by cytosolic DNA in a STING dependent manner will be identified and signaling pathways regulated by STING will be elucidated.

overall_design: hTERT-BJ1 cells were transfected with non-specific or STING siRNA for 72 hours followed by dsDNA90 stimulation for 3 hours. Total RNA was extracted for array analysis.

first: Glen

last: Barber


title: Gene expression profiles in the hippocampi and prefrontal cortex of Df16(A)+/- mice at embryonic day 17, postnatal day 6, and adult stages

status: Public on Jan 17 2013

city: New York

first: Bin

last: XU

state: NY

address: 1051 Riverside Drive

institute: columbia university

summary: Df16(A)+/- mice line is a model of human 22q11 microdeletion syndrome. We conducted an unbiased evaluation of the transcriptional difference in the prefrontal cortex and hippocampus areas between mutant and wild type animals at two early developmental stages (embryonic day 17 and postnatal day 6). These mice were generated by chromosomal engineering and carry a microdeltion of ~1.3Mb in the mouse locus syntenic to the human 22q11.1 The reasoning behind this expression profiling is that consistent alterations in transcriptional programs reflect either downstream (immediate or remote) effects of the deficiency or reactive (compensatory) changes, and can thus point to affected biological processes and molecular functions. Df(16)A+/- mice line is a model of human 22q11 microdeletion syndrome and Dp(16)B mice line is a model of human 22q11 microduplication. We conducted an unbiased evaluation of the transcriptional difference in the prefrontal cortex and hippocampus areas between the mice with microdeletion, microduplication and heterogygous balanced normal copy number of the mouse syntenic locus.

overall_design: Mutant mice and their wild type littermate from two development stages (embryonic day 17 and postnatal day 6) were selected. Hipocampal and prefrontal cortex tissues were dissected, total RNA were extracted, processed and hybridized on Affymetrix microarrays. We sought to obtain temporal gene expression difference of expression profiles between mutant and wild mice. Adult male mice of microdeletion, microduplication were used and mice with heterozygous balanced copy number as reference. Hipocampal and prefrontal cortex tissues were dissected, total RNA were extracted, processed and hybridized on Affymetrix microarrays. we attempted to distinguish primary versus secondary gene targets of the 22q11.2 microdeletion by looking for genes whose expression changes in negative correlation as a result of genomic losses or gains in this locus.

last: Xu

first: P

last: Hsu

first: K

last: Stark

first: J

last: Gogos

first: M

last: Karayiorgou


title: Human induced pluripotent stem cell-technology to study the effects of human cytomegalovirus infection on neural differentiation

status: Public on Jan 04 2013

city: Pittsburgh

first: Leonardo

last: D'Aiuto

state: PA

address: 3811 O’Hara Street

institute: UPMC

summary: Congenital human cytomegalovirus (HCMV) infection is one of the leading prenatal causes of mental retardation and congenital deformities world-wide.  Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV has been limited by difficulties in sustaining primary cultures.  Neuronal cells derived from human induced pluripotent stem (iPS) cells now provide a novel opportunity to investigate HCMV pathogenesis.  We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their permissiveness to infection with HCMV strain Ad169.  Analysis of iPS cells and nearly pure populations of iPS-derived neural stem cells (NSCs), neuroprogenitor cells (NPCs) and neurons suggests that (i) iPS cells are not permissive to HCMV infection; (ii) Neural stem cells have impaired differentiation when infected by HCMV; (iii) NPCs are fully permissive for HCMV infection; the supernatant from infected neural stem cells and NPCs (but not mock infected cells) induced cytopathic effects in human fibroblasts; (iv) most iPS-derived neurons are not permissive to HCMV infection; and (v) infected neurons have impaired calcium influx in response to glutamate.  Our approach offers powerful cellular models to investigate the effect of neurotropic viral agents on human neurodevelopment.

overall_design:
Adherent monolayer culture of neural progenitor cells (NPCs) were either infected with HCMV Ad169 in triplicate, with each individual sample harvested separately to provide biological replicates for expression analysis.  Infected and mock-infected cells were harvested 24 h p.i. RNA.
NPCs were 70-80% confluence.

first: Jaime

last: Miller

first: Vishwajit

last: Nimgaonkar


title: Genome-wide mapping of FOXM1 binding reveals co-binding with oestrogen receptor alpha in breast cancer cells (expression)

status: Public on Jan 07 2013

city: Cambridge

first: Dario

last: Beraldi

address: Robinson Way

institute: Cambridge Research Institute

summary: The forkhead transcription factor FOXM1 is a key regulator of the cell cycle and is overexpressed in cancer. Increased levels of FOXM1 are associated with both poor prognosis and oestrogen receptor (ERalpha) status in primary breast cancer. In this study, we map FOXM1 binding genome wide in both ERalpha-positive (MCF-7) and -negative (MDA-MB-231) breast cancer cells. We identify a common set of FOXM1 binding events at cell cycle-regulating genes, but in addition, in MCF-7 cells we find a high level of concordance with ERalpha-binding regions. FOXM1 binding at these co-binding sites is dependent on ERalpha binding, as depletion of ER protein levels reduced FOXM1 binding. FOXM1 interacts directly with both ERalpha co-activator CARM1 and is required for H3 arginine methylation at the ERalpha complex. Inhibition of FOXM1 activity with the ligand thiostrepton resulted in decreased FOXM1 binding at cca. 1400 sites genome wide and reduced expression of genes correlated with poor prognosis in ERalpha-positive tumour samples. These data demonstrate a novel role for the forkhead protein FOXM1 as an ERalpha cofactor and provide insight into the role of FOXM1 in ERalpha-positive breast cancer.

overall_design: MCF-7 cells were treated with either thiostrepton or DMSO for 6 hr. Each treatment was carried out in replicates of 6.

first: Deborah

last: Sanders

first: Caryn

last: Ross-Innes

first: Jason

last: Carroll

first: Shankar

last: Balsubramanian


title: Expression data from meningiomas and normal meninges

status: Public on Jan 05 2013

city: Salamanca

first: MariaDolores

last: Tabernero

address: Paseo San Vicente 58-182

country: Spain

institute: Hospital Universitario de Salamanca y Centro del Cáncer

summary: Correlate the gene expression profiles with the most relevant patterns of chromosome abnormalities (cytogenetic subgroups of meningiomas) and the gene expression profiles could help to explain the differences in clinical behaviour of meningiomas.

overall_design: The impact of tumor cytogenetics on the gene expression analyzed in meningiomas. Here, we analyzed the gene expression profiles (GEP)  of 47 tumors and correlated them with the most clinical relevant cytogenetic subgroups of meningiomas, including diploid tumors, isolated -22/22q-, del(1p36) alone and complex karyotypes associated with del(1p36) and/or -14q. In addition, 4 samples containing purified RNA extracted from normal meningeal cells (BioChain Institute, Hayward, CA and US Biological, Swampscott, MA, USA) were also processed.

first: Maria

first: Alberto

last: Orfao


title: Identification of ORB1 target genes using inducible overexpression system

city: Campinas

first: Camila

last: Caldana

state: Sao Paulo

address: Rua Giuseppe Máximo Scolfaro, 10.000

country: Brazil

institute: Brazilian Bioethanol Science and Technology Laboratory

summary:
The aim was to identify  genes associated to the  down-regulation TARGET OF RAPAMYCIN (TOR) pathway in Arabidopsis. For this purpose, three independent amiR-tor lines (amiR-tor9, amiR-tor17 and amiR-tor 20) and EV lines 3 and 6 days after EST- or non-induction were used for expression profile analysis using Affymetrix microarray.
Two weeks-old transgenic seedlings were transferred to MS plate with 20µM estradiol to induce the overexpression of amiR-tor (consequently, repression of AtTOR levels) under the control of an estradiol-(EST) inducible promoter. Identically treated wild-type Col-0 and pER8 empty-vector (EV) transformed seedlings were served as controls. Seedlings were harvested after 3 and 6 (amiR-tor lines) days.

overall_design: genetic modification

first: Patrick

last: Giavalisco


title: Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis

status: Public on Jan 14 2013

city: Rochester

first: Animesh

last: Pardanani

state: MN

address: 200 1st St SW

department: Hematology

institute: Mayo Clinic

summary: 17 patients with myelofibrosis contributed paired research samples; the time points were pre-study and 12 weeks after commencing study treatment with CYT387.Gene expression analysis was investigated to study the effects of drug treatment. Additional analysis invesitigated differences in expression patterns in groups of anemia responders and non-responders following drug treatment.

overall_design: 34 samples representing 17 patients. Each patient submitted 1 pre-treatment sample and 1 post 12 weeks of treatment.

first: Rebecca

last: Laborde

first: Terra

last: L. Lasho

first: Alexey

last: Leontovich

first: Ayalew

last: Tefferi


title: Predictors of depression in breast cancer patients during and after radiotherapy: Role of chemotherapy and the inflammatory response

status: Public on Jan 01 2013

city: Atlanta

first: Gregory

last: Doho

state: GA

address: 1365B Clifton Rd NE

institute: Emory University

summary: Chemotherapy and the inflammatory response were associated with persistent depressive symptoms in breast cancer patients undergoing radiation. Treatments targeting inflammation before radiation may reduce depression post radiation therapy, especially in patients who have been treated previously with chemotherapy.

overall_design: Total RNA was isolated from the peripheral blood mononuclear cells (PBMC) obtained from the women (n=61) with Stage 0-III breast cancer treated with or without chemotherapy.

first: Mylin

last: Torres

first: Thaddeus

last: Pace

first: Tian

last: Liu

first: Jennifer

last: Felger

first: Donna

last: Mister

middle: H

first: Jordan

middle: N

last: Kohn

first: Andrea

last: Barsevick

first: Qi

last: Long

first: Andrew


title: Breast cancer and liver tissue biopsies used to develop and validate an index for liver contamination in metastatic breast cancer

city: Woburn

first: Christos

last: Hatzis

address: 400 West Cummings Park, Suite 5350

institute: Nuvera Biosciences

summary:
PURPOSE: To develop an index capable of detecting and quantifying the extent of liver RNA contamination in liver biopsies of metastatic breast cancer
METHODS: We developed a microarray-based gene expression liver index by comparing the expression levels of genes in liver tissue biopsies and in primary breast cancer biopsies.  The predictive performance of the index was then evaluated in defined mixtures of liver and breast cancer RNA.  A calibration curve was established to allow estimation of the liver RNA content in unknown metastatic breast cancer samples.

overall_design: A set of liver biopsies and primary breast cancer biopsies were used to identify genes that were expressed significantly higher in liver tissue.  These genes were used in a liver index, which was validated in a new set of liver and primary breast cancer biopsies.  A set of liver/breast cancer RNA mixtures was used to establish a calibration curve to allow quantification of liver contamination in metastatic breast cancer samples.  The prediction error of the calibration curve was assessed in a new set of liver/breast cancer RNA mixtures and applied to estimate the liver content in a set of unknown metastatic breast cancer biopsies.

first: W

middle: F

last: Symmans


title: Transcriptomic analysis of a gut epithelial cell line after the depletion of selenoprotein Glutathione peroxidase 4

city: Newcastle

first: Simon

last: Cockell

address: Framlington Place

institute: Newcastle University

summary: GPx4 is an important antioxidant gene that is derived from selenium. A ploymorphism in GPx4 has been associated with increased risk of colorectal and prostate cancer. This experiment decsribes the effect of change in GPx4 expression in human intestinal epithelial cell line (Caco-2).Depletion of GPx4 expression led to changes in mitochondrial pathways including oxidative phosphorylation and ubiquinone biosynthesis pathway and genes involved in apoptosis regulation

overall_design: Total RNA obtained from Caco-2 cells following treatment for 72hrs with GPx4 specific siRNA, or a scrambled siRNA control at 60 and 120pmol concentrations.

first: Patience

last: Cole-Ezea

first: Daniel

last: Swan

first: Daryl

last: Shanley

first: Jonh

last: Hesketh


title: Human sarcoma cell lines and untransformed cells

city: London

first: Stephen

last: Henderson

address: Paul O'Gorman Building, Huntley Street

department: Cancer Institute

institute: UCL

summary: This study was performed with an overall aim to compare gene expression prolife in human sarcoma cell lines and in primary untransformed cells.

overall_design: Individual Cell Lines were collected from ATCC, DSMZ, HPA Cultures, Clonetics, Wolfson Insitute for Biomedical Research Cell bank, UCL, London, U.K. or were a gift from other researchers.

first: Leonid

last: Nikitenko

first: Chris

last: Boshoff

first: David

last: Guiliano


title: MicroRNA-182-5p targets a network of genes involved in DNA repair

city: Herston

first: Nicole

last: Cloonan

state: Queensland

address: 300 Herston Road

institute: QIMR Berghofer Medical Research Institute

summary: MicroRNAs are non-coding regulators of gene expression, which act by repressing protein translation and/or degrading mRNA. Many have been shown to drive tumorigenesis in cancer, but functional studies to understand their mode of action are typically limited to single target genes. In this study we use synthetic biotinylated miRNA to pull down endogenous targets of miR-182. We identified over 1000 genes as potential targets of miR-182, most of which have a known function in pathways underlying tumour biology. Specifically, functional enrichment analysis identified components of both the DNA damage response pathway and cell cycle to be highly represented in this target cohort. Experimental validation confirmed that miR-182 mediated disruption of the homologous recombination (HR) pathway is a consequence of its ability to target multiple components in that pathway. Although there is a strong enrichment for the cell cycle ontology, we do not see a direct biological effect as a consequence of miR-182 over expression. We highlight targets which could be responsible for miR-182 mediated disruption of other biological processes attributed in the literature so far. Finally we show that miR-182 is highly expressed in a panel of human breast cancer samples highlighting its role as a potential oncomir in breast cancer.

overall_design: HEK293T cells were transfected with biotinylated miR-182 or a mock control. The miRNAs and target mRNA were pulled down with streptavidin and compared to the control.


title: Differential functional effects of Indomethacin along the human fetal intestine

city: Sherbrooke

first: Jean-François

last: Beaulieu

state: Québec

address: 3001, 12ème avenue nord

department: Anatomie & biologie cellulaire

institute: Université de Sherbrooke

summary: Transcriptional profiling of small and large intestinal explants cultured in the absence or in the presence of Indomethacin (1 µM).

overall_design:
Two-condition experiment, control intestinal explants vs Indomethacin intestinal explants

#4 replicates were normalized in a separate batch from the other replicates.

first: Eric

last: Tremblay

first: Emanuela

last: Ferretti

first: Babakissa

last: Corentin

first: Nancy

last: Perron

first: Ernest

last: Seidman

first: Emile

last: Levy

last: Ménard


title: A novel proteomic approach reveals GREB1 as an Estrogen Receptor co-factor

first: Suraj

last: Menon

address: Li Ka Shing Center, Robinson Way

institute: Cambridge Research Institute, Cancer Research UK

summary: Methods for identifying protein-protein interactions have mostly been limited to tagged exogenous expression approaches. We now establish a rapid, robust and comprehensive method for finding interacting proteins using endogenous proteins from limited cell numbers. We apply this approach called ‘Rapid IP-Mass Spectrometry of Endogenous proteins (RIME)’ to identify ER, FoxA1 and E2F4 interacting proteins in breast cancer cells. From small numbers of starting cells, we find a comprehensive collection of known ER, FoxA1 and E2F4 targets, plus a number of novel unexpected interactors. One of the most ER (and FoxA1) associated interactors is GREB1, an estrogen induced gene with almost no known function. We apply RIME, in parallel with ER ChIP-seq, to identify ER protein interactors and ER binding events from solid tumor xenografts, resulting in the validation of the ER-GREB1 interactions. Furthermore, we establish a method for identifying endogenous interacting proteins from solid primary breast cancer samples, whih we apply to validate ER interactions with GREB1 and additional co-factors. Mechanistically, we show that GREB1 is recruited with ER to the chromatin where it functions as an essential estrogen-mediated regulatory factor required for effective ER transcriptional activity. Our novel approach enables, for the first time, the ability for discovery and validation of protein-protein interactions in whole tissue and solid tumors, revealing significant insight into ER regulatory factors.

overall_design: Cells were transfected with siControl or siGREB1. The cells were treated with 10nM ICI 182780 for 24 hr to further deplete ER. 48 hr after transfection, the cells were treated with 100nM of Estrogen or vehicle for 6 hr and total RNA was collected from four biological replicates

first: Hisham

last: Mohammed

first: Jason

middle: S

last: Carroll


title: Gene profile of glioblastoma cells treated with y15 and temozolomide

status: Public on Jan 12 2013

city: Buffalo

first: Qiang

last: Hu

address: Elm & Carlton Streets

institute: Roswell Park Cancer Institute

summary: The gene expression profiles were identified in glioblastoma cells treated with FAK inhibitor Y15, temozolomide alone or with combination of Y15 and Temozolomide

overall_design: DBTRG and U87 were treated with FAK inhibitor Y15 at 10 microM for 24 h; U87 cells were treated with Temozolomide 100 microM for 24 h and Y15+temozolomide at the same dose as each agent alone

first: Vita

last: Golubovskaya

first: William

last: Cance

first: Song

last: Liu

first: Jeffrey

last: Conroy

first: Grace

last: Huang

first: Baotran

last: Ho


title: Genome-wide analysis of human pluripotent cells after kd/oe of SNF5

city: LA

first: jueng soo

last: You

state: CA

address: 1441 Eastlake Ave

department: Norris Comprehensive Cancer Center

institute: USC

summary: Analysis of global gene expression by SNF5 level change in human pluripotent and differentiated cells. The core subunit of BAF complex SNF5 is at the nexus of the link between chromatin remodeling and tumor suppression. We demonstrated a role for the remodeler SNF5 as a key executor in regulating pluripotency gene networks during differentiation by using loss and gain of function experiments followed by gene-expression arrays.

overall_design: Total RNA obtained from pluripotent state, differentiated state, absense of SNF5 and overexpression of SNF5

first: Jones

last: Peter


title: Genome-wide analysis of the effect of PIAS1 knockdown by siRNA on the androgen regulated gene programs

city: Kuopio

first: Sari

last: Toropainen

address: Yliopistonranta 1 E

department: School of Medicine

country: Finland

institute: University of Eastern Finland

summary: Analysis of PIAS1 co-regulation in the androgen signaling pathways in prostate cancer cell line.

overall_design: VCaP cells were exposed to control (siSCR) or PIAS1 (siPIAS1) targeted siRNA for 96h. After 16h of 100 nM testosterone (or without) treatment the total RNA was isolated, each treatment included three replicates.

first: Marjo

last: Malinen

first: Tiina

last: Jääskeläinen

first: Sanna

last: Kaikkonen

first: Miia

last: Rytinki

first: Biswajyoti

last: Sahu

first: Olli

last: Jänne

first: Merja

last: Heinäniemi

first: Jorma

middle: J

last: Palvimo


title: Genome-wide analysis of impact of B cells from the peripheral blood of chronic lymphocytic leukemia (CLL) patients versus B cells from healthy donors on CD14+ PBMCs from healthy donors

city: Ulm

first: Nupur

last: Bhattacharya

address: Albert Einstein Allee 23

department: Department of Internal Medicine III

institute: University of Ulm

summary: CD14+ cells in the PBMCs of CLL patients are converted into NLCs. CD14+ PBMCs from healthy donors when cultured with CLL cells give rise to differentiated cells called CD14CLL-cells, which are immunophenotypically similar to NLCs. CD14+ PBMCs from healthy donors when cultured with non-malignant B cells give rise to differentiated cells called CD14B-cells. Transcriptome wide analysis reveals genes involved in immune response to be significantly deregulated between CD14B-cells and CD14CLL-cells/NLCs.

overall_design: Total RNA obtained from NLCs, CD14CLL-cells and CD14B-cells and hybridised to arrays (4 samples in each group)

first: Daniel

last: Mertens

first: Stephan

last: Stilgenbauer

first: Hartmut

last: Doehner


title: ABI3 TARGET approach

city: Montpellier

first: Gabriel

last: Krouk

address: 2 Place Pierre Viala

department: Biology

country: France

institute: CNRS

summary: Deciphering gene regulatory networks (GRNs) is a key for understanding gene expression regulations in living systems. Here, we describe the investigation of the ABSCISIC ACID INSENSITIVE 3 (ABI3) plant transcription factor GRN vicinity by a technique called Network Walking. The method involves transient transformation of protoplasts and inducible nuclear re-localization of transcription factors along with transcriptomic analysis. This genome-wide approach allowed the de novo  recovery of i) direct and indirect ABI3 target genes, ii) cis-binding site preference, and iii) biological processes regulated by this canonical abscisic acid response factor. This work improves our knowledge of ABI3 action by inferring network motifs (such as Feed Forwar Loops) under its influence. The novel high-throughput-oriented technique will help accelerate GRN systems investigations in plants, as well as in other organisms.

overall_design: This work studies ABI3 direct and indirect targets by a technique named Network Walking. Root/protoplasts were treated with or without dexamethasone (DEX) and cycloheximide (CHX). 3 reps each.

first: Bastiaan

last: Bargmann

first: Gloria

middle: M

last: Coruzzi


title: North American Brain Expression Consortium: Laser capture microdissection of Cerebellar Purkinje Cells

city: Bethesda

first: J Raphael

last: Gibbs

state: MD

address: 35 Convent Drive, Bldg 35/1A1015, MSC3707

department: Computational Biology Core

institute: National Institutue on Aging, NIH

summary:
Previous studies in bulk tissue suggest that there are abundant expression quantitative trait loci (eQTLs) in human brain. This sample series is of cerebellar Purkinje cells isolated using laser capture microdissection from human cases without neurological disease but of known genotypes. These data may be helpful in confirming eQTLs in bulk tissue or in mapping other gene expression traits in an enriched neuronal population.

Authorized Access data:
Mapping of GEO sample accessions to dbGaP subject/sample IDs is available through dbGaP Authorized Access, see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000249

overall_design: The aim of this study was to examine gene expression in isolated purkinje cells from the human cerebellum. We obtained frozen brain tissue from the cerebellum. We stained sections with cresyl violet and separated Purkinje cells based on morphology and location within the cerebellum using laser capture microdissection. Expression analyses were then performed.

first: Jesse

first: Azad

last: Kumar

first: Allissa

last: Dillman

first: Bryan

last: Traynor

first: Alexandra

last: Beilina

first: Mark

last: Cookson

first: Andrew

middle: B

last: Singleton

first: Robert

last: Johnson

first: H

last: Zielke

first: Juan

last: Troncoso

first: Richard

last: O'Brien

first: Alan

last: Zonderman

first: Luigi

last: Ferrucci


title: Using Blood-Informative Transcripts in Geographical Genomics: Impact of Lifestyle on Gene Expression in Fijians

status: Public on Dec 31 2012

first: artika

middle: Praveeta

last: Nath

email: anath6@gatech.edu, natar210@gmail.com

state: Georgia

address: Boggs Building, 770 State Street Georgia Institute of Technology

institute: Georgia Institute of Technology

summary: This study explores the impact of lifestyle and environment on gene expression through whole transcriptome profiling of peripheral blood samples in Fijian population (native Melanesians and Indians) living in the rural and urban areas.

overall_design: 41 individuals (14 urban Melanesians, 10 rural Melanesians and 17 urban Indians) of both gender were sampled under informed consents. Only healthy individuals aged between 18 and 65 were sampled. RNA from each sample was hybridized to an Illumina array. No replicates were done in this study

first: Greg

last: Gibson

first: Artika

first: Dalia

last: Arafat


title: The Histone H2B Monoubiquitination Regulatory Pathway is Required for Differentiation of Multipotent Stem Cells

status: Public on Jan 03 2013

city: Goettingen

first: Frank

last: Kramer

address: Humboldtallee 32

department: Department of Medical Statistics

institute: University Medical Center Göttingen

summary: Extensive changes in post-translational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs), various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSC. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSC cells and plays a central role in controlling stem cell differentiation.

overall_design: This set contains 29 microarray samples and includes the following 5 conditions: undifferentiated hMSCs, 2 day osteoblast differentiation, 5 day osteoblast differentiation, 2 day adipocyte differentiation, and 5 day adipocyte differentiation. 3 siRNA control samples and 3 RNF40 knockdown samples for each condition (except two control siRNA samples for 2 days osteoblast differentiation).

first: Oleksandra

last: Karpiuk

first: Zeynab

last: Najafova

first: Magali

last: Hennion

first: Christina

last: Galonska

first: Annekatrin

last: König

first: Nicolas

last: Snaidero

first: Tanja

last: Vogel

first: Andrei

last: Shchebet

first: Yvonne

last: Begus-Nahrmann

first: Moustapha

last: Kassem

first: Mikael

last: Simons

first: Halyna

last: Shcherbata

first: Tim

last: Beissbarth

first: Steven

last: Johnsen


title: Gene expression profiling of normal lung tissue adjacent to lung adenocarcinoma (ADCA)

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

institute: IRCSS Istituto Nazionale Tumori

summary:
Individual variations in the transcriptional profile of normal lung tissue may reflect the lung ADCA patients’ predisposition to a specific clinical stage
Associations between clinical outcome of cancer patients and the gene expression signature in primary tumors at time of diagnosis have been reported. To test whether gene expression patterns in the normal tissue surrounding the cancerous tissue might correlate with clinical stage, we compared transcriptome of normal lung samples of adenocarcinoma (ADCA) smoker patients of clinical stage I versus stage >I, and identified 55 differentially expressed genes. Eight out of 10 genes validated by quantitative real-time PCR confirmed statistical association with clinical stage, with 6 genes downregulated in high clinical stage patients, including the TMEM100 gene showing the best statistical association. Five of these 6 genes were also downregulated in lung ADCA tissue as compared to normal tissue. Functional studies in vitro indicated that four of them (SLC14A1, SMAD6, TMEM100, and TXNIP) inhibited colony formation when over-expressed by transfection in lung cancer cell lines, suggesting their potential tumor-suppressor activity. Our findings indicated that individual variations in the transcriptional profile of normal lung tissue may reflect the lung ADCA patients’ predisposition to a specific clinical stage.

overall_design: The 120 RNA samples from normal lung were combined in 24 small pools, with 12 pools constituted by stage I patients and 12 pools by stage >I patients (5 samples per pool)

first: Tommaso

last: Dragani

first: Elisa

last: Frullanti


title: Immune correlates of early prednisolone therapy in children and adolescents with dengue

city: Ho Chi Minh

first: Nguyen

middle: Hanh

last: Tien

address: 764 Vo Van Kiet

department: Dengue group

country: Viet Nam

institute: Oxford University Clinical Research Unit

summary: Dengue is the most important arboviral infection of humans.  A host pro-inflammatory immune response is widely believed to contribute to the clinical complications that occur in some patients with dengue. Here, immune correlates of early prednisolone therapy were defined in Vietnamese dengue patients enrolled in a randomized controlled trial, comparing a three day regimen of high (2mg/kg) or low (0.5mg/kg) dose prednisolone with placebo.  Prednisolone conferred a small change in the whole blood gene expression profile, with 81 transcripts from 64 genes differentially abundant between high-dose prednisolone and placebo treated patients. A prominent theme in the prednisolone gene expression signature was the under-abundance of transcripts from genes associated with T and NK cell cytolytic effector functions. Surprisingly, prednisolone therapy was not associated with attenuation of early-convalescent T cell responses or plasma cytokine levels. Collectively, these findings are consistent with a remarkably benign influence of prednisolone on immune response parameters in dengue patients, and are in line with the trial evidence showing lack of impact on clinical laboratory endpoints and clinical phenotype.

overall_design: The gene expression microarray assay was conducted on samples from the first 123 consecutive patients (placebo, 40; 0.5mg/kg prednisolone, 42; 2.0mg/kg prednisolone, 41).

first: Bridget

last: Wills

first: Cameron

last: Simmons


title: Time course effect of the glucocorticoid mometasone furoate on the proliferation of primary human lung fibroblasts

city: St. Gallen

first: Florent

last: Baty

address: Rorschacherstrasse 95

department: Lung Center

country: Switzerland

institute: Cantonal Hospital St. Gallen

summary: The effect of mometasone furoate on the proliferation of 2 patients of human lung fibroblasts was investigated at 8 different time points

overall_design: 2 patients, 8 time points

first: Martin

last: Brutsche


title: Global expression analysis of miR-32/455/181a/181b overexpression or PI3K knockdown in KYSE30 cells

status: Public on Dec 29 2012

city: Beijing

first: Weidong

last: Han

address: #28 Fuxing Road, HaiDian District

department: School of Life Sciences

country: China

institute: Chinese PLA General Hospital

summary: Analysis of the effect of the miRNA set (miR-32/455/181a/181b) on global gene expression. The hypothesis tested was that overexpression of these miRNAs would produce changes in gene expression similar to changes caused by PI3K knockdown. Data provided insight into genes that are disrupted with either individual miRNA and siRNA or the combination of miRNAs or siRNAs.

overall_design: Total RNA was isolated from KYSE30 cells transfected with either miRNA or siRNA for global expression analysis.

first: Qian

last: Mei

first: Xiang

last: Li


title: The dependency of cpr5-altered genes on SIM and SMR1 in Arabidopsis

city: Durham

first: shui

last: wang

state: NC

address: 124 Science Dr

institute: Duke University

summary: In plants, effector-triggered immunity (ETI) is often associated with programmed cell death (PCD). Although the intracellular immune receptors involved in ETI have been studied extensively, how their activation leads to PCD and disease resistance is poorly understood. We found that the Arabidopsis nuclear envelope protein, CPR5 (constitutive expresser of PR genes 5), plays a crucial role in controlling cell fate in response to stress, as the cpr5 mutant exhibits spontaneous cell death and heightened immunity. A genetic screen revealed that the Cip/Kip CKIs (cyclin-dependent kinase inhibitors), SIM (siamese) and SMR1 (siamese-related 1), are essential for CPR5 signaling, as the sim smr1 double mutant fully suppressed the cpr5 phenotype. More significantly, PCD and ETI are compromised in sim smr1 even with the wild-type CPR5.

overall_design:
10-day-old wild type (Col-0), cpr5, sim smr1 and cpr5 sim smr1. 12 samples total. Replicates are derived from three independent biological experiments.
We used microarrays to identify differentially expressed genes. We focused on those genes that were cpr5-altered (>2-fold) and SIM/SMR1-dependent.

first: Shui

last: Wang

first: Wei

first: Xinnian

last: Dong


title: Genome-wide expression analysis of genes regulated in primary human B cell and PBMC co-cultures stimulated with anti-IgM and superantigens

status: Public on Dec 26 2012

city: South San Francisco

first: Andrew

last: Melton

address: 310 Utah Suite 100

institute: BioSeek

summary: Illumina microarray analysis of primary human B cell and peripheral blood mononuclear cell (PBMC) co-cultures stimulated with anti-IgM and superantigens for 3 days (BT) compared to the same co-cultures without stimualtion (BTNo).

overall_design: Total RNA was extracted from co-cultures after 3 days in the presence or absence of stimulation with anti-IgM and superantigens.

middle: C


title: Serum predictors of susceptibility to infection with West Nile virus

city: New Haven

first: Hailong

last: Meng

state: CT

address: 300 George Str

institute: Yale University

summary: West Nile virus (WNV) is a mosquito-borne RNA flavivirus which has caused more than 31,000 cases in the USA from 1999-2011 including 1,262 fatalities. WNV infections are typically asymptomatic, but some patients, especially the elderly and immunocompromised, may experience severe neurological disease and even death. Control of WNV infection by the immune system is multifactorial. We profiled antibody and cytokine responses from a stratified cohort of WNV subjects to define immune responses that contribute to disease severity. While antibody levels were not significantly different between asymptomatic and severely ill subjects in our cohort, subjects with severe infections had lower levels of serum IL-4. Further, we detected 158 genes that were differentially expressed by asymptomatic and severely infected cohorts and using cluster analysis correlated WNV susceptibility with IL-4 related gene expression pathways. Our results suggest an important contribution for IL4 in more severe responses to WNV.

overall_design: Differential gene expression by human PBMCs from asymptomatic and severe patients with WNV infection were generated by microarray.

first: Ruth

last: Montgomery

first: Feng

last: Qian

first: Steven

last: Kleinstein


title: Gene expression analysis in bladder cancer cells lines

city: Miami

first: Avencia

last: Sanchez-Mejias

address: 1600 NW 10th Ave

department: Surgery

institute: University of Miami

summary: We have previously characterized two groups of bladder cancer cell lines based on their dependence on Hedgehog signaling for survival. Here, we examined the global gene expression in these cells. By comparing the gene expression profile within and between these two groups of cells, we identified list of genes and pathways that potentially account for their dependence on Hedgehog signaling, and specifically a gene signature for those cells more dependent to HH signaling for proliferation.

overall_design: We analized four different bladder cancer cell lines: J82, HT1376, T24, and Vmcub1. We performed triplicates of each sample, and completed a Hierarchical Condition Clustering, a Principal Component Analysis, and we also applied statistical analysis to identify genes that are diﬀerentially expressed between the different cell lines. We also put these lists of statistically significant genes into a biological context by performing Pathway Analysis.

first: Dennis

last: Liang Fei

first: David

last: Robbins

first: Teresa

last: Zimmers


title: Senescence impairs direct conversion of human somatic cells to neurons

status: Public on Dec 28 2012

city: Chengdu

first: chongkui

last: sun

state: Sichuan

address: No.14, Sec. 3, Renmin Road South

department: State key laboratory of oral diseases

institute: Sichuan University

summary: Direct conversion from fibroblasts to neurons is a potential cell replacement therapy for neurological disorders, and a variety of combinations of transcription factors have been tried. We notice that the efficiency of conversion from aging fibroblasts was much lower than in early stage cells, which is consistent with the notion that cellular senescence impairs conversion of fibroblasts to neurons. Here, we found that the transient knockdown of the p16Ink4a/p19Arf locus was sufficient to convert human fibroblasts to neurons. Futhermore, expression of hTERT alone, another mechanism behind immortalization, also induced neuron conversion. Our results show that the acquisition of immortality is a crucial step for the conversion of human fibroblasts into induced neurons.

overall_design: Transient knockdown of p16/p19 or p53 expression or exogenous overexpression of hTERT can induce primary fibroblasts to immortality. In the following, treated cells were cultured in neuron-induction medium. We can observe the morphology change and detect the neuronal markers. Also, some of the induced neurons could generate action potentials and neurotransmitter-induced currents in optimal conditions.

first: Chongkui

last: Sun

first: Di

last: Zhou

first: Zhen

last: Zhang

first: Liming

last: He

first: Fan

first: Xiaowei

first: Ling

middle: G

last: Wu

first: Qin

last: Yang


title: Gene expression profiling of 19 bladder cancers from the University of Virginia

status: Public on Dec 24 2012

city: Charlottesville

last: Smith

state: VA

department: Urology

institute: University of Virginia

summary: Given the heterogeneity of disease evident from study of the presentation, histomorphology, disease course, and molecular lesions of bladder cancer, a cohort of 8 non-muscle invasive and 11 muscle invasive bladder cancers were profiled for gene expression using the Affymetrix HG-U133A platform.

overall_design: Under an IRB-approved protocol, snap frozen tissues for 19 cases of bladder cancer were procured and profiled for gene expression using Affymetrix HG-U133A microarrays.

first: Dan

last: Theodorescu


title: Endothelial Raf1 activation regulates arterial morphogenesis

status: Public on Dec 18 2012

city: new haven

first: yong

last: deng

state: CT Connecticut

address: 300 george st room 749

department: cardiology

institute: Yale School of Medicine

summary: Analyze effect of Raf1 S259A on gene expression in HUVEC

overall_design: Total RNA obtained from HUVEC infected with empty lentiviral vector pLVX-IRES-puro (control) or that expressing human RAF1 WT (WT) or RAF1 S259A (S259A).

first: Yong

last: Deng

first: Michael

last: Simons


title: Integration-Free Induced Pluripotent Stem Cells Model Genetic and Neural Developmental Features of Down Syndrome Etiology

status: Public on Dec 17 2012

city: St. Lucia

first: Othmar

last: Korn

address: University of Queensland

institute: Australian Institute for Bioengineering and Nanotechnology

summary:
Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of iPSCs to model DS phenotypes, as a prototypical complex human disease, we generated bona-fide DS and wild-type (WT) non-viral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency, and had remarkably similar lineage potency, differentiation kinetics, proliferation and axon extension at early time points. However, at later time points DS cultures showed a two-fold bias towards glial lineages.
Moreover, DS neural cultures were up to two times more sensitive to oxidative stress induced apoptosis, and this could be prevented by the anti-oxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy-21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Non-viral DS iPSCs can therefore recapitulate features of complex human disease in vitro, and provide a renewable and ethically unencumbered discovery platform.

overall_design: Control (WT) and Down Syndrome iPSC lines were generated via episomal reprogramming of human donor fibroblasts. Two iPSC clones conforming to iPS criteria (determined by immunocytochemistry detection of pluripotency markers) were developed from each fibroblast donor.  Two control (WT) and DS lines each were further characterized and underwent neural differentiation. Multiple biological replicates of donor fibroblast and iPSC from both control (WT) and DS lines, including 3 euploid DS samples and 3 MEL1 hESC controls (total 54 samples) were hybridized to Illumina HT-12 v4 microarray for gene expression analysis.

first: J

last: Briggs


title: Changes in mRNA Stability Associated with Cold Stress in Arabidopsis Cells

status: Public on Dec 16 2012

city: Thuwal

first: Katsuhiko

last: Mineta

address: 4700 KAUST

country: Saudi Arabia

institute: King Abdullah University of Science and Technology

summary: Control of mRNA half-life is a powerful strategy to adjust individual mRNA levels to various stress conditions, because the mRNA degradation rate controls not only the steady-state mRNA level but also the transition speed of mRNA levels. Here, we analyzed mRNA half-life changes in response to cold stress in Arabidopsis cells using genome-wide analysis, in which mRNA half-life measurements and transcriptome analysis were combined. Half-lives of average transcripts were determined to be elongated under cold conditions. Taking this general shift into account, we identified more than a thousand transcripts that were classified as relatively stabilized or relatively destabilized. The relatively stabilized class was predominantly observed in functional categories that included various regulators involved in transcriptional, post-transcriptional and post-translational processes. On the other hand, the relatively destabilized class was enriched in categories related to stress and hormonal response proteins, supporting the idea that rapid decay of mRNA is advanta- geous for swift responses to stress. In addition, pentatricopeptide repeat, cyclin-like F-box and Myb transcription factor protein families were significantly over-represented in the relatively destabilized class. The global analysis presented here demonstrates not only the importance of mRNA turn-over control in the cold stress response but also several structural characteristics that might be important in the control of mRNA stability.

overall_design: To demonstrate the importance of mRNA stability control in cold stress response, we investigated global changes in mRNA half-lives in response to cold treatment by micaroarray using Arabidopsis suspension cell cultures (T87 cells). Control cells were collected prior to transcriptional inhibitor (cordycepin) treatment (0 h), and 1 and 3 h after the start of cordycepin treatment. For cold-treated cells, 6 h samples were also used for microarray analyses. The experiments were performed with triplicate sets for each time point.

first: Yukako

last: Chiba

first: Masami

middle: Y

last: Hirai

first: Yuya

last: Suzuki

first: Shigehiro

last: Kanaya

first: Hiro

last: Takahashi

first: Hitoshi

last: Onouchi

first: Junji

last: Yamaguchi

first: Satoshi

last: Naito


title: Transcript and protein profiling identify signaling, growth arrest, apoptosis and NFκB-survival signatures following GnRH receptor activation.

status: Public on Dec 21 2012

city: Carrington Crescent

first: Andrew

last: Sims

state: Edinburgh

address: Systems Medicine Building

department: Institute of Genetics and Molecular Medicine

institute: University of Edinburgh

summary: Gonadotrophin-releasing hormone (GnRH) significantly inhibits proliferation of a proportion of cancer cell lines by activating GnRH receptor-G protein signaling. Therefore, manipulation of GnRH receptor signaling may have an under-utilized role in treating certain breast and ovarian cancers. However, the precise signaling pathways necessary for the effect and the features of cellular responses remain poorly defined. We used transcriptomic and proteomic profiling approaches to characterize the effects of GnRH receptor activation in sensitive cells (HEK293-GnRHR, SCL60) in in vitro and in vivo settings, compared to unresponsive HEK293. Analyses of gene expression demonstrated a dynamic SCL60 response to the GnRH super-agonist Triptorelin. Early and mid-phase changes (0.5-1.0 h) comprised mainly transcription factors. Later changes (8-24 h) included a GnRH target gene, CGA, and up or down-regulation of transcripts encoding signaling and cell division machinery. Pathway analysis exposed identified altered mitogen-activated protein kinase and cell cycle pathways, consistent with occurrence of G2/M arrest and apoptosis. NFκB pathway gene transcripts were differentially expressed between control and Triptorelin-treated SCL60 cultures. Reverse phase protein and phospho-proteomic array analyses profiled responses in cultured cells and SCL60 xenografts in vivo during Triptorelin anti-proliferation. Increased phosphorylated NFκB (p65) occurred in SCL60 in vitro, and p-NFκB and IκBε were higher in treated xenografts than controls after 4 days Triptorelin. NFκB inhibition enhanced the anti-proliferative effect of Triptorelin in SCL60 cultures. This study reveals details of pathways interacting with intense GnRH receptor signaling, identifies potential anti-proliferative target genes and implicates the NFκB survival pathway as a node for enhancing GnRH agonist-induced anti-proliferation.

overall_design:
55 samples: 35 SCL60 (15 Control, 20 Treated), 20 HEK293 (12 Control, 8 Treated). Samples collected after 0, 0.5, 1, 2, 8 or 24h after treatment with Triptorelin (100nM) or vehicle control (20% Propylene Glycol solution).
SCL60 cells are HEK293 cells stably transfected with a high level of functional rat GnRHR.

first: Colette

last: Meyer

first: Simon

middle: P

last: Langdon


title: Expression data from Arabidopsis seedlings upon LRIS using NAA (1-Naphthaleneacetic acid) or non-auxin-like lateral root inducer naxillin

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary: The acquisition of water and nutrients by plant roots is a fundamental aspect of agriculture and strongly depends on root architecture. Root branching and expansion of the root system is achieved through the development of lateral roots and is to a large extent controlled by the plant hormone auxin. However, the pleiotropic effects of auxin or auxin-like molecules on root systems complicate the study of lateral root development. Here we describe a small-molecule screen in Arabidopsis thaliana that identified naxillin as what is to our knowledge the first non-auxin-like molecule that promotes root branching. By using naxillin as a chemical tool, we identified a new function for root cap-specific conversion of the auxin precursor indole-3-butyric acid into the active auxin indole-3-acetic acid and uncovered the involvement of the root cap in root branching. Delivery of an auxin precursor in peripheral tissues such as the root cap might represent an important mechanism shaping root architecture. To further explore the specificity of naxillin for lateral root development, we compared the early effects of naxillin at the transcriptome level with NAA (1-Naphthaleneacetic acid) in roots of 3-day-old seedlings after 2-h and 6-h treatment.

overall_design: Arabidopsis thaliana (L). Heynh., Col-0 seeds were germinated vertically on solid medium derived from standard MS medium supplemented with 10 μM NPA (1-N-Naphthylphthalamic acid). Three days after germination, plants were transferred to 10 μM NAA (1-Naphthaleneacetic acid) or 50 μM naxillin for 2 and 6 hours. Plants were sampled before (Roots at T0, NPA) or after treatment (Roots at T1 and T2). RNA isolation was performed on 500 root sections (only root without meristems) for each sample. All sampling points were performed in three independent experiments.

first: Bert

last: De Rybel

first: Dominique

last: Audenaert


title: Genome-wide pairwise analysis of normal and spontaneously transformed adipose tissue derived human multipotent stromal cells (hMSC)

status: Public on Dec 09 2012

city: Moscow

first: Denis

middle: Olegovich

last: Omelchenko

address: Moskvorechie, 1

department: Scientific Department

institute: FSBI "Research Center for Medical Genetics" RAMS

summary:
  hMSC are perspective source for applications in the field of regeneraitve medicine. Biosafety of cultivated in vitro multipotent cells prior transplantation is one of the important issues. According to cancer stem cell theory, hMSCs are the most probable source of soft tissue tumors (sarcomas). Adequate cell model would help to investigate potential oncomarkers and mechanism of this type of transformation in greater detail.
  Genome-wide pairwise expression analysis of normal and spontaneously transformed hMSCs was performed to determine aspects of immortalization and transformation mechanisms during cultivation of hMSCs.
  Data was processed by lumi (bioconductor package). Differential expression of transcripts was determined by SAM. GSEA and GO overrepresentation analysis on gene level has also been made.
  Results has provided insight into functionally connected genes and pathways involved in spontaneous transformation of hMSCs. It seems that transformation is connected with well-known oncogenic pathways (E2F, ATR/ATM, Ras, Rho). Expression profile of transformed hMSCs has also been determined along with 6 genes, aberrant expression of which hasn`t been dicussed before in terms of oncology (HSPB6, PLAC9, FEZ1, DTWD1, APH1A, ATP5L).

overall_design: Multipotent stromal cells (MSCs) were isolated from adipose tissue samples obtained from 6 healthy donors. Total RNA was isolated from 6 normal and 6 donor-matched spontaneously transformed hMSC cultures in vitro for pair-wise global comparison.

middle: O

first: Alla

last: Rzhaninova

first: Dmitry

middle: V

last: Goldshtein


title: Synthetic lethal screening with small molecule inhibitors provides a pathway to rational combination therapies for melanoma

status: Public on Dec 06 2012

first: Stephen

last: Turner

address: 1670 Discovery Drive

institute: Signature Science, LLC

summary: Recent data demonstrate that extracellular signals are transmitted through a network of proteins rather than hierarchical signaling pathways. This network model suggests why inhibition of a single component of a canonical pathway, even when targeting a mutationally activated driver of cancer, has insufficiently  dramatic effects on the treatment of cancer. The biological outcome of signals propagated through a network is inherently more robust and resistant to inhibition of a single network component due to compensatory and redundant signaling events. In this study, we performed a functional chemical genetic screen analogous to synthetic lethal screening in yeast genetics to identify novel interactions between signaling inhibitors that would not be predicted based on our current understanding of signaling networks. We screened over 300 drug combinations in nine melanoma cell lines and have identified pairs of compounds that show synergistic cytotoxicity. Among the most robust and surprising results was synergy between sorafenib, a multi-kinase inhibitor with activity against Raf, and diclofenac, a non-steroidal anti-inflammatory drug (NSAID). This synergy did not correlate with the known RAS and BRAF mutational status of the melanoma cell lines. The NSAIDs celecoxib and ibuprofen could qualitatively substitute for diclofenac. Similarly, the MEK inhibitor PD325901 and the Raf inhibitor RAF265 could qualitatively substitute for sorafenib. These drug substitution experiments suggest that inhibition of cyclo-oxygenase and MAP kinase signaling are components of the observed synergistic cytotoxicity. Genome-wide expression profiling demonstrates synergy-specific down-regulation of survival-related genes. This study provides proof of principle that synthetic lethal screening can uncover novel functional drug combinations and suggests that the underlying signaling networks that control responses to targeted agents can vary substantially depending on unexplored components of the cell genotype.

overall_design: RNA from VMM39, DM331, and SLM2 cells with/without mutations in Ras and/or Braf, treated with Sorafenib and/or Diclofenac.

first: Devin

last: Roller

first: Daniel

last: Gioeli


title: Genome-wide analysis of the BR response in msg2 and axr2

city: Shanghai

first: zhou

middle: xiao

last: yi

address: 300 fenglin Road

institute: Shanghai Institutes for Biological Science

summary:
Although a wide range of interactions between BRs and auxin have been recognized,  knowledge about the direct molecular mechanism of interaction between them in specific physiological processes is very limited. In this study we found that auxin resisitent mutant msg2/iaa19 and arf7 were also resisitant to the BR effect on morphogenensis of dark-grown Arabidosis seedlings. Moreover, BR signaling transcription factor BZR1 can directly bind to promoter regions of IAA19 and ARF7.
Microarray analysis revealed that a number of gene transcripts showed reduced BR response in msg2 and the control mutant axr2, suggesting the crucial role of IAA19 in mediating BR effects. Taken together, our results suggested that BRs regulate morphogenesis of dark-grown seedling by employing auxin signaling components IAA19 and ARF7.

overall_design: Four-day-old seedlings of WT, msg2 and axr2 grown on MS medium in the absence or presence of 24-eBL (100 nM) were used. Total RNA extraction and ATH1 microarray(Affymetrix) experiments were performend according to manufacturer’s protocols. Raw data were normalized by MAS 5.0 algorithm, Gene Spring Software 11.0. All experiments including two biological replicates and the Pearson correlation coefficient was analyzed to check the replicate quality.

first: Xiao-Yi

last: Zhou

first: Hong-Wei

last: Xue


title: Loss of Foxp3-driven epigenetic modification leads to regulatory T cell insufficiency

status: Public on Dec 07 2012

city: Memphis

first: David

last: Finkelstein

state: TN

address: 332 N. Lauderdale St.

department: Computational Biology

institute: St Jude Children's Research Hospital

summary: Regulatory T cells (Tregs) are responsible for limiting autoimmunity and chronic inflammation.  Foxp3 is a transcription factor that acts as a master regulator of Treg development and function. A serendipitous observation led to the realization that a well-characterized Foxp3gfp reporter mouse, which expresses an N-terminal GFP-Foxp3 fusion protein, is a hypomorph that causes profoundly accelerated autoimmune diabetes on a NOD background. Although natural Treg development and in vitro function is not significantly altered in Foxp3gfp NOD and C57BL/6 mice, Treg fitness function in inflammatory environments is perturbed and TGFβ-induced Treg development reduced. Foxp3gfpis unable to interact with the histone acetyltransferase Tip60, the histone deacetylase HDAC7, and the Ikaros family zinc finger 4, Eos, which leads to reduced Foxp3 acetylation and enhanced K48-linked polyubiquitylation. Collectively this leads to an altered transcriptional landscape and reduced Foxp3-mediated gene repression, notably at the hallmark IL-2 promoter. Loss of controlled Foxp3-driven epigenetic modification leads to Treg insufficiency that causes autoimmunity in prone environments.

overall_design: 16 samples overall split between 2 genotypes (wild type and Foxp3 knock in) and two cell types (Tregs and Tconv)

first: Matthew

middle: L

last: Bettini

first: Fan

last: Pan

first: Maria

first: Jerold

middle: E

last: Rehg

first: Stefan

last: Floess

first: Bryan

last: Bell

first: Steven

last: Zeigler

first: Jochen

last: Huehn

first: Drew

last: Pardoll

first: Dario

middle: A

last: Vignali


title: Genome-wide analysis of mDC transcriptional response to cyclic glucan

city: Dallas

first: Damien

last: Chaussabel

state: TX

address: 3434 Live Oak

institute: Baylor Institute for Immunology Research

summary: Analysis of transcriptional profiles in mDC sorted from apheresed PBMC and stimulated for 6 hours with cyclic glucan or LPS. The hypothesis tested is that cyclic glucan induces maturation and T cell-activation transcripts in human mDC.

overall_design: Total RNA extracted from mDC sorted from apheresed PBMC and activated for 6 hours with cyclic glucan or LPS.

first: Romain

last: Banchereau

first: Jean-Pierre

last: Gorvel


title: Human epidermal neural crest stem cells (hEPI-NCSC) - expanded versus pre-differentiated into neural stem cell-like cells

status: Public on Dec 03 2012

city: Newcastle upon Tyne

first: Maya

last: Sieber-Blum

address: Centre for Life

department: Institute of Genetic Medicine

country: United Kingdom

institute: Newcastle University

summary: hEPI-NCSC are neural crest derived multipotent somatic stem cells that persist in hair follicle stem cell niche, termed the bulge, and persist into adulthood (Clewes O et al, 2011). The purpose of this project was to generate two gene expression profiles, (1) of ex vivo expanded hEPI-NCSC (XP) and (2) of cells, whihc after expansion were grown in a culture medium (NP1), which was empirically designed to pre-differentiate the multipotent stem cells into neural stem–cell like cells.

overall_design: Cells were pooled from three different donors


title: Systemic elevation of PTEN induces a tumor suppressive metabolic state

status: Public on Dec 01 2012

city: Boston

first: Manoj

last: Bhasin

state: MA

address: 330 Brookline Avenue  RN 380E

country: USA

institute: Beth Israel Deaconess Medical Center

summary: Decremental loss of PTEN results in cancer susceptibility and tumor progression. In turn this raises the possibility that PTEN elevation might be an attractive option for cancer prevention and therapy. We have generated several transgenic mouse lines with variably elevated PTEN expression levels, taking advantage of BAC (Bacterial Artificial Chromosome)-mediated transgenesis. Super-PTEN mutants are viable and show reduced body size due to decreased cell number, with no effect on cell size. Unexpectedly, PTEN elevation at the organism level results in healthy metabolism characterized by increased energy expenditure and reduced body fat accumulation. Cells derived from these mice show reduced glucose and glutamine uptake, increased mitochondrial oxidative phosphorylation, and are resistant to oncogenic transformation. Mechanistically we find that PTEN elevation orchestrates this metabolic switch by regulating PI3K-dependent and independent pathways, and negatively impacts two of the most pronounced metabolic features of tumor cells: glutaminolysis and the Warburg effect.

overall_design: In order to elucidate the pathophysiological impact of PTEN elevation, we generated transgenic mice carrying additional copies of this critical tumor suppressor gene (referred to as Super-PTEN mice). In order to maintain the regulation properties of the endogenous Pten gene, we made use of large genomic fragments containing the entire Pten locus carried by BACs (Bacterial Artificial Chromosomes). We next generated mouse embryonic fibroblasts (MEFs) and confirmed successful overexpression of PTEN by the BAC transgenic system. Primary cells derived from Super-PTEN mice represent a powerful tool to elucidate the molecular mechanisms underlying dose-dependent PTEN actions. We therefore performed microarray analysis in primary cells (MEFs) derived from day 13.5 embryos obtained by crossing Super-PTEN mice with C57BL6 mice. Three independent embryos from each genotype were analyzed (background: >98%C57BL6 / CBA). Gene expression profile analysis in these cells will reveal target genes and pathways differentially regulated upon PTEN elevation.

first: Isabel

last: Garcia-Cao

first: Min

middle: S

last: Song

first: Robin

last: Hobbs

first: Gaelle

last: Laurent

first: Carlotta

last: Giorgi

first: Vincent

last: de Boer

first: Dimitrios

last: Anastasiou

first: Keisuke

last: Ito

first: Atsuo

last: Sasaki

first: Lucia

last: Rameh

first: Arkaitz

last: Carracedo

last: Vander Heiden

first: Lewis

last: Cantley

first: Paolo

last: Pinton

first: Marcia

last: Haigis

first: Pier

last: Pandolfi


title: Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine (part 2)

city: Urbana

first: Michael

last: Spinella

state: IL

address: 2001 South Lincoln Ave

department: Comparative Biosciences

institute: University of Illinois

summary: Human embryonal carcinoma (EC) cells are the stem cells of nonseminoma testicular germ cells tumors (TGCTs) and share remarkable similarities to human embryonic stem (ES) cells. In prior work we found that EC cells are hypersensitive to low nanomolar doses of 5-aza deoxycytidine (5-aza) and that this hypersensitivity partially depended on unusually high levels of the DNA methyltransferase, DNMT3B.  We show here that low-dose 5-aza treatment results in DNA damage and induction of p53 in NT2/D1 cells.  In addition, low-dose 5-aza results in global and gene specific promoter DNA hypomethylation.  Low-dose 5-aza induces a p53 transcriptional signature distinct from that induced with cisplatin in NT2/D1 cells and also uniquely downregulates genes associated with pluripotency including NANOG, SOX2, GDF3 and Myc target genes.  Changes in the p53 and pluripotency signatures with 5-aza were to a large extent dependent on high levels of DNMT3B.  In contrast to the majority of p53 target genes upregulated by 5-aza that did not show DNA hypomethylation, several other genes induced with 5-aza had corresponding decreases in promoter methylation.  These genes include RIN1, SOX15, GPER, and TLR4 and are novel candidate tumors suppressors in TGCTs.  Our studies suggest that the hypersensitivity of NT2/D1 cells to low-dose 5-aza is multifactorial and involves the combined activation of p53 targets, repression of pluripotency genes, and activation of genes repressed by DNA methylation.  Low-dose 5-aza therapy may be a general strategy to treat those tumors that are sustained by cells with embryonic stem-like properties.

overall_design: Total RNA obtained from wild-type NT2/D1 cells treated with vehicle (control) or 10 nM 5-aza deoxycytidine for 1 day (1day) or 10 nM 5-aza deoxycytidine for 3 days (3day) or treated with 0.5 uM cisplatin (cispl) for 6 hours followed by a 24 hour recovery before harvest.  Four groups in biological triplicate for total of 12 hybridizations on Illumina HT-12v4 beadarray.

middle: J


title: Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine (part 1)

overall_design: Total RNA obtained from NT2/D1-R1 sh control or NT2/D1-R1 sh DNMT3B knockdown cells treated with vehicle or 10 nM 5-aza deoxycytidine for 3 days.  Four groups in biological triplicate for total of 12 hybridizations on Illumina HT-12v3 beadarray.


title: Gene Expression Effects of IL-13 on Primary Human Airway Epithelial Cells

status: Public on Dec 04 2012

city: St. Louis

first: Anand

middle: Champak

last: Patel

state: MO

address: Campus Box 8116, 660 S. Euclid Ave.

department: Pulmonary/Critical Care Medicine

institute: Washington University School of Medicine

summary:
Primary culture airway epithelial cells, grown under physiologic air-liquid interface conditions, with, or without IL-13 in order to study the effects of this cytokine on mucous cell metaplasia, an important feature of asthma and COPD.
Keywords: IL13, mucus, goblet cell

overall_design: RNA was isolated from primary culture airway epithelial cells grown at air-liquid interface, treated with or without IL-13 for 21 days.

first: Yael

last: Alevy

first: Arthur

middle: D

last: Romero

first: Dhara

first: Jennifer

last: Tucker

first: William

middle: T

last: Roswit

first: Chantel

last: Miller

first: Richard

last: Heier

first: Derek

last: Byers

first: Tom

last: Brett

last: Holtzman


title: Genistein Cooperates with the Histone Deacetylase Inhibitor Vorinostat to Induce Cell Death in Prostate Cancer Cells

city: Atlanta

first: Khanjan

last: Gandhi

address: 1365-B Clifton Rd NE, Room 4107

institute: Winship Cancer Institute, Emory University.

type:
Expression profiling by array
Methylation profiling by array

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

overall_design: Refer to individual Series


title: Genistein Cooperates with the Histone Deacetylase Inhibitor Vorinostat to Induce Cell Death in Prostate Cancer Cells (expression data)

summary: We have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial-to-mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Using whole-genome expression profiling and whole-genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and a combination treatment, where cell death and cell proliferation was determined.

overall_design: ARCaP-E and ARCaP-M cells were analyzed for whole genome expression using the Illumina HumanHT-12 Expression BeadChip. Samples were treated with DMSO control, genistein, vorinostat, a combination of vorinostat and genistein, or 5-aza-deoxycytidine. Samples were prepared in triplicate on independent days.

first: Cornel

last: Phillip

first: Christopher

middle: K

last: Giardina

first: Yu

middle: H

last: Lai

first: Omer

last: Kucuk

first: Carlos

last: Moreno


title: Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine

first: Michael

last: Spinella


title: Genome-wide analysis of gene expression profiles in colorectal cancer cells treated with boswellic acids

first: Masanobu

last: Takahashi

address: 3500 Gaston Avenue, suite H-250

institute: Baylor University Medical Center

summary: Genome-wide analysis of boswellic acids-mediated gene regulation. The hypothesis tested in the present study was that boswellic acids up-regulate some subset of genes in part thorough demethylation of those promotor regions. Results provide important information on boswellic acids-mediated anti-cancer effects in human colon cancer.

overall_design: Total RNA obtained from the human colorectal cancer SW48 cells treated with DMSO alone or acetyl-11-keto-β-boswellic acid (AKBA).

first: Yan

last: Shen

first: Ajay

last: Goel