title: Expression data of human somatic cell types and induced pluripotent stem cells

city: Baltimore

first: Patrick

last: Cahan

address: 733 North Broadway, MRB 653

department: ICE and Biomedical Engineering

institute: Johns Hopkins University School of Medicine

summary:
Transcription factor-mediated reprogramming yields induced pluripotent stem cells (iPSC) by erasing tissue specific methylation and re-setting DNA methylation status to an embryonic stage. We compared bona fide human iPSC derived from umbilical cord blood (CB) and neonatal keratinocytes (K). Through both incomplete erasure of tissue specific methylation and de novo tissue specific methylation, CB-iPSC and K-iPSC are distinct in genome-wide DNA methylation profiles. Functionally, CB-iPSC displayed better blood formation in vitro, whereas K-iPSC differentiated better to a keratinocyte fate, implying that the tissue of origin needs to be considered in future therapeutic applications of human iPSCs.
We performed gene expression and global DNA methylation profiling on iPS and the source somatic cell types to search for evidence of epigenetic memory.

overall_design: We performed gene expression profiling to identify genes differentially expressed between keratinocytes and cord blood, and from induced pluripotent stem cells from these somatic tissues.

first: Kitai

last: Kim

first: Akiko

last: Doi

first: Andrew

last: Feinberg

first: George

middle: Q

last: Daley


title: Microarray data for rejuvenation experiments through reprogramming

status: Public on Dec 14 2011

city: Montpellier

first: Jean-Marc

last: Lemaitre

address: 141 rue de la cardonille

country: France

institute: INSERM

summary: Proliferative and replicative senescent fibroblasts from aged human donors were reprogrammed towards pluripotency and re-differentiated in fibroblasts and then further analyzed for rejuvenation assessment.

overall_design: Comparison of microarrays were performed by non hierarchical clustering visualized in with Treeview software

first: Laure

last: Lapasset

first: Ollivier

last: Milhavet

first: Alexandre

last: Prieur

first: Emilie

last: Besnard

first: Amelie

last: Babled

first: Nafissa

last: Aït-Hamou

first: Julia

last: Leschik

first: Dijon-Grinand

last: Maryline

first: John

last: De Vos

first: Sylvain

last: Lehmann


title: Gene Array Analyzer (GAA): Alternative usage of gene arrays to study alternative splicing events (MoGene array)

status: Public on Nov 28 2011

city: Bad Nauheim

first: Pascal

last: Gellert

address: Ludwigstr. 43

department: Cardiac Development and Remodelling

country: Germany

institute: Max Planck Institut for Heart and Lung Research

summary: The latest version of microarrays released by Affymetrix, the GeneChip Gene 1.0 ST Arrays (gene arrays), are designed in a similar fashion as exon arrays, which enables to identify differentially expressed exons, rather than only the expression level of whole transcripts. Here, we propose an extension, Gene Array Analyzer (GAA), to our previously published Exon Array Analyzer (EAA). GAA enables to analyse gene arrays on exon level and therefore supports to identify alternative splicing with gene arrays. To show the applicability of GAA, we used gene arrays to profile alternative splice events during the development of the heart. Further re-analysis of published gene arrays could show, that some of these splice events reoccur under pathological conditions. The web interface of GAA is user friendly, functional without set up and freely available at http://GAA.mpi-bn.mpg.de.

overall_design: Alternative splicing and gene expression analysis during development of the heart and cardiomyoyte differentiation.

first: Mizue

last: Teranishi

first: Katharina

last: Jenniches

first: Piera

last: De Gaspari

first: David

last: John

first: Karsten

last: grosse Kreymborg

first: Thomas

last: Braun

first: Shizuka

last: Uchida


title: ERG deregulation induces PIM-1 over-expression and aneuploidy in prostate epitheilial cells

status: Public on Nov 30 2011

city: Monza

first: Vera

last: Magistroni

address: via Cadore 48

department: Clinical Medicine and Prevention

country: Italy

institute: University of Milano-Bicocca

summary: The ERG gene belongs to the ETS family of transcription factors and has been found involved in atypical chromosomal rearrangements in several cancers. To gain insight into the oncogenic activity of ERG, we compared the gene expression profile of NIH-3T3 cells stably expressing the coding regions of the three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG,. We found that all the three ERG fusions significantly up-regulate PIM-1 expression in the NIH-3T3 cell line. PIM-1 is a serine/threonine kinase frequently over-expressed in cancers of haematological and epithelial origin. We show here that tERG expression induces PIM-1 in the non-malignant prostate cell line RWPE-1, strengthening the relation between tERG and PIM-1 up-regulation in the initial stages of prostate carcinogenesis. Silencing of tERG reversed PIM-1 induction. A significant association between ERG and PIM-1 expression in clinical prostate carcinoma specimens was found, suggesting that such a mechanism may be relevant in vivo. Chromatin Immunoprecipitation experiments showed that tERG directly binds to PIM-1 promoter in the RWPE-1 prostate cell line, suggesting that tERG could be a direct regulator of PIM-1 expression. The up-regulation of PIM-1 induced by tERG over-expression significantly modified CyclinB1 levels and increased the percentage of aneuploid cells in the RWPE-1 cell line after 24hrs of taxane-based treatment. Here we provide the first evidence for an ERG-mediated PIM-1 up-regulation in prostate cells in vitro and in vivo, suggesting a direct effect of ERG transcriptional activity in the alteration of genetic stability.

overall_design: NIH-3T3 cells stably expressing the coding regions of the three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG together with the empty vector where profiled in triplicate. Quality control using NUSE and RLE plots identified one array as problematic (R540_TMP-ERG_P1) which was removed.

first: V

first: L

last: Mologni

first: S

last: Sanselicio

first: J

middle: F

last: Reid

last: Redaelli

first: R

last: Piazza

first: M

last: Viltadi

first: G

last: Bovo

last: Strada

last: Grasso

last: Gariboldi

first: C

last: Gambacorti-Passerini


title: Expression data from WT and Aire KO thymic medullary epithelial cells (MECs)

status: Public on Nov 23 2011

city: Boston

first: CBDM

last: Lab

state: MA

address: 77 Avenue Louis Pasteur

department: Microbiology and Immunobiology

country: USA

institute: Harvard Medical School

summary: The aim of this study is to analyze the transcriptional effects of Aire deficiency in the thymus, using the Affymetrix MoGene platform to analyze variation in exon usage

overall_design: MECs were isolated from 4-6 wk-old WT or Aire KO ((B6xNOD)F1 background) mice. Three WT and three Aire-KO mice taken individually were used.

first: Matthieu

last: Giraud

first: Christophe

last: Benoist


title: Donor cell type influences the epigenome and differentiation potential of human induced pluripotent stem cells

status: Public on Nov 29 2011

first: Patrick

last: Cahan

state: MD

type: Methylation profiling by genome tiling array

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

overall_design: Refer to individual Series

first: Kitai

last: Kim

first: Akiko

last: Doi

first: Andrew

middle: P

last: Feinberg

first: George

last: Daley


title: Inflammatory gene profiling of Ewing sarcoma family of tumors (set A)

status: Public on Dec 01 2011

city: Helsinki

first: Suvi

last: Savola

address: Haartmaninkatu 3

department: Pathology

country: Finland

institute: University of Helsinki

summary:
Purpose: Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system related genes are activated and have prognostic significance in Ewing sarcoma family of tumours (ESFT). Experimental design: Data-analysis was performed on gene expression profiles of 44 ESFT patient, 11 ESFT cell line, and 18 normal muscle tissue samples. 238 inflammation related genes were selected based on literature and a macrophage gene expression signature was derived from SymAtlas. Differential expression of the genes was analysed by t-test and survival analysis was performed according to gene expression.
Results: Inflammatory genes are activated in ESFT patient samples, as 38 of 238 (16%) inflammatory genes were significantly upregulated (p<0.001) when compared to ESFT cell lines. This inflammatory gene activation was characterized by significant enrichment of macrophage related gene expression with 58 of 299 (19%) of these genes being upregulated (p<0.001). By combining expression data from ESFT patients, cell lines and muscle tissue samples we were able to identify a total of 32 presumptive inflammatory genes that characterize and distinguish tumour site in vivo from surrounding normal tissues. High expression of C5 correlated with better event free (p=0.01) and overall survival (p=0.004) in dose dependent manner. C5 and its receptor C5aR1 expression was verified at protein level by immunohistochemistry on tumor tissue microarray. Also, high expression of JAK1 correlated with favourable overall survival (p=0.04) and  high expression of IL8, derived presumably from infiltrating immune cells, resulted in poor overall survival in Ewing sarcoma (p=0.04). Conclusions: Immune system related gene activation is observed in ESFT patient samples and several prognostically significant inflammatory genes (C5, JAK1 and IL8) for ESFT were identified.

overall_design: 44 Ewing sarcoma family of tumor patient and 11 cell line samples were analysed for their gene expression.

first: Arto

last: Klami

first: Samuel

last: Myllykangas

first: Cristina

last: Manara

first: Katia

last: Scotlandi

first: Piero

last: Picci

first: Sakari

last: Knuutila

first: Jukka

last: Vakkila


title: Optic Vesicle Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease Treatment

city: Madison

first: David

last: Gamm

address: 1500 Highland Avenue

department: Department of Ophthalmology & Visual Sciences

institute: University of Wisconsin at Madison

summary: Microarray anlaysis was performed to investigate gene expression patterns of other transcription factors involved in early retinal and/or forebrain development using human embryonic stem cell-derived retinal and forebrain progenitor cells.  After 20 days of differentiation, vesicular neurospheres selectively expressed multiple retinal transcription factor genes appropriate for the OV stage of retinogenesis, whereas nonvesicular neurospheres expressed transcription factors indicative of the embryonic forebrain. Many transcription factor genes associated with retinal development were present at higher levels in vesicular vs. nonvesicular neurospheres. Nonvesicular neurospheres, on the other hand, expressed higher levels of transcription factors implicated in early forebrain development.  Taken together, results indicated that the vesicular and nonvesicular neurospheres harbored retinal progenitor cells and early forebrain populations, respectively.

overall_design: Compare the global gene expression of retinal progenitor cells and forebrain progenitor cells derived from human embryonic stem cells

first: Jason

middle: S

last: Meyer

first: Sara

middle: E

last: Howden

first: Kyle

middle: A

last: Wallace

first: Amelia

middle: D

last: Verhoeven

first: Lynda

last: Wright

first: Elizabeth

last: Capowski

first: Isabel

last: Pinilla

first: Jessica

middle: M

last: Martin

first: Shulan

last: Tian

first: Ron

last: Stewart

first: Bikash

last: Pattnaik

first: James

last: Thomson


title: Deciphering the Wnt-dependent gene signature in colorectal cancer cells

city: Amsterdam

first: Richard

last: Volckmann

state: Noord-Holland

address: van der Boechorststraat 6a

department: Laboratory of Experimental Oncology and Radiobiology

country: Netherlands

institute: msterdam UMC and University of Amsterdam

summary: Microarray-based gene expression data were generated from RNA from Ls174T colorectal carcinoma cell lines in which Wnt-dependent transcriptional activity can be abrogated by inducible overexpression of a dominant-negative form of Tcf4 or siRNA against β-catenin.

overall_design: shRNA against β-catenin, or a dominant-negative Tcf4 transgene, were induced in Ls174T cells for 72 or 24 hours, respectively. Uninduced cells were used as a control. Three replicates per condition.

first: Michal

last: Mokry

first: Pantelis

last: Hatzis

first: Ewart

last: de Bruijn

first: Jan

last: Koster

first: Rogier

last: Versteeg

first: Mark

last: van de Wetering

first: Victor

last: Guryev

first: Hans

last: Clevers

first: Edwin

last: Cuppen


title: Peripheral blood leukocyte genomic response one day post traumatic injury may predict early respiratory recovery

first: Wenzhong Xiao

address: 55 Fruit Street, GRV 1302

department: Department of Surgery

institute: Massachusetts General Hospital

summary:
This data was used as an example to illustrate a computational method for assessing statistical significance in microarray experiments
Contributed by 'The Inflammation and the Host Response to Injury Collaborative Research Program.'

Keywords: Two group comparison

overall_design: Genomic response one day post traumatic injury was compared between patients having early or late respiratory recovery

first: Douglas

last: Hayden


title: Effect of butyrate and DZNep on hESC HSF-6

status: Public on Nov 22 2011

city: Los Angeles

first: Silvia

middle: Veronica

last: Diaz-Perez

state: CA

address: 621 Charles Young DR

department: MCDB

institute: UCLA

summary: In order to recover nuclei with two active X chromosomes (class I), we developed a reprogramming strategy by supplementing hESC media with the small molecules sodium butyrate, and 3-deazaneplanocin A (DZNep).  In order to determine how B+D affects global gene expression, we performed microarray analysis in triplicate in the HSF-6 (8) C and HSF-6 (8) B+D treated cultures.  We also evaluated HSF-6 (S9) B+D in triplicate and identified no statistically significant changes in gene expression in HSF-6 (S9) B+D compared to HSF-6 (8) B+D treated cultures. This suggests that global transcriptional differences are more strongly modulated by presence or absence of B+D and not the percentage of class I, II or III nuclei.

overall_design:
We performed gene expression profiling on hESC HSF-6 (8, S9) in absent (control) and presence of butyrate and DZNep.
All cell were collected after 11 passages in absent and presence of butyrate and DZNep.

middle: V

first: Amander

middle: T

last: Clark


title: EZH2 mutations can be detected in 23% of PICALM-MLLT10 (CALM-AF10) positive acute leukemias

status: Public on Nov 25 2011

city: New York

first: Hans-Ulrich

last: Klein

state: NY

department: Neurology

institute: Columbia University Medical Center

summary:
Interest focuses on genes encoding histone demethylases in hematologic malignancies, such as EZH2 (enhancer of zeste homolog 2). EZH2 mutations were recurrently observed in lymphomas and chronic myeloid malignancies, but data in acute leukemias are limited. We investigated 13 PICALM-MLLT10 (=CALM-AF10) rearranged acute leukemia predominantly of T-lineage (7 m/6 f; 6–53 years) by deep-sequencing for EZH2mut and identified 3 (23%) EZH2mut carriers: one splice site mutation in exon 14, while two patients had missense mutations in the D1 region of exon 5 which interacts with different DNA methyltransferase genes (but no DNMT3Amut was detected in the 13 PICALM-MLLT10-positive patients).
In contrast, no EZH2mut was found in an independent cohort of 12 PICALM-MLLT10-negative T-ALL. Gene expression profiling revealed increased expression of genes with a role for transcription or intracellular transport processes in the PICALM-MLLT10-positive cases. The frequent occurrence of EZH2mut in PICALM-MLLT10-positive malignancies emphasizes a cooperative effect in acute leukemias.

overall_design: 29 patients analyzed with gene expression microarrays.

first: Vera

last: Grossmann

first: Ulrike

last: Bacher

first: Alexander

last: Kohlmann

first: Valentina

last: Artusi

first: Martin

last: Dugas

first: Susanne

last: Schnittger

first: Tamara

last: Alpermann

first: Wolfgang

last: Kern

first: Torsten

last: Haferlach

first: Claudia


title: Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy (ARVC)

city: Bad Oeynhausen

first: Patrick

last: Schwientek

address: Georgstr. 11

department: Klinik f. Thorax- & Kardiovaskularchirurgie

institute: Herz- & Diabeteszentrum NRW

summary:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown.
We therefore analyzed the transcriptomes of 6 ARVC specimen derived from heart transplantation candidates and compared our findings to 6 non-failing donor hearts (NF) which could not be transplanted for technical reasons. In addition, we compared our findings to 7 hearts from patients with idiopathic dilated cardiomyopathy. From each heart left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups.
Unsupervised cluster analyses of the six sample groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, unsupervised cluster analyses revealed no distinct expression pattern in LV and RV samples from ARVC-hearts. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only about 15-16% of the genes are commonly regulated compared to NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts.

overall_design: Microarrays were used to elucidate the differences between non-failing control hearts and those, suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC).

first: Anna

last: Gärtner

first: Peter

last: Ellinghaus

first: Holger

last: Summer

first: Stefan

last: Golz

first: Astrid

last: Kassner

first: Uwe

last: Schulz

first: Jan

last: Gummert

first: Hendrik

last: Milting


title: Gene expression profiling in myelodysplastic syndromes

city: St Louis

first: Rekha

last: Meyer

state: MO

address: 4320 Forest Park Av

institute: Washington University School of Medicine

summary: Myelodysplastic syndromes (MDS) are a heterogenous group of hematopoietic stem cell disorders characterized by dysplastic blood cell formation and peripheral blood cytopenias.  Up to 30% of patients with MDS will progress to a highly chemotherapy-resistant secondary acute myeloid leukemia (sAML).  We identified mutations in U2AF1 in MDS patients and patients with U2AF1 mutations are at an increased risk of developing sAML.

overall_design: We identified mutations in U2AF1 in patients with MDS and hypothesized that U2AF1 mutations may represent a novel mechanism that could alter gene expression in MDS. To elucidate gene expression changes associated with U2AF1 mutations, we analyzed the global mRNA expression profile obtained from bone marrow CD34+ cells purified from 6 MDS patients with a U2AF1 mutation, 9 MDS patients without a mutation, and 4 normal donors.

first: Matthew

middle: J

last: Walter

first: Timothy

last: Graubert

first: Tim

last: Ley

first: Rick

last: Wilson

first: Elaine

middle: R

last: Mardis

first: Dong

last: Shen

first: Li

last: Ding


title: The Apple Flavonoid Phloretin Inhibits Escherichia coli O157:H7 Biofilm Formation and Ameliorates Colon Inflammation in Rat

city: Gyeongsan-Si

first: Jintae

last: Lee

state: Gyeongsangbuk-Do

address: 214-1 Daedong

department: Chemical engineering

country: South Korea

institute: Yeungnam University

summary: Pathogenic biofilms have been associated with persistent infections due to high resistance to antimicrobial agents while commensal biofilms often fortify host immune system.  Hence, controlling biofilm formation of both pathogenic bacteria and commensal bacteria is important in bacteria-related diseases.  We investigated the effect of plant flavonoids on biofilm formation of both enterohemorrhagic Escherichia coli O157:H7 and three commensal E. coli K-12 strains.  Phloretin abundant in apples markedly reduced E. coli O157:H7 biofilm formation without affecting the growth of planktonic cells while phloretin did not harm commensal E. coli K-12 biofilms.  Also, phloretin reduced E. coli O157:H7 attachment to human colon epithelial cells.  Global transcriptome analyses revealed that phloretin repressed toxin genes (hlyE and stx2), autoinducer-2 importer genes (lsrACDBF), a curli gene (csgA), and a dozens of prophage genes in E. coli O157:H7 cells.  Electron microscopy confirmed that phroretin reduced the curli production in E. coli O157:H7.  In addition, phloretin suppressed TNF-α-induced inflammatory response in vitro using human colonic epithelial cells.  Moreover, in the trinitrobenzene sulfonic acid (TNBS)-induced rat colitis model, phloretin significantly ameliorated colon inflammation and body weight loss.  Taken together, our results suggest that phloretin may act as an inhibitor of E. coli O157:H7 biofilm formation as well as anti-inflammatory agent on inflammatory bowel diseases while leaving beneficial commensal E. coli biofilm intact.

overall_design: For the microarray experiments, E. coli O157:H7 EDL933 was inoculated in 25 ml of LB in 250 ml flasks with overnight cultures that were diluted at 1:100. Cells were shaken at 100 rpm and 37°C for 7 hrs.  Cells were immediately chilled with dry ice and 95% ethanol (to prevent RNA degradation) for 30 sec before centrifugation in 50 ml centrifuge tubes at 13,000 g for 2 min; cell pellets were frozen immediately with dry ice and stored -80°C.  RNA was isolated using Qiagen RNeasy mini Kit (Valencia, CA, USA). To eliminate DNA contamination, Qiagen RNase-free DNase I was used to digest DNA. RNA quality was assessed by Agilent 2100 bioanalyser using the RNA 6000 Nano Chip (Agilent Technologies, Amstelveen, The Netherlands), and quantity was determined by ND-1000 Spectrophotometer (NanoDrop Technologies, Inc., DE, USA).

first: Jin-Hyung

first: Jung-Ae

last: Kim

first: Sushil

middle: C

last: Regmi

first: Moo

middle: H

last: Cho

first: Hyungdon

last: Yun

first: Chang-Soo


title: CRC samples for FOLFOX therapy prediction

status: Public on Nov 21 2011

city: Meguro-ku

first: Shingo

last: Tsuji

state: Tokyo

address: 4-6-1 Komaba

department: Research Center for Advanced Science and Technology

country: Japan

institute: The University of Tokyo

summary: The aim of this study is to identify responders to FOLFOX therapy by applying the Random Forests (RF) algorithm to gene expression data. Eighty-three unresectable colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into training (54 patients) and test (29 patients) sets.

overall_design: Samples were divided (approximately 2:1 ratio) into training and test sets. As a result, 54 of 83 samples obtained in the first half of this period were selected for the training set, and the remaining 29 samples in the latter half were selected as the test set.


title: An interspecies analysis reveals sequence determinants of the bivalent chromatin state

status: Public on Nov 16 2011

city: Oxford

first: Magnus

middle: David

last: Lynch

address: John Radcliffe Hospital

department: Molecular Haematology Unit

country: United Kingdom

institute: Weatherall Institute of Molecular Medicine

type: Genome binding/occupancy profiling by high throughput sequencing

summary: The sequence determinants of chromatin bivalency remain unclear. We analysed sequence determinants of chromatin bivalency genome-wide in several mammalian species and performed a series of transgenic experiments in mouse ES cells.

sample_organism:
Mus musculus
Rattus norvegicus

platform_organism:
Mus musculus
Rattus norvegicus

overall_design: Genome-wide mapping of H3K27me3 in rat ES cells and ChIP-seq with anti-Ezh2 antibody in transgenic mouse ES cells


title: Mesenchymal Stem Cells Transfer Mitochondria to the Cells with Virtually Absent Mitochondrial Function but Not to the Cells Harboring Pathogenic Mitochondrial DNA Mutations

city: Seoul

first: mingoo

last: kim

address: Seoul

institute: SNUBI

summary: It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether MSCs transfer mitochondria to the cells under several different conditions of mitochondrial dysfunction, including human pathogenic mitochondrial DNA (mtDNA) mutations. Using biochemical selection methods, we found that exponentially growing cells in restrictive media (uridine-  and bromodeoxyuridine [BrdU]+) after coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mtDNA identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B rho0 cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. A chemotaxis inhibitory agent blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential “cell therapy-based mitochondrial restoration or mitochondrial gene therapy” for human diseases caused by mitochondrial dysfunction.

overall_design: time series

first: YoungMin

first: JuHan

first: Mingoo

first: SuJin

last: Park

first: SangHyeok

last: Koh

first: HyoSeop

last: Ahn

first: GyeongHoon

last: Kang

first: Jung-Bin

first: KyongSoo

first: HongKyu


title: Melanoma cell culture phenotypes

status: Public on Nov 17 2011

city: Zürich

first: Daniel

middle: Simon

last: Widmer

address: Gloriastrasse 31

department: Dermatology

country: Switzerland

institute: University Hospital Zürich


title: Oct4 and jhdm1b infected MEF with or without vitamin C treatment

city: guangzhou

first: Pei

middle: Duan

last: Qing

address: 190,Kaiyuan avenue

country: China

institute: Guangzhou Institute of Biomedicine and Health, CAS

summary:
Investigate the effect of jhdm1b on Oct4 mediated reprogramming
Investigate the effect of vitamin C on the function of jhdm1b

overall_design: oct4 and  jhdm1b infected MEF with or without vitamin C treatment

first: Tao

last: Wang

first: Keshi

last: Chen

first: Xiaoming

last: Zeng


title: Transcriptome Atlases Of Mouse Brain Reveals Differential Expression Across Brain Regions And Genetic Backgrounds

status: Public on Nov 19 2011

city: Chapel Hill

first: Vasyl

last: Zhabotynsky

state: NC

address: 120 Mason Farm Road   5000 D, Genetic Medicine Building

institute: University of North Carolina at Chapel Hill

summary:
Assessed steady-state transcription in whole brain and two more specific brain regions.
Studied the impact of strain genetic background on expression levels. In addition, we also studied the effects of acute clozapine exposure on gene expression in mouse brain.

overall_design: We analysed brain samples from adult male mice (forebrain, hindbrain and whole brain) contrasting the effects of strain (C57BL/6J versus NOD/ShiLtJ) and acute drug treatment vehicle) with four mice per cell (16 mice in total).

first: Wei

last: Sun

first: Seunggeun

last: Lee

first: Fei

last: Zou

first: Fred

last: Wright

first: Jim

last: Crowley

first: Zaining

first: Ryan

last: Buus

first: Darla

last: Miller

first: Jeremy

first: Leonard

last: McMillan

first: Fernando-Pardo

last: Manuel de Villena

first: Patrick

middle: F

last: Sullivan


title: Histone deacetylase inhibition decreases proliferation and potentiates the effect of ionizing radiation in atypical teratoid/rhabdoid tumor cells

status: Public on Nov 14 2011

city: Aurora

first: Diane

middle: K

last: Birks

state: CO

department: Neurosurgery

institute: University of Colorado, Denver - Anschutz Medical Campus

summary:
Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant CNS neoplasm whichprimarily occurs in children under three years of age. Due to poor outcomes with intense and toxicmultimodality treatment, new therapies are urgently needed. Histone deacetylase inhibitors (HDIs)have been evaluated as novel agents for multiple malignancies and have been shown to function asradiosensitizers. They act as epigenetic modifiers and lead to re-expression of inappropriatelyrepressed genes, proteins, and cellular functions. Due to the underlying chromatin remodeling genemutation in ATRT, HDIs are ideal candidates for therapeutic evaluation. To evaluate the role of HDIsagainst ATRT in vitro, we assessed the effect of drug treatment on proliferation, apoptosis, and geneexpression. Additionally, we examined HDI pretreatment as a radiosensitization strategy for ATRT.MTS and clonogenic assays demonstrated that HDI treatment significantly reduces the proliferativecapacity of BT-12 and BT-16 ATRT cells. Also, the HDI SNDX-275 was able to induce apoptosis in bothcell lines and induced p21Waf1/Cip1 protein expression as measured by Western blot. Evaluation ofdifferential gene expression by microarray and pathway analysis after HDI treatment demonstratedalterations of several key ATRT cellular functions. Finally, we showed that HDI pretreatmenteffectively potentiates the effect of ionizing radiation on ATRT cells as measured by clonogenic assay.These findings suggest that the addition of HDIs to ATRT therapy may prove beneficial, especiallywhen administered in combination with current treatment modalities such as radiation.
Keywords: ATRT; HDAC inhibitor; radiosensitization

overall_design: BT12 and BT16 cells were plated and subsequently treated for 24hr with IC25 concentrations of SNDX-275 (Sigma), at which time total RNA was collected.  IC25 concentrations were calculated based on MTS assay.For BT12, the SNDX-275 IC25 was 1.4uM. For BT16, it was 0.44uM.  The controls had DMSO added at equivalent volumes.

first: Jeffrey

last: Knipstein

first: Andrew

last: Donson

first: Nicholas

last: Foreman

first: Rajeev

last: Vibhakar

first: Irina

last: Alimova


title: Isolation and in vitro expansion of human colonic stem cells [Expression profile]

city: Barcelona

first: Eduard

last: Batlle

state: Barcelona

address: Baldiri i Reixac 10

department: Oncology

country: Spain

institute: Institute for Research in Biomedicine Barcelona

summary: Using the surface marker EPHB2, we have FACS-purified and profiled stem cell-enriched cell fractions from normal human mucosa, crypt proliferative progenitors and late transient amplifying cells to define a gene expression program specific for normal human colon epithelial stem cells

overall_design: We FACS purified human colonic crypt cells according to their EPHB2 surface abundance. We used Affymetrix chips to hybridize 3 samples from EPHB2-high, 3 samples from EPHB2-medium, 3 samples from EPHB2-low, and 2 samples from EPHB2-negative cells

first: Peter

last: Jung

first: Anna

last: Merlos-Suárez


title: Transcriptome of early postnatal brain development of eIF2B-R132H/R132H mutant mice relative to wild-types.

city: Tel Aviv

first: Liraz

last: Marom

address: Department of Cell Research and Immunology Tel Aviv University

department: Cell Research and Immunology

country: Israel

institute: Tel Aviv University

summary: Genome-wide mRNA expression in brains of wild-type and eIF2B-R132H/R132H mutant mice (Geva et al., BRAIN 133 (8), 2010) profiled at postnatal (P) days 1, 18 and 21 to reflect the early proliferative stage prior to white matter establishment (P1) and the peak of oligodendrocye differentiation and myelin synthesis (P18 and P21).

overall_design: 3 biological replicates (whole brain without the cerebellum) from each wild-type and eIF2B-R132H/R132H mutant mice at 3 postnatal (P) days 1, 18 and 21 were used for RNA extraction and hybridization on Affymetrix microarrays.

first: Igor

last: Ulitsky

first: Ron

last: Shamir

first: Orna

last: Elroy-Stein


title: Isolation and in vitro expansion of human colonic stem cells

type: Genome variation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Identification of a Potential Ovarian Cancer Stem Cell Gene Expression Profile from Advanced Stage Papillary Serous Ovarian Cancer

city: Boston

first: Michael

last: Birrer

address: 70 Blossom Street

department: Medicine

institute: MGH

summary:
To identify the potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma
Microarrays were used to interrogate the differentially expressed genes between side population (SP) and main population (MP)  isolated from fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma, and the results were analyzed by paired T-test using BRB-ArrayTools

overall_design: Gene expression profiling was completed for 10 SP and MP pairs using the Affymetrix human U133 Plus 2.0 Arrays

first: Vathipadiekal

last: Vinod

first: Deepa

last: Saxena

first: Samuel

last: Mok

last: Hauschka

first: Laurent

last: Ozbun


title: Gene expression regulated by AGN193109 and 4-diehtylaminobenzaldehyde (DEAB) in mIMCD-3 cells

status: Public on Nov 26 2011

city: London

first: Qihe

last: Xu

address: 123, Coldharbour Lane

institute: King's College London

summary:
All-trans retinoic acid (tRA) is the bioactive derivative of vitamin A that regulates gene expression by activating RA receptors (RAR). By using a reporter mouse model, we recently showed that endogenous tRA/RAR signaling was present in kidney collecting duct cells, and in mouse inner medullary collecting duct cell line (mIMCD-3).
In order to unveil target genes of endogenous tRA/RAR signaling in kidney collecting duct cells, whole genome microarray analysis was performed on mIMCD-3 cells treated with AGN193109, a pan-RAR antagonist, and 4-diethylaminobenzaldehyde (DEAB), an inhibitor of tRA synthesizing enzyme. Specificity of gene expression regulation was confirmed by determining the reversibility of the regulation by simultaneous addition of exogenous tRA.

overall_design: In the first set of experiment, mIMCD-3 cells were treated with either vehicle (0.1% ethanol and 0.1% DMSO) or 1 μM AGN193109 or 1 μM AGN193109+0.2 μM tRA. Three independent biological experiments were performed. In the second set of experiment, mIMCD-3 cells were treated with either vehicle (0.1% ethanol and 0.1% DMSO) or 25 μM DEAB or 25 μM DEAB+0.01 μM tRA. Three independent biological experiments were performed. Treatment period for both sets of experiments were 24 hours.

first: YuenFei

last: Wong


title: Eosinophil specific transcriptome in homeostatic intestine and lung

city: Cincinnati

first: Marc

last: Rothenberg

state: OH

address: 3333 Burnet Ave. MLC-7028

department: Allergy

institute: Cincinnati Children's Hospital Medical Center

summary:
Objective: To study the physiological role of eosinophils in the GI tract and lung under homeostatic conditions,
Method: we analyzed tissue-specific eosinophil gene expression patterns by genome-wide expression microarray analysis using RNA isolated from FACS-sorted eosinophils from the small intestine or lung of naive BALB/cmice (Live eosinophils were identified as DAPI-CCR3+Siglec-F+CD45+CD4-CD8a-CD19-B220-SSChigh cells).
Result: There are 513 genes that are differentially expressed by intestinal eosinophils and Lung eosinophils.
Conclusion: Eosinophils from different tissues have unique gene expression patterns for distinct functions.


title: Mixed Culture Gene Expression of E. coli and Pseudomonas aeruginosa

status: Public on Nov 09 2011

city: San Marcos

first: Robert

middle: JC

last: McLean

state: TX

address: 601 University Drive

department: Biology

institute: Texas State University-San Marcos

summary: Transcriptional profiles of Escherichia coli MG1655 in mixed culture with Pseudomonas aeruginosa PAO1 showed a number of E. coli genes to be upregulated including purA-F and other genes associated with purine synthesis. In contrast, genes associated with pyrimidine synthesis were unaffected. Competition experiments in both planktonic and biofilm cultures, using three purine synthesis mutants, purD, purH, and purT showed little difference in E. coli survival from the parent strain. As purines are components of the cell signals, cAMP and c-di-GMP, we conducted competition experiments with E. coli mutants lacking adenylate cyclase (cyaA), cAMP phosphodiesterase (cpdA), and the catabolite receptor protein (crp), as well as ydeH, an uncharacterized gene that has been associated with c-di-GMP synthesis. Survival of the cyaA and crp mutants during co-culture were significantly less than the parent strain. Supplementation of the media with 1mM cAMP could restore survival of the cyaA mutant but not the crp mutant. In contrast, survival of the cpdA mutant was similar to the parent strain. Survival of the ydeH mutant was moderately less than the parent, suggesting that cAMP has more impact on E. coli mixed culture growth than c-di-GMP. Addition of 1 mM indole restored the survival of both the cyaA and crp mutations. Mutants in genes for tryptophan synthesis (trpE) and indole production (tnaA) showed a loss of competition and recovery through indole supplementation, comparable to the cyaA and crp mutants. Overall, these results suggest indole and cAMP as major contributing factors to E. coli growth in mixed culture.

sample_organism:
Escherichia coli
Pseudomonas aeruginosa PAO1

platform_organism:
Pseudomonas aeruginosa
Escherichia coli

overall_design: Two replicates of LB grown E. coli ZK126 and P. aeruginosa PAO1 were grown in pure culture at 37C to an OD of 0.3 (log phase) and then mixed 1:1 and incubated for an additional 45 min. RNA was extracted, purified, reverse transcribed to cDNA and then analyzed on E. coli and P. aeruginosa chips from Affymetrix. Expression profiles were compared to pure culture E. coli and P. aeruginosa grown on LB.

first: Mary

last: Weber

first: Marvin

last: Whiteley


title: Endothelial cells present an innate resistance to glucocorticoid treatment: implications for therapy of primary vasculitis

status: Public on Nov 10 2011

city: Hannover

first: Dorothee

last: Viemann

state: Deutschland

address: Carl-Neuberg-Straße 1

department: Department of Pediatric Pulmonology, Allergy and Neonatology

institute: Hannover Medical School

summary: Morphogenesis of epithelial tissues relies on the precise developmental control of cell polarity and architecture. In the early Drosophila embryo, the primary epithelium forms during cellularisation, following a tightly controlled genetic programme where specific sets of genes are up-regulated. Some of them, for instance, control membrane invagination between the nuclei anchored at the apical surface of the syncytium.

overall_design: Huvec were treated for 4h and 16h with dexamethasone. Two independent experiments.

first: Paola

last: Koenen

first: Katarzyna

last: Barczyk

last: Wolf

first: Johannes

last: Roth


title: Expression data from human keratinocyte and PBMC-derived iPS cells

city: Rochester

first: Yasuhiro

last: Ikeda

state: MN

address: 200 First Street SW

institute: Mayo Clinic

summary:
Induced pluripotent stem cell (iPSC) technology allows for the generation of patient-specific pluripotent stem cells, from somatic cell sources, thereby providing a novel cell therapy platform for severe degenerative diseases. One of the key issues for clinical-grade iPSC derivation is the accessibility of donor cells used for reprogramming and subsequent feasiblity of reprogramming into a pluripotent state.
We used microarrays to detail the global gene expression profiles from blood cells. The use of blood cells allows for minimally invasive tissue procurement under GMP conditions and rapid cellular reprogramming, mobilized HPCs and unmobilized PBMCs would be ideal somatic cell sources for clinical-grade iPSC derivation.

overall_design: We examined the feasibility of reprogramming mobilized GMP-grade hematopoietic progenitor cells (HPCs) and mononuclear myeloid cells and tested the pluripotency of derived iPS clones.

first: Ohmine

last: Seiga

first: Ikeda

last: Yasuhiro


title: Gene expression changes in human hepatocytes exposed to VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate)

status: Public on Nov 11 2011

city: Silver Spring

first: Xiugong

last: Gao

address: 503 Robert Grant Ave

institute: Walter Reed Army Institute of Research

summary:
Organophosphorus compounds induce hepatotoxicity through currently unknown mechanisms, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis.
We used microarrays to study gene expression changes in human hepatocytes after exposure to VX, and identified pathways underlying these changes.

overall_design: Human hepatocytes were exposed to sublethal concentrations (0, 0.1, 10 μM) of VX. RNA were extracted at different timepoints (0, 6 h) after VX exposure and hybridized to Affymetrix microarrays. Four biological repeats were used for each condition.

first: Hsiuling

last: Lin

first: Radharaman

last: Ray

first: Prabhati


title: Preclinical analysis of the gamma secretase inhibitor PF-030840214 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia

city: New York

first: Adolfo

last: Ferrando

address: 1130 St. Nicholas Avenue, Irving Cancer Research Center, Room 402A

department: Institute for Cancer Genetics

institute: Columbia University

summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer frequently associated with activating mutations in NOTCH1. Early studies identified NOTCH1 as an attractive therapeutic target for the treatment of T-ALL through the use of gamma-secretase inhibitors (GSIs).  Here, we characterized the interaction between PF-03084014, a clinically-relevant GSI, and dexamethasone in preclinical models of glucocorticoid-resistant T-ALL. Combination treatment of the GSI PF-03084014 with glucocorticoids induced a synergistic antileukemic effect in human T-ALL cell lines and primary human T-ALL patient samples. Molecular characterization of the response to PF-03084014 plus glucocorticoids through gene expression profiling revealed transcriptional upregulation of the glucocorticoid receptor as the mechanism mediating the enhanced glucocorticoid response.  Moreover, treatment with PF-03084014 and glucocorticoids in combination was highly efficacious in vivo, with enhanced reduction of tumor burden in a xenograft model of T-ALL.  Finally, glucocorticoid treatment was highly effective at reversing PF-03084014-induced gastrointestinal toxicity via inhibition of goblet cell metaplasia. These results suggest that combination of PF-03084014 treatment with glucocorticoids may be well-tolerated and highly active for the treatment of glucorticoid-resistant T-ALL.

overall_design: Duplicate samples of the CUTLL1 T-ALL cell line were treated with vehicle only (DMSO), the gamma-secretase inhibitor PF-03084014 (1 microM), dexamethasone (1 microM), or PF-03084014 (1 microM).  plus dexamethasone (1 microM) for 48 hours. Gene expression profiling was analyzed to identify gene expression signatures assocuated with glucocorticoid treatment (dexamethasone), inhibition of NOTCH1 by gamma secretase inhibitor (PF-03084014) or the combination of both treatments.

first: Jeremy

middle: B

last: Samon


title: Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL

status: Public on Nov 08 2011

address: 1130 St Nicholas Avenue

summary:
The TLX1 and TLX3 transcription factor oncogenes play an important role in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL)1,2. Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This Systems Biology analysis defined TLX1 and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, network structure analysis of this hierarchical network identified RUNX1 as an important mediator of TLX1 and TLX3 induced T-ALL, and predicted a tumor suppressor role for RUNX1 in T-cell transformation. Consistent with these results, we identified recurrent somatic loss of function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 atop of an oncogenic transcriptional network controlling leukemia development, demonstrate power of network analysis to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor suppressor gene in T-ALL.

This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series.


title: Expression data obtained from ALLSIL cell line

summary:
The experiment was designed in order to knock down the expression of TLX1 gene in T-ALL cell line
We used microarrays to identify the gene expression signatures associated with TLX1 knock down in ALLSIL

overall_design: ALLSIL cell lines were infected with pLKO.1-shTLX1 and pLKO.1-luc control lentivirus. After 5 days of puromycin selection cells were collected and RNA was extracted in order to analyze the global changes in gene expression by Affymetrix U133 Plus 2 array.

first: Teresa

last: Palomero

first: Giusy

last: Della Gatta


title: Expression data obtained from HPBALL cell line

summary:
The experiment was designed in order to knock down the expression of TLX3 gene in T-ALL cell line
We used microarrays to identify the gene expression signatures associated with TLX3 knock down in HPBALL

overall_design: HPBALL cell lines were infected with pLKO.1-shTLX3 and pLKO.1-luc control lentivirus. After 5 days of puromycin selection cells were collected and RNA was extracted in order to analyze the global changes in gene expression by Affymetrix U133 Plus 2 array.


title: Human Monocytes to M-CSF differentiated Macrophages

status: Public on Nov 07 2011

city: Neuherberg

first: Dominik

last: Lutter

address: Ingolstädter Landstraße 1

department: Institute for Diabetes and Obesity

institute: Helmholtz Zentrum München

summary:
This dataset was created to study M-CSF dependent in vitro differentiation of human monocytes to macrophages as a model process to demonstrate that independent component analysis (ICA) is a useful tool to support and extend knowledge-based strategies and to identify complex regulatory networks or novel regulatory candidate genes.
Keywords: M-CSF, Monocytes, Macrophages

overall_design:
Samples for microarray analysis were isolated from healthy donors and from donors with Niemann-Pick type C disease. Monocytes were differentiated to macrophages for 4 days in the presence of M-CSF (50 ng/ml,R\&D Systems). Differentiation was confirmed by phase contrast microscopy. Total RNA was extracted from the tissue biopsies according to the manufacturer´s instructions using the RNeasy Protect Midi Kit (Qiagen). Purity and integrity of the RNA was assessed on the Agilent 2100 bioanalyzer with the RNA 6000 Nano LabChip reagent set (Agilent Technologies, Böblingen, Germany). The RNA was quantified spectrophotometrically and then stored at −80°C. Gene expression profiles were determined using Affymetrix HG-U133A and HG-U133plus2.0. Array scanning and expression analysis was performed using Microarray Analysis Suite 5.0 software. Each array was scaled to a target intensity of 100 (scaling to all probesets).

*** CEL files not provided for GSM247170 and GSM247407

first: Christoph

last: Moehle

first: Margot

last: Grandl

first: Guido

last: Maa Bared

first: Evelyn

last: Orso


title: miR-126 over-expression in highly metastatic LM2 breast cancer cells.

status: Public on Dec 16 2011

first: Nils

last: Halberg

address: 1230 York Avenue

institute: Rockefeller University

summary:
miR-126 were over-expressed using the miR-Vec system in highly metastatic LM2 cells. The LM2 cell line are described in detail in Minn et al. Nature 2005
This approach was used to conduct an unbiased search for specific miR-126 target genes in breast cancer cells.

overall_design: 4 Samples

first: Halberg

last: Nils

first: Png

last: Kim

first: Tavazoie

last: Sohail


title: Expression data from human bone marrow hematopoietic stem cells

city: Stanford

first: Debashis

last: Sahoo

address: 265 Campus Drive, Rm G3101B

department: Pathology

institute: Stanford University

summary:
In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. While the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have not yet been characterized.
Gene expression profiling revealed that aged human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, function, and gene expression profile of human HSC are significantly similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.

overall_design: In order to elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared to young HSC.

first: Wendy

middle: W

last: Pang

first: Elizabeth

middle: A

last: Price

first: Isabel

last: Beerman

first: William

last: Maloney

first: Derrick

last: Rossi

first: Stanley

middle: L

last: Schrier

first: Irving

last: Weissman


title: AMC colon cancer AJCCII

status: Public on Nov 05 2011

city: Amsterdam

first: Richard

last: Volckmann

address: van der Boechorststraat 6a

department: Laboratory of Experimental Oncology and Radiobiology

institute: msterdam UMC and University of Amsterdam

summary: Profiling project of CRC patient material collected in the Academic Medical Center (AMC) in Amsterdam, The Netherlands. We focused on a set of 90 AJCC stage II patients that underwent intentionally curative surgery in the years 1997-2006 (AMC-AJCCII-90). Extensive medical records are kept from these patients and long-term clinical follow-up is available for the large majority. Both paraffin-embedded as well as fresh frozen tissue is available from all these patients for analysis.

overall_design: Primary tumor resections from 90 AJCC stage II CRC patients, and matching normal colon tissue from 6 of these patients, are included in the study.

first: Jan

middle: P

last: Medema

first: Dick

last: Richel

first: Rogier

last: Versteeg

first: Felipe

last: de Sousa E Melo

first: Louis

last: Vermeulen

first: Marc

last: van de Vijver

last: Koster

first: Jurriaan

last: Tuynman

first: Steven

last: Pals

first: T

middle: M

last: Van Gulik

first: W

last: Bemelman

first: P

last: Tanis


title: Gene Level Expression Profiling of MEFs derived from wild type and Smurf2-/- embryos

city: Bethesda

first: Ying

middle: E

last: Zhang

state: Maryland

address: 37 Convent Dr., Bldg.37, Rm.2056

department: LCMB/CCR

institute: National Cancer Institute, NIH

summary:
Transcriptome analysis of RNAs extracted from early passage and late passage (immortalized) mouse embryonic fibroblasts (MEFs)
We compared the gene expression profiles of early (p.6-7) and immortalized (p.28-33) Smurf2KO cells to those of their wild-type counter parts, and selected the genes that were differentially expressed at a cut-off of 1.54 folds in both B6 and BL backgrounds.  The results showed a progressive increase in differential gene activities with the number of cell passages.  We detected 101 differentially expressed genes in the early passage and 668 in the immortalized Smurf2KO cells, with 49 in common between these two categories.  These data pointed to a global deregulation of gene expression as the cells became immortalized in the absence of Smurf2.

overall_design: We analyzed MEFs from wild type and Smurf2-/- embryos from both C57B6/L (B6) and mixed 129SVJ x NIH Black Swiss (BL) backgrounds  using the Affymetrix mouse Exon 1.0 ST platform. No techinical replicates were performed.

first: Michael

last: Blank


title: Gene expression in colon cancer stem cells (CSC) cultures identified by Wnt signaling levels

summary: Primary colon CSC cultures were transduced with a Wnt responsive construct (TOP-GFP). 10% highest and lowest TOP-GFP cell fractions were FACS sorted and arrayed.

overall_design: Primary colon CSC cultures with a responsive construct (TOP-GFP): high and low TOP-GFP cell fractions. 12 samples.

last: De Sousa E Melo

first: Selcuk

last: Colak

first: Pramudita

last: Prasetyanti


title: Gene expression analysis of osteosarcoma tumor-initiating cells (High) vs bulk tumor cells (Low)

status: Public on Nov 04 2011

city: Houston

first: Alexander

last: Yu

department: Pediatrics

institute: Baylor College of Medicine

summary: In the cancer stem cell model a cell hierarchy has been suggested as an explanation for intratumoral heterogeneity, and tumor formation is thought to be driven by this tumor cell subpopulation. The identification of cancer stem cells in osteosarcoma (OS) and the biological processes dysregulated in this cell subpopulation, also known as tumor-initiating cells (TICs), may provide new therapeutic targets. The goal of this study, therefore, was to identify and characterize the gene expression profiles of TICs isolated from human OS cell lines. We analyzed the self-renewal capacity of OS cell lines and primary OS tumors based upon their ability to form sphere-like structures (sarcospheres) under serum-starving conditions. TICs were identify from OS cell lines using the long-term label retention dye PKH26. OS TICs and the bulk of tumor cells were isolated and used to assess their ability to initiate tumor in NOD/SCID mice. Gene expression profiles of OS TICs were obtained from fresh orthotopic tumor samples. We observed that increased sarcosphere efficiency correlated with an enhanced tumorigenic potential in OS. PKH26High cells were shown to constitute OS TICs based upon their capacity to form more sarcospheres, as well as to generate both primary bone tumors and lung metastases efficiently in NOD/SCID mice. Genomic profiling of OS TICs revealed that both bone development and cell migration processes were dysregulated in this tumor cell subpopulation. PKH26 labeling represents a valuable tool to identify OS TICs and gene expression analysis of this tumor cell compartment evidences potential therapeutic targets.

overall_design: Gene expression analysis was performed in PKH26Hi cells (TICs) and PKH26Lo cells (non-TICs) obtained from five orthotopic bone tumors generated by each MNNG/HOS and 143B cell lines.The soft tissue component from each bone tumor was dissected, minced and processed. Immediately after FACS, 1.5x10^5 PKH26Hi cells and 7x10^5 PKH26Lo cells from each bone tumor sample were snap frozen and stored at -80°C until RNA processing. The microarray data were first evaluated for quality control using the AffyQCReport library of BioConductor 50.Two 143B PKH26Hi tumor samples  were processed together due to insufficient RNA material.

first: Nino

last: Rainusso

first: Tsz-Kwong

last: Man

first: Ching

last: Lau

first: John

last: Hicks

first: Jianhe

middle: J

last: Shen

first: Lisa

last: Wang

first: Jeffrey

last: Rosen


title: Expression data from five human leukemia cell lines treated with DMSO or tanshinone IIA

status: Public on Nov 03 2011

city: Beijing

first: jianqin

last: li

address: No. 151 Malianwa North Road, Haidian District

institute: The Institute of Medicinal Plant Development

summary:
Tanshinone IIA (Tan IIA) is a diterpene quinone extracted from the root of Salvia miltiorrhiza, a Chinese traditional herb. Although previous studies have reported the anti-tumor effects of Tan IIA on various human cancer cells, the underlying mechanisms are not clear.
We used microarrays to detail the global programme of gene expression underlying Tan IIA's apoptotic effects on leukemia cells and identified  significantly differentially expressed genes (SDEGs).

overall_design: Five human leukemia cell lines were selected for RNA extraction and hybridization on Affymetrix microarrays.To identify genes that are related to Tan IIA sensitivities, we carried out expression profiling on five cell lines.The sample named HL60, MEG01, MOLT,THP1 and U937_control were treated with DMSO. U937 cell line was selected with Tan IIA treatment for 12 h and 24 h, respectively.

first: Chang

last: Liu


title: The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression

status: Public on Nov 01 2011

city: Vienna

first: Maximilian

last: Kauer

address: Zimmermannplatz 10

department: Molecular Biology

country: Austria

institute: CCRI, St.Anna Children Cancer Research Institute

summary: Background: ETV6/RUNX1 (E/R) (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL) and also most likely the crucial factor for disease initiation, whereas its role in leukemia propagation and maintenance remains largely elusive. To address this issue we performed a shRNA-mediated knock-down (KD) of the E/R fusion gene and investigated the ensuing consequences on genome-wide gene expression patterns and deducible regulatory functions in two E/R-positive leukemic cell lines. Findings: Microarray analyses identified 777 genes whose expression was substantially altered. Although approximately equal proportions were either up- (KD-UP) or down-regulated (KD-DOWN), the effects on biological processes and pathways differed considerably. The E/R KD-DOWN set was significantly enriched for genes included in the cell activation, immune response, apoptosis, signal transduction and development and differentiation categories, whereas in the E/R KD-UP set only the PI3K/AKT/mTOR signaling and hematopoietic stem cells categories became evident. Comparable expression signatures obtained from primary E/R-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories stem cell properties, B-cell differentiation, immune response, cell adhesion and DNA damage with RT-qPCR. Conclusion: The results of our analyses provide the first preliminary evidence that the continuous expression of the E/R fusion gene interferes with regular B-cell development by repressing key functions that are necessary under physiological circumstances. E/R may thus constitute also the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets.

overall_design: Knockdown of ETV6/RUNX1 in two t(12;21) positive leukemic cell lines

first: Gerhard

last: Fuka

first: Reinhard

last: Kofler

first: Oskar

last: Haas

first: Renate

last: Panzer-Grümayer


title: mRNAs associated with human DAZ-interacting protein (DZIP1)

city: Curitiba

first: PATRICIA

last: SHIGUNOV

state: Paraná

address: Rua Prof. Algacyr Munhoz Mader, 3775

country: Brazil

institute: Instituto Carlos Chagas - FIOCRUZ-PR

summary:
DZIP (DAZ-Interacting Protein) containing a C2H2 zinc-finger domain is expressed predominantly in human embryonic stem cells and fetal and adult germ cells; DZIP colocalizes with DAZ and/or DAZL proteins in these tissues. DZIP may associate with DAZ and its other cofactors in an RNA-binding protein complex that functions in both embryonic stem cells and germ cells.
To identify mRNAs associated with human DZIP1 protein in HeLa cells, we used a modified Ribonucleoprotein-ImmunoPrecipitation Microarray (RIP-Chip).DZIP1 ribonucleoprotein (RNP) complexes were performed with 2 µg of anti-DZIP1 antibody (rabbit polyclonal, Santa Cruz Biotechnology, CA, USA) bound to protein A-agarose beads (Sigma, Deisenhofen, Germany). HeLa cells were lysed in polysome lysis buffer  (Tris-HCl pH 7,4 15mM, MgCl2 15 mM, NaCl 0,3 M, 1% Triton X-100, 1 mM DTT, 100 U / ml RNase Out, PMSF 1mM and E64 10uM) for one hour at 4°C. Beads were washed, then buffer and cell lysate were added, and the reaction mixtures were tumbled for 2 hours at 4°C. After this incubation, the beads were thoroughly washed again with polysome lysis buffer and then either RNA extracted for microarray and RT-PCR experiments using the RNeasy mini kit (Qiagen). To control for non-specifically enriched RNAs, identical IPs were performed with beads precoated with rabbit IgG as a negative control. RNA was processed for hybridization with GeneChip 3? IVT Express (Affymetrix - Santa Clara, USA), according to the manufacturers instruction. Briefly, cDNA was synthesized from immunoprecipitated RNA using reverse transcriptase followed by second strand synthesis to generate double-stranded cDNA. An in vitro transcription reaction was used to generate biotinylated cRNA. After purification and fragmentation, cRNA was hybridized onto GeneChip Affymetrix Human Genome U133 Plus 2.0 arrays. Post hybridization washes were preformed on an Affymetrix GeneChip® Fluidics Station 450. Arrays were scanned on an Affymetrix GeneChip® Scanner 3000. Scanned arrays were normalized using GCRMA in Partek software (Partek Incorporated. St. Louis, MO). Differentially enriched RNAs were found after performing One-way ANOVA analysis comparing immunoprecipitated samples against control samples. Final lists of genes were obtained by filtering the data from the statistical results according to fold enrichment more than 2 and false discovery rate (FDR 5%).

overall_design: DZIP IP and control IP samples were analyzed for each of 3 technical replicates.

first: Patrícia

last: Shigunov


title: Methylation of Cancer Stem Cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients

first: Richard

last: Volckmann

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

This dataset can be analyzed and visualized in the R2 platform: http://r2.amc.nl

overall_design: Refer to individual Series


city: Valbonne - Sophia-Antipolis

first: Kevin

last: Lebrigand

address: 660 route des lucioles

institute: IPMC/CNRS

summary:
In mammals, gonadal differentiation is the first step of sex determination, and the transcription factor Sox9 promotes testis differentiation. Here we used the XY Sox9flox/flox; Sf1:creTr/+ mouse model and show that the lack of Sox9 expression induces a full sex reversal of E13.5 XY Sox9flox/flox; Sf1:creTr/+ gonads compared to XY Sox9flox/flox.

Keywords: gonads gene expression profiling in WT and Sox9flox/flox; Sf1:creTr/+ mice

overall_design: 3 WT versus 3 Sox9flox/flox; Sf1:creTr/+ mice.

first: Rowena

last: Lavery

first: Chimène

last: Moreilhon

first: Kévin

first: Pascal

last: Barbry


title: Expression data from high grade astrocytoma surgical samples

status: Public on Oct 31 2011

city: Aurora

first: Andrew

last: Donson

institute: CU Anschutz Medical Campus

summary:
Survival in the majority of high grade astrocytoma (HGA) patients is very poor, with only a rare population of long-term survivors. A better understanding of the biological factors associated with long-term survival in HGA would aid development of more effective therapy and prognostication.
We used microarray gene expression profiling of 26 patient surgical samples with known clinical outcomes to discover novel prognostic markers.

overall_design: Gene expression profiles were generated from surgical tumor samples using Affymetrix HG-U133plus2 chips. All genes were correlated with survival as a continuous variable in order to identify ontologys associated with risk of recurrence.


title: Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine

first: Boris

last: Reizis

department: Microbiology and Immunology

institute: Columbia University Medical Center

summary: Dendritic cells (DCs) in tissues and lymphoid organs comprise distinct functional subsets that differentiate in situ from circulating progenitors. Tissue-specific signals that regulate DC subset differentiation are poorly understood. We report that DC-specific deletion of the Notch2 receptor caused a reduction of DC populations in the spleen. Within the splenic CD11b+ DCs, Notch signaling blockade ablated a distinct population marked by high expression of adhesion molecule Esam. The Notch-dependent Esamhi DC subset also required lymphotoxin beta receptor signaling, proliferated in situ and facilitated efficient CD4+ T cell priming. The Notch-independent Esamlo DCs expressed monocyte-related genes and showed superior cytokine responses. In addition, Notch2 deletion led to the loss of CD11b+ CD103+ DCs in the intestinal lamina propria and to the corresponding decrease of IL-17-producing CD4+ T cells in the intestine. Thus,Notch2 is a common differentiation signal for T cell-priming CD11b+ DC subsets in the spleen and intestine.

overall_design: We compared genome-wide expression profiles of wild-type Esam(hi) and Esam(lo) splenic CD11b+ DC populations, along with CD11b+ DCs from DC-RBPJΔ mice. Spleens from 2-3 Cx3cr1-GFP+ RBPJflox/flox CD11c-Cre+ mice or Cx3cr1-GFP+ RBPJflox/flox Cre-negative littermate controls were isolated, pooled and depleted of lymphoid and erythroid cells by negative selection on MACS columns. Live cells were stained for surface expression of CD11c, CD11b and Esam. CD11c(hi) CD11b+ DCs from control mice could be separated into Esam(lo) GFP(hi) versus Esam(hi) GFP(lo) subsets. CD11c(hi) CD11b+ DCs from RBPJ-targeted mice spleens  were uniformly Esam(lo) GFP(hi).  The two subsets from control mice and single Esam(lo) GFP(hi) subset from RBPJ-targeted mice were sorted using FACSAria II flow sorter and analyzed using GeneChip Mouse Gene 1.0 ST Array (Affymetrix).

first: Kanako

last: Lewis


title: Cerebellum from mice exposed to chronic low-level chlorpyrifos oxon

city: Seattle

first: Michael

last: Coon

state: WA

address: 4225 Roosevelt Way N.E., Suite 100

department: Center for Ecogenetics and Environmental Health

institute: University of Washington

summary:
Chlorpyrifos (CPF) is an organophosphorus (OP) insecticide that is still widely used despite statutory restrictions on home use. CPF is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver.  Paraoxonase (PON1) polymorphisms affects the catalytic efficiency of the hydrolysis of OPs, including CPO. We used both wt (PON1+/+) and PON1 knockout (PON1-/-) mice and PON1-/- mice carrying transgenes encoding the human alloforms tgHuPON1Q192 and tgHuPON1R192 to gain insight into the mechanisms of neurotoxicity of CPO throughout postnatal development, and to ascertain the importance of the PON1Q192R polymorphism for protecting against developmental toxicity of CPO. Whole-genome microarrays were used to measure gene expression changes associated with chronic CPO exposure of developing (PND 4-21) PON1-/-, tgHuPON1Q192R transgenic and PON1+/+ mice.
Expression profiles are derived from cerebella from wild-type C57/Bl6 and PON1-/- on a C57/Bl6 background and two transgenic strains (tgHuPON1Q192, tgHuPON1R192) expressing either human PON1Q192 or human PON1R192 on the PON1-/- C57/Bl6 background. The mice were subjected to chronic postnatal exposure to CPO (CPO).

overall_design:
Transgenic, PON1-KO and WT neonatal mice either treated with control (DMSO), 0.35 mg*kg-1*day-1 CPO or 0.5 mg*kg-1*day-1 CPO daily from PND 4 to PND 21. Chlorpyrifos (CPF) is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver.
55 arrays, 12 experimental groups (strain + treatment), due to QC issues the replicates are as follows; PON1-KO-0.35 (5), PON1-KO-.O5 (3), PON1-KO-DMSO (4), PON1-Q129-0.35 (5), PON1-Q129-0.5 (5), PON1-Q129-DMSO (4), PON1-R129-0.35 (5), PON1-R129-0.5 (5), PON1-R129-DMSO (4), WT-0.35 (6), WT-0.5 (3), WT-DMSO (6)

first: Toby

last: Cole

last: Beyer

first: Theodor

last: Bammler

first: Sarah

middle: S

last: Park

first: Federico

last: Farin

first: Lucio

middle: G

last: Costa

first: Clement

last: Furlong


title: Expression data from colorectal cancer cells

city: Guangzhou

first: Jianming

last: Li

address: Guangzhou North Road

institute: Southern Medical University

summary:
Gene expression profiling has been widely used to screen for metastasis-associated genes by comparing the difference in paired primary and metastatic colorectal carcinomas, orthotopic implantation mouse model or cells with different metastatic potential in the field of CRC research
In our study, we observed that the genes differentially expressed in M5 relative to its parent SW480 cell line

overall_design: Here we used the SW480, a human CRC cell line, as a model system. In vivo variant lines with increasing metastatic capacity were selected in a metastatic orthotopic model of human CRC. A subpopulation named as M5 with enhanced metastatic abilities to liver was isolated by in vivo selection of SW480 cells. We identified genes associated with tumor metastasis by comparing the difference between high metastatic subclone and its parent cells.

first: Yanqing

last: Ding

first: Shuang

last: Wang

first: Jun

last: Zhou


title: 18F-fluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basal-like breast cancers.

city: ALLSTON

first: Nicolaos

middle: Jay

last: Palaskas

state: MA

address: 15 North Beacon St #502

institute: UCLA

summary: Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways.  In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”.  FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC.  Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer.

overall_design: Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples.  Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays.  All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

first: Steven

last: Larson

first: Nikolaus

last: Schultz

first: Evangelia

last: Komisopoulou

first: Justin

last: Wong

first: Dan

last: Rohle

first: Carl

last: Campos

first: Joseph

middle: R

last: Osborne

first: Richard

last: Taschereau

first: Seema

last: Plaisier

first: Chris

last: Tran

first: Adriana

last: Heguy

first: Hong

last: Wu

last: Sander

last: Phelps

first: Cameron

last: Brennan

first: Jason

middle: T

last: Huse

first: Elisa

last: Port

first: Thomas

last: Graeber

first: Ingo

last: Mellinghoff


title: High Myc activity is an independent negative prognostic factor for diffuse large B cell lymphomas

city: Regensburg

first: Stefan

last: Bentink

state: Bayern

address: Josef Engertstr. 9

department: Institute of Functional Genomics

institute: University of Regensburg

summary:
In this study we investigated to which extend aberrant c Myc activity plays a functional role in other aNHL and whether it is independent from MYC translocations. Based on a combined microarray analysis of human germinal centre (GC) B cells transfected with c Myc and 220 aNHLs cases, we developed a ‘c Myc index’.
This data set contains expresssion profiles from Germinal center B-cells transfected with control or Myc expression vectors. The corresponding lymphoma gene expression profiles are included in the series with GEO accession GSE4475.

overall_design: Expression profiling of germinal center B-cells extracted from human tonsils with and without ectopic expression of Myc.

first: Alexandra

last: Schrader

first: Martina

last: Vockerodt


title: Validated Gene Expression Signatures of Idiopathic Pulmonary Fibrosis

city: Durham

first: Eric

middle: B.

last: Meltzer

department: Department of Medicine, Division of Pulmonary, Allergy and Critical Care

institute: Duke University

summary: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease that is difficult to diagnose and follows an unpredictable clinical course. The object of this study was to develop a predictive gene signature model of IPF from whole lung tissue. We collected whole lung samples from 11 IPF patients undergoing diagnostic surgical biopsy or transplantation. Whenever possible, samples were obtained from different lobes. Normals consisted of healthy organs donated for transplantation. We measured gene expression on microarrays. Data were analyzed by hierarchical clustering and Principal Component Analysis. By this approach, we found that gene expression was similar in the upper and lower lobes of individuals with IPF. We also found that biopsied and explanted specimens contained different patterns of gene expression; therefore, we analyzed biopsies and explants separately. Signatures were derived by fitting top genes to a Bayesian probit regression model. We developed a 153-gene signature that discriminates IPF biopsies from normal. We also developed a 70-gene signature that discriminates IPF explants from normal. Both signatures were validated on an independent cohort. The IPF Biopsy signature correctly diagnosed 76% of the validation cases (p < 0.01), while IPF Explant correctly diagnosed 78% (p < 0.001). Examination of differentially expressed genes revealed partial overlap between IPF Biopsy and IPF Explant and almost no overlap with previously reported IPF gene lists. However, several overlapping genes may provide a basis for developing therapeutic targets.

overall_design: 17 samples from 11 patients with IPF (6 patients provided a pair of samples from upper and lower lobes;  5 patients contributed singleton samples); 6 control specimens were obtained from routine lung volume reduction of healthy donor lungs at the time of lung transplantation.


title: Beta-catenin status effects in human adrenocortical carcinomas (33), adenomas (22), and normal adrenal cortex (10)

status: Public on Nov 02 2011

city: Ann Arbor

first: Rork

last: Kuick

state: MI

address: University of Michigan, SPH II, 1415 Washington Heights, Room M2533

institute: University of Michigan

summary: We scored adrenocortical carcinomas and adenomas for abnormal beta-catenin staining, and sequenced the beta-catenin gene in some samples. We compared adrenocortincal carcinomas with and without abnormal beta-catenin staining and found many significant expression differences and significant results from enrichment testing. A similar comparison in the adenomas gave relatively few differences, and they did not correlate to differences found for the carcinomas.  Abnormal beta-catenin staining was associated with mitotic rate and poorer patient survival in the carcinomas.  In a second independent data set (given in a supplement) we again found beta-catenin associated with poor survival.  The array data given is the same as GEO series GSE10927, with additional characteristics about beta-catenin, and new patient followup data.  The analysis shown in a supplementary Excel file is also new.

overall_design: Human samples of 33 adrenocortical carcinomas, 22 adrenocortical adenomas, and 10 normal adrenal cortex samples, each from a different patient, had mRNA assays performed using Affymetrix HG_U133_plus_2 arrays, with 54675 probe-sets.  23 of the carcinomas were used in survival analysis.  27 additional samples without array data were also used in a survival analysis.

first: Joanne

middle: H

last: Heaton

first: Michelle

last: Wood

first: Alex

middle: C

last: Kim

first: Lorena

middle: O

last: Lima

first: Ferdous

last: Barlaskar

first: Madson

middle: Q

last: Almeida

first: Maria

last: Fragosa

first: Antonio

last: Lerario

first: Derek

last: Simon

first: Ibere

last: Soares

first: Elizabeth

last: Starnes

first: Dafydd

last: Thomas

first: Ana

last: Latronico

last: Giordano

first: Gary

middle: D

last: Hammer


title: OXPHOS complex I deficiency leads to transcriptional changes of the Nrf2-Keap1 pathway and selenoproteins.

city: Hasselt

first: An

last: Voets

address: Martelarenlaan 42

department: BIOMED

country: Belgium

institute: Hasselt University

summary:
Defective complex I (CI) is the most common type of oxidative phosphorylation (OXPHOS) disease in patients, with an incidence of 1 in 5,000 live births. Complex I deficiency can present in infancy or early adulthood and shows a wide variety of clinical manifestations, including Leigh syndrome, (cardio)myopathy, hypotonia, stroke, ataxia and lactic acidosis. A number of critical processes and factors, like superoxide production, calcium homeostasis, mitochondrial membrane potential and mitochondrial morphology, are known to be involved in clinical CI deficiency, but not all factors are yet known and a complete picture is lacking.
Therefore, whole genome gene expression profiling was performed in fibroblasts of CI deficient patients and controls, comparing glycolytic and oxidative conditions. Linear regression and pathway analysis identified a number of key adaptive processes.

overall_design: Fibroblasts were derived from skin biopsies of five patients homozygous or compound heterozygous for nuclear complex I mutations and five controls. The groups were matched for age and sex.

first: Merei

last: Huigsloot

first: Patrick

last: Lindsey

first: Anne

last: Leenders

first: John

last: Esseling

first: Werner

last: Koopman

first: Peter

last: Willems

first: Richard

last: Rodenburg

first: Jan

middle: A

last: Smeitink

first: Hubert

last: Smeets


title: Gene expression data for pathological stage I-II lung adenocarcinomas

city: Chuo-ku

first: Takashi

last: Kohno

address: 5-1-1 Tsukiji

institute: National Cancer Center Research Institute

summary:
Identification of genes up-regulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas.
To elucidate molecular characteristics of lung adenocarcinomas (ADCs) with ALK mutations and those without EGFR, KRAS and ALK mutations, 226 primary lung ADCs of pathological stage I-II, examined for the status of EGFR, KRAS and ALK mutations, were subjected to genome-wide expression profiling, and genes up-regulated in lung ADCs with ALK mutations and those without EGFR, KRAS and ALK mutations were identified.  One hundred and seventy-four genes, including ALK, were selected as being up-regulated specifically in 79 lung ADCs without EGFR and KRAS mutations.  These 79 cases were divided into:  11 cases of ALK-positive ADCs, 36 cases of group A triple-negative ADCs, and 32 cases of group B triple-negative ADCs, by unsupervised clustering according to the expression of the 174 genes.  In ALK-positive ADCs, 30 genes, including ALK itself and GRIN2A, were significantly overexpressed.  Group A triple-negative ADC cases showed significantly worse prognoses for relapse and death than ADC cases with EGFR, KRAS or ALK mutations and group B triple-negative ADC cases.  Nine genes were identified as being significantly up-regulated in group A triple-negative ADC cases and critical for predicting their prognosis.  The nine genes included DEPDC1, which had been identified as a candidate diagnostic and therapeutic target in bladder and breast cancers.  Genes discriminating this group of ADCs will be useful for selection of patients who will benefit from adjuvant chemotherapy after surgical resection of stage I-II triple-negative ADCs and also informative for the development of molecular targeting therapies for these patients.

overall_design: Expression profiles in of 226 lung adenocarcinomas (127 with EGFR mutation, 20 with KRAS mutation, 11 with EML4-ALK fusion and 68 triple negative cases).

first: T


title: Sustained axon regeneration induced by a synergy of PTEN and SOCS3 deletion

status: Public on Oct 28 2011

city: Boston

first: Tao

last: Lu

address: 77 Ave Louis Pasteur

department: Genetics

institute: Harvard Medical School

summary: A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either Phosphatase and tensin homolog (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signaling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around two weeks after the crush injury. Remarkably, we now find that simultaneous deletion of both PTEN and SOCS3 enable robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only result in the induction of many growth-related genes, but also allow RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as a key for sustaining long-distance axon regeneration in adult CNS, a crucial step toward functional recovery.

overall_design: RNAs were extracted from FACS sorted YFP positive mouse retinal cells, and gene-profiled using affymetrix 1.0 ST expression arrays. Three hybridizations were performed for each group (Wild type after crush, PTEN Knockout+crush, SOCS3 Knockout+crush, and PTEN/SOCS3 double knockout+crush) with RNA samples collected from three independent FACS purifications. Data were analyzed using dChIP and SAM.

first: Fang

last: Sun

first: Kevin

middle: K

last: Park

first: Stephane

last: Belin

first: Dongqing

last: Wang

first: Gang

last: Chen

first: Kang

last: Zhang

first: Cecil

last: Yeung

first: Guoping

last: Feng

first: Bruce

last: Yankner

first: Zhigang

last: He


title: GlcNAcylation of histone H2B facilitates its monoubiquitination [Affymetrix data]

status: Public on Oct 27 2011

city: Tokyo

first: Ryoji

last: Fujiki

address: 1-1-1 yayoi, Bunkyo-ku

department: Institute of Molecular and Cellular Biosciences

institute: The university of Tokyo

summary: We have found that histone H2B is GlcNAcylated at residue S112 by O-GlcNAc transferase and that H2B S112 GlcNAcylation fluctuates in response to extracellular glucose level. We have also found that H2B S112 GlcAcylation promotes H2B K120 ubiquitination. To investigate whether these histone modification correlate to transcriptional activation, we performed comprehensive gene expression analysis using Affymetrix GeneChip in HeLa cell cultured with different conditions, i.e. without glucose, with glucose and with FBS.

overall_design: HeLa cells were cultured in DMEM with the following three conditions, 1) DMEM without glucose for 24 hours, 2) DMEM without glucose for 24 hours and followed by treatment with 4.5 g/L glucose for another 24 hours, 3) normal culture condition (DMEM with FBS). Total RNA was purified from these cells and each RNA was linearly amplified and hybridized to Affymetrix GeneChip.

first: Katsuhide

last: Igarashi

first: Shigeaki

last: Kato


title: Expression data from E. coli cells overexpressing either GreA or GreB in ppGpp0 cells in the dksA+ or dksA- background

city: Bethesda

first: Katarzyna

last: Potrykus

state: MD

address: 6 Center Drive, 6B rm 316

department: NICHD

institute: NIH

summary:
Strains devoid of ppGpp (ΔrelA ΔspoT; called ppGpp0), and ppGpp0 dksA- exhibit several amino acid requirements for growth on minimal media. We found that overexpression of DksA can complement some of those requirements. Since DksA is a factor that binds to the RNA polymerase secondary channel, we wondered if other secondary channel proteins might also exert a similar role with respect to growth on minimal media. In our study we found that GreA and partially GreB can in fact complement these requirements under certain conditions. Here, we wished to investigate a broader effect of GreA and GreB on ppGpp0 and ppGpp0 dksA- strains. Since the parent strains are unable to grow in minimal media, we had to supplement the M9 glucose medium with a set of amino acids (DFHILQSTV). We found that both, GreA and GreB can affect a much larger set of genes in the absence of dksA, than in its presence. Also, GreA seems to affect more genes than GreB, under both conditions.
We used microarrays to detail the effects of overproducing either GreA or GreB in cells devoid of ppGpp, in the dksA+ or dksA- background

overall_design: E. coli cells harbouring plasmids carrying either greA (pA = pHM1873) or greB (pB = pHM1874) genes, or vector control (pGB2), were monitored in an effort to elucidate the effects of their protein products. This was done in two backgrounds- either in E. coli ppGpp0 cells (ΔrelA, ΔspoT) carrying wt dksA gene or a dksA deletion.

first: Daniel

last: Vinella

first: Michael

last: Cashel


title: Hypothalamic gene expression profile indicates a reduction in G-protein signaling in the wfs1 mutant mice

city: Perth

first: Sulev

last: Koks

state: Western Australia

address: 90 South Street

department: Centre for Molecular Medicine and Innovative Therapeutics

country: Australia

institute: Murdoch University

summary: WFS1 gene is coding protein with unknown function but its functional deficiency causes different neuropsychiatric and neuroendocrine syndromes. In the present study we aimed to find the functional networks influenced by the Wfs1 deficiency in the hypothalamus. We performed gene expression profiling (Mouse Gene 1.0 ST Arrays) in Wfs1 deficient mice (ko). Modified t-statistics was used for comparison of groups (wt vs ko). Functional annotation of the alterations in RNA levels was performed with Ingenuity Pathway Analysis. 305 genes were differentially expressed with nominal p-value less than 0.01. FDR adjusted p-values were significant (0.007) only for two genes – C4b (t=9.66) and Wfs1 (t=-9.03). However, several genes related to the G-protein signalling were very close to the FDR adjusted significance. For instance, Rgs4 (regulator of G-protein signalling 4) was down-regulated (-0.34, t=-5.4) in Wfs1 deficient mice. Changes in Rgs4 and C4B expression were confirmed by QRT-PCR. In humans, Rgs4 is in the locus for bipolar disease (BPD) and its expression is down-regulated in BPD. C4b is the gene related to the neurodegenerative diseases. In conclusion, hypothalamic gene expression profiling indicates alterations in some functionally relevant molecular pathways explaining the clinical syndrome in the Wolfram syndrome patients.

overall_design: 18 samples, two genotypes (wild type and mutant), in 129S6 genetic background

first: Ursel

last: Soomets

first: Cathy

last: Fernandes

first: Mario

last: Plaas

first: Anton

last: Terasmaa

first: Valo

last: Tillmann

first: Klari

last: Noormets

first: Eero

last: Vasar

first: Leo

last: Schalkwyk


title: Expression data from human corneal endothelial cells

status: Public on Oct 30 2011

city: Setagaya-ku

first: Akihiro

last: Umezawa

department: Center for Regenerative Medicine

institute: National Center for Child Health and Development

summary: Human corneal endothelial cells (HCEC) form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na+- and K+-dependent ATPase (Na+/K+-ATPase). Because HCEC proliferative activity is low in vivo,we tried to activate proliferation of HCEC by inhibiting cyclin-dependent kinase inhibitors.We have here demonstrated microarray data of transduced human corneal endothelial cell lines.

overall_design: Affymetrix human U133 plus 2.0 array was used to transcriptionally profile to compare cultured human corneal endothelial cells and transduced human corneal endothelial cells.

first: T

last: Yokoi

first: Y

last: Seko

first: H

last: Makino

first: S

last: Hatou

first: M

last: Yamada

last: Kiyono

first: A

last: Nishina

first: N

last: Azuma


title: Gene expression changes in human cardiomyocytes exposed to VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate)

status: Public on Oct 29 2011

city: Silver Spring

first: Xiugong

last: Gao

address: 503 Robert Grant Ave

institute: Walter Reed Army Institute of Research

summary:
Organophosphorus compounds induce cardiotoxicity through currently unknown mechanisms, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis.
We used microarrays to study gene expression changes in human cardiomyocytes after exposure to VX, and identified pathways underlying these changes.

overall_design: Human cardiomyocytes were exposed to sublethal concentrations (0, 0.1, 10 μM) of VX. RNA were extracted at different timepoints (0, 6, 24, 72 h) after VX exposure and hybridized to Affymetrix microarrays. Four biological repeats were used for each condition.

first: Hsiuling

last: Lin

first: Radharaman

last: Ray

first: Prabhati


title: Apoptosis regulation by Kaposi’s sarcoma microRNAs

city: Rehovot

first: Jean

last: Hausser

address: Herzl St.

institute: Weizmann Institute of Science

summary: Herpesviruses are known to encode micro (mi)RNAs and to use them to regulate the expression of both viral and cellular genes. The genome of Kaposi’s sarcoma herpesvirus (KSHV) encodes a cluster of twelve miRNAs, which are abundantly expressed during both latency and lytic infection. Relatively few cellular targets of KSHV miRNAs are known. Here, we used a microarray expression profiling approach to analyze the transcriptome of both B lymphocytes and endothelial cells stably expressing KSHV miRNAs and monitor the changes induced by the presence of these miRNAs. We generated a list of potential cellular targets by looking for miRNA seed-match-containing transcripts that were significantly down regulated upon KSHV miRNAs expression. Interestingly, the overlap of putative targets identified in B lymphocytes and endothelial cells was minimal, suggesting a tissue-specific target-regulation by viral miRNAs. Among the putative targets, we identified caspase 3, a critical factor for the control of apoptosis, which we validated using luciferase reporter assays and western blotting. In functional assays we obtained further evidence that KSHV miRNAs indeed protect cells from apoptosis.

overall_design: Single-channel hybridization to Affymetrix oligonucleotides microarrays. DG75 and EA.hy926 cells were transducted in triplicates with the K10/12 and K12/12 lentiviral constructs expressing the KSHV miRNAs, or with a GFP-expressing construct as control. The K10/12 construct expressed only the ten intronic miRNAs miR-K12-1 to 9 and miR-K12-11 while the K12/12 construct also expressed miR-K12-10 and miR-K12-12 in addition.

first: Guillaume

last: Suffert

first: Georg

last: Malterer

first: Liisa

last: Lappalainen

first: Tomi

last: Ivacevic

first: Vladimir

last: Benes

first: Frédéric

last: Gros

first: Olivier

last: Voinnet

first: Mihaela

last: Zavolan

first: Päivi

last: Ojala

first: Juergen

last: Haas

first: Sébastien

last: Pfeffer


title: Role of S100A7 in regulating inflammatory pathways during mammary tumorigenesis

city: Columbus

first: Yadwinder

last: Deol

state: Ohio

address: 344 TMRF Building, 12th ave

institute: The Ohio State University

summary:
Psoriasin (S100A7) has been shown to be highly expressed in invasive estrogen receptor negative breast cancers. Expression of S100A7 in human breast tumors represents a poor prognostic marker and correlates with lymphocyte infiltration in high-grade morphology. Recent studies have shown that S100A7 downregulation in ERα- cells lines inhibits tumor growth in in vivo mouse model systems. However, not much is known about its mechanisms in regulating breast cancers.
We used microarrays to determine the global differential gene expression in S100A7 overexpressing breast cells and vector control cells and found out that most of the genes involved in inflammatory pathways were differentially regulated.

overall_design: S100A7 was sub-cloned into pIRES2-EGFP plasmid which was then transfected into MDA-MB 231 breast cancers cells to select stable cells. Cells transfected with into pIRES2-EGFP only served as vector control. Then microarray analysis was done on these cells to determine the genes which were regulated by S100A7.

first: Mohd

last: Nasser

first: Ramesh

last: Ganju


title: Gene expression in synovial membranes from patients with early and end-stage osteoarthritis

city: Chicago

first: Carla

last: Scanzello

state: IL

address: 1611 W. Harrison St., Ste. 510

department: Rheumatology

institute: Rush University Medical Center

type:
Expression profiling by array
Third-party reanalysis

summary:
Osteoarthritis is characterized by degeneration of cartilage and bone in the synovial joints. Recent findings suggest that inflammation may play a role in osteoarthritis, with synovitis being associated with the clinical symptoms of osteoarthritis. Furthermore, we have found that levels of inflammatory complement components are abnormally high in the synovial fluid of individuals with osteoarthritis.
To determine whether synovial membranes could be a source of complement and other inflammatory molecules in osteoarthritic joints, we characterized the expression of genes in synovial membranes from patients with early-stage or end-stage osteoarthritis.

overall_design:
Samples of synovial membrane were obtained from the suprapatellar pouch of patients with osteoarthritis who were treated at the Hospital for Special Surgery.  Specifically, samples were from 10 patients with early-stage knee osteoarthritis who were undergoing arthroscopic procedures for degenerative meniscal tears (with documented cartilage degeneration but no full-thickness cartilage loss, Kellgren Lawrence score </=2), and from 9 patients with end-stage knee osteoarthritis ( diffuse full thickness cartilage erosion)  who were undergoing total knee joint replacement. Raw data from microarray analysis of healthy synovial membranes, which were run on the same platform and array as our osteoarthritic samples, were downloaded from the NCBI Gene Expression Omnibus (accession number GSE12021) and used for comparison.
The 19 new Samples of this Series were analyzed (RMA) together with 7 previously submitted healthy individual Samples (GSM175810, GSM175812, GSM176290, GSM176291, GSM176292, GSM176268, GSM176269). The complete RMA data are provided as a supplementary file on the Series record.
The GSE12021 reanalyzed data are also provided as a supplementary file on the Series record. GSE32317_12genes.txt includes data from figure 1 of the paper.

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