title: Expression of genetic adaptability of cancer cells under treatment selection pressure in multiple myeloma patients

city: Saint Herblain

first: Wilfried

last: Gouraud

address: bd Jacques Monod

department: Integrated Center of Oncology René Gauducheau

institute: ICO (Integrated Center of Oncology Nantes)

summary: Series GSE25262 patients on expression side.

overall_design: [Exon study] 11 myeloma patients at diagnosis and relapse examined with Exon expression chip

first: Florence

last: Magrangeas

first: Hervé

last: Avet-Loiseau

first: Olivier

last: Decaux

first: Kenneth

last: Anderson

first: Philippe

last: Moreau

first: Nikhil

last: Munshi

first: Stéphane

last: Minvielle


title: Transcriptional analysis of organ-specific toxicity induced by a panPPAR agonist in mice: Identification of organ-specific toxicity biomarkers

status: Public on Feb 19 2013

city: Glasgow

first: Manikhandan

middle: A V

last: Mudaliar

state: Scotland

address: Room B528, Sir Graeme Davies Building, 120 University Place

department: College of Medical, Veterinary and Life Sciences

country: United Kingdom

institute: University of Glasgow

summary: In this study, we aim to identify candidate biomarkers which may be useful as surrogate indicators of toxicity for pre-clinical development of panPPAR-agonist drug candidates. Gene expression microarray, histopathology and clinical chemistry data were generated from liver, heart, kidney and skeletal muscles of three groups of mice administered with three different dosages of an experimental pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, PPM-201, for 14 days. The histopathology and clinical chemistry data were compared with the gene expression analysis and candidate biomarker genes were identified.

overall_design: Nine wild type mice (strain: C57BL/6J) were randomly divided into three groups - Group-I, II and III. PPM-201 in the vehicle base was administered daily for 14 days at 6 mg/kg body weight dose rate to each mouse in Group-II and at 20mg/kg body weight dose rate to each mouse in Group-III while the mice in Group-I received only the vehicle base. On 15th day, the mice were sacrificed to harvest blood, heart, skeletal muscle, liver and kidney tissues for clinical chemistry, microarray and histopathology analysis. In the clinical chemistry analysis, alanine aminotransferase (ALT, U/L), aspartate aminotransferase (AST, U/L), creatinine kinase (CK, U/L), blood urea nitrogen (BUN, mmol/L), creatinine (umol/L) and lactate dehydrogenase (LDH, U/L) were measured from the blood of each mouse. Two sections of liver, two sections of kidney, one or two sections of skeletal muscle, and one section of heart were prepared from each mouse, stained with hematoxylin and eosin (H&E), and examined by a veterinary pathologist. RNA was extracted and processed as per the established protocol from heart, skeletal muscle, liver and kidney tissue samples of all the 9 mice for profiling with Affymetrix Mouse Genome 430 2.0 Array and in total 36 chips were prepared. Using various quality control measures, the data was analysed for its quality. As it was found to be good in quality, the data from all the 36 chips were used for further analysis. The results from histopathology and clinical chemistry analysis were compared with the gene expression to determine if the dosages selected for the study were associated with findings in target organs.

first: Daniel

middle: J

last: Crowther

middle: A

first: Ross

middle: D

last: Haggart

first: Gino

last: Miele


title: Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging

status: Public on Feb 14 2013

city: Boston

first: Isabel

last: Beerman

state: MA

address: 200 Longwood Ave, WAB 156

country: USA

institute: Boston Childrens Hospital

type:
Expression profiling by array
Third-party reanalysis

summary: Gene Expression profiling of HSCs isolated at different stages of ontogeny to address correlation between gene expression and changes in DNA methylation

overall_design: Gene expression profiling of hematopoietic stem cells isolated from e14.5 fetal liver (lineage- ckit+ sca1+CD150+ CD48- Mac1+), 3 month old mice (lineage- ckit+ sca1+ CD34- Flk2-) and 25 month old mice  (lineage- ckit+ sca1+ CD34- Flk2-)


title: Expression data from mouse embyonic stem cell, neural progenitor and neuron

status: Public on Feb 09 2013

city: Bethesda

first: Iris

last: Zhu

state: Maryland

address: 9000 Rockville Pike

institute: National Institute of Health

summary: The effect of HMGN1 protein on gene expression of mouse ESC, NP and Neurons were investigated by comparing the transcriptome between Hmgn1+/+ and Hmgn1 -/- cells.

overall_design: three cell types, two genotypes, three reps per sample type

first: Michael

last: Bustin

first: David

last: Landsman

first: Tao

last: Deng


title: Minor clone provides a reservoir for relapse in multiple myeloma

status: Public on Feb 13 2013

first: Wilfried

last: Gouraud

country: France

type:
Expression profiling by array
Genome variation profiling by SNP array
SNP genotyping by SNP array

summary:
In this study we addressed subclonal evolutionary process after treatment and subsequent relapse in multiple myeloma (MM) in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. Because MM is a highly heterogeneous disease coupled with a large number of DNA copy number alterations (CNAs) and loss of heterozygosity (LOH), we focused our study on the secondary genetic events: 1q21 gain, NF-kB activating mutations, RB1 and TP53 deletions, that seem to reflect progression. By using genome-wide high resolution SNP arrays we identified subclones with nonlinear complex evolutionary histories in a third of patients with myeloma, the relapse clone apparently derived from a minor subclone at diagnosis. Such reordering of the spectrum of genetic lesions during therapy is likely to reflect selection of genetically distinct subclones not initially competitive against the dominant population that survived chemotherapy, thrived and acquired new anomalies. In addition we found that emergence of minor subclones at relapse was significantly associated with bortezomib treatment. Altogether, these data support the idea of new strategy of future clinical trials in MM that would combine targeted therapy and subpopulations control to eradicate all myeloma subclones in order to obtain long-term remission.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series

first: Laurence

last: Lodé

middle: C


title: Co-expression of genes with ERG in prostate cancers and cell lines

status: Public on Feb 11 2013

city: Rotterdam

first: Guido

last: Jenster

department: Urology

country: Netherlands

institute: Erasmus MC

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


title: The role of Ldb1 in hemangioblast development: genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis (Affymetrix)

city: Oxford

first: Supat

last: Thongjuea

address: Headington

department: MRC Molecular Haematology Unit

institute: The Weatherall Institute of Molecular Medicine

summary:
The first site exhibiting hematopoietic activity in mammalian development is the yolk sac blood island, which originates from the hemangioblast. Here we performed differentiation assays, as well as genome-wide molecular and functional studies in BL-CFCs to gain insight into the function of the essential Ldb1 factor in early primitive hematopoietic development. We show that the previously reported lack of yolk sac hematopoiesis and vascular development in Ldb1-/- mouse result from a decreased number of hemangioblasts and a block in their ability to differentiate into erythroid and endothelial progenitor cells. Transcriptome analysis and correlation with the genome wide binding pattern of Ldb1 in hemangioblasts revealed a number of direct target genes and pathways misregulated in the absence of Ldb1. The regulation of essential developmental factors by Ldb1 defines it as an upstream transcriptional regulator of hematopoietic/endothelial development. We show the complex interplay that exists between transcription factors and signaling pathways during the very early stages of hematopoietic/endothelial development and the specific signalling occurring in hemangioblasts in contrast to more advanced hematopoietic developmental stages. Finally, by revealing novel genes and pathways, not previously associated with early development, our study provides novel candidate targets to manipulate the differentiation of hematopoietic and/or endothelial cells.
We used microarrays to detail the global programme of gene expression underlying  the Ldb1+/+ and Ldb1-/- in Flk1+ cells.

overall_design: RNA was isolated from Ldb1+/+ and Ldb1-/- Flk1+ cells with the QIAGEN RNeasy Mini Kit and integrity was checked on the Agilent 2100 Bioanalyzer. RNA was converted to biotin-labelled cRNA, hybridised on the Mouse Genome 430 2.0 Array and analyzed with the Affymetrix GeneChip® Scanner 3000 according to the manufacturer protocol.

first: Athina

last: Mylona

first: Charlotte

last: Andrieu-Soler

first: Andrea

last: Martella

first: Eric

last: Soler

first: Rudd

last: Jorna

first: Jun

last: Hou

first: Christel

last: Kockx

first: Wilfred

last: van Ijcken

first: Boris

last: Lenhard

first: Frank

last: Grosveld


title: Gene expression data from rapamycin resistant and sensitive cell lines

status: Public on Feb 08 2013

city: NY

first: Hana

last: Totary-Jain

address: 150, St. NICHOLAS AVE

institute: Columbia University

summary: The mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation. Inhibitors of mTOR are being evaluated as anti-tumor agents. Given the emerging role of microRNAs (miRNAs) in tumorgenesis we hypothesized that miRNAs could play important roles in the response of tumors to mTOR inhibitors. Rapamycin resistant myogenic cells developed by long-term rapamycin treatment showed extensive reprogramming of miRNAs expression, characterized by up-regulation of the mir-17~92 and related clusters and down-regulation of tumor-suppressor miRNAs. Antagonists of oncogenic miRNA families and mimics of tumor suppressor miRNAs (let-7) restored rapamycin sensitivity in resistant tumor cells. This study identified miRNAs as new downstream components of the mTOR-signaling pathway, which may determine the response of tumors to mTOR inhibitors.

overall_design: Total RNA extraction and hybridization on Affymetrix microarrays  of rapamycin sensitive (RS) cells (BC3H1, mouse brain tumor cell line with myogenic properties, ATCC)  cultured in Dulbecco’s modified essential medium (DMEM) media supplemented with 20% fetal bovine serum (FBS), penicillin (100 U/ml) and streptomycin (100 mg/ml). Rapamycin resistant cells (RR1) were developed by culturing BC3H1 cells in the presence of 1 uM rapamycin for 6 months. Three samples in triplicates: 1) Rapamycin sensitive cells treated with DMSO for 24 h(BC3H1, reference), 2) Rapamycin sensitive cells treated for 24 h with 100 nM rapamycin (BC3H1+R), 3) Rapamycin resistant cells constantly treated with 1uM Rapamycion (RR1+R).

first: Despina

last: Sanoudo

first: Iddo

middle: Z

last: Ben-Dov

first: Cula

middle: N

last: Dautriche

first: Paolo

last: Guarieri

first: Steven

middle: O

last: Marx

first: Thomas

last: Tuschl

first: Andrew

middle: R

last: Marks


title: MicroRNAs and gene expression profiles of rapamycin sensitive and resistant myogenic tumor cell line

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


title: Expression data from developing mouse livers

status: Public on Feb 04 2013

city: Los Angeles

first: Kinji

last: Asahina

state: CA

address: 1333 San Pablo Street

department: Pathology

institute: University of Southern California

summary:
Roles of mesothelial cells (MCs) are poorly understood during liver development and injury. We identified podoplanin (Pdpn) as a cell surface markers for mesothelial cells in E12.5 mouse developing liver.
To identify genes uniquely expressed in MCs, we isolated MCs from E12.5 mouse livers by FACS using anti-Pdpn antibodies and performed microarray analysis.

overall_design: The E12.5 liver was digested with trypsin-EDTA and incubated with antibodies against Pdpn.  MCs were isolated as Pdpn+ population by FACS. Total RNA was extracted with RNAqueous Micro (Ambion) and the probes for the microarray were synthesized using the Ovation RNA amplification system V2 and FL-Ovation cDNA Biotin module V2 (Nugen). The labeled probes were hybridized with GeneChip Mouse Genome 430 2.0 arrays (Affymetrix) and signals were analyzed with Genomic Suite software (Partek).


title: The transcription factor Otx2 regulates choroid plexus development and function

status: Public on Feb 05 2013

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum Muenchen

summary: The choroid plexuses (ChPs) are the main regulators of cerebrospinal fluid (CSF) composition and thereby also control the composition of a principal source of signaling molecules that is in direct contact with neural stem cells in the developing brain. The regulators of ChP development mediating the acquisition of a fate that differs from the neighboring neuroepithelial cells are poorly understood. Here, we demonstrate in mice a crucial role for the transcription factor Otx2 in the development and maintenance of ChP cells. Deletion of Otx2 by the Otx2-CreERT2 driver line at E9 resulted in a lack of all ChPs, whereas deletion by the Gdf7-Cre driver line affected predominately the hindbrain ChP, which was reduced in size, primarily owing to an increase in apoptosis upon Otx2 deletion. Strikingly, Otx2 was still required for the maintenance of hindbrain ChP cells at later stages when Otx2 deletion was induced at E15, demonstrating a central role of Otx2 in ChP development and maintenance. Moreover, the predominant defects in the hindbrain ChP mediated by Gdf7-Cre deletion of Otx2 revealed its key role in regulating early CSF composition, which was altered in protein content, including the levels of Wnt4 and the Wnt modulator Tgm2. Accordingly, proliferation and Wnt signaling levels were increased in the distant cerebral cortex, suggesting a role of the hindbrain ChP in regulating CSF composition, including key signaling molecules. Thus, Otx2 acts as a master regulator of ChP development, thereby influencing one of the principal sources of signaling in the developing brain, the CSF.

overall_design: We performed gene expression microarray analysis of fourth ventricular choroid plexus tissue from Otx2 k.o. mice compared to wildtype mice from the same litters.

first: Pia

last: Johansson

first: Martin

last: Irmler

first: Dario

last: Acampora

first: Antonio

last: Simeone

first: Magdalena

last: Goetz


title: Differentially expressed genes between oncogene-transformed and non-transformed fetal liver progenitor cells

status: Public on Feb 02 2013

city: Shanghai

first: Yongzhong

last: Liu

address: Xietu Road 2200, 25

country: China

institute: Shanghai Cancer Institute

summary: The activation of different oncogenic signals may primarily contribute to the heterogeneity of cancer cells. However, the exact mechanisms underlying different oncogenic transformation are still unclear. We used the c-Myc, H-Ras and Akt transformed liver cell model to define mRNA expression profiles in the non-transformed and the three types of oncogene-transformed cells

overall_design: Purified p53-/- mouse fetal liver progenitor cells were transformed by three oncogenic genetic factors, c-Myc, H-RasV12 and myristoylated-AKT1(myr-Akt). The gene expression profilings of transformed cells and control cells were analyzed through microarray.

first: Aihui

last: Ma


title: Effects of Dcp1a and Dcp2 knockdown during mouse oocyte maturation

status: Public on Feb 06 2013

city: Prague 4

first: Matyas

last: Flemr

address: Videnska 1083

country: Czech Republic

institute: Institute of Molecular Genetics

summary:
Oocyte maturation is accompanied by a transition from mRNA stability to instability.  We investigated the role of DCP1A and DCP2, proteins responsible for mRNA decapping,  in mRNA destabilization during mouse oocyte maturation.
siRNA-mediated knockdown of both Dcp1a and Dcp2 transcripts prior to initiation of maturation inhibited the maturation-associated increase of DCP1A and DCP2, stabilized a set of maternal mRNAs that are normally degraded during maturation, and inhibited development beyond the 2-cell stage, likely a consequence of failure to activate fully the zygotic genome.

overall_design: Total RNA from 30 MII eggs was used in each sample. Three independent biological replicates were analyzed for each condition.

first: Jun

first: Petr

last: Svoboda

first: Richard

middle: M

last: Schultz


title: A predictive signature gene set for discriminating active from latent TB in Warao Amerindian children

city: Utrecht

first: Aldert

last: Zomer

address: Yalelaan 1

department: Department of Infectious Diseases and Immunology,Faculty of Veterinary Medicine

institute: Utrecht University

summary:
While blood transcriptional profiling has improved diagnosis and understanding of disease pathogenesis of adult tuberculosis (TB), no studies applying gene expression profiling of children with TB have been described so far. In this study, we have compared whole blood gene expression in childhood TB patients, as well as in healthy latently infected (LTBI) and uninfected (HC) children in a cohort of Warao Amerindians in the Delta Amacuro in Venezuela. We identified a 116-gene signature set by means of random forest analysis that showed an average prediction error of 11% for TB vs. LTBI and for TB vs. LTBI vs. HC in our dataset. Furthermore, a minimal set of only 9 genes showed a significant predictive value for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. Additionally, a minimal gene set of 42 genes with a comparable predictive value to the 116-gene set in both our dataset and the previously published literature cohorts for the comparsion of TB vs. LTBI vs. HC was identified. In order to identify a robust representative gene set that would hold stand among different ethnic populations, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these ten genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to diagnose 78% of the TB cases correctly with 100% specificity.   We conclude that our data justify the further exploration of our signature set as biomarkers to diagnose childhood TB. Furthermore, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts.
In this study, 27 children 1 to 15 years of age with TB (n=9), LTBI (n=9) and HC (n=9) were recruited between May 2010 and December 2010. Tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assay (QFT-GIT) were performed on all children. A sputum sample was collected from all children with expectoration and a gastric aspirate was taken from all children under 6 years of age. Children with active TB were diagnosed based on culture of M. tuberculosis (n=2) or on the basis of clinical, epidemiological and radiological features (n=7). The latter group were children with a TST = 10 mm or a positive QFT-GIT result who presented all of: persistent fever >38°C objectively recorded daily for at least two weeks, persistent cough for more than three weeks, weight loss (>5% reduction in weight compared with the highest weight recorded in last three months) or failure to thrive (documented crossing of percentile lines in the preceding three months), persistent lethargy or decrease in playfulness/activity reported by the parent and absence of clinical response on broad-spectrum antibiotics. Standard antero-posterior and lateral chest radiographs (CXRs) were taken from all children. Two independent experts, blinded to all clinical information, evaluated the CXRs and documented their findings on a standard report form. Where the two objective experts disagreed, a third expert was consulted and final consensus was achieved. A diagnosis of TB was only made when the CXR was consistent with TB9 and the child showed a positive clinical response to anti-TB treatment. Children were followed up clinically, radiologically and, in case of a negative TST at inclusion, by means of TST at six and 12 months after inclusion. LTBI was defined as a TST = 10mm and a positive QFT-GIT with a negative culture result on inclusion in the absence of radiological and clinical evidence of TB disease on inclusion as well as on t=6 and t=12 months. HC were children with a TST = 0 mm at inclusion and at t=6 and t=12 months. The HC had a negative QFT-GIT and a negative culture result at inclusion without radiological or clinical evidence of TB disease on inclusion nor on t=6 and t=12 months. TB patients were sampled before initiation of anti-TB treatment. Of three of the nine TB patients, a follow-up sample was taken when the patient was in anti-TB treatment for five months. All children were HIV-negative.

overall_design: 27 samples in total where analyzed,  active TB infection (TB, n=9), Latent TB infection (LTBI, n=9) and healthy controls (HC, n=9) . Gene expression values were log2-transformed and differentially expressed genes were identified based on log2 fold changes (M-values). P values were calculated with a Bayes-regularized one-way ANOVA. Random Forest recursive feature elimination was used to find a signature geneset capable of discrimination active TB from latent TB and from non-infected individuals.

first: Lilly

last: Verhagen


title: GATA factors efficiently direct cardiac fate from ESCs

city: New York

first: Todd

last: Evans

state: New York

address: 1300 York Avenue  Box 282

institute: Weill Medical College of Cornell University

summary:
Gata5 efficiently promotes cardiomyocyte fate from murine ESCs.By removing serum from the culture conditions, GATA4 and GATA6 are each also able to efficiently promote cardiogenesis in ESC derivatives, with some distinctions. Thus, GATA factors can   function in ESC derivatives upstream of other cardiac transcription factors to direct specification of progenitors with cardiac potential.
We used microarray to compared the global gene expression of Gata5-induced cardiac cells with other growth factor directed ESC-derived cardiac cells

overall_design: iGata5 ESCs were induced with doxycycline at day 4 and harvested at day16 for RNA extraction and hybridization on Affymetrix microarrays.

first: Harma

middle: K

last: Turbendian

first: Miriam

last: Gordillo

first: Su-Yi

last: Tsai

first: Jia

last: Lu

first: Guoxin

last: Kang

first: Ting-Chun

first: Alice

last: Tang

first: Susanna

first: Glenn

middle: I

last: Fishman


title: Co-expression of genes with ERG in prostate cancers

first: Guido

last: Jenster

summary: ERG overexpression is the most frequent molecular alteration in prostate cancer. We analyzed different stages of prostate cancer to identify genes that were coexpressed with ERG overexpression. In primary prostate tumors, it was shown that TDRD1 expression was the strongest correlated gene with ERG overexpression and we suggest TDRD1 as a direct ERG target gene.

overall_design: 48 Prostate cancer samples from radical prostatectomies were included in this study. These samples contained more than 70% cancer and less than 30% stromal tissue. Each sample was analyzed once.

first: Joost

middle: L

last: Boormans

first: Jan

last: Trapman


title: Expression data from mouse ALDH1 positive and ALDH1 negative ovarian surface epithelium (OSE) cells

status: Public on Jan 31 2013

city: Ithaca

first: Alexander

last: Nikitin

address: T2 014A VRT Campus Road

department: Biomedical Sciences

institute: Cornell University

summary:
The hilum region of the mouse ovary, the transitional/junction area between OSE, mesothelium and tubal (oviductal) epithelium is identified as a previously unrecognized stem cell niche of the OSE. OSE cells with high ALDH1 activity have been predominantly detected in the hilum region by immunohistochemical staining.
For additional phenotypical characterization, we used microarrays to detail the gene expression profiling between the ALDH1 positive and ALDH1 negative OSE cells.

overall_design: Three independent pools (10 mice each) were analyzed. ALDH1 positive and ALDH negative OSE cells were isolated by FACS and their mRNA used for hybridization onto Affymetrix Mouse Genome 430 2.0 array. Microarray data were analyzed with GeneSifter software. To identify genes significantly altered in ALDH positive population, we performed paired two group analysis with Significance Analysis of Microarrays (SAM) software and visualized with Treeview software.

middle: Y

first: Chang-il

last: Hwang


title: Co-expression of genes with ERG in prostate cancer cell lines

overall_design: 6 Prostate cancer cell lines and 11 prostate cancer xenografts are included in this study. Each sample was analyzed once.


title: Expression data from Ly6G+ and Ly6G- dendritic cells (DC)

status: Public on Feb 01 2013

city: Toledo

first: Hironori

last: Matsushima

state: OH

address: 3000 Arlington Avenue Mail Stop 1021

department: Medical Microbiology and Immunology

institute: University of Toledo College of Medicine

summary: To investigate the functional properties of Ly6G+ DC,  we employed GeneChip analysis to compare the gene expression profiles between Ly6G+ DC and Ly6C- DC.

overall_design: Crude bone marrow (BM) cells prepared from C57BL/6 mice were cultured in the presence of GM-CSF. On day 6, CD11c+/MHC II+/Ly6G+ cells and CD11c+/MHC II+/Ly6G- cells were simultaneously sorted from the same cultures by FACSAria. Total RNA were extracted and hybridized on Affymetrix microarrays.

first: Shuo

last: Geng

first: Akira

last: Takashima


title: Evaluation of effect of PTEN gene deletion in mouse CD4+ Th1 clones after stimulation

city: Chicago

first: yuanyuan

last: zha

state: IL

department: Department of Pathology

institute: University of Chicago

summary: PTEN is thought to play a critical role in T cell activation by negatively regulating the PI3K signaling pathway important for cellular activation, growth, and proliferation.  T cells from mice in which PTEN was conditionally deleted in the thymus were reported to display CD28-independent IL-2 production and relative resistance to anergy induction.  However, such observations could have stemmed from alterations in T cell development due to early deletion in thymocytes.  To directly eliminate PTEN in post-thymic T cells, we utilized CAR Tg x PTENflox/flox mice which enabled gene deletion using a Cre adenovirus in vitro.  Gene expression profiling revealed a small subset of induced genes that were augmented upon PTEN deletion and T cell stimulation.  Our results indicate that deletion of PTEN can augment the activation of post-thymic T cells.  Nonetheless, PTEN inhibition may be a viable target for immune potentiation due to increased cytokine production by activated CD4+ cells.

overall_design: It was of interest to determine the spectrum of transcripts regulated by PTEN using gene expression profiling.  To this end, CAR Tg x PTENflox/flox Th1 clones were either treated with adeno-Cre or adeno-EV, then confirmed to have PTEN protein abscence by western blot, then stimulated for 6 hours with anti-CD3/anti-CD28 mAb- coated beads and analyzed (2 total conditions). The experiment was replicated so there are 2 samples for each condition.

first: Frederick

last: Locke

first: Thomas

middle: F

last: Gajewski

first: Yuanyuan

last: Zha


title: Gene expression profile in platelets of mouse regulated by Smad4 gene

status: Public on Jan 29 2013

first: Junling

last: Liu

address: No.280 Chongqing Road

institute: Shanghai Jiaotong University

summary:
Mutations of SMAD family member 4 (Smad4) gene caused Hereditary Hemorrhagic Telangiectasia (HHT). It was believed that bleeding disorders were caused by arteriovenous malformation in this syndrome. Although several studies indicated dysfunction of platelets from HHT patient, the role(s) of smad4 in platelet function has not been examined. In this study, using megakaryocyte/platelet-specific Smad4-deficient mice, we investigated the physiological function of Smad4 in platelet activation and the underlying mechanism.
Microarray data demonstrated that the level of mRNA for multiple genes changed in Smad4 deficient platelet.

overall_design: For microarray analysis, total mRNA was extracted from washed platelets from Smad4f/f or Smad4−/− mice (for each group, n=6). mRNA was labeled and hybridized to Affymetrix Mouse Genome 430 2.0 chips according to manufacturer's instructions (Affymetrix).

first: Yanhua

last: Wang


title: Histone H3K9 Methyltransferase G9a Represses PPARγ Expression and Adipogenesis [Affymetrix expression data]

first: Kai

last: Ge

state: MD

address: 50 South Dr Rm 4154

department: NIDDK

institute: NIH

summary: PPARγ promotes adipogenesis while Wnt proteins inhibit adipogenesis. However, the mechanisms that control expression of these positive and negative master regulators of adipogenesis remain incompletely understood. By genome-wide histone methylation profiling in preadipocytes, we find that among gene loci encoding adipogenesis regulators, histone methyltransferase (HMT) G9a-mediated repressive epigenetic mark H3K9me2 is enriched on the entire PPARγ locus. H3K9me2 and G9a levels decrease during adipogenesis, which correlates inversely with induction of PPARγ. Removal of H3K9me2 by G9a deletion enhances chromatin opening and binding of adipogenic transcription factor C/EBP-beta to PPARγ promoter, which promotes PPARγ expression. Interestingly, G9a represses PPARγ expression in an HMT activity-dependent manner but facilitates Wnt10a expression independent of its enzymatic activity. Consistently, deletion of G9a or inhibiting G9a HMT activity promotes adipogenesis. Finally, deletion of G9a in mouse adipose tissues increases adipogenic gene expression and tissue weight. Thus, by inhibiting PPARγ expression and facilitating Wnt10a expression, G9a represses adipogenesis.

overall_design: Examination of gene expression changes in G9a KO brown preadipocytes

first: Lifeng

first: Shiliyang

last: Xu


title: Expression data of mouse preoptic region 5 h after LPS-administration comparing wt and mPGES-1 KO mice.

city: Linköping

first: Camilla

last: Nilsberth

address: Cellbiology dept.

department: IKE

country: Sweden

institute: Linköping University

summary:
WT mice and mPGES-1 KO mice were treated with 120 mikrogram/kg LPS and sacrificed 5 h later.
The preoptic region was dissected by LCM and analyzed using GeneChip Mouse Genome 430 2.0 arrays (Affymetrix).

overall_design: Groups: WT LPS-treated versus mPGES-1 KO LPS-treated mice.


title: IL-33 induces a hypo-responsive human mast cell phenotype

city: Hamilton

first: Dan

last: Sturdevant

state: MT

address: 903 S 4th street

department: NIAID

summary: Interleukin-33 (IL-33) is elevated in afflicted tissues of patients with mast cell-dependent chronic allergic diseases. Based on its acute effects on mouse mast cells (MCs), IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of chronic IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. We now find that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to antigen. This reduction required >72 h exposure to IL-33 for onset and 1-2 wk for reversion following IL-33 removal. This hypo-responsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation including antigen-mediated calcium mobilization and cytoskeletal reorganization; potentially as a consequence of down-regulation of the expression of PLCg1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to down-regulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease.

overall_design: Mouse bone marrow-derived mast cells treated with IL3 or IL3+IL33. 6 replicates each.

first: Mi

last: Jung

first: Daniel

last: Smrž

first: Avanti

last: Desai

first: Geethani

last: Bandara

first: Tomonobu

last: Ito

first: Shoko

last: Iwaki

first: Jeang

middle: H

last: Kang

first: Michael

last: Beaven

first: Dean

last: Metcalfe

first: Alasdair

last: Gilfillan


title: Expression data from the adipose tissue of mice fed a normal diet and a high fat diet.

status: Public on Jan 30 2013

city: Hidaka

first: Yasushi

last: Okazaki

state: Saitama

address: 1397-1 Yamane

department: Research Center for Genomic Medicine

country: Japan

institute: Saitama Medical University

summary:
To identify novel Peroxisome Proliferator-Activated Receptor gamma (PPARg) responsive secretory and/or transmembrane genes that is related to obesity, we integrated the expression data from the adipose tissue derived from obese mice with the other two data sets: expression profiling of adipocyte differentiation using ST2 cells and siRNA-mediated knockdown of Pparg during ST2 cell adipogenesis.
We used microarrays to detect the up-regulated genes in adipose tissue derived from mice fed a high fat diet compared to a control.

overall_design: Total RNA from adipose tissue was obtained and from mice fed a high fat diet HFD32 (MOUSE_HFD) from 6 week-old to 18 week-old, or a normal diet CE-2 (MOUSE_ND) as a control. Pooled RNAs of each three animals were analyzed by the Affymetrix GeneChip microarray system.

first: Yzumi

last: Yamashita-Sugahara

first: Yoshimi

last: Tokuzawa

first: Yutaka

last: Nakachi

first: Yukiko

last: Kanesaki-Yatsuka

first: Yosuke

last: Mizuno


title: The Molecular Signature Induced by HMGA1 During Lymphoid Tumorigenesis

city: Baltimore

first: Linda

last: Resar

address: 720 Rutland Ave

department: Hematology

institute: Johns Hopkins University

summary: We are exploring the molecular pathways activated during lymphoid transformation with the long term goal of developing better therapies. Our focus is the HMGA1a oncogene because our studies indicate that it plays an important role in aggressive human lymphoid leukemia and lymphoma. We have developed the transgenic mouse over-expressing HMGA1a in lymphoid cells that develop aggressive lymphoid tumors by 8-10 months with histopathologic findings resembling human T-cell acute lymphocytic leukemia. By analyzing the gene expression profiles of our HMGA1a mouse model we plan to identify molecular pathways activated by HMGA1a in lymphoid transformation. Results from these studies will enhance our understanding of the pathogenesis of lymphoid malignancies and should lead to the development of better therapies.

overall_design: A total of 20,669 genes represented on the Affymetrix Mouse 430 2.0 GeneChipTM array were screened with cRNA prepared from lymphoid cells of HMGA1a transgenic mice at different stages in tumorigenesis. These mice develop lymphoid tumors with complete penetrance at 8-12 months of age. We isolated RNA from splenocytes at 2 months (before tumors develop) and at 12 months (after tumors are well-established). These results were compared to splenocytes from control littermates. We used two statistical approaches to define differentially expressed genes, including a parametric (Partek genomics suite analysis) and nonparametric (CAM) approach.

first: Andrew

last: Schuldenfrei

first: Jeanne

last: Kowalski

first: Hua-Ling

last: Tsai

first: Conover

last: Talbot

first: Amy

last: Belton


title: Gene expression data from the mesenchymal stem cell line OP9M2 that supported expansion of human hematopoietic stem and progenitor cells in vitro

first: Mattias

last: Magnusson

address: 621 Charles E Young Drive South, 2204

department: MCDB

institute: UCLA

summary: One of the long-standing goals in the field has been to establish a culture system that would allow maintenance of HSC properties ex vivo. In the absence of such system, the ability to model human hematopoiesis in vitro has been limited, and there has been little progress in the expansion of human HSCs for clinical application. To that end, we defined a mesenchymal stem cell co-culture system based on a monoclonal OP9 stromal cell line (OP9M2), for expansion of clonally multipotent human HSPCs that were protected from apoptosis and immediate differentiation, and retained the HSPC phenotype. To identify the supportive mechanisms, we performed a genome-wide gene expression analysis of OP9M2 stromal cells and compared the expression to a non-supportive stomal line (BFC012). This co-culture system provides a new, well-defined platform for studying mechanisms involved in HSC-niche interactions and protection of critical HSC properties ex vivo.

overall_design: To determine the cellular identity and the supportive mechanism of the OP9M2 cells, we compared the OP9M2 cells with non-supportive BFC012 stromal cells using Affymetrix mouse microarrays.

first: Maria

last: Sierra

first: Rajkumar

last: Sasidharan

first: Sacha

last: Prashad

first: Pamela

last: Saarikoski

first: Melissa

last: Romero

first: Ben

last: Van Handel

first: Andy

last: Huang

first: Xinmin

last: Li

first: Hanna

last: Mikkola


title: Different levels of canonical Wnt signaling exert distinct roles in the colonic epithelium

status: Public on Jan 22 2013

city: Tokyo

first: Yasuhiro

last: Yamada

address: 7-3-1 Hongo, Bunkyo-ku

department: Department of Molecular Pathology

institute: University of Tokyo

summary: There is a gradient of β-catenin expression along the colonic crypt axis with the highest levels at the crypt bottom. However, it remains unclear whether different levels of canonical Wnt signaling exert distinct roles in the colonic epithelium. In the present study, we first showed that the canonical Wnt signaling is active in the proliferative compartment of normal colonic crypts by separating actively proliferating progenitor cells from non-proliferating cells in the colon using transgenic mice expressing a histone H2B-green fluorescent protein (GFP) fusion protein under the control of a tetracycline responsive regulatory element. Subsequently, we investigated the dose-dependent effect of canonical Wnt activation on colonic epithelial differentiation by controlling the expression levels of stabilized β-catenin using a doxycycline-inducible transgenic system in mice. We show that elevated levels of Wnt signaling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells. In contrast, lower levels of β-catenin induction enhanced cell proliferation rates of epithelial progenitors without affecting crypt fission rates. Notably, slow-cycling cells produced by β-catenin activation exhibit activation of Notch signaling and the treatment of β-catenin expressing mice with a Notch inhibitor turned such slow-cycling cells into actively proliferating cells. Our results indicate that the activation of the canonical Wnt signaling pathway is sufficient for de novo crypt formation, and suggest that different levels of canonical Wnt activations, in cooperation with Notch signaling, establish a hierarchy of slower-cycling stem cells and faster-cycling progenitor cells characteristic for the colonic epithelium.

overall_design: To separate actively proliferating cells from non-proliferating cells in normal colon, we used transgenic mice expressing a histone H2B-GFP fusion protein under the control of a tetracycline responsive regulatory element (H2B-GFP mice). In H2B-GFP mice, all colonic crypt cells exhibited strong nuclear GFP signal 7 days after doxycycline administration. When doxycycline was withdrawn for 2 days after the labeling period, nuclear GFP signal was diluted in proliferating cells whereas non-proliferating cells retained GFP. GFPhigh non-proliferating and GFPlow proliferating epithelial cells were sorted from the isolated crypts by FACS for microarray analysis. In addition, to investigate the effects of acute Wnt activation in colon, we generated doxycycline-inducible β-catenin mice. Colonic crypts were isolated from untreated mice and mice fed doxycycline in the drinking water (2.0 mg/ml) for 5 days and subjected to microarray analysis.

first: Akihiro

last: Hirata

first: Satoshi

last: Yamashita


title: Global transcriptomic profiling of nitric oxide-mediated neuronal death

status: Public on Jan 23 2013

city: Hobart

first: Minghui Jessica

last: Chen

state: Tasmania

address: Menzies Research Institute, University of Tasmania, Private Bag 24

department: Neuroscience group

country: Australia

institute: Menzies Research Institute

summary:
Nitric oxide (NO) is implicated in the pathogenesis of various neuropathologies characterised by oxidative stress. NO has been reported to be involved in the exacerbation of oxidative stress by various mechanisms, including protein modification, genotoxic damage and elevated production of reactive oxygen species resulting in deregulation and disruption of cellular homeostasis.
Although multiple roles for NO has been reported in neuronal death signaling, existent data fail to provide a holistic description of how nitrergic pathobiology elicits neuronal injury. Here we provide a comprehensive description of mechanisms contributing to NO-induced neuronal injury by global transcriptomic profiling.

overall_design: Microarray analysis was carried out using 14 GeneChip Mouse Genome 430 2.0 array (Affymetrix, Santa Clara, CA). The assignment of the arrays (GeneChip) was as follows: vehicle-treated control (n=5); NOC-18-treatment for 8, 15 and 24 hour (n=3 for each time-point).

first: Nam

middle: S

last: Cheung

first: Minghui

first: Zhao

last: Peng

first: Jayapal

last: Manikandan


title: Trpm4-induced gene expression changes in Th1 and Th2 cells

city: St Louis

first: K. Scott

last: Weber

state: MO

address: 425 South Euclid Ave

institute: Washington University in St. Louis

summary:
T helper cell subsets have unique calcium (Ca2+) signals when activated with identical stimuli.  The regulation of these Ca2+ signals and their correlation to the biological function of each T cell subset remains unclear.  Trpm4 is a Ca2+-activated cation channel that we found is expressed at higher levels in Th2 cells compared to Th1 cells.  Inhibition of Trpm4 expression increased Ca2+ influx and oscillatory levels in Th2 cells and decreased influx and oscillations in Th1 cells.  This inhibition of Trpm4 expression also significantly altered T cell cytokine production and motility.  Our experiments revealed that decreasing Trpm4 levels divergently regulates nuclear localization of NFAT. Consistent with this, gene profiling did not show Trpm4 dependent transcriptional regulation and T-bet and GATA-3 levels remain identical.  Thus, Trpm4 is expressed at different levels on T helper cells and plays a distinctive role in T cell function by differentially regulating Ca2+ signaling and NFAT localization.
T helper cell gene expression levels when Trpm4 is inhibited by siRNA or dominant negative Trpm4 construct.

overall_design: The ion channel Trpm4 was inhibited in Th1 or Th2 cells using either siRNA or a dominant negative Trpm4 retrovirus and changes in gene profiles were analyzed.

first: K

first: P

last: Allen


title: Expression data from mammary gland during pregnancy and lactation of CBA/CaH, QSi5 and Advanced Intercross Line (AIL; CBA/CaH X QSi5, the 14th generation)

city: The University of Sydney

first: Jerry

last: Wei

state: NSW

address: B19  RMC Gunn

department: Facuulty of Veterinary Science

institute: University of Sydney

summary:
Previously we have shown significant differences in lactation performance, mammary gland histology and expression profiles of mammary transcriptome during peak-lactation (lactation day 9; L9) between the ordinary CBA/CaH (CBA) and the superior QSi5 strains of mice. In the present study, we compared mammary gland histology between CBA and QSi5 at mid-pregnancy (pregnancy day 12; P12). We assessed lactation performance during the first 8 days of lactation of the 13th - 14th generation of the Advanced Intercross Line (AIL) (CBA X QSi5) mice.
We utilized an integrative approach to analyzing mammary microarray expression profiles of CBA and QSi5 at P12 and CBA, AIL and QSi5 at L9.

overall_design: The inguinal mammary glands of CBA/CaH and QSi5 during mid-pregnancy (Pregnancy day 12; P12), and the glands of CBA/CaH, AIL and QSi5 during peak lactation (Lactation day 9; L9) were collected and total RNA was extracted for Affymetrix microarray (mouse genome 430 2) assay

first: Palaniappan

last: Ramanathan

first: Peter

last: Williamson


title: Regulation of the epithelial adhesion molecule CEACAM1 is essential for palate formation.

city: Suita

first: Takayoshi

last: Sakai

state: Osaka

address: 1-8 Yamadaoka

department: Oral-Facial Disorders

institute: Osaka Univ Grad Sch Dent

summary:
Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at the various developmental stages before, during, and after palate fusion using GeneChip? microarrays. Ceacam1 was one of the highly up-regulated genes during and after fusion in palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was expressed at a very low level in palatal epithelium before fusion, but highly expressed in the midline of the palate during and after fusion. To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture. Palatal fusion was inhibited by this function-blocking antibody. To investigate the subsequent  developmental role of CEACAM1, we characterized Ceacam1-deficient (Ceacam1-/-) mice. Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1-/- mice. TGF?3 expression, apoptosis, and cell proliferation in palatal epithelium were not effected in the palate of Ceacam1-/-mice. CEACAM1 expression was down-regulated in Tgfb3-/- palate. However, exogenous TGF?3 did not induce CEACAM1 expression. These results suggest that CEACAM1 has roles in both the initiation of palate formation via epithelial cell adhesion and TGF signaling has some indirect effect on CEACAM1.

Global gene expression profiling of palatal processes before, during and after fusion of palatal shelves
We used microarray to investigate the gene expression of palatal tissue during palatal development.

overall_design: Palatal processes were microdissected  at the stages of palatal development (before, during and after fusion) for RNA extraction and hybridization on Affymetrix microarrays.


title: Expression data from mouse T cells after CLIP (Crosslinking immunoprecipitation) procedures (mRNA)

status: Public on Jan 19 2013

city: Ann Arbor

first: yaping

last: sun

state: Michigan

address: 1500 E Medical Center Dr.

department: internal medicine

institute: university of michigan

summary:
Molecular networks based on genome-wide mRNA and miRNA expression in activated T cells are interated by co-regulation with miRNA and protein-coding genes during immune responses, however, accurate prediction of miRs and their targets remains a challenge. Furthermore, the specific changes in the expression of miRNAs and/or mRNAs in allogeneic activated T cells during HCT would be distinct from those responding to non-specific stimulation.
Recently, Ago-CLIP has been demonstrated to provide a robust platform for identification of precise miRNA-mRNA interactions by definitively distinguishing direct from indirect miRNA-target interactions. We utilized CLIP procedure followed by screening with standard microarray platforms for miRNA and mRNA transcripts to demonstrate the miR-mRNA landscape and identify novel molecular targets for modulating T cell responses.

overall_design: Mixed cell culture was performed with T cells in the presence of syngeneic 57BL/6, or allogeneic BALB/c dendritic cells or cultivated with anti-CD3e and anti-CD28 mAB9 for 24 h.  Purified T cells were processde for CLIP procedures and followed by RNA isolation (TRIzol LS and miReasy Kit) and hybridization on Affymetrix microarrays and Exiqon 6th generation miRCURY LNA microRNA Arrays . We sought to obtain that the specific changes in the expression of miRNAs and/or mRNAs in allogeneic activated T cells during hematopoietic cells transplantation and that would be distinct from those responding to non-specific stimulation.

first: Yaping

last: Sun

first: Pavan

last: Reddy


title: Expression data from mouse T cells after CLIP (Crosslinking immunoprecipitation) procedures

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

overall_design: Refer to individual Series


title: Expression data from WT and E2A-deficient murine DN2 cells

first: Barbara

last: Kee

address: 924 East 57th Street

department: Pathology

summary: The E2A transcription factors promote the development of thymus-seeding cells but it remains unknown whether these proteins play a role in T lymphocyte lineage specification or commitment. By examining E2A-dependent genes in developing T cells, we will address whether these proteins are involved in these processes.

overall_design: DN2 cells from WT and E2A-deficient murine fetal thymi were FACS sorted. Subsequently RNA was extracted, labelled and hybridized to Affymetrix microarrays. The goal of this study is to investigate E2A-dependent genes in developing T cells

first: Wei

last: Xu

first: Tiffany

last: Carr

first: Kevin

last: Ramirez

first: Stephanie

last: McGregor

first: Mikael

last: Sigvardsson


title: Hepatic glucose sensing is required to preserve beta-cell glucose competence

status: Public on Jan 18 2013

city: Lausanne

first: Frédéric

last: Schütz

address: Batiment Amphipole

country: Switzerland

institute: Swiss Institute of Bioinformatics

summary: We assessed the impact of glucose transporter Glut2 gene inactivation in adult mouse liver (LG2KO mice). This suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was normal early after Glut2 inactivation but intolerance developed at later time. This was caused by progressive impairment of glucose-stimulated insulin secretion even though beta-cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinate down-regulation of cholesterol biosynthesis genes in LG2KO mice. This was associated with reduced hepatic cholesterol in fasted mice and a 30 percent reduction in bile acid production. We showed that chronic bile acids or FXR agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from fxr-/- mice. Collectively, our data show that glucose sensing by the liver controls beta-cell glucose competence, through a mechanism that likely depends on bile acid production and action on beta-cells.

overall_design: three replicates each of ps_ctrl_refed, ps_tamox_refed, ps_ctrl_fasted, ps_tamox_fasted

first: Pascal

last: Seyer

first: David

last: Vallois

first: Carole

last: Poitry-Yamate

first: Salima

last: Metref

last: Tarussio

first: Pierre

last: Maechler

first: Bart

last: Staels

first: Bernard

last: Lanz

first: Rolf

last: Grueter

first: Julie

last: Decaris

first: Scott

last: Turner

first: Anabela

last: da Costa

last: Preitner

first: Kaori

last: Minehira

first: Marc

last: Foretz

last: Thorens


title: Notch Pathway Activation Targets AML Cell Homeostasis and Differentiation: MLL-AF9 transformed LGMP

city: Paris

first: Camille

last: Lobry

address: 16 rue de la Grange aux Belles

department: IRSL Inserm U944 / CNRS UMR7212

institute: Inserm

summary: To determine role of Notch signaling in AML leukemia initiating cells we used a conditional mouse knock-in model of Notch1-IC to induce Notch1-IC expression in MLL-AF9 transformed LGMP. WT and Notch1-IC+ LGMP were analyzed to determined genes controlled by Notch signaling.

overall_design: 12 weeks old wt lethaly irradiated mice were transplanted with 50000 cKit+ MLL-AF9-IRES-YFP infected cells from MLL-AF9 EF1 wt/wt ROSAwt/CreERT2 or MLL-AF9 EF1 wt/lsl-N1-IC ROSAwt/CreERT2 mice + 250000 support wt total bone marrow cells. 4 weeks after transplant mice were injected 2 times with tamoxifen (0.2mg/g body weight) every other day. Mice were sacrificed and analyzed 6 days after last injection. LGMP were flow purified for RNA extraction and hybridization on Affymetrix microarrays.

first: Iannis

last: Aifantis


title: PRDM14 Ensures a Naïve Pluripotency by a Dual Mechanism Involving Signaling and Epigenetic Pathways in Mouse Embryonic Stem Cells

city: Nara

first: Kazuki

last: Kurimoto

address: 840 Shijo-Cho, Kashihara

department: School of medicine

institute: Nara Medical University

summary: Mouse embryonic stem cells (mESCs) fluctuate between a naïve inner cell mass (ICM)-like state and a primed epiblast-like state of pluripotency in serum, but are harnessed exclusively in a distinctive, apparently more naïve state of pluripotency (the ground state) with inhibitors for mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i).  Understanding the mechanism ensuring a naïve state of pluripotency would be critical in realizing a full potential of ESCs.  We show here that PRDM14, a PR domain-containing transcriptional regulator, ensures a naïve pluripotency by a dual mechanism: Antagonizing fibroblast growth factor receptor (FGFR) signaling that is activated paradoxically by the core transcriptional circuitry for pluripotency and directs a primed state and repressing de novo DNA methyltransferases that create a primed epiblast-like epigenome.  PRDM14 exerts these functions by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression.

overall_design: Mouse Embryonic Stem Cells (mESCs) or mESC-like cells with different Prdm14 genotypes {Prdm14(+/+), Prdm14(-/-), and Prdm14(-/-) rescued with Avitag-EGFP-Prdm14 transgene [Prdm14(-/-)+AGP14]} are cultured on MEF in different medium [2i, Serum(day 2), Serum+MEK inhibitor (PD0325901) (day 2), Serum without LIF (day2)].

first: Masashi

last: Yamaji

first: Jun

last: Ueda

first: Katsuhiko

last: Hayashi

first: Hiroshi

last: Ohta

first: Yukihiro

last: Yabuta

first: Ryuichiro

last: Nakato

first: Yasuhiro

last: Yamada

last: Shirahige

first: Mitinori

last: Saitou


title: Gene expression of cerebellar granule cell layer

status: Public on Jan 17 2013

city: Uruma

first: Nozomu

last: Nakamura

state: Okinawa

address: 12-22 Suzaki

department: Molecular Neuroscience Unit

institute: Okinawa Institute of Science and Technology

summary:
We performed gene-expression analysis of mouse cerebellar granule cell layer as compared to that of Purkinje cells. DNA microarray analysis detected genes in cerebellar granule cell layer, most of which are classified into functional molecule categories.
Our comparative analysis between Purkinje cells and the granule cell layer showed that the characteristic expression pattern in Purkinje cells was particularly represented by “the neural communication system” components.

overall_design: Pukinje cells and granule cell layer of the mouse cerebellum were collected by laser microdissection for RNA extraction and hybridization on Affymetrix microarrays.

first: Kiyotaka

last: Akiyama

first: Takayuki

last: Naito


title: miR-1061 and miR-591 are involved in paclitaxel-resistance and their regulation increases the sensitivity to paclitaxel

city: Sungnam

first: Hee

last: An

address: 351 Yatap-dong

country: South Korea

institute: CHA University

summary: MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared to that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and real-time RT-PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays.

overall_design: Total RNA obtained from four different chemo-resistant subcell lines (skp 41,43,44,46) compared to parent cell line (skov3), human ovary cacinoma


title: Gene expression of cerebellar Purkinje cells and granule cell layer


title: Gene Expression-Based Classifiers Identify Staphylococcus aureus Infection in Mice and Humans

status: Public on Jan 11 2013

city: Durham

first: Sun Hee

last: Ahn

state: NC

address: Stead Bldg, RM 1546A

department: Medicine

institute: Duke University

summary: Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host’s inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 95 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.82). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.94, respectively).  The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections.  Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: To create a host gene expression-based classifier for S. aureus infection, mice from a variety of experimental conditions were utilized.  Seven different strains of inbred mice (n=187 total) were challenged with four different S. aureus strains via intraperitoneal inoculation and sacrificed at various time points as described in Methods.  The comparator group for model derivation included 50 A/J or C57BL/6J mice inoculated with E. coli (O18:K1:H7) as well as 54 uninfected mice. Next, the murine S. aureus classifier was externally validated in outbred CD-1 mice with S. aureus infection (Sanger 476 or USA300), E. coli infection (O18:K1:H7), or uninfected controls (10 animals per condition).   Method: All experiments were performed on mice 6-8 weeks old.  For the murine S. aureus predictor, seven inbred mouse strains (3 mice/strain: 129S1/SvImJ, A/J, AKR/J, BALB/cByJ, C57BL/6J, C3H/HeJ, and NOD/LtJ) were IP inoculated with 107 CFU/g of S. aureus Sanger476, euthanized at 2h after injection, and bled. This was repeated using four different S. aureus strains (USA100, USA300, MW2, and Sanger476) in A/J mice (n=3 per S. aureus strain). For time series experiments, both A/J and C57BL/6J mouse strains were IP inoculated with S. aureus Sanger476 as above, and sacrificed at 2, 4, 6, and 12h after injection (n=5 per time point).

first: Sun

first: Ephraim

last: Tsalik

first: Derek

last: Cyr

first: Yurong

last: Zhang

first: Raymond

last: Langley

first: Jennifer

last: van Velkinburgh

first: Seth

middle: W

last: Glickman

first: Charles

middle: B

last: Cairns

first: Aimee

last: Zaas

first: Emanuel

middle: P

last: Rivers

first: Ronny

last: Otero

first: Stephen

last: Kingsmore

first: Joseph

last: Lucas

first: Christopher

last: Woods

first: Tim

last: Veldman

first: Geoffrey

last: Ginsburg

first: Vance

middle: G

last: Fowler


title: Gene expression profiling of murine liver NK cells

status: Public on Jan 09 2013

city: Hefei

first: Hui

last: Peng

address: 443 Huangshan Road

institute: University of Science and Technology of China

summary: The NK cell pool is composed of distinct NK cell subsets with divergent phenotypic and functional features. In order to determine whether DX5- and DX5+ NK cells from murine livers represent different NK cell subsets, DX5- and DX5+ liver NK cells of adult mice were respectively sorted for gene expression analysis using the Affymetrix GeneChip Mouse Genome 430 2.0 arrays.

overall_design: DX5-NK1.1+CD3- cells and DX5+NK1.1+CD3- cells were sorted from the liver of naive B6 wild-type mice. RNA of each sample was then extracted and hybridized on Affymetrix microarrays to detail differences between DX5- and DX5+ liver NK cells in gene expression.

first: Xiaojun

last: Jiang

first: Yonglin

last: Chen

first: Haiming

last: Wei

first: Rui

last: Sun

first: Zhigang

last: Tian


title: Gene expression profiling of mouse B cell progenitors

status: Public on Jan 14 2013

city: Memphis

first: Shann-Ching

state: TN

address: 262 Danny Thomas Place

institute: St. Jude Children's Research Hospital

summary: Gene expression profiling was performed of Pax5 wild type bone marrow subsets from common lymphoid progenitors through to Hardy stage F cells. These cells were obtained by flow sorting of bone marrow.

overall_design:
Gene expression profiling was performed on 41 samples of RNA extracted from flow sorted B cell precursor populations from common lymphoid progenitor (CLP) through to Hardy stage F.
Note that several of the genes expressed in normal mouse B cell progenitors are also involved by deletion/mutation in hypodiploid ALL.
Related hypodiploid ALL studies:
Gene expression data: GEO GSE27237
SNP & Sequencing data: dbGaP phs000341.v1.p1

first: James

last: Downing

last: Mullighan


title: Effects of Hsp72 on astrocyte activation following stroke in the mouse

city: Stanford

first: Robin

last: White

address: Grant Building S272, 300 Pasteur Drive

department: Anesthesia

institute: Stanford University

summary: Astrogliosis is a hallmark of the response to brain ischemia, comprised of changes in gene expression and morphology. Hsp72 protects from cerebral ischemia, and although several mechanisms of protection have been investigated, effects on astrocyte activation are unknown.  To identify potential mechanisms of protection, gene expression was assessed in mice subjected to middle cerebral artery (MCAO) or sham surgery, of either wildtype (WT) or Hsp72-overexpressing (Hsp72Tg) mice. After stroke, both genotypes exhibited genes related to cell death, stress response, and immune response.  Furthermore, genes indicative of astrocyte activation, including cytoskeletal proteins and cytokines, were upregulated.  To measure astrocyte activation after stroke, detailed histological and morphological analyses were performed in the cortical penumbra after stroke using unbiased stereology.  Consistent with other reports, we observed a marked and persistent increase in glial fibrillary acidic protein (GFAP ) as soon as 3 hours after MCAO.  In contrast, vimentin immunoreactivity appeared 12-24 hours after stroke, peaked at 72 hours, and returned to baseline after 30 days.  Surprisingly, no change in overall astrocyte number was observed based on glutamine synthetase (GS) immunoreactivity.  To determine if Hsp72Tg mice exhibited altered astrocyte activation compared to WT controls, morphological evaluation by fractal analysis was used.  Overexpression of Hsp72 reduced astrocyte cell area, arbor area, and to a lesser extent fractal dimension, 72 hours following stroke.  In conclusion, in vivo overexpression of Hsp72 alters gene expression following stroke, including genes involved in astrocyte activation, and decreases astrocyte activation acutely following MCAO.  Thus, modulation of astrogliosis may be a neuroprotective mechanism exerted by Hsp72 after ischemia.

overall_design: A total of 10 samples were analyzed, with 5 of each genotype, wildtype (WT) and Hsp72-overexpressing (Hsp72Tg) mice.  Of the 5 in each group, 3 received middle cerebral artery occlusion (MCAO) and 2 received a sham surgery.  The sham samples serve as the controls for the MCAO samples in each genotype.  All samples were taken from the ischemic or control hemisphere 24 hours after surgery.

first: George

last: Barreto

first: Xiaoyun

first: Lijun

last: Xu

middle: E

first: John

last: Emery

first: Curtis

last: Palm

first: Rona

last: Giffard


title: Expression data from mouse colon tissue response  to T cell transfer at week 0, 2, 4 and 6

city: Shreveport

first: Kevil

last: Christopher

state: LA

address: 1501 Kings Highway

institute: Louisiana State University Health Science Center, Shreveport

summary:
Temporal geneome profiling of T cell transfer colitis model
T cells critically regulate clinical inflammatory bowel diseases and T cell dependent experimental colitis models have gained prominent favor as useful models to identify potential pathogenic mechanisms. The naïve CD4+CD45Rbhigh cell transfer model into recombinase activating gene-1 deficient (RAG-/-) mice induces both colitis and small bowel inflammation reflecting Crohn's disease with unclear pathogenic mechanisms. Given the pathological similarities between the T cell transfer model of colitis and clinical disease, we sought to identify changes in whole genome expression profiles over time during the delelopment of colitis.

overall_design: Male RAG-1-/- C57BL/6 mice were injected with a half million CD4+CD45RBhigh T cells from healthy wild type C57BL/6 male mice. The colon tissue from individual cohorts were collected at weeks 0, 2, 4 and 6. Total RNA were extracted from the colon tissue and detected by Affymetrix GeneChip Mouse Genome 430 2.0 Array.

first: C

last: Kevil

first: K

last: Fang


title: Effect of transgenic human IL8 on gene expression in mouse colon cancer tumors

city: New York

first: Timothy

middle: Cragin

last: Wang

state: NY

address: 1130 St. Nicholas Av

department: Medicine- Digestive and Liver Diseases

institute: Columbia University

summary:
mRNA expression in  colon cancer tumores
of CBA/C57BL/6 transgenic mice
bearing a BAC which contains the human IL8 gene and promoter
was compared to that of CBA/C57BL/6 controls.

overall_design:
A. CBA/C57BL/6 mice controls (n=3)
B. human IL8 transgenic CBA/C57BL/6 mice (n=3).

first: Samuel

last: Asfaha

first: Alexander

last: Dubeykovskiy

first: Hiroyuki

last: Tomita

first: Xiangdong

last: Yang

first: Sarah

last: Stokes

first: Wataru

last: Shibata

first: Richard

middle: A

last: Friedman

first: Hiroshi

last: Ariyama

first: Zinaida

last: Dubeykovskaya

first: Sureshkumar

last: Muthupalani

first: Russell

last: Ericksen

first: Harold

last: Frucht

last: Fox

middle: C


title: Gene expression of cerebellar Purkinje cells

first: Nozomu

last: Nakamura

summary:
We performed gene-expression analysis of mouse Purkinje cells as a model “single-type neuron”. DNA microarray analysis detected at least 7,055 genes in Purkinje cells, most of which are classified into functional molecule categories.
Our comparative analysis between Purkinje cells and the granule cell layer showed that the characteristic expression pattern in Purkinje cells was particularly represented by “the neural communication system” components.

first: Kiyotaka

last: Akiyama

first: Takayuki

last: Naito


title: Influence of T and B lymphocytes on the antigen presentation capacities of splenic conventional dendritic cells

city: Munich

first: Jacek

last: Puchałka

address: Lindwurmstrasse 2a

department: University Children's Hospital

institute: Munich University Hospital

summary: The goal of this project was to characterize DCs from lymphopenic mice, like RAG (recombination activated gene) deficient mice and to examine the influence of mature B and T cells on the antigen presenting ability of splenic cDCs. We demonstrate how cellular cross-talk can shape the character and function of cDCs. Lymphopenic conditions, where splenic cDCs have to develop and differentiate, drastically change their character and their ability to cross-present soluble antigen.

overall_design: In this approach we sorted out two populations (CD8α+ and CD8α-) of splenic dendritic cells (DCs) from untreated WT, and RAG2-/- C57Bl/6 mice. The age of mice was between 8-10 weeks. Further we isolated RNA and performed microarray analysis. Each DCs population was repeated twice.

first: Natalia

last: Ziętara

first: Marcin

last: Łyszkiewicz


title: Global gene expression profile and splicing events of iPS-derived motorneurons from SMA patient, unaffected father and TGC-treated cells

status: Public on Jan 04 2013

city: Milan

first: Stefania

last: Corti

address: via F. Sforza 35

department: Neurological Sciences

country: Italy

institute: University of Milan

summary:
Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease and is the second most common genetic disorder leading to death in childhood. Motoneurons derived from induced pluripotent stem cells (iPSC) obtained by reprogramming SMA patient and his healthy father fibroblasts, and genetically corrected SMA-iPSC obtained converting SMN2 into SMN1 with target gene correction (TGC), were used to study gene expression and splicing events linked  to pathogenetic mechanisms.
Microarray technology was used to assess the global gene expression profile as well as splicing events of iPS-derived motorneurons from SMA patient, unaffected father and TGC-treated cells.

overall_design: The microarray data derived from three different groups: SMA patient, healty father and treated SMA patient's cells. Each population consists of three RNA profiling cell samples.

first: Dario

last: Ronchi

first: Giulietta

last: Riboldi


title: Human transcriptome analysis of acute responses to glucose ingestion reveals a role of leukocytes in hyperglycemia induced inflammation.

status: Public on Jan 06 2013

city: Chungbuk

first: Kim

last: Hye-Ryun

address: Osong Health Technology Administration Comples

institute: Korea Centers for Disease Control & Prevention

summary: Objective was to examine acute gene expression responses to physiologic oral glucose ingestion in human circulating leukocytes. Microarray study of human circulating leukocytes sampled before, 1 hour after and 2 hours after glucose ingestion was performed. The present study demonstrated 36 genes which showed acute gene expression change in human leukocytes within 1 hour after glucose ingestion and suggest that leukocytes participate in the inflammatory process induced by acute hyperglycemia.

first: HyungJin

last: Choi

first: HyeSun

last: Yun


title: Expression data from livers in  wildtype and Sox17+/-mice at 17dpc

city: Tokyo

first: Mami

last: Uemura

address: Yayoi 1-1-1, Bunkyo-ku

department: Veterinary Anatomy

institute: The University of Tokyo

summary:
The onset of the liver inflamentation in the Sox17+/- embryos.
The expression of Cxcl10, Cxcl2, Cxcl1 and stress-induced heat shock protein Hspa1a and Hspa1b were elevated in Sox17+/- livers at 17dpc, as compared with the wildtype livers.

overall_design: Total RNAs from liver tissues of wildtype and Sox17+/- mice at 17dpc were subjected to microarray analyses. Two biological replicates of each genotype were analyzed.

first: Yoshiakira

last: Kanai


title: Expression data from cerebrum in a spontaneous mutant mouse, laggard.

status: Public on Jan 07 2013

city: Kobe

first: Toshiaki

last: Sakisaka

state: Hyogo

address: Kusunoki-cho 7-5-1, Chuou-ku

department: Physiology and Cell Biology

institute: Kobe University Graduate School of Medicine

summary:
We found a new spontaneous mutant mouse, laggard, characterized by general weakness in movements and retardation in growth.
We used microarray to identify genes whose expression levels are affected downstream from the mutation.

overall_design: RNA was extracted from the cerebrum of each mutant mouse or its littermate, performing hybridization to Affymetrix DNA chip with cRNA probe. The profiles were compared comprehensively between them to investigate the molecular pathology in the mutant mouse.


title: Gene expression data from adult postnatal cerebellum, prefrontal cortex and liver: comparison on tissue differences

city: Shanghai

first: Ning

last: Fu

address: 320# Yue-Yang Road

department: Shanghai Institute for Biological Sciences

institute: Chinese Academy of Sciences

summary:
To understand the roles of molecules in functional differentiation among adult human tissues, we performed a systematic survey of mRNA, protein, and protein phosphorylation as well as miRNA expression, in three tissues: cerebellum, prefrontal cortex and liver. We found that tissues were clearly distinct from one another at all levels. Furthermore, our results showed that miRNA differently expressed between tissues have significant, but modest effect on expression of mRNA and somewhat stronger effect on expression of proteins among the tissues.

Notably, miRNA preferentially targeted gene regulators, transcription factors and kinases, in all three tissues studied. Following this path, we found that miRNA effect was further amplified through expression changes of target transcription factors and kinases, leading to further changes in their targets’ expression and phosphorylation levels. Importantly, miRNA regulation leads to reduced, rather than increased gene expression variation among individuals between two brain regions. These observations uncover the complexity of miRNA regulatory interactions and are compatible with suggested role of miRNA in gene expression canalization.

overall_design: Adult human post-mortem tissue samples: cerebellum, prefrontal cortex and liver, were collected. Each tissue contains three individuals totalling 9 samples in this datasets. RNA extracted from these dissected tissue was hybridized to Affymetrix Human Exon 1.0 ST arrays.

first: Mehmet

last: Somel

first: Philipp

last: Khaitovich

first: Rong

last: Zeng


title: Transcriptional changes in intraepithelial CD4 lymphocytes

status: Public on Jan 08 2013

city: la jolla

first: Hilde

last: Cheroutre

state: California

address: 9420 athena circle

department: Developmental Immunology

institute: La Jolla Institute for Allergy and Immunology

summary:
We investigated transcriptional changes in CD4CD8aa and CD4 intraepthelial lymphocytes.
TCRαβ thymocytes differentiate to either CD8αβ cytotoxic T lymphocytes or CD4 T helper cells. This functional dichotomy is controlled by key transcription factors, including the T helper master regulator, ThPOK, which suppresses the cytolytic-program in MHC class II restricted CD4 thymocytes. ThPOK continues to repress CD8-lineage genes in mature CD4 T cells, even as they differentiate to T helper effector subsets. Surprisingly, we show here that the T helper-fate is not fixed and that mature antigen-stimulated CD4 T cells can switch off Thpok expression and reactivate CD8-lineage genes. This unexpected plasticity results in the post-thymic termination of the T helper program and the functional differentiation of distinct MHC class II restricted CD4 cytotoxic T lymphocytes.

overall_design: Intraepithelial_CD4_CD8a neg vs CD8a pos.  Two sample set of CD4CD8aa and CD4 intraepthelial lymphocytes (IEL) from small intestine of RAG knockout mice ( 8 weeks after transfer of naive CD4 cells, adoptive tranfer model of colitis), were prepared via  cell sorting, and RNA was prepared by TRIZol (Invitrogen, USA) . Data were analyzed in GeneSpring GX10.  For microarray analysis, RNA was labeled and hybridized to GeneChip Mouse Genome 430 2.0 arrays according to the Affymetrix protocols. Data were analyzed in GeneSpring GX10.


title: Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A

city: Gaithersburg

first: Zheng

last: Liu

address: One Medimmune Way

institute: Medimmune LLC

summary:
Toll-like receptor (TLR)4 agonists are known potent immunostimulatory compounds. These compounds can be formulated as part of novel adjuvants to enhance vaccine medicated immune responses. However, the contribution of the formulation to the innate in vivo activity of TLR4 agonist compounds is not well understood.
Molecular expression profiles and cellular responses in a mouse model were used to compare for GLA-SE, GLA, Alum, SE, PBS. This study was to evaluate the mechanism of actions of different adjuvants and to identify potential biomarkers for clinical evaluation.

overall_design:
Muscle, lymphnode, and blood tissues from Balb/c mice were examined after treatments with GLA-SE, GLA, SE and Alum.  A time course study at 0, 6h, day 1, day 2, and day 4 were carried out.
ACF Study No.  078-10-007 and Study No.  078-11-008

first: Stacie

last: Lambert

first: Chin-Fen

last: Yang

first: Rose

last: Sweetwood

first: Jackie

last: Zhao

first: Jennifer

last: Woo

first: Hong

last: Jin


title: Cycad Genotoxin Methylazoxymethanol (MAM) Modulates Cellular Pathways Involved in Cancer and Neurodegenerative Disease

status: Public on Jan 10 2013

city: Seattle

first: James

middle: William

last: MacDonald

state: WA

address: 4225 Roosevelt Way NE

department: Environmental and Occupational Health Sciences

institute: University of Washington

summary: Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of young adult mice treated with a single systemic dose of MAM display DNA damage (O6-methylguanine lesions) that peaks at 48 hours and decline to near-normal levels at 7 days post-treatment.  By contrast, at this time, MAM-treated mice lacking the gene encoding the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT), showed persistent O6-methylguanine DNA damage. The DNA damage was linked to cell-signaling pathways that are perturbed in cancer and neurodegenerative disease.  These data are consistent with the established carcinogenic and developmental neurotoxic properties of MAM in rodents, and they support the proposal that cancer and neurodegeneration share common signal transduction pathways. They also strengthen the hypothesis that early life exposure to the MAM glucoside cycasin has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for medicine and/or food.  Exposure to environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer’s disease, as well as cancer.

overall_design: Mouse brains from eleven-week-old male C57BL6 wild-type and Mgmt-/- mice were exposed to either MAM or Vehicle for 6 hr, 24 hr, 48 hr, 168 hr. Five or six mice per group for a total of 94 mice.

first: Richard

last: Beyer

first: Theodore

last: Bammler

first: Monica

last: Churchwell

first: Alex

last: Cranson

first: Anna-Luiza

last: Crawford

first: Daniel

last: Doerge

first: Rebecca

last: Fry

first: Glen

last: Kisby

first: Michael

last: Lasarev

first: Lisiane

last: Meira

first: Valerie

last: Palmer

first: Xuefeng

last: Ren

first: Robert

last: Sullivan

first: Terrance

middle: J

last: Kavanagh

first: Leona

middle: D

last: Samson

first: Helmut

last: Zarbl

first: Peter

last: Spencer


title: Gene expression in control and cilia deleted growth plate chondrocytes

status: Public on Jan 02 2013

city: Birmingham

first: Rosa

last: Serra

state: AL

address: 1918 University Blvd. 660 MCLM

department: Cell Biology

institute: University of Alabama at Birmingham

summary: Proliferative zone chondrocytes were microdissected from control and Ift88-deleted growth plates to determine gene expression profiles regulated by primary cilia.

overall_design: Four total samples were analyzed. Two biological replicates of proliferative zone chondrocytes microdissected from control mice and two biological replicates from Ift88 deleted (Col2aCre;Ift88fl/fl) mice. Control and experimental mice were in the Bl/6 background.


title: Methylation profiling in intraepithelial neoplasia and cervical cancer

status: Public on Jan 01 2013

city: Bogotá

first: Dabeiba

middle: Adriana

last: García Robayo

address: Carrera 7 No 40-62

department: Odontología

country: Colombia

institute: Pontificia Universidad Javeriana

summary: Identification of promoter methylation profile associated with cervical cancer progression. The Ilumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs from 19 cervical samples (including normal, CIN I-II, in situ and invasive cervical cancer tissues).

overall_design: Bisulphite converted DNA from the 19 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2

first: D

last: Garcia

first: A

last: Arregui


title: Gene expression accompanying the promotion of hepatocellular carcinoma by intestinal microbiota and Tlr4 in mice.

status: Public on Jan 03 2013

last: Schwabe

address: Russ Berrie Pavilion, 1150 St. Nicholas Avenue

summary: The effect of Tlr4P712H mutation (rendering TLR4 non-functional), or gut-sterilization by antbiotics, on the induction of tumorgenesis by CCl4 and diethylnitrosamine (DEN) was characterized. Affymetrix Mouse 430 2.0 gene expression measurements were used to characterize the transcriptomic basis of the effects of the above treatments and genotypes on tumorgenesis.

overall_design: Gene expression of mouse livers of A. Normal liver from WT C3H/HeOuJ mice, B. HCC from WT C3H/HeOuJ mice treated with CCl4 and DEN, C.HCC from TLR4-mutant C3H/HeJ mice (Tlr4P712H) treated with CCl4 and DEN and D.HCC from WT C3H/HeOuJ mice treated with antibiotics (a combination of ampicillin (1 g/l), neomycin [1 g/l], metronidazole[1 g/l]  and vancomycin [500 mg/l] in drinking water) and CCl4 and DEN were characterized.

first: Dianne

last: Dapito

first: Ali

last: Mencin

first: Geum-Youn

last: Gwak

first: Jean-Philippe

last: Pradere

first: Myoung-Kuk

last: Jang

first: Adebowale

last: Adeyemi

first: Ingmar

last: Mederacke

first: Hossein

last: Khiabananian

first: Ramon

last: Bataller

first: Jay

last: Lefkowitch

first: Richard

last: Friedman

first: Raul

last: Rabadan


title: Expression data from the dorsal and lateral lobes of the prostates of TRAMP mice treated with OSU-CG5

city: Columbus

first: Lisa

last: Berman-Booty

state: OH

address: 500 West 12th Avenue

department: Division of Medicinal Chemistry

institute: The Ohio State University

summary:
Cells undergoing malignant transformation often shift their cellular metabolism from primarily oxidative phosphorylation to aerobic glycolysis (the Warburg effect). Energy restriction-mimetic agents (ERMAs), such as 2-deoxyglucose and resveratrol, that target this shift in cellular metabolism have been effective in inhibiting cancer cell growth in vitro, and xenograft tumor growth in vivo.
We recently developed a novel ERMA, OSU-CG5, that exhibits higher in vivo activity than previously described ERMAs. In this study, we investigated the effect of OSU-CG5 on global gene expression in the dorsal and lateral lobes of the prostate of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, and on its ability to suppress lesion progression in these mice.

overall_design: Intact male TRAMP mice were randomized into 2 groups and treated for 4-weeks (from age 6 to 10 weeks) with a vehicle or 100 mg/kg/day OSU-CG5 via oral gavage. At the end of the study, the urogenital tracts were collected and prostates microdissected. RNA was extracted from the dorsal and lateral lobes of the prostates from 3 mice per group, and Affymetrix microarrays were performed.

first: Ching-Shih

last: Chen

first: Samuel

middle: K

last: Kulp


title: Implantation Failure of Blastocysts Derived from Oocyte-directed Connexin 43 depleted Mice is Associated with Impaired Ribosomal and Translational Machinery Gene Expression

city: Rehovot

first: Amit

last: Zeisel

address: Weizmann Institute

department: Physics of complex systems

country: Israel

institute: Weizmann Institute of Science

summary: Oocyte quality is a well- established determinant of embryonic fate. However, the molecular participants and biological markers that affect and predict adequate embryonic development are largely elusive. We have previously reported that oocyte- directed Connexin 43 (Cx43) depletion leads to embryo implantation defects, although both the morphology of the oocyte and processes presiding embryo implantation appear to undergo normally. In the context of previous data determining Cx43 indispensability to oocyte and embryonic development, we show here that the timing of Cx43 depletion from the oocyte and the ovarian follicle is crucial in determining the severity of subsequent embryonic defects. Specifically, we show that the implantation defects of blastocysts resulting from oocyte- directed Cx43- depleted follicles (depletion occurs at day 3 postnatal), is not due to maternal luteal insufficiency but rather depends solely on the defective blastocysts. Gene expression microarray analysis revealed global defects in the expression of ribosomal proteins, translation initiation factors and other genes associated with cellular biosynthetic and metabolic processes in these defective oocytes and specifically blastocysts. We therefore propose that timely expression of Cx43 in the oocyte and ovarian follicles is a major determinant of oocyte developmental competence, by determining the ability of the resulting blastocyst to facilitate biomass expansion and undergo adequate embryo implantation

overall_design: To study the effect of CX43 on the transcriptom of the pre implantation stages, we compared CX43 KO oocytes to the WT oocytes in three different stages of the very early development. First comparison MII oocytes, second comparison blastocysts, third comparison implantation site.

first: Vicki

last: Plaks

first: Eran

last: Gershon

last: Ziesel

first: Inbal

last: Kirenberg

first: Jasmine

last: Jacob-Hirsch

first: Michal

last: Neeman

first: Elke

last: Winterhager

first: Gideon

last: Rehavi

first: Eytan

last: Domany

first: Nava

last: Dekel


title: Plasma microRNA profiling by microarray elucidates several candidate biomarkers for colorectal cancer screening

city: Barcelona

first: María Dolores

last: Giráldez

state: Barcelona

address: Villarroel 170

department: Gastroenterology

country: Spain

institute: Hospital Clínic

summary: MicroRNAs (miRNAs) are small non-coding RNA molecules which function as negative gene regulators. The tissue expression profile of miRNAs shows great promise as a novel biomarker for diagnosis of cancer and other diseases. In addition, some recent reports have demonstrated that are present in human serum and plasma which could make them an ideal non-invasive biomarker for diagnosis of cancer. The aim of this study is to analyze the value/efficacy of the expression profile of plasma miRNAs in differentiating between patients with advanced adenomas and CRC and healthy individuals.

overall_design: The microRNA profiling study comprises serum plasmas from 20 Control, 21 colorectal cancer,20 advanced adenomas.The study also include some samples from patients after treatment.

first: M

last: Giraldez

first: J

last: Lozano

first: G

last: Ramirez

first: A

last: Castells

last: Gironella


title: The impact of cell source, culture methodology, culture location and individual donors on gene expression profiles of bone marrow-derived and adipose-derived stromal cells.

city: Nijmegen

first: Ruurd

last: Torensma

address: GeertGrooteplein 28

department: Tumorimmunology

institute: Radboud University Nijmegen Medical Centre

summary: Gene expression was influenced most by the tissue source, followed by culture methodology, next by location where the cells were cultured and lastly the donor variability.

overall_design: On the normalized log2 expression values per gene a multifactorial Analyses of Variance (ANOVA) was conducted. Factors CELL CULTURES (cell source), MEDIUM (culture methodology), LOCATION (culture location), and SCAN DATE (hybridization batch) were included in the ANOVA model as independent factors. The following pairwise comparisons were made; Fetal calf serum vs. Human platelet lysate, Bone marrow vs. Adipose tissue, Utrecht vs. Leiden, Utrecht vs Nijmegen, and Leiden vs Nijmegen. Changes ≥2  and Benjamini Hochberg corrected p-values <0.05 were considered significant.

first: Henk-Jan

last: Prins

first: Ellen

last: Schrama

first: Eugène

middle: T

last: Verwiel

first: Anton

last: Martens

first: Helene

last: Roelofs

first: Bastiaan

last: Jansen


title: Expression data of  GMP and MDP from wild-type and Trib1-/- mice

city: Suita

first: Takashi

last: Satoh

address: 3-1 Yamada-oka

department: RIMD

institute: Osaka university

summary:
Trib1 is critical for some myeloid cell differentiation.
Therefore we used microarrays to investigate gene expression profiles in wild-type and Trib1-/- progenitor of myeloid cells.

overall_design: Progenitor cells, such as GMP and MDP, obtained from wild-type and Trib1-/- mice were sorted, followed by RNA extraction. Then hybridization on affymetrix microarrays was performed.

first: T


title: HIV downregulates interferon stimulated genes in primary macrophages.

city: London

first: Akul

last: Singhania

address: 1 Midland Road

institute: The Francis Crick Institute

summary: HIV is able to outpace the innate immune response, including the response mediated by interferon (IFN), to establish a productive infection.  However, monocyte derived macrophages (MDMs) may be protected from HIV infection by treatment with type I IFN before virus exposure.  The ability of HIV to modulate the type I IFN-mediated innate immune response when it encounters a cell that has already been exposed to IFN was investigated.

overall_design: To investigate the presence of HIV on an established IFN response, MDMs were subjected to four different conditions: (1) IFN-treated only, (2) IFN-treated followed by HIV infection, (3) HIV infected only, and (4) a mock-treated and mock-infected control.  Microarray gene expression analysis was performed on a total of 24 samples derived from the 4 conditions assessed at 3 time points (1, 4 and 8 days following treatment/infection) for both IFN-α2 or -ω.  Initially, ISGs were identified as those that were upregulated greater than 2-fold by IFN alone (condition 1) at both Days 4 and 8.  Then, the IFN-treated condition was compared to the IFN-treated followed by HIV-infection condition in order to identify those ISGs that were downregulated at least 1.5-fold by the presence of HIV at both days.  Assuming that it would be counterproductive for HIV infection by itself to induce the expression of ISGs with putative anti-HIV effects, those ISGs that were upregulated greater than 2-fold in the HIV control were removed.  Finally, ISGs that passed these filters and were concordant with both IFN-treatments (IFN-α2 and -ω) were identified and corresponded to the following 8 ISGs: AXL receptor tyrosine kinase (AXL), interferon-alpha inducible protein 27 (IFI27), interferon-induced protein 44 (IFI44), interferon-induced protein 44-like (IFI44L), ISG15, OAS1, OAS3 and XIAP associated factor 1 (XAF1).  It should be noted that the IFN-α2 and -ω microarray experiments were performed in different batches but batch effects were not corrected since genes were identified by the filtering approach just described within each batch.

first: Seong-Heon

last: Wie

first: Christopher

last: Woelk


title: Gene expression profiling reveals mast cell-dependent inflammation in the meninges in early EAE.

city: Milwaukee

first: Martin

last: Hessner

state: WI

address: 8701 Watertown Plank Road

department: Pediatrics

institute: Medical College of Wisconsin

summary: The meninges are generally considered relatively inert tissues that house the CSF and provide protection for the brain and spinal cord. However, our previous studies using Kit mutant (Kit W/Wv) mast cell-deficient mice demonstrated that mast cells residing in the dura mater and pia mater exacerbate the severity of experimental autoimmune encephalomyelitis (EAE), the rodent model of the CNS demyelinating disease, multiple sclerosis. These data suggest that the meninges are sites of active immune responses in disease. Gene expression profiles of meningeal tissue from wild type and mast cell deficient mice prior to and at day 6 post-EAE induction were found highly distinct. Increases in both mast cell- and neutrophil-associated transcripts were among the notable disease-related changes observed in wild type mice. Kinetic analyses show that meningeal mast cells are activated within 24 hours of disease induction to express multiple mediators including IL-1b and TNF as well as the neutrophil chemoattractant, CXCL2, an observation corresponding with an influx of neutrophils to the meninges. Neutrophil recruitment as well as the disease-related loss of BBB integrity is dependent on mast cell-derived TNF. These data provide unequivocal evidence that the meninges are sites of early inflammatory events in EAE. Mast cells residing within these tissues promote disease by orchestrating an early and efficient immune cell co-localization resulting in a robust local inflammatory response and a breach of the proximal BBB. We hypothesize that these events reflect an aberrant manifestation of the normal immune surveillance role of the meninges in infection settings.

overall_design: Immunized WT and Kit W/Wv mice were sacrificed on Day 6 post-immunization and perfused with PBS as were naïve littermate control mice. The dura mater was immediately removed from the calvarium of the skull and pooled (10 mice/group, 4 groups). RNA was isolated using SV Total RNA Isolation System (Promega).  Each pool was analyzed in technical triplicates. Briefly, cRNA was synthesized and amplified/labeled using the Affymetrix Express Kit, then fragmented and hybridized to the The GeneChip® Mouse Genome 430 2.0 Array in accordance to the Affymetrix GeneChip expression analysis technical manual (Affymetrix, Santa Clara, CA).  After hybridization, arrays were washed and stained with Affymetrix fluidics protocol FS450_0001 and scanned with a 7G Affymetrix GeneChip Scanner.  Image data were analyzed with Affymetrix Expression Console™ software and normalized with Robust Multichip Analysis (RMA; www.bioconductor.org/)  to determine signal log ratios (CITE: Gentleman, R.C., Carey, V.J., Bates, D.M., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004). Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5, R80.).   The mean fold change was calculated from 3 independent technical replicates for each of the four experimental conditions and assessed by a non-parametric rank product test (CITE: Hong, F., Breitling, R., McEntee, C.W., Wittner, B.S., Nemhauser, J.L., and Chory, J. (2006). RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics 22, 2825-2827).  Heat maps were generated with Genesis (Cite: Sturn, A., Quackenbush, J. and Trajanoski, Z. (2002) Genesis: cluster analysis of microarray data. Bioinformatics, 18, 207-208).

first: Melissa

last: Brown


title: Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (mRNA)

city: Houston

first: Jiexin

last: Zhang

state: TX

address: 1515 Holcombe Blvd

department: Bioinformatics & Computational Biology

institute: UT MD Anderson Cancer Center

summary:
Oral cavity squamous cell carcinoma (OSCC) is a disease with extensive morbidity and mortality and few useful molecular targets.
Multiplatform integrated genomic analysis was performed in order to identify genomic drivers and molecularly discernible tumor subtypes.
mRNA, miRNA and methylation data are all submitted to GEO

overall_design: We measured gene expression of 43 OSCC cases with the Affymetrix Human Exon 1.0 ST Array

first: Curtis

middle: R

last: Pickering

first: Mitchell

last: Frederick

first: Jeffrey

middle: N

last: Myers