title: Multiscale Gene Networks Dissect the Complexity of Breast Cancer

first: Yongzhong

last: Zhao

state: New York

address: 1470 Madison Avenue btw. 101st and 102nd Streets

department: Genetics

institute: Mount Sinai Medical Center

summary: Despite the enormous amounts of molecular, cellular, and clinical data that are increasingly available for many different types of cancer, it remains a challenge to integrate different dimensions of data to construct mechanistic models that can robustly distinguish key driver genes from passenger genes, predict tumor progression, and tailor therapies optimally for individual patients. We present an integrative biology approach to constructing and analyzing multiscale regulatory networks of breast cancer. We systematically uncover not only known and novel gene subnetworks (modules) linked to breast cancer, but also their key drivers, the majority of which are not transcription factors or signaling molecules. A number of independent lines of evidence support that the predicted key drivers play central roles in breast cancer biology. We predict and experimentally validate ARF1 as a key driver of breast tumor phenotypes, and then demonstrate the ARF1-controlled subnetwork is a novel regulator of intra- and inter- cellular vesicle dynamics involved in epithelial-mesenchymal transition (EMT).

overall_design: We aimed to study the underlying mechanism by which ARF1 has been predicted playing crucial role during carcinogenesis and metastasis.  To attest the key function of ARF1 during epithelial mesenchymal transition (EMT), loss of function in vitro study by means of siRNA knockdown of ARF1 in MDA-MB-231 breast cancer cell line was designed. Genome-wide gene expression of nine ARF1 knockdown samples and three control samples were profiled by using the Illumina HumanHT-12 V4.0 expression beadchip platform.

first: Bin

last: Zhang


title: Affymetrix gene expression array data for cardia and non-cardia gastric cancer  samples

status: Public on Jul 19 2013

city: Bethesda

first: Howard

last: Yang

state: MD

address: 37 CONVENT DR, Room 5120

department: CCR

country: USA

institute: NCI

summary: We identified different and common dysregulated genes in cardia and non-cardia gastric cancer in the two type of gastric cancer

overall_design: cardia and non-cardia gastric tumors and normal glands

first: Gangshi

last: Wang

last: Hu

middle: H

first: Maxwell

middle: P

last: Lee

first: Philip

middle: R

last: Taylor


title: Expression data from tissues during somatic embryogenesis in Arabidopsis

status: Public on Jul 17 2013

city: Winnipeg

first: Mark

middle: Findlay

last: Belmonte

state: Manitoba

address: 50 Sifton Road

department: Biological Sciences

country: Canada

institute: University of Manitoba

summary:
We collected tissues from bent cotyledon stage zygotic embryos, proliferating tissue at day 7 and day 14 induction of somatic embryogenesis and mature somatic emrbyos in a wild type (Col-0) and vtc2 (SALK_146824) insertion.
We used microarrays to identify global patterns of gene activity during somatic embryogenesis in a wild type (Col-0) and vitamin C deficient mutant (vtc2)

overall_design: RNA was extracted and amplified from four stages of somatic embryogenesis (bent cotyledon, day 7 induction, day 14 induction, and mature somatic embryos) in a wild type (Col-0) and vitamin C deficient mutant (vtc2) before being hybridized to the Arabidopsis ATH1 GeneChip in duplicate (two biological replicates).

first: Ainsley

last: Chan

first: Michael

last: Becker

first: Sherry

last: Mao

first: Samantha


title: Knockdown of breast cancer master regulators: siRNA targeting PTTG1 and SPDEF in MCF-7 cells.

city: Cambridge

first: Mauro

middle: Antonio

last: Alves Castro

address: Robinson Way

country: United Kingdom

institute: Cambridge Research Institute

summary: Genome-wide association studies for breast cancer have identified over 80 different risk regions in the genome, with the FGFR2 locus consistently identified as the most strongly associated locus. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease.  Here we use a systems biology approach to elucidate the regulatory networks operating in breast cancer and examine the role of FGFR2 in mediating risk. Using model systems we identify FGFR2-regulated genes and, combining variant set enrichment and eQTL analysis, show that these are preferentially linked to breast cancer risk loci. Our results support the concept that cancer-risk associated genes cluster in pathways

overall_design: The data consists of 18 microarray samples after knocking down PTTG1 and SPDEF in MCF-7 cells. The data have been pre-processed in R using the Beadarray package, and are presented in the form of log2 expression values. The experiment was carried out on Humanv4 BeadChips arrays interrogating 48107 randomly-distributed bead-types, and in this experiment there was a mean of 22 beads per bead-type (Standard Deviation of 5)

last: Castro

last: Fletcher

first: Florian

last: Markowetz

first: Kerstin

last: Meyer


title: Spatially restricted position-dependent implications of lamin A promoter occupancy on gene activity (expression)

status: Public on Jul 14 2013

city: Oslo

first: Philippe

last: Collas

address: PO Box 1112 Blindern

department: Institute of Basic Medical Sciences

country: Norway

institute: University of Oslo

summary: Interactions between the nuclear lamina (NL) and chromatin are thought to occur through large lamin association domains (LADs) and correlate with gene repression in these domains. We show that binding of lamin A/C (LMNA) to promoters occurs on discrete domains that are associated with distinct transcriptional outputs. Chromatin immunoprecipitation identifies thousands of LMNA-bound promoters, primarily linked to signaling functions. LMNA often occupies narrow domains on promoters, yet LMNA-bound promoters are often contiguous. LMNA-bound genes are overall repressed, but repression correlates with co-enrichment in repressive histone marks rather than LMNA occupancy per se. Genes marked by LMNA and H3K4me3 escape LMNA-associated repression in the absence of repressive histone marks. Positioning of LMNA on promoters relative to the TSS correlates with distinct transcriptional outputs: whereas upstream-distal binding can be transcriptionally permissive, TSS occupancy is associated with promoter inactivity. Perturbation in NL organization causes reorganization of lamin promoter occupancy and uncouples LMNA binding from promoter inactivity. Our results show the existence of many spatially restricted LMNA binding events on promoter regions, with distinct position-dependent transcriptional outputs.

overall_design: Total RNA obtained from ASCs and ASCs depleted of LMNA (LMNA-KD) and processed for microarray hybridization.

first: P

first: E

last: Lund


title: Expression data from mitochondrial protease ClpP knock-out mice.

city: Tuebingen

middle: H.

last: Walter

address: Calwer Str. 7

department: Department of Medical Genetics

country: Germany

institute: University of Tuebingen

summary: The peptidase ClpP is conserved from bacteria to human. In the mitochondrial matrix, it multimerizes and forms a macromolecular proteasome-like cylinder. Because of its known relevance for the mitochondrial unfolded protein response during cell stress, we characterized two ClpP knock-out mouse founder lines and documented similar phenotypes. Ubiquitously, ClpP absence led to accumulation of its interactor protein ClpX without transcript upregulation. Interestingly, most wild-type tissues with substantial ClpP amounts had no detectable ClpX. This inverse correlation suggests that ClpX levels and degradation are regulated by ClpP. The expectation of similar protein levels, in view of a reported association of heptameric ClpP rings with hexameric ClpX rings, was confirmed only in testis of wild-type animals. Germline tissue was exceptional also in its vulnerability to ClpP deletion, with both founder lines showing complete infertility for males and females. Otherwise, ubiquitous mitochondrial dysfunction was apparent from severe growth retardation and reduced spontaneous motor activity of the animals, and from a pronounced decrease in pre-/postnatal survival. Spermatogenesis was found aborted at the spermatid stage, acrosomes and axonemes were not formed. Overall, tissue-specific roles of ClpP were evident by this massive effect for germ cells, mild bioenergetic deficits in muscle and liver tissues, and excellent compensation in brain. ClpX was previously reported to chaperone unfolded proteins and also DNA condensation in mitochondria, so it is likely that this pathway is particularly susceptible in germ cells. In conclusion, our study indicates that the role of ClpP in quality control is indispensable during development for cells with rapid changes of mitochondrial numbers, and is relevant during aging for growth and survival of the organism.

overall_design: Factorial design comparing ClpP knock-out mice with wild type littermates in five different tissues (brain, testis, liver, skeletal and heart muscle)

first: Suzana

last: Gispert

first: Dajana

last: Parganlija

last: Klinkenberg

first: Stefan

last: Dröse

first: Ilka

last: Wittig

first: Michel

last: Mittelbronn

first: Pawel

last: Grzmil

first: Sebastian

last: Koob

first: Andrea

last: Hamann

first: Andreas

last: Reichert

first: Ulrich

last: Brandt

first: H

middle: D

last: Osiewacz

first: Marina

last: Jendrach

first: Georg

last: Auburger


title: Stimulation of endogenous FGFR1b and FGFR2b

first: Mauro

last: Alves Castro

overall_design: The data consists of 46 microarray samples from MCF-7 cells treated under different conditions, at 3 time points (0, 6 and 24 h) in order to perturb FGFR 1b and 2b signalling. The data have been pre-processed in R using the beadarray package, and are presented in the form of log2 expression values. The experiment was carried out on 4 Humanv4 arrays using 12 samples per array. The original arrays contain 48324 features, with an average of 22 beads per feature (Standard Deviation of 5)

last: Castro

first: Michael

last: Fletcher

first: Florian

last: Markowetz

first: Kerstin

last: Meyer


title: Over-expression of FGFR2b from a tetracycline-inducible expression vector

overall_design: The data consists of 125 microarray samples from MCF-7 cells treated under different conditions, at 5 time points (0, 3, 6, 12 and 24 h) in order to perturb FGFR2 signalling by overexpressing the full length FGFR2b from a tetracycline-inducible expression vector. The data have been pre-processed in R using the beadarray package, and are presented in the form of log2 expression values. The experiment was carried out on 11 Humanv4 BeadChips using 12 samples per BeadChip. The original arrays contains 48324 features, with a mean of 22 beads per feature (Standard Deviation of 5)


title: Cyclodextrin protects podocytes in diabetic kidney disease [HumanHT-12 V4.0 array]

status: Public on Jul 13 2013

city: Miami

first: Sandra

last: Merscher-Gomez

address: 1580 NW 10th Avenue

department: Medicine

institute: University of Miami

summary:
Analysis of gene expression changes in differentiated human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). The hypothesis is that the three groups can be distinghed by their differential
gene expression pattern. The results obtained revealed important information regarding differences in gene expression in human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C).

overall_design: Human podocytes were contacted with the serum from patients with diabetes and kidney disease (DKD+) or without kidney disease (DKD-) and compared to normal human podocytes contacted with serum from patients without diabetes (C).

first: Johanna

last: Guzman

first: Markku

last: Lehto

first: Robier

last: Aguillon-Prada

first: Armando

last: Mendez

first: Mariann

middle: I

last: Lassenius

first: Carol

last: Forsblom

first: TaeHyun

last: Yoo

first: Christopher

middle: E

last: Pedigo

first: Rodrigo

last: Villarreal

first: Dony

last: Maiguel

first: Kevin

last: Johnson

first: Ronald

last: Goldberg

first: Viji

last: Nair

first: Ann

last: Randolph

first: Matthias

last: Kretzler

first: Robert

middle: G

last: Nelson

first: George

middle: W

last: Burke III

first: Per-Henrik

last: Groop

first: Alessia

last: Fornoni


title: Lamin A/C-promoter interactions specify chromatin state-dependent transcription outcomes

first: Philippe

last: Collas

type: Genome binding/occupancy profiling by genome tiling array

type: Methylation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: PTEN loss defines a PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma

status: Public on Jul 09 2013

city: Münster

first: Michael

last: Grau

state: Nordrhein-Westfalen

address: Albert-Schweitzer-Campus 1

department: Faculty of Medicine

institute: University of Münster

type: Genome variation profiling by genome tiling array

summary: Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous diagnostic category with distinct molecular subtypes that can be defined by gene expression profiling. However, even within these defined subtypes, heterogeneity prevails. To further elucidate the pathogenesis of these entities, we determined the expression of the tumor suppressor phosphatase and tensin homolog (PTEN) in 248 primary DLBCL patient samples. These analyses revealed that loss of PTEN was detectable in 55% of germinal center B-cell-like (GCB) DLBCLs, whereas this abnormality was found in only 14% of non-GCB DLBCL patient samples. In GCB DLBCL, the PTEN status was inversely correlated with activation of the oncogenic PI3K/ protein kinase B (AKT) pathway in both DLBCL cell lines and primary patient samples. Re-expression of PTEN induced cytotoxicity in PTEN-deficient GCB DLBCL cell line models by inhibiting PI3K/AKT signaling, indicating an addiction to this pathway in this subset of GCB DLBCLs. PI3K/AKT inhibition induced down-regulation of the transcription factor MYC. Re-expression of MYC rescued GCB DLBCL cells from PTEN-induced toxicity, identifying a regulatory mechanism of MYC expression in DLBCL. Finally, pharmacologic PI3K inhibition resulted in toxicity selectively in PTEN-deficient GCB DLBCL lines. Collectively, our results indicate that PTEN loss defines a PI3K/ AKT-dependent GCB DLBCL subtype that is addicted to PI3K and MYC signaling and suggest that pharmacologic inhibition of PI3K might represent a promising therapeutic approach in these lymphomas.

overall_design: This GEO dataset is comprised of a) GEP measurements for 34 primary DLBCL patient samples plus two reference samples, b) 8 paired GEP measurements of the HT DLBCL cell line and c) aCGH measurements for two DLBCL cell lines in addition to previously published cell lines in GSE43272 (i.e., Sample GSM1059798). All of these data were used in the paper cited below.

first: Georg

last: Lenz


title: CD8 T cells induce perforin-dependent pathology in Leishmania braziliensis infection

status: Public on Jul 08 2013

city: Philadelphia

first: daniel

last: beiting

state: PA

address: 380 S. University Ave

department: Pathobiology

institute: University of Pennsylvania

summary: The mechanisms that mediate immunopathologic responses in infectious diseases are often less well understood than how the pathogens are controlled.  Here, we have investigated what causes increased pathology following infection with the protozoan parasite, Leishmania braziliensis.  We focused on CD8 T cells since their presence in leishmanial lesions has been correlated with increased disease.  By adoptively transferring CD8 T cells to L. braziliensis infected RAG mice, we found that unregulated CD8 T cells promote severe pathology at the infection site, as well as the development of metastatic lesions in other skin sites.  In mice with severe pathology, we visualized CD8 T cells degranulating and lysing L. braziliensis infected cells, and in parallel studies with L. braziliensis patients we confirmed that CD8 T cells within lesions exhibit a cytolytic phenotype.  We found that perforin deficient CD8 T cells failed to induce disease, indicating that the increased disease induced by CD8 T cells was due perforin-dependent cytotoxicity.  In contrast, although we found that CD8 T cells made both IFN-γ and IL-17, neither of these cytokines is required for the development of pathology.  Thus, we show for the first time that immunopathology in leishmaniasis can be mediated by cytolytic CD8 T cells.

overall_design: Twelve skin biopsy samples were analyzed, including 2 normal skin biopsies obtained from patients in N. America, and 10 skin biosies obtained from Leishmania brazilensis infected patients presenting at the Corte de Pedra Health Post in Corte de Pedra, Bahia, Brazil

first: Daniel

last: Beiting

first: Phillip

last: Scott

first: Fernanda

last: Novais

first: Edgar

last: Carvalho

first: Lucas


title: Capturing drug responses by quantitative promoter activity profiling

status: Public on Jul 10 2013

city: Yokohama

first: Kazuhiro

last: Kajiyama

state: Kanagawa

department: Center for Life Science Technologies

country: Japan

institute: RIKEN

summary: Quantitative analysis of cellular responses to signaling inhibitors.

overall_design: Total RNA obtained from MCF7 human breast cancer cell lines treated with 1uM gefitinib, 500nM U0126 or 10nM wortmannin for 6hr.

first: Harukazu

last: Suzuki

first: Mariko

last: Okada-Hatakeyama

first: Hideya

last: Kawaji


title: Translating Dosage Compensation to Trisomy 21

status: Public on Jul 12 2013

city: Worcester

first: Benjamin

last: Carone

state: Massachusetts

address: 364 Plantation St

department: BMP

institute: UMass Medical School

summary: Down syndrome is a common disorder with enormous medical and social costs, caused by trisomy for Chr21. We tested the concept that gene imbalance across an extra chromosome can be de facto corrected in DS patient stem cells by manipulating a single gene, XIST. Using zinc finger nucleases, we targeted a large, inducible XIST transgene into the Chr21 DYRK1A locus, in DS pluripotent stem cells. XIST RNA coats Chr21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a “Chr21 Barr Body.” This provides a model to study human chromosome inactivation and creates a system to investigate genomic expression changes and cellular pathologies of trisomy 21, free from genetic and epigenetic noise.  In this study, we used microarrays to understand the genome-wide impacts of inducible XIST expression on Chr21 in trisomy 21 human iPS cell lines, and to evaluate the extent of Chr21 silencing trisomic samples versus a disomic male iPS cell line.

overall_design: Three independently targeted subclones plus the parental Chr21 trisomic (non-targeted) iPS cell line were grown ± doxycycline (2 µg/ml) for 22 d.  Normal male iPS line was also cultured for 22 d and total RNA was extracted with a High Pure RNA extraction kit (Roche) in triplicate for each, processed with a Gene Chip 3’ IVT Express Kit (Affymetrix), and hybridized to Affymetrix human gene expression PrimeView arrays.  Array normalization was performed with Affymetrix Expression Console Software with Robust Multichip Analysis (RMA).  Probesets with the top 60% of signal values were considered present and “expressed” and were used for all further analysis.  In total 9 RNA samples were prepared in triplicate for a total of 27 arrays.

first: Jun

middle: J

last: Jiang

first: Dawn

middle: M

first: Fyodor

last: Urnov

first: Jeanne

middle: B

last: Lawrence


title: The rsa1-1 mutation affects global gene expression in Arabidopsis thaliana with or without salt stress

status: Public on Jul 07 2013

city: College Park

first: Jianhua

last: Zhu

address: 2102 Plant Sciences Building

department: Plant Science and Landscape Architecture

institute: University of Maryland

summary:
Salt stress is one of the most severe environmental conditions which cause huge losses in crop production worldwide. We identified a novel calcium-binding protein and used the Affymetrix whole-genome arrays to define downstream targets of this important protein.
We used the microarrays to reveal the effect of rsa1-1 mutation on global gene expression in response to 120 mM Nacl for 0 or 24 h. A set of genes differentially expressed in rsa1-1 with or without salt stress are identified.

overall_design: Six-day-old seedlings of Arabidopsis thaliana wild type (Columbia gl1 expressing RD29A::LUC transgene) and rsa1-1 mutant seedlings subjected to salt stress with 120 mM NaCl for 0, or 24 h were used for total RNA extraction and hybridizations with Affymetrix ATH1 GeneChips. There are three biological replicate per genotype.

first: Qingmei

last: Guan

first: Jianmin

last: Wu

first: Xiule

last: Yue

first: Yanyan

last: Zhang


title: SCL and c-Kit controlled gene expression in erythroid progenitor cell line

status: Public on Jul 06 2013

city: Montreal

first: mathieu

last: tremblay

state: QC

address: 2950 Chemin de Polytechnique, pav marcelle-coutu 1432

institute: Université de Montréal/IRIC

summary: SCL/TAL1, a tissue-specific transcription factor of the basic helix-loop-helix (bHLH) family, and c-Kit, a tyrosine kinase receptor, control hematopoietic stem cell survival and quiescence. Here we report that SCL and c-Kit signaling control a common gene expression signature, of which 19 genes are associated with apoptosis. In vivo, SCL levels are limiting for the clonal expansion of Kit+ multipotent and erythroid progenitors. In addition, increased SCL expression specifically enhances the sensitivity of multipotent and megakaryocyte/erythroid progenitors to Steel factor (KIT ligand), whilst a DNA binding mutant antagonizes KIT function and induces apoptosis in progenitors. We conclude that Scl operates downstream of Kit to support the survival of megakaryocyte/erythroid progenitors. Finally, higher SCL expression upregulates Kit in normal bone marrow cells and increases chimerism after bone marrow transplantation, indicating that Scl is also upstream of Kit. We conclude that Scl and Kit establish a positive feedback loop in multipotent and megakaryocyte/erythroid progenitors.

overall_design: c-Kit regulated genes were extrapolated from gene expression profiles of TF-1 erythroid progenitor cells (empty MSCV vector) stimulated with SF (Kit ligand), Epo or GM-CSF. Second, SCL-regulated genes were obtained by expressing a DNA binding-defective SCL mutant (DbSCL) and selecting genes that were differentially expressed in bSCL cells versus control cells (MSCV) stimulated with the same cytokines.

first: M

last: Tremblay

first: J

last: Lacombe

first: S

last: Lemieux

first: T

last: Hoang


title: Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia

status: Public on Jul 01 2013

city: Umeå

first: Sofie

last: Degerman

state: Sweden

address: NUS, Blg 6M, 2nd floor

department: Medical Biosciensces

country: Sweden

institute: Umeå University

type:
Expression profiling by array
Methylation profiling by array


title: Genome-wide profiling of whole blood from healthy adult volunteers before and after receiving non-live vaccines including seasonal influenza or pneumococcal vaccine or placebo (saline) injections I

city: Dallas

first: Damien

last: Chaussabel

state: TX

address: 3434 Live Oak

institute: Baylor Institute for Immunology Research

summary: The objective of this study is to: 1) Characterize the cellular origin of transciptional signatures observed on day 1 after vaccination with 2009/10 seasonal influenza and pneumococcal vaccine discovered by transcriptional profiling of whole blood samples in data set “WholeBlood_SysVax”. 2) Discover potential biomarkers for immune-responsiveness to non-live vaccines.

overall_design: In this Series, a total of 72 samples of leukocyte subsets (neutrophils, monocytes, CD4+ T and CD8+ T lymphocytes) were isolated before and 24 hours after vaccination from 6 healthy adult individuals receiving seasonal influenza and 4 healthy adult individuals receiving pneumococcal vaccine. From each subject, neutrophils and peripheral blood mononuclear cells were obtained by Ficoll gradient separation and then CD14+ monocytes, CD4+ T and CD8+ T cells were purified by sequential positive bead selection. Cells were transferred into RLT buffer and stored at -80ºC until mRNA extraction.


title: GENE-EXPRESSION PROFILES OF HUMAN LIVER BIOPSIES CORRELATE WITH POST-TRANSPLANT ALLOGRAFT FUNCTION AND ARE DETERMINED BY DONOR TYPE.

city: Barcelona

first: Juanjo

last: Lozano

address: C/ Rosselló 153

department: Plataforma de Bioinformatica

country: Spain

institute: CIBEREHD

summary: Ischemia-reperfusion injury during liver transplantation is responsible for early allograft dysfunction (EAD) and failure, both of which are associated with a high risk of morbidity and mortality in the recipient. The purpose of this study was to study major transcriptional alterations in livers procured from different types of human liver donors in order to identify genetic profiles predictive of post-implantation function. We have analyzed samples form living donors (LD), donors after cardiac death (DCD), donors after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and donors after brain death without EAD (DBD). Two samples were obtained from each donor: sample A was taken immediately before cold perfusion (baseline) and sample B 2h after portal reperfusion. We identified clear differences in gene expression patterns according to donor source. Both samples A and B from DBD-EAD and DCD demonstrated over-expression of pro-apoptotic and inflammatory transcripts. However, in DBD and LD, expression of these genes was low at baseline and rose only after reperfusion. DBD and LD demonstrated the greatest increase in overall genetic expression after reperfusion when sample B was contrasted with A, indicating less baseline graft injury in these two groups. Grafts from LD were characterized by activation of transcripts related to anti-ischemic and regenerative processes and fewer pro-inflammatory gene transcripts. This transcriptional events occurring in liver allografts could allow for the prediction of post-transplant function. Pro-inflammatory and ischemic transcriptional changes in the grafts are directly related to donor type and may be useful targets for the development of future therapeutic strategies.

overall_design: The complete database comprised the expression for samples taken from 33 liver grafts. Sample A was taken immediately before cold perfusion (baseline) and sample B 2 h after portal reperfusion. Donors were from one of four groups: living (LD); after cardiac death (DCD); after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and after brain death without EAD (DBD). RNA was extracted from the 66 samples and analyzed using Illumina Beadarray technology. A group of 3 samples from healthy volunteers and 3 samples form LD taken at the start of surgery are included as controls or reference samples.

first: C

last: Fondevila

first: E

last: Flores

last: Muñoz

middle: A

last: Loera

first: P

last: Taura

last: Fuster

first: A

last: Rimola

middle: C

last: Garcia-Valdecasas


title: Expression analysis of MDA-MD-231 cells that express lysine racemase (lyr) when grown on D-Lysine versus L-Lysine

status: Public on Jun 30 2013

city: New York

first: Nicholas

last: Gauthier

state: NY

address: 1275 York Avenue, Box #460

institute: MSKCC

summary: This experiment aimed to investigate whether cells that express the L-Lysine-producing enzyme lyr exhibit any mRNA changes when grown on precursor D-Lysine relative to L-Lysine.

overall_design: Total RNA obtained from lyr-expressing MDA-MB-231 cells after 3 days in culture with amino acid precursor D-Lysine, L-Lysine, or starved of both.

first: Boumediene

last: Soufi

first: William

last: Walkowicz

first: Virginia

last: Pedicord

first: Konstantinos

last: Mavrakis

first: Boris

last: Macek

first: David

middle: Y

last: Gin

first: Chris

last: Sander

first: Martin

middle: L

last: Miller


title: Genome wide gene expression array analysis in T-ALL

last: Degerman

summary:
In short: The objective with the gene expression array (Illumina HT-12 v.4) analysis of 17 T-ALL samples was to correlate gene expression levels with DNA promoter methylation status.
Manuscript Abstract:
Background: Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided.
Design and Methods: Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n=43) using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n= 32).
Results: Based on CpG island methylator phenotype (CIMP), T-ALL samples were subgrouped as CIMP+ (high methylation) and CIMP- (low methylation). CIMP- T-ALL patients had significantly worse overall and event free survival (p=0.02 and p=0.001, respectively) compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes.
Conclusions: We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL.

overall_design:
RNA was extracted with TRIZOL according to manufacturer instructions. Total RNA was amplified bu the Illumina TotalPrep RNA Amplification kit.
Gene expression array analysis was performed on the 17/43 pediatric T-ALL samples from which RNA was availible. 2 control samples of stimulted T-cells were included and one replicate.

first: Magnus

last: Borssen

first: Lars

last: Palmqvist

first: Kristina

last: Karrman

first: Jonas

last: Abrahamsson

first: Mikael

last: Behrendtz

first: Jesper

last: Heldrup

first: Erik

last: Forestier

first: Göran

last: Roos


title: Activation of FGFR2-kinase domain (iF2 construct)

first: Mauro

last: Alves Castro

overall_design: The data consists of 71 microarray samples from MCF-7 cells treated under different conditions, at 3 time points (0, 6 and 24 h) in order to perturb FGFR2 signalling using the iF2 construct system. The data have been pre-processed in R using the beadarray package, and are presented in the form of log2 expression values. The experiment was carried out on 6 Humanv4 BeadChips using 12 samples per BeadChip. The original arrays contain 48324 features, with a mean of 22 beads per feature (Standard Deviation of 5)

last: Castro

first: Michael

last: Fletcher

first: Florian

last: Markowetz

first: Kerstin

last: Meyer


title: Expression data from WT, camta1/2, camta1/3, camta2/3, camta1/2/3 mutants

city: Beltsville

first: Sunchung

last: Park

address: 10300 Baltimore ave, Bldg001

department: ARS-NEA

institute: USDA -ARS

summary:
CAMTA3 is known to be involved in regulation of induction of early cold-responsive genes, CBF1 and CBF2 at cold conditions and of suppression of SA production at warm temperature.
Considering a functional redundancy of CAMTA family members in both warm and cold conditions, high-order of camta mutants, camta double and triple mutants, were generated and used to determined the effects of their regulation using microarray analysis.

overall_design: Global gene expression profile of WT and camta mutants was compared with the plants at warm temperature or at cold condition, 4°C for 24 hrs.

first: Yongsig

last: Kim

first: Sarah

last: Gilmour

last: Thomashow


title: Expression data from WT, sid2-1

summary:
Salicylic acid (SA) levels increase in Arabidopsis upon exposure to low temperature for more than a week.  This cold-induced SA biosynthesis was found to proceed through the isochorismate synthase (ICS) pathway. The sid2-1 mutant is deficient in ICS1 and does not make SA at low temperature.
We used microarray analysis to examine the genes differentially regulated by low temperature that were dependent on SA

overall_design: We used the sid2-1 mutant and a WT control at 22⁰C and after 3 weeks at 4⁰C. All samples were in triplicate.


title: Genome-wide analysis of GW3965-responsive genes in 4 different breast cancer cell lines, MCF-7, T-47D, SK-BR-3, and MDA-MB-231

city: Houston

first: Trang

last: Vu

address: 3605 Cullen Blvd., SERC Bldg 545

department: The Center for Nuclear Receptors and Cell Signaling

institute: The University of Houston

summary: Analysis of differentially expressed genes in response to the LXR agonist GW3965 in the MCF-7, T-47D, SK-BR-3, and MDA-MB-231 breast cancer cell lines.  It was previously reported that GW3965 has antiproliferative effects on these 4 different breast cancer cell lines. In the present study, we additionally determine the effects of the LXR ligand on breast cancer cells and determine their mechanism of action in reducing cell proliferation.

overall_design: Total RNA obtained from 4 different breast cancer cell lines (MCF-7, T-47D, SK-BR-3, MDA-MB-231) grown in culture treated with ethanol (control) or GW3965 (GW-treated, experimental) for 48 hours. Triplicates were performed.

first: Chin

last: Lin


title: mTORC1 couples immune signals and metabolic programming to establish Treg cell function

status: Public on Jun 24 2013

city: Memphis

first: Geoffrey

last: Neale

state: TN

address: 262 Danny Thomas Place

department: Hartwell Center

institute: St Jude Childrens Research Hospital

summary: The mechanistic target of rapamycin (mTOR) pathway integrates diverse environmental inputs, including immune signals and metabolic cues, to direct T cell fate decisions1. Activation of mTOR, comprised of mTORC1 and mTORC2 complexes, delivers an obligatory signal for proper activation and differentiation of effector CD4+ T cells2,3, whereas in the regulatory T cell (Treg) compartment, the Akt-mTOR axis is widely acknowledged as a crucial negative regulator of Treg de novo differentiation4-8 and population expansion9. However, whether mTOR signaling affects the homeostasis and function of Tregs remains largely unexplored. Here we show that mTORC1 signaling is a pivotal positive determinant of Treg function. Tregs have elevated steady-state mTORC1 activity compared to naïve T cells. Signals via T cell receptor (TCR) and IL-2 provide major inputs for mTORC1 activation, which in turn programs suppressive function of Tregs. Disruption of mTORC1 through Treg-specific deletion of the essential component Raptor leads to a profound loss of Treg suppressive activity in vivo and development of a fatal early-onset inflammatory disorder. Mechanistically, Raptor/mTORC1 signaling in Tregs promotes cholesterol/lipid metabolism, with the mevalonate pathway particularly important for coordinating Treg proliferation and upregulation of suppressive molecules CTLA-4 and ICOS to establish Treg functional competency. In contrast, mTORC1 does not directly impact the expression of Foxp3 or anti- and pro-inflammatory cytokines in Tregs, suggesting a non-conventional mechanism for Treg functional regulation. Lastly, we provide evidence that mTORC1 maintains Treg function partly through inhibiting the mTORC2 pathway. Our results demonstrate that mTORC1 acts as a fundamental ‘rheostat’ in Tregs to link immunological signals from TCR and IL-2 to lipogenic pathways and functional fitness, and highlight a central role of metabolic programming of Treg suppressive activity in immune homeostasis and tolerance.

overall_design: We used microarrays to explore the gene expression profiles differentially expressed in regulatory T-cells from wild-type and CD4(cre) x Raptor(fl/fl) mice

first: Hu

last: Zeng

first: Hongbo

last: Chi


title: Leukemia associated mutant Wilms' tumour gene 1 protein promotes expansion of human hematopoietic progenitor cells

status: Public on Jun 21 2013

city: Lund

first: Karina

last: Vidovic

address: Klinikgatan 26

department: Hematology and Transfusion Medicine

institute: Lund University

summary: Analysis of gene expression levels in hematopoietic progenitor cells retrovirally transduced with full-length WT1(+/-) or a WT1-mutant lacking zinc-finger, WT1(delZ) cultured in vitro for 14 days. The hypothesis tested in this study was that the WT1-mutant confers an increased proliferation rate after 14 days in culture and an erythroid phenotype. Results provide information of upregulation of some genes associated with cellcycle progression, upregulated genes connected with erythropoiesis and downmodulation of some genes associated with myeloid differentiation.

overall_design: Total RNA obtained from CD34+ progenitor cells in suspension cultures for 14 days.

first: Tove

last: Ullmark

first: Bodil

last: Rosberg

first: Tor

last: Olofsson

first: Andreas

last: Lennartsson

first: Björn

last: Nilsson

first: Urban

last: Gullberg


title: Gene Expression profiling in healthy population samples

status: Public on Jun 28 2013

city: Tartu

first: Tonu

last: Esko

address: Riia 23b

country: Estonia

institute: Estonian Genome Center, University of Tartu

summary:
734 whole-blood RNA samples from Estonian Biobank were profiled to find molecular mechanisms behind human complex diseases

deidentified clinical and serum metabolite data requested but not provided

overall_design: 734 whole-blood RNA samples were profiled with Illumina HT12v3 array. Same samples are genotyped and profiled for serum metabolites.

first: Andres

last: Metspalu


title: The effect of sucrose and sulfamethoxazole on the Arabidopsis transcriptome

city: Toronto

first: Malcolm

middle: M.

last: Campbell

state: ON

address: 25 Willcocks Street

department: Cell & Systems Biology

institute: University of Toronto

summary: A chemical screen was performed in search of compounds that modify plant responses to sucrose. This screen uncovered that sulfamethoxazole (SMX), a folate biosynthesis inhibitor, acted synergistically with sucrose to inhibit hypocotyl elongation, suggesting interaction between these two pathways. Transcriptome analysis was performed to identify changes in transcript abundance that may underpin crosstalk between sucrose and SMX. Three-day-old dark-grown seedlings were treated to sucrose and SMX at concentrations that induced no change in hypocotyl elongation when administered independently, yet restricted elongation when both were present in the growth media (10mM and 0.2µM, respectively). This analysis uncovered multiple core auxin signalling components that exhibit altered  transcript abundance in response to co-treatment with sucrose and SMX, suggesting that auxin signalling mediates crosstalk between these two pathways. This study highlights an input through which metabolic status can shape plant growth and development through hormone signalling.

overall_design: 12 arrays total. Three arrays as non-treated control, three arrays from seedlings raised in presence of 0.2µM SMX, three arrays from seedlings raised in presence of 10mM sucrose, and three arrays from seeldings raised in presence of both 10mM sucrose and 0.2µM SMX. Three biological replicates were produced for each growth treatment.

first: Michael

last: Stokes

first: Abhishek

last: Chattopadhyay

first: Olivia

last: Wilkins

first: Eiji

last: Nambara


title: Gene expression in Early-Onset Preeclampsia Placentas and Controls

city: Vancouver

first: Wendy

last: Robinson

state: BC

address: 950 W 28th Ave

department: Medical Genetics

institute: University of British Columbia

summary: We investigated the DNA methylation and gene expression of 20 chorionic villi samples from early onset preeclampsia placentas to 20 gestational age matched controls. From this we were able to see a widespread disregulation in DNA methylation across a subset of genes in the genome. This may help to elucidate the underlying biological problems that lead to early onset preeclampsia. We noted that there were DNA methylation changes in many genes of importance as well as in different genomic elements such as enhancers.

overall_design: RNA from 8 Early Onset Preeclampsia placentas and 8 gestational age matched controls

first: John

last: Blair

first: Ryan

middle: K

last: Yuen

first: Peter

last: von Dadelszen

middle: P


title: Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association.

city: Exeter

first: Hanieh

last: Yaghootkar

address: Magdalen Road

department: Genetics

institute: University of Exeter Medical School

summary: The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work.

overall_design: Gene expression data was determined of peripheral blood samples (n=705) from InChianti cohort.


title: Gene expression changes caused by YAP overexpression and Nf2 deletion in the developing mouse brain

status: Public on Jun 19 2013

first: Geoffrey

last: Neale

summary: The transcriptional coactivator YAP is the key downstream effector of the Hippo pathway. YAP overexpression in the developing mouse brain results in excessive expansion of the neural progenitor pool and severe perturbation of brain development. Nf2/Merlin is a tumor suppressor whose mutations are found in many human cancers. Loss of Merlin during brain development causes overexpansion of the neural progenitor pool. We used microarrays to identify the gene expression changes caused by YAP overexpression and Nf2 deletion.

overall_design: We used a double-transgenic system to overexpress YAP in the developing mouse brain by crossing mice carrying a doxycycline-dependent allele of YAP1-S127A (TetO-YAP1) with those expressing the reverse tetracycline-dependent transactivator rtTA under the control of the neural progenitor-specific Nestin promoter (Nes-rtTA) and feeding the dam with doxycycline-containing food (200 mg/kg) from E7.5. We conditionally deleted Nf2 using the telencephalon-specific Emx1-Cre.

first: Xinwei

last: Cao


title: RNA analysis in Finnish Schizophrenia Families

city: Helsinki

first: William

last: Hennah

address: FIMM, PO Box 20

country: Finland

institute: Institute for Molecular Medicine Finland, FIMM

summary: 18 Families (66 individuals) from an established cohort for schizophrenia in Finland provided RNA for analysis of genome-wide gene expression levels in blood lymphocytes. These have been collected for the analysis of genetic risk variants for mental illness that are present within these families, under the hypothesis that genetic variants will lead to changes in the biological functioning that represent the mechanisms altered in the etiology of major mental illness, with gene expression providining a means to observe such alterations.

overall_design: Total RNA was extracted from fresh blood samples donated by 66 individuals from 18 families ascertained for schizophrenia. Gene expression was measured using 6 chips, with two individuals (samples 2 and 8) replicated across chips.  The non-normalized matrix contains the complete data, including replicates.

first: Jaana

last: Suvisaari

first: Liisa

last: Tomppo

first: Minna

last: Torniainen

first: Tiina

last: Paunio

first: Alfredo

last: Ortega-Alonso

first: Jouko

last: Lönnqvist


title: STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett’s adenocarcinomas

status: Public on Jun 16 2013

city: Lübeck

first: Hauke

last: Busch

state: Schleswig-Holstein

address: Ratzeburger Allee 160

department: Lübeck Institute of Experimental Dermatology

institute: University of Lübeck

summary: Signal transducer and activator of transcription 3 (STAT3) is altered in several epithelial cancers and represents a potential therapeutic target. Here, STAT3 expression, activity and cellular functions were examined in two main histotypes of esophageal carcinomas. In situ, immunohistochemistry for STAT3 and STAT3-Tyr705 phosphorylation (P-STAT3) in esophageal squamous cell carcinomas (ESCC) and Barrett’s adenocarcinomas (BAC) revealed similar STAT3 expression in ESCCs and BACs, but preferentially activated P-STAT3 in ESCCs. In vitro, strong STAT3 activation was seen by EGF-stimulation in OE21 (ESCC) cells, whilst OE33 (BAC) cells showed constitutive weak STAT3 activation. STAT3 knockdown significantly reduced cell proliferation of OE21 and OE33 cells and reduced cell migration in OE33, but not in OE21 cells. Transcriptome analysis identified STAT3-knockdown associated down-regulation of cell cycle processes and the selective down-regulation of cyclins and cyclin dependent kinaes  associated genes in both OE21 and OE33 cells. Moreover, the transcriptome response showed changes in cell migration/invasion related genes that correlated with the associated phenotype measurements.  This study demonstrates the importance of STAT3 expression and activation in esophageal carcinomas, whereby the extent differs between ESCCs and BACs. STAT3 knockdown significantly reduces cell proliferation in both types of esophageal cancer cells and inhibits migration in BAC cells. Thus, STAT3 may be further exploited as potential novel therapeutic target for esophageal cancers.

overall_design: The effect of STAT3 knock-down in OE33 and OE21 cells was calculated from three biologically independent experiments.  3x10e4 cells were seeded in triplicate in 24 well-plates  and were transfected with twice 100nM STAT3 siRNA (pool of 4 STAT3 sequences, siGENOME®SMARTpool®, Dharmacon RNAi Technologies, Thermo Fisher Scientific, Lafayette, USA) or Silencer® negative siRNA control (Invitrogen/Life Technologies GmbH, Darmstadt, Germany) using 1µl DharmaFECT (Dharmacon RNAi Technologies, Thermo Fisher Scientific, Lafayette, USA) transfection reagent for OE33 cells or siPORTTM NeoFXTM (Invitrogen/Life Technologies GmbH, Darmstadt, Germany) transfection reagent for OE21 cells. Differential gene regulation was quantified 72 hours after the first transfection by comparing separately for the OE21 and OE33 cells the STAT3 siRNA replicates and the respective cell lines containing the scrambled siRNA vector.

first: Melanie

last: Boerries

first: Silke

last: Lassmann


title: Transcriptional profiling of gastric epithelial cells infected with wild type or arginase-deficient Helicobacter pylori

status: Public on Jun 15 2013

city: New Orleans

first: Jovanny

last: Zabaleta

state: LA

address: 1700 Tulane Ave

department: Interdisciplinary Oncology

institute: LSUHSC

summary: We studied the differential gene expression in the gastric cell line AGS infected with wild type (WT) or arginase gene mutant (rocF) Helicobacter pylori (Hp). We found that the presence of the gene regulates the inflammatory responses in terms of IL8 and MIP-1B. We conclude that arginase may be involved in regulating inflammatory responses which improves the chances of survival against the human immune response.

overall_design: AGS cells were infected for 16 hours with WT, the rocF, or a complemented H. pylori strain (rocF+). The RNA was extracted with TRIzol, treated with DNAse I (both from invitrogen). cRNA was made with the Illumina TotalPrep RNA amplification Kit (ambion AMIL1791).

first: Songhee

middle: H

last: Kim

first: Rosa

last: Sierra

first: David

last: McGee


title: Gene expression profiles in mouse common myeloid progenitor (CMP) and leukemia cells expressing full-length MN1 or truncated versions of MN1 protein

status: Public on Jun 13 2013

summary: We used Affymetrix microarrays to characterize gene expression profiles that were perturbed in common myeloid progenitor (CMP) cells due to enforced expression of full-length or truncated forms of MN1. Expression profiles of MN1-induced leukemias arising from whole bone marrow transduction were also compared with the profiles obtained from the CMP cells.

overall_design: Lineage negative mouse bone marrow cells were transduced with retroviral vectors expressing full-length or truncated MN1 proteins. After 2 days in culture, cells were FACS-sorted for GFP expression and cultured for a further 3 days in growth media. After 5 days total, RNA was isolated and processed for microarray analysis. RNA was also prepared for microarray analysis from leukemias arising in mice following whole bone marrow transduction with full-lenght MN1.

first: Ayten

last: Kandilci

first: Gerard

last: Grosveld


title: Identification of microarray probe signals constantly present in multiple sample types (part 1)

status: Public on Jun 10 2013

city: Detroit

first: Stephen

last: Krawetz

state: MI

address: 275 E. Hancock

department: Center for Molecular Medicine and Genetics

institute: Wayne State University School of Medicine

summary: The correlation of the RNA profiles obtained by microarray analysis was compared with that obtained from RNA-Seq by using reduced complexity sperm datasets. This resolved as a series of discordant probes. The extent of discordancy among other datasets was then determined.

overall_design: A correlative study between probe’s signal intensity from Illumina bead arrays with its transcript level detected by next generation sequencing technique was performed. RNAs from sperm and testis samples were applied

first: Shihong

last: Mao

first: Aletheia

last: Lima-Souza

first: Robert

last: Goodrich


title: Time series of global gene expression after trivalent influenza vaccination in humans

status: Public on Jun 18 2013

city: Bethesda

first: Luis

last: Franco

address: 9000 Rockville Pike

department: National Institute of Allergy and Infectious Diseases

institute: National Institutes of Health

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

overall_design: Refer to individual Series


title: Time series of global gene expression after trivalent influenza vaccination in humans (male cohort)

summary: The purpose of the study was to assess the patterns of global gene expression in peripheral blood cells before and at three time points after the administration of a trivalent influenza vaccine in human male subjects, and to relate these to the antibody response to the vaccine. The antibody titer data for these subjects is provided as a supplemental file.

overall_design: 119 healthy male human volunteers ages 19 - 41 years were recruited in the study. Whole-blood RNA samples were collected in PaxGene tubes before and at three time points after administration of a trivalent influenza vaccine. Baseline samples (before vaccination) are labeled as day 0. The three additional time points are days 1, 3, and 14 after vaccination. A total of 431 arrays, corresponding to 116 individuals, passed quality control and are included in this data set. These are distributed as follows:  Day 0: 111 Samples  Day 1: 110 Samples  Day 3: 101 Samples  Day 14: 109 Samples

first: Chad

last: Shaw

first: John

last: Belmont

last: Couch


title: Genome-wide expression profiling of complex regional pain syndrome

status: Public on Jun 06 2013

city: Daejeon

first: EunHeui

last: Jin

address: Munhwaro

country: South Korea

institute: Chungnam national university

summary: we successfully identified pain-related genes through genome-wide expression profiling in blood from CRPS patients. We found that 80 genes were differentially expressed between 4 CRPS patients (2 CRPS I and 2 CRPS II) and 5 controls (cut-off value: 1.5-fold change and p < 0.05). Most of those genes were associated with signal transduction, developmental processes, cell structure and motility, and immunity and defense. The expression levels of 12 genes selected from the microarray were confirmed in 24 CRPS patients and 18 controls by quantitative reverse transcription-polymerase chain reaction. We focused on matrix metalloproteinase 9 (MMP9) that showed statistically significant difference from controls and the highest relative fold change in CRPS II patients to controls by qPCR validation (6.4 ± 2.47 times and p = 0.001).

overall_design:
Identification of pain-related genes in peripheral blood of complex regional pain syndrome (CRPS) using cDNA microarray.
Comparative gene expression profiles in peripheral blood of 5 healthy controls and 4 CRPS patients.

first: E

first: W

last: Lee


title: Anti-proliferative effects of continued mitogen activated protein kinase pathway inhibition following acquired resistance to BRAF and/or MEK inhibition in melanoma: Implications for treatment beyond disease progression

city: Westmead

first: Gulietta

last: Pupo

state: NSW

address: Darcy Road

country: Australia

institute: University of Sydney

summary: Inhibitors of the MAPKs, BRAF and MEK, induce tumor regression in the majority of patients with BRAF-mutant metastatic melanoma. The clinical benefit of MAPK inhibitors is restricted by the development of acquired resistance with half of those who benefit having progressed by 6-7 months and long-term responders uncommon.  There remains no agreed treatment strategy on disease progression in these patients. Without published evidence, fears of accelerated disease progression on inhibitor withdrawal have led to the continuation of drugs beyond formal disease progression. We now demonstrate that treatment with MAPK inhibitors beyond disease progression can provide significant clinical benefit, and the withdrawal of these inhibitors led to a marked increase in the rate of disease progression in two patients. We also show that MAPK inhibitors retain partial activity in acquired resistant melanoma by examining drug-resistant clones generated to dabrafenib, trametinib or the combination of these drugs.  All resistant sublines displayed a markedly slower rate of proliferation when exposed to MAPK inhibitors, and this coincided with a reduction in MAPK signalling, decrease in BrdU incorporation and S-phase inhibition. This cytostatic effect was also associated diminished levels of cyclin D1 and p-pRb.. Two short-term melanoma cultures generated from resistant tumour biopsies also responded to MAPK inhibition with comparable inhibitory changes in proliferation and MAPK signalling. These data provide a rationale for the continuation of BRAF and MEK inhibitors after disease progression and support the development of clinical trials to examine this strategy.

overall_design: Total RNA obtained from melanooma cell lines treated for 24h with dabrafenib, trametinib or combination of dabrafenib and trametinib

first: Helen

last: Rizos


title: Global peripheral blood gene expression study [HumanHT-12 V4.0]

status: Public on Jun 08 2013

city: Seattle

first: Daniel

last: Enquobahrie

state: Washington

address: 1730 Minor Avenue

department: Cardiovascular Health Research Unit

institute: University of Washington

summary: Samples were collected from 'control participants' of the Heart and Vascular Health (HVH) study that constitutes a group of population based case control studies of myocardial infarction (MI), stroke, venous thromboembolism (VTE), and atrial fibrillation (AF) conducted among 30-79 year old members of Group Health, a large integrated health care organization in Washington State.

overall_design: Total RNA was isolated from peripheral collected using PAXgene tubes and gene expression was profiled using the Illumina platform.

first: Mark

last: Christiansen

first: Bruce

last: Psaty


title: Global peripheral blood gene expression study [HumanHT-12 V3.0]


title: Targeting BCL-2 with the BH3 mimetic ABT-199 in ER-positive breast cancer

status: Public on Jun 09 2013

city: Parkville

first: Matthew

last: Ritchie

state: Victoria

address: 1G Royal Parade

department: Epigenetics and Development Division

institute: The Walter and Eliza Hall Institute of Medical Research

summary: A bank of human breast tumor xenografts was established by serial passage of primary breast tumor fragments in the cleared mammary fat pads of immuno-compromised NOD-SCID-IL2Rgammac-/- mice. The expression profiles from four different tumors (23T, 315T, 50T and 838T) were classified using diagonal discriminant analysis. The training data set consisted of 1992 samples from Curtis et al. (2012, PMID: 22522925); class labels were based on tumor subtype information provided (Basal-like, Luminal A, Luminal B, HER2-enriched and Normal breast-like).

overall_design: Total RNA obtained from xenograft tumors from different patients have been profiled on the Illumina HT-12 BeadChip platform.


title: Associations between gene expression variations and ovarian cancer risk alleles identified from genome wide association studies

city: buffalo

first: Dan

last: Wang

address: Elm & Carlton Streets

institute: RPCI

summary: We evaluated the genome-wide mRNA expression profiles in lymphoblastoid cell lines of familial ovarian cancer patients and controls

overall_design:
Comparing the mRNA expression data of 74 ovarian cancer cases with  47 healthy controls.

Genotype information of the 7 risk alleles is linked to the bottom of the Series record.

first: Hua

last: Zhao

first: Jie

last: Shen

first: Steven

last: Gregory

first: Leonard

last: Medico

first: Qiang

last: Hu

first: Li

last: Yan

first: Kunle

last: Odunsi

first: Shashikant

last: Lele

first: Christine

last: Ambrosone

first: Song

last: Liu


title: Time series of global gene expression after trivalent influenza vaccination in humans (female cohort)

first: Luis

last: Franco

state: MD

summary: The purpose of the study was to assess the patterns of global gene expression in peripheral blood cells before and at three time points after the administration of a trivalent influenza vaccine in human female subjects, and to relate these to the antibody response to the vaccine

overall_design: 128 healthy female human volunteers ages 19 - 41 years were recruited in the study. Whole-blood RNA samples were collected in PaxGene tubes before and at three time points after administration of a trivalent influenza vaccine. Baseline samples (before vaccination) are labeled as day 0. The three additional time points are days 1, 3, and 14 after vaccination. A total of 417 arrays, corresponding to 110 individuals, passed quality control, corresponded to individuals where at least two of the four arrays in the series were available, and corresponded to individuals who were ethnically homogeneous as determined by identity-by-state and multidimensional scaling analysis of their genotype data. That set of 417 arrays was used for analysis in the associated publication and was therefore included in this GEO upload. These are distributed as follows:  Day 0: 107 Samples  Day 1: 107 Samples  Day 3: 105 Samples  Day 14: 98 Samples

first: Chad

last: Shaw

first: John

last: Belmont

first: Robert

last: Couch


title: Global peripheral blood gene expression study

first: Daniel

last: Enquobahrie

first: Mark

last: Christiansen

first: Bruce

last: Psaty


title: Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embyronic and induced pluripotent cells

status: Public on Jun 01 2013

city: Hamilton

first: Mickie

last: Bhatia

state: Ontario

address: 1200 Main Street West

department: Stem Cell and Cancer Research Institute (SCC-RI)

institute: McMaster University

summary: Notch signaling regulates several cellular processes including cell fate decisions and proliferation in both invertebrates and mice. However, comparatively less is known about the role of Notch during early human development. Here, we examined the function of Notch signaling during hematopoietic lineage specification from human pluripotent stem cells (hPSCs) of both embryonic and adult fibroblast origin. Using immobilized Notch ligands and siRNA to Notch receptors we have demonstrated that Notch1, but not Notch2 activation, induced HES1 expression and generation of committed hematopoietic progenitors. Using gain and loss of function approaches, this was shown to be attributed to Notch signaling regulation through HES1, that dictated cell fate decisions from bipotent precursors either to the endothelial or hematopoietic lineages at the clonal level. Our study reveals a previously unappreciated role for the Notch pathway during early human hematopoiesis, whereby Notch signaling via HES1 represents a toggle switch of hematopoietic vs. endothelial fate specification.

overall_design: Human pluripotent stem cells (hPSCs) have differentiation potential into three embryonic germ layers including blood. Notch signaling is one of important signaling pathways involved in blood differentiation of hPSCs. Thus, in order to examine the effect of Notch signaling pathways during hematopoietic differentiation of hPSCs, embryoid bodies (EBs) were formed and cultured for 10 days in the combination of cytokines and growth factors (Chadwick, Blood, 2003; 300 ng/ml of SCF, 300 ng/ml of Flt-3L, 10 ng/ml of IL-3, 10 ng/ml of IL-6, and 50 ng/ml of G-CSF) to induce differentiation into blood. Additionally, CD31+CD45- bipotent hemogenic precursors were isolated from day10 hematopoietic EBs (Wang et al., Immunity, 2004)

first: Jung-Bok

last: Lee

first: Tamra

last: Werbowetski-Ogilvie

first: Jong-Hee

first: Brendan

last: McIntyre

first: Angelique

last: Schnerch

first: Seok-Ho

last: Hong

first: In-Hyun

last: Park

first: George

middle: Q

last: Daley

first: Irwin

last: Bernstein


title: Crosstalk between the STAT3, NF-kB and Notch signaling pathways in glioblastoma stem cells

city: Memphis

first: Jo

middle: Meagan

last: Garner

state: United States

address: 19 S. Manassas St.

department: Pathology

institute: University of Tennessee Health Science Center

summary: In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-κB signaling. We demonstrate that adherent glioma CSCs exhibit characteristics previously described for CSCs grown in suspension culture. The expression of CD133, Sox2 and Nestin increased when compared to glioma cells grown in monolayer, and the adherent CSCs were ~100 times more tumorigenic in vivo than monolayer cultured glioma cells. We also found that while the STAT3 and NF-κB signaling pathways are constitutively activated in glioma lines, these pathways are dramatically activated in glioma CSCs. Treatment with STAT3 inhibitors led to a loss of nuclear activation of STAT3 signaling and suppression of growth in both monolayer and CSC conditions. There was a markedly greater growth suppressive effect on glioma CSCs, suggesting that targeted therapy of these key pathways in glioma CSCs may be possible. To further investigate potential biomarkers in glioma CSCs, microarray analysis was performed and revealed deregulation of the Notch signaling pathway.  This constitutive activation of STAT3, NF-κB, and Notch pathways in glioma CSCs helps identify novel therapeutic targets for the treatment of glioma.

overall_design: GBM6 cells were continuously maintained as subcutaneous xenografts in NSG mice, and monolayer and CSC cultures were derived from freshly harvested tumor tissue. A total of 6 samples were subjected to microarray analysis, with three biological replicates for each experimental condition.

first: Meiyun

last: Fan

first: Chuan

last: Zang

first: Ziyan

last: Du

first: Michelle

last: Sims

first: Andrew

last: Davidoff

first: Lawrence

last: Pfeffer


title: The effects of treatments in dermal fibroblasts

status: Public on Jun 04 2013

city: Port St. Lucie

first: Xiaoyong

last: Sun

state: FL

address: 9801 SW Discovery Way

institute: VGTI, FL

summary: Progressive fibrosis of the skin and internal organs accounts for the intractable nature and the high mortality of scleroderma. As the principal effector cells responsible for fibrosis, stromal fibroblasts and myofibroblasts contribute to excessive deposition of collagens and other extracellular matrix proteins. Transforming growth factor β (TGF-β), which stimulates collagen synthesis, myofibroblast differentiation and epithelial-mesenchymal transition (EMT), is implicated as a key initiating factor in both physiological and pathological tissue remodeling. However, the mechanism responsible for the persistence of the fibrotic process associated with pathological repair remains poorly understood. In this study, we analyzed the gene expression in dermal fibroblasts using different treatments (Poly I:C, IFN-beta, Egr-3 overexpression and other conditions).

overall_design: Primary fibroblast cultures were established by explantation from neonatal foreskin. Biopsy protocols were approved by the Institutional Review Board at Northwestern University. Fibroblasts were maintained in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) (Lonza, Basel, Switzerland), 50 µg/ml penicillin, and 50 µg/ml streptomycin in a humidified atmosphere of 5% CO2 at 37°C, and studied between passages 2-8. At confluence, serum-free media supplemented with 0.1% bovine serum albumin (BSA) were added to the cultures for 24 h prior to the treatment of Poly I:C for 2 hours or 24 hours (10 ug/ml), or IFN-β (100 U/ml) or other reagents for 24 hours, or infected with Ad-Egr-3 or Ad-GFP at 50 MOI for 48 hours. Total RNA was isolated using RNeasy Mini Plus Kits (Qiagen, Valencia, CA). The integrity of RNA was determined using Agilent Bioanalyzer (Santa Clara, CA). Fluorescently labeled cDNA was prepared (Ambion, Austin, TX), and was hybridized to Illumina Human HT-12 Version 4 microarray chips containing 44,000 probes (Illumina, San Diego, CA). Raw signal intensities for each probe were obtained using Illumina BeadStudio data analysis software and imported to the Bioconductor lumi package for transformation and normalization. The data were preprocessed using a variance stabilization transformation method followed by quantile normalization. Data from probes that produced signals near or below background levels (estimated based on Illumina negative control probes) with all samples were discarded.

first: Feng

last: Fang

first: John

last: Varga


title: Geometric control of the coronary artery endothelial cell transcriptome

city: El Paso

first: Brad

middle: Allen

last: Bryan

state: Texas

address: 5001 El Paso Drive

department: Biomedical Sciences

institute: Texas Tech University Health Sciences Center

first: Dianne

last: Mitchell


title: Geometric control of the coronary artery endothelial cell transcriptome following serum starvation

summary:
Analysis of the effects of cell shape on human coronary artery endothelial cell transcription.  The hypothesis is that defined alterations in endothelial cell shape uniquely affect the endothelial transcriptome.
Human coronary artery endothelial cells were plated onto spatially defined micropatterns (Cytoo) forcing them to conform to Disc, Crossbow, H, Y, or L shapes.  As a control, human coronary artery endothelial cells were plated on non-restrictive areas of the Cytoo growth plate.  Cells were serum starved for 48 hours prior to mRNA collection.

overall_design: RNA was collected after 48 hours growth on the restricted or non-restricted growth patterns and subjected to whole genome microarray analysis.


title: Geometric control of the coronary artery endothelial cell transcriptome following standard growth condition

summary:
Analysis of the effects of cell shape on human coronary artery endothelial cell transcription.  The hypothesis is that defined alterations in endothelial cell shape uniquely affect the endothelial transcriptome.
Human coronary artery endothelial cells were plated onto spatially defined micropatterns (Cytoo) forcing them to conform to Disc, Crossbow, H, Y, or L shapes.  As a control, human coronary artery endothelial cells were plated on non-restrictive areas of the Cytoo growth plate.

overall_design: RNA was collected after 24 hours growth on the restricted or non-restricted growth patterns and subjected to whole genome microarray analysis.


title: Expression data from Arabidopsis leaves after gamma irradiation of 200 Gy

city: Jeongeup-si

first: Jin-Hong

last: Kim

state: Jeonbuk-do

address: 29 Geumgu-gil

institute: Korea Atomic Energy Research Institute

summary:
Arabidopsis cmt3 mutant showed neither DNA hypomethylation nor transcriptional activation of silenced repeats by gamma rays, which was found in wild type (WT). We used microarrays to compare the global transcriptional changes between the WT and cmt3 after the irradiation of 200 Gy.
Transcriptions of transposition-related genes seemed to be differently affected in the WT and cmt3 by gamma rays, depending on the epigenetic codes of the genome. However, genome-wide transcriptions of the WT and cmt3 couldn't be positively correlated with the different levels of DNA methylation after the irradiation of 200 Gy.

overall_design: Rosette leaves from more than 10 plants were pooled for total RNA extraction and hybridization on Affymetrix Arabidopsis ATH1 genechips. We performed two independent array experiments using totally different biological replicates of WT and cmt3 mutant plants with or without gamma irradiation.

first: JiEun


title: Glycosylation regulates the stability of c-MYC

status: Public on May 30 2013

city: Oslo

first: Ian

last: Mills

address: Gaustadalleen 21

department: Centre for Molecular Medicine Norway

institute: University of Oslo

summary: Tumorigenesis is characterised by changes in transcriptional regulation and the androgen receptor (AR) has been identified as a key driver in prostate cancer. In this study, we show that the hexosamine biosynthetic pathway (HBP) genes are overexpressed in clinical prostate cancer and androgen-regulated in cell-lines. HBP senses metabolic status of the cell and produces an essential substrate for O-GlcNAc transferase (OGT), which regulates target proteins via glycosylation. Using immunohistochemistry, we found that OGT is up-regulated in the protein level in prostate cancer (n=1987) and its expression correlates with high Gleason Score, pT and pN stages and biochemical recurrence (for all, p<0.0001). Both a small molecule inhibitor and siRNAs targeting OGT decreased prostate cancer cell growth. Microarray profiling revealed that the principal effects of the OGT inhibitor in prostate cancer cells are on cell cycle progression and DNA replication. We identified MYC as a candidate upstream regulator of these genes and found that OGT inhibitor caused a dose-dependent loss of c-MYC protein but not mRNA in cell lines. Finally, we observed a statistically significant co-expression between c-MYC and OGT in human prostate cancer samples (n=1306, p=0.0012).

overall_design: Total RNA was extracted and experiment has three biological replicates for each condition, conditions are: 12 hours ST045849, 24 hours ST045849, 12 hours vehicle, 24 hours vehicle, 12 hours siOGT, 24 hours siOGT, 12 hours scrambled, 24 hours scrambled

first: Harri

last: Itkonen

first: Sarah

last: Minner

first: Ingrid

last: Guldvik

first: Mareike

last: Sandman

first: Maria

last: Tsourlakis

first: Viktor

last: Berge

first: Aud

last: Svinland

first: Thorsten

last: Schlomm


title: HOTAIR reprograms gene expression profiling in esophageal squamous cell carcinoma (ESCC) KYSE180 cells

status: Public on Jun 05 2013

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: To investigate the functional role of HOTAIR in esophageal squanmous cell carcinoma (ESCC) cells, RNAi-mediated knockdown of HOTAIR and overexpression of HOTAIR were carried out using KYSE180 cells. Gene expression microarray analysis revealed that a number of reported HOTAIR target genes were regulated by HOTAIR. Moreover, gene ontology analysis revealed enrichment of genes closely related to tumorigenesis, such as cell migration, regulation of cell cycles.

overall_design: For RNAi-mediated knockdown of HOTAIR, two different stealth siRNAs against HOTAIR were generated by Invitrogen, after which a mixture of the two was used for transfection. KYSE180 cells in 6-well plates were transfected with 100 pmol of Stealth siRNA (Invitrogen) or a Stealth RNAi Negative Control Medium GC (Invitrogen) using Lipofectamine2000 (Invitrogen). For HOTAIR overexpression, KYSE180 cells were transfected with LZRS_HOTAIR vector using Polyfect Transfection Reagent (Qiagen). Total RNA was extracted 48 h after transfection.

first: X

last: Li

first: W


title: Protein Tyrosine Phosphatase UBASH3B is Overexpressed in Triple-Negative Breast Cancer and Promotes Invasion and Metastasis

city: Singapore

first: Peiyong

last: Guan

address: 60 Biopolis Street, Genome, #02-01

country: Singapore

institute: Genome Institute of Singapore

summary: Efforts to improve the clinical outcome of highly aggressive triple-negative breast cancer (TNBC) have been hindered by the lack of effective targeted therapies. Thus, it is important to identify the specific gene targets/pathways driving the invasive phenotype to develop more effective therapeutics. Here we show that ubiquitin-associated and SH3 domain-containing B (UBASH3B), a protein tyrosine phosphatase, is overexpressed in TNBC, where it supports malignant growth, invasion, and metastasis largely through modulating epidermal growth factor receptor (EGFR). We also show that UBASH3B is a functional target of anti-invasive microRNA200a (miR200a) that is down-regulated in TNBC. Importantly, the oncogenic potential of UBASH3B is dependent on its tyrosine phosphatase activity, which targets CBL ubiquitin ligase for dephosphorylation and inactivation, leading to EGFR up-regulation. Thus, UBASH3B may function as a crucial node in bridging multiple invasion-promoting pathways, thereby providing a potential therapeutic target for TNBC.

overall_design: Breast cancer tissues and breast cancer cell lines

first: Shuet

middle: T

last: Lee

first: Min

last: Feng

first: Yong

last: Wei

first: Chew

last: Wong

first: Yuanyuan

last: Qiao

first: Zhimei

first: Jinhua

last: Wang

first: Xia

last: Jiang

first: K

last: Karuturi

first: Ern

last: Tan

first: Dave

last: Hoon

first: Yibin

last: Kang

first: Qiang

last: Yu

first: Juntao

first: Kelly

last: Huynh


title: Genome-wide transcriptome comparison between primary cultures of human dermal microvascular endothelial cells and infantile hemangioma endothelial cells

first: Brad

last: Bryan

summary: Whole transcriptome comparisons of proliferating pure cultures of neonatal dermal microvacsular endothelial cells to infantile hemangioma endothelial cells.

overall_design: The total RNA was obtained from human dermal microvascular endothelial cells and infantile hemangioma endothelial cells.  Illumina microarrays were performed to determine the whole genome expression differences between the cell lines.

first: Dianne

last: Mitchell


title: Genome-wide analysis of NPC_astrocytes and Olig2PC_astrocytes  gene expression

city: Houston

first: Ying

last: Liu

address: 1825 Pressler

institute: UTHealth

summary: Analysis of the differences between NPC derived astrocytes and Olig2PC derived astrocytes at gene expression level. Olig2PC-Astros show differences in functions and gene expression profiles from NPC-Astros in vitro, providing clues of superior neuroprotection effect of Olig2PC-astrocytes.

overall_design: Total RNA obtained from cultured NPC_astrocytes and Olig2PC_astrocytes. One hundred ng total RNA was used for amplification and hybridization to Illumina Human HT12_V4 chip according to the Manufacturer's instructions (Illumina). Array data were processed using Illumina GenomeStudio software (Illumina). Background was subtracted and arrays were normalized using quantile. Gene expression levels were considered significant only when their detection p-value ≤0.01.

first: Liu

last: Ying

first: Deng

last: Wenbin


title: Inhibition of dihydroorotate dehydrogenase by doxorubicin and brequinar sensitize cancer cells to TRAIL-induced apoptosis

city: Turku

first: Tao

last: He

address: Itäinen Pitkäkatu 4C

institute: VTT

summary: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent in selectively killing tumor cells. However, TRAIL monotherapy has not been successful as many cancer cells are resistant to TRAIL. Chemotherapeutic agents, such as doxorubicin have been shown to act synergistically with TRAIL, but the exact mechanisms of actions are poorly understood. In this study, we performed high-throughput small interfering RNA screening and genome-wide gene expression profiling on doxorubicin-treated U1690 cells to explore novel mechanisms underlying doxorubicin-TRAIL synergy. The screening and expression profiling results were integrated and dihydroorotate dehydrogenase (DHODH) was identified as a potential candidate. DHODH is the rate-limiting enzyme in the pyrimidine synthesis pathway, and its expression was downregulated by doxorubicin. We demonstrated that silencing of DHODH or inhibition of DHODH activity by brequinar dramatically increased the sensitivity of U1690 cells to TRAIL-induced apoptosis both in 2D and 3D cultures, and was accompanied by downregulation of c-FLIPL as well as by mitochondrial depolarization. In addition, uridine, an end product of the pyrimidine synthesis pathway was able to rescue the sensitization effects initiated by both brequinar and doxorubicin. Furthermore, several other cancer cell lines, LNCaP, MCF-7 and HT-29 were also shown to be sensitized to TRAIL by brequinar. Taken together, our findings have identified a novel protein target and its inhibitor, brequinar, as a potential agent in TRAIL-based combinatorial cancer therapy and highlighted for the first time the importance of mitochondrial DHODH enzyme and pyrimidine pathway in mediating TRAIL sensitization in cancer cells.

overall_design: Total RNA obtained from small cell lung cancer U1690 cells either treated with DMSO control or 1 µM doxorubicin for 12 or 24h.

first: Saija

last: Haapa-Paananen

first: Pekka

last: Kohonen

first: Merja

last: Perälä


title: ERG is a critical regulator of Wnt/LEF1 signaling in prostate cancer

status: Public on May 29 2013

city: Chicago

first: Longtao

last: WU

state: IL

address: 303 E Superior St.

department: Hematology/Oncology

institute: Northwestern University

summary: Chromosomal translocations juxtaposing the androgen-responsive TMPRSS2 promoter with the ETS-family transcription factor ERG result in aberrant ERG up-regulation in approximately 50% of prostate cancers.  Studies to date have demonstrated important roles of ERG in inducing oncogenic properties of prostate cancer.  Its molecular mechanisms of action, however, are yet to be fully understood.  To address these questions, we generated engineered LNCaP cells with ERG overexpression followed by LEF1 knockdown as well as control cell lines. To further investigate the role of LEF1 in ERG fusion positive samples, we also knockdown ERG in VCaP cell line.

overall_design: We performed microarray analysis on LNCaP cells with ERG overexpression followed by LEF1 knockdown using siRNA. We also knockdown endogenous ERG in fusion-positive cell line VCaP.

first: Jindan

last: YU


title: Cohesin is required for expression of the estrogen receptor-alpha (ESR1) gene

status: Public on May 20 2013

city: Goettingen

first: Frank

last: Kramer

address: Humboldtallee 32

department: Department of Medical Statistics

institute: University Medical Center Göttingen

summary: In this study we show that depletion of the cohesin subunit SMC3 or the Mediator subunit MED12 significantly impairs the ERα-regulated transcriptome. Surprisingly, SMC3 depletion appears to elicit this effect indirectly by rapidly decreasing ESR1 transcription and ERα protein levels. Moreover, we provide evidence that both SMC3 and MED12 colocalize on the ESR1 gene and are mutually required for occupancy as well as for transcriptional elongation. Finally, we show that extended proteasome inhibition decreases the mRNA expression of cohesin subunits which accompanies a decrease in ESR1 mRNA and ERα protein levels as well as estrogen-regulated transcription. Conclusions: These results identify the ESR1 gene as a cohesin/Mediator-dependent gene and indicate that this regulation may potentially be exploited for the treatment of estrogen-dependent breast cancer.

overall_design: This set contains 18 microarray samples with triplicates for each condition. 3 control siRNA, 3 control estrogen stimulated, 3 siRNA Med12 knockdown, 3 siRNA Med12 knockdown estrogen stimulated, 3 siRNA Smc3 knockdown, 3 siRNA Smc3 knockdown estrogen stimulated.

first: Tanja

last: Prenzel

first: Upasana

last: Bedi

first: Sankari

last: Nagarajan

first: Tim

last: Beissbarth

first: Steven

last: Johnsen


title: Expression and functional pathway analysis of nuclear receptor NR2F2 in Ovarian cancer

city: Indianapolis

first: Shannon

last: Hawkins

state: IN

address: 550 N University Blvd UH2440

institute: Indiana University School of Medicine

summary: Analysis of NR2F2 knockdown at whole genome level

overall_design: Total RNA isolated 48 hours after NR2F2 knockdown with siRNA compared to siRNA with non-targeting control

first: Matthew

last: Anderson


title: Genome-wide analysis of the affect of neutrophil-derived microparticles on HUVECs

status: Public on May 22 2013

city: London

first: Trinidad

last: Montero

address: Charterhouse Square

department: Biochemical Pharmacology

institute: Whilliam Harvey Research Institute, Bart's and The London School of Medicine; Queen Mary University of London

summary: Analysis of the role of neutrophil-derived microparticles (MP) on gene expression modulation on HUVECs. This study shows that MP can influence gene expression on target cells, demonstrating that these MP are functional entities.

overall_design: Total RNA obtained from HUVECs treated with two different subsets of MP: suspension MP or Adherent MP and vehicle control.

first: Jesmond

last: Dalli

last: Montero-Melendez

first: Mauro

last: Perretti


title: Adenovirus E1A oncogene induces re-replication of cellular DNA and alters DNA replication dynamics

first: Ghata

last: Singhal

state: Illinois

address: 303 E Chicago Avenue

department: Microbiology-Immunology

summary: Human adenovirus type 5 oncogene E1A was shown to induce massive re-replication of cellular DNA in late S phase.  Using DNA combing analysis, it was shown that DNA replication dynamics including replicon length, fork velocity and inter-origin distance were dramatically altered in E1A expressing cells as compared to that of normal serum stimulated cells.  It was also shown that c-Myc that is induced in E1A expressing cells is essential for the efficient entry of E1A expressing cells into S phase.

overall_design: Serum starved cells were infected with an adenovirus expressing only the transforming E1A protein, and with Adbeta-galactosidase (control) were analyzed by flow cytomery.  DNA prepared from such cells were analyzed by DNA combing analysis and data obtained were examined statistically.  Requirement of Myc in E1A induced S phase entry was also examined by using antisense Myc vector.

first: Elizabetta

last: Leo

first: Saayi

last: Krushna

first: Gadham

last: Setty

first: Yves

last: Pommier

first: Bayar

last: Thimmapaya


title: Prostate-specific Pten deletion and Pten-Lrf deletion

status: Public on May 19 2013

first: Guocan

last: Wang

state: TX

address: 1515 Holcombe Blvd, T7.3900

institute: MD Anderson Cancer Center

summary: We used microarrays to analyze the global gene expression and identified differentially expressed gene list between wild-type anterior prostates and Pb-Cre4;PtenLoxP/LoxP anterior prostates, Pb-Cre4;PtenLoxP/LoxP;LrfLoxP/LoxP anterior prostates at 12 weeks of age.

overall_design: Prostate-specific Pten deletion (Pb-Cre4;PtenLoxP/LoxP) results in prostate intraepithelial neoplasia (PIN) which, following a long latency, can progress to high-grade adenocarcinoma, albeit with minimally invasive and metastatic features. However, inactivation of Lrf in the prostate epithelium in combination of Pten results in aggressive prostate tumors. To understand the molecular mechanisms by which loss of Lrf promotes Pten-loss-driven prostate tumorigenesis, we conducted transcriptome comparison of three wild-type anterior prostates, three Pb-Cre4;PtenLoxP/LoxP PIN, and three Pb-Cre4;PtenLoxP/LoxP;LrfLoxP/LoxP anterior prostate tumors.

first: Jianwen

last: Zhang


title: Gene expression profile in offspring born before vs. after maternal bariatric surgery

status: Public on May 16 2013

city: Quebec

first: Frederic

last: Guenard

address: 2440, Hochelage blvd

institute: Laval University

summary: Evaluate differences in gene expression levels between offspring born after maternal bariatric surgery and their siblings born before surgery

overall_design: Offspring born after maternal bariatric surgery (AMS, N=23) vs. offspring born before maternal surgery (BMS, N=23)

first: Frédéric

last: Guénard

last: Deshaies

first: Katherine

last: Cianflone

first: John

middle: G

last: Kral

first: Picard

last: Marceau

first: Marie-Claude

last: Vohl


title: Genome-wide analysis of the effects of the rs4919510C>G genotypes on the miRNA-608 target genes expression

status: Public on May 15 2013

city: Suzhou

first: Li

last: Wei

state: Jiangsu

address: 199# ren’ai road

department: Medical College of Soochow University

institute: soochow university

summary: Analysis of the effects of the rs4919510C>G SNP on miRNA-608 target gene expression. The hypothesis tested in the present study was that the rs4919510C>G SNP may influence the expression of miRNA-608 target genes. Results provide important information of the effects of the rs4919510C>G SNP on miRNA-608 target genes, including immunity and defense genes, DNA repair genes, cell growth-related genes, tumor invasion and metastasis-related genes, cancer stem cell-related genes, and cell death-related genes.

overall_design: Total RNA was extracted from the cultured cells in both experimental (CNE-1-miRNA-608-C and CNE-1-miRNA-608-G) and control (CNE-1-empty vector) groups.

first: Yifeng

last: Zhou

first: Jian

last: Zheng


title: Apelin/APJ signaling mediated by G alpha 13 and MEF2 in endothelial cells

status: Public on May 11 2013

city: New Haven

first: hyung

last: chun

state: CT

address: 300 George St Room 770H

department: Internal Medicine

institute: Yale University

summary: Evaluation of gene transcripts that are downstream of apelin/APJ signaling in HUVECs

overall_design: Duplicates per group, subjected to: 1) control siRNA, 2) MEF2A and MEF2C siRNA, 3) G alpha 13 siRNA, and 4) apelin and APJ siRNA

first: Hyung

last: Chun


title: Gene expression profile of ETV1 knockdown in LNCaP prostate cancer cells

status: Public on May 10 2013

city: New York

first: Yu

last: Chen

state: NY

address: 1275 York Ave, Box 20

department: Human Oncology and Pathogenesis Program

institute: Memorial Sloan Kettering Cancer Center

summary: Over half of prostate cancer harbor overexpression of ETS transcription factors including ERG and ETV1. LNCaP prostate cancer cells have an ETV1 translocation to the MIPOL1 locus on 14q13.3-13q21.1. To determine genes regulated by ETV1, we performed shRNA mediated knockdown of ETV1 using two lentiviral constructs as well as a scrambled shRNA in triplicate. Two pLKO.1 constructs against ETV1 (ETV1sh1: TRCN0000013923, targeting GTGGGAGTAATCTAAACATTT in 3'(B UTR; and ETV1sh2: TRCN0000013925, targeting CGACCCAGTGTATGAACACAA in exon 7) were purchased from Open Biosystems and pLKO.1 shScr (targeting CCTAAGGTTAAGTCGCCCTCG) was purchased from Addgene.  RNA was harvested 3 days after infection and gene expression profiling was performed. Among genes downregulated were many well characterized androgen regulated genes.

overall_design: LNCaP cells logarthmically growing in full serum was infected with three different shRNA lentiviruses. Three days after infection

first: Charles

last: Sawyers


title: Analysis for expression of genes in multiple myeloma cells treated with PRIMA-1Met or dimethyl sulfoxide (DMSO) control

status: Public on May 04 2013

city: Toronto

first: Hong

last: Chang

address: 200 Elizabeth St.

institute: University Health Network

summary: Targeting p53 by the small molecule PRIMA-1Met/APR-246 has shown promising preclinical activity in various cancer types. However, the mechanism of PRIMA-1Met-induced apoptosis is not completely understood and its effect on multiple myeloma (MM) cells is unknown. In this study we evaluated anti-tumor effect of PRIMA-1Met alone or combined with current anti-myeloma agents in MM cell lines, patient samples, and a mouse xenograft model. Results of our study showed that PRIMA-1Met decreased the viability of MM cells irrespective of p53 status with limited cytotoxicity toward normal hematopoietic cells. PRIMA-1Met restored wild type conformation of mutant p53 and induced activation of p73 up-regulating Noxa and down-regulating Mcl-1 without significant modulation of p53 level. Importantly, PRIMA-1Met delayed tumor growth and prolonged survival of mice bearing MM tumor.  To identify the potential targets of PRIMA-1Met, we performed gene expression profiling (GEP) by microarray in three different cell lines harboring wild type, mutant or null p53 and analysed differential expression of target genes between PRIMA-1Met treated and non-treated samples. Based on our we conclude that treatment of MM cells with PRIMA-1Met lead to induction of p73-mediated apoptosis by up-regulating Noxa and down-regulating Mcl-1 irrespective of p53 status.

overall_design: MM.1S, U266, and 8266R5 cells were treated with 20, 40, and 40 µM PRIMA-1Met, respectively for 8 hrs and total RNA was isolated. Gene expression was analyzed with Illumina RNA analysis Beadchips (Illumina Inc. San Diego, CA) representing 48,000 human genes (Human HT12). Array data analysis was carried out with Bead Studio software. Genes showing at least a 2.0-fold difference in expression levels between control and PRIMA-1Met-treated cells were considered to be modulated by PRIMA-1Met.

first: Manujendra

middle: N

last: Saha


title: MicroArray Gene Expression Profiling of NKX2.1-GFP+ MGE-like Interneuron Precursors Derived from Human Embryonic Stem Cells

status: Public on May 03 2013

city: San Francisco

first: Cory

middle: R

last: Nicholas

state: CA

address: 35 Medical center way

department: Neurology

institute: UCSF

summary:
Human embryonic stem cells with a GFP reporter knock-in into the NKX2.1 locus were differentiated and purified by FACS sorting for global gene expression analysis.
Directed differentiation from human pluripotent stem cells (hPSCs) has seen significant progress in recent years. Most differentiated populations, however, exhibit immature properties of an early embryonic stage, raising concerns about their ability to model and treat disease.  Here, we report the directed differentiation of hPSCs into medial ganglionic eminence (MGE)-like progenitors and their maturation into forebrain type interneurons.  We find that early stage progenitors progress via a radial glial-like stem cell enriched in the human fetal brain.  Both in vitro and post-transplantation into the rodent cortex, the MGE-like cells develop into GABAergic interneuron subtypes with mature physiological properties along a prolonged intrinsic timeline of up to seven months, mimicking endogenous human neural development.  MGE-derived cortical interneuron deficiencies are implicated in a broad range of neurodevelopmental and degenerative disorders, highlighting the importance of these results for modeling human neural development and disease.

overall_design: Human embryonic stem cells with a GFP reporter knock-in into the NKX2.1 locus were differentiated for 20, 35, and 55 days in vitro and GFP+ cells were purified by FACS sorting.  Total RNA was prepared from each timepoint and compared to undifferentiated human embryonic stem cells.  hESC = one sample and three technical replicates.  D20 = three independent samples.  D35 = one sample and two technical replicates.  D55 = one sample and one technical replicate.

first: Jiadong

first: Arnold

last: Kriegstein

first: Arturo

last: Alvarez-Buylla

last: Rubenstein


title: Post-transcriptional regulation by Alu within mRNA

status: Public on May 13 2013

city: Taipei

first: Kung-Hao

last: Liang

address: Tung Hwa North Road

country: Taiwan

institute: Chang Gung Memorial Hospital

summary: An extrachromosomal replication system was established to examine the perturbation of Alu-carrying genes in response to elevated Alu RNAs in the opposite direction. The null hypothesis is that the Alu-carrying RNA duplex cannot trigger subsequent post-transcriptional regulation, manifesting a random perturbation of expression levels.

overall_design: Comparing HEK293 cells transfected and not-transfected with pDR2-Alu vectors.

first: Kung

first: Chau

last: Yeh


title: Expression data from human response to invasive pneumococcal disease.

status: Public on May 23 2013

city: Liverpool

first: Benard

last: Kulohoma

address: Department of Women's and Children's Health, Institute of Translational Medicine, Alder Hey Children's Hospital

institute: University of Liverpool

summary: There is differential expression of genes between cases and controls using microarray analysis, and genes that are crucial for host defence responses are significantly up-regulated in cases during pneumococcal infection.

overall_design: Affymetrix microarray technology was used to compare the levels of mRNA between cases and controls and to evaluate whether  this is influenced by underlying HIV cormobidity, and if association with different disease outcomes (death vs. survival) exists.

first: Enitan

last: Caroll


title: Human embryonic stem cells derived by somatic cell nuclear transfer

city: Beaverton

first: Shoukhrat

last: Mitalipov

address: 505 N.W. 185th Avenue

institute: Oregon National Primate Research Center

summary:
In this study, we derived human embryonic stem cell via SCNT.
Transcriptional analysis was performed to compare characteristics of SCNT-derived ESCs to their IVF counterpart.

overall_design: The transcriptomes of human embryonic stem cells (hESO-NT1) derived from human skin fibroblasts (HDF-f) via somatic cell nuclear transfer (SCNT) was compared with IVF-derived counterpart (hESO-7) derived using oocytes from identical donor and parental skin fibroblast (HDF-f). . Three biological replicates of each cell line (A, B, C) were analyzed.

first: Masahito

last: Tachibana

first: Paula

last: Amato

last: Ma

first: Hathaitip

last: Sritanaudomchai


title: cDNA microarray data after influenza A virus infection in nasal epithelial cells

status: Public on May 02 2013

city: Seoul

first: Hyun Jik

last: Kim

address: 101 Daehak-ro, Jongno-gu

department: Department of otorhinolaryngology

institute: Seoul National University

summary: A comparative gene expression analysis was performed using cDNA microarray technology in passage-2 normal human nasal epithelial cells to identify the differentially expressed genes between influenza A virus infected and uninfected cells.

overall_design: Two samples were analyzed. RNA was extracted from normal human nasal epithelial cells, which were further divided as H1N1 PI 0 day and H1N1 PI 2 day (influenza A virus infection for 48 hr).

first: H

middle: J

first: J

last: Yoon