title: Downstream Signaling Modeling of Cancer Signaling Pathways Enables Systematic Drug Respositioning for Subtypes of Breast Cancer Metastases

first: Guangxu

last: Jin

address: 6670 Bertner Ave

institute: The Methodist Hospital Research Institute

summary: Gene Expression Profiling of Breast Cancer Patients with Brain Metastases  Brain metastases confer the worst prognosis of breast cancer as no therapy exists that prevents or eliminates the cancer from spreading to the brain. We developed a new computational modeling method to derive specific downstream signaling pathways that reveal unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available gene expression data of patients. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed the specific CSBs for each metastasis that satisfy that (1) CSB proteins are activated by the maximal number of enriched signaling pathways specific to this metastasis, and (2) CSB proteins involve in the most differential expressed coding-genes specific to the specific breast cancer metastasis. The identified signaling networks for the three types of metastases contain 31, 15, and 18 proteins, respectively, and are used to reposition 15, 9, and 2 drug candidates for the brain, lung, and bone metastases of breast cancer. We performed in vitro and in vivo preclinical experiments as well as analysis on patient tumor specimens to evaluate the targets and repositioned drugs. Two known drugs, Sunitinib (FDA approved for renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor) and Dasatinib (FDA approved for chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia), were shown to prohibit the metastatic colonization in brain.

overall_design: The TMH-52 cohort includes 11 patients who were examined with brain metastasis at the time of breast cancer diagnosis. The other 41 patients were examined with other organ metastasis at the time of breast cancer diagnosis.

first: Hong

last: Zhao

first: Kemi

last: Cui

first: Ding

last: Ren

first: Fuhai

last: Li

first: Yubo

last: Fan

first: Angel

last: Rodriguez

first: Jenny

last: Chang

first: Stephen

last: Wong


title: Variable D. melanogaster Y chromosomes into the genetic background JIL-1/+, Mod(mdg4)/+, and Su(var)205/+.

status: Public on May 01 2013

city: Boston

first: Alan

last: Branco

address: 665 Huntington Ave.

department: Environmental Health

country: USA

institute: Harvard School of Public Health

summary: Fly strains were obtained from the Bloomington Stock Center. The chromosomes containing the gene deletion mod(mdg4)L3101 {y[1] w[1118]; P{w[+mC]=lacW}mod(mdg4)[L3101]/TM3, Ser[1]}, HP1 {In(1)w[m4h]; Su(var)205[5]/In(2L)Cy,In(2R)Cy, Cy[1]}, mod(mdg4)G16853 {w[1118]; P{w[+mC]=EP}mod(mdg4)[G16853]/TM6C, Sb[1]}, and Jil-1Scim {y[1]; P{y[+mDint2] w[BR.E.BR]=SUPor-P}JIL-1[Scim] ry[506]} were introgressed into the genetic background y[1]; bw[1]; e[4]; ci[1] ey[R] to generate the strains Mod(mdg4)/+, Su(var)205/+ and JIL-1/+. All females used in the introgression were collected within 7 hours after eclosion. For gene expression analyses, flies were grown in incubators at 25°C, 65% of relative humidity, and constant light. Newly emerged male adults flies harboring the mutations and the Y chromosomes Yohio and Ycongo(Mod(mdg4)/+;Yohio and Mod(mdg4)/+;Ycongo, Su(var)205/+;Yohio and Su(var)205/+;Ycongo, and JIL-1/+;Yohio and JIL-1/+;Ycongo) were collected and aged for 2 days at the same rearing condition before they were flash-frozen in liquid nitrogen. Four replicas of each sample were collected and stored at -80°C. Total RNA was extracted from whole flies using TRIzol (Life Technologies). The synthesis of cDNA and its labeling with fluorescent dyes (Cy3 and Cy5) as well as hybridization reactions were carried out using 3DNA protocols and reagents (Genisphere). The genetic interaction of the Y chromosome and the mutation was studied by the following contrasts: 1) male flies Mod(mdg4)/+;Yohio versus male flies Mod(mdg4)/+;Ycongo; 2) male flies Su(var)205/+;Yohio versus male flies Su(var)205/+;Ycongo; 3) male flies JIL-1/+;Yohio versus male flies JIL-1/+;Ycongo). As reference we used the same genetic background without the mutations [+/+;Ycongo (background 2) and +/+;Yohio (background 2)]. Slides were scanned using Axon 400B scanner (Axon Instruments) and GenePix Pro 6.0 software. Foreground fluorescence of dye intensities was normalized by the Loess method in Bioconductor / Limma.

overall_design: Dye "swaps," loop design.

middle: T

first: Bernardo

last: Lemos


title: Expression profile of the endocrine therapy sensitive breast cancer cells MCF7 depleted of PBX1

city: Lebanon

first: luca

last: magnani

state: NH

address: NCCC one medical drive

department: Genetics

institute: Dartmouth College

summary: Effect of PBX1 silencing on global gene expression of MCF7 cells stimulated with EGF. The hypothesis tested was that PBX1 is essential for EGF signaling in ERa positive breast cancer cells.

overall_design: Total RNA was obtained from MCF7 cells treated with siRNA directed at PBX1 or an siControl for 72h. Cells were then stimulated with estradiol (EGF) for 3h prior to RNA extraction.

first: Luca

last: Magnani

first: Mathieu

last: Lupien


title: Human melanoma samples comparing nevi and primary and metastatic melanoma

city: Houston

first: Lawrence

middle: N

last: Kwong

state: TX

address: 1901 East Rd

institute: UT MD Anderson Cancer Center

summary: We sought to identify genes and gene signatures which correlate with progression by sampling human melanomas from nevi, primary, and metastatic tumors. The large number of samples also permits analysis within groups.

overall_design: Human melanoma samples were isolated from historical frozen patient specimens. RNA was extracted and run on the human Affymetrix U133A microarray chip.

first: Kwong

last: Lawrence

first: Kabbarah

last: Omar

first: Noguiera

last: Cristina

first: Wagner

last: Stephan

first: Chin

last: Lynda


title: Expression profile of the  endocrine therapy resistant breast cancer cells LTED depleted of PBX1 or treated with the gamma-secretase inhibitor MRK003

summary: Analysis of the response to PBX1 deprivation either using an siRNA approach or using a chemicalcompound indirectly targeting it. Deprivation of PBX1 is hypothesized to be essential for the growth of endocrine therapy resistant breast cancer cells (LTED)

overall_design: Total RNA was obtained from cells treated with siPBX1 or a control siRNA. The second set contains RNA from cells treated with MRK003 or a control (DMSO).


title: Estrogen-Related Receptor γ (ERRγ) Regulates Oxygen-Dependent Expression of Voltage-gated Potassium (K+) Channels and Tissue Kallikrein during Human Trophoblast Differentiation

status: Public on Apr 30 2013

first: Scott

middle: Andrew

last: Ochsner

address: One Baylor Plaza

department: Molecular and Cellular Biology

institute: Baylor College of Medicine

summary: Estrogen-related receptor γ (ERRγ) serves a critical O2-dependent regulatory role in differentiation of human cytotrophoblasts to syncytiotrophoblast. In this study, we investigated expression of genes encoding tissue kallikreins (KLK1) and voltage-gated K+ channels (KV7) during differentiation of human trophoblasts in culture and the roles of ERRγ and O2 tension in their regulation. Expression of KLK1 and the KV7 channel subunits, KCNQ1, KCNE1, KCNE3, KCNE5, increased during differentiation of cultured human trophoblast cells in a 20% O2 environment. Notably, together with ERRγ, expression of KLK1, KCNQ1, KCNE1, KCNE3 and KCNE5 was markedly reduced when cells were cultured in a hypoxic environment (2% O2). Moreover, upon transduction of trophoblast cells with shRNAs for endogenous ERRγ, KLK1, KCNQ1, KCNE1 and KCNE3 expression was significantly decreased. Promoter and site-directed mutagenesis studies in transfected cells identified putative ERRγ response elements (ERREs) within the KLK1 and KCNE1 5'-flanking regions required for ERRγ -stimulated transcriptional activity. Binding of endogenous ERRγ to these ERREs increased during trophoblast differentiation in culture and was inhibited by hypoxia. The KV7 blocker linopirdine reduced hCG secretion and aggregation of cultured human trophoblasts, suggesting a possible role of KV7 channels in cell fusion and differentiation. Illumina gene expression arrays of cultured human trophoblast cells revealed several genes upregulated during syncytiotrophoblast differentiation and downregulated upon ERRγ knockdown involved in cell differentiation, adhesion, and synthesis of steroid and peptide hormones required for placental development and function. Collectively, these findings suggest that ERRγ mediates O2-dependent expression of genes involved in human trophoblast differentiation, function and vascular homeostasis.

overall_design: Illumina whole genome gene expression array analysis was performed on human trophoblasts before culture, or 72 h after infection with recombinant lentiviruses expressing ERRγ shRNA, or a control, nonsilencing shRNA. RNA from three independent experiments using placental tissues from three abortuses was extracted by miRNeasy® Mini Kit (Qiagen, Maryland, USA). RNA was labeled and hybridized to an Illumina HumanHT-12 v4 BeadChip, according to the manufacturer’s protocol.

first: Yanmin

last: Luo

first: Premlata

last: Kumar

first: Carole

middle: R

last: Mendelson


title: Expression data from myelo-dendritic progenitors as well as from mature myeloid and dendritic cells

status: Public on Apr 27 2013

city: Berlin

first: Marie

last: Gebhardt

address: Robert-Rössle-Str. 10

department: Cancer

country: Germany

institute: Max-Delbrück-Center for Molecular Medicine

summary: Dendritic cells (DCs) are essential regulators of immune responses; however, transcriptional mechanisms establishing DC lineage commitment are poorly defined. Here we report that the PU.1 transcription factor induces specific remodeling of the higher-order chromatin structure at the Interferon Regulatory Factor-8 (Irf8) gene to initiate DC fate choice. Generation of an Irf8 reporter mouse enabled us to pinpoint an initial progenitor stage at which DCs separate from other myeloid lineages in the bone marrow. In the absence of Irf8, this progenitor undergoes DC-to-neutrophil reprogramming, indicating that DC commitment requires an active, Irf8-dependent escape from alternative myeloid lineage potential. Mechanistically, myeloid Irf8 expression depends on high PU.1 levels, resulting in local chromosomal looping and activation of a lineage- and developmental stage-specific cis-enhancer. These data delineate PU.1 as a concentration-dependent rheostat of myeloid lineage selection by controlling long-distance contacts between regulatory elements, and suggest that specific higher-order chromatin remodeling at the Irf8 gene determines DC differentiation.

overall_design: Mature macrophages, Granulocytes and DCs were isolated from wildtype mouse spleens for successive RNA extraction and hybridization on Affymetrix microarrays. 3 different pools, each consisting of splenic cells from 5 mice were prepared. Cell populations were isolated by flow cytometry. MDPs were isolated from Wildtype and IRF8 deficient bonemarrow by flowcytometry, again creating 3 biological replicates, each consisting of pooled cells from 5 mice. Differential gene expression between wildtype and IRF8 deficient MDPs was subgrouped into macrophage, granuloctic and DC signatures, derived from expression data of these cell populations.

first: Joerg

last: Schoenheit

first: Frank

last: Rosenbauer

first: Miguel

middle: A

last: Andrade-Navarro

middle: L


title: Direct conversion of fibroblasts to neurons by a new mechanism – p53 regulation

status: Public on Apr 26 2013

city: Chengdu

first: chongkui

last: sun

state: Sichuan

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

department: State key laboratory of oral diseases

country: China

institute: Sichuan University

summary: Direct conversion from fibroblast to neuron has recently been successfully induced bypassing the pluripotent state. However, the conversion takes a few months with low percentages of success. Here we found that depletion of p53, which can converted fibroblasts into three major neural lineages: neurons, astrocytes and oligodendrocytes. Furthermore, our method provided a high efficiency of conversion in aging fibroblasts, where published methods failed. This finding may help developing a prototype for neuron replacement therapy, including foraging people vulnerable to neurological disorders.

overall_design: p53 has been shown to inhibit reprogramming of fibroblasts to iPS cells, by depletion of p53 in human fibroblasts, we study the function of p53 in induced neuron process. By induction of p53 knockdown fibroblasts with special neuron medium, we can get mature neurons directly. In the induction process, many neurogenic transcription factors were up-regulated, and we prove that p21 is not involved in this process.

first: Di

last: Zhou

first: Zhen

last: Zhang

first: Liming

last: He

first: Juan

last: Du

first: Fan

first: Chong-kui

last: Sun

first: Yu

first: Ge

last: Lin

first: Keming

last: Song

first: Ling-gang

last: Wu

first: Qin

last: Yang


title: DNA Methylation Dynamics During Lgr5+ Intestinal Stem Cell Differentiation (Affymetrix Arrays)

status: Public on Apr 25 2013

city: Amsterdam

first: Richard

last: Volckmann

state: Noord-Holland

address: van der Boechorststraat 6a

department: Laboratory of Experimental Oncology and Radiobiology

country: Netherlands

institute: msterdam UMC and University of Amsterdam

summary: The identification of Lgr5 as an intestinal stem cell marker has made it possible to isolate and study primary stem cells from small intestine and skins. Applying genome-wide resequencing of bisulfite-treated genomic DNA, we profiled the DNA methylation changes of FACS-sorted Lgr5+ve stem cells and their immediate undifferentiated daughter cells from small intestine and skin. In addition to this, we also analyzed terminally differentiated villus cells. We find that terminal differentiation of an adult solid-tissue stem cell does not require DNA methylation dynamics at transcriptional start sites, but is characterized by hypo-methylation of enhancer-like domains.

overall_design: We used cell fractions of intestines from Lgr5-EGFP-ires-CreERT2 mice, expressing GFP under the control of the Lgr5 promoter. RNA was isolated from several FACS-sorted cell populations, one expressing GFP at high levels (GFPhi) and the other expressing GFP at low levels (GFPlow), both from small intestine and skin. We also isolated RNA from intestinal epithelial villus cells. Differentially labelled cRNA from GFPhi, GFPlow and villus cells from three different sorts (each combining three different mice) were hybridized on Affymetrix HT MG-430 PM arrays.

first: Marc

last: van de Wetering

first: Hans

last: Clevers


title: Implications of time-series gene expression profiles of replicative senescence

status: Public on Apr 24 2013

city: Suwon

first: Hyun Goo

last: Woo

address: 164 Worldcup-ro Yeongtong-gu

country: South Korea

institute: Ajou University School of Medicine

summary: Although senescence has long been implicated in aging-associated pathologies, it is not clearly understood how senescent cells are linked to these diseases. To address this knowledge gap, we profiled cellular senescence phenotypes and mRNA expression patterns during replicative senescence in human diploid fibroblasts. We identified a sequential order of gain-of-senescence phenotypes: low levels of reactive oxygen species, cell mass/size increases with delayed cell growth, high levels of reactive oxygen species with increases in senescence-associated β-galactosidase activity (SA-β-gal), and high levels of SA-β-gal activity. Gene expression profiling revealed four distinct modules in which genes were prominently expressed at certain stages of senescence, allowing us to divide the process into four stages: early, middle, advanced, and very advanced. Interestingly, the gene expression modules governing each stage supported the development of the associated senescence phenotypes. Senescence-associated secretory phenotype-related genes also displayed a stage-specific expression pattern with three unique features during senescence: differential expression of interleukin isoforms, differential expression of interleukins and their receptors, and differential expression of matrix metalloproteinases and their inhibitory proteins.

overall_design: The analysis of time series gene expression level during replicaive senescence.

first: Hyun

middle: G


title: Engineering Bone Tissue Substitutes from Human Induced Pluripotent Stem Cells

city: New York

first: Giuseppe Maria

last: de Peppo

state: NY

address: 3960 Broadway

department: Research and Development

institute: The New York Stem Cell Foundation

summary: Global gene expression data of human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cells before and after culture onto osteoinductive scaffolds in perfusion bioreactors. The hypothesis tested in the present study was that perfusion culture in bioreactors influenced the expression levels of several genes involved in proliferation and osteogenic differentiation. Results provide important information of the response of human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cell to osteogenic stimulation under perfusion cultures, such as genes involved in cell proliferation and division as well as osteogenic differentiation and bone development.

overall_design: Total RNA obtained from human embryonic stem cell-, human induced pluripotent stem cell- and bone marrow-derived mesenchymal progenitor cells before and after culture under osteogenic conditions in perfusion bioreactors for 5 weeks.

first: Gisueppe

middle: M

first: Ivan

last: Campos

first: David

last: Kahler

first: Dana

last: Alsalman

first: Linshan

last: Shang

first: Gordana

last: Vunjak-Novakovic

first: Darja

last: Marolt


title: CD133/CD140a-Based Isolation of Distinct Human Multipotent Neural Progenitor Cells and Oligodendrocyte Progenitor Cells

status: Public on Apr 23 2013

city: Buffalo

first: Fraser

middle: James

last: Sim

address: 3435 Main Street

department: Pharmacology

institute: University at Buffalo

summary: The mechanisms underlying the specification of oligodendrocyte fate from multipotent neural progenitor cells (NPCs) in developing human brain are unknown. In this study, we sought to identify antigens sufficient to distinguish NPCs free from oligodendrocyte progenitor cells (OPCs). We investigated the potential overlap of NPC and OPC antigens using multicolor fluorescence-activated cell sorting (FACS) for CD133/PROM1, A2B5, and CD140a/PDGFaR antigens. Surprisingly, we found that CD133, but not A2B5, was capable of enriching for OLIG2 expression, Sox10 enhancer activity, and oligodendrocyte potential. As a subpopulation of CD133- positive cells expressed CD140a, we asked whether CD133 enriched bone fide NPCs regardless of CD140a expression. We found that CD133+CD140a- cells were highly enriched for neurosphere initiating cells and were multipotent. Importantly, when analyzed immediately following isolation, CD133+CD140a- NPCs lacked the capacity to generate oligodendrocytes. In contrast, CD133+CD140a+ cells were OLIG2-expressing OPCs capable of oligodendrocyte differentiation, but formed neurospheres with lower efficiency and were largely restricted to glial fate. Gene expression analysis further confirmed the stem cell nature of CD133+CD140a- cells. As human CD133+ cells comprised both NPCs and OPCs, CD133 expression alone cannot be considered a specific marker of the stem cell phenotype, but rather comprises a heterogeneous mix of glial restricted as well as multipotent neural precursors. In contrast, CD133/CD140a-based FACS permits the separation of defined progenitor populations and the study of neural stem and oligodendrocyte fate specification in the human brain.

overall_design: 12 samples, 4 groups (FACS-sorted cell populations),3 replicates in each group, each replicate is from a separate patient sample

first: Jing

last: Wang

first: Melanie

last: O'Bara

first: Suyog

middle: U

last: Pol

middle: J


title: Expression data from B6, Sle1b and Sle1b.BACSlamf6-H1 CD4+ T cells

first: Marton

last: Keszei

state: MA

address: 3 Blackfan Cir., CLS building room 928

department: Medicine

institute: Beth Israel Deaconess Medical Center

summary: We recently showed that the Slamf6 protein isoform Slamf6-H1 markedly diminishes T cell–dependent disease upon introduction of a Slamf6-H1–expressing transgene into the lupus-prone Sle1b mouse, which lacks this isoform. In this study we purified CD4+ T cells from Sle1b, Sle1b.Slamf6-H1, or B6 mice and a global gene expression profile was analyzed.

overall_design: Comparison of isolated cells from three strains of mice (12wk old females) at three time points of anti-CD3 activation with three biological replicates for each group (unless indicated otherwise).

first: Cynthia

last: Detre

first: Wilson

last: Castro

first: Cox

last: Terhorst


title: Gene expression profile of TARDBP in hepatocellular carcinoma cell line (SK-Hep1)

status: Public on Apr 22 2013

first: Yun-Yong

last: Park

address: 7435 Fannin St.

department: Systems Biology

institute: UT, MD Anderson Cancer Center

summary: TARDBP is TARDBP (TDP-43) is a DNA/RNA binding protein and was mutated in human amyotrophic lateral sclerosis (ALS). However, its function in human cancer has not been fully identified, yet.Thus, We carried out microarray to investigate the down-stream target genes of TARDBP after silencing TARDBP in liver cancer cell SK-Hep1.

overall_design: To identify the role of TARDBP in hepatocellular carcinoma cell line, we performed microarray after knocking down TARDBP in hepatocellular carcinoma cell line (3 siLuc, 3 siTARDBP)

first: Sang

middle: B

last: Kim

first: Ju-seog

last: Lee


title: Deriving Dopaminergic Neurons for Clinical Use. A Practical Approach.

city: La Jolla

first: Francesca

last: Boscolo

state: CA

address: 9500 Gilman Drive

department: Reproductive Medicine

institute: UCSD

summary: Identification of new small molecules that regulate the step-wise differentiation of hPSC into dopaminergic neurons population.  Furthermore, the naturally occurring steroid, guggulsterone, was found to be the most effective inducer of neural stem cells into dopaminergic neurons.

overall_design: Total RNA extracted at different stages of neural differentiation from human pluripotent stem cells

first: Rodolfo

last: Gonzalez

first: Ibon

last: Garitaonandia

first: Tatiana

last: Abramihina

first: Gerald

middle: K

last: Wambua

first: Alina

last: Ostrowska

first: Mathew

last: Brock

first: Alexander

last: Noskov

middle: S

first: John

last: Craw

first: Louise

middle: C

last: Laurent

first: Evan

last: Snyder

first: Ruslan

last: Semechkin


title: The effect of Neuroserpin expression upon HeLa cell gene expression

status: Public on Apr 20 2013

city: Cambridge

first: Timothy

last: Newton

address: Addenbrooke's Hospital

country: United Kingdom

institute: University of Cambridge

summary: HeLa cells were stably transfected using the Tet-On® Advanced Cell Line system with Wildtype, G392E and Delta Neuroserpin with neuroserpin expression induced with doxycycline.  Gene expression was examined in the absence or presence of 2 ug/ml doxycycline.

overall_design: Four cell lines were analysed:  Untransfected  Parental Cells; and cells transfected with wild type, G392E and Delta Neuroserpin Mutants.  Each cell line had three replicate samples.

first: Benoit

middle: D

last: Roussel

first: Nikol

last: Simecek

first: Stefan

last: Marciniak

first: David

last: Lomas


title: Expression data from untreated and valproic acid (VPA) treated CD34+ Hematopoietic Stem Cells (HSCs)

status: Public on Apr 11 2013

city: Modena

first: Rossella

last: Manfredini

address: Via Gottardi 100

department: Life Sciences

country: Italy

institute: Centre for Regenerative Medicine

summary:
Histone deacetylase (HDAC) inhibitors are widely utilized in hematopoietic malignance therapy; nevertheless, little is currently known concerning their effects on normal myelopoiesis. In order to investigate a putative interference of HDAC inhibitors in myeloid commitment of hematopoietic stem/progenitor cells (HSPCs) we treated CD34+ cells with valproic acid (VPA). Moreover, we investigate changes in gene expression induced by VPA treatment on HSPCs, by means of microarray analysis in VPA treated and untreated (CTR) CD34+ cells.
VPA treatment induced H4 histone acetylation in CD34+ cells and blocked them in G0-G1 phase of cell cycle. CD34 expression is maintained for a longer time in VPA treated cells, while the physiological decrease of CD34 antigen occurred in CTR cells. Moreover, VPA favored erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage lineages, as demonstrated by immunophenotyping, morphological and clonogenic analysis. Finally, we demonstrated that VPA up-regulated master gene regulators of erythrocyte and megakaryocyte differentiation (GFI1B and MLLT3) through histone iper-acetylation of their promoters. These results indicate that VPA treatment enhances erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage one. Microarray data provide for the first time a detailed molecular support for the biological effects promoted by VPA treatment in HSPCs.

overall_design: Human CD34+ cells were purified from umbilical Cord Blood (CB) samples. After an initial 24 hours of incubation, CD34+ cells were exposed to VPA. Total cellular RNA was extracted from untreated (CTR) and VPA treated CD34+ HSCs after 48 hours of treatment.

first: Roberta

last: Zini

first: Ruggiero

last: Norfo

first: Elisa

last: Bianchi

first: Simona

last: Salati

first: Francesco

last: Ferrari

first: Sergio


title: Characterizing gene expression changes that accompany succinate dehydrogenase subunit B (SDHB) RNA editing in monocyte-enriched peripheral blood mononuclear cell cultures

status: Public on Apr 10 2013

first: Biao

last: Liu

address: Elm and Carlton streets

department: Center for Personalized Medicine

institute: Roswell Park Cancer Institute

summary: The goal of this study is to identify global changes in gene expression that accompany induction of site-specific RNA editing that targets the SDHB gene in monocyte-enriched peripheral blood mononuclear cell cultures. The results provide important information to understand the function of this programmed SDHB RNA mutation within the context of global gene expression changes that occur in cultured immune cells when the editing is induced. The study also specifically tests whether expression changes occur in SDH subunit genes, cytidine deaminase family of genes and hypoxia-inducible pathways.

overall_design: Overall design includes pairwise comparison of total gene expression profiles from uncultured cold-aggregated PBMCs (day 0), low-editing (culture day 3) and high-editing (culture days 5-8) samples, each from 4 donors. Submitted manuscript reported summary results from comparison of cultured low- and high-editing samples.

first: Bora

middle: E

last: Baysal

first: Kitty

last: De Jong

first: Jianmin

last: Wang

first: Paul

last: Wallace

first: Robert

last: Taggart


title: Molecular profiles of cognitive aging

status: Public on Apr 19 2013

city: West 168th Street

first: Scott

middle: a

last: Small

institute: Colubmia University

summary: Gene expression was measured from the dentate gyrus and entorhinal cortex harvested from human postmortem samples.

overall_design: We harvested the dentate gyrus DG from healthy human brains ranging from 33 to 88 years of age. Additionally, from each brain we harvested the entorhinal cortex (EC) as a within-brain control. Using Affymetrix microarray chips we generated gene-expression profiles of each individual tissue samples. DG expression levels were first normalized against the EC, and the normalized DG transcripts were then correlated against age. Submitter cannot locate the CEL files.


title: Expression data in response to WRKY40 and WRKY63 knock-out/overexpression (and in response to high light stress)

status: Public on Apr 17 2013

city: Bundoora

first: Reena

last: Narsai

address: 5 Ring road

country: Australia

institute: La trobe University

summary:
In response to WRKY40 and WRKY60 perturbation (and high light stress), significant transcriptional re-programming occurs particularly for genes encoding stress responsive mitochondrial and choloplast proteins.
We used microarrays to analyse the response to WRKY40 and WRKY63 KO/OE in resonse to high light stress.

overall_design: Wild-type (Col0) and transgenic WRKY40 and WRKY60 knock-out/over-expressing Arabidopsis plants were grown to 21-days and leaf samples were collected with/without high light treatment.


title: Baseline expressions in human whole blood

city: Stanford

last: Furman

institute: Stanford University

summary: This study aims at identifying genes whose expression at baseline predicts the immune response to seasonal influenza vaccination. Blood samples were collected from healthy volunteers before their vaccination

overall_design: 91 Samples


title: Androgen receptor-independent function of FoxA1 in prostate cancer metastasis

status: Public on Apr 05 2013

city: Chicago

first: Hong-Jian

last: Jin

state: IL - Illinois

address: 303 E Superior St

institute: Northwestern University

summary: FoxA1 has been shown critical for prostate development and prostate-specific gene expression regulation. In addition to its well-established role as an AR pioneering factor,several studies have recently revealed significant AR binding events in prostate cancer cells with FoxA1 knockdown. Furthermore, the role of FoxA1 itself in prostate cancer has not been carefully examined.  Thus, it is important to understand the role of FoxA1 in prostate cancer and how it interacts with AR signaling. To address these questions, we generated engineered LNCaP cells with  FoxA1 knockdown using shRNA or siRNA, 22RV1 cells with stable FoxA1 knockdown and PC3M cells with FoxA1 stable overexpression.  We performed microarray analysis of these cells.

overall_design: We performed microarray analysis on LNCaP cells with  FoxA1 knockdown using shRNA or siRNA, 22RV1 cells with stable FoxA1 knockdown and PC3M cells with FoxA1 stable overexpression

first: Jindan

last: Yu


title: Expression data from low R:FR - SA crosstalk in Arabidopsis

status: Public on Apr 03 2013

city: Utrecht

first: Ronald

last: Pierik

address: Padualaan 8

department: Plant Ecophysiology

institute: Utrecht University

summary:
Low R:FR signaling through phytochromes induces shade avoidance responses, including petiole elongation. Salicylic acid-mediated defense against pathogens is inhibited under these conditions.
Using microarrays we studied the crosstalk between low R:FR and SA at the global gene expression level in Arabidopsis thaliana.

overall_design: Plants were exposed for 2 h. to the following treatments: high R/FR with mock spray, low R/FR with mock spray, high R/FR with SA spray, low R/FR with SA spray. Gene expression was determined in petioles.

first: Mieke

last: de Wit


title: Gene Expression Profiles Predict Infliximab Treatment Response in Patients with Treatment-Resistant Depression

status: Public on Apr 01 2013

city: Munich

first: Divya

last: Mehta

institute: MPI

summary:
To further explore predictors and targets of response to infliximab, differential gene expression was examined at baseline and after 6 and 24 hours and 2 weeks after the first infusion of infliximab in TRD patients who were infliximab responders versus nonresponders, and compared to placebo-treated patients.
All subjects were administered either infliximab (5mg/kg, n=30) or placebo (n=30) through an indwelling catheter at the Emory Division of Digestive Diseases at 3 separate time points (baseline, 2 weeks and 6 weeks). Infliximab infusion dosing protocol and scheduling were matched to the standard intravenous induction routine for the treatment of inflammatory bowel disease.

overall_design: In a recent clinical trial, the TNF antagonist infliximab was found to reduce depressive symptoms compared to placebo but only in patients with increased inflammation as reflected by a CRP >5 mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined at baseline and after 6 and 24 hours and 2 weeks after the first infusion of infliximab in TRD patients who were infliximab responders versus nonresponders, and compared to placebo-treated patients.

first: D


title: Expression data from Arabidopsis thaliana seedlings with altered enzymes activity of the tetrapyrrole biosynthesis pathway

first: Hagen

last: Schlicke

address: Philippstr. 13, building 12

department: Institute of Biology

institute: Humboldt University Berlin

summary: The CHLD and CHLM genes encode proteins involved in tetrapyrrole biosynthesis pathway. It was proposed that intermediates like magnesium protoporphyrin might play a role in retrograde plastid-to-nucleus signaling. In the present work we provide evidence that altered enzymes activity of the tetrapyrrole biosynthesis pathway are causing changes in gene expression of over 200 nuclear genes.

overall_design: The expression of the CHLD gene was diminished after inducing the RNAi system by spraying dexamethasone. The expression of the CHLM gene was increased after inducing the overexpressor system by spraying ß-estradiol.

first: Bernhard

last: Grimm


title: Impact of delay to cryopreservation on RNA integrity and genome-wide expression profiles in resected tumor samples.

city: LYON

first: FLORENCE

last: LE CALVEZ-KELM

address: 150 Cours Albert Thomas

country: France

institute: International Agency for Research on Cancer

summary: Using Illumina HumanHT-12 v3 Expression BeadChips, providing a genome-wide coverage of over 24,000 genes, we have analysed gene expression variation in samples of 3 hepatocellular carcinomas (HCC) and 3 lung carcinomas (LC) cryopreserved at times up to 2 hours after resection.

overall_design: Total RNA obtained 3 frozen Hepatocellular Carcinomas and 3  Lung Carcinomas cryopreserved at 5 min, 15min, 30min and 120min after resection. Tissue samples from the center and the peripheral of the tumours were frozen for each time point.

first: Elodie

last: Caboux

first: Florence

last: Le Calvez-Kelm


title: The effect of knock-down of neuroblastoma associated lncRNA on transcriptome

city: Taipei

first: Aliaksandr

last: Yarmishyn

address: No. 201, Section 2, Shipai Road, Beitou District

country: Taiwan

institute: Taipei Veterans General Hospital

summary: As part of functional characterization of neuroblastoma associated lncRNA HOXD-AS1, we performed its knock-down in neuroblastoma cell line SH-SY5Y, which resulted in modulation of expression levels of a set of genes involved in angiogenesis and inflammation, the hallmarks of metastatic cancer.

overall_design: SH-SY5Y cells were transfected with non-targeting siRNA control and two siRNAs targeting lncRNA HOXD-AS1. Two days after transfection total RNA was isolated and hybridized to microarray, each sample was done in four replicas.

first: Arsen

middle: O

last: Batagov

first: Igor

middle: V

last: Kurochkin


title: Whole genome microarray of  T lymphoma invasion and metastasis (Tiam1) silenced retinoblastoma Y79 cells

status: Public on Mar 31 2013

city: Bangalore

first: madavan

last: vasudevan

state: Karnataka

address: Kasturi Nagar

country: India

institute: Theomics International Private Limited

summary: We hypothesized that Tiam1 is involved in invassiveness of retinoblastoma. The fuctional role of Tiam1 in cell progression and metastasis was tested by siRNA mediated knockdown of Tiam1 in retinoblastoma Y79 cells. The genes de-regulated in response to Tiam1 knockdown was analysed by cDNA microarray in which most of the actin cytoskeleton regulation proteins and apoptotic proteins were de-regulated. our results prove that Tiam1 modulates actin cytoskeleton and cell invasion in retinoblastoma.

overall_design: Retinoblastoma Y79 cells were treated with Tiam1 siRNA for 48hrs and cDNA microarray was performed to analyze the genes regulated by Tiam1 silencing compared to untreated Y79 cells. Experiments were performed in triplicates.

first: Subramanian

last: Nithya

first: N

last: Saranya

first: Krishnakumar

last: Subramanian


title: Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal T cells via TGF-β

status: Public on Apr 04 2013

city: Dallas

first: Chun

middle: I

address: 3434 Live Oak St

institute: Baylor Institute for Immunology Research

summary: In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-β1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells.

overall_design: Total RNA were isolated from purified human CD1c+ (BDCA1+) and CD141+ (BDCA3+) mDCs sorted from different tissues, including human blood, spleen and lungs of humanized mice, and human lungs. Eighteen samples in total were analyzed from different donors and tissues.

first: Christian

last: Becker

first: Yuanyuan

last: Wang

first: Florentina

last: Marches

first: Julie

last: Helft

first: Marylene

last: Leboeuf

first: Esperanza

last: Anguiano

first: Stephane

last: Pourpe

first: Kristina

last: Goller

first: Virginia

last: Pascual

first: Jacques

last: Banchereau

first: Miriam

last: Merad

first: Karolina

last: Palucka


title: Differential regulation of HSFA1s and HSFA2 after heat shock in Arabidopsis

status: Public on Apr 09 2013

city: Shulin City, Taipei County

first: Hsiang-chin

last: Liu

address: 9F., No.332, Xuefu Rd.

institute: Academia sinica

summary: HSFA1s are a gene family of HSFA1 with four members, HSFA1a, HSFA1b, HSFA1d, and HSFA1e. HSFA1s are the master regulators of heat shock response. As a part of the heat shock response, HSFA2 can prolong the heat shock response and amplify the heat shock response in response to repeat heat shock. To identify the heat-shock-responsive genes differentially regulated by HSFA1s and HSFA2, we compared the transcriptomic differences of plants containing only constitutively expressed HSFA1s or HSFA2 after heat stress.

overall_design: hsfa2 (the KO mutant of HSFA2, Col-0 background) and A2QK-10 (CaMV 35S:HSFA2 in QK mutant; QK is HSFA1a/b/d/e quadruple KO mutant) were used to compare the difference of heat shock response when plants lack HSFA1s or HSFA2. The aim is to find the HSFA1s- and HSFA2-preferred regulating genes after heat stress. As the control samples, wild type is the plant with normal heat shock response, and QK (HSFA1s KO mutant, Col-0 and Ws mixed background) is the plant that lost the heat shock response controlled by HSFA1s.

first: Hsiang

first: Yee

middle: Y

last: Charng


title: microRNA-190-mediated transcriptional changes

status: Public on Mar 29 2013

city: Boston

first: christine

middle: elaine

last: briggs

address: 736 Cambridge Street

department: Center for Cancer Systems Biology

institute: christine briggs

summary: Previously, we showed that miRNA-190 (miR-190) is among the most upregulated miRNAs in all dormant tumors analyzed. Up-regulation of miR-190 led to prolonged tumor dormancy in otherwise fast-growing glioblastomas and osteosarcomas. In this study, we investigated transcriptional changes induced by miR-190 expression in cancer cells and show similar patterns of miR-190-mediated transcriptional reprogramming in both glioblastoma and osteosarcoma cells. The data suggests that miR-190-mediated effects rely on an extensive network of molecular changes in tumor cells and that miR-190 affects several transcriptional factors, tumor suppressor genes and interferon response pathways.

overall_design: For each cancer cell type, gene expression patterns in control cells that express GFP-only were compared to cells over-expressing microRNA-190.

first: Christine

last: Briggs

first: Nava

last: Almog


title: Identification of glucose-TOR signaling early target genes in Arabidopsis seedling autotrophic transition stage

first: Jen

last: Sheen

address: 185 Cambridge st. CPZN7620

department: Molecular Biology

institute: Massachusetts General Hospital

summary: The goal of this experiment was to explore the molecular network of glucose-TOR signaling in Arabidopsis seedling autotrophic transition stage. We used the whole-genome microarrays to detail the global program of gene expression mediated by glucose and TOR.

overall_design: Arabidopsis WT and estradiol inducible RNAi-tor seedlings were germinated in low light condition for 3 days to deplete seed nutrient supply. Fifteen mM glucose was adding back to reactivate the quiescent seedlings and the samples were harvested for RNA isolation.  Transcript profiles were analyzed and compared between with and without glucose treatment to identify early glucose-TOR target genes. Each experimental condition was repeated three times and total 12 samples were generated.

first: Yan

last: Xiong

first: Chengbin

last: Xiang

first: Matthew

last: McCormack


title: Arabidopsis cold regulated transcriptome, translatome and CSP1 RNA regulon

city: Riverside

first: Piyada

last: Juntawong

address: 900 University ave

department: Botany and Plant Sciences

institute: University of California Riverside

summary: Transcriptome, translatome, and CSP1 RNA regulon analysis of 25-d-o Arabidopsis rosettes exposed to 12h low temperature (4C) treatment.

overall_design: 38 samples, 3 genotypes (35S:HF-RPL18, 35S:AtCSP1-FH#11, and atcsp1-1), 2 conditions (non-stress and cold), 3 RNA pools (total, polysomal, and CSP1 associated mRNAs), 2-3 biological replicates

first: Julia

last: Bailey-Serres


title: Gene-expression differences in peripheral blood between lithium responders and non-responders in the “Lithium Treatment -Moderate dose Use Study” (LiTMUS)

status: Public on Mar 26 2013

city: New Haven

first: Robert

last: Beech

state: CT

address: 34 Park St

department: Psychiatry

institute: Yale University

summary:
Analysis of gene-expression changes in treatment responders vs non-responders to two different treatments among subjectrs participating in LiTMUS.
Results provide information on pathways that may be involved in the clinical response to Lithium in patients with bipolar disorder.

overall_design: Total RNA isolated from PAXgene blood RNA tubes from 60 subjects with bipolar disorder, randomized to 2 treatment groups (OPT, Li+OPT) at 2 time-points (baseline, 1 month after treatment)


title: Gene Expression Profiles Predict Postpartum-onset Depression  Patients with Treatment-Resistant Depression    Patients with Treatment-Resistant Depression

first: Divya

last: Mehta

summary: To identify early predictive biomarkers for postpartum depression using peripheral blood gene expression profiles

overall_design: RNA was isolated from peripheral blood collected in Tempus RNA tubes (Applied Biosystems, Darmstadt, Germany) at all three investigated time points for each woman in the discovery sample. RNA was isolated using the Versagene kit (Gentra Systems, Minneapolis, U.S.A.), quantified using the Nanophotometer and quality checks were performed on the Agilent Bioanalyzer.

first: D


title: Gene expression data from OX1 human induced Pluripotent Stem cells

city: Oxford

first: Sally

middle: A

last: Cowley

address: South Parks Road

department: Sir William Dunn School of Pathology

institute: University of Oxford

summary:
human induced Pluripotent Stem cells (hiPSc) and their differentiated progeny have great potential for modelling disease. To realise this potential, robust protocols need to be developed for deriving authentic differentiated cell lineages and these lineages need to be rigorously characterised. We have generated hiPSc using retrovirus-mediated delivery of reprogramming factors, and have used them for assessing the efficiency of a defined protocol for differentiation to monocytes and macrophages. hiPSc lines have been screened using SNP array to assess chromosomal stability, and validation of the pluripotency of the hiPSc lines is provided by Pluritest assessment of transcriptome datasets.
van Wilgenburg B, Browne C and Cowley SA, submitted for publication

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

first: Bonnie

last: van Wilgenburg

first: Cathy

last: Browne


title: Root nitrate response of Col-0 plants and tga1/tga4 mutant plants

city: Santiago

first: Jose

middle: Miguel

last: Alvarez

state: Santiago

address: Alameda 340

department: Genética Molecular y Microbiología

country: Chile

institute: Pontificia Universidad Católica

summary: Nitrate regulates plant growth and development and acts as a potent signal to control gene expression in Arabidopsis. Using an integrative bioinformatics approach we identified TGA1 and TGA4 as putative regulatory factors that mediate nitrate responses in Arabidopsis thaliana roots. We showed that both TGA1 and TGA4 mRNAs accumulate strongly and quickly after nitrate treatments in root organs in a tissue-specific manner. Phenotypic analysis of tga1/tga4 double mutant plants indicated that TGA1 and TGA4 are necessary for nitrate modulation of both primary and lateral root growth. Global gene expression analysis revealed that 97% of the genes with altered expression in tga1/tga4 double mutant plants are regulated by nitrate treatments indicating these transcription factors have a specific role in nitrate responses in Arabidopsis root organs. Among the nitrate-responsive genes that depend on TGA1/TGA4 for normal regulation of gene expression, we found nitrate transporters NRT2.1, NRT2.2 and nitrite reductase (NIR) genes. Specific binding of TGA1 to its cognate DNA sequence on the target gene promoters was confirmed by chromatin immunoprecipitation assays. These results identify TGA1 and TGA4 as important regulatory factors of the nitrate response in Arabidopsis roots.

overall_design: Arabidopsis seedlings of the Col-0 and tga1/tga4 genotypes were grown on hydroponic medium containing 1X MS salts without Nitrogen, supplemented with 0.5 mM ammonium succinate as Nitrogen source and 3 mM sucrose on a Percival chamber under a photoperiod of 16 hours of light (100 μE/m2/sec) and 8 hours of dark at 22°C for 14 days. The plants were treated at the onset of the light cycle with 5 mM KNO3 or 5 mM KCl as control for 2 hours. Whole roots were cut from seedlings and frozen on liquid Nitrogen. Total RNA was extracted using the TriZol reagent. 3 independent biological replicates were performed.

first: Eleodoro

last: Riveras

first: Diana

last: Gras

first: Elena

last: Vidal

first: Orlando

last: Contreras-López

first: Karem

middle: P

last: Tamayo

first: María

last: Gómez

first: Sandrine

last: Ruffel

first: Laurence

last: Lejay

first: Xavier

last: Jordana

first: Rodrigo

last: Gutiérrez


title: SNP and expression data from human induced Pluripotent Stem cells derived from OX1 normal human dermal fibroblasts.

type:
Expression profiling by array
SNP genotyping by SNP array

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

overall_design: Refer to individual Series


title: Identification of WUSCHEL direct targets.

city: SAS Nagar

first: Ram

middle: Kishor

last: Yadav

state: Punjab

address: Sector 81

department: Biology

institute: Indian Institute of Science Education and Research Mohali

summary:
Cell-cell communication is critical for stem cell maintenance. Shoot apical meristem (SAM) located at the shoot tip harbors stem cells within the central zone (CZ). Their progeny differentiate in the adjacent peripheral zone (PZ). WUSCHEL (WUS) is a homeodomain transcription factor produced in a few cells of the organizing center (OC), located beneath the CZ. It has been shown to specify stem cell fate and also activate CLAVATA3 (CLV3) expression in cells of the CZ. CLV3 is a secreted peptide that activates a membrane bound receptor kinase-CLAVATA1 to restrict WUS transcription to the OC. It has been hypothesized that WUS activates CLV3 expression and stem cell fate in adjacent cells of the CZ by activating a non-cell autonomous signal. Contrary to this hypothesis, here we show that the WUS protein after being synthesized in cells of the OC, migrates into the superficial cell layers of the CZ where it activates CLV3 transcription by binding to its promoter elements. WUS also migrates laterally into the PZ to repress the expression of differentiation promoting transcription factors by binding to their regulatory regions. Migration of a stem cell inducing transcription factor into adjacent cells to activate a negative regulator, whereby restricting its own accumulation is unique to plant stem cell niches. While stem cell promoting transcription factor directly repressing differentiation promoting transcription factors to prevent premature differentiation of stem cell progenitors is conserved among diverse stem cell niches.
A dexamethasone inducible version of WUSCHEL was used to identify its direct tragets.

overall_design: To analyze WUS-regulated gene expression programs at a higher spatial resolution, we introduced a dexamethasone (Dex)-inducible form of WUS consisting of the WUS protein-coding region fused to sequences coding for the ligand-binding domain of the rat glucocorticoid receptor (GR), expressed under a ubiquitous promoter (35S::WUS-GR) into apetala1-1;cauliflower1-1 (ap1-1;cal1-1) double mutant background. 35S::WUS-GR; ap1-1;cal1-1 SAMs were either treated with 10μM Dex or mock solution for four hours and RNA samples were hybridized to Arabidopsis ATH1 gene Chip (Affymmetrix). To identify putative genes that are directly regulated by WUS, in independent experiments, SAMs were simultaneously treated with 10μM Dex and 10μM Cycloheximide (Cyc), protein synthesis inhibitor and Cyc alone for four hours. A comparison of Dex-treated samples with mock identified 641 genes as differentially expressed [DEGs] (≥/≤2 fold; p < 0.01) and comparison of Dex+Cyc with Cyc identified 457 genes as DEGs (≥/≤2 fold; p < 0.01).

first: R

first: G

last: Reddy


title: Dynamic genome-wide transcriptional response of human monocyte-derived dendritic cells to IL-6 and Il-10

city: New York

first: David

last: Braun

address: 1 Gustave Levy Place

department: Neurology / Computational Biology

institute: Mount Sinai School of Medicine

summary: Single cell timecourse experiments demonstrated that though IL-6 and IL-10 activate STAT3, they generate different temporal patterns of activation, with IL-6 generating a transient activation of STAT3, and IL-10 generating a sustained STAT3 response. We hypothesized that these different STAT3 activation dynamics would dictate the differing cellular responses to the two cytokines.

overall_design: Human monocyte-derived denditic cells from four different donors were treated with IL-6 or IL-10 for either 0min, 45min, 2hr, 4hr, 8hr, or 12hr. Total RNA was isolated from each sample and used for gene expression analysis.

first: Miguel

last: Fribourg

first: Stuart

last: Sealfon


title: Molecular analysis of precursor lesions in familial pancreatic cancer

status: Public on Mar 27 2013

city: London

first: Claude

last: Chelala

state: London

address: Charterhouse square

department: Institute of Cancer

institute: Barts & The London School of Medicine (QMUL)

summary:
Background: With less than a 5% survival rate pancreatic adenocarcinoma (PDAC) is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical.
Methods and Findings: We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses.
Conclusions: Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic pancreatic adenocarcinoma.

overall_design: Gene expression of 13 PanIN samples was compared to profiling data of whole biopsies from normal donor pancreas (N1 to 4, two replicated samples) and sporadic PDAC (PDAC1 to 6).Ttwo PDAC samples (PDAC 3 and 4) and a replicate of one normal specimen (N4) were removed during the hybridisation quality assessment.

first: Tatjana

last: Crnogorac-Jurcevic

first: Sayka

last: Barry

first: Tomohiko

last: Harada

first: Vipul

last: Bhakta

first: Sam

last: Lattimore

first: Stipo

last: Jurcevic

first: Mary

last: Bronner

first: Nicholas

middle: R

last: Lemoine

first: Teresa

last: Brentnall


title: Whole genome expression after  modulation of miR-30a expression

status: Public on Mar 22 2013

city: Bron

first: Hector

last: Hernandez-Vargas

state: Rhone

address: 36 bis Rue de la Batterie

institute: Genomics Consulting

summary: A subset of breast cancer cells displays increased ability to self-renew and reproduce breast cancer heterogeneity (so called, breast tumour-initiating cells or BT-ICs). As microRNAs (miRNAs) control developmental programs in stem cells, BT-ICs may also rely on specific miRNA profiles for their sustained activity. We analyzed miRNA expression in a model of putative BT-ICs and found that miR-30 family regulates growth under “stemness” conditions. A target screening revealed that miR-30 family modulates the expression of apoptosis and proliferation-related genes. The importance of miR-30 in tumour progression and breast cancer stemness was demonstrated in vivo using a mouse mammary cancer model. This is the first analysis of target prediction in a whole family of microRNAs potentially involved in survival of putative BT-ICs.

overall_design: Total RNA from cells transfected with Pre-miR-30 and KD-miR-30 family and control KD-miR-159 was extracted and reverse-transcribed and hybrized on HT12 Human bead chips


title: Derivation of small molecule Human Neural Precursor Cells (smNPCs) from human pluripotent stem cell lines

city: Münster

first: Peter

last: Reinhardt

address: Von-Esmarch-Straße 54

institute: Max Planck Institute for Molecular Biomedicine

summary:
We have developed a method for derivation of smNPCs from human embryonic (hESC) and induced pluripotent stem cells (hIPSC), that are only dependent on small molecules stimulating WNT and SHH signalling for their propagation.
These smNPC cultures were enzymatically split every five to six days.

overall_design: Human pluripotent stem cells were differentiated into the neural lineage using double SMAD inhibition, together with stimulation of WNT and SHH pathways. This led to expansion of neural epithelium, which was further cultured for 20 passages.


title: Hypoxia-responsive gene expression profile of U87 MG glioblastoma cells and their exosomes.

status: Public on Mar 20 2013

city: Lund

first: Paulina

last: Kucharzewska

address: Barngatan 2B

department: Clinical Sciences

country: Sweden

institute: Lund University

summary: How cancer cells adapt to hypoxia during tumor development remains an important question. The hypothesis tested in the present study was that tumor cell-derived exosome vesicles (also known as microvesicles or extracellular vesicles) are mediators of  hypoxia-dependent intercellular signaling in glioblastoma (GBM), i.e. highly aggressive brain tumors characterized by hypoxia and a vascular density that is among the highest of all human malignancies. In vitro hypoxia experiments and studies with patient materials reveal the enrichment in exosomes of hypoxia-regulated mRNAs and proteins, several of which were associated with poor patient prognosis. We show that cancer cell exosomes mediate hypoxia-dependent, phenotypic modulation of stromal cells in vitro and ex vivo, resulting in accelerated GBM tumor angiogenesis and growth in mice. These data suggest that exosomes constitute potent mediators of hypoxia-driven tumor development, and circulating multiparameter biomarkers of tumor hypoxia.

overall_design: U87 MG glioblastoma cells were grown at normoxic (21% oxygen) or hypoxic (1% oxygen) conditions for 48 hours. Conditioned media from normoxic and hypoxic cells were then used to isolate exosomes by differential centrifugation. Both cells and exosomes were lysed in Trizol reagent, and RNA was isolated.Total RNA from all samples (four types of samples in three biological repilicates) was subjected to genome-wide transcriptional analysis with Illumina HumanHT-12 V3.0 expression beadchip. Gene expression profile obtained from hypoxic U87 MG glioblastoma cells was compared to the profile of normoxic control cells. Analogically, gene expression profile obtained from hypoxic U87 MG cells was compared to the profile of exosomes secreted by normoxic U87 MG cells.

first: P

first: H

last: Christianson

first: J

last: Welch

first: K

middle: J

last: Svensson

first: E

last: Fredlund

first: M

last: Ringnér

last: Mörgelin

last: Bourseau-Guilmain

last: Bengzon

last: Belting


title: Genetic, functional and molecular features of glucocorticoid receptor binding (expression)

city: Chicago

first: Joseph

last: Maranville

state: IL

address: 920 E. 58th Street

institute: 920 E. 58th Street

summary: Glucocorticoids (GCs) are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR), which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI) and 4 Tuscans (TSI) lymphoblastoid cell lines (LCLs), we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative) depending on the presence of specific interacting TFs. Accordingly, when we performed ChIP-seq for GR and NF-kB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches.

overall_design: Total RNA obtained from lymphoblastoid cell lines treated with either dexamethasone or EtOH (vehicle for dexamethasone) for 2, 4, 8, 12, 16, or 24 hours.

first: Francesca

last: Luca

first: Allison

middle: L

last: Richards

first: David

middle: B

last: Witonsky

first: Matthew

last: Stephens

first: Anna

last: Di Rienzo


title: Genome wide analysis of pancreatic cancer cell gene expresison exposed to stromal pancreatic stellate cells in 3D gel matrix

status: Public on Mar 23 2013

first: Hemant

last: Kocher

address: Charterhouse Square

institute: Barts and the London

summary: Capan1 (well differentiated pancreatic cancer cell line) was co-cultured with pancreatic stellate cell line (PS1) embedded in a 3D organotypic model and gene expression was analysed in comparison to cancer cells cultured alone without stellate cells.

overall_design: Pancreatic stellate cells were embedded within a gel matrix composing collagen type I and Matrigel, and cancer cells were seeded on top. The gel was lifted on to metal grid after 24 hour and fed from below. Gels were harvested on day 10 and frozen sections obtained. The cancer cell layer on top of the gel was captured by laser microdissection for RNA extraction.

first: R

last: Kadaba

middle: M


title: The E3 ubiquitin ligase Siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity

status: Public on Mar 19 2013

first: Natasha

last: Sahgal

address: Old Road Campus

department: Ludwig Institute of Cancer Research

summary: Analysis of gene expression altered upon knockdown of Siah2 in prosate cancer cells. The objective is to elucidate which signaling pathways or transcription factors are regulated by the E3 ubiquitin ligase Siah2 in human prostate cancer cells.

overall_design: CWR22Rv1 cells were in fected with pLKO.1 control or Siah2 shRNA, and selected with 1ug/ml of puromycin to get stable transfectants.  Total RNA was extracted for micorarray analysis to compare the diffentially expressed genes between pLKO.1 control and Siah2 knockdown cells.

first: Jianfei

last: Qi

first: Manisha

last: Tripathi

first: Susan

last: Ettinger

first: William

last: Placzek

first: Giuseppina

last: Claps

first: Leland

middle: K

last: Chung

last: Bowtel

first: Martin

last: Gleave

first: Neil

last: Bhowmick

first: Ze’ev

last: Ronai


title: Transcriptome analysis of ire1 mutants after treatment with or without tunicamycin in the presence of actinomycin D

city: Yokohama

first: Yukihisa

last: Shimada

state: Kanagawa

address: Maiokacho, Totsuka

department: Kihara Institute for Biological Science

country: Japan

institute: Yokohama City University

summary: Arabidopsis seedlings of wildtype or ire1a ire1b double mutant were treated with or without tunicamycine in the presence of actinomycin D (ActD).

overall_design: 12 samples

first: Nozomu

last: Koizumi


title: in-vitro differentiated midbrain dopaminergic neurons from isogenic human induced pluripotent stem cells

status: Public on Mar 07 2013

first: Peter

last: Reinhardt

summary:
We have generated isogenic induced pluripotent stem cell lines by reprogramming human fibroblasts from patients carrying the LRRK2 G2019S mutation with subsequent zinc finger nuclease - mediated targeted correction of the diseased allele.
These iPS cell lines were differentiated for 30 days using a direct differentiation protocol towards midbrain dopaminergic neurons (mDANs).

overall_design: Isogenic human iPS cells carrying the LRRK2 WT and G2019S locus were differentiated to dopaminergic neurons to detect gene expression changes associated with mutated LRRK2.


title: Dual inactivation of Akt and ERK by small molecule TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction and potent anti-tumor effects

status: Public on Mar 08 2013

city: Hershey

first: Joshua

middle: E

last: Allen

state: PA

address: 500 University Drive

institute: Penn State Hershey Medical Ctr

summary: TIC10-induced transcriptional changes at 48hrs in HCT116 p53-null cells (10uM).

overall_design: Six samples of HCT116 p53-null cells with TIC10 (10uM) or DMSO treatment. Three replicates each.

first: Wafik

middle: S

last: El-Deiry


title: Transcriptome Analysis of Human Injured Meniscus Reveals a Distinct Phenotype of Meniscus Degeneration with Aging

status: Public on Mar 18 2013

city: St. Louis

first: Muhammad Farooq

last: Rai

state: MO

address: 660 S. Euclid Ave.

department: Orthopaedic Surgery

institute: Washington University School of Medicine

summary: In this study, we have tested the variation in gene expression signatures in human injured meniscus with age and degree of chondrosis in the knee. We found several genes that were differentially regulated with each of these factors and they represent important biological pathways in osteoarthritis research.

overall_design: Total RNA obtained from isolated injured meniscus tissues from patients undergoing arthroscopic partial meniscectomy.

first: Muhammad

middle: F

first: Debabrata

last: Patra

first: Linda

last: Sandell

first: Robert

middle: H

last: Brophy


title: MLN4924 in chronic lymphocytic leukemia

status: Public on Mar 05 2013

city: Portland

first: Alexey

last: Danilov

state: OR

address: 3181 SW Sam Jackson Pk Rd

institute: Oregon Health and Science Univeristy

summary: CLL cells obtained from patients with CLL were treated with MLN4924 to determine whether NFkB transcription targets were affected by the drug.

overall_design: CLL cells were treated with 1 microM  MLN4924 or vehicle control for 24 hours. Cells were collected by centrifugation and B-cell were purified using negative selection (B cell purification Kit, Multenyi Biotech). RNA was isolated and submitted for Gene expression analysis


title: Expression data from primary human dermal fibroblasts with STAT2 deficiency and control fibroblasts treated with interferon

city: Edinburgh

first: Paul

last: Dickinson

address: 49 Little France Crescent

department: Division of Infection and Pathway Medicine

institute: University of Edinburgh

summary: Primary human dermal fibroblasts were isolated from an individual showing a genetic defect in innate antiviral immunity associated with profound failure of type 1 interferon signaling and absence of the STAT2 protein. The transcriptional response of these cells to a 10h treatment with interferon-alpha was compared with that of control dermal fibroblasts.

overall_design:
We used microarrays to detail the global program of gene expression resulting from interferon-alpha treatment in STAT 2 deficient and control fibroblasts.
Primary human dermal fibroblasts were grown in the presence or absence of 1,000U/ml interferon-alpha (IFNa) for 10 hours before RNA extraction and hybridization on Affymetrix microarrays.

first: Sophie

last: Hambleton

first: Stephen

last: Goodbourn

first: Dan

last: Young

first: Siti

last: Mohamad

first: Manoj

last: Valappil

first: Andrew

last: Cant

first: Scott

last: Hackett

last: Ghazal

middle: V

last: Morgan

first: Richard

last: Randall


title: Impaired TLR3-mediated immune responses from macrophages of patients chronically infected with Hepatitis C virus

first: Ruth

last: Montgomery

address: 300 Cedar St.

department: Internal Medicine

institute: Yale University School of Medicine

summary: Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States with the majority of patients becoming chronically infected and a subset (20%) progressing to cirrhosis and hepatocellular carcinoma. Individual variations in immune responses may help define successful resistance to infection with HCV. We have examined the immune response in primary macrophages from patients who have spontaneously cleared HCV (viral load negative, VL-, n = 37) compared to HCV genotype 1 chronically infected (VL+) subjects (n=32) and found that macrophages from VL- subjects have an elevated baseline expression of Toll-like receptor 3 (TLR3). Macrophages from HCV patients were stimulated ex vivo through the TLR3 pathway and assessed using gene expression arrays and pathway analysis. We found elevated TLR3 response genes and pathway activity from VL- subjects. Furthermore, macrophages from VL- subjects showed higher production of IFN-b and related IFN response genes by Q-PCR, and increased phosphorylation of STAT-1 by immunoblot. Analysis of polymorphisms in TLR3 revealed a significant association of intronic TLR3 polymorphism (rs13126816) with the clearance of HCV and the expression of TLR3. Of note, PBMCs from the same donors showed opposite changes in gene expression, suggesting ongoing inflammatory responses in PBMCs from VL+ HCV patients. Our results suggest that an elevated innate immune response enhances HCV clearance mechanisms and may offer a potential therapeutic approach to increase viral clearance.

overall_design: Differential gene expression by primary human macrophages and PBMCs from patients with spontaneous clearance of HCV (VL-) and patients with chronic HCV infection (VL+) were generated by microarray.


title: MicroRNA-198 an inhibitor of keratinocyte migration

status: Public on Mar 02 2013

city: Singapore

first: Prabha

last: Sampath

state: Singapore

address: 8A Biomedical Grove

department: Institute of Medical Biology

country: Singapore

institute: Institute of Medical Biology

summary:
This study identifies miR-198 as a potential inhibitor of keratinocyte migration in skin
This study identifies genes differentially expressed during the early phases of wound healing using an ex vivo organ culture model of human skin

overall_design:
Total RNA from N/TERT-1 keratinocytes transfected with a negative control miRNA or miR-198  were subjected to microarray analysis
Skin from elective plastic surgery were subjected to wounding using ex vivo organ culture model. Total RNA from skin biopsies were isolated at 0hr and 24hr post injury and subjected to mircoarray analysis

first: Gopinath

last: Sundaram

first: John

last: Common


title: FSTL1 promotes keratinocyte migration.

summary: This study identifies FSTL1 as key component of intiating keratinocyte migration in skin

overall_design: Total RNA from N/TERT-1 keratinocytes transfected with a non-targeting siRNA or Smartpool siRNA against FSTL1  were subjected to microarray analysis


title: Gene expression profiles of MCF7 breast cancer cells following estrogen and anti-estrogen treatment.

status: Public on Mar 01 2013

city: Rochester

last: Hawse

state: MN

address: 200 1st St. SW

department: Biochemistry and Molecular Biology

institute: Mayo Clinic

summary: We have previously demonstrated that endoxifen is the most important tamoxifen metabolite responsible for eliciting the anti-estrogenic effects of this drug in breast cancer cells expressing estrogen receptor-alpha. The goals of this study were to compare the gene expression profiles elicited by endoxifen to that of other anti-estrogens in MCF7 cells.  We also examined the gene expression profiles elicited by various endoxifen concentrations in the presence of tamoxifen and its other primary metabolites in order to better understand the molecular contributions of endoxifen to the effects of tamoxifen.

overall_design: Total RNA was isolated from parental MCF7 cells following 24 hour treatments with various individual or combined ligands.  All studies were conducted in replicates of 3.


title: Genome-wide analysis of mRNA expression after stable transfection of Lin-28B or Ago2 in H1299 cells

city: Nanjing

first: Yan

last: Zeng

state: Jiangsu

address: XuanWu District, No.1 WeiGang

institute: Nanjing Agricultural University

summary: Analysis of gene expression as a result of long-term Lin-28B or Ago2 overexpression in H1299 cells.

overall_design: Total RNA was isolated from the exponentially growing, stable cell lines, labeled, and hybridized to Illumina human HT-12 Beadchips.

first: Zeng

last: Yan


title: Blood-Informative Transcripts Define Nine Common Axes of Peripheral Blood Gene Expression

first: Jinhee

last: Kim

address: 676 North St. Clair Street Arkes Suite 2330

department: Infectious Disease

institute: Northwestern University

summary: Whole peripheral blood samples collected into Tempus tubes from 189 adult participants in the Center for Health Discovery and Well Being study of Emory University and Georgia Tech, in Midtown Atlanta.  The sample is of mixed ethnicity, and is part of a survey of the impact of genetics and lifestyle on gene expression and clinical attributes. Sample annotations include gender, self-reported ethnicity, zipcode of current address, and percent body fat, as well as technical features of the study (Sentrix plate ID, date of  hybridization, and RNA quality RIN score.

overall_design: 189 individuals in the Center for Health Discovery and Well Being study of Emory University and Georgia Tech, in Midtown Atlanta., 65 men and 124 women. The age of individulas were between 26 and 79 (mean 51). 140 Caucasian (CAU), 37 African American (AFR), 11 Asian (ASN), 1 American Indian (AMI).

first: Marcela

last: Preininger

first: Dalia

last: Arafat

first: Youssef

last: Idaghdour

first: Kenneth

middle: W

last: Brigham

first: Greg

last: Gibson


title: Phenotypic changes in PMN in Periodontits patients

status: Public on Feb 26 2013

city: Toronto

first: Flavia

last: Lakschevitz

state: ON

address: 150 College st room 221

department: Faculty of Dentistry

country: Canada

institute: University of Toronto

summary: The goal of this study is to use a rapid method for oral neutrophil isolation and use a transcriptomics approach to characterize and compare the neutrophil gene expression profile in the blood and oral compartment of healthy individuals, chronic periodontitis patients and refractory periodontitis patients.

overall_design: Total RNA obtained from isolated neutrophils from blood and oral samples of Healthy patients, chronic periodontits patients and refractory periodontitis patients

first: Guy

last: Aboodi

first: Michael

last: Glogauer


title: Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition

status: Public on Feb 25 2013

city: Cambridge

first: Gabriela

last: Alexe

state: MA

address: 415 Main St.

department: Computational Biology and Bioinformatics

institute: Broad Institute

summary:
Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically-defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition. We characterized the mechanistic and translational significance of this finding in neuroblastoma, a childhood cancer with frequent amplification of MYCN. Genome-wide expression analysis demonstrated downregulation of the MYCN transcriptional program accompanied by suppression of MYCN transcription. Functionally, bromodomain-mediated inhibition of MYCN impaired growth and induced apoptosis in neuroblastoma. BRD4 knock-down phenocopied these effects, establishing BET bromodomains as transcriptional regulators of MYCN. BET inhibition conferred a significant survival advantage in three in vivo neuroblastoma models, providing a compelling rationale for developing BET bromodomain inhibitors in patients with neuroblastoma.
Significance: Biomarkers of response to small-molecule inhibitors of BET bromodomains, a new compound class with promising anti-cancer activity, have been lacking. Here, we reveal MYCN amplification as a strong genetic predictor of sensitivity to BET bromodomain inhibitors, demonstrate a mechanistic rationale for this finding, and provide a translational framework for clinical trial development of BET bromodomain inhibitors for pediatric patients with MYCN-amplified neuroblastoma.

overall_design:
JQ1 is a novel thieno-triazolo-1,4-diazepine, which displaces BET bromodomains from chromatin by competitively binding to the acetyl lysine recognition pocket.
BE(2)-C and Kelly cells were treated in triplicate with 1 µM JQ1 or DMSO for 24 hours.  RNA was extracted and a decrease in MYCN transcript was confirmed by real time RT-PCR as described above. The samples were profiled using the Affymetrix PrimeView Human Gene Expression Array (Affymetrix) at Beth Israel Deaconess Medical Center (Boston, MA, USA).

first: Kimberley

last: Stegmaier


title: Expression data profile of A498 cells inoculated with E. coli 83972 and E. coli CFT073

status: Public on Feb 23 2013

first: Nataliya

last: Lutay

address: Sölvegatan 23

summary:
Urinary tract infections (UTIs) constitute a highly relevant model of microbial adaptation, in which the contrasting effects of pathogens and commensals on host tissues are clearly displayed. While virulent Escherichia coli cause severe, potentially life-threatening disease by breaking the inertia of the mucosal barrier and infecting the kidneys, the most common outcome of bacteriuria is an asymptomatic carrier state resembling commensalism at other mucosal sites. It remains unclear if the lack of destructive inflammation merely reflects low virulence or if carrier strains actively inhibit disease associated responses in the host. To address this question, we examined the effects of asymptomatic bacterial carriage on host gene expression.
A498 cell line has been validated as a model of uropathogenic E. coli infection; the cells express functional receptors for bacterial virulence ligands and the response to virulent strains reflects human UTI. The cells were infected with asymptomatic and pathogenic E. coli in vitro, and harvested RNA was subjected to whole genome transcriptome analysis.

overall_design: A498 human kidney epithelial cells were infected with the asymptomatic (E. coli 83972) or virulent strains (E. coli CFT073) for 4 hours. The cells with culture medium alone were used as a control. The experiment was performed in biological duplicates or triplicates.

first: Jingyao

last: Zhang

first: Catharina

last: Svanborg


title: Parental MeWo and highly metastatic LM2 human melanoma cell line derivatives with or without miR-199a or miR-1908

status: Public on Feb 10 2013

first: Nora

last: Pencheva

state: NY

address: 1230 York Avenue, Box 194

institute: Nora Pencheva

summary: Human melanoma MeWo cells and their respective LM2 metastatic derivatives, generated through in vivo selection, were transcriptomically profiled in the context of miR-199a and miR-1908 gain- and loss-of-function in order to identify putative target genes for these miRNAs,

overall_design: MeWo cells and their respective LM2 metastatic derivatives in the context of miR-199a and miR-1908 gain- and loss-of-function

first: Hien

last: Tran

first: Colin

last: Buss

first: Marija

last: Drobnjak

first: Klaus

last: Busam

first: Sohail

last: Tavazoie


title: The rcf1-1 mutation affects global gene expression in Arabidopsis thaliana with or without cold stress.

city: College Park

first: Jianhua

last: Zhu

state: MD

address: 2102 Plant Sciences Building

department: Plant Science and Landscape Architecture

institute: University of Maryland

summary:
Cold stress is one of the most severe environmental conditions which cause huge losses in crop production worldwide. We identified an essential regulator of cold-responsive genes and used the Affymetrix whole-genome arrays to define downstream targets of this important protein.
We used the microarrays to reveal the effect of rcf1-1 mutation on global gene expression with or without cold stress at 4°C. A set of genes differentially expressed in rcf1-1 with or without cold stress are identified.

overall_design: Fourteen-day-old seedlings of Arabidopsis thaliana wild type (Columbia gl1 expressing CBF2::LUC transgene) and rcf1-1 mutant seedlings subjected to cold stress at 4°C for 0, 12, and 24 h were used for total RNA extraction and hybridizations with Affymetrix ATH1 GeneChips. There are two biological replicate per genotype.

first: Qingmei

last: Guan

first: Jianmin

last: Wu

first: Yanyan

first: Changhua

last: Jiang

first: Chenglin

last: Chai

first: Renyi

last: Liu


title: A Systems Approach for Decoding Mitochondrial Retrograde Signaling Pathways

status: Public on Feb 12 2013

city: Pohang, Gyungbuk

first: Sehyun

last: Chae

address: San 31, Hyoja-Dong, Nam-Gu

department: Department of Interdisciplinary Bioscience and Bioengineering(I-BIO)

institute: POSTECH

summary: The mitochondrial and nuclear genomes contribute to mitochondrial function, and when mitochondrial function is compromised, mitochondrial retrograde signaling alters nuclear gene expression. We performed gene expression profiling of engineered cells that had mitochondria containing a disease-associated mutation that causes mitochondrial dysfunction. By generating networks of transcription factors that targeted these genes, the authors revealed putative mitochondrial retrograde signaling pathways. One such pathway involved retinoic acid receptor alpha (RXRA), the mRNA for which was reduced in the mutant cells. Network analysis and experiments in cells suggested that mitochondrial dysfunction caused by the mutation initiated a positive feedback loop that aggravated mitochondrial dysfunction: Reduced RXRA abundance further compromised expression of genes encoding products involved in mitochondrial function and translation. This gene-transcription factor mapping-network approach may reveal targets for therapeutic intervention of diseases associated with mitochondrial dysfunction.

overall_design:
To investigate retrograde signaling pathways induced by the mitochondrial dysfunction caused by the mt3243 mutation, we generated the three types of cybrid cells using a mitochondria-mediated transformation method. Cells lacking mtDNA (rho0) were fused with mtDNAs with the mt3243 mutation isolated from platelets of a diabetic patient with sensorineural hearing loss. We then isolated three types of cybrid cells: W cells had wild-type mtDNA (3243A homoplasmy), H cells had both the mutant and wild-type mtDNA (3243A/G heteroplasmy) with 70% of the mtDNA containing 3243G, and M cells with only mutant mtDNA (3243G homoplasmy).
Gene expression profiles of cybrid cells were generated using Illumina HumanHT-12-v3-BeadChip (Illumina, San Diego, CA), which includes 49,896 probes corresponding to 25,202 annotated genes. According to the Illumina protocols, three biological triplicates of each type of cybrid cells were analyzed. Total RNA (500ng) was isolated from cybrid cells using RNeasy Mini Kit (Qiagen, GmbH, Germany). RNA integrity number (RIN) was in the range of RIN = 9.2  and 10 when measured with an Agilent 2100 Bioanalyzer. RNA was reversely transcribed and amplified using IlluminaTotalPrep RNA amplification kit (Ambion, Austin, TX). In vitro transcription was then carried out to prepare cRNA. The cRNAs were hybridized to the array and then labeled with Cy3-streptavidin (Amersham Bioscience, Little Chalfont, UK). The fluorescent signal on the array was measured with a BeadStation 500 System (Illumina, San Diego, CA).

first: ByungYong

last: Ahn

first: Kyunghee

last: Byun

first: YoungMin

last: Cho

first: Myeong-Hee

last: Yu

first: Bonghee

last: Lee

first: Daehee

last: Hwang

first: KyongSoo

last: Park


title: Genome-wide analysis of MAOA on Norepinphrine induced HCC gene expression

city: Shanghai

first: zhigang

last: zhang

address: No. 800, Dong Chuan Road

department: Shanghai cancer Institute

institute: Shanghai Jiaotong University

summary: Gene analysis of HCC cells transfected with Lenti-vector, Lenti-MAOA and stimulated with Norepinephrine

overall_design: Total mRNA obtained from SMMC-7721 cells transfected with Lenti-vector, Lenti-MAOA and stimulated with Norepinephrine


title: Transcription forms and remodels supercoiling domains unfolding large scale chromatin structures [Illumina transcription]

status: Public on Feb 17 2013

first: Nick

last: Gilbert

address: Crewe Rd South

department: Institute of Genetics and Molecular Medicine

institute: The University of Edinburgh

summary:
This study was designed to investigate DNA supercoiling across the human genome and to understand how supercoiling domains impact on higher levels of genome organisation.
DNA supercoiling is an inherent consequence of twisting DNA and is critical for regulating gene expression and DNA replication. However, DNA supercoiling at a genomic scale in human cells is uncharacterized. To map supercoiling we used biotinylated-trimethylpsoralen as a DNA structure probe to show the genome is organized into supercoiling domains. Domains are formed and remodeled by RNA polymerase and topoisomerase activities and are flanked by GC-AT boundaries and CTCF binding sites. Under-wound domains are transcriptionally active, enriched in topoisomerase I, “open” chromatin fibers and DNaseI sites, but are depleted of topoisomerase II. Furthermore DNA supercoiling impacts on additional levels of chromatin compaction as under-wound domains are cytologically decondensed, topologically constrained, and decompacted by transcription of short RNAs. We suggest that supercoiling domains create a topological environment that facilitates gene activation providing an evolutionary purpose for clustering genes along chromosomes.

overall_design: The gene transcription of 3 independent biological replicates were investigated

first: Catherine

last: Naughton


title: Transcription forms and remodels supercoiling domains unfolding large scale chromatin structures

type: Genome binding/occupancy profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Probiotic and Prebiotic Supplementation of Antiretroviral Therapy Improves Gastrointestinal Immunity in SIV-infected Macaques

status: Public on Feb 06 2013

city: Cleveland

first: Peter

last: Wilkinson

state: Ohio

address: 2103 Cornell Road

department: Pathology / Systems Biology & Bioinformatics

institute: Case Western Reserve University

summary: HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation, which are not completely ameliorated with suppression of viremia by antiretroviral (ARV) therapy. Furthermore, increased morbidity and mortality of ARV-treated HIV-infected individuals is associated with these dysfunctions. Thus, in order to enhance GI tract immunity, we treated SIV-infected pigtail macaques with ARVs supplemented with probiotics and prebiotics or with ARVs alone. In the colon, this synbiotic treatment resulted in increased expression of genes associated with antigen presenting cells (APCs), increased frequency and functionality of APCs, enhanced reconstitution and functionality of CD4+ T-cells and reduced fibrosis of lymphoid follicles. Thus, supplementing ARV treatment with synbiotic treatment in HIV-infected individuals may improve GI tract immunity and thereby mitigate inflammatory sequelae, ultimately improving prognosis.

overall_design: CD45+ (clone MB4-6D6) leukocytes were sorted from thawed colon samples from 4 ARV + probiotics animals and 4 ARV alone animals

first: Lauren

last: Canary

first: Xiaoyong

last: Sun

first: Carol

last: Vinton

first: Nicholas

middle: T

last: Funderburg

first: David

last: Morcock

first: Mariam

last: Quiñones

first: Clayton

last: Deming

first: Molly

last: Perkins

first: Daria

last: Hazuda

first: Michael

middle: D

last: Miller

last: Lederman

first: Julie

last: Segre

first: Jeffrey

last: Lifson

first: Elias

last: Haddad

first: Jacob

last: Estes

first: Jason

last: Brenchley


title: Gene expression analysis in Drosophila introgression hybrids

status: Public on Feb 15 2013

city: Bloomington

first: Colin

last: Meiklejohn

state: IN

address: Jordan Hall, 1001 E. 3rd St.

department: Biology Department

institute: Indiana University

summary: RNA was extracted from adult male and adult female Drosophila simulans carrying small genomic segments introgressed from Drosophila mauritiana

sample_organism:
Drosophila mauritiana
Drosophila simulans

overall_design: Seven introgression genotypes were profiled, as well as the parental D. simulans and D. mauritiana strains.  Each sex-by-genotype was assayed on four replicate arrays incorporating a dye swap

first: Joseph

last: Coolon

first: Daniel

last: Hartl

first: Patricia

last: Wittkopp


title: Genome-wide analysis of gene expression profile of Xenograft Tumors (HT29 cells) grown in Nu/Nu Athymic Female Mice infected with Control (Ad-VP16) or LXRa (VP16hLXRa) Adenovirus

status: Public on Feb 05 2013

city: Santa Maria Imbaro

first: Antonio

last: Moschetta

address: Via Nazionale 8A

institute: University of Bari & Consorzio Mario Negri Sud

summary: Changes in gene expression profile of Xenograft Tumors (HT29 cells) grown in Nu/Nu Athymic Female Mice infected with Control (Ad-VP16) or LXRa (VP16hLXRa) Adenovirus. The hypothesis tested in the present study was that LXRa overexpression influence cancer growth modulating lipid metabolism in cancer cells. Results provide the information that LXRa induces genes encoding proteins able to regulate cholesterol efflux thus reducing tumor growth.

overall_design: Total RNA obtained from Xenograft Tumors (HT29 cells) grown in Nu/Nu Athymic Female Mice infected with LXRa (VP16hLXRa) Adenovirus was compared to total RNA extracted from Xenografted Tumors (HT29 cells) grown in Nu/Nu Athymic Female Mice infected with Control (Ad-VP16) Adenovirus.

first: Fabiola

last: Bovenga

first: D'Orazio

last: Andria


title: Liver X Receptors play an antitumoral role in the intestine

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells (mRNA)

city: Helsinki

first: Olli

middle: A.

last: Jänne

department: Inst. of Biomedicine/Physiology

country: Finland

institute: University of Helsinki

summary: We report the androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell lines, LNCaP-1F5 and VCaP in response to physiological androgen 5a-dihydrotestosterone (DHT) using ChIP-sequencing. We compare the AR recruitment by DHT to that by partial agonist/antagonist cyproterone acetate and mifepristone (RU486) in LNCaP-1F5 cells. We also report the role of glucocorticoid receptor recruitment in presence of dexamethasone (Dex) in androgen responsive prostate cancer cells. The AR and GR cistrome analysis is subsequently compared with gene expression data and RNA Pol II analysis. The ChIP-seq has been performed using AR, GR, RNA Pol II antibodies.

overall_design: Expression profiling by microarray of LNCaP-1F5 cells treated with vehicle, 100 nM 5a-dihydrotestosterone (DHT), 100 nM dexamethasone (Dex), 1000 nM cyproterone acetate (CPA), 100 nM mifepristone (RU486) and combination of 100 nM DHT,100 nM Dex for 24 hours.

first: Biswajyoti

last: Sahu

first: Marko

last: Laakso

first: Päivi

last: Pihlajamaa

first: Kristian

last: Ovaska

first: Ievgenii

last: Sinielnikov

first: Sampsa

last: Hautaniemi

middle: A


title: H3K4me3 Interactions with TAF3 Regulate Preinitiation Complex Assembly and Selective Gene Activation [Illumina BeadArray]

city: Frederick

first: Xiaolin

last: Wu

address: 8560 Progress Drive, C3001

department: Cancer Research Technology Program

country: USA

institute: Frederick National Laboratory for Cancer Research/SAIC-Frederick Inc

summary: Histone modifications regulate chromatin-dependent processes, yet the mechanisms by which they contribute to specific outcomes remain unclear. H3K4me3 is a prominent histone mark that is associated with active genes and promotes transcription through interactions with effector proteins that include initiation factor TFIID. We demonstrate that H3K4me3-TAF3 interactions direct global TFIID recruitment to active genes, some of which are p53 targets. Further analyses show that (i) H3K4me3 enhances p53-dependent transcription by stimulating preinitiation complex (PIC) formation; (ii) H3K4me3, through TAF3 interactions, can act either independently or cooperatively with the TATA box to direct PIC formation and transcription; and (iii) H3K4me3-TAF3/TFIID interactions regulate gene-selective functions of p53 in response to genotoxic stress. Our findings indicate a mechanism by which H3K4me3 directs PIC assembly for the rapid induction of specific p53 target genes.

overall_design: Total RNAs from control or TAF3 knockdown cells before and after doxorubicin treatment were subjected to Illumina microarray analyses.

first: Shannon

last: Lauberth

first: Takahiro

last: Nakayama

first: Andrea

last: Ferris

first: Zhanyun

last: Tang

first: Stephen

last: Hughes

first: Robert

middle: G

last: Roeder


title: mRNA profiling of LNCaP cells treated with miR-31

city: New York

first: Pei-Chun

last: Lin

address: 1300 York Ave

department: Pathology and Laboratory Medicine

institute: Cornell Weill Medical College

summary: To determine the altered microRNA expression signature in human prostate cancer compared to benign prostate tissue. To determine the altered mRNA expression signatures upon overexrpession miR-31 in prostate cancer cells.

overall_design: Two condition experiments:1) Total RNA from 21 pairs of prostate cancers and matched benign prostate tissues were collected and processed for microRNA detection. 2) In LNCaP prostate cancer cells, miR-31 was overexpressed and compared to control miR-NC.

middle: C

first: Ya-lin

last: Chiu

first: Samprit

last: Banerjee

first: Francesca

last: Demichelis

first: Mark

last: Rubin


title: Paired human prostate cancer and benign prostate tissues, and LNCaP cells treated with miR-31

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

platform_organism:
Homo sapiens
synthetic construct


title: Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF mutant thyroid carcinomas.

status: Public on Feb 01 2013

first: Cristina

last: Montero-Conde

department: HOPP

institute: MSKCC

summary: Analysis of transcriptome kinetics of SW1736 thyroid cancer cell line vs SK-MEL-28 melanoma cell line at various times after addition of 2 µM vemurafenib. The hypothesis tested was that SW1736 cells (vemurafenib-refractory) differentially express genes compared to SK-MEL-28 cells (vemurafenib sensitive) that confer resistance to the RAF inhibitor.

overall_design: Total RNA was obtained from lysates of SW1726 and SK-MEL-28 cells treated with 2 µM vemurafenib for 0, 1, 6 and 48 h. Experiment was made by triplicate.

first: Sergio

last: Ruiz-Llorente

first: Jose

last: Dominguez

first: Jeffrey

last: Knauf

first: Agnes

last: Viale

first: Eric

middle: J

last: Sherman

first: Mabel

last: Ryder

first: Ronald

last: Ghossein

first: Neal

last: Rosen

first: James

last: Fagin


title: Gene expression profiling of GFP-positive cancer stem-like cells(CSLC) derived from MDA-MB453 cells, compared with GFP-negative non-cancer stem cells (non-CSLC).

city: Seoul

first: Young Dong

last: Yoo

address: 28 Yeon-gun dong Jongnogu

institute: Seoul National University

summary: Analysis of genes that differentially expressed in CSLC cells compared with non-CSLC cells, which are derived from the same parental MDA-MB453 cell line.

overall_design: Total RNAs were isolated from two pairs of GFP-positive CSLCs (ST1, ST2) and GFP-negative non-CSLCs (NS1, NS2) on different days. Two batches of RNAs were combined for microarray analysis.

first: Yong

last: Kwon

first: Young


title: Imprinting of the Y chromosome depending on parent of origin provides insight into chromatin-modulating mechanisms underlying the Y chromosome's ability to affect gene expression diversity

first: Pan-Pan

last: Jiang

address: 16 Divinity Ave c/o Hartl Lab

department: Organismic and Evolutionary Biology

institute: Harvard University

summary: These arrays were done in a study to probe Y-by-parent-of-origin effects on gene expression across two geographically diverse (Ohio, USA and Republic of Congo, Africa) Y-chromosome lineages (Cs or Con), and two modes of Y chromosome transmission (paternally or maternally).

overall_design: Males harbor one of two Y chromosomes extracted from natural populations. Y chromosomes are inherited maternally or paternally. Therefore, 4 nodes in the design matrix. Each node was competitively hybridized to each of the other three nodes in 2 dual-channel arrays, dye-swapped.

first: Pan

middle: P

first: Daniel

middle: L

last: Hartl