title: Cancer-associated adipocytes mRNA

summary: The role of adipocytes in cancer microenvironment has gained focus during the recent years. However, the characteristics of the cancer-associated adipocytes (CAA) in human breast cancer tissues and the underlying regulatory mechanism are not clearly understood. We reviewed pathology specimens of breast cancer patients to understand the morphologic characteristics of CAA, and profiled the mRNA and miRNA expression of CAA by using indirect co-culture system in vitro.

overall_design: We analyzed transcriptional changes in adipocytes (3T3-L1) induced by the paracrine effect of breast cancer cell MCF7 and MDA-MB-231 by using indirect co-culture system. Differentiated adipocytes were cultured in the bottom chamber of the transwell co-culture system with or without the breast cancer cells seeded in the top inserts. After the co-culture for certain periods, the adipocytes at the bottom wells were collected and used for further analysis.

first: Jiwoo

last: Lee


title: Pals1 haplo-insufficiency in nephrons results in proteinuria and cyst formation

status: Public on Mar 07 2017

city: Muenster

first: Jochen

last: Seggewiss

address: Roentgenstr. 21

department: Integrated Functional Genomics

country: Germany

institute: University of Muenster

summary: Mammalian nephrons are the physiological subunits of mammalian kidneys which consist of different highly apicobasally polarized epithelial cell types. In epithelial cells polarization is controlled by evolutionary conserved CRB, PAR, or SRIB complexes. Here, we focused on the role of Pals1/Mpp5 in the nephron. Pals1, a core component of the apical membrane determining CRB complex, is highly expressed in renal tubular epithelial and glomerular epithelial cells (podocytes). Surprisingly, haplo-deficient mice, lacking one Pals1/Mpp5 allele in the nephron developed a strong phenotype, accompanied by cyst formation and severe renal filtration barrier defects, which subsequently lead to death after 6-8 weeks. Supporting studies in Drosophila nephrocytes, and epithelial cell culture models elucidated the role of Pals1 as a dose dependent upstream regulator of the crosstalk between Hippo- and TGFβ-signaling during nephrogenesis.

overall_design: 2 groups, 3 samples each (triplicates)

first: Maria

last: Edeling


title: Murine MTHFD1-synthetase deficiency, a model for the human MTHFD1 R653Q polymorphism, decreases tumor growth in males

status: Public on Mar 01 2017

city: Montreal

first: Rima

last: Rozen

state: Qc

address: 1001 Decarie Blvd

department: Human genetics

country: Canada

institute: McGill University

summary: [Abstract] The R653Q variant in the synthetase domain of the folate-metabolizing enzyme MTHFD1 has been shown to increase risk for birth defects, but it does not affect risk for development of colorectal cancer (CRC). However, since we have shown that this variant reduces purine synthesis, the goal of this study was to determine whether it could affect tumor growth. Using our mouse model for MTHFD1-synthetase deficiency (Mthfd1S+/-), we induced tumor formation with azoxymethane (AOM) and dextran sodium sulfate (DSS) in male and female wild-type and Mthfd1S+/- mice. Tumor size was significantly smaller due to mutant genotype, particularly in males. Tumor size was increased in female mice compared with males, regardless of genotype. Tumor number was not influenced by genotype and was lower in females. Inflammation within tumors of male Mthfd1S+/- mice was lower than in wild-type mice. Proliferation of mouse embryonic fibroblasts from mutant lines was slower than that in wild-type fibroblasts. Gene expression analysis in tumor adjacent normal (preneoplastic) tissue identified several genes involved in proliferation (Fosb, Fos, Ptk6, Esr2, Atf3) or inflammation (Atf3, Saa1, TNF-α) that were downregulated in mutant male mice. Female mutants did not have changes in expression for those genes, nor in tumor inflammation levels, compared with wild-type, suggesting a different mechanism directing tumor growth in females. We suggest that restriction of purine synthesis and reduced expression of critical tumor-promoting genes leads to slower tumor growth in MTHFD1-synthetase deficiency. These findings may have implications for CRC tumor growth and prognosis in individuals with the R653Q variant.

overall_design: Affymetrix Mouse Gene 2.0 ST Array Chips were used to assess gene expression in normal colonic mucosa of four male Mthfd1S+/+ and two male Mthfd1S+/- BALB/c mice.

first: Nancy

last: Lévesque

first: Karen

middle: E

last: Christensen

first: Lauren

last: Van Der Kraak

first: Ana

middle: F

last: Best

first: Liyuan

last: Deng

first: Don

last: Caldwell

first: Amanda

last: MacFarlane

first: Nicole

last: Beauchemin


title: Analysis of gene expression along the Hoxa cluster at five time-points during motor neuron differentiation

city: Taipei

first: Jun-An

last: Chen

address: 128 Academia Road, Section 2

department: Institute of Molecular Biology

country: Taiwan

institute: Academia Sinica

summary: To dissect the significance underlying the delay between Hox transcription and translation, we  profiled global Hox gene expression using an in vitro ESC-derived motor neuron differentiation system

overall_design: Total RNA were isolated from WT ES derived motor neurons. Subsequently, ES cell derived motor neuron transcriptome was analyzed by Agilent SurePrint G3 Mouse GE 8x60K Microarray (Agilent-G4858A-028005).

first: Ya-Ping

last: Yen


title: STAT6-regulated genes in mouse B cells

status: Public on Mar 06 2017

city: Erlangen

first: David

last: Vöhringer

state: Bavaria

address: Wassersturmstr 3-5

department: Microbiology

institute: University Hospital Erlangen

summary: The IL-4-induced and STAT6-dependent gene expression profile in mouse B cells was analyzed. Untouched B cells from 9 weeks old female Ly5.1-congenic wild-type and Ly5.2-congenic STAT6-deficient mice, both on BALB/c background, were isolated from the spleen and stimulated for 4 days in vitro with LPS and anti-CD40 in the presence or absence of IL-4.

overall_design: There are 12 samples in total. Triplicates for the following conditions were analyzed: wild-type without IL-4 (WT_contr), STAT6-deficient without IL-4 (STAT6_contr), wild-type with IL-4 (WT_IL-4) and STAT6-deficient with IL-4 (STAT6_IL-4).

last: Voehringer


title: The impact of hepatocyte specific Cyp51 disruption on development and sexual dimorphism in mice

status: Public on Feb 23 2017

city: Ljubljana

first: Peter

last: Juvan

address: Zaloska 4

department: Institute of Biochemistry

country: Slovenia

institute: Faculty of Medicine, University of Ljubljana

summary:
Unperturbed cholesterol homeostasis is important for normal development and sexual maturation in mice. Cyp51 is the rate limiting step in the post-lanosteorl part of cholesterol biosynthesis. Unlike the full body knockout, hepatocyte specific Cyp51 knockout mice survive throughout adulthood, however their livers are severly affected. Several of the hepatocyte specific Cyp51 knockout mice develop severe liver injury or die prior to reaching adulthood (from 4-10 weeks of age; designated as runts). We aim to uncover the timing and the mechanistic background governing the liver damage and sex differences.
Hepatocyte-specific Cyp51 knockout and wild type mice on a mixed background (129/Pas (10%) × C57BL/6J (90%)) of both sexes (F and M) were investigated at the pre pubertal (3 weeks), late pubertal (6 weeks) and adult (19 weeks) stage of development. This age span allows us to also observe the impact of sexual maturation on the disease development, as the liver is one of the most sexually dimorphic non-reproductive organs. Runt mice were evaluated to differentiate them from the other KO mice with milder conditions.

overall_design: 3 factor experimental design: 3 ages (3, 6 and 19 weeks), 2 genotypes (WT, Cyp51 KO), 2 sexes (F, M); 2 biological replicates per condition, 24 mice altogether. Runt mice were also included in the experiment as a separate phenotype (5-7 weeks of age, F and M, Cyp51 KO); 3 biological replicates per sex. A total of 30 microarrays were used.

first: Žiga

last: Urlep

first: Damjana

last: Rozman


title: Acquired resistance to BRAF-inhibitors restores melanoma tumor immune suppression

city: Lebanon

first: Tammara

last: Wood

state: NH

address: WTRB 674

department: Biomedical Data Science

country: USA

institute: Dartmouth Medical School

summary: The acquisition of resistance to BRAF-inhibitors results in MAPK-driven, CCL2-mediated repopulation of intratumoral myeloid-derived suppressor cells (MDSCs) in a mouse model of melanoma, and the depletion of MDSCs allows for effective immunotherapy against drug-resistant tumors.

overall_design: Gene expression and intrinsic subset assignment were measured in 16 mouse biopsies

first: S

middle: M

last: Steinberg

first: V

last: Martyanov

first: A

last: Boni

first: M

middle: J

last: Turk

first: T

middle: B

last: Shabaneh

first: Z

last: Li

first: B

middle: T

last: Malik

first: P

last: Zhang

middle: A

middle: L

last: Whitfield


title: Diurnal regulation of RNA polymerase III transcription is under the control of both feeding-fasting response and circadian clock [Affymetrix]

city: Lausanne

first: Francois

last: Mange

state: VAUD

address: Genopode building

department: Center for Integrative Genomic

country: Switzerland

institute: University of Lausanne

summary: RNA polymerase III (pol III) synthesizes short non-coding RNAs, many of which, including tRNAs, Rpph1 RNA, Rn5s rRNA, and Rmrp RNA, are essential for translation. Accordingly, pol III activity is tightly regulated with cell growth and proliferation by factors such as MYC, RB1, TRP53, and MAF1. MAF1 is a repressor of pol III transcription whose activity is controlled by phosphorylation; in particular, it is inactivated through phosphorylation by mTORC1 kinase, a sensor of nutrient availability. Pol III regulation is thus sensitive to environmental cues, yet a diurnal profile of pol III transcription activity is so far lacking. Here we document pol III occupancy of its target genes in mouse liver during the diurnal cycle and show that pol III occupancy rises before the onset of the night, stays high during the night, when mice normally ingest food and when translation is increased, and decreases in daytime. By comparing diurnal pol III occupancy in wild-type mice, arrhythmic mice owing to inactivation of the Arntl gene, mice fed at regular intervals during both night and day, and mice lacking the Maf1 gene, we show that whereas higher pol III occupancy during the night reflects a MAF1-dependent response to feeding, the rise of pol III occupancy before the onset of the night reflects a circadian clock-dependent response. Thus, pol III transcription during the diurnal cycle is regulated both in response to nutrients and by the circadian clock, which allows anticipatory pol III transcription.

overall_design: To characterize our mice models, gene expression was measured and a cosine function was fitted to the data to estimate the phase and the amplitude. Mice liver were collected from control mice, constantly fed mice, Arntl KO mice, and Maf1 KO mice every 4 hours  during 3 consecutive days (control, Arntl KO mice, and MAF1 KO mice) and 4 to 6 consecutive days in constantly fed mice.

first: François

first: Viviane

last: Praz

first: Eugenia

last: Migliavacca

first: Ian

last: Willis

first: Frédéric

last: Schütz

first: Nouria

last: Hernandez


title: Comparison of wild type mouse lung cancer cell lines to transfected cell lines with Spp1 sh RNA

city: Munich

first: Georgios

last: Stathopoulos

state: Bayern

address: Max-Lebsche-Platz

department: Comprehensive Pneumology Center

institute: Helmholz Zentrum Munich

summary: We compared different mouse cancer cell lines to identify their unique cell signatures.

overall_design: Samples from different cancer cell lines were analyzed using Genespring 12.5 GX to obtain the  data.

first: Nikolaos

middle: I

last: Kanellakis


title: Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2.

status: Public on Feb 28 2017

city: Osaka-shi

first: Masaki

last: Takasugi

state: Osaka

address: 1-4-3 Asahimachi, Abeno-ku

department: Graduate School of Medicine

country: Japan

institute: Osaka Metropolitan University

summary: Cellular senescence prevents the proliferation of cells at risk for neoplastic transformation.  However, the altered secretome of senescent cells can promote the growth of the surrounding cancer cells.  Although extracellular vesicles (EVs) have emerged as new players in intercellular communication, their role in the function of senescent cell secretome has been largely unexplored.  Here, we show that exosome-like small EVs (sEVs) are important mediators of the pro-tumorigenic function of senescent cells.  sEV-associated EphA2 secreted from senescent cells binds to ephrin-A1 that is highly expressed in several types of cancer cells and promotes cell proliferation through EphA2/ephrin-A1 reverse signalling.  sEV sorting of EphA2 is increased in senescent cells due to its enhanced phosphorylation resulting from oxidative inactivation of PTP1B phosphatase.  Our results demonstrate a novel mechanism of reactive oxygen species (ROS)-regulated cargo sorting into sEVs, which is critical for the potentially deleterious growth-promoting effect of the senescent cell secretome.

overall_design: To investigate the function of sEV-associated EphA2, we cultured breast cancer cell line MCF7 in the conditioned medium (CM) prepared from doxorubicin-induced senescent RPE1 expressing control or two different EphA2 shRNA. The effects of sEV-associated EphA2 on the gene expression profile of MCF7 were investigated using microarray. Microarray experiments were conducted using SurePrint G3 Human GE microarray 8 x 60K ver 2.0 (Agilent). Total RNA was isolated by Trizol Reagent. cDNA labelling, hybridizations, and scanning were performed by DNA ChiP Research Inc. (Japan), an Agilent-certified service provider. Data were then normalized to 75th percentile for inter-array comparison.

first: Ryo

last: Okada

first: Akiko

last: Takahashi

first: David

middle: V

last: Chen

first: Sugiko

last: Watanabe

first: Eiji

last: Hara


title: Lipopolysaccharide (LPS) effect on ficolin deficient spleen

status: Public on Feb 22 2017

city: Copenhagen

first: Peter

last: Garred

address: Ole Maaløesvej 26

department: Department of Clinical Immunology, Section 7631

country: Denmark

institute: Rigshospitalet, University of Copenhagen

summary: Analysis of spleens from ficolin knockout and wildtype mice treated without and with LPS to induce inflammation. Ficolins are pattern recognition molecules that initiate the lectin pathway of complement. Results provide insigt into the molecular basis of the inflammatory response of ficolin knockout mice.

overall_design: Gene expression was investigated in spleens from the following groups (n=3 mice/group): untreated ficolin knockout (KO) mice; untreated wildtype (WT) mice; ficolin KO mice treated with 10mg/kg LPS for 6 hours; WT mice treated with 10mg/kg LPS for 6 hours.

first: Ninette

last: Genster

first: Olga

last: Østrup


title: Dense time series gene expression data from striatum of Huntington’s disease CAG knock-in mice across multiple genetic backgrounds

city: Seattle

first: Jocelynn

middle: Renee

last: Pearl

state: Washington

address: 401 Terry Ave N

institute: Institute for Systems Biology

summary: Huntington’s disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, molecular and cellular phenotypes in the striatum of six distinct knock-in mouse models of the HD mutation. We studied the effects of the HttQ111 allele on the C57BL/6J, CD-1, FVB/NCr1, and 129S2/SvPasCrl genetic backgrounds, and of two additional alleles, HttQ92 and HttQ50, on the C57BL/6J background. We describe the emergence of a transcriptomic signature in HttQ111/+ mice involving hundreds of differentially expressed genes and changes in diverse molecular pathways. We also show that this time course spanned the onset of mutant huntingtin nuclear localization phenotypes and somatic CAG-length instability in the striatum. Genetic background strongly influenced the magnitude and age at onset of these effects. This work provides a foundation for understanding the earliest transcriptional and molecular changes contributing to HD pathogenesis.

overall_design: Huntington's disease mouse model with CAG expansion in Htt compared to wildtype littermate controls; mouse striatum sampled weekly (n=1-5 per week depending on group) from 4 weeks of age to 20 weeks of age.  C57BL/6J, CD-1, FVB/NCr1, and 129S2/SvPasCrl genetic backgrounds.  Included Htt.Q111/+ and WT in each strain and additional shorter CAG lengths Htt.Q92/+ and Htt.Q50/+ in the C57BL/6J background.  Total n =791 mice.

first: Seth

last: Ament

middle: R


title: Gene expression data from WT and TET2cKO CD8+ T cells activated in vitro

city: Ann Arbor

first: Shannon

last: Carty

state: MI

address: 109 Zina Pitcher Place

institute: University of Michigan

summary:
The epigenetic modifier TET2 plays a role in cell fate decisions in hematopeotic stem cells and CD4+ Th1 and Th17 differentiation. Here, we demonstrate that loss of TET2 promotes CD8+ memory differentiation following acute viral infection with LCMV-Armstrong.
To identify early gene expression changes following TCR activation in WT versus TET2cKO CD8+ T cells, we isolated naive CD8+ T cells and activated them for three days with anti-CD3/CD28+IL-2 and performed microarray analysis.

overall_design: Naive (CD44lo CD62Lhi) CD8+ T cells were isolated and sorted from WT C57BL/6  and TET2fl/flCD4Cre+ mice. These cells were activated with plate-bound anti-CD3/CD28 for 3 days in the presence of 100U/ml hIL-2. RNA from these in vitro activated CD8+ T cells were processed, amplified, labeled and hybridized to  Affymetrix GeneChip MoGene 2.0 ST microarrays.

first: Gary

last: Koretzky

first: Martha

middle: S

last: Jordan


title: Gene expression profile of CD8+ T cell subtypes

status: Public on Feb 21 2017

city: Boston

first: Youdong

last: Pan

state: MA

address: 77 Avenue Louis Pasteur

department: Dermatology

institute: Harvard Medical School

summary:
OT-I naïve T cells, central memory T cells, effector memory T cells and skin infiltrating T cells were sorted out from mice at different timepoints post infection
OT-I cells from 15-20 mice were pooled together for each microarray dataset

overall_design: By comparing the gene expression profile among different T cell subtypes, we aimed to identify core regulatory genes in skin CD8+ tissue resident memory T cell differentiation and maintenance in epithelia tissue

first: Thomas

last: Kupper


title: siRNA knockdown of GALNT2 in gastric adenocarcinoma AGS cells

status: Public on Feb 13 2017

first: Min-Chuan

last: Huang

address: No. 1, Sec. 1, Ren-Ai RD, Taipei, Taiwan, R.O.C.

department: Graduate Institute of Anatomy and Cell Biology

institute: National Taiwan University

summary: To determine the whole genome profile of GALNT2 silenced AGS cells

overall_design: AGS cells were transfected with non-targeting and GALNT2 specific siRNA with Lipofectamine RNAiMAX for 48 hours and extracted for total RNAd

first: I-Rue

last: Lai


title: Gene expression analysis of Thy1+LSK bone marrow cells from Nol3+/+ and Nol3-/- MPN mice

status: Public on Feb 17 2017

city: Bronx

first: Robert

last: Stanley

state: New York

address: 1300 Morris Park Avenue, Chanin Building Rm 601

department: Cell Biology

institute: Albert Einstein College of Medicine

summary:
Apoptosis Repressor with Caspase Recruitment Domain (ARC) was recently found to be highly expressed in solid tumors and in blast cells of patients with acute myeloid leukemia (AML). In this study, we assessed the functional and molecular consequences of loss of ARC on the hematopoietic system. We found, unexpectedly, that deletion of Nol3 (the gene that encodes ARC) in mice leads to development of a myeloproliferative neoplasm (MPN) resembling primary myelofibrosis (PMF). Nol3-/--induced MPN is transplantable into secondary recipient mice and is characterized by anemia, thrombocytopenia, extramedullary hematopoiesis, and bone marrow fibrosis.  Despite an overall reduction in bone marrow cellularity Nol3-/- MPN mice have an expanded Thy1+LSK stem cell population with increased cell cycling, in addition to a myelomonocytic differentiation bias. Molecularly, the Nol3-/--induced phenotype is, at least in part, mediated by activation of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6) and MYC. Nol3-/- MPN Thy1+LSK cells show significant molecular similarities with primary CD34+ cells isolated from patients with PMF. Furthermore, we found that Nol3 is deleted in patients with human myeloid malignancies and has decreased expression in a subset of patients with de novo AML. Our results reveal a novel role of Nol3 in normal hematopoiesis and in the pathogenesis of myeloid malignancies.
To obtain insight into the molecular mechanism of the Nol3-/- -induced MPN, we performed gene expression profiling on Thy1+LSK bone marrow cells from Nol3+/+ and Nol3-/- MPN mice

overall_design: RNA was isolated from Thy1+LSK bone marrow cells from 11-18 month old Nol3+/+ or Nol3-/- MPN mice.

first: Ulrich

last: Steidl


title: Elucidation of roles of Nr4a nuclear orphan receptors and Foxp3 in thymic Treg cell development

status: Public on Feb 10 2017

city: Ichikawa

first: Takashi

last: Sekiya

state: Chiba

address: 1-7-1 Kohnodai

institute: National Center for Global Health and Medicine

summary: Both Nr4a family nuclear orphan receptors and Foxp3 had been revealed to be crucial transcription factors in Treg cell development. In this study, to reveal their roles in a Treg cell developmental transcriptional programs, we compared transcriptomes among wild-type conventional CD4 T (Tconv) cells, wild-type Treg cells, Nr4a-triple-knockout (Nr4a-TKO) Treg precursor (preTreg) cells, and Foxp3-KO preTreg cells by microarray.

overall_design: Total RNA was extracted from wild-type Tconv (CD4-single positive (CD4SP),CD25-low) thymocytes, wild-type thymic Treg (CD4SP, Foxp3+), Nr4a-TKO preTreg (CD4SP, CD25-high, GITR-high, Nr4a3-high), and Foxp3-KO preTreg (CD4SP, CD25high, Foxp3-reporter+) cells. Each cell population was analyzed with two biological replicates.

first: Akihiko

last: Yoshimura


title: Autophagy deficient keratinocytes under paraquat stress

status: Public on Feb 14 2017

city: Vienna

first: Markus

last: Jeitler

address: Lazarettgasse 14

country: Austria

institute: Medical University Vienna

summary: Autophagy is a mechanism that regulates cellular metabolism and clearance of damaged macromolecules and organelles. Impaired degradation of modified macromolecules contributes to cellular dysfunction and is observed in aged tissue and senescent cells. We have inactivated Atg7, an essential autophagy gene, in murine keratinocytes and have found in an earlier study that this resulted in increased baseline oxidative stress and reduced capacity to degrade crosslinked proteins after oxidative ultraviolet stress. To investigate whether autophagy deficiency would promote cellular aging, we studied, how Atg7 deficient (KO) and Atg7 bearing cells (WT) would respond to stress induced by Paraquat (PQ), an oxidant drug commonly used to induce cellular senescence.

overall_design: This study was performed in biological triplicates for autophagy competent and deficient mouse Keratinocytes treated with 20µM Paraquat for 48h or sham treated

first: Xiuzu

last: Song

first: Marie-Sophie

last: Narzt

first: Ionela-Mariana

last: Nagelreiter

first: Johannes

last: Grillari

first: Erwin

last: Tschachler

first: Florian

last: Gruber


title: Whole Blood RNA Transcript Models Predict Clinical Response in Two Clinical Studies Advanced Melanoma Patients Treated with Tremelimumab

status: Public on Feb 15 2017

city: Cambridge

first: Karl

middle: George

last: Wassmann

address: 245 First Street Suite 1800-109

institute: CheckPoint Sciences Inc.

summary:
Background: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions.  Methods: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset). A central panel of radiologists determined objective response using RECIST criteria. Gene expression for 169 mRNA transcripts was measured using quantitative PCR. A 15-gene pre-treatment response-predictive classifier model was identified. An independent population (N=150) of refractory melanoma patients receiving tremelimumab after chemotherapy enrolled in a worldwide phase II study (validation dataset). The classifier model using the same genes, coefficients and constants for objective response and one-year survival after treatment was applied in the validation dataset.
Results: A 15-gene pre-treatment classifier model (containing ADAM17, CDK2, CDKN2A, DDP4, ERBB2, HLA-DRA, ICOS, ITGA4, LARGE, MYC, NAB2, NRAS, RHOC, TGFB1, and TIMP1) achieved an area under the curve (AUC) of 0.86 (p< 0.0001) in the discovery set. This model was validated in the validation set with AUCs of 0.641 (p= 0.049) for objective response and 0.68 for one-year survival (p=0.0002).   Conclusions: To our knowledge, this is one of the largest blood-based biomarker studies of a checkpoint inhibitor, tremelimumab, which demonstrates a validated pre-treatment mRNA classifier model that predicts clinical response. The data suggest that the models capture biological signatures representative of genes needed for a robust anti-cancer immune response. They also identify non-responders to tremelimumab significantly prior to radiological evidence of progression.

overall_design: Patient Population and Gene Selection: Both the discovery and validation datasets resulted from pre-treatment blood samples collected in multinational, open-label studies of tremelimumab administered to advanced melanoma patients. Only patients in which both a pre- and post-treatment blood sample were available were included in our analysis. The pre-treatment discovery dataset was a randomized phase III study which enrolled 210 patients, with N=28 responders and N=182 non-responders. The pre-treatment validation dataset was a non-randomized phase IIb study which enrolled 150 patients, with N=20 responders and N=130 non-responders. In both studies response was determined by RECIST criteria. The patients in the pre-treatment discovery dataset were treatment-naïve, while the patients in the pre-treatment validation dataset were chemotherapy-refractory. The selection process for the 169 genes tested included genes associated with inflammation, immunity, the CTLA4 pathway, oncogenes, and melanoma-specific genes. Whole-blood was collected in PAXgene® tubes and processed to RNA that met quality and integrity standards (RNA integrity number ≥6.3) per the Bioanalyzer 2100 in combination with the RNA 6000 Nano or Pico Series II LabChip. First-strand complementary DNA was synthesized from random hexamer-primed RNA templates using TaqMan® reverse-transcription reagents. Individual target-gene amplification was multiplexed with the 18S rRNA endogenous control and run in triplicate in 384-well format on the 7900HT fast real-time PCR system.

first: Philip

last: Friedlander

first: Alan

last: Christenfeld

first: David

last: Fisher

first: Chrisann

last: Kyi

first: John

last: Kirkwood

first: Nina

last: Bhardwaj

first: William

middle: K

last: Oh


title: The global transcriptome analysis of HCT116 cells transfected with scrambled or CBX4 shRNA

city: Guang Zhou

first: Xin

last: Wang

state: State...

address: Dongfengdong road 651

country: China

institute: Sun Yat-sen University Cancer Center

summary: To investigate the molecular mechanism of CBX4 in CRC, the global transcriptomes were analyzed in HCT116 cells in which CBX4 was knocked down with shRNA, and these transcriptomes were compared to those of HCT116 cells transfected with scrambled shRNA.

overall_design: Two pairs of small hairpin RNAs (shRNAs) were used to dramatically reduce endogenous CBX4 expression in HCT116 cell line. The global transcriptomes were analyzed in HCT116 cells in which CBX4 was knocked down with shRNA, and these transcriptomes were compared to those of HCT116 cells transfected with scrambled shRNA.

first: Tiebang

last: Kang


title: Increased activity of canonical NF-kB signaling in muscle fibers alters the satellite cell niche and restrains muscle stem cell function during aging

first: Jonathan

last: Dreyfuss

address: 1 Joslin Pl

department: Bioinformatics & Biostatistics Core

institute: Joslin Diabetes Center

summary: It has been known for some time that muscle repair potential becomes increasingly compromised with advancing age, and that this age-related defect is associated with reduced activity of muscle satellite cells and with the presence of chronic, low grade inflammation in the muscle. Working from the hypothesis that a heightened inflammatory tone in aged muscle could contribute to poor regenerative capacity, we developed genetic systems to inducibly alter inflammatory gene expression in satellite cells or muscle fibers by modulation of the activity of nuclear factor κB (NF-κB), a master transcriptional regulator of inflammation whose activity is upregulated in many cell types and tissues with age. These studies revealed that activation of NF-κB activity in muscle fibers, but not in satellite cells, drives muscle dysfunction and that lifelong inhibition of NF-κB activity in myofibers preserves muscle regenerative potential with aging via cell-non-autonomous effects on satellite cell function. Further analysis of differential gene expression in muscles with varying NF-κB activity identified a secreted phospholipase (PLA2G5) as a myofiber-expressed NF-κB-regulated gene that governs muscle regenerative capacity with age. Together, these data suggest a model in which NF-κB activation in muscle fibers increases PLA2G5 expression and drives the impairment in regenerative function characteristic of aged muscle. Importantly, inhibition of NF-κB function reverses this impairment, suggesting that FDA-approved drugs, like salsalate, a prodrug form of sodium salicylate, may provide new therapeutic avenues for elderly patients with reduced capacity to recover effectively from muscle injury.

overall_design: 3 groups of mice: old wild type, young wild type, and old “MISR” mice harboring a transgene that dominantly blocks NF-κB signaling in skeletal muscle via constitutive expression of the IκB super-repressor (ISR) under the muscle fiber-specific muscle creatine kinase (MCK) promoter. There are 2-3 biological replicates per group.

first: Juhyun

first: Indranil

last: Sinha

first: Kah

middle: Y

last: Tan

first: Bernard

last: Rosner

first: Ornela

last: Gjata

first: Peter

last: Tran

first: Steven

last: Shoelson

first: Amy

last: Wagers


title: Comparison of wild type mouse lung cancer cell lines to transfected cell lines with Nras sh RNA

first: Georgios

last: Stathopoulos

first: Nikolaos

last: Kanellakis


title: Identification of hypoxia-induced HIF1A targets in melanocytes reveals a molecular profile associated with poor prognosis for melanoma [gene expression]

status: Public on Feb 20 2017

city: Bethesda

first: Stacie

last: Loftus

address: 49 Convent Dr

institute: National Human Genome Research Institute

summary: These datasets describe a melanocyte specific, HIF1A-Dependent / Hypoxia-Responsive gene expression signature defined by the regulation of genes critical to metabolism, chromatin and transcriptional regulation, vascularization and cellular invasivness. These genes provide lineage specific targets for refinement of diagnostic markers associated with primary melanoma tumor metastatic potential, and also provides novel molecular targets for therapeutic strategies targeting metastatic disease progression.

overall_design:
Microarray gene expression analysis was performed in biological triplicate for each condition of immortal melanocyte cell line, melan Ink4a-Arf  grown  cells.
contributor: NISC Comparative Sequencing Program

first: Laura

last: Baxter

first: Julia

middle: C

last: Cronin

first: Temesgen

middle: D

last: Fufa

last: Pavan


title: Transcriptional Profiling of the Immune Response to Ebola Infection

first: Ignacio S.

last: Caballero

address: 620 Albany St., NEIDL 401V

department: NEIDL/Microbiology

institute: Boston University School of Medicine

summary: Ebola virus is the causative agent of a severe syndrome in humans with a fatality rate that can approach 90%. During infection, the host immune response is thought to become dysregulated, but the mechanisms through which this happens are not entire understood. In this study, we use microarrays to determine the host response to Ebola infection in the PBMCs of cynomolgus macaques.

sample_organism:
Macaca fascicularis
Homo sapiens

overall_design: RNA was isolated from a total of 36 PBMC samples from 14 cynomologus macaques infected with Ebola Virus. Samples were obtained at sequential timepoints post-infection, and included a pre-infection specimen from each animal. These samples were then processed and hybridized onto the Agilent 2-color arrays.

first: Judy

last: Yen

first: Ignacio

first: Anna

middle: N

last: Honko

first: Lisa

last: Hensley

first: John

middle: H

last: Connor


title: Gene Expression Data from Adult and Embryo Thymic Epithelial Cells (TEC)

city: London

first: Tessa

last: Crompton

address: 30 Guilford Street

department: Immunobiology

country: United Kingdom

institute: UCL

summary: We used Affymetrix microarrays to understand the genome wide differences in Adult and fetal cortical thymic epithelial cells (cTEC) and medullary thymic epithelial cells (mTEC)

overall_design: Embryonic day 14.5 (E14.5) wildtype fetal thymi were cultured for 7 days on AIM-V and cortical and medullary thymic epithelial cells were sorted from these embryos. We also isolated cortical and medullary thymic epithelial cells from 1-2 week old adult mice. RNA was extracted from these samples and hybridized on Affymetrix Mouse Gene microarrays to help understand the genome wide changes in adult and fetal cTEC and mTEC.

first: José

last: Saldaña


title: Gene expression patterns  from mice hearts with myocardial infarction pretreated with miR-433 inhibition or not

status: Public on Feb 12 2017

city: Shanghai

first: Yihua

last: Bei

address: 133 Nanchen Road

department: School of Life Science

institute: Shanghai University

summary: This study was to identify the role of miR-433 and to clarify the underlying molecular mechanisms in cardiac remodeling post myocardial infarction.

overall_design: To determine if inhibition of miR-433 is sufficient to prevent cardiac fibrosis in vivo, mice were injected via tail vein with 80 mg/kg miR-433 antagomir or the scramble control for 3 consecutive days and subjected to left anterior descending coronary artery (LAD) ligation.Twenty-one days post myocardial infarction, gene arrays were conducted to compare the difference of gene expressions between miR-433 antagomir (n=3) or scrambled negative control (n=3) post myocardial infarction.

first: Lichan

last: Tao

first: Junjie

last: Xiao

first: Xinli

last: Li


title: Analysis of graft-infiltrating CD8+ T cell profile after CD3 antibody therapy

city: Paris

first: Sylvaine

last: You

address: Hôpital Necker, Bâtiment Hamburger, 5ème étage, 149  rue de Sèvres

department: Immunology

country: France

institute: INSERM U1151 - University Paris Descartes

summary: We performed a global gene expression analysis comparing intragraft tolerant CD8+ T cells from CD3 antibody-treated mice showing permanent islet graft survival to intra-graft effector CD8+ T cells isolated from untreated mice showing acute rejection of islet allografts. The objective was to emphasize the anergic profile of CD8+ T cells residing within the pancreatic islet allograft of mice rendered tolerant following CD3 antibody therapy.

overall_design: Five hundreds graft-infiltrating CD8+ T cells from individual tolerant CD3 Ab-treated recipients (n=8) or untreated recipients (n=8) were FACS sorted, lysed using SuperAmpTM lysis buffer (Miltenyi Biotec) and stored at -80°C until all samples were collected. Amplification of RNA, sample hydridization (Agilent whole mouse genome oligo microarrays), scanning and data acquisition were performed by Miltenyi Biotec (Cologne, Germany).


title: Identification of transcriptional changes upon genetic deletion of Vhl, Pbrm1 and double deletion of both Vhl and Pbrm1

city: New York

first: Jeffrey

last: Zhao

state: NY

address: 1275 York Avenue

department: Genomics Core

institute: Memorial Sloan Kettering Cancer Center

summary: To determine why double deficiency of Vhl and Pbrm1 but not single deficiency of either gene resulted in ccRCC, we performed gene expression profiling of RNA isolated from renal cortices of 3-month-old WT, VhlF/FKsp-Cre, Pbrm1F/FKsp-Cre, and VhlF/FPbrm1F/FKsp-Cre mice.

overall_design: The transcripts from WT, VhlF/FKsp, Pbrm1F/FKsp, VhlF/FPbrm1F/FKsp-Cre 3 month old animals were compared to identify the initial transcriptional events that may be important in ccRCC tumor formation

first: Amrita

middle: M

last: Nargund

first: James

middle: J

last: Hsieh


title: Expression data from colorectal tumors of mice

status: Public on Feb 09 2017

first: Markus

last: Jeitler

summary:
Myeloid cells can inhibit the anti-tumor responses of T cells. The mechanism for this cross-talk is not fully elucidated but is known to require STAT3.
We employed mice with conditional deletion of STAT3 in myeloid cells to investigate myeloid STAT3 functions in colitis-associated colorectal tumors in mice. We found that STAT3 is required for suppression of anti-tumor T cell responses in the tumor stroma and identified several signaling pathways in tumor cells that might be implicated in immune escape.

overall_design: Azoxymethane/Dextransulfate (AOM/DSS)-induced colitis-associated colorectal tumors were obtained from wild-type mice and mice with conditional deletion of STAT3 in myeloid cells. Tumor and stroma tissue from colorectal tumors was separated by laser-capture-microdissection and corresponding RNA was used for Affymetrix microarray experiments to identify stromal changes that depent on STAT3 signaling in the myeloid compartment.

first: Paulina

last: Pathria

first: Robert

last: Eferl


title: The transcriptional profile analysis of mice peritoneal cavity B1a cells from p40-/-CD25-/- mice

city: Hefei

first: yanqing

last: yang

address: huangshan road 443

institute: USTC

summary: We have found many differences between B1a cells from p40-/-CD25-/- mice and control mice. To better understand the whole change of transcriptions profile between B1a cells in PC of  p40-/-CD25-/- mice and control mice. By using flow cytometry and high-resolution microarrays, we have studied qualitative and quantitative characteristics of B1a cells of p40-/-CD25-/- mice and control mice.

overall_design: There are 2 group of cells, each group have triplicate samples. At least 6 independent experiments were performed for all sample, and each sample with a minimum of 3 mice.

first: Yanqing

last: Yang


title: Critical role of PI3K signaling for NF-κB–dependent survival in a subset of activated B-cell–like diffuse large B-cell lymphoma cells

status: Public on Feb 08 2017

city: Münster

first: Michael

last: Grau

state: Nordrhein-Westfalen

address: Albert-Schweitzer-Campus 1

department: Faculty of Medicine

institute: University of Münster

summary: The activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) represents a very aggressive human lymphoma entity. Constitutive NF-κB activation caused by chronic active B-cell receptor (BCR) signaling is common feature of many ABC DLBCL cells; however, the pathways linking BCR signaling to the NF-κB prosurvival network are largely unknown. Here we report that constitutive activity of PI3K and the downstream kinase PDK1 are essential for the viability of two ABC DLBCL cell lines that carry mutations in the BCR proximal signaling adaptor CD79B. In these cells, PI3K inhibition reduces NF-κB activity and decreases the expression of NF-κB target genes. Furthermore, PI3K and PDK1 are required for maintaining MALT1 protease activity, which promotes survival of the affected ABC DLBCL cells. These results demonstrate a critical function of PI3K-PDK1 signaling upstream of MALT1 pro-  tease and NF-κB in distinct ABC DLBCL cells and provide a rationale for the pharmacologic use of PI3K inhibitors in DLBCL therapy.

overall_design: This GEO dataset is comprised of three experiments: a) 4 paired (2-color) GEP measurements following treatment with the PI3K inhibitor 15e in the DLBCL cell line HBL1. b) 4 paired (2-color) GEP measurements following treatment with the same PI3K inhibitor 15e in the DLBCL cell line TMD8. c) 4 paired (2-color) GEP measurements following treatment with the IKKbeta inhibitor MLN120b in the DLBCL cell line HBL1.

first: Georg

last: Lenz


title: Differential gene expression of periostin-overexpressing MC3T3-E1 cells

city: Oviedo

first: Alvaro

last: Obaya

state: Asturias

address: Julian Claveria s/n

department: Biología Funcional

country: Spain

institute: Universidad de Oviedo

summary: Periostin participates in different processes involved in connective tissue homeostasis. It is also involved in repairment of damaged tissues. We used the osteoblast murine cell line MC3T3-E1 cell line to show how overexpresion of periostin is able to increase their adhesion properties while diminishing their migration capacity.  By differential gene expression we evaluated putative targets involved in those cellular properties.

overall_design: An isolated clone of MC3T3-E1 periostin-overexpressing cells was selected to compare differential gene expression with MC3T3-E1 cells.


title: Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice

city: Fukuoka

first: Toyoshi

last: Yanagihara

state: Fukuoka

address: Maidashi, Higashi-ku

department: Immunobiology and neuroscience

institute: Medical institute of bioregulation, Kyushu University

summary: Background and objective: The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been addressed. We previously demonstrated that DNA damage was found in bronchiole at early phase, and subsequently extended to alveolar cells at later phase in bleomycin-induced pulmonary fibrosis in mice. Club cells are progenitor cells for bronchiole, and are recognized to play protective roles against lung inflammation and damage. The aim of the study was to elucidate the role of club cells in the development of pulmonary fibrosis.   Methods: C57BL/6J mice were received naphthalene intraperitoneally at day -2 to deplete club cells, and were given intratracheal bleomycin or vehicle at day 0. Lung tissues were obtained at day 1, 7, and 14, and bronchoalveolar lavage was performed at day 14. Gene expression was analysed from bronchiolar ephithelial cells sampled by laser captured microdissection at day 14.  Results: Surprisingly, naphthalene-induced club cell depletion protected mice from bleomycin-induced lung injury and fibrosis. We conclude that club cells are involved in the development of lung injury and fibrosis.

first: Tetsuya

last: Yokoyama

first: Kunihiro

last: Suzuki


title: Gene expression and CGH analysis of aneuploid embryonic stem cells

city: Beijing

first: Meili

last: Zhang

address: Dong Dan San Tiao 5

department: State Key Laboratory of Medical Molecular Biology, Department of Medical Genetics

institute: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College

type: Genome variation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Gene expression of splenocytes 6 hours after bortezomib or cyclophosphamide injection

city: Sendai

first: Hiroshi

last: Fujii

state: MIyagi

address: Seiryo 1-1, Aoba-ku

department: Department of Hematotology and Rheumatology

institute: Tohoku University, School of Medicine

summary:
Background: Bortezomib (Bz) is a proteasome inhibitor that directly targets antibody-producing plasma cells. We recently reported the first randomized control trial that evaluated the effects of Bz in patients with systemic lupus erythematosus (SLE). In that study, we demonstrated that Bz treatment is associated with many adverse reactions in patients with refractory disease. In the present study, we examine the therapeutic and toxic effects of Bz on MRL/MpJ-lpr/lpr (MRL/lpr) mice with severe disease activity.
Methods: Female MRL/lpr mice at 10 and 14 weeks of age were treated with phosphate-buffered saline (PBS) (n = 13), Bz (750 μg/kg twice weekly) (n = 12), and cyclophosphamide (Cyc) (1 mg/body, once in 2 weeks) (n = 15). Cellular subsets, serum immunoglobulin, anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibody titer, and a pathological index of glomerulonephritis were then analyzed at 22 weeks of age. Survival curves of the 10 and 14 weeks-Bz-treated groups were compared. Blood counts, creatinine, liver enzymes, and serum cytokine levels were measured 1 week after Bz treatment. Gene expression profiling of spleens from Bz and Cyc treatment mice were compared with those from control mice.
Results: The anti-dsDNA antibody levels were significantly higher in 14- than in 10-week-old mice, indicating a higher disease activity at 14 weeks. A significant decrease in the number of splenic cells and glomerulonephritis index was observed in Bz- and Cyc-treated mice. Bz, but not Cyc, significantly decreased serum immunoglobulin and anti-dsDNA antibody titer levels. Survival curve analysis revealed a significantly higher mortality rate in 14- than in 10-week-old Bz-treated and control groups. Following two injections of Bz, serum IL-6 and TNF-α levels were significantly more elevated in 14- than in 10-week-old mice. Potentially immunogenic molecules, such as heat shock proteins and calreticulin, were specifically upregulated in spleens of Bz- but not Cyc-treated mice.
Conclusions: In spite of its therapeutic effect, Bz treatment had more toxic effects associated with increased pro-inflammatory cytokine levels in mice with a higher disease activity. Understanding the mechanism of the toxicity and developing preventive strategies against it is important for the safe clinical application of Bz in human SLE.

overall_design: Fourteen-week-old MRL/lpr mice were injected with bortezomib (750 µg/kg, subcutaneously), cyclophosphamide (1mg/body, intraperitoneally) or PBS. The mice were sacrificed, and the spleens were removed 6 h after injecting the drugs. To clarify the change of gene expression profiling, total RNA from spleen tissues were extracted and analysed with microarray.

first: Tomoko

last: Ikeda


title: Epigenetic Gene Regulation by Janus Kinase 1 in Diffuse Large B Cell Lymphoma (Agilent)

first: Louis

middle: M.

last: Staudt

state: MD

address: 9000 Rockville Pike, Bldg 10, Rm 4N114

department: Lymphoid Malignancies Branch

institute: National Cancer Institute

summary: JAK kinases classically signal by activating STAT transcription factors, but can also regulate gene expression by epigenetically phosphorylating histone H3 on tyrosine 41 (H3Y41-P). In diffuse large B cell lymphomas (DLBCL), JAK signaling is a feature of the ABC subtype and is triggered by autocrine production of IL-6 and IL-10. Whether this signaling involves STAT activation, epigenetic modification of chromatin or both mechanisms is unknown. Here we use genetic and pharmacological inhibition to show that JAK1 signaling sustains the survival of ABC DLBCL cells. While STAT3 contributed to the survival of ABC DLBCL cell lines, forced STAT3 activity could not protect these cells from death following JAK1 inhibition, suggesting epigenetic JAK1 action. JAK1 regulated the expression of nearly 3,000 genes in ABC DLBCL cells, and the chromatin surrounding many of these genes was modified by H3Y41-P marks that were diminished by JAK1 inhibition. These JAK1 epigenetic target genes encode important regulators of ABC DLBCL proliferation and survival, including IRF4, MYD88 and MYC. A small molecule JAK1 inhibitor cooperated with the BTK inhibitor ibrutinib in reducing IRF4 levels and acted synergistically to kill ABC DLBCL cells, suggesting that this combination should be evaluated in clinical trials.

overall_design: Samples from an ABC DLBCL cell line, TMD8, were exposed to 2 uM AZD1480 for 1, 3, 6, and 24 hours (n=4).


title: Gene expression alternations in the offspring liver from chromium restriction diet dams

first: Qian

address: No. 1 Shuaifuyuan, Dongcheng District

institute: Peking Union Medical College Hospital

summary: Maternal chromium restriction may disturb susceptibility in offspring. Liver from maternal chromium diet has 264 up- and 199 down- regulated genes, compared to control. Especially, Insulin signaling pathway and WNT pathway were affected.

overall_design: We performed microarray analyses of offspring liver from chromium restriction dams and control diet dams at 32 week (n=3 per group).

first: Xiaofang

last: Sun

first: Xinhua

last: Xiao

first: Jia

last: Zheng

first: Ming

last: Li

first: Miao

last: Yu

first: Fan

last: Ping

first: Zhixin

last: Wang

first: Cuijuan

last: Qi

first: Tong

first: Xiaojing


title: Gene expression profiling of mouse uterus during experimentally induced decidualization

city: Urbana

first: Juanmahel

last: Davila

state: Illinois

address: 2001 S. Lincoln Avenue

department: Comparative Biosciences

institute: University of Illinois

summary: To gain insights into the genes whose expression levels are altered during stromal cell differentiation (decidualization), gene microarray profiling was performed following the experimentally induced decidualization protocol.

overall_design: CD-1 adult female mice were primed with steroid hormone, estrogen and progesterone, following experimentally induced decidualization protocol. One uterine horn was injected with corn oil to stimulate decidualization, the other horn served as unstimulated control. Uterine tissues were collected 72 h post stimulation. The uterine horns, from 3 animals/treatment, were pooled and total RNA was isolated and then hybridized to high-density Affymetrix microarrays according to the Affymetrix protocol.

first: Quanxi

first: Indrani

last: Bagchi

first: Milan


title: Expression date from db/db mice with or without treatment of traditional Chinese medicine Tang-shen Formula

status: Public on Jan 25 2017

first: Hailing

last: Zhao

address: Yinghua DongLu Hepingli Chaoyang District

institute: China–Japan Friendship Hospital

summary:
The Chinese herbal granule Tangshen Formula (TSF) has been proven to decrease proteinuria and improve estimated glomerular filtration rate (eGFR) in diabetic kidney disease (DKD) patients with albuminuria. Nevertheless, little was known on the underlying mechanisms of TSF on treating DN.
We used microarrays to detail to explore the target genes of TSF in the treatment of DN.

overall_design: Renal cortical tissues were selected from db/m mice, db/db mice and db/db mice with TSF-treatment for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain to identify the therapeutic target of TSF in diabetic renal injuries through microarray-based gene expression profiling.

first: Ping

first: Tingting

first: Haojun

first: Meihua

last: Yan


title: The effect of VGLL4  on HCT116 colorectal cancer cell line

first: Shi

last: Jiao

address: 320 Yue Yang Road

institute: Shanghai Institutes of Biological Sciences

summary: VGLL4, a tumor suppressor, is negative regulator of Hippo/YAP signaling. To explore the role of VGLL4 during colorectal cancer cell line, we explore microarray analysis of HCT116 cells after stable transfection of VGLL4 and shVGLL4 for 48 h.

overall_design: Scr-1, Scr-2, shVGLL4-1, shVGLL4-2

first: Zhaocai

last: Zhou


title: Gene expression in mouse embryonic stem cells trisomic for chromosome 6, 8, 11 and 15

first: Meili

last: Zhang

summary: Aneuploidy, an uneven number of chromosomes, leads to severe developmental defects in mammals and is also a hallmark of cancer. However, whether aneuploidy is a driving cause or a consequence of tumor formation remains controversial. Paradoxically, existing studies based on aneuploid yeast and mouse fibroblasts have shown that aneuploidy is usually detrimental to cellular fitness. Here, we examined the effects of aneuploidy on mouse embryonic stem cells. Using a novel genetic scheme, we generated a series of aneuploid cell lines that each carries an extra copy of single chromosomes and then characterized the traits shared by these cell lines. All the aneuploid cell lines had rapid proliferation rates and enhanced colony formation efficiencies. They were less dependent on growth factors for self-renewal and showed a reduced capacity to differentiate in vitro. Moreover, xenografted aneuploid stem cells formed teratomas more efficiently, with features of neoplastic progression. These findings demonstrate that aneuploidy enhances the self-renewal capacities of stem cells and reduces their differentiation abilities.

overall_design: We used the wild-type AB1 mouse ES cells (male) as control. The mouse ES cell lines with three copies of chromosome 6, 8, 11 or 15 were the experimental samples. Two biological replicates were used for each cell line. The samples were: WT (P18 and P20), Ts6 (P9 and P18), Ts8 (P10 and P13), Ts11 (P8 and P11), Ts15 (P11 and P14). Gene expression profiles of all the cell lines were analyzed on the Agilent SurePrint G3 Mouse Gene Expression 8×60 K microarrays. They include probes to mRNAs and long intergenic non-coding RNAs (lincRNAs).

first: Yuyan

last: Jia

first: Guang

last: Liu

first: Shuhui

last: Song

first: Li

last: Cheng

first: Allan

last: Bradley

first: Yue

last: Huang


title: Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression

status: Public on Jan 03 2017

first: Thomas

last: Weichhart

address: Waehringerstraße 10

department: Center for Pathobiochemistry and Genetics

institute: Medical University of Vienna

summary:
Gene expression analysis of primary CSF1-deprived bone marrow-derived macrophages (BMDM) of Tsc2fl/fl LysM+/+ and TSC2fl/fl LysM+/cre mice
Maintenance of tissue homeostasis requires a tight control of the in situ-proliferative capacity of tissue-resident macrophages. Here we show that specific deletion of Tsc2 in myeloid cells breaks quiescence and strongly induces macrophage proliferation and hypertrophy leading to granuloma formation in vivo in an mTORC1-dependent manner. Intriguingly, the growth factor CSF1 induces expression of cyclin-dependent kinase 4 (CDK4) via TSC2-mTORC1 to stimulate cell proliferation, while simultaneously NF-κB signaling and apoptosis are inhibited. Tsc2-deficient macrophages show constitutive CDK4 expression and enhanced M2-like polarization that is supported by a metabolic reprogramming towards increased glycolysis and mitochondrial metabolism. Strikingly, mTORC1 activation and macrophage proliferation are identified as a hallmark of the human granulomatous disease sarcoidosis and correlate with a clinically progressive disease outcome. In conclusion, TSC2-mTORC1 integrates macrophage quiescence, polarization, and metabolism to prevent granulomatous disease. Fundamentally, we show that the macrophage cell cycle is controlled by a growth factor-induced expression of CDK4.

overall_design: Total RNA of CSF1-deprived bone marrow-derived macrophages (BMDM) of Tsc2fl/fl LysM+/+ and TSC2fl/fl LysM+/cre mice (n=4/group) was subjected to microarray analysis on Affymetrix GeneChip® Mouse Gene 2.0 ST arrays. Array data were processed using Affymetrix Expression Console. No technical replicates were performed.

first: Monika

last: Linke

first: Ha

middle: T

last: Pham

first: Karl

last: Katholnig

last: Schnöller

first: Anne

last: Miller

first: Florian

last: Demel

first: Birgit

last: Schütz

first: Margit

last: Rosner

first: Boris

last: Kovacic

first: Nyamdelger

last: Sukhbaatar

last: Niederreiter

first: Stephan

last: Blüml

first: Peter

last: Kuess

first: Veronika

last: Sexl

first: Mathias

last: Müller

first: Mario

last: Mikula

first: Wolfram

last: Weckwerth

first: Arvand

last: Haschemi

first: Martin

last: Susani

first: Markus

last: Hengstschläger

first: Michael

last: Gambello


title: Gene expression profile of colon endothelial cells in early GVHD with Microarray

status: Public on Jan 27 2017

city: Berlin

first: Katarina

last: Riesner

address: Augustenburger Platz 1

department: Hematology, Oncolgy and Tumorimmunology

institute: Charité University Medicine

summary:
During inflammatory diseases, infiltrating immune cells can induce endothelial activation and angiogenesis by cytokines and other mediators. The inhibition of inflammation-associated angiogenesis ameliorates inflammatory diseases by reducing the recruitment of tissue infiltrating leukocytes. However, there is limited evidence on initial mechanisms of both processes. We show in experimental models that angiogenesis precedes leukocyte infiltration during graft-versus-host disease (GVHD). GVHD, a systemic inflammatory disease caused by host-reactive T cells primarily attacking the epithelial cells of the GVHD target organs liver, skin and intestines, leads to substantial morbidity and mortality after allogeneic hematopoetic stem cell transplantation. A key feature of GVHD is the incompletely understood organ tropism to skin, liver and the intestines. We demonstrate that angiogenesis initiates GVHD in target organs whereas in non-target organs no angiogenesis and no subsequent inflammation occurred. To shed light into the initiation phase of angiogenesis we looked at classical endothelial cell activation signs, such as upregulation of the Vegfa/VEGFR1+2 pathway or adhesion molecules, but could not find an association. However, endothelial cells in early GVHD showed profoundly higher deformation in real-time deformability cytometry suggesting enhanced migratory and proliferating potential of endothelial cells during the initiation of angiogenesis in GVHD target organs.
We used microarrays to detect alternative pathways in endothelial cells of the GVHD target organ colon that could be responisble for initial angiogenesis in GVHD. We identified several up-and down-regulated genes during this process. Strikingly, we found several cytoskeleton as well as metabolic-associated and related gene alterations which may explain the enhanced migration and proliferation of endothelial cells in initiating GVHD. Our study adds evidence to the hypothesis that angiogenesis can initiate inflammation and provides novel insight in pathophysiology and tropism of GVHD.

overall_design: Total RNA was isolated from FACS-sorted (CD45-CD11b-CD31+) endothelial cells from GVHD target organ colon of allogeneic (n=4, allo107, allo108, allo109, allo111) and syngeneic (n=4, syn115, syn116, syn117, syn118) transplanted mice at day+2 after transplantation using the mirVana miRNA Isolation Kit (Ambion) and subjected to microarray analysis (GeneChip Mouse Gene 2.0 Array, Affymetrix).

first: Sabine

last: Schmidt

first: Giannino

last: Patone

first: Aleixandria

last: McGearey

first: Sarah

last: Mertlitz

first: Martina

last: Kalupa

first: Olaf

last: Penack


title: Genome wide host gene expression analysis in Mice infected with Pasteurella multocida

status: Public on Jan 01 2017

city: Karnal

first: Ravi Kumar

last: Gandham

state: Haryana

address: Makrampur

country: India

institute: ICAR-NBAGR

summary: Using microarray technology, we aim to identify the host gene expression for understanding the cross talk of signaling pathways that leads to the death of mice under P.multocida infection.

overall_design: Liver, spleen and lung were collected at the onset(6h) and late(18h) stages of P.multocida infection to identify the global gene expression changes vis - a - vis the control in the host

first: Bhuvana

last: Priya

first: Arun

middle: P

last: Milton

first: K

last: Viswas

first: R

last: Agarwal

first: Ravi


title: ProNGF Drives Localized and Cell Selective Parvalbumin Interneuron and Perineuronal Net Depletion in the Dentate Gyrus of Transgenic Mice: a microarray study in proNGF-overexpressing transgenic mouse

status: Public on Jan 26 2017

city: Roma

first: Ivan

last: Arisi

address: viale Regina Elena 295

department: Bioinformatics Facility

country: Italy

institute: European Brain Research Institute

summary: The NGF precursor proNGF has conflicting effects compared to NGF, depending also on the panel of receptors expressed by target cells; although in physiological conditions proNGF is the most abundant form in the brain, it is known to increase further in Alzheimer’s Disease (AD) cortex, relative to mature NGF. The correct balance between the levels and signaling of mature NGF and its precursor proNGF, are therefore critical factors in maintaining brain homeostasis. In a previous study, we demonstrated that proNGF\NGF imbalance determines Abeta peptide processing, neurodegeneration and learning and memory deficit in lines of transgenic mice (TgproNGF#3 and TgproNGF#72) expressing postnatally furin-resistant proNGF in the neuronal compartment. In this work, we analyzed the hippocampal transcriptional profile of TgproNGF#3 mice before and in early and late phases of neurodegeneration, demonstrating that proNGF imbalance induces a broad down-regulation of transcripts, including mRNAs relevant for synaptic transmission and extracellular matrix (ECM) components, essential in shaping plasticity. Consistently, the aberrantly down-regulated transcription profile underlies a functional deficit in long-term potentiation (LTP) in the dentate gyrus (DG) and an alteration of the excitatory/inhibitory (E\I) balance, as revealed by spontaneous epileptiform events detected by multi-electrode arrays (MEA) in the entorhinal cortex-hippocampal (EC-HP) network. A greatly reduced number of parvalbuminergic interneurons was observed in the DG, accompanied by alterations in the expression of selected BDNF splice variants. Selective and region-specific progressive alterations of the interneuron\perineuronal net (PNN) system are detected in the DG accompanied, in aged mice, by depletion of calbindin in granule cells. Since the onset of spontaneous discharges in the EC-HP network precedes the transcript profile changes and the plasticity deficit, we conclude that changes in E\I homeostasis are a primary consequenceof unbalanced proNGF\NGF signaling.

overall_design: Transcriptional profile (mRNAs) was measured in the brain hippocampus of TgproNGF#3 mice, a model of proNGF over-expression, at 1, 3 and 12 months of age. In each time point 4 TgproNGF#3 samples were compared to 4 corresponding Wild Type (strain C57Bl/6xDBA/2) except the 12m timepoint which has 3 replicates.

first: Luisa

last: Fasulo

first: Rossella

last: Brandi

first: Federico

last: La Regina

first: Capsoni

last: Simona

first: Nicola

last: Berretta

first: Mara

last: D’Onofrio

first: Antonino

last: Cattaneo


title: Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells [expression 2]

status: Public on Jan 06 2017

city: Kyoto

first: Shinya

last: Yamanaka

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

institute: Center for iPS Cell Research and Applicaton (CiRA), Kyoto University

summary: Nat1 (also known as p97/Dap5/Eif4g2) is a ubiquitously expressed cytoplasmic protein that is homologous to the c-terminal two thirds of eukaryotic translation initiation factor 4G (also known as Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mESCs) were resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as eIF3, eIF4A and ribosomal proteins. However, NAT1did not bind to eIF4E or poly A binding proteins, which are critical for cap-dependent translation initiation. In contrast, compared to eIF4G1, NAT1 preferentially interacts with eIF2, FMR and related proteins, and especially PRRC2 family members. We also found that Nat1-null mESCs possess a transcriptional profile similar, though not identical, to ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and GSK3 signaling pathways. In Nat1-null mESCs, the ERK pathway is suppressed even without inhibitors. Ribosome profiling revealed that translation of Map3k3 and Sos1 is suppressed in the absence of Nat1. Forced expression of Map3k3 induced differentiation of Nat1-null mESCs. These data collectively showed that Nat1 is involved in translation of proteins that are required for cell differentiation.

overall_design: The effects of Map3k3 expression in Nat1-null mouse embryonic stem cells, N=15; wild-type mouse embryonic stem cells, N=3, Nat1-null mouse embryonic stem cells, N=3, tet-Map3k3-expressing Nat1-null mouse embryonic stem cells cultured with Dox, N=3, tet-Map3k3-expressing Nat1-null mouse embryonic stem cells cultured without Dox, N=3, tet-EGFP-expressing Nat1-null mouse embryonic stem cells cultured with Dox, N=3

first: H

last: Sugiyama

first: M

last: Narita


title: Plasmodium-exhausted Nfat1+/+ versus Nfat1-/- CD4+ T cells

status: Public on Dec 31 2016

city: Bronx

first: Fernando

last: Macian

address: 1300 Morris Park Av.

department: Pathology

institute: Albert Einstein College of Medicine

summary: Expression data from antigen-experienced Nfat1+/+ and Nfat1-/- CD4+ T cells following 21 days of Plasmodium yoelii 17XNL infection.

overall_design: Total RNA was isolated from CD4+ CD49d+ CD11a-high cells sorted from spleens following 21 days Plasmodium yoelii 17XNL infection and subjected to microarray analysis.


title: A Homeostatic Shift Facilitates Endoplasmic Reticulum Proteostasis through Transcriptional Integration of Proteostatic Stress Response Pathways [expression]

status: Public on Dec 21 2016

first: Eri

last: Kobayashi

state: Miyagi

address: 2-1 Seiryo-machi, Aobaku

department: Medical Biochemistry

institute: Tohoku University Graduate School of Medicine

summary: Eukaryotic cells maintain protein homeostasis through the activity of multiple basal and inducible systems, which function in concert to allow cells to adapt to a wide range of environmental conditions. Although the transcriptional programs regulating individual pathways have been studied in detail, it is not known how the different pathways are transcriptionally integrated such that a deficiency in one pathway can be compensated by a change in an auxiliary response. One such pathway that plays an essential role in many proteostasis responses is the ubiquitin-proteasome system, which functions to degrade damaged, unfolded, or short half-life proteins. Transcriptional regulation of the proteasome is mediated by the transcription factor Nrf1. Using a conditional knockout mouse model, we found that Nrf1 regulates protein homeostasis in the endoplasmic reticulum (ER) through transcriptional regulation of the ER stress sensor ATF6. In Nrf1 conditional-knockout mice, a reduction in proteasome activity is accompanied by an ATF6-dependent downregulation of the endoplasmic reticulum-associated degradation machinery, which reduces the substrate burden on the proteasome. This indicates that Nrf1 regulates a homeostatic shift through which proteostasis in the endoplasmic reticulum and cytoplasm are coregulated based on a cell's ability to degrade proteins.

overall_design: Gene expression in the liver obtained from Nrf1 CKO and control mice. Nrf1flox/flox::CYP1A1-Cre mice subcutaneously injected with 40 mg/kg body weight of 3-methylcholanthrene (3MC) were used as Nrf1 CKO mice, while Nrf1flox/flox mice similarly treated with 3MC were used as control mice. Livers were obtained 2 weeks after the 3MC injection.

first: Liam

last: Baird

first: Tadayuki

last: Tsujita

first: Ryo

last: Funayama

first: Takeshi

last: Nagashima

first: Keiko

last: Nakayama

first: Masayuki

last: Yamamoto


title: Gene Expression Profile Changes due to Bleomycin-Induced DNA Damage in Human Fibroblasts in Space

status: Public on Jan 20 2017

city: Houston

first: Tao

last: Lu

state: Texas

address: 2101 E NASA Pkwy

department: Radiation Research

institute: NASA Johnson Space Center

summary: To understand gene expression responses in confluent human fibroblast in microgravity conditions to bleomycin treatment.

overall_design: Confluent human fibroblasts AG01522 were flown to the International Space Station (ISS). After three day on ISS, the cells were treated with bleomycin at 1.0 microg/ml for 3 hours. The cells were washed and fixed with RNALater. Total RNA were isolated after the samples were returned to earth and subject to microarray analysis.

first: Ye

last: Zhang

first: Kidane

last: Yared

first: Honglu

last: Wu


title: Expression data from bone marrow derived DCs stimulated with different peptide-based nanovaccine formulations against L. infantum infection

status: Public on Dec 24 2016

city: Philadelphia

first: Theresa

last: Busch

state: PA

address: 13400 Civic Center Blvd

department: Radiation Oncology

institute: University of Pennsylvania

summary: Visceral leishmaniasis (VL), caused by Leishmania spp protozoan parasites, can provoke overwhelming and protracted epidemics, with high case–fatality rates. Despite extensive efforts towards the development of an effective prophylactic vaccine, no promising vaccine is available yet for humans. Multi-epitope peptide based vaccine development is manifesting as the new era of vaccination strategies against VL. Aim of the study was the design of chimeric peptides from immunogenic L. infantum proteins for encapsulation in PLGA nanoparticles (NPs) alone or in combination with MPLA adjuvant, or in PLGA NPs surface modified with an octapeptide mimicking TNF-alpha for DCs targeting, in order to construct a peptide-based nanovaccine. The in vitro evaluation of the above nanoformulations was performed in DCs isolated from HLA-A2.1 transgenic mice. Characterization of DCs transcriptional responses to these vaccine candidates via microarrays could improve our understanding of their mechanisms of action on DCs' functional differentiation and the type of adaptive immunity subsequently induced.

overall_design: For the 5 different conditions (4 stimulated and 1 unstimulated - control), 15 samples were analyzed. Experiments were conducted in biological triplicate.

first: Evita

last: Athanasiou

first: Maria

last: Agallou

first: Spyros

last: Tastsoglou

first: Artemis

middle: G

last: Hatzigeorgiou

first: Olga

last: Kammona

first: Costas

last: Kiparissides

first: Evdokia

last: Karagouni


title: The function of cullin 3 in macrophage

city: Omaha

first: Xinghui

last: Li

state: Ne

address: 985965 Nebraska Medical Center

department: Pathology and microbiology

institute: the University of Nebraska Medical Center

summary: To further understanding the function of cullin 3 during inflammation in macrophages, we have employed mouse bone marrow derived macrophages microarray expression profiling to identify the gens that involve in regulationg inflammatory respones upon LPS challenge.  Mouse BMM were stimulated with LPS for 6 hours and RNA was extracted for microarray. Ogt was indentified by comparison between wildtype and Cullin 3 knockout BMM.

overall_design: Mouse BMM were stimulated with LPS for 6 hours and RNA was extracted for microarray.  Samples were in duplicate and the microarray was done once.

first: Haitao

last: Wen

first: Zhibin


title: Response to poly(I:C) in WT and GADD34ΔC/ΔC MEFs

status: Public on Jan 16 2017

city: Marseille cedex 09

first: Philippe

last: Pierre

address: Case 906

institute: Centre d’Immunologie de Marseille-Luminy

summary:
The stress-inducible GADD34 was shown to be induced during dsRNA sensing and is a stress-inducible PP1 cofactor responsible for dephosphorylation of translation initiation factor eIF2alpha. Its activity was shown to be required for efficient cytokine production in MEFs after poly(I:C) delivery.
A microarray-based mRNA transcription analysis was used to compare the transcriptional response of WT and GADD34ΔC/ΔC MEFs lipofected with poly(I:C)

overall_design: MEFs WT and GADD34ΔC/ΔC were left untreated or were lipofected with 2.5µg/ml of HMW poly(I:C) during 6 hours. Their RNA content was extracted with phenol/chloroforme and purified. Three independent experiments were performed.

first: Alexandre

last: Dalet

first: Tobias

last: Weil


title: Expression regulation by Pcgf6 in mouse embryonic stem cells

status: Public on Jan 14 2017

city: Nanjing

first: Wukui

last: Zhao

state: Jiangsu

address: 12 Xuefu Road

department: Model Animal Research Center

institute: Nanjing University

summary: The Polycomb group (PcG) proteins have an important role in controlling the expression of key genes implicated in embryonic development, differentiation and decision of cell fates. Emerging evidence suggests that Polycomb repressive complexes 1 (PRC1) is defined by the six Polycomb group RING finger protein (Pcgf) paralogs and Pcgf proteins can assemble into noncanonical PRC1 complexes. However, little is known about the precise mechanisms of differently composed noncanonical PRC1 in the maintenance of the pluripotent cell state. Here we disrupt the Pcgf genes in mouse embryonic stem cells by CRISPR-Cas9 to investigate Pcgf6 function. Microarray experiments were performed using wildtype ,Pcgf6 KO and Pcgf6 KO + Pcgf6_flag ES cells.

overall_design: Gene expression profiling of wildtype ,Pcgf6 KO and Pcgf6 KO + Pcgf6_flag ES cells.

first: Huan

last: Tong

first: Yikai

last: Huang

first: Yun

last: Yan

first: Jinzhong

last: Qin


title: Forced Expression of MIST1 in Hepatocytes

city: Houston.

first: Jason

last: Mills

state: T

address: One Baylor Plaza

department: Gastroenterology, Medicine

institute: Baylor College of Medicine

summary: MIST1 over-expression has not been analyzed in a cell type that does not express endogenous MIST1.  Here, we force-express ectopic MIST1 in the hepatocytes of mouse livers.  We extracted mRNA and compared gene expression levels between MIST1-expressing mouse livers to controls.

overall_design: One mouse from each condition (MIST1-expressing and control) was injected with AAV8-TBG-iCre at 7 weeks. Mouse was subsequently sacrificed 2 weeks later and RNA extracted and hybridized on Affymetrix microarrays.  Two separate mRNA extracations from separate liver cubes were performed on each mouse

first: Hei-Yong

last: Lo


title: NorUrsodeoxycholic Acid Ameliorates Cholemic Nephropathy in Common Bile Duct Ligated Mice

city: Graz

first: Karin

last: Wagner

state: Styria

address: Stiftingtalstrasse 24

department: Molecular Biology

institute: Medical University Graz

summary: Cholestasis may cause cholemic nephropathy that can be modelled in common bile duct ligated (CBDL) mice. We aimed to explore the therapeutic efficacy and mechanisms of norursodeoxycholic acid (norUDCA) in cholemic nephropathy. To determine whether norUrsodeoxycholic acid (norUDCA) prevents cholemic nephropathy in long-term CBDL mice, a norUDCA-enriched diet (0.125% w/v, corresponding to 200 mg/kg/day for a mouse of 25 g body weight eating about 4g daily) or a standard mouse diet (Sniff, Soest, Germany) were started 5 days prior to CBDL and were continued until harvesting 3 weeks thereafter. For transcriptional profiling using microarray technology, we compared sham-operated (SOP) mice and 3-week CBDL mice that were either fed 0.125% norUDCA-enriched or standard mouse diets.

overall_design: We analyzed 3 samples per experimental group (SOP, 3w CBDL, 3w CBDL/norUDCA)

first: Elisabeth

last: Krones

first: Peter

last: Fickert


title: Expression data from radiation-induced pulmonary fibrosis mouse models

status: Public on Jan 12 2017

city: Busan

first: Beomseok

last: Son

address: 322 Biology Building, 2 Busandaehakro 63beon-gil, Geumjeong-gu

country: South Korea

institute: Pusan National University

summary:
Radiation-induced pulmonary fibrosis (RIPF) is one of the most common side effects of lung cancer radiotherapy. In the mouse lungs developing RIPF, excessive accumulation of extracellular matrix and myofibroblasts with scar formation occurs.
We used microarrays to detail the global program of gene expression underlying development of radiation-induced pulmonary fibrosis and identified a variety of genes whose expression were up-regulated during this process.

overall_design: Seven-week-old male C57BL/6 mice were exposed to thoracic irradiation. After 25 weeks, animals were euthanized and lung samples were harvested. Development of radiation-induced pulmonary fibrosis was confirmed by western blotting for α-smooth muscle actin and hematoxylin and eosin staining.

first: TaeWoo

last: Kwon

first: BuHyun

last: Youn


title: ALD-PPARβ/δ

status: Public on Jan 04 2017

city: University Park

first: Pei-Li

last: Yao

address: 312 Life Sciences Building

institute: Pennsylvania State University

summary: Alcoholic liver disease is a pathological condition caused by over-consumption of alcohol. Due to the high prevalence of morbidity and mortality associated with this disease, there remains a need to elucidate the molecular mechanisms underlying the etiology to develop new treatments. Since peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) modulates ethanol-induced hepatic effects, the present study examined alterations in gene expression that may contribute to this disease.

overall_design: Age-matched (8-10 weeks) male Pparβ/δ+/+ and Pparβ/δ-/- mice were fed ad libitum daily with either liquid control or ethanol diets for 16 weeks (N=10 per group). The ethanol diet contained 4% (v/v) ethanol.

first: Takayuki

last: Koga

first: Maryam

last: Goudarzi

first: Iain

middle: A

last: Murray

first: Gayathri

last: Balandaram

first: Frank

last: Gonzalez

first: Gary

last: Perdew

first: Albert

last: Fornace Jr

first: Jeffrey

last: Peters


title: FACS-array profiling in retinal endothelial cells from living mouse retinas without pericyte coverage

city: Kobe

first: Sentaro

last: Kusuhara

state: Hyogo

address: 7-5-2 Kusunoki-cho, Chuo-ku

department: Department of Surgery

institute: Kobe University Graduate School of Medicine

summary: Pericytes confer vascular stability in the retina, and the loss of pericytes can cause the blood-retina barrier breakdown seen in diabetic retinopathy. To identify endothelial-specific genes expressed in pericyte-deprived retinal vessels, we purified genetically labeled endothelial cells from Tie2-GFP transgenic mice treated with neutralizing antibody against PDGFRb (APB5) and performed gene expression profiling using DNA microarray. To find out endothelial-specific genes associated with the loss of pericyte coverage, the comparison of microarray data was carried out between retinal endothelial cells (data from GSE27238) and APB5-treated retinal endothelial cells.

overall_design: Nine arrays are included. Utilizing fluorescence-activated cell sorting (FACS), we isolated retinal endothelial cells from P8 Tie2-GFP transgenic mice treated with intraperitoneal injections of neutralizing antibody against PDGFRb (APB5) from P0 to P7. RNA extracts from sorted cells were amplified and then hybridized to Affymetrix MGU74v2 series arrays in triplicate.

first: Akiyoshi

last: Uemura

first: Lars

last: Jakt

first: Mitsuhiro

last: Okada

first: Shin-Ichi

last: Nishikawa


title: Interaction network of Talin-1 in promoting hepatocellular carcinoma progression

city: Hefei

first: Peng

last: Chen

state: Anhui province

address: Jixi road

institute: liver

summary:
Talin-1, a macromolecular cytoskeletal protein, promotes hepatocellular carcinoma (HCC) progression. However the underlying mechanism of Talin-1 in HCC remains unclear.
Analysis of the gene expression profiles of normal control HCC cell (MHCC-97L) and knockdown Talin-1 HCC cells (sh-Talin-1 MHCC-97L).

overall_design: We analyzed the gene expression proﬁles of normal control HCC cells (MHCC-97L) and knockdown Talin-1 HCC cells (sh-Talin-1 MHCC-97L) using an oligonucleotide microarray, to identify changed genes in knockdown Talin-1 HCC cells comparing with those in normal control HCC cells (MHCC-97L cell).

first: Yeben

last: Qian


title: Whole transcriptome analysis of the ventrolateral hypothalamic parvafox nucleus in mice

status: Public on Dec 28 2016

city: Fribourg

first: Viktoria

last: Szabolcsi

address: Rte Albert-Gockel 1

institute: University of Fribourg, Anatomy

summary:
The ventrolateral hypothalamic parvafox (formerly called PV1-Foxb1) nucleus is an anatomical entity of recent discovery and unknown function. With a view to gaining an insight into its putative functional role(s), we conducted a gene-microarray analysis.
The parvafox nucleus was specifically sampled by laser-capture microdissection and the transcriptome was subjected to a microarray analysis on Affymetrix chips. Eighty-two relevant genes were found to be potentially more expressed in this brain region than in either the cerebral cortex or the hippocampus. When the expression patterns of these genes were counterchecked in the Allen-Database of in-situ hybridizations and in the B*-microarray database, their localization in the parvafox region was confirmed for thirteen. For nine novel genes, which are particularly interesting because of their possible involvement in neuromodulation, the expression was verified by quantitative real time-PCR. Of particular functional importance may be the occurrence of glycine receptors, the presence of which indicates that the activity of the parvafox nucleus is under ascending inhibitory control.

overall_design: Regions encompassing the parvafox nucleus, the cerebral cortex (piriform and entorhinal cortex) and the hippocampus (CA2-CA3 area) were sampled by laser capture-microdissection from two adult C57BL/6 mice (mouse 355 and mouse 511). Total RNA was extracted and subjected to quality control followed by whole-transcript amplification, the labelling process and the gene-chip hybridization on an Affymetrix Mouse Gene 2.0 ST Array. Data were pre-processed and normalized using the robust multi-array average (RMA) approach and  the software Expression Console provided by Affymetrix (version 1.2.1.20). The data were evaluated using the programming language R (version 2.14.2). The expression profiles of the genes in the parvafox nucleus were compared to those of cortex and hippocampus as reference structures.

first: Gioele

middle: W

last: Albisetti

first: Marco

last: Celio


title: Dopaminergic subset specification as a model for molecular mechanisms of neural vulnerability in Parkinson's Disease

city: Amsterdam

first: Martijs

last: Jonker

address: Science Park 904

department: Microarray Department

country: Netherlands

institute: University of Amsterdam

summary: Mesodiencephalic dopaminergic (mdDA) neurons critically regulate locomotory behavior and   emotion, and dysfunction is associated with psychiatric and neurodegenerative diseases, including   Parkinson's Disease (PD). A pathological hallmark of PD is the specific degeneration of Substantia  Nigra (SN) neurons, whereas Ventral Tegmental Area (VTA) neurons are relatively unaffected.  Differential molecular programming of the developing SN versus VTA may underly this specific  vulnerability, and indeed molecularly distinct mdDA subsets have been identified during  development. Driven by the hypothesis that the molecular signature of the SN and VTA originates  from differential developmental programming and position along the rostral/caudal axis, we  performed genome-wide expression profiling of FACS-purified rostral versus caudal mdDA  neurons. Here, we present the distinct transcriptomes of these mdDA subsets and demonstrate how,  on a genome-wide scale: 1) transcription factor regulation relates to developmental position, 2)  rostral and caudal mdDA neurons differ in their functional genome, 3) the molecular signature of  rostral versus caudal mdDA neurons relates to the SN versus VTA molecular profile in adult mice  and human and 4) human homologues of rostrally enriched genes are mostly downregulated in the  SN of PD patients. Our analyses substantiate the relationship of developmental positions with the  SN versus VTA distinction in adult, and suggest cross-species conservation of molecular programs.  Driven by these observations, we present 69 target genes that are rostral enriched and  downregulated in PD, and thus provide new leads for the investigation of both the complex coding  of developing mdDA subsets and and the molecular mechanisms underlying subset-specific  vulnerability in PD.

overall_design: Microarrray analysis was performed in quadruple. Each biological replicate consisted of a pool of   Pitx3(Gfp/+) rostral or caudal samples from 5-7 individual embyros that were interleaved across  litters to account for litter-to-litter variation, or a pool of Gfp-negative cells from the same  specimens as a common reference.

first: Jesse

middle: V

last: Veenvliet

last: von Oerthel

last: Jacobs

first: Nina

middle: L

last: Haring

first: Marian

last: Groot Koerkamp

first: Rob

last: Dekker

first: Marten

last: Smidt


title: Increased osteoblast viability at alkaline pH in vitro provides a new perspective on bone regeneration

city: Dummerstorf

first: Alexander

last: Rebl

address: Wilhelm-Stahl-Allee 2

department: Institute of Genome Biology

country: Germany

institute: Research Institute for Farm Animal Biology

summary: Developing osteoblasts undergo a sequence of three consecutive phases: cell proliferation, extracellular matrix maturation, and mineralization. We investigated pH effects on these phases using the osteoblast-like cell line MC3T3-E1.

overall_design: MC3T3sc14 cells were cultured at pH 7.4, 7.8 or 8.4 for 14 days before gene expression analysis was run with Affymetrix GeneChip Mouse 2.0 ST Arrays (4 samples each)

first: Anne-Marie

last: Galow

first: Dirk

last: Koczan

first: Jan

last: Gimsa


title: Temporal Gene Expression Profiling of Astrocyte Precursors During Development

status: Public on Dec 16 2016

first: Chad

last: Creighton

state: TX

address: One Baylor Plaza, Mail Stop: BCM305

department: Biostatistics, Ducan Cancer Center

summary: Lineage development is a step-wise process, governed by stage-specific regulatory factors and associated markers. Astrocytes are one of the principle cell types in the CNS and the stages associated with their development remain very poorly defined. To identify these stages we performed gene expression profiling on astrocyte precursor populations in the spinal cord, identifying distinct patterns of gene induction during their development. Validation studies identified a new cohort of astrocyte-associated genes during development and demonstrated their expression in reactive astrocytes in human white matter injury (WMI).

overall_design:
To begin dissecting the intermediate stages of astrocyte development, we performed in vivo temporal gene expression profiling of astrocyte precursor cells from the spinal cord of Glast-dsRed mice. Glast is a glutamate transporter and its induction coincides with the gliogenic switch and continues into mature astrocytes in the spinal cord. We chose 6 time points between mE12.5, the initiation of gliogenesis, and mP7, an early post-natal stage where astrocytes express mature markers. During this developmental interval, Glast-expressing cells emerge from the VZ, populating both the mantle zone and the white matter. However, a subset of Glast-expressing cells remains in the ventricular zone (VZ), where progenitor cells are located, marking cell populations in various lineages and differentiative states during spinal cord development. To sub-fractionate prospective Glast-expressing astrocyte precursors from other potential Glast-expressing lineages, we used the cell surface marker LexA/CD15, which has been used previously to purify astrocytes and various progenitor populations. Upon dissection of glast-dsRed spinal cords, we incubated dissociated cells with CD15 antibody prior to FACS isolation. We isolated 3 populations at each time point: Glast-dsRed+/CD15- (henceforth +/-), Glast-dsRed+/CD15+ (henceforth +/+), Glast-dsRed-/CD15- (henceforth -/-).

Please note that "-/+" and "+/-" are the same.

first: Benjamin

last: Deneen

first: Fengju

last: Chen

first: Lesley

middle: S

last: Chaboub


title: IgH Isotype-Specific B Cell Receptor Dosage Regulates B Cell Fate

city: Boston

first: Duane

middle: R.

last: Wesemann

state: MA

address: 77 Avenue Louis Pasteur

department: Medicine, Division of Allergy and Clinical Immunology

institute: Brigham and Women's Hospital

summary: We use polyclonal Ighγ1/γ1 and Ighε/ε mice (which initially produce only IgG1 or IgE from their respective native genomic configurations) to examine the role of IgH isotype on BCR function. We use microarray expression analysis to compare the internal state of the three IgH isotype specific B-cells. Microarray was used to compare the expression level of various genes in splenic follicular B-cells of Ighε/ε,  Ighγ1/γ1 and Ighwt mice. Each mouse strain also had a naturally pre-assembled Ig light chain (VJk5).

overall_design: The follicular B-cells were sorted form spleen of polyclonal Ighε/ε, Ighγ1/γ1 and Ighwt mice. RNA extracted from trizol was used for the analysis. 3 independent replicates were performed.

first: Pei

last: Tong

first: Alessandra

last: Granato

first: Teng

last: Zuo

first: Neha

last: Chaudhary

first: Seung

last: Han

first: Rakesh

last: Donthula

first: Akritee

last: Shrestha

first: Debattama

last: Sen

middle: R


title: Single six hours sleep deprivation causes glucose intolerance and hepatic steatosis.

status: Public on Dec 27 2016

city: Tokyo

first: Fumika

last: Shigiyama

address: 6-11-1, Omori Nishi, Otaku

department: Internal Medicine

institute: Toho University

summary: To assess the effect of sleep deprivation on glucose metabolism and elucidate the mechanism, we established the mouse model wth C57BL/6J that is useful for the intervention on sleep deprivation associated diabetes and evaluate the liver metabolism and gene expression. Single six hours sleep deprivation induced increased hepatic glucose production assessed by pyruvate tolerance test and the hepatic triglyceride content was significantly higher in the sleep deprivation group than freely sleeping control group. Liver metabolites such as ketone bodies were increased in sleep deprivation group. Some gene expressions which associated with lipogenesis were increased.

overall_design: In order to disturb the sleep, the cage changing method, the water platform method and the gentle handling method was performed using the C57BL/6J male mice. Intraperitoreal glucose tolerance tests were performed with each model. Using the model which shown impaired glucose tolerance by sleep deprivation, the plasma glucose and insulin levels were evaluated. Triglyceride content assay, metabolomics analysis, gene expression analysis by real-time PCR and gene microarray were also performed with liver tissue.

first: Naoki

last: Kumashiro


title: Expression profile of P7 control and Lhx2 cKO somatosensory cortex

status: Public on Dec 15 2016

city: Taipei

first: Shen-Ju

last: Chou

address: 128 Sec. 2, Academia Rd, Nankang

department: Institute of Cellular and Organismic Biology

institute: Academia Sinica

summary: Microarray analysis of control and Lhx2 cKO somatosensory cortices to determine differentially expressed genes at P7 resulting from the loss of Lhx2 in post-mitotic neurons.

overall_design: RNA from primary somatosensory cortices (S1) of three control (Lhx2f/f) and three Lhx2 cKO (Lhx2f/f;Nex-Cre) cortices were collected at postnatal day 7 for microarray analysis.

first: Chia-Fang

last: Wang

first: Hsiang-Wei

last: Hsing

first: Zi-Hui

last: Zhuang

first: Meng-Hsuan

last: Wen


title: Differentially expressed genes in c2c12 myoblasts

status: Public on Dec 23 2016

city: suzhou

first: congcong

last: shen

address: renai road

institute: suzhou university

summary:
Proteosome inhibitors such as bortezomib (BTZ) have been used to treat muscle wasting in animal models. However, direct effect of BTZ on skeletal muscle cells has not been reported. In the present study, our data showed that C2C12 cells exhibited a dose-dependent decrease in cell viability in response to increasing concentrations of BTZ.
We used microarrays to detail the differentially expressed genes in c2c12 myoblasts with different culture conditions.

overall_design: c2c12 cells cultured with different conditions were selected for RNA extraction and hybridization on Affymetrix microarrays. Culture conditions: 10C(cultured with 10%FBS);10B(cultured with 10%FBS,treated with 10 nM BTZ for 24h);10T(cultured with 10%FBS,treated with 50ng/ml TNF-α for 24h);2C(cultured with 10%FBS,then add 2% differentiation medium, harvest at 5th day);2B(cultured with 10%FBS,then add 2% differentiation medium, treated with 10 nM BTZ at 4th day, harvest at 5th day);2T(cultured with 10%FBS,then add 2% differentiation medium, treated with 50ng/ml TNF-α at 4th day, harvest at 5th day)

first: Congcong

last: Shen


title: Brief exposure to small molecules allows induction of mouse embryonic fibroblasts into neural crest-like precursors

status: Public on Mar 22 2017

city: Tsukuba

first: Yasuyuki

last: Kida

state: Ibaraki

address: Central 5-41, Higashi 1-1-1

institute: National Institute of Advanced Industrial Science and Technology (AIST)

summary: In this study, we propose a novel method for inducing neuronal cells by briefly exposing them to small-molecule cocktails in a step-by-step manner. Global gene expression analysis with immunohistochemical staining and calcium flux assays reveal the generation of neurons from mouse embryonic fibroblasts (MEFs). In addition, time-lapse imaging of neural precursor-specific enhancer expression and global gene expression analyses show that the neurons are generated by passing through a neural crest-like precursor stage. Consistent with these results, the neural crest-like cells are able to differentiate into neural crest lineage cells, such as sympathetic neurons, adipocytes, osteocytes, and smooth muscle cells. Therefore, these results indicate that brief exposure to chemical compounds could expand and induce a substantial multipotent cell population without viral transduction.

overall_design: Gene expression of MEFs was measured before and after exposure to small molecular cocktails. MEF_day0: before treatment (ctrl). MEF_day10: after treatment (chem). Experiments were triplicated for each condition.

first: Yuzo

last: Takayama

first: Tamami

last: Wakabayashi

first: Hiroko

last: Kushige

first: Yutaka

last: Saito

first: Yoichiro

last: Shibuya

first: Shinsuke

last: Shibata

first: Wado

last: Akamatsu

first: Hideyuki

last: Okano


title: Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells [expression]

city: Kyoto

first: Shinya

last: Yamanaka

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

institute: Center for iPS Cell Research and Applicaton (CiRA), Kyoto University

summary: Nat1 (also known as p97/Dap5/Eif4g2) is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (also known as Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mESCs) were resistant to differentiation. In the current study, we found that Nat1 and Eif4g1 share many binding proteins, such as Eif3s, Eif4s and ribosomal proteins. However, Nat1 did not bind to Eif4e or poly A binding proteins, which are critical for cap-dependent translation initiation. In contrast, Nat1 binds to Eif2s, Fmr and related proteins, and Prrc2 proteins more preferentially than does Eif4g1. We also found that Nat1-null mESCs possess a status partially similar to ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and GSK3 signaling pathways. In Nat1-null mESCs, the ERK pathway is suppressed even without inhibitors. Ribosomal profiling revealed that translation of Map3k3 and Sos1 is suppressed in the absence of Nat1. Forced expression of Map3k3 induced differentiation of Nat1-null mESCs. These data collectively showed that Nat1 is involved in translation of proteins that are required for cell differentiation.

overall_design: The effects of 2i in mouse embryonic stem cells, N=12: wild-type mouse embryonic stem cells cultured in LIF, N=3; wild-type mouse embryonic stem cells cultured in 2i+LIF, N=3; Nat1-null mouse embryonic stem cells cultured in LIF, N=3; Nat1-null mouse embryonic stem cells cultured in 2i+LIF, N=3.

first: H

last: Sugiyama

first: K

last: Takahashi

first: M

last: Narita