title: Genome Wide Profiling of p53 Response to Differentiation or DNA Damage of Human Embryonic Stem Cells

city: Houston

first: Kadir

middle: Caner

last: Akdemir

address: 1515 Holcombe Blvd

country: USA

institute: MD Anderson Cancer Center

summary: Tumor suppressor p53 promotes differentiation of human embryonic stem cells (hESCs), but an in-depth understanding of mechanism is lacking. Here, we define p53 functions in hESCs by genome wide profiling of p53 chromatin interactions and intersection with gene expression during early differentiation and in response to DNA damage. During differentiation, p53 targets and regulates a unique collection of genes, many of which encode transcription factors and developmental regulators with chromatin structure poised by OCT4 and NANOG and marked by repressive H3K27me3 in pluripotent hESCs. In contrast, genes associated with cell migration and motility are bound by p53 specifically after DNA damage. Surveillance functions of p53 in regulation of cell death and cell cycle genes are conserved during both DNA damage and differentiation. Our findings expand the registry of p53 -regulated genes in hESCs and define specific functions of p53 in opposing pluripotency, which are highly distinct from stress-induced p53 response in stem cells.

overall_design: Identification of p53 binding sites in hESC under three conditions: Pluripotent, DNA damaged, Differentiating

middle: C


title: Expression data from mouse embryonic fibroblasts and pluripotent stem cells

status: Public on Oct 17 2013

city: Kyoto

first: Takuya

last: Yamamoto

address: 53 Kawahara-cho, Shogoin, Sakyo-ku

department: CiRA

country: Japan

institute: Kyoto University

summary: Splicing profiles in pluripotent stem cells are different from those in somatic cells. Generally, alternative splicing is regulated by RNA binding proteins. To identify the candidate RNA-binding protein-encoding genes, we performed gene expression profiling experiments.

overall_design: Expression levels were profiled in mouse embryonic fibroblasts (MEFs), 2 iPS cell lines (492B4, 178B5), and ES cells (v6.5).

first: Sho

last: Ohta


title: Identification of bone morphogenetic protein (BMP)-7 as a key instructive factor for human epidermal Langerhans cell differentiation and proliferation

status: Public on Oct 18 2013

city: Graz

first: Karin

last: Wagner

state: Styria

address: Stiftingtalstrasse 24

department: Molecular Biology

country: Austria

institute: Medical University Graz

summary: Langerhans dendritic cells represent abundantly occuring and evolutionary highly conserved DCs specifically located in the stratified epithelial tissues. LCs are unique among DC family members in that they express epithelial-type adhesion molecules, allowing them to form a tight three-dimensional network in basal and suprabasal epidermal keratinocyte layers and developmentally dependent on the cytokine TGF-β1. In the present study, we identified BMP-7 as another key factor inducing LC differnetiation. Here we have performed comparative analysis of highly purified CD207+/CD1a+ in vitro generated Langerhans cells in the presence of BMP-7 and TGF-β1. We have identified that both BMP-7-LCs and TGF-β1-LCs are closely related to each other.

overall_design: CD34+ hematopoietic stem cells were isolated from freshly obtained cord blood and cultured in the presence of GM-CSF, SCF, Flt3L, TNFa and either TGF-β1 or BMP-7 for 7 days to get immature LCs. RNA was isolated from these in vitro genetared LCs.

first: Nighat

last: Yasmin

first: Wagner

last: Karin

first: Herbert

last: Strobl


title: Alteration of renal gene expression affected by atypical chemokine receptor D6 knockout in diabetic OVE26 (OVE) mice

status: Public on Oct 10 2013

city: Louisville

first: Shirong

last: Zheng

state: KY

address: 570 S Preston St.

department: Pediatrics

institute: University of Louisville

summary:
The D6 receptor can bind and internalize inflammatory chemokines without activating intracellular pathways. D6 can reduce tissue inflammation, presumably by scavenging inflammatory chemokines. In diabetic kidney there is extensive inflammation but the possible role of the D6 receptor has never been tested.
In this study, we included the renal gene expression dataset generated from whole kidney RNA extraction in diabetic mice with or without D6 gene knockout, their controls are age and sex matched D6 deficient or wild type mice on FVB background. These data are used to analyze the effects of D6 deletion on progression of diabetic nephropathy.

overall_design: D6 knockout mice were crossing with FVB stain to produce D6 knockout mice in FVB background (D6). Then D6 was crossed with diabetic mice (OVE) to produce D6 defficient diabetic mice (OVE-D6). These mice were followed up for albuminuria from 2 month old, and sacrificied at 6 months for gene expression and renal morphology analysis. 12 kidney samples (3 per group) were used in this gene array study.

first: Paul

last: Epstein


title: Transcriptional profile of Escherichia coli K12  strain JM109 harboring pUCA1501

status: Public on Oct 15 2013

city: Bei Jing

first: Liang

last: Li

state: Bei Jing

address: Zhongguan Cun Nanda Jie No.12

department: Biotechnology Research Institute

country: China

institute: Chinese Academy of Agricultural Sciences

summary: A1501 aroA is a gene derived from Pseudomonas stutzeri A1501, encoding a class II glyphosate-tolerant EPSP synthase. To understand the effect of class II EPSP synthase to E. coli under glyphosate shock, we constructed the class II EPSP synthase-expressing plasmid pUC-A1501. And pUC18 is the empty vector used as a control.

overall_design: RNA extracted from cells of E. coli K-12 JM109 cells with pUCA1501 till OD600 to achieve 0.4, or cells with pUC18 when their OD600 achieved 0.4.

first: Min

last: Lin

first: Wei

last: Lu

first: Wujun

last: Jin

first: Yusong

last: Wan


title: Gene expression of triclosan susceptible and tolerant E. coli O157:H19 in response to triclosan exposure

city: Dublin

first: Julieanne

last: Molloy

address: Ashtown

department: Food Safety

country: Ireland

institute: Teagasc Food Research Centre

summary:
Triclosan is a biocidal active agent commonly found in domestic cleaning products, hand sanitizers, cosmetics and personal care products. It is used to control microbial contamination and has a broad-spectrum of activity against many Gram-positive and Gram-negative bacteria. The development of triclosan tolerance with potential cross resistance to clinically relevant antibiotics in zoonotic pathogens is of concern given the widespread use of this active agent in clinical, food processing and domestic environments. Some studies have proposed that an over-dependence on triclosan-containing products could lead to the emergence of clinically important pathogens that are highly tolerant to both biocides and antibiotics. Currently, there is limited understanding of the mechanisms contributing to the emergence of triclosan tolerance in foodborne pathogens at a genetic level.
We used microarray analysis to compare gene expression between a wildtype E. coli O157:H19 isolate (WT) with a minimum inhibitory concentration (MIC) to triclosan of 6.25 ug/ml and its laboratory generated triclosan tolerant mutant (M) with a MIC of >8000 ug/ml.

overall_design: Gene expression profiling was performed on untreated E. coli O157:H19 wildtype (WTu) and mutant (Mu), and on the wildtype and mutant treated with 6 ug/ml triclosan for 30 minutes (WTt and Mt respectively). RNA was extracted from three independent biological replicates for WTu, Mu, WTt & Mt for hybridization on Affymetrix GeneChip E. coli Genome 2.0 Arrays. Micorarray analysis including pre-processing, normalisation and statistical analysis were performed using R (R, 2007) version 2.6 and Bioconductor (Gentleman et al. 2004, Genome Biol. 5:R80) version 2.1 as previously described by Morris et al.(2009, Physiol. Genomics 39:28-37).

first: Mary

last: Lenahan

first: Aine

last: Sheridan

first: Dermot

last: Morris

first: Geraldine

last: Duffy

first: Seamus

last: Fanning

first: Catherine

last: Burgess


title: SBV - Gene Expression Profiles of Lung Cancer Tumors - Adenocarcinomas and Squamous Cell Carcinomas

city: Neuchatel

first: Sam

last: Ansari

state: Neuchatel

address: Quai Jeanrenaud 5

department: Research & Development

country: Switzerland

institute: Philip Morris Products SA

summary: This dataset encompassing the profiles of 150 lung cancer tumors was developed to serve as test dataset in the SBV IMPROVER Diagnostic Signature Challenge (sbvimprover.com). The aim of this subchallenge was to verify that it is possible to extract a robust diagnostic signature from gene expression data that can identify stages of different types of lung cancer. Participants were asked to develop and submit a classifier that can stratify lung cancer patients in one of four groups – Stage 1 of Adenocarcinoma (AC Stage 1), Stage 2 of Adenocarcinoma (AC Stage 2), Stage 1 of Squamous cell carcinoma (SCC Stage 1) or Stage 2 of Squamous cell carcinoma (SCC Stage 2). The classifier could be built by using any publicly available gene expression data with related histopathological information and was tested on the independent dataset described here.

overall_design: 150 non-small cell lung cancer tumors (adenocarcinoma, AC and squamous cell carcinoma, SCC) of stages I and II were collected by surgical resection from patients who have provided consent. Adenosquamous and large cell tumor samples were excluded. The number of smokers and non-smokers was balanced: there were 41 AC1 (adenocarcinoma stage I), 36 AC2, 34 SCC1, and 39 SCC2 samples. Study pathologists at each of the seven sites (Lebanon, Republic of Moldova, Romania, Russian Federation, Ukraine, Vietnam and United States of America) reviewed both the tumor permanent sections and the frozen sections of the samples. Clinical information was also collected about tumor staging, history of prior cancers, lymph node involvement by lymph node sampling/dissection, smoking history, age, gender.

first: Marja

last: Talikka

first: Walter

last: Schlage

first: Stephanie

last: Boue

first: Yang

last: Xiang

first: Florian

last: Martin

first: Julia

last: Hoeng

first: Manuel

last: Peitsch


title: Gene expression profiling of Barrett's esophagus, adenocarcinoma, esophageal squamous epithelium and squamous cell carcinoma

city: Berlin

first: Qing

last: Wang

state: Berlin

address: Robert Rössle Str. 10

department: Surgical Oncology

country: Germany

institute: Charite-Berlin

summary: The aim of this study is to generate and validate biomarkers to stratify patients with Barrett’s esophagus in terms of risk for developing cancer. We studied gene expression profiling in 69 frozen specimens, consisting of esophageal squamous epithelium from 19 healthy subjects, 20 specimens from patients with Barrett’s esophagus and 21 cases of esophageal adenocarcinoma, 9 cased of esophageal squamous cell carcinoma by whole genome microarray analysis. Laser capture microdissection technique was applied to procure cells from defined regions of Barrett’s esophagus metaplasia and esophageal adenocarcinoma. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent cohort consisting of 42 cases. Furthermore, immunohistochemistry was performed using antibodies to two selected target molecules on a third independent cohort of 36 specimens, consisting of 36 cases. A total of 1176 genes were associated significantly with esophageal adenocarcinoma. The expression pattern of a 4 gene signature with the highest discriminant score based on linear discriminant analysis (GeneSpring GX10.2), was identified and validated by qRT-PCR in independent cohort.

overall_design: Gene expression profiling of 20 specimens of Barrett's esophagus patients, 21 specimens of adenocarcinoma patients and 19 biopsies from patients with normal esophageal squamous epithelium, 9 specimens of squamous cell carcinoma were studied.


title: Integrative genomics identifies candidate microRNAs for pathogenesis of experimental biliary atresia

city: Cincinnati

first: Jorge

middle: A

last: Bezerra

state: OH

address: 3333 Burnet Ave.

department: Gastroenterology, Hepatology & Nutrition

institute: Cincinnati Children's Hospital Medical Center

type:
Other
Expression profiling by array

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

overall_design: Refer to individual Series


title: TET2 loss-of-function mutations associate with a DNA hypermethylation signature in diffuse large B-cell lymphoma (DNA methylation)

city: Los Angeles

first: Vasu

last: Punj

state: CA

address: Biggy Street

institute: USC

type: Methylation profiling by genome tiling array

summary: Genome wide DNA methylation profiling of patient samples with TET2 mutations and Wild type TET2 status . The Illumina Infinium HumanMethylation 450_15017482_v.1.1 was used to obtain DNA methylation profiles across approximately 482,421  CpGs in fresh frozen lymphoma  samples. Samples include 19 TET2 wild type and 12 TET2 mutant samples.

overall_design: Bisulphite converted DNA from the 31 samples were hybridised to the Illumina Infinium HM450K Human Methylation Beadchip v1.2

first: Fazila

last: Asmar

first: Jesper

last: Christensen

first: Marianne

middle: T

last: Pedersen

first: Anja

first: Anders

middle: B

last: Nielsen

first: Christoffer

last: Hother

first: Ulrik

last: Ralfkiaer

first: Peter

middle: D

last: Brown

first: Elisabeth

first: Kristian

last: Helin

first: Kirsten

last: Gronbaek


title: A common rejection module for acute rejection in multiple organs identifies novel therapeutics.

status: Public on Oct 04 2013

city: Stanford

first: Purvesh

last: Khatri

address: 279 Campus Dr., Beckman B235A

department: Medicine

institute: Stanford University

summary:
Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol  biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for non-transplant indications, could regulate specific CRM genes and reduce the number of graft infiltrating cells during acute rejection. We treated mice with HLA-mismatched murine cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatina on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning and rational drug design.
The eight transplant data sets used for discovery include  GSE4315, GSE2596, GSE4470, GSE9377,  GSE1563, GSE9493, GSE13440, GSE6095. The two additional independent cohorts of 151 transplant biopsies are GSE25902 and GSE1563. Not all samples from all studies were used. Only the samples marked as either AR or STA in each data set were used for analysis.

overall_design: The 101 samples in this study were used as case-control experiment between acute rejection (AR) and stable (STA) in renal transplant. The samples in this series are one of the three independent validation cohorts. The other two cohorts are described in GSE21374 and GSE36059


title: Gestational Age-Dependent Changes in Gene Expression of Metabolic Enzymes and Transporters in Pregnant Mice

status: Public on Oct 08 2013

city: Seattle

first: James

middle: William

last: MacDonald

state: WA

address: 4225 Roosevelt Way NE

department: Environmental and Occupational Health Sciences

institute: University of Washington

summary: Knowing the gene expression profiles of drug-metabolizing enzymes and transporters throughout gestation is important for understanding the mechanisms of pregnancy-induced changes in drug pharmacokinetics. In this study, we compared gene expression of drug-metabolizing enzymes and transporters in the maternal liver, kidney, small intestine, and placenta of pregnant mice throughout gestation by microarray analysis. Specifically, we investigated cytochrome P450 (Cyp), UDP-glucuronosyltranserase (Ugt), and sulfotransferase (Sult), as well as ATP-binding cassette (Abc) and solute carrier (Slc) transporters. We found that relatively few Ugt and Sult genes were impacted by pregnancy in maternal tissues and placenta. Cyp1a2, most Cyp2 isoforms, Cyp3a11, and Cyp3a13 in the liver were down-regulated, with the greatest changes occurring on gestation days (gd) 15 and 19 compared to non-pregnant controls (gd 0). However, Cyp2d40, Cyp3a16, Cyp3a41a, Cyp3a41b, and Cyp3a44 in the liver were induced throughout pregnancy. Cyp expression in mid-gestation placenta (gd 10 and 15) was generally greater than that in term placenta (gd 19). There were also notable changes in Abc and Slc transporters. Abcc3 in the liver was down-regulated by 60%, and Abcb1a, Abcc4, and Slco4c1 in the kidney were down-regulated by 30-60% on gd 15 and 19 versus gd 0. Abcc5 in the placenta was induced 3-fold on gd 10 versus gd 15 and 19, whereas Slc22a3 expression in the placenta on gd 10 was 90% lower than that on gd 15 and 19. Overall, this study demonstrates important gestational age-dependent expression of drug-metabolizing enzymes and transporter genes, which may have mechanistic relevance to human pregnancy.

overall_design: Ninety pregnant mice at gestational days 0, 7.5, 10, 15, and 19 (n = 5-6 per gestational age) were used for the maternal liver, kidney, small intestine and placenta. The placentas were collected on gestational days 10, 15, and 19.

first: Theodor

middle: K

last: Bammler

first: Richard

middle: P

last: Beyer

first: Federico

middle: M

last: Farin

first: Diana

middle: L

last: Shuster

middle: W

first: Jesse

last: Tsai

first: Mary

middle: F

last: Hebert

first: Kenneth

middle: E

last: Thummel

first: Qingcheng

last: Mao


title: TWEAK-treated time course in ACHN cells

city: Watertown

last: Simcox

state: MA

address: 500 Arsenal St

institute: Forma Therapeutics

summary: Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.

overall_design: ACHN cells untreated or treated with 1090-TW (TWEAK) for 4 hours, 8 hours, or 24 hours.  Four replicates for each condition were performed.

first: Windy

last: Berkofsky-Fessler

first: Holly

last: Hilton

first: Saumya

last: Pant


title: Gene expression profiles of pediatric IBD remission patients

city: Utrecht

first: Pieter

last: van Lierop

address: Lundlaan 6

country: Netherlands

institute: UMC Utrecht

summary:
Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation
We performed (un)supervised clustering analysis of IBD-associated genes and applied Ingenuity® pathway software to identify specific molecular profiles between patients.

overall_design: We analyzed RNA gene expression profiles of peripheral blood leucocytes (PBL) from pediatric IBD patients in clinical remission and age-matched controls.

first: Sigrid

last: Swagemakers


title: TWEAK-treated time course in MDA-MB-436 cells

overall_design: MDA-MB-436 cells untreated or treated with 1090-TW (TWEAK) for 15 minutes, 1 hour, 4 hours, 8 hours, or 24 hours.  Five replicates for each condition were performed.


title: EZH2 over-expression is associated with gain of chromosome arm 7q and essential for cell cycle progression and a marker of poor prognosis in neuroblastoma

status: Public on Oct 06 2013

city: Amsterdam

last: Volckmann

state: Noord-Holland

address: van der Boechorststraat 6a

department: Laboratory of Experimental Oncology and Radiobiology

institute: msterdam UMC and University of Amsterdam

summary: Neuroblastoma is an often aggressive childhood cancer with several large chromosomal regions showing recurrent gains or losses. Chromosome 7q is gained in 40-60% of neuroblastomas, but despite being the second most frequent genomic aberration, no oncogenes have been linked to 7q gain.

overall_design: We performed expression profiling and array CGH on 88 primary neuroblastoma tumors to identify a 7q oncogene. We assayed neuroblastoma cell lines and combined bioinformatic analyses on the in vitro and in vivo data.

first: Hinco

middle: J

last: Gierman

first: Mireille

middle: H

last: Indemans

first: Jan

last: Koster

last: Molenaar

first: Chrisoula

last: Efstathiadou

first: Peter

last: van Sluis

first: Dirk

last: Geerts

first: Katleen

last: de Preter

first: Ingrid

last: Øra

first: Frank

last: Speleman

first: Rogier

last: Versteeg

first: Marli

last: Ebus


title: Development pathway for skin resident memory CD103+CD8+ T cells

status: Public on Oct 01 2013

city: Parkville

first: Joel

middle: Zhi-Iong

last: Ma

state: Victoria

address: Grattan Street

country: Australia

institute: University of Melbourne

summary: Tissue resident memory T cells (TRM) provide superior protection against infection localised to extra-lymphoid compartments in the body.  Here we show that CD103+CD8+ TRM cells develop in skin from killer cell lectin-like receptor (KLR)G1-negative precursors that selectively infiltrate the epithelial layer.  In the skin, a combination of chemokine-guided epithelial entry, local interleukin (IL)-15 and transforming growth factor (TGF)-β signalling is required for formation and survival of these long-lived memory cells. Importantly, TRM differentiation results in the gradual acquisition of a unique transcriptional profile that differs from that expressed by memory cells in the circulation and other types of skin-resident intra-epithelial T cells, such as the dendritic epidermal T cells (DETC). We provide a comprehensive molecular and developmental framework for the local differentiation of a distinct type of peripheral memory T cell that contributes to an important first-line of immune defence in barrier tissues such as skin and mucosa.

overall_design: 24 samples were analyzed: 3 replicates of memory gB-T CD8+. CD103+ T cells isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of memory P14 CD8+ T cells isolated from gut of mice on  day 60 p.i. with LCMV Armstrong. 3 replicates of memory gB-T CD8+ T cells from the lung of mice on day 30 p.i. with influenza WSN. 3 replicates of memory CD62L high CD8+ T cells from the spleen of mice on day 30 p.i. with HSV KOS. 3 replicates of memory CD62L low CD8+ T cells from the spleen of mice of day 30 p.i. with HSV KOS. 3 replicates of γδ-DETC  isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of αβ-DETC from naive TCRδ-/- mice; and 3 replicates of naive gB-T CD8+ T cells from the spleen of naive gB-T transgenic mice.

first: L

last: Mackay

first: A

last: Rahimpour

first: J

middle: Z

first: N

last: Collins

last: Stock

first: M

last: Hafon

last: Vega-Ramos

first: P

last: Lauzurica

first: S

middle: N

last: Mueller

first: T

last: Stefanovic

first: D

last: Tscharke

first: W

middle: R

last: Heath

last: Inouye

last: Gebhardt

first: F

last: Carbone


title: Focal amplification of HOXD-harboring chromosome region is implicated in multiple-walled carbon nanotubes-induced carcinogenicity

status: Public on Oct 02 2013

city: Taipei

first: Ping

last: Wu

address: NO.1 JEN AI ROAD SECTION 1 TAIPEI 100 TAIWAN R.O.C.

department: department of medicine

country: Taiwan

institute: Graduate Institute of Toxicology

summary:
Amplificaition of HOXD9 and HOXD13 genes was found in MWCNTs induced carcinogencity. By overexpression or silence of of HOXD9 and HOXD13 gene may alter tumorigenicity.
To investigate the realted signaling pathways invovled in HOXD regulated tumorigencity, we analyzed the gene expression profile of the HOXD9 or HOXD13 overexpression HEK293 cells, which compared to vehicle expressing cells

overall_design: HEK293 cells was transfected with HA-tag-HOXD9 and V5-tag HOXD13 vector, and further selected by G418. Three independnent clones and mix clones of each genes were selected, and compared to corresponding tag control cell. (HA-HOXD9-mix, a, b, c v.s HA-MOCK-1, 2, 3) (V5-HOXD13-mix, a, b, c v.s V5-MOCK-1, 2, 3)

first: Shin-Sheng

last: Yuan

first: Chao-Chi

last: Ho

first: Wan-Yu

last: Hsieh

first: Wei

last: Chen

first: Ker-Chau

last: Li

first: Pan-Chyr

last: Yang

first: Huei-Wen


title: TWEAK-treated time course in CAKI cells grown as xenografts

first: Mary

last: Simcox

platform_organism:
Homo sapiens
Mus musculus

overall_design: CAKI cells impanted as xenografts in Athymic, Nu/Nu nude mice, treated with anti-TWEAK antibody (TW212) or Vehicle for 24 hours.  Four replicates for each condition were performed.  RNA was extracted from xenografts, processed and hybridized to human and mouse chips.

first: Windy

last: Berkofsky-Fessler

first: Holly

last: Hilton

first: Saumya

last: Pant


title: Clinical, Molecular and Genetic Validation of a Murine Orthotopic Xenograft Model of Pancreatic Adenocarcinoma using Fresh Human Specimens

city: Charlottesville

first: Edik

middle: Matthew

last: Blais

state: Virginia

address: 415 Lane Road

department: Biomedical Engineering

institute: University of Virginia

summary:
This project describes the establishment and validation of a murine orthotopic xenograft model using fresh human tumor samples that recapitulates the critical components of human pancreatic adenocarcinoma.  The authors discuss the proven and theoretical advantages of the model as well as future translational implications.
Background:  Relevant preclinical models that recapitulate the key features of human pancreatic ductal adenocarcinoma (PDAC) are needed in order to provide biologically tractable models to probe disease progression and therapeutic responses and ultimately improve patient outcomes for this disease.  Here, we describe the establishment and clinical, pathological, molecular and genetic validation of a murine, orthotopic xenograft model of PDAC.  Methods: Human PDACs were resected and orthotopically implanted and propagated in immunocompromised mice.  Patient survival was correlated with xenograft growth and metastatic rate in mice. Human and mouse tumor pathology were compared.  Tumors were analyzed for genetic mutations, gene expression, receptor tyrosine kinase (RTK) activation, and cytokine expression.  Results: Fifteen human PDACs were propagated orthotopically in mice.   Xenografts developed peritoneal and liver metastases. Time to growth and metastatic efficiency in mice each correlated with patient survival.  Tumor architecture, nuclear grade and stromal content were similar in patient and xenografted tumors. Propagated tumors closely exhibited the genetic and molecular features known to characterize pancreatic cancer (e.g. high rate of KRAS, p53, SMAD4 mutation and EGFR activation). The correlation coefficient of gene expression between patient tumors and xenografts propagated through multiple generations was 93 to 99%.  Analysis of gene expression demonstrated distinct differences between xenografts from fresh patient tumors versus commercially available PDAC cell lines.  Conclusions:  Our orthotopic xenograft model derived from fresh human PDACs closely recapitulates the clinical, pathologic, genetic and molecular aspects of human disease. This model has resulted in the identification of rational therapeutic strategies to be tested in clinical trials and will permit additional therapeutic approaches and identification of biomarkers of response to therapy.

overall_design: 47 Samples in total were generated for normal pancreatic tissue in patients, pancreatic tumors in patients, pancreatic tumors propagated in a mouse xenograft model, and pancreatic cancer cell lines in vitro. Clustering analysis was performed to evaluate the differences between patient tumors, xenograft tumors, established cancer cell lines, and cell lines derived from xenografts.

first: Dustin

last: Walters

first: Jayme

last: Stokes

first: Sara

last: Adair

first: Edward

last: Stelow

first: Cheryl

middle: A

last: Borgman

first: Bryce

middle: T

last: Lowrey

first: Wenjun

last: Xin

first: Jae

last: Lee

first: Jason

last: Papin

first: J

last: Parsons

first: Todd

last: Bauer


title: Expression data from MCF7 and BT474 cell lines after long term estrogen deprivation culture

city: Stockholm

first: Nicholas

last: Tobin

address: Cancer Center Karolinska

country: Sweden

institute: Karolinska Institutet

summary: MCF7 and BT474 cell lines were exposed to LTED culture for 0 and 2 days, 6 weeks and 10 months and monitored for changes in gene expression

overall_design: MCF7 0 days vs 2 days, 6 weeks and 10 months, BT474 0 days vs 2 days, 6 weeks and 10 months

first: Tobin

last: Nicholas P


title: Integrated, genome-wide screening for hypomethylated oncogenes in salivary gland adenoid cystic carcinoma

city: Baltimore

first: chunbo

last: shao

state: MD

address: 1550 Orleans Street

department: Otolaryngology

institute: Johns Hopkins University

summary: Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy amongst head and neck tumors that is poorly understood on a molecular level. We sought to perform a comprehensive approach for novel oncogene candidate screening under the control of promoter methylation in order to learn more about the molecular basis of this unusual disease.

overall_design:
We performed global demethylation of normal salivary gland cell strains using 5-aza-deoxycytidine (5-Aza dC) and trichostatin (TSA). Expression arrays were performed, and the profiles of treated and untreated cells compared.
We then used expression microarray analysis of primary ACC and normal salivary gland samples to generate ACC-specific expression profiling. Next, we integrated the two profiles to identify a subset of genes for further validation of decreased methylation in the promoter region in ACC vs normals. Finally, only genes that showed decreased methylation in ACC compared to normal were further validated for mRNA, protein, and promoter methylation levels in a larger ACC cohort.

first: Chunbo

last: Shao

first: Wenyue

last: Sun

first: Marietta

last: Tan

first: Chad

last: Glazer

first: Sheetal

last: Bhan

first: Xiaoli

last: Zhong

first: Carole

last: Fakhry

first: Rajni

last: Sharma

first: William

last: Westra

first: Christopher

last: Moskaluk

first: David

last: Sidransky

first: Joseph

last: Califano

first: Patrick

last: Ha


title: TWEAK-treated time course in U2OS cells.

first: Mary

last: Simcox

summary: Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14.  In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models.  Phase I pharmacodynamic data from patients are consistent with preclinical results.  TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression.  Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability.  Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.

overall_design: U2OS cells untreated or treated with 1090-TW (TWEAK) for 15 minutes, 1 hour, 4 hours, 8 hours, or 24 hours.  Five replicates for each condition were performed.

first: Windy

middle: D

last: Berkofsky-Fessler

first: Holly

last: Hilton

first: Saumya

last: Pant


title: Phrenic neuron determinant gain-of-function screen in M. musculus ES cell-derived motor neurons

city: London

first: Eric

last: Blanc

address: New Hunt's House

department: MRC Centre for Developmental Neurobiology

country: United Kingdom

institute: King's College London

summary:
Expression response after induction of putative phrenic neuronal determinants in ES cell-derived motor neurons was compared to a pre-determined list of genes over-expressed in FACS-sorted primary.
Transcription factor Pou3f1 was identified as a major determinant of phrenic identity.

overall_design: Expression in induced cell lines were compared to YFP controls, and over-representation of phrenic genes was computed for the list of differentially expressed genes in each indiced cell lines.

first: Carolina

last: Barcellos-Machado

first: Ivo

last: Lieberam


title: Comprehensive gene expression profile of mouse extrahepatic bileducts and gallbladder during a mouse model of biliary atresia.

first: Jorge

last: Bezerra

summary: Newborn Balb/c mice were injected with 1.5x10^6 fluorescent-forming units (ffu) of Rhesus rotavirus type-A or 0.9% NaCl (normal saline) intraperitoneally within 24 hours of birth to induce experimental model of biliary atresia. The extrahepatic bile ducts including gallbladder were microdissected en bloc at 3, 7 and 14 days after rhesus rotavirus or saline injection. GeneChip® Mouse Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was differently regulated after rhusus rotavirus injection compare to the normal saline controls.

overall_design: Gene expression profiling.  Each experimental conditon has 3 sets of samples . Two to six extrahepatic bileducts were pooled prior to isolating total RNA depending on the size to ensure adequate RNA quantities to perform experiments quantifying mRNA expression.

first: Kazuhiko

last: Bessho

first: Kumar

last: Shanmukhappa

first: Rachel

last: Sheridan

first: Pranavkumar

last: Shivakumar

first: Reena

last: Mourya

first: Stephanie

last: Walters

first: Vivek

last: Kaimal

last: Dilbone

first: Anil

middle: G

last: Jegga


title: Comparison of gene expression profile of SMEI patient iPSCs and control human Embryonic stem cells

city: Beijing

first: Jiao

last: Jiao

address: No.7 Science park Road

institute: National Institute of Biological Sciences, Beijing

summary: SMEI patient induced pluripotent stem cells (iPSCs) were derived from patient fibroblasts. In order to test the similarity between patient iPSCs and human embryonic stem (hES) cells, microarry analysis was carried out on SMEI patient iPSCs and human embryonic stem cells.

overall_design: SMEI patient iPSCs were derived from patient fibroblasts. Human embryonic stem cells were derived from human blastocyst.And we use the microarray method to compare the global expression of patient iPSCs and embryonic stem cells.

first: Yuanyuan

last: Yang


title: Gene expression patterns of mesenchymal stem cells from bone marrow and Wharton's jelly of umbilical cord

status: Public on Sep 30 2013

first: Jui-Yu

last: Hsieh

address: No. 155, Sec 2, Li-Nong Street

institute: National Yang-Ming University

summary: Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton's jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. We isolated MSCs from Wharton’s jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their transcriptional profiles.

overall_design: In this study, BM-MSCs and WJ-MSCs were isolated from 4 and 3 independent donors, respectively.

first: Shing-Jyh

last: Chang

first: Hsei-Wei

last: Wang

first: Ko-Hsun

last: Liao

first: I-Hui

last: Lee

first: Wei-Shiang

last: Lin

first: Chun-Hsien

last: Wu

first: Wen-Yu

first: Shu-Meng

last: Cheng


title: Expression data from knockdown of ZXDC1/2 in PMA-treated U937

city: Kansas City

first: Joseph

last: Fontes

state: KS

address: 3901 Rainbow Blvd

department: Biochemistry and Molecular Biology

institute: Univ Kansas Medical Center

summary:
ZXDC1 augments the expression of various markers of monocyte/macrophage differentiation when over-expressed in the U937 cell line treated with the phorbol ester PMA.  Likewise, knockdown of ZXDC1 restricts the induced expression of these markers.  We sought to identify specfic gene targets of ZXDC1 during the process of monocyte/macrophage differentiation in U937 by performing gene expression profiling in cells exhibiting reduced expression of ZXDC1 compared to controls.
We used microarray to identify genes regulated by ZXDC during PMA-induced differentiation of U937 monoblasts towards a monocyte/macrophage phenotype

overall_design: An inducible shRNAmir (Tet-On) cell line was established in the U937 background that displayed significant, reproducible, and doxycycline inducible knockdown of ZXDC1.  Using this cell line, we created four experimental groups to identify gene targets of ZXDC1 during PMA-induced differention towards a monocyte/macrophage phenotype: Vehicle alone; Vehicle+Doxycycline; PMA alone; PMA+Doxycycline. Each independent group was used for RNA extraction and hybridization on Affymetrix microarray chips.

first: Jon

last: Ramsey


title: Phrenic neuronal determinants screen in M.Musculus

first: Eric

last: Blanc

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

overall_design: Refer to individual Series


title: TET2 loss-of-function mutations associate with a DNA hypermethylation signature in diffuse large B-cell lymphoma

first: Vasu

last: Punj


title: Integrative transcriptome sequencing identifies trans-splicing events with important roles in human embryonic stem cell pluripotency

first: Chun

middle: Ying

last: Yu

address: 128 Academia Road, Section 2

department: Genomic Research center

institute: Academia sinica

summary: Trans-splicing is a post-transcriptional event that joins exons from separate pre-mRNAs. Detection of trans-splicing is usually severely hampered by experimental artifacts and genetic rearrangements. Here, we develop a new computational pipeline, TSscan, which integrates different types of high-throughput long-/short-read transcriptome sequencing of different human embryonic stem cell (hESC) lines to effectively minimize false positives while detecting trans-splicing. Combining TSscan screening with multiple experimental validation steps revealed that most chimeric RNA products were platform-dependent experimental artifacts of RNA sequencing. We successfully identified and confirmed four trans-spliced RNAs, including the first reported trans-spliced large intergenic noncoding RNA ("tsRMST"). We showed that these trans-spliced RNAs were all highly expressed in human pluripotent stem cells and differentially expressed during hESC differentiation. Our results further indicated that tsRMST can contribute to pluripotency maintenance of hESCs by suppressing lineage-specific gene expression through the recruitment of NANOG and the PRC2 complex factor, SUZ12. Taken together, our findings provide important insights into the role of trans-splicing in pluripotency maintenance of hESCs and help to facilitate future studies into trans-splicing, opening up this important but understudied class of post-transcriptional events for comprehensive characterization

overall_design: We disrupt the expression of tsRMST by introducing shRNA that targeted the no-co-linear junction site of tsRMST in hESCs using lentiviral vectors. shLuc was used as control.

first: Chan-Shuo

first: Chun-Ying

first: Ching-Yu

last: Chuang

first: Hung-Chih

last: Kuo

first: Trees-Juen


title: Transcriptional responses of control and MDV3100 resistant lines to DMSO or MDV3100

city: Cambridge

first: Joshua

middle: M

last: Korn

address: 250 Mass Ave

institute: Novartis

summary:
LNCaP-derived MDV3100-resistant clones were treated with MDV3100 for 24h prior to collection
This experiment is designed to see if MDV3100 resistant clones remain responsive to MDV3100

overall_design: Control and resistant clones were seeded in 6-well plates for 3d prior to treatment with DMSO or MDV3100 for 24h

first: Manav

last: Korpal


title: TWEAK-treated time course in ACHN cells grown as xenografts

first: Mary

last: Simcox

summary: Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.

overall_design: ACHN cells impanted as xenografts in Athymic, Nu/Nu nude mice, treated with anti-TWEAK antibody (TW212), B20 antibody control or Vehicle for 4 hours, 8 hours, or 24 hours.  Five replicates for each condition were performed.

first: Windy

last: Berkofsky-Fessler

first: Holly

last: Hilton

first: Saumya

last: Pant


title: Testing rescue of AR signaling by ectopic expression of mutant AR allele in the presence of MDV-3100

summary:
Genetically engineered LNCaPs overexpressing various AR alleles were treated with 0.1% DMSO or 10uM MDV3100 for 24h prior to collection
This experiment is designed to see if expressing the F876L/T877A mutant AR can rescue AR signaling in the presence of MDV3100

overall_design: Engineered lines were seeded in 6-well plates for 3d with 100ng/ml doxycycline prior to treatment with 0.1% DMSO or 10uM MDV3100 for 24h


title: The CURELUNG Project from the Epigenetics Side (Patients dataset)

status: Public on Oct 03 2013

city: L'Hospitalet de Llobregat

first: Manel

last: Esteller

state: Barcelona

address: Hospital Duran i Reynals Av. Gran Via s/n km, 2.7

department: PEBC

country: Spain

institute: IDIBELL

summary: Non-small cell lung cancer (NSCLC) is a very common solid tumor where only small advances in the reduction of relapse-free survival and overall survival have been accomplished. The issue is particularly critical for stage I patients where there are not available biomarkers, in the absence of detectable nodal or other metastatic involvement, that might indicate which high-risk patients should receive the beneficially proved adjuvant chemotherapy. We aimed to find DNA methylation markers with prognostic value that could be helpful in this regard and complement the conventional staging. A DNA methylation microarray that analyzes 450,000 CpG sites in the human genome was used to study primary tumoral DNA obtained from a multicenter cohort of 490 patients with NSCLC, corresponding to 339 adenocarcinomas, 133 squamous carcinomas and 18 large cell carcinomas, in addition to 25 normal lung epithelium samples. The obtained prognostic DNA methylation markers were validated by the development of a single methylation-pyrosequencing assay in an independent cohort of 143 patients with stage I NSCLC. The unsupervised clustering of the studied primary NSCLC distinguished two branches with distinct clinical outcomes. Those CpG sites that were the best predictors of recurrence in stage I NSCLC patients were further confirmed in the described independent cohort. Both the global DNA methylation classifier and the highly-ranked aberrantly methylated single genes improved prognostic accuracy beyond standard stagings.

overall_design: DNA was quantified by Quant-iT PicoGreen dsDNA Reagent (Invitrogen) and the integrity was analyzed in a 1.3% agarose gel. Bisulfite conversion of 600 ng of each sample was performed according to the manufacturer's recommendations for the Illumina Infinium Assay. Effective bisulfite conversion was checked for three controls that were converted simultaneously with the samples. 4 ul of bisulfite-converted DNA were used to hybridize on an Infinium HumanMethylation 450 BeadChip, following the Illumina Infinium HD Methylation protocol. Chip analysis was performed using the Illumina HiScan SQ fluorescent scanner. The intensities of the images were extracted using GenomeStudio (2011.2) Methylation module (1.8.5) software. The methylation score of each CpG is represented as a beta value. This dataset includes 444 patient samples.

first: Sebastian

last: Moran

first: Antonio

last: Gomez

first: Juan

last: Sandoval

first: Jesús

last: Méndez


title: Blocking TWEAK inhibits tumor growth through inhibition of tumor cell proliferation and survival and by enhancing the host antitumor immune response

sample_organism:
Homo sapiens
Mus musculus


title: Expression data from mouse embryo (E5) cultured in the narrow and wide cavity

status: Public on Sep 27 2013

city: Izumi

first: Isao

last: Matsuo

state: Osaka

address: 840 Murodo-cho

department: Department of Molecular Embryology

institute: Osaka Medical Center and Research Institute for Maternal and Child Health

summary: The mouse anterior-posterior (A-P) axis polarization is preceded by formation of the distal visceral endoderm (DVE). However, the mechanism of the emergence of DVE cells is not well understood. Here, we show by in vitro culturing of embryos immediately after implantation in micro-fabricated cavities (narrow; 90 micro-meter, wide; 180 miro-meter in diameter) that the external mechanical cues exerted on the embryo, i.e. cultured in the narrow cavity, are crucial for DVE formation as well as elongated egg cylinder shape. This implies that these developmental events immediately after implantation are not simply embryo-autonomous processes but require extrinsic mechanical factors. Further whole genome-wide gene expression profiles with DNA microarray revealed that no significant difference of transcripts were evident with or without mechanical cues except DVE-related markers. Thus, we propose that external mechanical cues rather than not specific molecular pathways can trigger the establishment of the A-P axis polarization, which is one of the fundamental proccesses of mammalian embryogenesis.

overall_design: To identify the differences between the embryos cultured with or without external mechanical cues, we collected mouse embryos at E5.0 and cultured in the narrow (90 micro-meter in diameter) or the wide (180 micro-meter in diameter) cavities for 8 hours for RNA extraction and hybridization on Affymetrix microarrays. Arrays were performed using Affymetrix mouse Gene 1.0 ST arrays. Analysis was performed on three biological replicates of the mouse embryos cultured in the narrow and wide cavities for 8 hours.


title: Gene expression in human healthy control and ISCU myopathy patient muscle biopsies

status: Public on Sep 23 2013

city: Newark

first: Chuming

last: Chen

state: DE

address: 15 Innovation Way, Suite 205

department: Computer and Information Sciences

institute: University of Delaware

summary: We performed microarray analysis on ISCU myopathy patient muscle biopsies to identify transcriptional modulation of pathways involved in the cellular response to Fe-S cluster deficiency.

overall_design: We included RNA samples from five healthy control individuals as well as three different ISCU myopathy patients.

first: Daniel

last: Crooks

first: Tracey

last: Rouault


title: Gene expression of SUM159 breast cancer cell line expressing microRNA--203

city: Houston

first: Joe

last: Taube

state: Texas

address: 7435 Fannin St

department: Translational Molecular Pathology

institute: MD Anderson Cancer Center

summary: Determine the effect of miR-203 expression on the global mRNA expression in mesenchymal breast cancer cell line.

overall_design: Generate control (pBabe puro) and miR-203 (pBabe puro miR-203) cells using retroviral transduction and puromycin selections.  Extract total RNA using Trizol.

first: Joseph

first: Sendurai

last: Mani


title: Effect of H19 Knockdown by siRNA on gene expression in C2C12 cells

city: ct

first: haifeng

last: zhang

address: new haven

department: pathology

institute: yale

summary: We used microarrays to characterize the global changes in gene expression in C2C12 cells due to siRNA knockdown of long non-coding RNA H19

overall_design: Control siRNA or siRNA specific for mouse H19 were transfected into day1 differentiating C2C12 myoblasts in triplicates. 40 H later total RNAs were isolated and subjected with microarray analysis.

first: Amanda

last: Kallen

first: Xiao-Bo

last: Zhou

first: Jie

last: Xu

first: Chong

last: Qiao

first: Jing

last: Ma

first: Lei

last: Yan

first: Lingeng

last: Lu

first: Chaochun

last: Liu

first: Jae-Sung

last: Yi

first: Haifeng

last: Zhang

first: Wang

last: Min

first: Anton

last: Bennett

first: Richard

middle: I

last: Gregory

first: Ye

last: Ding

first: Yingqun

last: Huang


title: Expression analysis from Runx2-deficient pDCs from mouse

city: New York

first: Catherine

last: Sawai

state: New York

address: 701 W. 168th Street - HHSC 9-906

institute: Columbia University Medical Center

summary: Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical dendritic cells (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. Runx2-deficient murine pDCs developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes including chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.

overall_design: Total BM cells were isolated from Runx2-/- and wildtype fetal liver chimeras 2 months post-reconstitution. BM cells were stained with antibodies against surface markers CD11b, CD11c, BST2, and B220. CD11b- BST2+ B220+ pDCs were purified by flow cytometry on a BD FACS Aria. RNA was purified immediately and prepared for microarray analysis using the Ambion WT labeling kit. Expression was analyzed using Affymetrix Mouse Gene 1.0 ST.

first: Boris

middle: V

last: Reizis


title: Expression data from mouse model using targeted deletion of hepatic RICTOR (Albumin-Cre Rictor LoxP/LoxP)

city: Providence

first: Joan

last: Boylan

state: RI

address: 593 Eddy Street

department: Pediatrics

institute: Rhode Island Hospital

summary:
Recent work using mouse models has revealed that mTORC2, which unlike mTORC1 is not acutely sensitive to rapamycin, plays a key role in the regulation of organismal physiology. The substrates and pathways regulated by mTORC2 are at present relatively unknown
Using a mouse model with a targeted deletion of hepatic RICTOR, we investigated the loss of mTORC2 on the murine liver transcriptome

overall_design: Rictor floxed (RKO) and control mice (n=4 per group) were fasted overnight, refed for 3 hr, then sacrificed. Livers were removed, rinsed in PBS, and flash frozen in liquid nitrogen. RNA was extracted and hybridized to  Affymetrix Genechip Mouse Gene 1.0 ST arrays

first: Dudley

middle: W

last: Lamming

first: David

last: Sabatini

first: Philip

last: Gruppuso


title: Expression data from Ctla4-/- and DKO CD4+ Tconv cells

status: Public on Sep 25 2013

city: Worcester

first: Joonsoo

last: Kang

address: 368 Plantation St. ASC9-1047

institute: UMass Medical School

summary:
Ctla4-/- mice suffer from a severe autoimmunity characterized by indiscriminate self-reactive T cell activation. Itk-/-Ctla4-/- (DKO) mice are protected from lethal autoimmunity despite a fulminant autoimmune process in the LNs as self-reative T cells fail to migrate to destroy tissues.
We used microarray to identify underlying differences in gene expression that could account for lack of migration of DKO T cells into tissues.

overall_design: CD4+CD25neg T cells from 3 weeks old male Ctla4-/- or DKO mice were sorted in duplicates, RNA was extracted using TRIzol reagent and microarray analysis performed with the Affymetrix MoGene 1.0 ST array

first: Nitya

last: Jain


title: Gamma-secretase inhibitor plus fludarabine in CLL

status: Public on Sep 21 2013

city: BARCELONA

first: DOLORS

last: COLOMER

address: VILLARROEL 170

institute: IDIBAPS-HOSPITAL CLINIC

summary:
Combination of GSI with fludarabine has a synergistic antileukemic effect in primary NOTCH1-mutated CLL cells
We used microarrays to detail the mechanism of synergy of GSI and fludarabine combination in NOTCH1-mutated CLL cells

overall_design: Global RNA expression in CLL primary cells treated with  GSI, fludarabine and the combination at 48 hours of treatment

first: Monica

last: Lopez-Guerra

first: Silvia

last: Xargay-Torrent

first: Dolors

last: Colomer


title: Influence of 3,5,3'-Triiodothyronine (T3) on differentiating progenitor cells of the enteric nervous system (ENS)

city: Tuebingen

first: Roland

middle: Alexander

last: Mohr

address: Oesterbergstrasse 3

department: Experimental Embryology

institute: Institute of Anatomy

summary: Differentiation assays with neural progenitor cells of the enteric nervous system (ENS) showed elongated neurite outgrowth under influence of 3,5,3'-Triiodothyronine (concentrations 50 nm and 100 nm). For analysis, neural cells were stained with TUJ1 (beta-Tubulin III). Microarray analysis should enlighten these results on a genetical basis and give hints about the regulation pathways.

overall_design: We analyzed 2 groups with 3 samples each: 1 group consistent of cells treated with 100 nm T3 for 1 day and 1 control group consistens of cells without T3 treatment

first: Lothar

last: Just


title: DNA methylation analysis of melanoma progression to brain metastasis

status: Public on Sep 19 2013

city: Santa Monica

first: Dave

last: Hoon

address: 2200 Santa Monica Boulevard

department: Translational Molecular Medicine

institute: Saint John's Cancer Institute

summary: Melanoma is one of the most aggressive and treatment-resistant cancers. It represents the most life-threatening neoplasm of the skin, and its incidence has been increasing for the last three decades. Melanoma evolves from the local transformation of melanocytes to primary tumors, which can metastasize to multiple organs. Brain metastases represent one of the most significant causes of death in cutaneous melanoma patients. Despite aggressive multi-modality threapy, patients with melanoma brain metastasis have a median survival of less than a year, with a majority of these patients dying as a result of their intracranial disease. We aimed to find brain metastasis-specific molecular markers. To identify alterations in DNA methylation related to brain metastasis, we used Illumina 450K BeadChips to assess differentially methylated regions in melanocytes, primary melanomas, lymph node metastases, and brain metastases.

overall_design: Bisulphite-converted DNA from 40 specimens was hybridised to the Illumina Infinium 450k Human Methylation BeadChip.

first: Sharon


title: Expression data from two breast cancer cell lines

status: Public on Sep 26 2013

city: Boston

first: Xiaole

middle: Shirley

last: Liu

address: 450 Brookline Avenue, CLS 11007

department: Department of Biostatistics and Computational Biology

institute: Dana-Farber Cancer Institute, Harvard School of Public Health

summary:
During cancer progression, carcinoma cells encounter a variety of cytotoxic stresses such as hypoxia, nutrient deprivation, and low pH as a result of inadequate vascularization. To maintain survival and growth in the face of these physiologic stressors, a set of adaptive response pathways are induced. One adaptive pathway well studied in other contexts is the unfolded protein response (UPR), of which XBP1 is an important component.
We used microarrays to detect transcriptome profile changes after XBP1 knockdown in breast cancer cell lines, and identify genes and pathways regulated by XBP1, which could help elucidate how XBP1 mediates the adaptive response of breast cancer to cytotoxic stresses.

overall_design: We extracted RNA and hybridized it to Affymetrix microarrays in two breast cancer cell lines (T47D and MDA-MB-231) under treated (hypoxia and glucose deprivation) or untreated conditions with XBP1 knockdown or not.

first: Chen

last: Xi

first: Glimcher

last: Laurie


title: Genome-wide analysis of Crohn's disease and ulcerative colitis biopsy samples.

first: Trinidad

last: Montero

address: Charterhouse Square

department: Biochemical Pharmacology

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

summary: Gene expression patterns of Crohn's disease (CD) and ulcerative colitis (UC) colonic specimens were analyzed using whole-genome microarrays. Healthy control samples were included in order to detect gene expression changes associated with CD or UC. CD and UC samples were also compared in order to identify the molecular mechanisms that distinguish both fenotypes of inflammatory bowel disease.

overall_design: Total RNA obtained from intestinal biopsies were analyzed using whole-genome microarrays.

last: Montero-Melendez

first: Xavier

last: Llor

first: Mauro

last: Perretti

first: Antonio

last: Suarez


title: Expression data from heart tissue

status: Public on Sep 17 2013

city: Lodnon

first: Xiufen

last: Zheng

state: Ontario

address: 339 windermere Road,LHSC-UC, B4-235

department: Pathology

country: Canada

institute: university of Western Ontario

summary:
Ischemia reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation, leading to graft failures and lower long-term survival rate of the recipient. IR causes apoptosis / death of cardiomyocytes, resulting from up-regulation of apoptotic genes and down-regulation of anti-apoptotic genes.
We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.

overall_design: We used microarrays to detect gene expression profile of ischemia reperfusion injured hearts and identified distinct classes of up-regulated and down regulated genes during this I/R.


title: Region-specific gene expression profiles in left atria of patients with valvular atrial fibrillation

status: Public on Sep 18 2013

city: TauYau

first: Yun-Shien

last: Lee

state: Taiwan

address: TauYau

department: Dept. Biotechnology

institute: Ming Chuan Univ

summary: Of 54,675 expressed sequence tags, microarray analysis revealed that 391 genes were differently expressed (>1.5-fold difference) between LA-PV junction and LAA, including genes related to arrhythmia, cell death, fibrosis, hypertrophy, and inflammation. Microarray and q-PCR produced parallel results in analyzing the expression of particular genes. The expression of paired like homeodomain-2 (PITX2) and its target protein (short stature homeobox-2 [SHOX2]) was greater in LA-PV junction than in LAA, which may contribute to arrhythmogenesis. Five genes related to thrombogenesis were up-regulated in LAA, which may implicate for the preferential thrombus formation in LAA. Genes related to fibrosis were highly expressed in LAA, which was reflected by intense ultrastructural changes in this region

overall_design: Paired LA-PV junction and left atrial appendage (LAA) specimens were obtained from 16 patients with persistent AF receiving valvular surgery. The Paired specimens were sent for microarray comparison. Selected results were validated by quantitative real time-PCR (q-PCR) and Western blotting. Ultrastructural changes in the atria were evaluated by immunohistochemistry.

first: Yung-Hsin

last: Yeh

first: Chi-Tai

last: Kou

first: Yi-Hsin

last: Chan

first: Yen-Chen

last: Lin

first: Yuan-Min

first: Stanley

last: Nattel

first: Feng-Chun

last: Tsai

first: Wei-Jan

last: Chen


title: Microarray data of leukemia cells with or without IKK inhibitor treatment

city: Stanford

first: HSU-PING

last: KUO

address: 265 Campus Dr.

institute: Stanford University

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

overall_design: Refer to individual Series

first: Hsu-Ping

last: Kuo

first: Zhong

last: Wang

first: Dung-Fang

first: Masayuki

last: Iwasaki

first: Jesus

last: Duque-Afonso

first: Stephen

middle: H

last: Wong

first: Maria

middle: E

last: Figueroa

first: Jie

last: Su

first: Ihor

last: Lemischka

first: Michael

middle: L

last: Cleary

first: Chiou-Hong


title: Molecular changes induced by melanoma cell conditioned medium (MCM) in HUVEC cells.

city: rotterdam

first: Mario

last: Pescatori

address: Westplein 11

institute: Health e-genomics

summary: Malignant melanoma is a complex genetic disease and the most aggressive form of skin cancer. Melanoma progression and metastatic dissemination fundamentally relies on the process of angiogenesis. Melanomas produce an array of angiogenic modulators that mediate pathological angiogenesis. Such tumor-associated modulators arbitrate the enhanced proliferative, survival and migratory responses exhibited by endothelial cells, in the hypoxic tumor environment. The current study focuses on melanoma-induced survival of endothelial cells under hypoxic conditions. Melanoma conditioned media were capable of enabling prolonged endothelial cell survival under hypoxia, in contrast with the conditioned media derived from melanocytes, breast and pancreatic tumors. To identify the global changes in gene expression and further characterize the pro-survival pathway induced in endothelial cells, we performed microarray analysis on endothelial cells treated with melanoma conditioned medium under normoxic and hypoxic conditions.

overall_design: Huvec cells were grown in melanoma conditioned medium or DMEM 10% FCS for 12 h under hypoxic or normoxic conditions. In order to identify the transcripts modulated by melanoma CM,  samples treated with MCM were compared to those grown in DMEM alone.

first: Asha

last: Das

first: Timo

last: Hagen


title: Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization [Expression Array]

city: Baltimore

first: Kasper

middle: Daniel

last: Hansen

state: Maryland

address: 615 N Wolfe St. E3527

department: Biostatistics

institute: Johns Hopkins

summary: To determine what DNA methylation and gene expression changes occur following EBV transformation. B-cells were isolated from 3 donors.  Resting, CD40 activated and EBV transfromed cells from each donor was analyzed. Each sample was assayed using Affymetrix expression arrays and whole genome bisulfite sequenicng.  Additional time points during transformation and activation were sequenced as well, but not assayed for expression.

first: Sarven

last: Sarbunciyan


title: Hypoxia-inducible factors enhance CD8+ T cell effector responses to persistent antigen.

status: Public on Sep 29 2013

city: La Jolla

first: Andrew

last: Doedens

state: CA

address: 9500 Gilman Drive, 0377

department: Division of Biology

institute: Univerisity of California, San Diego

summary: Cytolytic activity by CD8+ cytotoxic T lymphocytes (CTL) is a powerful tactic in the elimination of intracellular pathogens and tumor cells. The destructive capacity of CTL is progressively dampened during chronic infection - yet the environmental cues and molecular pathways controlling immune “exhaustion” remain unclear. We find CTL immunity is regulated by the central transcriptional response to hypoxia, mediated by the von-Hippel-Lindau/Hypoxia-Inducible-Factor (VHL/HIF) pathway. Deletion of VHL, the primary negative regulator of HIF, leads to lethal CTL-mediated immunopathology during chronic infection, and VHL-deficient CTL display enhanced control of persistent viral infection and neoplastic growth. We find HIF and oxygen influence expression of pivotal CTL transcription, effector and costimulatory-inhibitory molecules, which is relevant to strategies to promote viral and tumor clearance.

overall_design: To understand the role of the VHL/HIF pathway in regulating T cell responses to acute and persistant antigen in vivo, a mixture of ~10^4 WT and Vhl KO virus-specific CD8+ T cells (P14s) was transferred iv into uninfected WT host mice. After infection with either LCMV-Armstrong (acute viral infection) or LCMV-clone13 (persistent viral infection) we double-FACS isolated the responding P14 donor cells from pooled spleens from two sets of host mice to obtain duplicates for microarray for the four conditions, resulting in eight samples (2 WT Arm, 2 VHL KO Arm; 2 WT cl13, 2 VHL KO cl13) at 6 to 7 days post-infection. All conditions were sorted on KRLG1lo P14 cells.  Note this was a mixed P14 transfer, so WT and KO cells were responding to infection in the same WT host mice to aid in normalizing effects such as antigen load and cytokine environment.

first: Anthony

last: Phan

first: Martin

last: Stradner

first: Jessica

middle: K

last: Fujimoto

last: Nguyen

first: Edward

last: Yang

first: Randall

middle: S

last: Johnson

first: Ananda

last: Goldrath


title: Low grade gliomas

city: Genova

first: annalisa

last: barla

state: GE

address: via Dodecaneso 35

department: DIBRIS

country: Italy

institute: Università degli Studi di Genova

summary: Categorisation of LGGs related to their lesion site (infratentorial vs. supratentorial)

overall_design: 40 Low grade gliomas samples

first: Samantha

last: Mascelli

first: Annalisa

last: Barla


title: Expression data for HT29 cells treated with 5-aza-deoxy-cytidine [Affymetrix]

city: Stony Brook

first: Xiao

last: Xu

state: NY

address: Stony Brook University

institute: Stony Brook University BME

summary:
The RNA samples from HT-29 (ATCC) colon cancer cell line were reverse transcribed into cDNAs and categorized in 3 groups with different concentrations of 5-aza-deoxy-cytidine (5-Aza); in each group three replicative 150 mm cultures were treated with: 1) dimethyl sulfoxide (vehicle alone, 0 μM 5-Aza); 2) 5μM 5-Aza and 3) 10 μM 5-Aza; for five days
We then used Affymetrix microarray platform to profile the gene expression of the 3 HT29 cell groups (3 replicates in each group) in order to search for differentially expressed genes

overall_design: The transcriptional response of HT-29 (ATCC) colon cancer cell line under 3 concentrations of 5-aza-deoxy-cytidine was investigated based on their RNA expression profiles

first: Ellen

last: Li

first: Jennie

last: Williams

first: W

middle: R

last: McCombie

first: Paula

last: Denoya


title: Transcriptional profiling of intestinal samples from Atg4b knock-out mice during chemical-induced colitis

status: Public on Sep 16 2013

city: Oviedo

first: Alvaro

middle: F

last: Fernandez

state: Asturias

address: C/Fernando Bongera s/n

department: Dpto de Bioquimica y Biol. Mol., IUOPA

institute: Universidad de Oviedo

summary: The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase paralleling the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b-/- mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. Atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn’s disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b-/- mice. Taken together, these results provide additional evidence on the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that Atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency

overall_design: Seven samples were collected in total: three from wild-type mice (1 from the ileum and the colon of control mice, and 1 from the colon of a DSS-treated mouse) and four from Atg4b knock-out mice (1 from the ileum and the colon of control mice, and 2 from the colon of DSS-treated mice).

first: Sandra

last: Cabrera

first: Álvaro

last: Fernández

first: Guillermo

last: Mariño

first: José

last: Freije

first: Carlos

last: Lopez-Otin


title: Gene expression analysis in a variety of normal, premalignant and squamous cell carcinomas of the cervix

city: Cambridge

first: Ian

last: Roberts

address: Hills Road

department: Cancer Cell Unit

institute: Hutchison MRC Research Centre

summary: We sought to apply the technologies of gene expression profiling to detect genes significant in the aetiology of cervical carcinoma .  We investigated 14 normal (NAD), 11 low grade squamous intrapepithelial lesions (LSIL), 21 high grade squamous intraepithelial lesions (HSIL) and 28 squamous cell carcinomas by Affymetrix GeneChip whole transcriptome profiling.  Two SCC cell lines were also included in the cohort.  Normal and SILS were profiled using the Affymetrix U133A platform, while SCCs and Cell lines were profiled using the Affymetrix U133A plus 2.0 array.

overall_design: This submission describes the transcriptional profiles of  a cohort totalling 77 cervical normal, premalignant lesions, and squamous cell carcinomas

first: Konstantina

last: Karagavriilidou

first: Stephanie

last: Carter

first: Grace

last: Ng

first: Emma

last: Gooding

first: Anasuya

last: Chattopadhyay

first: Mark

last: Pett

first: Matthew

last: Murray

first: David

last: Winder

first: Baljinder

last: Muralidhar

first: Dawn

last: Ward

first: Pamela

last: Stacey

first: Marie

last: Philips

first: Cinzia

last: Scarpini

first: Geeta

last: Mukherjee

first: Nicholas

last: Coleman


title: Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation

city: New Haven

first: Valerie

last: Horsley

state: CT

address: 266 Whitney Avenue

department: Department of Molecular, Cellular and Developmental Biology

institute: Yale University

summary:
Cyclosporine A (CSA) leads to the precocious onset of hair follicle growth, which is driven by premature activation and proliferation of hair follicle stem cells.  Here, we identify gene expression changes associated with
CSA treatment in hair follicle stem cells prior to the onset of proliferation as a readout for the early events in stem cell actvation.

overall_design: Hair follicle bulge stem cells were FACS-isolated from mouse skin during the 2nd telogen.  Two biological replicated were performed.

first: Jill

last: Goldstein


title: Gene expresion changes following knockdown of KDM4C in primary fibroblasts

status: Public on Sep 14 2013

city: Philadelphia

first: Vivian

last: Cheung

state: PA

address: 3615 Civic Center Blvd

institute: University of Pennsylvania/HHMI

summary:
Epigenetic and genetic regulations are sometimes considered as separate mechanisms that influence gene expression and phenotypes.  However, there are DNA sequence variants in epigenetic regulators that could affect gene regulation.  The histone demethylase, KDM4C, promotes transcriptional activation by removing the repressive histone mark, tri-methylation of lysine 9 of histone H3 (H3K9me3), from its target genes.  In this study, we uncovered cis-acting DNA sequence variants in KDM4C that contribute to individual differences in its expression.  Utilizing this natural variation, we performed genetic analyses in B-cells in order to identify target genes that are regulated by KDM4C.
We used microarrays to investigate gene expression changes in the target genes from our genetic analyses following knockdown of KDM4C in primary fibroblasts.

overall_design: Primary fibroblasts with stable expression of shRNA targeting KDM4C or a control construct were selected for RNA extraction and hybridization to Affymetrix microarrays.  Following selection for stable expression of the shRNA constructs we selected clones expressing 3 non-overlapping constructs targeting KDM4C (shKDM4C) and 2 clones expressing the control construct (shCtr) for analysis by microarray.

first: Brittany

last: Gregory


title: Microarray data of mouse MLL-AF10 leukemia cells with or without IKK inhibitor treatment

first: HSU-PING

last: KUO

summary: MLL fusion proteins in leukemia induce aberrant transcriptional elongation and associated chromatin perturbations, however the upstream signaling pathways and activators that recruit or retain MLL oncoproteins at initiated promoters are unknown. Through functional and comparative genomic studies, we identified an essential role for NF-kB signaling in MLL leukemia. Suppression of NF-kB led to robust anti-leukemia effects that phenocopied loss of functional MLL oncoprotein or associated epigenetic cofactors. The NF-kB subunit RELA occupies promoter regions of crucial MLL target genes and sustains the MLL-dependent leukemia stem cell program. IKK/NF-kB signaling is required for wild-type MLL and fusion protein retention and maintenance of associated histone modifications providing a molecular rationale for enhanced efficacy in therapeutic targeting of this pathway in MLL leukemias.

overall_design: MLL-AF10 cells were treated with 0.5µM IKK inhibitor or vehicle. Each group contains triplicate samples.

first: Hsu-Ping

last: Kuo

first: Zhong

last: Wang

first: Dung-Fang

last: Lee

first: Masayuki

last: Iwasaki

first: Jesus

last: Duque-Afonso

first: Stephen

last: Wong

first: Maria

last: Figueroa

first: Jie

last: Su

first: Ihor

last: Lemischka

first: Michael

last: Cleary


title: DNA methylation profiling in X;autosome translocations supports a role for L1 repeats in the spread of X chromosome inactivation

status: Public on Sep 13 2013

city: New York

first: Andrew

last: Sharp

address: Hess CSM Building Floor Floor 8 Room 116

department: Genetics and Genomics

institute: Icahn School of Medicine at Mount Sinai

summary: In order to test the hypothesis that X chromosome inactivation shows sequence specificity, we have analysed the spread of XCI into autosomal chromatin by performing DNA methylation profiling in six unbalanced X;autosome translocations. Using promoter hypermethylation as an epigenetic signature of XCI, we have determined the inactivation status of 1,050 autosomal genes after translocation onto the inactive X. By performing a comparative sequence analysis of autosomal genes that are either subject to or escape the X inactivation signal, we identified a number of common repetitive elements, including LINEs, and DNA motifs that are significantly enriched around inactive autosomal genes. We show that these same motifs predominantly map to L1P elements, are significantly enriched on the X chromosome versus the autosomes, and also occur at higher densities around X-linked genes that are subject to X inactivation compared to those that escape X inactivation. These results are consistent with a potential causal relationship between DNA sequence features such as L1s and the spread of XCI, lending strong support to Mary Lyon's 'repeat hypothesis'.

overall_design: Genome-wide measurement of CpG methylation levels by hybridizing bisulphite-converted DNA to Infinium HumanMethylation450 BeadChips. Eight DNA samples extracted from individuals carrying X;autosome translocations were processed according to manufacturer's recommended protocols, and array data processed using the Methylation Module of GenomeStudio v1.8 software with default parameters.

first: Neeta

last: Bala-Tannan

first: Manisha

last: Brahmachary

first: Paras

last: Garg

first: Christelle

last: Borel

middle: J


title: The Tight Junction Protein Claudin-2 Controls Mucosal Permeability, Immune Tolerance and Colitis in Mice

status: Public on Sep 15 2013

city: Nashville

first: amar

middle: b

last: singh

state: TN

department: Surgery

institute: Vanderbilt University

summary: The mucosal epithelium plays a key role in regulating immune homeostasis. Dysregulation of epithelial barrier function is associated with mucosal inflammation. Expression of claudin-2, a pore-forming tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Furthermore, claudin-2 also regulates colonic epithelial cell proliferation and intestinal nutrient absorption. However, the precise role of claudin-2 in regulating colonic epithelial and immune homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic (Cl-2TG) mice, that increased colonic claudin-2 expression unexpectedly protects mice against experimentally induced colitis and colitis-associated cancer. Notably, Cl-2TG mice exhibited increased colon length and permeability as compared with wild type (WT) littermates. However, despite their leaky colon, Cl-2TG mice subjected to experimental colitis were immune compromised, with reduced induction of TLR-2, TLR-4, Myd-88 expression and NF-kB and STAT3 activation. Most importantly, colonic macrophages in Cl-2TG mice exhibited an anergic phenotype. Claudin-2 overexpression also increased colonocyte proliferation and provided protection against colitis-induced colonocyte death. Taken together, our findings have revealed a critical role of claudin-2 in regulating colonic homeostasis, suggesting novel therapeutic strategies for inflammatory conditions of the gastrointestinal tract.

overall_design: 8-10 weeks old male Villin-Claudin-2 transgenic mice and WT littermates were provided either normal drinking water (control) or Dextran Sodium Sulfate (DSS: 4% w/v) for 10 days. 3 replicates each.

first: Amar

last: Singh

first: Rizwan

last: Ahmad

first: Punita

last: Dhawan

first: Rupesh

last: Chaturvedi

first: Tanwir

last: Habib


title: Genome-wide differential gene expression signatures in pediatric acute lymphoblastic leukemia subtypes

city: Uppsala

first: Jessica

last: Nordlund

address: Academic Hospital, Entrance 70, 3rd floor

department: Medical Sciences

institute: Uppsala University

summary: We surveyed the genome-wide DNA methylation levels and gene expression patterns in patients with pediatric acute lymphoblastic leukemia. Using Affymetrix U133 Plus 2.0 GeneChips, we identified a relatively small set of CpG sites that are highly correlated with gene expression.

overall_design: Genome-wide expression analysis of 108 primary ALL samples by Affymetrix Human Genome U133 Plus 2.0 GeneChips used to investigate relationships between subtype-specific DNA methylation patterns and gene expression in 93 patients with both gene expression and DNA methylation data.

first: Ann-Christine

last: Syvänen


title: Prostaglandin-modulated umbilical cord blood hematopoietic stem cells

status: Public on Sep 12 2013

city: San Diego

first: Dave

last: Robbins

address: 3535 General Atomics Court Ste. 200

institute: Fate Therapeutics

summary:
Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching.  However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the “effective dose” of HSCs.
Molecular profiling with Affymetrix GeneChips were used to determine the optimal ex vivo modulation conditions (e.g., temperature and media) for use in a clinical setting by measured pathway induced expression changes.

overall_design: Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span (SS) media evaluating three treatment temperatures (4 deg C, 25 deg C, and 37 deg C) with 10uM 16,16-dmPGE2 or Vehicle (DMSO) for 2 hours.  To evaluate optimal media, similar CD34+ cells were incubated ex vivo in either Stem Span-SFEM (SS) media or 8% Low Molecular Weigh Dextran 40/5% HSA solution (LMD/HSA) with 10uM 16,16-dmPGE2 or Vehicle (DMSO) for 2 hours at 37 deg C.  Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.

first: D


title: Prostaglandin dose response on hematopoietic stem cells (4 deg C)

summary:
Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching.  However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the “effective dose” of HSCs.
Molecular profiling with Affymetrix GeneChips were used to evaluate if increasing the concentration of prostaglandin could compensate for the reduced biological responses observed with incubations at 4 deg C.

overall_design: Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span (SS) media evaluating three concentrations of 16,16-dmPGE2 (10uM, 50uM, and 100uM) or Vehicle (DMSO) for 2 hours at 4 deg C.  To evaluate if increasing the concentration of prostaglandin could compensate for the reduced biological responses observed with incubations at 4 deg C.  Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.


title: Prostaglandin dose response on hematopoietic stem cells (25 & 37 deg C)

summary:
Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the "effective dose" of HSCs.
Molecular profiling with Affymetrix GeneChips were used to evaluate if increasing the concentration of prostaglandin at 25 and 37 deg C could increase biological responses.

overall_design: Isolated human CD34+ cells from umbilical cord blood were incubated ex vivo in Stem Span (SS) media evaluating five concentrations of 16,16-dmPGE2 (0.1uM, 1uM, 10uM, 50uM, and 100uM) or Vehicle (DMSO) for 2 hours at 25 or 37 deg C. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.


title: microRNA and gene expression profile in ischemia reperfusion injury in heart transplantation

first: Xiufen

last: Zheng

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

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

platform_organism:
Mus musculus
synthetic construct


title: Prostaglandin duration required to elicit maximum response on hematopoietic stem cells

summary:
Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching.  However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the “effective dose” of HSCs.
Molecular profiling with Affymetrix GeneChips were used to evaluate if prostgandin is required for the entire 2 hour incubation to elicit the maximum pathway activated gene expression response.

overall_design: Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span (SS) media with 10uM 16,16-dimethyl prostaglandin E2 for varying amounts of time within a two hour incubation window to evaluate if the entire 120 minutes is required to elicit the maximum pathway activated gene expression response or if shorter incubation times were sufficent.  Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.


title: Gene expression analysis in TGFbeta/TNFalpha treated A549 spheroid cultures

city: Charlottesville

first: Marcin

middle: Piotr

last: Cieslik

state: VA

address: 400 Stribling Ave Ext

institute: University of Virginia

summary: TGFbeta/TNFalpha treated spheroid A549 cultures are a model of the epithelial-mesenchymal transition (EMT). These experiments capture the changes in global gene expression that result from cells being induced to undergo EMT (3D control vs 3D treated), but also the differences in gene expression when A549 is grown in spheroid cultures (2D control vs 3D untreated). EMT is efficiently induced only in the spheroid culture model.

overall_design: A total of 8 samples are analyzed, corresponding to 4 conditions (2D control, 2D treated, 3D control, 3D treated) and 2 biological replicates.

first: Marty

last: Mayo

first: Stefan

last: Bekiranov

first: Natalya

last: Baranova

first: David

last: Allison

first: Jake

last: Wamsley

first: Lisa

last: Gray

first: Sanjay

last: Chodaparambil

first: Manish

last: Kumar

first: Stephen

last: Hoang

first: Xiaojiang

last: Xu


title: Optimized CD8 effector TL

city: MARSEILLE

first: Nathalie

last: AUPHAN-ANEZIN

address: Parc Scientifique de Luminy

country: France

institute: CIML

summary: Transcriptome analyses of naive, effector and memory CD8 TCRP1A lymphocytes expressing or not an active form of the transcription factor Stat5.

overall_design:
TCRP1A CD8 T lymphocytes were activated by their cognate Ag for 72h to induce their differentiation in effector T cells (TCRP1A eTL 72h: 4 replicates S1, S2, S3, S4). In some samples, an active form of Stat5 was introduced (TCRP1A Stat5ca eTL 72h: 2 replicates S9, S10).  These 72h activated T cells were either purified and analyzed directly (samples mentioned above) or injected in congeneic hosts and recovered more than 20 days later from the host spleen and lymph nodes: TCRP1A eTL >d20: 2 replicates– S30, S32; TCRP1A Stat5ca eTL >d20: 4 replicates S11, S12, S13, S14). Naive TCRP1A CD8 T lymphocytes (TCRP1A-naive: 4 replicates S33, S34, S35, S36) are included as controls.

TCRP1A CD8 T lymphocytes were activated by anti-CD3/CD28. After 24h, an active form of Stat5 was introduced in activated cells. Culture was continued for another 48h to induce their differentiation in effector T cells. These 72h activated T cells were either directly  injected in congeneic hosts and recovered more than 14 days later from the host spleen and lymph nodes: T-BetKO Stat5ca >d14: 3 replicates S39, S40, S41.

last: Auphan-Anezin

first: Anne-Marie

last: Schmitt-Verhulst

first: P

last: Barbry

first: K

last: Lebrigand


title: Expression data from Escherichia coli O157:H7, strain EDL933, cultivated in caecal content of rats associated with the human intestinal microbiota

status: Public on Sep 10 2013

city: St-Hyacinthe

first: Guillaume

last: Le Bihan

state: Québec

address: 3200 Sicotte

institute: GREMIP, UdM

summary:
The human intestinal microbiota associated with rats produces in vivo a soluble(s) factor(s) that down-regulates the expression of genes encoding for the Shiga toxin II in E. coli O157:H7. The Shiga toxin II is one of the major virulence factors of E. coli enterohemorragic leading to the deadly hemolitic and uremic syndrome. Investigation of the effect of the human intestinal microbiota on the whole transcriptome of EHEC O157:H7 is of major importance to increase our understanding of the pathogen transcriptomic adaptation in response to the human microbiota.
We analysed by microarray hybridization the gene expression pattern of EHEC O157:H7 grown in the caecal content of germ-free rats or rats associated with the human microbiota of a healthy human subject. By doing so, we increased our understanding of the regulatory activities of the human gut microbiota on E. coli O157:H7

overall_design: A first group of twelve weeks old, male, germfree rats was colonized with the human fecal microbiota and a second group was kept germfree and condidered as a controle group. Rats were  fed for two weeks with a sterile human type diet, and were sacrificed. E. coli O157:H7 was cultivated for 6 hours in the caecal content of germfree rats and rats associated with the human intestinal microbiota. RNAs were extracted and cDNAs were synthesized, fragmented and biotinylated before being hybridized on Affymetrix E. coli genome 2.0 arrays.  The effect of the human intestinal microbiota was investigated by comparing the  gene expression level in the caecal content of rats associated with the human microbiota with their expression level in the caecal content of the germfree rats.

first: Philippe

last: Garneau

first: Christophe

last: Del'homme

first: Grégory

last: Jubelin

first: Christine

last: Martin

first: Josée

last: Harel


title: Gene Expression Across the Human Growth Plate

city: Jacksonville

first: Ed

last: Mougey

state: FL

address: 807 Children's Way

department: Biomedical Research

institute: Nemours Children's Clinic

summary:
Chondrocytes advance through the long bone growth plate in synchrony, allowing their segregation into one of four zones each corresponding to a different phase of maturation. Beginning from the epiphysis the recognized zones are: reserve, proliferative, prehypertrophic, and hypertrophic. A fifth zone, the perichondrium is located in apposition to the growth plate at its circumferential surface. The progression of chondrocytes through these zones, and hence growth, is regulated by a complex interplay of signaling pathways, defects in which lead to osteochondrodysplasias. At present, there are over 370 recognized skeletal disorders, slightly more than half of which have been explained at the molecular level. Through a combination of laser microdissection, linear mRNA amplification, and GeneChip analysis, our laboratory has acquired the zone specific expression profile of chondrocytes from the distal femoral growth plates of two normal patients. On average, transcripts interrogated by 12,193 or 18,454 GeneChip probe sets (out of a possible 54,000 probe sets) were present in patients 1 and 2, respectively. The homologous inter-array correlations for the log(2) intensities were ≥ 0.91±0.01.
Keywords: Chondrocyte differentiation program.

overall_design: Populations of cells corresponding to the hypertrophic, prehypertrophic, proliferative, reserve, and perichondrium, were separately isolated by laser microdissection from cryostat sections of human growth plates using a Leica AS-LMD microscope.  RNA was prepared from the isolated cells, amplified using a T7 linear amplification protocol, and analyzed by hybridization to Affymetrix microarrays.  The distal femoral growth plate (left or right) was exclusively used for this study. Patient 1 of this study is an 11-10/12 year old Caucasian female and patient 2 is a 13-3/12 year old Caucasian male.

first: Edward

middle: B

first: Robert

middle: C

last: Olney

first: Patricia

last: Soteropoulos


title: Gene expression from SCID-hu mice treated with saline (control) or intermittent PTH

city: Little Rock

first: Shmuel

last: Yaccoby

state: AR

address: 4301 W Markham, Slot 776

department: Myeloma Institute for Research and Therapy

institute: University of Arkansas for Medical Sciences

summary: The data present global gene expression profile of whole human bones, implanted in SCID mice (SCID-hu model), then engrafted with the myeloma cell line, Hg, and treated with saline or PTH for 4 weeks.

overall_design: SCID-hu mice were prepared by subcutaneous implantation of human bone in SCID mice. The human myeloma cell line, Hg was injected directly into the implanted bone in SCID-hum mice. Upon establishment of myeloma growth as determined by measurement of circulating human immunoglobulins in SCID-hu mice sera, the mice were treated with saline or intermittent PTH (parathyroid hormone, 80 ug/kg/day) for 4 weeks. At the end of the experiment, the human bones from SCID-hu mice were snap frozen in liquid nitrogen. RNA extracted from these bones was subjected to global gene expression profile using Affymetrix U133-Plus microarray.

first: John

last: Shaughnessy


title: Expression data from mouse liver tissue from SKH:QS mice treated with 68ZnO sunscreens

status: Public on Sep 11 2013

city: North Ryde

first: Megan

last: Osmond-McLeod

address: 11 Julius Avenue

institute: CSIRO

summary:
ZnO nanoparticles can elicit a range of perturbed cell responses in vitro.  Exposure to topically applied sunscreens containing ZnO particles may or may not elicit a biological effect in mice.
We aimed to determine whether exposure to topically applied ZnO particles manufactured as either microparticles or nanoparticles could elicit a biological response in liver tissue isolated from treated mice, compared to the sunscreen formulation only or untreated mice.

overall_design: Sunscreens containing 68ZnO microparticles, 68ZnO nanoparticles or no metal oxide particles at all (formulation only) were applied to the backs of SKH:QS mice six times over four days. On the fifth day mice were sacrificed and liver tissue was harvested for RNA isolation and whole genome transcriptional profiling, comparing the expression profiles of treated mice with untreated mice.  Two separate experiments were conducted, one using virgin mice and the other using pregnant mice (~17d gestation)

last: Osmond

first: Yalchin

last: Oytam