title: Expression data of human fetal liver hematopoietic stem and progenitors cells [Set 1]

city: Los Angeles, CA

first: Hanna

last: Mikkola

address: 615 Charles E Young Drive South

department: MCDB

institute: UCLA

summary:
Advances in pluripotent stem cell and reprogramming technologies have given hope of generating hematopoietic stem cells (HSC) in culture. To succeed, greater understanding of the self-renewing HSC during human development is required. We discovered that glycophosphatidylinositol-anchored surface protein GPI-80 (Vanin 2) defines a distinct subpopulation of human fetal hematopoietic stem/progenitor cells (HSPC) with self-renewal ability. CD34+CD90+CD38-GPI-80+ HSPC were the sole population that maintained proliferative potential and undifferentiated state in bone marrow stroma co-culture, and engrafted in immunodeficient mice. GPI-80 expression also enabled tracking of HSC migration between human fetal hematopoietic niches. The most highly enriched surface protein in GPI-80+ HSPC as compared to their progeny was Integrin alpha-M (ITGAM), which in leukocytes cooperates with GPI-80 to support migration.  Knockdown of either GPI-80 or ITGAM was sufficient to perturb undifferentiated HSPC in stroma co-culture.  These findings indicate that human fetal HSC utilize common mechanisms with leukocytes for cell-cell interactions governing HSC self-renewal.
We used microarrays to identify genes enriched in the CD90+ hematopoietic stem and progenitor population in fetal liver.

overall_design: RNA was extracted from enriched fetal liver hematopoietic stem and progenitor cells, and downstream progenitors, for comparison based on Affymetrix arrays.

first: Sacha

last: Prashad

first: Catherine

last: Yao

first: Vincenzo

last: Calvanese

first: Joshua

last: Kaiser

first: Raj

last: Sasidharan

first: Mattias

last: Magnusson


title: Expression data of human fetal liver hematopoietic stem and progenitors cells [Set 2]

status: Public on Jan 23 2015

state: CA

country: USA

summary:
Advances in pluripotent stem cell and reprogramming technologies have given hope of generating hematopoietic stem cells (HSC) in culture. To succeed, greater understanding of the self-renewing HSC during human development is required. We discovered that glycophosphatidylinositol-anchored surface protein GPI-80 (Vanin 2) defines a distinct subpopulation of human fetal hematopoietic stem/progenitor cells (HSPC) with self-renewal ability. CD34+CD90+CD38-GPI-80+ HSPC were the sole population that maintained proliferative potential and undifferentiated state in bone marrow stroma co-culture, and engrafted in immunodeficient mice. GPI-80 expression also enabled tracking of HSC migration between human fetal hematopoietic niches. The most highly enriched surface protein in GPI-80+ HSPC as compared to their progeny was Integrin alpha-M (ITGAM), which in leukocytes cooperates with GPI-80 to support migration.  Knockdown of either GPI-80 or ITGAM was sufficient to perturb undifferentiated HSPC in stroma co-culture.  These findings indicate that human fetal HSC utilize common mechanisms with leukocytes for cell-cell interactions governing HSC self-renewal.
We used microarrays to identify genes enriched in the GPI-80+ hematopoietic stem and progenitor population in fetal liver.


title: In vivo investigations of the effect of short- and long-term recombinant growth hormone treatment on DNA-methylation in humans

city: Kiel

first: Susanne

last: Bens

address: Arnold-Heller-Str.3 (Haus 10)

department: Institute of Human Genetics

country: Germany

institute: Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein

type: Methylation profiling by genome tiling array

summary: Treatment with recombinant human growth hormone (rhGH) has been consistently reported to induce transcriptional changes in various human tissues including peripheral blood. For other hormones it has been shown that the induction of such transcriptional effects is conferred or at least accompanied by DNA-methylation changes. To analyse effects of short term rhGH treatment on the DNA-methylome we investigated a total of 24 patients at baseline and after 4-day rhGH stimulation. We performed array-based DNA-methylation profiling of paired peripheral blood mononuclear cell samples followed by targeted validation using bisulfite pyrosequencing. Unsupervised analysis of DNA-methylation in this short-term treated cohort revealed clustering according to individuals rather than treatment. Supervised analysis identified 239 CpGs as significantly differentially methylated between baseline and rhGH-stimulated samples (p<0.0001, unadjusted paired t-test), which nevertheless did not retain significance after adjustment for multiple testing. An individualised evaluation strategy led to the identification of 2350 CpG and 3 CpH sites showing methylation differences of at least 10% in more than 2 of the 24 analysed sample pairs. To investigate the long term effects of rhGH treatment on the DNA-methylome, we analysed peripheral blood cells from an independent cohort of 36 rhGH treated children born small for gestational age (SGA) as compared to 18 untreated controls. Median treatment interval was 33 months. In line with the groupwise comparison in the short-term treated cohort no differentially methylated targets reached the level of significance in the long-term treated cohort. We identified marked intra-individual responses of DNA-methylation to short-term rhGH treatment. These responses seem to be predominately associated with immunologic functions and show considerable inter-individual heterogeneity. The latter is likely the cause for the lack of a rhGH induced homogeneous DNA-methylation signature after short- and long-term treatment, which nevertheless is well in line with generally assumed safety of rhGH treatment.

overall_design: Bisulfite-converted DNA of PBMC from 24 patients before and after 4 days of rhGH treatment were hybridized to the Illumina Infinium HumanMethylation 450k BeadChip.

first: Julia

last: Kolarova

first: Ole

last: Ammerpohl

first: Jana

last: Gutwein

first: Maik

last: Welzel

first: Inka

last: Baus

first: Felix

middle: G

last: Riepe

first: Thomas

last: Eggermann

first: Almuth

last: Caliebe

first: Paul

middle: M

last: Holterhus

first: Reiner

last: Siebert


title: Expression data of human fetal liver hematopoietic stem and progenitors cells

first: Hanna

last: Mikkola

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

overall_design: Refer to individual Series

first: Sacha

last: Prashad


title: Expression profiling of breast cancer samples from Institut Curie (Maire cohort) --Affy CDF

city: PARIS

first: Thierry

last: Dubois

address: 26 rue d’Ulm

department: Recherche Center

country: France

institute: Institut Curie

summary: Transcriptome analysis of 130 breast cancer samples (41 TNBC ; 30 Her2 ; 30 Luminal B and 29 Luminal A), 11 normal breast tissue samples and 14 TNBC cell lines.

overall_design: This dataset contains 178 arrays. 153 arrays were used to analyze 130 unique breast cancer samples from as many patients and 23 technical duplicates. In addition 11 “Normal” samples from healthy breast tissue obtained from mammoplasty are included, as well as a collection of 14 breast cancer cell lines. Data production involved different array batches and hybridation series which were accounted for in the pre-processing of the data.


title: Integrated genomics identifies a new AT/RT-like yet INI1-positive brain tumor subtype among primary pediatric embryonal tumors

status: Public on Jan 22 2015

city: Taipei

first: Tsung-Han

last: Hsieh

address: No.250, Wusing St., Xinyi Dist., Taipei City 112, Taiwan (R.O.C.)

department: Institute of Microbiology and Immunology

country: Taiwan

institute: Taipei Medical University

summary: Pediatric embryonal brain tumor (PEBT), which includes medulloblastoma (MB), primitive neuroectodermal tumor (PNET) and atypical teratoid/rhabdoid tumor (AT/RT), is the second most prevalent pediatric tumor type among brain tumors of childhood. AT/RT is highly malignant and is often misdiagnosed as MB and PNET. Distinguishing AT/RT from PNET/MB is of clinical significance since the survival rate of AT/RT patients is much lower. The diagnosis of AT/RT relies primarily on the morphologic assessment and immunohistochemistry (IHC) staining on a few known markers such as the lack of INI1 protein expression. However, in our clinical practice we observed several AT/RT-like tumors, which fulfilled histopathologic and all other biomarker criteria for AT/RT diagnosis, still showed retained INI1 immunoreactivity. Recent studies also reported retained INI1 immunoreactivity among certain diagnosed AT/RTs. It is therefore necessary to re-evaluate INI1(+), AT/RT-like cases. Sanger sequencing, array CGH and mRNA microarray analyses were performed on PEBT samples for studying their genomics landscapes. AT/RT and INI(+) AT/RT-like patients had similar survival rate, and global array CGH analysis and INI1 gene sequencing showed there is no differential chromosomal aberration marker between INI1(-) AT/RT and INI(+) AT/RT-like cases. We did not misdiagnose MB or PNET as AT/RT-like cases since transcriptome profiling revealed that not only AT/RT and INI(+) AT/RT-like cases expressed distinct mRNA and microRNA profiles, and their gene expression patterns were different from those of MBs and PNETs. AT/RTs shared the closest transcriptome profile to embryonic stem cells, INI1(+) AT/RT-like tumors were more similar to somatic neural stem cell, while MBs were closer to fetal brain. Novel biomarkers were identified to distinguish INI1(-) AT/RTs, INI1(+) AT/RT-like cases and MBs. Our studies disclosed a novel INI1(+) ATRT-like subtype among Taiwanese pediatric cases. New diagnostic biomarkers, as well as new therapeutic tactics, can be developed according to the transcriptome information unveiled in this work.

overall_design: 2 AT/RT-like cases and 7 AT/RT cases are subjected to transcriptome analysis.

first: Hsei-Wei

last: Wang


title: Expression profiling of HCT116 cells transfected with shCTRL or shKSR1

status: Public on Jan 28 2015

city: Omaha

first: Beth

last: Clymer

institute: University of Nebraska Medical Center

summary:
We engineered HCT116 cells by transfecting a non targeting control hairpin or 2 different short hairpin against KSR1 to knockdown KSR1 and microarrays were performed on non-transfected controls, non-targeting shRNA controls, shRNA #1 targeting KSR1, and shRNA #2 targeting KSR1.
We used microarray for molecular profiling of colon cancer cells in presence or in absence of KSR1, an important scaffold of Raf/MEK/ERK pathway and identify genes which are regulated by KSR1

overall_design: Cell lines were measured in as single biological replicates 1. HCT116 untransfected 2 HCT116 + shCTRL 3.HCT116 + shKSR1#1 4. 3.HCT116 + shKSR1#2

first: K

middle: W

last: Fisher


title: Track normalization and averaging of bislufite-seq DNA methylation data across various cell and tissue types

status: Public on Jan 20 2015

city: Bethesda

first: Ian

last: Fingerman

state: MD

address: 45 Center Dr.

department: NCBI Epigenomics

institute: National Institutes of Health

type: Methylation profiling by high throughput sequencing

summary: Data tracks from bisulfite sequencing (BS-seq) experiments were sorted by tissue or cell types and processed using an in-house algorithm that provides normalization functionality followed by generation of a track average.

overall_design: Re-analysis of Roadmap Epigenomics DNA methylation datasets using an in-house algorithm to create an average data track.


title: Genetic Variation, Not Cell Type of Origin, Underlies Regulatory Differences in iPSCs

status: Public on Jan 19 2015

city: Chicago

first: Nicholas

middle: E

last: Banovich

state: IL

address: 920 E. 58th Street, CLSC 317

department: Human Genetics

institute: University of Chicago


title: Track normalization and averaging of epigenetic features across various cell and tissue types derived from Roadmap Epigenomic datasets

type: Genome binding/occupancy profiling by high throughput sequencing


title: Gene expression profiles of patients with multiple myeloma who have been treated previously

city: Little Rock

first: Christoph

middle: J

last: Heuck

state: AR

address: 4301 W Markham

department: Myeloma Institute for Research and Therapy

institute: University of Arkansas for Medical Sciences

summary: This Series represents the gene expression profiles of patients with multiple myeloma who have been treated previously. In brief, Total Therapy 6 (TT6) is an open label phase 2 protocol for patients with symptomatic multiple myeloma, who had been treated with more than one cycle of prior therapy excluding autologous hematopoietic stem cell transplant. This protocol was approved by the institutional review board on March 25, 2009 (IRB#108053). The TT6 treatment regimen consists of induction therapy  with Melphalan/Bortezomib/Thalidomide/Dexamethasone/Cisplatin/Doxorubicin/Cyclophosphamide/Etoposide (M-VTD-PACE) followed by a  high dose M-VTD-PACE based tandem transplant. Maintenance therapy consists of Bortezomib/Lenalidomide/Dexamethasone alternating with Borteomib/Melphalan/Dexamethasone every months for 3 years.

overall_design: We analyzed CD138+ selected cells of previously treated MM patients by microarray.


title: PW1/Peg3 expression regulates the key properties that determine mesoangioblast stem cell competence

city: Milan

first: Giulio

last: Pavesi

address: Via Celoria 26

department: Biosciences

country: Italy

institute: Università di Milano

summary: Mesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of the developmental stage at which they are isolated. Here we show that PW1/Peg3 is expressed at high levels in mesoangioblasts obtained from mouse, dog and human tissues and its level of expression correlates with their myogenic competence. Silencing PW1/Peg3 markedly inhibits myogenic potential of mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/Peg3 abrogates mesoangioblast ability to cross the vessel wall and to engraft into damaged myofibers through the modulation of the junctional adhesion molecule-A. We conclude that PW1/Peg3 function is essential for conferring proper mesoangioblast competence and that the determination of PW1/Peg3 levels in human mesoangioblasts may serve as a biomarker to identify the best donor populations for therapeutic application in muscular dystrophies.

overall_design: Ctrl Mesoangioblasts (MABs) transduced with a Lentiviral vector shControl (2 replicates, Ctrl_1 and Ctrl_2) and shPW1 Mesoangioblasts transduced with a Lentiviral vector shPW1 (2 replicates, PW1-siRna_1 and PW1-siRna_2)

first: Chiara

last: Bonfanti

first: Graziella

last: Messina


title: Genetic Variation, Not Cell Type of Origin, Underlies Regulatory Differences in iPSCs [Methylation]

summary: Analysis of contribution of cell type of origin and individual to gene expression differences in iPSCs. The hypothesis tested in the present study was that cell type of origin affects iPSC gene expression. Results show that individual has a much stronger effect than cell type of origin on differences between iPSCs derived from multiple individuals.

overall_design: DNA obtained from feeder-free iPSCs derived from multiple individuals and tissues and their corresponding cell type of origin

first: Courtney

middle: L

last: Kagan

first: Bryan

last: Pavlovic

first: Kristen

last: Patterson

first: Irene

last: Gallego Romero

first: Jonathan

middle: K

last: Pritchard


title: YM155 treated KYSE410

status: Public on Jan 16 2015

city: Beijing

first: Yang

last: Xu

address: No.17 Panjiayuan Nanli, Chaoyang district

country: China

institute: Cancer Hospital

summary: We used microarrays to detail the gene expression profiles of KYSE410 cell line to identify distinct up and down-regulated genes during treatment with cisplatin.

overall_design: KYSE410 cell line were treated with 20 nM YM155 for 6 hrs and selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to gene expression profiles of KYSE 410 cell line treated with cisplatin.


title: Lymph node CD4+ T cell expression data from naïve female offspring of C57BL/6J and C57BL/6J-ChrY^SJL

city: Burlington

first: Laure

last: Case

address: 89 Beaumont Ave

institute: University of Vermont

summary: The prevalence of some autoimmune diseases (AID) is greater in females compared with males, notwithstanding that disease severity is often greater in males. The reason for this sexual dimorphism (SD) is unknown, but may reflect negative selection of Y chromosome (ChrY) bearing sperm during spermatogenesis or male fetuses early in the course of conception/pregnancy. Previously, we showed that the SD in experimental autoimmune encephalomyelitis (EAE) is associated with copy number variation (CNV) in ChrY multicopy genes. Here, we test the hypothesis that CNV in ChrY multicopy genes influences the paternal parent-of-origin effect on EAE susceptibility in female mice.  We show that C57BL/6J consomic strains of mice possessing an identical ChrX and CNV in ChrY multicopy genes exhibit a female biased sex-ratio and sperm head abnormalities, consistent with X-Y intragenomic conflict arising from an imbalance in CNV between homologous ChrX:ChrY multicopy genes. These males also display paternal transmission of EAE to female offspring and differential loading of miRNAs within the sperm nucleus. These findings provide evidence for a genetic mechanism at the level of the male gamete that contributes to the SD in EAE and paternal parent-of-origin effects in female mice, raising the possibility that a similar mechanism may contribute to the SD in MS.

overall_design: Three biological replicates for each strain were pooled from the axillary, brachial, and inguinal lymph nodes from 5 mice for each replicate. RNA was isolated from CD4+TCRB+ FAC sorted cells.

first: Emma

middle: H

last: Wall

first: Erin

last: Osmanski

first: Julie

middle: A

last: Dragon

first: Naresha

last: Saligrama

first: James

middle: F

last: Zachary

first: Bernardo

last: Lemos

first: Elizabeth

middle: P

last: Blankenhorn

first: Cory

last: Teuscher


title: Copy number variation in Y chromosome multicopy genes is linked to a paternal parent-of-origin effect on CNS autoimmune disease in female offspring

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

platform_organism:
Mus musculus
synthetic construct


title: Effect of Drosophila immune proteins on gene expression in E. coli

status: Public on Jan 13 2015

city: Aomori

first: Yuji

last: Nakai

state: Aomori

address: 2-1-1, Yanagawa

department: Institute of Regional Innovation

country: Japan

institute: Hirosaki University

summary: Interaction between the host and invading pathogen determines the fate of both organisms during the infectious state.  The host is equipped with a battery of immune reactions, while the pathogen displays a variety of mechanisms to compromise host immunity.  Although bacteria alter their pattern of gene expression when they enter host organisms, studies to elucidate the mechanism behind this are only in their infancy.  In the present study, we examined the possibility that host immune proteins directly participate in the change of gene expression in bacteria.  To this end, Escherichia coli was treated with a mixture of the extracellular region of membrane-bound peptidoglycan recognition protein LC (PGRP-LC) and the antimicrobial peptide attacin of Drosophila, and subsequently subjected to DNA microarray analysis for the repertoire of mRNA.  We identified nearly 200 genes whose mRNA increased after the treatment, and at least four of them were induced in response to PGRP-LC.  One such gene, lipoprotein-encoding nlpI, showed a transient increase of its mRNA level in adult flies depending on PGRP-LC, and NlpI-lacking E. coli had a smaller pathogenic effect with lowered growth/viability than the parental strain in adult flies.  These results suggest that a host immune receptor triggers a change of gene expression in bacteria simultaneously to their recognition of the invader and induction of immune responses.

overall_design: The E. coli strain BW25113 (2 x 10^9) suspended with insect saline (0.13 M NaCl, 4.7 mM KCl, 1.9 mM CaCl2), was incubated with a mixture of GST-attacin (0.125 μM), GST-PGRP-LCa (0.5 μM), GST-PGRP-LCx (1 μM), and GST-PGRP-LCy (0.5 μM) for 10 min at room temperature.  As a negative control, incubation of E. coli was done in the presence of GST alone (3 μM).

first: Qingquan

last: Kong

first: Nanae

last: Kuroda

first: Akiko

last: Shiratsuchi

first: Kaz

last: Nagaosa

first: Yoshinobu

last: Nakanishi


title: NSCLC Driven by DDR2 Mutation is Sensitive to JQ1 and Dasatinib Combination Therapy

status: Public on Jan 14 2015

city: Boston

first: Chunxiao

state: MA

address: 450 Brookline Ave

department: Medical Oncology

institute: Dana Farber Cancer Institute

summary:
Genetically engineered mouse models of lung cancer have demonstrated an important role in understanding the function of novel lung cancer oncogenes and tumor suppressor genes identified in genomic studies of human lung cancer. Further, these models are important platforms for pre-clinical therapeutic studies. Here, we generated a mouse model of lung adenocarcinoma driven by mutation of the Discoidin Domain Receptor 2 (DDR2) gene combined with loss of TP53. DDR2L63V;TP53L/L mice developed poorly differentiated lung adenocarcinomas in all transgenic animals analyzed with a latency of 40-50 weeks and a median survival of 67.5 weeks. Mice expressing wild-type DDR2 with combined TP53 loss did not form lung cancers. DDR2L63V; TP53L/L tumors displayed robust expression of DDR2 and immunohistochemical markers of lung adenocarcinoma comparable to previously generated models of lung adenocarcinoma though also displayed concomitant expression of the squamous cell markers p63 and SOX2. Tumor-derived cell lines were not solely DDR2 dependent and displayed up-regulation of and partial dependence on MYCN. Combined treatment with the BET inhibitor JQ1 and the mutltitargeted DDR2 inhibitor dasatinib inhibited tumor growth in vitro and in vivo. Together, these results suggest that DDR2 mutation can drive lung cancer initiation in vivo and provide a novel mouse model for lung cancer therapeutics studies.
We used microarrays to detail the gene expression profile of mouse primary lung tumor cell lines driven by DDR2L63V;p53L/L and KrasG12D;p53L/L.

overall_design: When DDR2L63V; p53 and KrasG12D;p53L/L mice developed lung tumors confirmed by MRI, the mice were sacrificed and lung tumor nodules were harvested, finely minced, and cultured in 100 mm dishes with RPMI 1640/10% FBS/1% pen-strep/2mM L-Glutamine. After 3 passages, frozen stocks of these short-term cultures were prepared, and further characterized by genotyping. DDR2 expression was induced by treating cells with 2 ug/ml DOX every 2 to 3 days and confirmed by western blot analysis. The cells were cultured in RPMI 1640/10% FBS/1% pen-strep/2mM L-Glutamine. All cells were cultured at 37oC in a humidified incubator with 5% CO2.

first: Peter

middle: S

last: Hammerman

first: Kwok-Kin

last: Wong


title: Molecular regulation of acute kidney injury (mRNA)

status: Public on Jan 15 2015

city: Vienna

first: Julia

last: Wilflingseder

address: Währinger Gürtel 18-20

department: Nephrology and Dialysis

country: Austria

institute: Medical University of Vienna

summary: 18 zero-hour and 18 selected post-transplant (Tx) biopsy samples from 18 kidney allografts  (8 acute kidney injury (AKI), 10 PBx - protocol biopsies - controls) were analyzed by using the Affymetrix GeneChip® Human Gene 2.0 ST Array.

overall_design: comparison between control group (protocol biopsies) and indication biopsies with histological lesions of acute tubular necrosis without rejection (ATN)

first: Rainer

last: Oberbauer


title: Wnt ligands from the embryonic surface ectoderm regulate bimetallic strip optic cup morphogenesis in the mouse

city: Cincinnati

first: Richard

last: Lang

state: Oh

address: 3333 Burnet Ave, 2447 TCHRF

department: Ophthalmology Research

institute: Cincinnati Children's Medical Center

summary:
Wnt signaling in early eye development, specifically the lens placode shows expression of 12 out of 19 Wnt ligands.  We these Wnt activities were suppressed using conditional deletion of Wntless, dramatic phenotypic changes in morphogensis occurred.
Microarray analysis of the genes that were changed in response to deletion of Wnt ligands in the developing eye region show direct or indirect responses from the surface ectoderm to the developing RPE and optic cup curvature, creating an overal shape change phenotype in the bilayerd epithelium of the optic cup.

overall_design: Mouse embryos at embryonic stage e10.5 were disected into pbs and eye regions were disected and removed for RNA extraction and hybridization to Affymetrix microarrays.  We sought to identify the genes that were changed in response to deletion of Wls from the developing surface ectoderm of the eye region.  Genes changed could be the direct or indirect result from deleltion of Wls from the surface ectoderm using the LeCre recombinase gene as a tool for analysis.

first: April

last: Smith


status: Public on Jan 12 2015

city: London

first: Reiner

last: Schulz

address: 8th floor Guy's Tower

department: Medical & Molecular Genetics

country: United Kingdom

institute: King's College London

summary: Genomewide methylation analysis in Silver Russell syndrome patients compared to healthy controls

overall_design: Bisulphite converted DNA from the 24 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: Adam

middle: R

last: Prickett

first: Miho

last: Ishida

first: Sabrina

middle: V

last: Böhm

first: Jennifer

last: Frost

first: William

last: Puszyk

first: Sayeda

last: Abu-Amero

first: Phillip

last: Stanier

first: Gudrun

last: Moore

first: Rebecca

last: Oakey


title: Molecular regulation of acute kidney injury

platform_organism:
Homo sapiens
synthetic construct


title: ARSD expression correlates with IgVH mutational status, ZAP-70 and disease progression in chronic lymphocytic leukemia

city: Padova

first: Barbara

last: Di Camillo

address: via Gradenigo 6B

department: Information Engineering Department

institute: University of Padova

summary: Several studies demonstrated IgVH mutation status and ZAP-70 expression as the most relevant prognostic markers in CLL, suggesting the separation of two patient subgroups: with good (MTZAP-70-) and poor prognosis (UMZAP-70+).  We determined gene expression of B cells in 112 CLL patients divided into three classes: the first with IgVHMT and ZAP-70-, the second with IgVHUM and ZAP-70+, and the third included both IgVHUM ZAP-70- and IgVHMT ZAP-70+. We found LPL, AGPAT2, MBOAT1, CHPT1, AGPAT4, PLD1 genes encoding enzymes involved in lipid (glycerolipid/glycerophospholipid) metabolism overexpressed in UMZAP-70+.   In addition, this study demonstrates the role of ARSD, a gene belonging to the sphingolipid metabolism, as a new gene significantly overexpressed in UMZAP-70+ in respect to MTZAP-70-.   ARSD protein was found at significantly higher concentrations in UMZAP-70+ compared to MTZAP-70- CLL B cells and B cells from healthy individuals by Western blotting. Statistical analysis identified a strong correlation between ARSD and IgVH mutation status; ARSD protein level was associated with the requirement of therapy for CLL patients and for this purpose it is as good as IgVH mutational status.  Our study highlights ARSD as a promising new prognostic factor in CLL and sphingolipid metabolism as a putative new biological mechanism in CLL.

overall_design: In this study we performed gene expression profiling of B cells on 112 CLL patients divided into three classes based on IgVH mutational status and ZAP-70 protein expression: class one with mutated IgVH and ZAP-70-, class two with unmutated IgVH and ZAP-70+, and class three included CLL patients with unmutated IgVH and ZAP-70-, or mutated IgVH and ZAP-70+, respectively. The decision to divide CLL patients in three categories was due to the clinical feature and the molecular heterogeneity of CLL, in order to elaborate different molecular signature capable of reveal biological mechanisms, and to identify new potential molecular predictors for prognostic assessment or genetic risk. RNA was extracted and quantified for high-density oligonucleotide microarrays Human Genome U133 Plus 2.0 GeneChip (Affymetrix, Santa Clara, CA).  A first cohort of 62 subjects was analyzed using GeneChip Expression 3' Amplification One-Cycle Target Labeling Kit, while a second cohort of 50 subjects using GeneChip 3'IVT Express Kit, according to manufacturer’s protocol (Affymetrix), respectively.

first: Alessandra

last: Trojani

last: Tedeschi

first: Milena

last: Lodola

first: Simona

last: Montesano

first: Francesca

last: Ricci

first: Eleonora

last: Vismara

first: Antonino

last: Greco

first: Silvio

last: Veronese

first: Anna

last: Colosimo

last: Scarpati

first: Aldo

last: Orlacchio

first: Sabata

last: Martino

first: Chiara

last: Colombo

first: Mariangela

last: Mura

first: Michele

last: Nichelatti

first: Marco

last: Montillo

first: Enrica

last: Morra


title: Gene array analysis of anaplastic thyroid carcinoma tissue versus matched and unmatched normal thyroid tissue

city: Jacksonville

first: John

last: Copland

state: Florida

address: 4500 San Pablo Rd

department: Cancer Research

institute: The Mayo Clinic, Jacksonville FL

summary: Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with anaplastic thyroid carcinoma (ATC), a very rare and lethal variant of thyroid cancer. ATC is resistant to chemotherapy, radiation, and targeted therapies currently available. In an effort to identify novel tumor-specific therapeutic targets, we performed high throughput gene array analysis screening numerous patient ATC tumor tissues, and compared their gene expression levels to matched and unmatched normal thyroid tissue samples.

overall_design: RNA was extracted from flash frozen patient tumor and normal samples. Gene array analysis was performed, and resulting expression levels were compared between normal and tumor samples.

first: Christina

last: von Roemeling

first: Han

last: Tun


title: Expression profile for BW25113 ΔmqsRA with deoxycholate stress

status: Public on Jan 09 2015

city: State College

first: Thomas

middle: K.

last: Wood

state: PA

address: Room 161 Fenske Laboratory, University Park

department: Chemical Engineering & Biochemistry and Molecular Biology

institute: Pennsylvania State University

summary:
MqsR/MqsA is a well-characterized toxin/antitoxin system with several regulatory roles.
Deletion of mqsRA reduced growth with deoxycholate stress.  Here we performed a microarray to determine the expression profile with and without mqsRA under deoxycholate stress to determine transcriptional regulation.

overall_design: Escherichia coli K-12 BW25113 with and without mqsRA was exposed to deoxycholate stress.

first: Kwan

last: Brian

first: Wood

last: Thomas


title: Expression Data from Gastrointestinal Stromal Tumor (GIST) Cell Lines

status: Public on Jan 08 2015

city: Cambridge

first: Fang

last: Li

address: 250 Massachusetts Avenue

institute: Novartis Institutes for BioMedical Research, Inc.

summary:
Activating mutations in either KIT or PDGFRA are present in approximately 90% of gastrointestinal stromal tumors (GISTs).  Although treatment with the KIT and PDGFR inhibitor imatinib can control advanced disease in about 80% of GIST patients, the beneficial effect is not durable.  Here, we report that ligands from the FGF family reduced the effectiveness of imatinib in GIST cells, and FGF2 and FGFR1 are highly expressed in all primary GIST samples examined.  The combination of KIT and FGFR inhibition showed increased growth inhibition in imatinib-sensitive GIST cell lines in the presence or absence of added FGF2 in vitro, and delayed tumor regrowth in vivo.  In addition, inhibition of mitogen-activated protein kinase (MAPK) signaling by imatinib was not sustained in GIST cells.  An extracellular signal-regulated kinase (ERK) rebound occurred through activation of FGF signaling, and was repressed by FGFR1 inhibition.  Downregultation of Sprouty proteins played a role in the imatinib-induced feedback activation of FGF signaling in GIST cells.
We used micorarrays to quantify the gene expression levels in GIST cell lines.

overall_design: Four GIST cell lines were split and cultured overnight.  Cells were harvested for RNA extraction and hybridization on Affymetrix U133plus2 microarrays.


title: Expression profiling of breast cancer samples from Institut Curie (Maire cohort)

city: PARIS

first: Thierry

last: Dubois

address: 26 rue d’Ulm

institute: Institut Curie

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

overall_design: Refer to individual Series


title: Expression comparison of mutant EGFR-driven gliomas with relapse tumors upon mutant EGFR ablation

city: Houston

first: Haoqiang

last: Ying

state: Texas

address: 1515 Holcombe Blvd

institute: M. D. Anderson Cancer Center

summary:
To determine the roles of oncogenic EGFR signaling in gliomagenesis and tumor maintenance, we generated a novel glioma mouse model driven by inducible expression of a mutant EGFR (EGFR*). Genetic suppression of EGFR* induction led to significant tumor regression and prolonged survival. But in spite of the initial response, the tumors relapsed invariably and propagated independent of EGFR*.
We used microarrys to directly compare geen expression of control and relapse tumors and identified gene sets specifically activated in relapse tumors.

overall_design: Control and relasped glioma samples upon mutant EGFR extinction were selected for RNA extraction and hybridization on Affymetrix microarrays.

first: Stefan

last: Klingler

first: Baofeng

last: Guo

first: Jun

last: Yao

first: Haiyan

last: Yan

first: Ling

last: Zhang

first: Angelina

last: Vaseva

first: Sida

last: Chen

first: Peter

last: Canoll

first: James

last: Horner

first: Y

last: Wang

first: Ji-hye

last: Paik

first: Hongwu

last: Zheng


title: Hdac3 is essential for DNA replication and differentiation of hematopoietic stem and progenitor cells

city: Nashville

first: Pengcheng

last: Lu

state: TN

address: 2200 Pierce Avenue

institute: Vanderbilt University

summary:
Background:  To define changes in gene expression from stem cells and early progenitor cells lacking histone deacetylase 3 (Hdac3), we purified bone marrow Lineage Negative, Sca1/cKit positive and Flt3 negative cells from wild type and Vav-Cre/Hdac3Flox/- mice.  These lineage-specific knock out mice lack Hdac3 throughout the hematopoietic system.  To ensure that only cells lacking Hdac3 were measured, we used a Lox-STOP-Lox-ROSA26-GFP transgene such that any cell containing active Cre also expresses GFP.

Methods:  Bone marrow cells were harvested from 10-30 mice and the lineage negative fraction was separated using the Lineage Cell Depletion Kit and MACS columns (Miltenyi Biotec). The lineage negative fraction was then stained with antibodies for flow cytometry and the GFP positive fraction of the LSK/Flt3 cells were sorted on a Becton Dickinson FACSAria. Total RNA was isolated from the sorted bone marrow cells using a PerfectPure RNA extraction kit (5 Prime).  LSK/Flt3- cells pooled from 2 groups of 5 null mice were compared to LSK/Flt3- or LSK/Flt3+ cells pooled from 30 wild type mice. The expression of individual genes was verified using reverse transcriptase (RT) PCR.

Conclusion: Hematopoietic stem and early progenitor cells fail to express gene that are typically turned on early during lymphoid development.

overall_design: Gene expression array analysis of pooled cell samples that were sorted by flow cytometry from 5-30 mice

first: Scott

last: Hiebert

first: Xi


title: LLGL1 depletion effect on pancreatic ductal adenocarcinoma cell line CAPAN2

status: Public on Jan 06 2015

city: Hong Kong

first: Chi Han Samson

last: Li

address: Shatin

department: School of Biomedical Sciences

country: Hong Kong

institute: The Chinese University of Hong Kong

summary: Identification of gene regulated by LLGL1 in pancreatic ductal adenocarcinoma cell line CAPAN2

overall_design: CAPAN2 cells were transduced by lentivirus carrying either shRNAs targeting human LLGL1 or control shRNAs

first: Yangchao


title: Genomic landscape of Epstein-Barr virus nuclear antigen 3A

first: Hufeng

last: Zhou

address: 181 Longwood Ave,

department: Department of Microbiology and Molecular Genetics

institute: Harvard Medical School

summary: We undertook ChIP-Seq of HA-tagged EBNA3A in Lymphoblastoid Cell Lines to understand the effects of this essential viral transcription factor on the cell DNA. We discovered that EBNA3A bound to DNA with BATF, IRF4 and RUNX3, making these Transcription Factors the ones that tether EBNA3A to DNA, allowing it to mediate its downstream effects.

overall_design: ChIP-Seq of 2 biological replicates of HA-tagged EBNA3A were performed. Input was obtained by reverse-crosslinking the cross-linked DNA

first: Stefanie

middle: C

last: Schmidt

first: Sizun

last: Jiang

first: Bradford

last: Willox

first: Amy

last: Holthaus

first: Eric

last: Johannsen

last: Kharchenko

first: Bo

last: Zhao

first: Elliott

last: Kieff


title: A687V EZH2 is a driver of histone H3 lysine 27 (H3K27) hyper-trimethylation

status: Public on Jan 07 2015

first: Matteo

last: Righi

state: London

address: The MediaWorks, 191 Wood Ln

institute: Autolus Therapeutics

summary: Gene expression changes were analyzed in 2 acute lymphoblastic leukemia cell lines treated with the GSK126 EZH2 inhibitor using  Affymetrix Human Genome U133 Plus 2.0 arrays.

overall_design: Two ALL cell lines (SUP-B8, NALM-6) were treated with DMSO (control) or GSK126 at 0.5 uM for 72 hours. Two biological replicates are included for each treatment group.

first: Heidi

last: Ott

first: Yuchen

last: Bai

first: Caretha

last: Creasy

first: Michael

last: McCabe


title: Geminin regulates self-renewal and fate commitment decisions in fetal hematopoietic stem cells.

city: Patras

first: Stavros

last: Taraviras

state: Achaia

address: Asklipiou 1

department: School of Medicine

country: Greece

institute: University of Patras

summary:
Conditional deletion of Geminin from the entire hematopoietic compartment using Vav1:iCre mice led to defective hematopoiesis/dyserythropoiesis in E15.5 mouse embryos.
The present data set includes data from lineage-negative cells isolated from homogenized livers that were dissected from E15.5.dpc embryos. The two conditions compared were  wild-type versus Geminin-KO Lin- cells. The cells were collected from littermates.

overall_design: Six samples were analyzed: three samples from each wild-type and Geminin-KO Lin- cells. For our analyses, we set cutoff values FC>1.5 and p-value <0.05. The analysis was carried out using the genotype criterion, but non-averaged for the three biological replicates.


title: Gene expression data from bone marrow CD34+ cells of patients with myelodysplastic syndromes (MDS) and healthy controls

city: Oxford

first: Andrea

last: Pellagatti

address: John Radcliffe Hospital

department: NDCLS, RDM

institute: University of Oxford

summary: We aimed to determine the impact of the common mutations on the transcriptome in myelodysplastic syndromes (MDS). We linked genomic data with gene expression microarray data and we deconvoluted the expression of genes into contributions stemming from each genetic and cytogenetic alteration, providing insights into how driver mutations interfere with the transcriptomic state. We modelled the influence of mutations and expression changes on diagnostic clinical variables as well as survival.

overall_design: 159 patients with MDS patients and 17 healthy controls were included in the study. CD34+ cells were isolated from bone marrow samples obtained from MDS patients and healthy controls. Samples were hybridized to Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays


title: Expression data from colonic mucosal biopsies from healthy controls and patients with active ulcerative colitis

status: Public on Jan 21 2015

city: Dublin 4

first: Aine

last: Balfe

address: Belfield

department: School of Medicine and Medical Science

country: Ireland

institute: University College Dublin

summary: Expression data was used to evaluate changes to the transcriptional signatures across the healthy and inflamed colon. A comparison between healthy controls and active ulcerative colitis signatures was also made.

overall_design: Mucosal biopsy specimens were harvested at four anatomical locations within the colon from healthy volunteers and patients with active ulcerative colitis. specimens were fixed in RNA later for 24 hours at room temperature and stored at -80°C for a further 24 hours prior to RNA extraction and microarray analysis.

first: Grainne

last: Lennon

first: Ronan

last: O'Connell


title: Circadian Enhancers Coordinate Multiple Phases of Rhythmic Gene Transcription In Vivo

city: RTP

first: Logan

last: Everett

state: North Carolina

address: 109 T.W. Alexander Dr

department: Office of Research and Development

institute: U.S. Environmental Protection Agency

summary:
Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock.  We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver.  Unbiased examination of eRNAs that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs).  We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression.  Integrated genomic analyses also revealed novel mechanisms by which a single circadian factor controls opposing transcriptional phases.  These findings shed new light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ.
The goal of this experiment was to determine direct targets of Rev-erb{alpha} in mouse liver. All samples were collected at ZT10, when Rev-erb{alpha} protein levels and genomic binding are maximal.

overall_design: All mice were housed and harvested together (n=5 per genotype). All mice were male, 10-12 week old on C57Bl/6 background. RNA was extracted, processed, and hybridized from each mouse liver individually (each sample represents a single mouse).

first: Bin

last: Fang

first: Jennifer

last: Jager

first: Erika

last: Briggs

first: Sean

last: Armour

first: Dan

last: Feng

first: Ankur

last: Roy

first: Zachary

last: Gerhart-Hines

first: Zheng

last: Sun

first: Mitchell

last: Lazar


title: Differential gene expression in Lrig1null duodenal tumors compared to normal duodenum

status: Public on Jan 04 2015

first: Robert

last: Coffey

address: 2213 Garland Ave

department: Medicine/GI

institute: Vanderbilt University Medical Center

summary:
Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) is a pan-ErbB negative regulator and intestinal stem cell marker downregulated in many malignancies. Over 91% Lrig1-CreERT2/CreERT2 (Lrig1-/-) mice developed duodenal adenomas, providing the first in vivo evidence Lrig1 acts as a tumor suppressor. We thus characterize the differential expressing transcripts in these duodenal adenomas to explore the pathegenesis. Elevated expression of the Egfr ligands was detected in adenomas compared to adjacent normal tissue. These adenomas also expressed the gastric-specific genes Gastrokine1 and Mucin5ac, indicating gastric metaplasia.
In this dataset, we include the expression data obtained from proximal adenomas as well as adjacent normal tissue and wildtype proximal duodenum. These data are used to obtain 679 upregulated and 874 downregulated transcripts in tumors.

overall_design: Total RNA from matched duodenal tumors or adjacent normal or wildtype duodenum was isolated with Rneasy (with Dnase digestion)  and used to probe the Affymetrix Mouse Gene 1.0 ST chip; the probe was prepared with Ambion Expression Target preparation Kit P/N 4411974.

first: Yang

last: Wang


title: Expression data from SDH-disabled GIST

status: Public on Jan 02 2015

city: Bethesda

first: Yuelin

middle: Jack

last: Zhu

address: 9000 Rockville Pike

department: Genetics Branch, Center for Cancer Research

institute: NCI

summary: Pediatric GIST commonly harbors a disabled succinate dehydrogenase complex (SDH), which yields tumors with highly conserved genomes but characteristic epigenomic signatures. Mysteriously, nearly half of such SDH-deficient GIST, including tumors from Carney Triad patients, lack identifiable mutations in SDH component genes and genes required for complex assembly (SDHA, SDHB, SDHC, SDHD, SDHAF, termed SDHx). Genomic sequencing coupled with DNA methylation and transcriptional profiling have exposed SDHC promoter-specific CpG island epimutation and concomitant gene silencing in the majority of SDHx-WT GIST.

overall_design: We performed whole genome expression profiling on 20 FFPE dSDH GIST tumors using Affymetrix U133P2 arrays which contain >54K gene target probesets. Included here were data from 7 SDHx-w.t. and 13 SDHx mutants that passed array QC.

first: Killian

last: Keith

first: Meltzer

last: Paul

first: Helmen

last: Lee


title: Field of Cancerization in Peripheral Airway Epithelium

city: new york

first: Jun-Chieh

middle: James

last: Tsay

state: NY

address: 562 First Ave. NBV 7N27

department: Medicine

institute: NYU Langone Medical Center

type:
Expression profiling by array
Expression profiling by RT-PCR


title: Intestinal epithelial gene expression - TRE-MSI2

status: Public on Jan 05 2015

city: Philadelphia

first: Christopher

last: Lengner

address: 3800 Spruce Street, Room 390EA

department: Biomedical Sciences

institute: University of Pennsylvania

summary: Comparison of gene expression in intestinal epithelial cells in the presence or absence of ectopic induction of MSI2 in vivo

overall_design: Total RNA was isolated from preparations of total intestinal epithelial cells taken from the jejunum from 3 control (R26-M2rtTA +doxycycline for 24 hrs) and 3 experimental (TRE-MSI2::R26-M2rtTA +doxycycline for 24 hrs) and subjected to profiling on affymetrix Gene 1.0ST arrays

first: Zhengquan

last: Yu

first: Chris


title: Expression data from C4-2 prostate cancer cells treated with taxanes

status: Public on Jan 01 2015

first: Karen

last: Knudsen

state: Pennsylvania

institute: Thomas Jefferson University - Kimmel Cancer Center

summary:
Comparison of the new generation taxane cabazitaxel with docetaxel in prostate cancer cells
Cabazitaxel impacts distint molecular pathways as compared to docetaxel, which could underlie its efficacy after docetaxel treatment has failed in castration resistant prostate cancer patients

overall_design: 12 samples were analysed. A genome-wide expression array was performed on a GeneChip Human Gene 2.0ST Array (Affymetrix, 902112) with C4-2 cells, treated for 16h with 1nM cabazitaxel, docetaxel or vehicle (EtOH), in duplicates. The expression data were RMA normalized, and filtered to remove low-expressing genes. Differential gene expression with corresponding p-values (student’s ttest) was determined of drug-treated over control.


title: LNCaP and C4-2 prostate cancer cells treated with taxanes


title: Field of Cancerization in Peripheral Airway Epithelium: Gene Expresssion

summary:
Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer.
This  study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients.

overall_design: We collected peripheral airway brushings from the contral-lateral lung of the tumor from cancer patients (n=17) and smoker controls (n=13); Total RNA were obtained from the peripheral airway epithelium.

first: William

middle: N

last: Rom


title: Decreased expression of cell proliferation-related genes in clonally derived skin fibroblasts from children with Silver-Russell syndrome is independent of the degree of 11p15 ICR1 hypomethylation

city: Heidelberg

first: Doreen

last: Heckmann

institute: DKFZ

summary:
The in-vitro analysis of the hypomethylation of the imprinting control region 1 (ICR1) within the IGF2/H19 locus is challenged by the mosaic distribution of the epimutation in tissues from children with Silver-Russell syndrome (SRS).
For excluding mosaicism, clonal cultures of skin fibroblasts from four children with SRS and three controls were analyzed. Cell proliferation, IGF-II secretion, and expression of IGF2 and H19 were measured. Microarray expression analysis was performed.
Single cell expansion established severely ICR1 hypomethylated clones (SRShypo) and normomethylated clones (SRSnormo) from patients and controls (Cnormo). IGF2 expression was below the detection limit of the qRT-PCR assay, while H19 expression was detectable, without differences between fibroblast clones. Cell count-related IGF-II release was comparable in supernatants of SRShypo and Cnormo. Cell proliferation was diminished in SRShypo compared to Cnormo (p=.035). Microarray analysis revealed gene expression changes in SRS clones predicting a decrease of cell proliferation and a delay of mitosis.
The analysis of severely ICR1 hypomethylated clonal fibroblasts did not reveal any functional differences towards the normomethylated clones with respect to IGF2 and H19 expression. Furthermore, a clear difference to the clones from healthy individuals was not detected except from a lower proliferation rate arisen from impaired cell cycle progression.

overall_design: 16 samples: 8 SRShypo, 4 SRSnormo, 4 Cnormo

first: Gerhard

last: Binder


title: Changes in Gene Expression Profile in two Multidrug Resistant Cell Lines derived from a same Drug Sensitive Cell line

city: Rio de Janeiro

first: Miguel

middle: Angelo Martins

last: Moreira

state: Riio de Janeiro

address: André Cavalcanti, 37

department: Genetics Program

country: Brazil

institute: Instituto Nacional de Câncer

summary: Resistance to chemotherapy is one of the most relevant aspects of treatment failure in cancer. Cell lines are used as models to study resistance. We analyze the transcriptional profile of two multidrug resistant (MDR) cell lines (Lucena 1 and FEPS) derived from the same drug-sensitive cell K562. Microarray data identified 130 differentially expressed genes (DEG) between K562 vs Lucena, 1,932 between K562 vs FEPS, and 1,211 between Lucena 1 versus FEPS. The NOTCH pathway was affected in FEPS with overexpression of NOTCH2 and HEY1. The highly overexpressed gene in MDR cell was ABCB1, and both presented the ABCB1 promoter unmethylated.

overall_design: Gene expression profiles were obtained with the GeneChip® Human Genome U133 Plus 2.0 Array (Affymetrix, Singapore) according to the manufacturer´s instructions; all hybridization experiments were carried out in duplicate. The following samples were analyzed: human K562 cell line RNA from cells grown without drugs; human Lucena 1 cell line RNA from cells grown in medium with vincristine (Lucena 1+VCR); Lucena 1 cell line RNA from cells grown in medium without drugs (Lucena 1-VCR); human FEPS cell line RNA from cells grown in medium with daunorubicin (FEPS +DNR), and FEPS cell line RNA from cells grown in medium without drugs (FEPS -DNR).Comparisons of microarray expression data were carried out between K562 vs Lucena 1 grown in medium without vincristine; K562 vs FEPS grown in medium without daunorubicin; Lucena 1 grown in medium without vincristine vs FEPS grown in medium without daunorubicin. Additionally, we compared expression profiles of each multidrug resistant cell line (Lucena 1 and FEPS) grown in different conditions: Lucena 1 grown in medium without vincristine vs Lucena 1 grown in medium with vincristine, and FEPS grown in medium without daunorubicin vs FEPS grown in medium with daunorubicin.

first: Carolina

last: Bagni

first: Marcos

middle: B

last: de Pinho

first: Nathalia

last: Daflon-Yunes

first: Vivian

middle: M

last: Rumjanek


title: Gene expression profiling of the tumor angiogenic switch in Rip1Tag2 mice

city: Strasbourg

first: Thomas

last: Hussenet

address: 3 avenue Molière

institute: INSERM

summary:
Angiogenesis represents a rate-limiting step during tumor progression. Molecular mechanisms driving tumor angiogenesis (e.g. implicating signaling by VEGFs and their receptors) have been elucidated and allowed to design targeted therapies. However, limits of such anti-angiogenic therapies have emerged, notably because tumor cells adapt and tumors recur in more aggressive fashions. There is therefore a need to identify novel mechanisms implicated in tumor angiogenesis that have a potential towards translational applications.
Using a transgenic murine model of pancreatic neuroendocrine cancer (Hanahan, Nature 315, 1985) where angiogenesis represents an early and discrete step of multi-stage tumor progression (Folkman et al. , Nature 339, 1989), we compared non-angiogenic and angiogenic early tumors to obtain a comprehensive description of the tumor angiogenic switch at the level of gene expression.

overall_design: Early tumor islets from 8 weeks old  Rip1Tag2 mice were differentially isolated to compare the transcriptome of angiogenic versus non-angiogenic islets.

first: Benoit

last: Langlois

first: Falk

last: Saupe

first: Tristan

last: Rupp

first: Christiane

last: Arnold

first: Gertraud

last: Orend


title: Mithramycin Depletes Sp1 and Activates p53 to Mediate Senescence and Apoptosis of Pleural Mesothelioma Cells

first: Mahadev

last: Rao

address: 10 Center drive

department: TGBI

summary: We used microarrays to detail the global gene expression of mithramycin treated cells, xenografts and sp1 depleted cells with p53 overexpression.

overall_design: MPM cells and xenografts were treated with mithramycin or SP1 depleted/p53 overexpressed MPM cells were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to see the invitro and invivo effect of mithramycin (pharmacological model) and depletion of SP1 and overexpression of p53 (genetic model).

first: Scott

last: Atay

first: Xinmin

last: Li

first: David

last: Schrump


title: Aortic macrophages and endothelial cells of apoE KO mice aortas after plaque regression induced apoE adenoviral transfer

city: New York

first: Emmanuel

last: GAUTIER

address: 1425 Madison ave

institute: Mount Sinai School of Medecine

summary: Aortic macrophages and endothelial cells of apoE KO mice were sorted and analyzed by microarray 2 weeks after regression was induced by adenoviral transfer of apoE.

overall_design: Aortic macrophages (CD45+ F4/80+ CD11b+) and endothelial cells (CD45- CD31+) were sorted from apoE KO mice and the RNA extracted and hybridized to Affymetrix Mouse Gene 1.0 ST array. We pooled aortas from 5 mice for each sort.

first: Gwendalyn

last: Randolph


title: Gene expression in RNP autoantibody+ systemic lupus erythematosus (SLE) patient blood

city: Indianapolis

first: Robert

middle: W

last: Hoffman

state: IN

address: Lilly Corporate Center

department: Lilly Bio-Medicines/Immunology

institute: Eli Lilly and Company

summary: The goal of this study was to characterize gene expression profiles in RNP autoantibody+ SLE versus healthy blood donors with a focus on select cytokines that may be important in B cell activation and differentiation, including BAFF, IL-21, and IL-33. We utilized Affymetrix microarrays to characterize the global program of gene expression in the SLE patients, and to identify differentially expressed genes in patients compared to healthy controls. We examined a cohort of 79 consecutive patients classified as anti-ribonuclear protein (anti-RNP)+ systemic lupus erythematosus (SLE). All patients provided RNA samples obtained after providing informed consent. There were 73 female and 6 male subjects. Disease duration ranged from 0 to 453 months with a median of 37.5 months. SLE Disease Activity Index (SLEDAI) ranged from 0 to 31 with a median of 6.

overall_design: mRNA from the blood of a SLE cohort (79 patients with some repeat visits for a total of 99 arrays) and 30 healthy volunteers (one array per volunteer) were analyzed.

first: Eric

middle: L

last: Greidinger

first: Narayanan

last: Perumal


title: Expression data from wild type (WT) and TREM2 null alveolar macrophages (AM)

city: Vienna

first: Jacques

last: Colinge

address: Lazarettgasse 14, AKH BT-25.3

institute: CeMM

summary:
TREM-2 has been described to be a phagocytic receptor. We assessed the influence of TREM-2 on gene expression in alveolar macrophages (AM)
In this data-set we characterised the differences in basal gene expression using affymetrix mouse 1.0 ST arrays between WT and TREM2-/- AM and observed TREM2 -/- AM to exhibt higher expression of opsonins

overall_design: 4 samples were analysed in biological duplicate (2 x WT and 2 x TREM2-/-)

first: Omar

last: Sharif

first: Tiina

last: Berg

last: Kralovics

first: Sylvia

last: Knapp


title: Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants

city: NEDLANDS

last: Martino

state: Western Australia

address: Perth Childrens Hospital, 15 Hospital Avenue

country: Australia

institute: Telethon Kids Institute

summary:
Genome wide DNA methylation profiling study of PBMC from 71 unique primary patient blood samples. The Illumina Human Methylation 450k array was used. 29 challenge proven food allergy, 29 sensitized but oral tolerant, 13 non food allergics
Mixture of food allergy phenotypes (egg allergic (15), peanut allergic (14)), food sensitization phenotypes (egg sensitized (14), peanut sensitized (15)). 4 samples had technical replicate hybridzations.

overall_design: Bisulphite converted DNA from the 75 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2. Technical replicates were combined during processing, resulting in normalized Beta values for 71 unique primary patient blood samples.

middle: J


title: Transcriptome of oviducts from non-hormonally stimulated mice

city: Worcester

first: Keith

middle: a

last: Sutton

address: 55 Lake Avenue North

department: Cell Biology

institute: UMASS Medical School

summary: RNA was prepared from the oviducts of CD-1 female mice. Data sets were from d21 (sexually immature) and sexually mature naturally cycling females in either estrus or diestrus phase of the cycle

overall_design: 9 samples

middle: A

first: Harvey

last: Florman


title: The TIMP3/Apelin axis Regulates Atherosclerosis and Heart Metabolism leading to increased mortality in ApoE null Mice

city: Roma

first: Ivan

last: Arisi

address: viale Regina Elena 295

department: Bioinformatics Facility

institute: European Brain Research Institute

type: Expression profiling by high throughput sequencing

summary: The role of TIMP3 in the context of cardiovascular remodeling is relatively unexplored when considering classical risk factors such as hypercholesterolemia, diabetes and hypertension. To learn more the role of TIMP3 in the progression of cardiovascular disease we combined genetics, metabolomics and in vivo phenotypical analysis using the hypercholesterolemic ApoE null mice to generate ApoE-/-Timp3-/- mice, the latter showing increased atherosclerosis, increased mortality and arrhythmias compared to ApoE-/- mice.  We have previously described Timp3-/-mice in ( Fiorentino, L., et al., Regulation of TIMP3 in diabetic nephropathy: a role for microRNAs. Acta Diabetol, 2013) . To generate ApoE-/-Timp3-/- knockout animals we crossbred the 2 strains. Offsprings were then backcrossed into ApoE animals for 6 generations to generate a pure lineage.   Collectively, metabolite profiles, gene and protein expression consistently suggested a role for TIMP3 to underlie a decreased activation of PPARα/AMPK to dampen fatty acids β-oxidation eventually leading to atherosclerotic plaque composition vulnerability and perturbation of heart metabolism. mRNA profiling in ApoE-/-Timp3-/- mice revealed a TIMP3 effect to regulate Apelin, which we found decreased in the circulation due to its specific downregulation at the myocardial level but not in other well known sites of expression such as the adipose tissue.

overall_design: mRNA sequencing of the heart of ApoE-/-Timp3-/- mice vs  ApoE-/- littermates controls.

last: Stoehr

first: Michele

last: Cavalera

first: Daniela

last: Carnevale

first: Maria

last: Mavilio

first: Stefano

last: Menini

first: Viviana

last: Casagrande

last: Rizza

first: Marina

last: Cardellini

first: Antonino

last: Cattaneo

first: Rama

last: Khokha

first: Giuseppe

last: Pugliese

first: Rossella

last: Menghini

first: Alessandro

last: Mauriello

last: Lembo

first: Massimo

last: Federici


title: Expression profiling of proliferative T-HEp3 and dormant D-HEp3 HNSCC cells in vivo

first: Julio

middle: Alberto

last: Aguirre-Ghiso

address: One Gustave L Levy Place

department: Medicine and Otolaryngology

institute: Ichan School of Medicine at Mount Sinai

summary: The objective of this study was to obtain expression profiles of proliferative T-HEp3-GFP and dormant D-HEp3-GFP cells after one week in vivo. The second objective was find tumor cells quiescence associated genes in dormant D-HEp3 cells that are only quiescent when injected in vivo. In this case we compared cells one week growing vs. dormant for the indicated cells in chick embryo CAMs. After one week 5 embryos per cell line carrying the indicated cells were isolated, tumors collagenased as described below and sorted for GFP-high cells usig a MoFlo machine. The sorted cells > 5x10^4 were used to extract RNA and the pure RNA was used to perform expression profiling using the Affymetrix HG-u133plus2 arrays. Because of the low amount of D-HEp3 (dormant) cells recovered all tumor cells from the dormant nodules were pooled. The same was done for proliferative-sorted T-HEp3-GFP cells to allow comparisons. Arrays were performed in triplicate.

overall_design: 5 T-HEp3-GFP tumors and 5 D-HEp3-GFP nodules were processed for preparation of single cells suspensions, RNA extracted and then pools of  T-HEp3-GFP and D-HEp3-GFP sorted cells were analyzed in triplicate arrays

last: Sosa

first: Paloma

last: Bragado

first: Ajish

last: George


title: Expression data from Werner syndrome iPSCs

status: Public on Dec 31 2014

city: Hiroshima City

first: Akira

last: Shimamoto

state: Hiroshima

address: 1-2-3 Kasumi, Minami-ku

department: Department of Cellular and Molecular Biology

institute: Hiroshima University, Graduate School of Biomedical & Health Sciences

summary:
Werner syndrome (WS) is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency.
We used microarrays to examine whether global gene expression profile of WS iPSCs is similar to that of normal iPSCs and human ESCs, as well as premature senescence phenotype is suppressed by reprogramming.

overall_design: Total RNAs extracted from WS fibroblasts, WS iPSCs, normal iPSCs, and human ESCs were hybridized onto Human Genome U133 Plus 2.0 Arrays to compare global gene expression profile of WS iPSCs with normal human pluripotent stem cells, as well as the parental fibroblasts.

first: Hiroyuki

last: Seimiya


title: The gene expression profile of renal cell carcinoma cell line (786-O) versus prostate cancer cell line (PC3) in co-culture with primary murine muscle progenitor cells

city: Rochester

first: Chao

last: Xie

address: 601 Elmwood Ave. Box665

department: Orthopaedics

institute: University of Rochester

summary: Patients with metastatic renal cell carcinoma (RCC) have a life expectancy of 6 months to 1 year. The deadly nature of RCC compared to other tumors that metastasize to bone, such as prostate cancer (PC), is associated with extensive arteriogenesis that requires recruitment of muscle progenitor cells to form the vascular smooth muscle around these large vessels. To identify potential genes that are involved in RCC recruitment of muscle progenitor cells we performed a microarray analysis to evaluate the global gene expression of human RCC (786-O) cells that form these large vessels in murine xenografts, versus human PC (PC3) that do not form these large vessels during osteolytic bone metastasis in mice (Xie C, et al. J Orthop Res. 2011;30(2):325-33). To assess changes in gene expression that occur when tumor cells interact with muscle progenitor cells, primary myoblast isolated from 5-day-old C57BL/6-Tg GFP neonatal mouse limbs were co-cultured with RCC or PC cells.

overall_design: The experiment contained five groups: [Group 1] pure 786-O cells; [Group 2] pure PC3 cells; [Group 3] 1:1 co-culture of myoblast with 786-O cells; [Group 4] 1:1 co-culture of myoblasts with PC. All cultures were plated at 80% confluence, and the cells were harvested 12 hours later to isolate total RNA.

first: Edward

last: Schwarz

first: Wakenda

last: Tyler


title: The Calcineurin-NFAT-Angiopoietin 2 signaling axis in lung endothelium is critical for the establishment of lung metastases

city: Tokyo

first: Shogo

last: Yamamoto

address: 4-6-1 Komaba, Megro-ku

department: Research Center for Advanced Science and Technology

institute: The University of Tokyo

summary: The pre-metastatic niche is a pre-determined site of metastases, awaiting the influx of tumor cells. Here we demonstrate that the calcineurin-NFAT pathway is activated specifically in lung endothelium prior to the detection of tumor cells that preferentially metastasize to the lung. We previously showed that DSCR-1 functions in a negative feedback loop to attenuate calcineurin signaling. Upregulation of the calcineurin pathway via loss of Dscr-1 leads to a significant increase in lung metastasis due to the increased expression of a newly identified NFAT target, Angiopoietin (Ang)-2. An increase in VEGF levels specifically in the lung versus other organ microenvironments triggers a threshold of calcineurin-NFAT signaling that transactivates Ang2 in lung endothelium. Further, we demonstrate that overexpression of DSCR-1 or the Ang-2 receptor, soluble Tie2, prevents activation of the lung endothelium inhibiting lung metastases in our mouse models. Our studies provide insights into mechanisms underlying angiogenesis in the pre-metastatic niche and offers novel targets for lung metastases.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Whole lung total RNA were harvested from wildtype or Dscr-1 null mutation mice (C57BL6/J background), and subjected to Affymetrix Mouse 430 2.0 array in duplicate conditions. Alternatively, primary cultured human lung endothelial cells (LONZA) were transfected with either siRNA, control or DSCR-1, or adenovirus expressing DSCR-1 or mock control. Adenovirally transfected lung endothelial cells were serum-starved (EBM-2 (LONZA) plus 0.5% FBS) and treated with 50ng/ml VEGF for indicated time points. After the treatments, total RNA was harvested and subjected to Affymetrix Human U133 Plus 2.0 array.

first: Takashi

last: Minami

first: Mai

last: Miura

first: Tsuyoshi

last: Osawa


title: Activation of the JAK/STAT pathway in Behcet’s Disease

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary: Th1/Th17-type T-cell responses are upregulated in Behcet’s disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using mRNA of isolated CD14+ monocytes and CD4+ T-cells from PBMC in patients with BD (n=9) and healthy controls (HC) (n=9). Flow cytometric analysis of unstimulated (US) and stimulated (PHA) STAT3 and pSTAT3 expressions of PBMCs were also analysed (BD and HC, both n=26). JAK1 was observed to be upregulated in both CD14+ monocytes (1.94 fold) and CD4+ T-lymphocytes (1.40 fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14+ monocytes (p=2.95E-06) and in CD4+ lymphocytes (p=8.13E-04) in BD. Interferon (p=1.02E-07) and IL-6 (p=8.91E-03) signaling pathways were also prominent in CD14+ monocytes. Basal unstimulated total STAT3 expression was significantly higher in BD (1.2 vs 3.45, p<0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, IFNγ, IL-6, IL-17 and IL-23.

overall_design: Gene expression profile from two cell types sorted from PBMCs: CD4+ and CD14+. CD4+ profiling has 3 controls and 9 patients samples, CD14+ has 9 controls and 8 patients samples.

first: Aysın

last: Tulunay

middle: G

first: Filiz

last: Ture-Ozdemir

first: Vuslat

last: Yilmaz

first: Emel

last: Eksioglu-Demiralp

first: Fatma

last: Alibaz-Oner

first: Gülsen

last: Ozen

first: Jonathan

middle: D

last: Wren

first: Guher

last: Saruhan-Direskeneli

first: Amr

middle: H

last: Sawalha

first: Haner

last: Direskeneli


title: Gene expression in pluripotent and Oct4+Tet1 induced cells

city: Shanghai

first: jiayu

last: chen

address: No1239, Siping Road

institute: Tongji University

summary:
Detection of gene expression profiles during OT(Oct4+Tet1)-mediated iPSC induction and demonstration the pluripotency of OT-iPSC.
We used microarray to explore the global expression change during the reprogramming process.

overall_design: In the study presented here, microarray analysis is used to detect the overall gene expression profile of starting fibroblast cells, intermediated reprogramming cells, fully reprogrammed iPS cells and wildtype ES cells.

first: Jiayu

last: Chen

first: Yawei

last: Gao

first: Shaorong

first: Tao

last: Cai


title: MOF regulates cell cycle progression

city: Freiburg im Breisgau

first: Thomas

last: Manke

address: Stuebeweg 51

department: Bioinformatics and Deep-Sequencing Unit

institute: Max-Planck-Institute for Immunobiology and Epigenetics

summary: We utilized primary MEFs to further delineate the role of MOF in proliferating cells and demonstrate that MOF directly activates genes required for cell cycle progression.

overall_design: MEFs of both genders are conditionally depleted of MOF using the Cre-Lox system. Consequences at the transcriptional level are assessed using the Mouse Gene 1.0 ST array by Affymetrix

first: Jacopo

last: Lucci

first: Sarah

last: Diehl


title: Expression data from LNCaP prostate cancer cells treated with taxanes

first: Karen

last: Knudsen

institute: Thomas Jefferson University - Kimmel Cancer Center

summary:
Comparison of the new generation taxane cabazitaxel with docetaxel in prostate cancer cells
Cabazitaxel impacts distint molecular pathways as compared to docetaxel, which could underlie its efficacy after docetaxel treatment has failed in castration resistant prostate cancer patients

overall_design: 12 samples were analysed. A genome-wide expression array was performed on a GeneChip Human Gene 2.0ST Array (Affymetrix, 902112) with LNCaP cells infected with a control plasmid (MSCV-LMP), treated for 16h with 1nM cabazitaxel, docetaxel or vehicle (EtOH), in duplicates. The expression data were RMA normalized, and filtered to remove low-expressing genes. Differential gene expression with corresponding p-values (student’s ttest) was determined of drug-treated over control.


title: Gene expression data for 39 inbred mice strains for neutrophils

city: Boston

first: Liang

last: Yang

address: 77 Avenue Louis Pasteur

department: Pathology

institute: Harvard Medical School

summary: Genome-wide expression data were generated for polymorphonuclear neutrophils (granulocytes, GN) across 39 strains in the MPD “Priority Strain Panel”.

overall_design: Inbred mouse strains from the MDP Priority Strain Panel, representing 39 strains, were obtained from the Jackson Laboratory production facility in Bar Harbor, Maine, at five weeks of age. All mice were bred in the Jackson Laboratory production facility under SPF conditions. CD11b+Ly6G+ bone marrow granulocytes were sorted from pools of two to three mice. Two biological replicates were generated for each strain using the ImmGen standard operating protocol (SOP; www.immgen.org). Gene expression data was generated for bone marrow granulocytes (GN)  using Affymetrix ST1.0 microarrays resulting in the quantification of expression levels for 25,134 probes corresponding to 21,951 unique genes.

first: Mostafavi

last: Sara

first: Adriana

last: Ortiz-Lopez

first: Diane

last: Mathis

first: Christophe

last: Benoist


title: Gene expression data for 39 inbred mice strains for CD4+ T cells

summary: Genome-wide expression data were generated for CD3+CD4+CD62L+ naïve T splenocytes  across 39 strains in the MPD “Priority Strain Panel”.

overall_design: Inbred mouse strains from the MDP Priority Strain Panel, representing 39 strains, were obtained from the Jackson Laboratory production facility in Bar Harbor, Maine, at five weeks of age. All mice were bred in the Jackson Laboratory production facility under SPF conditions. CD3+CD4+CD62L+ naïve T splenocytes  were sorted from pools of two to three mice. Two biological replicates were generated for each strain using the ImmGen standard operating protocol (SOP; www.immgen.org). Gene expression data was generated for bone marrow granulocytes (GN)  using Affymetrix ST1.0 microarrays resulting in the quantification of expression levels for 25,134 probes corresponding to 21,951 unique genes.

first: Sara

last: Mostafavi


title: Interleukin-32 is progressively expressed in Mycosis Fungoides independent of helper T-cell 2 and helper T-cell 9 polarization

first: Mayte

last: Suarez-Farinas

address: 1425 Madison Ave, L2-70C, Box 1077,

institute: Mount SinaiSchool of Medicine

summary: Mycosis Fungoides (MF) is typically characterized by a mature CD4+ memory T-cell phenotype, and regarded as a helper T-cell (Th)2-skewed disease. Here, using skin samples from MF (n=21), healthy volunteers (n=17), atopic dermatitis (n=17), and psoriasis (n=9), we performed RT-PCR to show highest interleukin (IL)-32 mRNA expression in MF compared to benign inflammatory diseases, and its increasing expression with disease progression. By immunohistochemistry and immunofluorescence, we confirmed IL-32 protein expression by numerous CD3+CD4+ T-cells and some epidermotropic T-cells in MF lesions. IL-32 is expressed by MyLa cells (MF cell line) and promoted their proliferation and viability in a dose-dependent fashion. IL-32-treated MyLa and HH cells (CTCL cell line) showed upregulation of cell proliferation and survival genes. Of major 'polar' T-cell cytokines, only IFN-γ mRNA increases with MF progression and positively correlates with IL-32 mRNA expression levels. Th2 cytokines do not show consistent increases with MF progression nor positive correlation with IL-32 mRNA expression levels. Furthermore, by flow cytometry, IL-32 production by circulating activated T-cells in healthy individulas was found in IFN-γ+ and IFN-γ- cells but not in IL-4+ or IL-13+ cells. In conclusion, we identified IL-32+ cells as likely tumor cells in MF, and clearly showed that IL-32 mRNA expression levels increase with MF progression. We found that IL-32 mRNA expression levels in MF are significantly higher than those in other skin diseases, and that some IL-32+ T-cells are independent from defined Th subsets. Thus IL-32 may play a unique role in MF progression as an autocrine cytokine.

overall_design: The conditions that we used for our experiments;  1) MyLa cells cultured in 0.1% FCS without IL-32g for 40 hours, 2) MyLa cells cultured in 0.1% FCS with 5ng/ml IL-32g for 40 hours, 3) HH cells cultured in 0.1% FCS without IL-32g for 40 hours, 4) HH cells cultured in 0.1% FCS with 5ng/ml IL-32g for 40 hours.

last: suarez-Farinas

first: James

last: Krueger

first: Hanako

last: Omatsu


title: Gene expression data for 39 inbred mice strains for neutrophils and CD4+ T cells

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

overall_design: Refer to individual Series


title: NHP Liver treated with Vehicle or LXR Ligand

city: Los Angeles

first: Cynthia

last: Hong

state: CA

address: 675 Charles E Young Dr. S

institute: UCLA

summary: The LXR-regulated E3 ubiquitin ligase IDOL controls LDLR receptor stability independent of SREBP and PCSK9, but its relevance to plasma lipid levels is unknown.  Here we demonstrate that the effects of the LXR–IDOL axis are both tissue- and species-specific.  In mice, LXR agonist induces Idol expression in peripheral tissues but not in liver, and does not change plasma LDL levels.  Accordingly, Idol-deficient mice exhibit elevated LDLR protein levels in peripheral tissues but not in the liver and have minimal change in plasma LDL levels.  By contrast, LXR activation in cynomolgus monkeys induces hepatic IDOL expression, reduces LDLR protein, and raises plasma LDL levels.  Knockdown of IDOL in monkeys with an antisense oligonucleotide blunts the effect of LXR agonist on LDL levels.  These results implicate IDOL as a modulator of plasma lipid levels in primates and support further investigation into IDOL inhibition as a strategy for LDL lowering in humans.

overall_design: 6 affymetrix chips - 3 chips for vehicle and 3 for LXR treatment.  Each chip represents an individual animal

first: Stephanie

last: Marshall

first: Allison

last: McDaniel

first: Mark

last: Graham

first: Joseph

last: Layne

first: Lei

first: Elena

last: Scotti

first: Rima

last: Boyadjian

first: Jason

last: Kim

first: Brian

middle: T

last: Chamberlain

first: Rajendra

middle: K

last: Tangirala

first: Michael

middle: E

last: Jung

first: Loren

last: Fong

first: Richard

last: Lee

first: Stephen

last: Young

first: Ryan

last: Temel

first: Peter

last: Tontonoz


title: Transcriptional profiling of HEPG2 cells after treatment with TRIB1-inducing compounds

city: Cambridge

first: Marek

last: Nageic

state: MA

address: 7 Cambridge Center

department: Center for the Development of Therapeutics

institute: Broad Institute

summary:
Treatment of HEPG2 cells with TRIB1-inducing compounds and Oncostatin M
Transcriptional response of HEPG2 cells was measured after treatment with TRIB1-inducing compound BRD8518 and Oncostatin M, compared to DMSO control treatment at 1, 6 and 24 hours.

overall_design: Transcriptional response was compared between BRD8518- and OSM-treated cells and untreated (DMSO) cells at 1, 6 and 24 hours.

last: Nagiec

first: Adam

last: Skepner

first: Eleanor

last: Howe

first: Michelle

last: Palmer

first: Jose

last: Perez


title: Ingestion of Cryptococcus neoformans by macrophages damages multiple host cellular processes

first: Bin

last: Ye

address: 1301 Morris Park Ave

department: Genetics

institute: Albert Einstein College of Medicine

summary: Human infection with Cryptococcus neoformans (Cn), a prevalent fungal pathogen, occurs by inhalation and deposition in the lung alveoli of infectious particles. The subsequent host pathogen interaction is multifactorial and can result either in eradication, latency or extra-pulmonary dissemination. Successful control of Cn infection is dependent on host macrophages as shown by numerous studies. However in vitro macrophages display little ability to kill Cn. Recently, we reported that ingestion of Cn by macrophages induces early cell cycle progression that is subsequently followed by mitotic arrest, an event that almost certainly reflects damage to the host cell. The goal of the present work was to understand macrophage pathways affected by Cn toxicity. Infection of J774.16 macrophage-like cell line macrophages by Cn in vitro was associated with changes in gene pattern expression.  Concomitantly we observed depolarization of macrophage mitochondria and alterations in protein translation rate. Our results indicate that Cn infection impairs multiple host cellular functions. Therefore we conclude Cn intracellular residence in macrophages undermines the health of these critical phagocytic cells interfering with their ability to clear the fungal pathogen.

overall_design: Total of 24 arrays included in this study. cDNA of control after 2 hour (N=4); cDNA of 2 hour after infected with live Cn (N= 4); cDNA of 2 hour after infected with heat killed Cn (N= 4); cDNA of control after 24 hour (N=4); cDNA of 24 hour after infected with live Cn (N= 4); cDNA of 24 hour after infected with heat killed Cn (N= 4);

first: Carolina

last: Coelho

first: Ana

middle: C

last: Souza

first: Lorena

last: Derengowski

first: Carlos

last: de Leon-Rodriguez

first: Bo

last: Wang

first: Rosiris

last: Leon-Rivera

first: Anamelia

last: Bocca

first: Teresa

last: Gonçalves

first: Arturo

last: Casadevall


title: Microarray of Mst1/2 deleted epithelial cells from E18.5 mouse lungs

city: Cincinnati

first: Alexander

last: Lange

state: OH

address: 3333 Burnet Ave

institute: Cincinnati Children's Hospital Reseach Foundation

summary:
ShhCre;Mst1/2flx/flx (Mst1/2 D/D) mice were generated to conditionally delete Mst1 and Mst2 from epithelial progenitors during lung morphogenesis.  Lungs from E18.5 control and Mst1/2 D/D mice were mechanically and enzymatically dissociated to generate single cell suspension.  Epcam(+) cells were isolated using magnetic microbeads.
Microarray analysis of mRNAs isolated from Epcam(+) epithelial cells from E18.5 control and Mst1/2 D/D mice was performed to identify transcriptional changes following deletion of the mammalian Hippo kinases (Mst1 and Mst2) from the embryonic lung.

overall_design: The mammalian Hippo kinases, Mst1 and Mst2, were conditionally deleted in epithelial progenitors of the developing lung using ShhCre.  Epcam(+) epithelial cells were isolated from the lungs of E18.5 control and Mst1/2 deleted mice.  mRNA isolated from Epcam(+) epithelial cells was analyzed by microarray.

first: Jeffrey

last: Whitsett


title: Large-scale gene expression profiling  of 81 hepatocellular carcinomas

city: Paris

first: Sandrine

last: Imbeaud

address: 15 rue de l'Ecole de Médecine

department: INSERM UMRS1138-EQUIPE 28, Sorbonne Université-Inserm-Université de Paris

institute: Centre de Recherche des Cordeliers

summary: Hepatocellular carcinoma (HCC) is ranked second in cancer-associated deaths worldwide. Most cases of HCC are secondary to either a viral hepatitis infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis). It is a complex and heterogeneous tumor due to activation of multiple cellular pathways and molecular alterations.

overall_design: HCC liver tumors corresponding to 81 patients. In all cases, tumor samples were frozen (-80°C) after hepatic resection at diagnosis. Normal liver samples were used as reference samples. Comparative gene expression analysis was done using Affymetrix U133plus v2 array (GPL570)

first: Jessica

last: Zucman-Rossi

first: Gabrielle

last: Couchy


title: The Sweden Canceromics Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine

city: Lund

first: Lao

last: Saal

address: Scheelevägen 2, MV404B2

department: Department of Oncology and Pathology

country: Sweden

institute: Lund University

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

overall_design: Refer to individual Series.


title: DNA methylation, H3K27me3, and gene expression statuses of human cancer cell lines and normal cells.

city: Shinagawa-ku

first: Hideyuki

last: Takeshima

state: Tokyo

department: Institute for Advanced Life Sciences

institute: Hoshi University

type: Genome binding/occupancy profiling by genome tiling array

summary: DNA methylation, H3K27me3, and gene expression statuses in cancer cell lines and normal cells.

overall_design: DNA methylation, H3K27me3, and gene expression statuses of cancer cell lines were compared to those in normal cells in three different tissues.


title: Effect of Brwd1 mutation on the mouse oocyte transcriptome

city: Bar Harbor

first: Timothy

middle: Michael

last: Stearns

state: ME

address: 600 Main Street

department: Computational Sciences

institute: The Jackson Laboratory

summary:
The Brwd1 mutation, though having dramatic effects on the spermatocyte transcriptome, had little effect on the oocyte transcriptome.

Postmeiotic gene expression is essential for development and maturation of sperm and eggs. In B6/C3H females, Brwd1 ablation causes severe chromosome condensation and structural defects associated with abnormal telomere structure. In contrast to males, transcriptome analysis at the germinal vesicle stage revealed only minor changes in gene expression including a  >2 fold overexpression of the histone methyltransferase MLL5 and LINE-1 elements transposons. Thus, loss of BRWD1 function interferes with the completion of oogenesis and spermatogenesis through sexually dimorphic mechanisms. Our results demonstrate that BRWD1 is essential for the epigenetic control of chromosome stability during female meiosis while playing a critical role in haploid gene transcription during the post-meiotic differentiation events of spermiogenesis.

overall_design: Oocytes isolated from B6/C3H wild type (WT) and homozygous Brwd1 mutants were subjected to transcriptome analysis by microarrays. Three replicates of 100 oocytes each were prepared from WT and mutant oocytes.

first: John

last: Eppig

last: Schimenti


title: Leptin protects hosts cells from E. histolytica cytotoxicity via a STAT-3 dependent mechanism

city: Charlottesville

first: Stephen

last: Turner

address: 1670 Discovery Drive

institute: Signature Science, LLC

summary: Undernutrition increases susceptibility to diarrheal diseases.  The adipocytokine leptin imparts protection from amebiasis.  We tested the role of leptin signaling in cellular resistance to E. histolytica cytotoxicity in HEK cells transfected to express the leptin receptor.  Protection from amebic killing was conferred by the leptin receptor.  It required activation of the transcriptional regulator STAT3 by the leptin receptor, as mutation of the STAT3 activation domain of the receptor, or addition of a STAT3 small-molecule inhibitor, reversed protection.  In contrast, a leptin receptor containing a common polymorphism (Q223R) known to increase susceptibility to amebiasis in humans provided significantly less protection.  Consistent with the importance of STAT3, the Q223R polymorphism decreased l leptin-dependent STAT3 activation by 21% relative to the WT receptor (P=0.035).   Microarray analysis identified potential downstream effectors of STAT3-mediated protection, most importantly TRIB1 and SOCS3, which appear to having opposing roles in the regulation of E. histolytica induced apoptosis. Together these data demonstrated that leptin increased the resistance of host cells to E. histolytica cytotoxicity via a STAT3-dependent mechanism.  Additionally we found that the Q223R polymorphism in the leptin receptor, known to increase susceptibility to E. histolytica infection, decreased STAT3 activation and decreased host resistance to amebic cytotoxicity.  This is the first demonstration of a host-signaling pathway that restricts amebic pathogenesis. Additionally, this finding represents an important advance in our mechanistic understanding of the role of leptin in the relationship between undernutrition and increased susceptibility to infection.

overall_design: HEK293 cells were transfected with WT LepR or Y1138L (STAT3-mutant) leptin receptor.  48 hours post-transfection cells were made quiescent by incubation in optimum plus 0.5% BSA for 3 hours.  Cells were then stimulated with 100ng of leptin or maintained in optimum plus 0.5% BSA for an additional 3 hours.  Three biological replicates of each sample were hybridized to Human Genome U133 Plus 2.0 gene chips (Affymetrix) and read using the GeneChip Scanner 3000 7G (Affymetrix).

first: Chelsae

middle: S

last: Marie

first: William

last: Petri


title: Growth factor independence 1b (Gfi1b) is required for erythroid cell maturation and regulates embryonic globin expression

city: Essen

first: Cyrus

last: Khandanpour

state: NRW

address: Hufelandstr. 55

department: Department of Hematology

institute: University Hospital Of Essen


title: Differential regulation patterns of anti-CD20 mAbs in MCL

city: Penzberg

first: Helmut

last: Burtscher

address: Nonnenwald 2

institute: Roche Pharma

summary:
We investigated the differential regulation patterns of type I anti-CD20 monoclonal antibody (mAb) rituximab and type II obinutuzumab on a transcriptional level. Using a panel of MCL cell lines, we determined the effects of obinutuzumab and rituximab as monotherapies as well as in combination on cell viability and proliferation.
Obinutuzumab induced a higher reduction in cell proliferation in each mantle cell lymphoma cell line than rituximab did. Results indicate a common pattern of expression changes after binding of anti-CD20 mAbs, but also reveal a significant difference between type I and type II treatment. Combination treatment resulted in a rituximab-like expression pattern. Many deregulated genes were associated with stress signalling, cell death, immune response and other functional clusters. Our analyses identified different and antibody-specific downstream expression patterns of obinutuzumab and rituximab, which may represent the molecular basis of the superior effect of obinutuzumab in comparison to rituximab.

overall_design: 25 samples with 3 replicates each


title: Growth factor independence 1b (Gfi1b) is required for erythroid cell maturation and regulates embryonic globin expression [MoGene-1_0]

summary:
Growth factor independence 1b (Gfi1b) is a DNA binding repressor of transcription with vital functions in hematopoiesis. Gfi1b-null embryos die at midgestation very likely due to defects in erythro- and megakaryopoiesis. To analyze the full functionality of Gfi1b in embryonic erythropoiesis, we used conditionally deficient mice that harbor floxed Gfi1b alleles and one EpoR-Cre knock-in allele.
We used fetal liver cells from wild type C57BL/6 embryos or conditional Gfi1b knock-out embryos at day 14.5 p.c., both carrying one EpoR-cre knock-in allele. Ter119 positive erythroid cells were isolated by flow cytometry and RNA from these cells was isolated using the Trizol procedure according to the manufacturers instructions for gene expression analysis on Affymetrix Gene 1.0 ST arrays (GPL 6246)

overall_design: We used microarray-based gene expression profiling to analyze the effect of loss of Gfi1b expression in Ter119 positive erythroid cells from mouse fetal liver at day 14.5 post coitum.

first: L

last: Vassen

first: H

last: Beauchemin

first: W

last: Lemsaddek

first: J

last: Krongold

first: M

last: Trudel

first: T

last: Möröy


title: Associations of inflammation, iron and early death in sickle cell disease

city: Bethesda

first: Yanqin

last: Yang

state: Maryland

address: 10 Center Dr.

institute: NIH

summary:
Expression profiling using a defined set of iron regulated genes identifies co-regulation of genes and pathways related to inflammatory cytokines
In this dataset, we include the whole genome expression data obtained from PBMCs from steady state HbSSs with Sickle Cell Disease and healthy  HbAAs . Unsupervised two-way hierarchical clustering using a predefined iron regulated gene list identified 3 groups of subjects with high, low and intermediate expression of iron activated genes.In analysis of these three iron regulated gene clusters, we found 98 genes which were consistently and significantly differentially expressed.

overall_design: Samples from 24 subjects with SCA and 9 healthy subjects were analysed. With approval from the institutional review board, RNA was isolated from PBMCs and plasma was stored for analysis of baseline laboratory parameters. All RNA was hybridized on Affymetrix’ (Santa Clara, CA) Human Genome U133 Plus 2.0 Amicroarray in the same batch. Signal intensity values were achieved by well-accepted processing procedures including background correction, quantile normalization and median polish summarization. comparison of the resulting clustering groups were used to find differentially expressed genes with the filter of a change greater than 40% between the clustering groups and 10% false discovery rate (FDR).  Functional analysis was performed on Ingenuity Pathway Analysis (IPA) System.

first: Eduard

last: van Beers

first: Nalini

last: Raghavachari

first: Gregory

last: Kato


title: Flexible multiplatform RNA profiling at the single cell level applied to enriched cancer initiating cells: Affymetrix array data

city: Manchester

first: Ged

last: Brady

address: Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Rd

department: Clinical and Experimental Pharmacology

institute: Caner Research UK Manchester Institute

summary: Accurate profiling of RNA expression of single cells is a valuable approach for broadening our understanding of cancer biology and mechanisms of dissemination, but requires the development of reliable methods for their molecular characterization. Here we evaluate a single cell methodology which generates microgram amounts of cDNA suitable for next generation sequencing (RNA-Seq), high throughput RT-qPCR and Affymetrix array analysis. The approach was tested by comparing expression profiles of amplified single MCF7 and MCF10A cells to profiles generated from unamplified RNA. The expression profiles were compared by Affymetrix-U133 arrays, RNA-Seq and high-density qPCR.  There were strong cross-platform correlations of >80% and concordance between single cell and unamplified material of >70%. We exemplify the approach through analysis of rare sorted cancer initiating cells (CICs) derived from a NSCLC patient-derived xenograft. Populations of 10 cells from total tumour and two distinct subsets of CIC, putatively involved in primary tumor maintenance or metastasis formation were FACS sorted then directly amplified. CIC expression profiles strongly correlated with published stem-cell and epithelial-mesenchymal transition (EMT) signatures. Our results confirm the utility of the amplification system and our methodology to detect and distinguish RNA profiles in rare cell populations that inform on EMT and stem-cell characteristics. This GEO dataset comprises the Affymetrix U-133 Plus 2.0 data for MCF7 and MCF10A cDNA amplified from 1ng RNA and single cell samples.

overall_design: 20 samples. 5 biological replicates each of MCF7 cDNA generated from 1 ng amplified RNA (control), MCF10A cDNA generated from 1 ng amplified RNA (control), MCF7 cDNA generated from amplified RNA from a single cell and MCF10A cDNA generated from RNA amplified from a single cell  (cDNA generated from the same single cells used to generate the single cell cDNA samples used for RNA-Seq analysis in this super series, i.e. same set of samples analysed using both platforms). Genes found to be differentially expressed between the cell lines (MCF7 and MCF10A) using Affymetrix arrays were compared between the test (single cell) and control (1ng) samples. All were compared to a reference sample set generated from Affymetrix arrays of 10μg of unamplified RNA for each cell line (Bitton, D.A., Okoniewski, M.J., Connolly, Y. and Miller, C.J. (2008) Exon level integration of proteomics and microarray data. BMC Bioinformatics, 9, 118).

first: Dominic

last: Rothwell

first: Yaotong

last: Li

first: Gillian

last: Newton

first: Yvonne

last: Hey

first: Mahmood

last: Ayub

first: Catriona

last: Tate

first: Louise

last: Carter

first: Suzanne

last: Faulkner

first: Stuart

last: Pepper

first: Crispin

last: Miller

first: Fiona

last: Blackhall

first: Giulia

last: Bertolini

first: Luca

last: Roz

first: Caroline

last: Dive


title: Snf2h and Satb2-dependent chromatin remodeling establishes callosal projection neuron identity through clustered protocadherin gene regulation.

city: Ottawa

first: David

last: Picketts

state: Ontario

address: 501 Smyth Road

country: Canada

institute: University of Ottawa

summary:
Mouse cortex (dorsal telencephalon) analysis from Snf2h cKO-Emx1 mice versus control littermates at birth (P0).
P0 mouse cortex, 3 cortices pooled per sample, n=2 per genotype.

overall_design: Cortex samples at birth (P0) from Snf2h cKO-Emx1 mice and control littermates were analyzed. Three cortices were pooled per sample and there are two replicates per genotype.