title: Analysis of aortic gene expression in ovariectomized ApoE-deficient mice substituted with medroxyprogesterone acetate, norethisterone acetate or placebo

status: Public on Jun 30 2014

city: Duesseldorf

first: Karl

last: Koehrer

address: Universitaetsstr. 1

department: BMFZ

institute: University of Duesseldorf

summary: Agilent 4x44k Whole Mouse Genome v1 Microarrays were used to analyze aortic transcriptome of mice substituted with medroxyprogesterone acetate, norethisterone acetate or placebo after having been ovariectomized. The aim of this experiment was to detect genes regulated in the gestagen-treated groups as compared to placebo that might be involved in thrombotic events

overall_design: Aortic gene expression was analyzed in ApoE-deficient mice after ovariectomy and 90 days of hormone- or placebo-treatment (medroxyprogesterone acetate or norethisterone acetate) and feeding a high-fat Western-type diet.

first: T

last: Freudenberger

first: R

last: Deenen

first: I

last: Kretschmer

first: A

last: Zimmermann

first: L

last: Seiler

first: P

last: Mayer

first: H

last: Heim

first: K

last: Köhrer

first: J

last: Fischer


title: Network Analysis of Breast Cancer Progression and Reversal with a Tree-Evolving Network Algorithm

status: Public on Jul 24 2014

city: Pittsburgh

first: Ankur

last: Parikh

address: 5000 Forbes Ave.

country: USA

institute: CMU

summary: The HMT3522 progression series of breast cells has been used to discover the roles of tissue architecture, microenvironment and signaling molecules in nonmalignant and malignant breast cell growth and behaviors, including the potential of various factors to cause phenotypic reversion of malignant cells to nonmalignant states. Despite many efforts to delineate key signaling pathways governing the malignant as well as the phenotypic reversion behaviors of T4 cells, much remains to be elucidated about the regulatory mechanisms underlying these cell states at the systems level. Here, we analyzed gene expression microarray profiles obtained from this progression series in both phenotypically malignant and reverted states using our newly developed tree-lineage-based network detection algorithm, Treegl.  Our work suggests analysis of various conditions of reversion (including non-reverted) of the HMT3522 cells using Treegl can be a model system to study drug effects on breast cancer cells, and may become a tool for effective drug discovery and target identification.

overall_design: Gene expression microarray data was obtained using Affymetrix GeneChip Human Genome U133A arrays to analyze 15 total RNA samples prepared from the HMT3522 breast cells grown in 3D lrECM and treated with various reverting agents or vehicle control.

first: Wei

last: Wu


title: PBMC expression profiles of BCG vaccine protected infants and of BCG vaccinated infants who develop tuberculosis disease

city: London

first: Helen

middle: Alison

last: Fletcher

address: Keppel Street

department: IID

country: United Kingdom

institute: London School of Hygiene & Tropical Medicine

summary: Analysis of PBMC from 10 week old infants vaccinated with BCG at birth. During follow-up 26 infants developed tuberculosis (TB) (non-protected by BCG) and 20 infants did not develop TB despite documented exposure (protected by BCG). PBMC were stimulated with media only or reconstituted BCG for 4 and 12 hours. Results provide insight into the mechanisms behind the failure of BCG to protect against disease.

overall_design: Set of arrays that are part of repeated experiments

middle: A

first: Willem

last: Hanekom


title: Maternal microRNAs secreted by the endometrium act as  transcriptomic regulators of the pre-implantation embryo

status: Public on Jun 02 2014

city: Valencia

first: Juan

middle: M

last: Moreno-Moya

address: Catedrático Agustín Escardino

country: Spain

institute: FIVI

summary: The developmental origins of adult disease are now recognized to reflect intrauterine conditions during embryonic and fetal life. Cell-cell communication between the maternal endometrium and the pre-implantation embryo can occur by several means. Here, we show that maternal miRNAs are secreted by the endometrial epithelium to the endometrial fluid. Microarray assessments revealed the presence of specific miRNAs that are associated with the window of implantation and therefore in direct contact with the human preimplantation embryo. These miRNAS are transported as free or exosome-associated molecules secreted to the endometrial fluid and then uptake into the pre-implantation embryo through the trophoectoderm. Finally, these maternal miRNAsS were able to induce transcriptional and functional modifications of the embryo. Therefore, we propose an innovative model whereby endometrial maternal miRNAS may function as transcriptomic regulators during early embryo development offering a new perspective on the developmental origins of adult diseases such as obesity, type 2 diabetes, and others that are now recognized to reflect intrauterine conditions.

overall_design: This is a prospective study in which endometrial fluid was obtained from healthy patients that had no underlying endometrial pathology and had regular menstrual cycles of between 25 and 33 days. None of these women had received a hormonal preparation in the 3 months preceding biopsy (fluid) collection. Endometrial (fluid) samples were distributed in five groups according to the phase in the cycle: group 1, Early Proliferative (EP) (days 1–8); group 2, Late Proliferate (LP) (days 9–14); group 3, Early Secretory (ES) (days 15–18); group 4, Window of Implantation (WOI) (days 19–22); and group 5, Late Secretory (LS) (days 23–28) according to the criteria of Noyes {Noyes:1975vl}. A total of 20 patients were included, four per group

first: Felipe

last: Vilella-Mitjana

first: Sebastian

last: Martinez-Escribano

first: Antonio

last: Marcilla

first: Carlos

last: Simón


title: Deletion of the Synechocystis sp. PCC 6803 kaiAB1C1 gene cluster causes impaired cell growth under light-dark conditions

status: Public on Jun 18 2014

city: Freiburg

first: Jan

last: Mitschke

address: Schaenzlestr. 1

department: Biologie III

country: Germany

institute: University of Freiburg

summary: In contrast to Synechococcus elongatus PCC 7942, which has been the model cyanobacterium for the study of the prokaryotic circadian clock for more than 20 years, only few data exist on the circadian behaviour of the widely used cyanobacterium Synechocystis sp. PCC 6803. The standard kaiABC operon present in this organism was shown to encode a functional KaiC protein which interacts with KaiA, similar to the Synechococcus elongatus PCC 7942 clock. Inactivation of this operon in Synechocystis sp. PCC 6803 resulted in a mutant with a strong growth defect in light-dark cycles, which was even more pronounced when glucose was added to the growth medium. In addition, mutants showed a bleaching phenotype. No effects were detected in mutant cells grown in constant light. Microarray experiments performed with cells grown for one day in a light-dark cycle revealed many differentially regulated genes with known functions in the ΔkaiABC mutant in comparison to the wild type. Most interestingly, we identified genes like the gene encoding the cyanobacterial phytochrome Cph1 and the light repressed protein LrtA as well as several hypothetical open reading frames with a complete inverse behaviour in the light cycle. These transcripts showed a stronger accumulation in the light but a weaker accumulation in the dark in ΔkaiABC cells in comparison to the wild type. In addition, we found a considerable overlap with microarray data obtained for hik31 and sigE mutants. These genes are known to be important regulators of cell metabolism in the dark.

overall_design: Three timepoints with two samples (WT and Mutant). Two replicates for each timepoint/sample. RNA hybridization.

first: Anja

middle: K

last: Dörrich

first: Olga

last: Siadat

first: Annegret

last: Wilde


title: Gene expression in the pancreatic lymph nodes (PLN) of hyperglycemic 16-week-old Non-Obese Diabetic (NOD) mice compared to expression the PLN of euglycemic 16-week-old NOD mice.

status: Public on Jun 01 2014

city: Stanford

first: Linda

last: Yip

state: CA

address: 269 Campus Drive West, CCSR Building Rm. 2240

department: Medicine

institute: Stanford University

summary: These experiments were performed to identify differentially expressed genes in the pancreatic lymph nodes of hyperglycemic NOD mice with high levels of destructive insulitis compared to euglycemic mice with lower levels of insulitis.

overall_design: The pancreatic lymph nodes of 16-week-old hyperglycemic and euglycemic NOD mice were isolated and homogenized in Trizol reagent (Invitrogen).  Total RNA was extracted from the aqueous phase using the RNeasy mini kit (Qiagen). RNA quality was assessed using the Agilent 2100 Bioanalyzer and the RNA 6000 Nano Reagent Kit (Agilent). Total RNA from the PLN of hyperglycemic mice (n=2) were labelled with Cy5 and run individually against a pool of Cy3-labeled total RNA isolated from euglycemic mice (n=2). Microarrays were performed using the Whole Mouse Genome Microarray Kit, 4×44K 2-color arrays (Agilent Technologies).


title: The transcriptomic signature of myostatin inhibitory influence on the differentiation of mouse C2C12 myoblasts

status: Public on Jul 23 2014

city: Warsaw

first: Zofia

last: Wicik

state: mazovia

address: Pawinskiego 5

department: Department of Human Epigenetics

country: Poland

institute: Mossakowski Medical Research Center

summary: GDF8 (myostatin) is a unique cytokine strongly affecting the skeletal muscle phenotype in human and animals. The aim of the present study was to elucidate the molecular mechanism of myostatin influence on the differentiation of mouse C2C12 myoblasts, using the global-transcriptome analysis with the DNA microarray technique. Treatment with exogenous GDF8 strongly affected the growth and development of C2C12 mouse myoblasts. This was manifested by the inhibition of proliferation and differentiation as well as the impairment of cell fusion. DNA microarray analysis revealed 778 genes regulated by GDF8 in differentiating myoblasts. Ontological analysis revealed their involvement in 17 types of biological processes, 10 types of molecular functions and 68 different signaling pathways. The effect of GDF8 was mainly mediated by the disruption of the cell cycle, calcium and insulin signaling pathways and expression of cytoskeletal and muscle specific proteins.

overall_design: After scanning of hybridized microarrays, quantitation of slide images was performed using Feature Extraction Software 9.1.1.1 (Agilent) using default parameters. The raw data were exported to GeneSpring GX 12 (Agilent, Santa Clara, CA). For identification of genes significantly altered in cell compared with the control normal gene set, total detected entities were filtered by flags (present, marginal) to remove very low signal entities and to select reproducible signal values of entities among the replicated experiments, respectively. In statistical analysis (GDF8 treated myoblasts vs untreated myoblasts) was used t-test unpaired (p < 0.05) and fold change cutoff over 1.6. Analysis of GO and signaling pathway was carried out using KEGG and PANTHER Classification System.

first: Michał

last: Jank

first: Tomasz

last: Sadkowski

last: Motyl


title: The pluripotency factor NANOG regulates the mitotic program of adult stratified epithelia.

status: Public on Jun 27 2014

city: Madrid

first: Daniela

last: Piazzolla

state: España

address: Calle Melchor Fernandez Almagro 3

department: Molecular Oncology

institute: CNIO

summary: NANOG is a key transcription factor for pluripotency in embryonic stem cells. However, its role in adult tissues remains largely unexplored. Here, we show that mouse NANOG is expressed in the progenitor layer of stratified epithelia, including esophagus, forestomach and skin. Accordingly, the Nanog promoter is hypomethylated in the epithelial layers of the esophagus and forestomach. Interestingly, ubiquitous transgenic overexpression of NANOG in mice induces hyperplasia in stratified epithelia, but not in other tissues. Mechanistically, we show that NANOG transcriptionally activates the mitotic program selectively in stratified epithelia, and endogenous NANOG directly binds the Aurora kinase A (Aurka) promoter in keratinocytes. Finally, human and mouse squamous cell carcinomas (SCCs) express NANOG and its levels positively correlate with those of AURKA in human head and neck SCCs. Together, these results implicate a lineage-restricted mitogenic role of NANOG in normal stratified epithelia and its derived carcinomas.

overall_design: 2 conditions (genotypes) in 2 independent organs (esophagus and liver), 3 biological replicates per genotype. The experiment compares gene expression in Nanog overexpressing esophagus (Col1a1tetO-Nanog/+;Rosa26rtTA/+, indicated as TG) vs control esophagus (Col1a1+/+;Rosa26rtTA/+, indicated as CTR) and in Nanog overexpressing liver (Col1a1tetO-Nanog/+;Rosa26rtTA/+, indicated as TG)  vs control liver (Col1a1+/+;Rosa26rtTA/+, indicated as CTR) all treated with 0.2 mg/ml doxycycline for 48 h. All mice of around 8 months of age.

first: Adelaida

middle: R

last: Palla

first: Marta

last: Cañamero

first: Sagrario

last: Ortega

first: Gonzalo

last: Gómez-López

first: Orlando

last: Dominguez

first: Diego

last: Megías

first: Jose

middle: L

last: Luque-Garcia

first: Beatriz

last: Fernandez-Tresguerres

first: Agustin

middle: F

last: Fernandez

first: Mario

last: Fraga

first: Manuel

last: Rodriguez-Justo

first: Miguel

last: Manzanares

last: Sánchez-Carbayo

last: Serrano


title: Global gene expression in response to SARS mouse adapted variants MA-15, MA-15epsilon, and MA-15-gamma in young and aged mice

city: Seattle

first: Michael

last: Katze

state: WA

address: Rosen Building 960 Republican St.

department: Microbiology

institute: University of Washington

summary: Purpose of this experiment was to study the host-transcriptional response to MA-15, MA-15epsilon, and MA-15-gamma in both young and aged mice to further understand the differences between response within each age group, and the age-related differences in response to each virus.

overall_design: Young (8 weeks old) and aged (1 year old) female BALB/c mice were  intranasally infected with 10^5 PFU of either MA15, MA15 gamma, MA15 epsilon, or phosphate buffer solution (PBS; mock-infection). Lungs from aged mice were harvested at 12, 24, and 48 hours post-infection. Lungs from young mice were harvested at 12, 24, 48, and 96 hours post-infection.  For the aged mice, 3 biological replicates were collected for microarray analysis at each time point from the infected groups. 3 mocks at 12h, 2 mocks each at 24 and 48h time points.For the young mice, 4 biological replicates were collected for microarray analysis at each time point from the infected groups.

first: Deborah

last: Diamond

first: Sudhakar

last: Agnihothram

first: Haifeng

last: Wang

first: Sarah

middle: E

last: Belisle

first: Alan

middle: C

last: Whitmore

first: Matthew

middle: B

last: Frieman

first: Sara

last: Kelly

first: Lisa

last: Gralinski

first: Elizabeth

last: Rosenzweig

first: G

last: Law

first: Ralph

middle: S

last: Baric

middle: G


title: Age dependence of hematopoietic progenitor survival and chemokine family gene induction after gamma-irradiation in bone marrow tissue in C3H mice

city: Chiba

first: Kentaro

last: Ariyoshi

state: Chiba

address: Inage-ku, anagawa 4-9-1

country: Japan

institute: NIRS

summary: To identify the age dependent radiation response in C3H mouse bone marrow cells.

overall_design: Changes in gene expression in 1 week old and 8 weeks old C3H mouse (female) bone marrow after 2Gy irradiation. Bone marrow samples  were collected un-irradiated control, 6 hours and 24 hours after irradiation. Three mice were used at each time course.

last: ARIYOSHI

first: Yoshiya

last: SHIMADA


title: Epinecidin-1 has immunomodulatory effects, facilitating its therapeutic use in a mouse model of Pseudomonas aeruginosa sepsis

status: Public on May 27 2014

city: Ilan

first: Jyh-Yih

last: Chen

address: 23-10, Dahuen Rd., Jiaushi, Ilan

country: Taiwan

institute: Academia Sinica

summary: Antimicrobial peptides (AMPs) are garnering attention as possible alternatives to antibiotics. Here, we describe the antimicrobial properties of epinecidin-1 against multi-drug resistant clinical isolates of P. aeruginosa (P. aeruginosa (R)) and P. aeruginosa from ATCC (P. aeruginosa (19660)) in vivo. The minimum inhibitory concentrations (MICs) of epinecidin-1 against P. aeruginosa (R) and P. aeruginosa (19660) were determined, and compared with those of imipenem. Epinecidin-1 was found to be highly effective at combating peritonitis infection caused by P. aeruginosa (R) or P. aeruginosa (19660) in mouse models, without inducing adverse behavioral effects, or liver or kidney toxicity. Taken together, our results indicate that epinecidin-1 enhances the survival rate of mice infected with the bacterial pathogen P. aeruginosa through both antimicrobial and immunomodulatory effects.

overall_design: RNA from mice treated with epinecidin-1 were individually compared to RNA from PBS control mice.

first: Chieh-Yu

last: Pan


title: Expression microarray screen for genes regulated by the unliganded glucocorticoid receptor

status: Public on May 11 2014

city: Kingston

first: Christopher

last: Mueller

state: Ontario

address: 18 Stuart Street

department: Cancer Research Institute

country: Canada

institute: Queen's University

summary: To further characterize the role of the unliganded glucocorticoid receptor (GR) in breast cells, we used an shRNA vector directed against GR to create EPH-4 mouse mammary cell lines with depleted endogenous levels of this receptor. RNA prepared from normal (EV-50) and GR-depleted (shGR-19) cells was used in an expression microarray screen for targets of unliganded GR. This analysis revealed 260 targets of negaive regulation by unliganded GR, and 343 targets of positive regulation by unliganded GR, several of which were involved in pro-apoptotic networks, and opposed the activity of liganded GR targets. This work presents the first screen for targets of unliganded GR. We propose that the balance between liganded and unliganded GR signaling is responsible for controlling differentiation and apoptosis, respectively, and suggest that gene regulation by unliganded GR may represent a mechanism of reducing the risk of breast tumourigenesis.

overall_design: RNA was prepared from EV-50 and shGR-19 cells and RNA integrity was determined using an Agilent 2100 Bioanalyzer. RNA was hybridized to the array in duplicate. The duplicates of each EV-50 and shGR-19 were averaged, and the shGR-19 data was subsequently compared to the EV-50 data.

first: Heather

last: Ritter


title: PI3K/AKT pathway is activated by miRNA-22 in the proliferative CLL subset (miRNA)

status: Public on May 15 2014

city: Montevideo

first: Tamara

last: Fernandez-Calero

state: Montevideo

address: Mataojo 2020

department: Bioinfomatics Unit

country: Uruguay

institute: Institut Pasteur de Montevideo

summary: Understanding the crosstalk between malignant B-cells and their milieu could provide clues on the molecular and clinical biology of Chronic Lymphocytic Leukemia (CLL). Aiming to generate novel therapeutic strategies, different groups have studied different CLL proliferative fractions. We previously, identified one of these proliferative subsets in the peripheral blood from progressive unmutated CLL patients. Since the presence of this small subset appears to be a hallmark of a proliferative disease in which B lymphocytes are being constitutively activated in the proliferative centers of these patients, we performed gene expression analysis comparing the global mRNA and microRNAs expression of this leukemic subpopulation. Our results suggest that the proliferative behaviour of this fraction appears to depend on microRNA-22 over-expression, which induces PTEN downregulation and PI3K/AKT pathway activation. Transfection experiments demonstrated that miR-22 overexpression in CLL B-cells switches on PI3K/AKT leading to FOXO1 inactivation, p27-Kip1 downregulation, and overexpression of Survivin and Ki-67 proteins. We also demonstrated that this pathway could be triggered by microenvironment signals like CD40L/IL4 and more importantly, that this regulatory loop is also present in lymph nodes from progressive UM patients. Altogether, these results underline the key role of PI3K/AKT pathway in the generation of the CLL proliferative pool and provide rationale for the usage of PI3K inhibitors.

overall_design: B cells from Chronic Lymphpcytic Leukaemia patients were isolated from blood. By sorting experiments we purify the QF from PF from progressive patients. We extract the total RNA from 8 samples and perform microRNA arrays.

first: Florencia

last: Palacios

first: Cecilia

last: Abreu

first: Daniel

last: Prieto

first: Santiago

last: Ruiz

first: Pablo

last: Morande

first: Hugo

last: Naya

first: Gabriela

last: Libisch

first: Carlos

last: Robello

first: Ana

middle: I

last: Landoni

first: Raúl

last: Gabús

first: Guillermo

last: Dighiero

last: Oppezzo


title: Coxiella burnetii, the agent of Q fever, persists in adipocytes

status: Public on May 25 2014

city: Lyon

first: Julien

last: Textoris

address: Hôpital Edouard herriot - Pavillon P; 5 place d'Arsonval

department: Medical Diagnostic Discovery Department (MD3)

country: France

institute: bioMérieux

summary: Coxiella burnetii, the agent of Q fever, persists in humans despite specific immune responses: however, its reservoir remains unknown. We detected C. burnetii in adipose tissue from BALB/c and C57/BL6 mice 4 months after infection when no bacteria were found in other tissues. C. burnetii infected cultivated adipocytes, replicated within late phagosomes and induced a transcriptional program that was enriched for the expression of genes associated with inflammatory response, hormonal responses and cytoskeleton.

overall_design: 3T3-L1 (ATCC) differentiated adipocytes were stimulated or not with Coxiella burnetii (NMI) at a ratio of 50 bacteria per cell. Four biological replicates were analyzed in each group. Due to technical reason, one unstimulated sample was discarded from the analysis.

first: Yassina

last: Bechah

first: Johanna

last: Verneau

first: Amira

last: Amara

first: Christian

last: Capo

first: Eric

last: Ghigo

first: Jean-Louis

last: Mège


title: Characterizing the transcriptomic response of mice infected with A/Anhui/01/2013 (H7N9), A/Netherlands/219/2003 (H7N7), and A/Vietnam/1203/2004 (H5N1), and a pandemic H1N1 human virus, A/Mexico/4482/2007 (H1N1)

first: Michael

last: Katze

summary: Modulating the host response is a promising approach to treating influenza, a virus whose pathogenesis is determined in part by the host response it elicits. Though the pathogenicity of emerging H7N9 influenza virus has been reported in several animal models, these studies have not included a detailed characterization of the host response following infection. To this end, we characterized the transcriptomic response of BALB/c mice infected with H7N9 (A/Anhui/1/2013) virus and compared it to the responses induced by H5N1 (A/Vietnam/1203/2004), H7N7 (A/Netherlands/219/2003) or H1N1 (A/Mexico/4482/2009) viruses. We found that responses to the H7 subtype viruses were intermediate to those elicited by H5N1 and H1N1 early in infection, but that they evolved to resemble the H5N1 response as infection progressed. H5N1, H7N7 and H7N9 viruses were pathogenic in mice, and this pathogenicity correlated with increased cytokine response, decreased lipid metabolism and decreased coagulation signaling. This three-pronged signature has previously been observed in mice infected with pathogenic H1N1 strains such as the 1918 virus, indicating that it may be predictive of pathogenicity across multiple influenza strains.

overall_design: Groups of 6- to 8-week-old BALB/c mice were infected with either A/Anhui/01/2013 (H7N9), A/Netherlands/219/2003 (H7N7), A/Vietnam/1203/2004 (H5N1), or pandemic H1N1 human virus, A/Mexico/4482/2007 (H1N1). Infections were done at 10^5 PFU or time-matched mock infected. Time points were 1, 3 and 5 d.p.i. There were 4-5 infected and 3 mock infected animals/time point. Lung samples were collected for virus load and transcriptional analysis. Weight loss and animal survival were also monitored.

first: Terry

last: Tumpey

first: Laurence

last: Josset

first: Nicolas

last: Tchitchek

first: Juliet

last: Morrison

first: Jessica

last: Belser

first: Jean

last: Chang


title: Exposure to ionizing radiation induced persistent gene expression changes in mouse mammary gland

status: Public on May 01 2014

city: Logan

first: Daniel

last: Hyduke

state: UT

address: 4105 Old Main Hill ENGR 402S

department: Biological Engineering

institute: Utah State University

summary: Six to eight week old female C57BL/6J mice were exposed to 2 Gy of whole body γ radiation and mammary glands were surgically removed 2-month after radiation. RNA was isolated and microarray hybridization performed for gene expression analysis.

overall_design: 5 samples were analyzed: 2 controls at 2 months, 1 2 Gy at 2 months, and 2 7 Gy at 2 months

first: Kamal

last: Datta

first: Shubhankar

last: Suman

first: Bo-Hyun

last: Moon

middle: D

last: Johnson

first: Albert

middle: J

last: Fornace


title: Transcriptomic Profiling of Collaborative Cross Founder Mouse Embryonic Fibroblasts stimulated with Type I, II and III Interferons

summary: Collaborative Cross (CC) mouse embryonic fiborolasts (MEF) cells obtained from the eight Founder animals [PWK/PhJ, NZO/HILtJ, NOD/ShiLtJ, WSB/EiJ, A/J, CAST, C57BL/6J, and 129/SvlmJ] were immortalized and the cell lines used to assess differences in transcriptional responses following treatment with type I, II and III recombinant mouse interferon.

overall_design: We collected transcriptome profiles for 8 CC MEF cell lines stimulated with either IFN-α or IFN-β for a total of 16 different biological conditions. Treated and mock samples were collected at 18 hr post-treatment and RNAs extracted and subjected to microarray.

first: David

last: Threadgill

first: Jennifer

last: Tisoncik-Go

first: Elizabeth

last: Rosenzweig


title: Testis expression in Mus musculus domesticus WSB/EiJ x Mus musculus musculus PWD/PhJ F2 hybrids

city: Ploen

first: Leslie

last: Turner

address: August-Thienemann Str 2

department: Evolutionary Genetics

institute: Max Planck Institute for Evolutionary Biology

summary: To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL  - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.

overall_design: Gene expression was measured in whole testis in males aged 70(±5) days. Samples include 294 WSB/EiJ x PWD/PhJ F2s, 11 PWD/PhJ x WSB/EiJ F2s, 8 WSB/EiJ, 8 PWD/PhJ, 6 PWD/PhJ x WSB/EiJ F1s and 4 WSB/EiJ x PWD/PhJ F1s.


title: Genes and miRNAs regulated by Gadd45a during somatic cell reprogramming

status: Public on Apr 22 2014

city: Guangzhou

first: Keshi

last: Chen

address: 190 Kai Yuan Avenue

country: China

institute: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science

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

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

overall_design: Refer to individual Series


title: Mouse utero-tubular junction (UTJ): 1: females in estrous no mating; 2: females in estrous mated with vasectomized male; 3: females in estrous mated with normal male: 1 vs. 2; 1 vs. 3; 2 vs. 3.

status: Public on Apr 10 2014

city: Kyoto

first: Gen

last: Kondoh

state: Kyoto

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

department: Institute for Frontier Medical Sciences

institute: Kyoto University

summary: Gene expression profiles comparing controls (1) with females mated with vasectomized male (2) or normal males (3).

overall_design: Three-condition experiment:  1 vs. 2; 1 vs. 3; 2 vs. 3. RNA source: 1. pool of 10 females control; 2. pool of 10  females in estrous mated with vasectomized male; 3. pool of 10 females in estrous mated with normal male.

first: Hitomi

last: Watanabe


title: IM013 - Mouse infection with A/Vietnam/1203/2004 (H5N1)

status: Public on Apr 02 2014

first: Michael

last: Katze

summary: To determine the host response (C57BL/6 mouse model) to A/Vietnam/1203/2004 (H5N1) virus at 10^3 and 10^4PFU.

overall_design: Groups of 22-week-old C57BL/6 mice were infected with A/Vietnam/1203/2004 (H5N1) virus at 10^3 or 10^4 PFU or time-matched mock infected. Time points were 1, 2, 4 and 7 d.p.i. There were 3-4 animals/dose/time point. Lung samples were collected for virus load, transcriptional and proteomic analysis. Weight loss and animal survival were also monitored.

first: Yoshiro

last: Kawaoka

first: Lynn

last: Law

first: Amie

last: Eisfeld

first: Nicholas

last: Tchitchek


title: Genes regulated by Gadd45a during somatic cell reprogramming

summary: Gadd45a can enhance somatic cell reprogramming significantly. To explore the roles of  Gadd45a playing in reprogramming, we performed whole genome microarray to identify genes and signals pathways that regulated by Gadd45a.

overall_design: Genes expression of MEFs was measured at day8 in reprogramming. Three samples were set: MEFs infected with SKO plus Flag, MEFs infected with SKO plus Gadd45a and MEFs infected with SKO plus G39A which is a negative mutant of Gadd45a.

first: Qi

last: Long

first: Xingguo

last: Liu


title: IM015 - Influenza infection of C57BL6 and RIPK3 knock-out mice

summary: This purpose of this experiment was to investigate the transcriptional differences between C57BL6, RIPK3 knock-out mice infected with influenza strain A/CA/04/2009 (H1N1) virus.

overall_design: Overview of Experiment: Groups of 6-8 week-old C57BL6 and RIPK3 knock-out mice were infected with influenza A/CA/04/2009 virus. Infections were done at 10^5 PFU or time-matched mock infected. Time points were 2 and 4 d.p.i.  There were 2-3 animals/dose/time point. Lung samples were collected for virus load and transcriptional analysis. Weight loss and animal survival were also monitored.

first: Jean

last: Chang


title: Profile analysis of endogenous and exosomal microRNAs in human colon cancer cell lines-2

status: Public on Apr 01 2014

city: Chuo-ku

first: Naoto

last: Tsuchiya

state: Tokyo

address: Tsukiji 5-1-1

institute: National Cancer Center Reasearch Institute

summary:
MicroRNAs (miRNAs) are intrinsic regulators in the various cellular processes, and their abnormalities are considered to be involved in the onset of human disorders, including cancer. Circulating miRNA is focused as new cancer biomarker however it is regarded that circulating RNA are released not only from tumor but also by various pathways. Recently, exosomes, small membrane vesicles, have been a major interest in cancer research field, because of their unique biological properties. Exosomes are secreted from various cells and the components (Lipids, mRNAs, miRNAs and proteins) reflect origin of the cells secreting them. Identification of exosomal miRNAs from cancer cells is expected to provide useful biomarkers of cancer.
To identify specific exosomal miRNAs as candidate biomarkers for colorectal cancer, we compared exosomal miRNA profiles of 5 colon cancer cell lines with that of normal colon-derived epithelial cells, and isolated a subset of miRNAs as commonly-secreted miRNAs from colon cancer cells

overall_design: Endogenously expression of microRNAs were analyzed by Agilent Human miRNA V3 Microarray (G4470C) using  total RNA of three human colon cancer cell lines (HT-29 cells, SW48 cells, and RKO cells)  at two independent experiments.  Exosomal microRNAs were analyzed by microRNA microarray using total RNA of exosomes from conditioned media of three human colon cancer cell lines, HT-29 cells, SW48 cells, and RKO cells at three independent experiments. Exosomes were prepared by step-wise ultra-centrifugation methods. RNA was prepared by Trizol or Trizol-LS reagent (Invitrogen) and RNeasy mini spin column (Qiagen).

first: Hiroko

last: Ogata-Kawata


title: microRNA profiles of serum exosomes in healthy controls and colorectal cancer patients-1

summary:
MicroRNAs (miRNAs) are intrinsic regulators in the various cellular processes, and their abnormalities are considered to be involved in the onset of human disorders, including cancer. Circulating miRNA is focused as new cancer biomarker however it is regarded that circulating RNA are released not only from tumor but also by various pathways. Recently, exosomes, small membrane vesicles, have been a major interest in cancer research field, because of their unique biological properties. Exosomes are secreted from various cells and the components (Lipids, mRNAs, miRNAs and proteins) reflect origin of the cells secreting them. Identification of exosomal miRNAs from cancer cells is expected to provide useful biomarkers of cancer.
To identify specific exosomal miRNAs as candidate biomarkers for colorectal cancer, we profiled exosomal miRNAs in sera of colon cancer patients (n=88) at various TNM stages (I to IV) and healthy controls (n=11) and selected significantly higher microRNAs in serum exosomes of colorectal cancer patients than that of healthy controls. Moreover, we tried to detect their serum exosome levels of using samples from patients after surgical resection of primary tumors (n=24).

overall_design: Serum exosomes were prepared by step-wise ultra-centrifugation methods in 11 healthy controls and 88 colorectal cancer patients with various TNM stages (I; n=20, stage II; n=20, stage IIIa; n=20, stage IIIb: n=16, stage IV; n=12)  (age; 35-65) .Exosome fraction was mixed with Trizol-LS reagent (Invitrogen), and aqueous phase was collected by adding chloroform. After addition of ethanol to the aqueous phase, it was placed on to an RNeasy mini spin column (Qiagen) for the purification of total RNAs. The total RNAs were analyzed by Agilent Human miRNA V3 Microarray (G4470C) according to the manufacturer's instructions.


title: microRNA profiles of serum exosomes in healthy controls and colorectal cancer patients-2

overall_design: Serum exosomes were prepared by step-wise ultra-centrifugation methods in 24 colorectal cancer patients (age; 35-65) after surgical resection of primary tumor (TNM stage I; n=6, stage II; n=5, stage IIIa; n=5, stage IIIb; n=5, stage IV; n=3) .Exosome fraction was mixed with Trizol-LS reagent (Invitrogen), and aqueous phase was collected by adding chloroform. After addition of ethanol to the aqueous phase, it was placed on to an RNeasy mini spin column (Qiagen) for the purification of total RNAs. The total RNAs were analyzed by Agilent Human miRNA V3 Microarray (G4470C) according to the manufacturer's instructions.


title: The Menin-Bach2 axis is critical for regulating CD4 T cell senescence and cytokine homeostasis

status: Public on Mar 27 2014

city: Toon-shi

first: Makoto

last: Kuwahara

state: Ehime

address: Shitsukawa

department: Department of Immunology

institute: Graduate School of Medicine, Ehime University

summary: Although CD4 T cell senescence plays an important role in immunosenescence, the mechanism behind this process remains unclear.  Here we show that T cell-specific Menin deficiency results in the premature senescence of CD4 T cells, which is accompanied by the senescence-associated secretory phenotype after antigenic stimulation and dysregulated cytokine production.  Menin is required for the expansion and survival of antigen-stimulated CD4 T cells in vivo and acts by targeting Bach2, which is known to regulate immune homeostasis and cytokine production.  Menin binds to the Bach2 locus, and controls its expression through maintenance of histone acetylation.  Menin binding at the Bach2 locus and the Bach2 expression are decreased in the senescent CD4 T cells.  These findings reveal a critical role of the Menin-Bach2 pathway in regulating CD4 T cell senescence and cytokine homeostasis, thus indicating the involvement of this pathway in the inhibition of immunosenescence.

overall_design: Gene expression in Menin WT-TH and Menin KO-TH

first: Junpei

last: Suzuki

first: Soichi

last: Tofukuji

first: Takeshi

last: Yamada

last: Kanoh

first: Akira

last: Matsumoto

first: Saho

last: Maruyama

first: Kohei

last: Kometani

first: Tomohiro

last: Kurosaki

first: Osamu

last: Ohara

first: Toshinori

last: Nakayama

first: Masakatsu

last: Yamashita


title: Profiling of endogenous and exosomal microRNAs in colon cancer

sample_organism:
Homo sapiens
Bos taurus


title: Defining a Th9 transcriptome

status: Public on Mar 26 2014

city: Indianapolis

first: Mark

middle: H

last: Kaplan

state: IN

address: 635 Barnhill Dr. MS 420

department: Microbiology and Immunology

institute: Indiana University

summary: Microarray analyses were performed to compare gene expression in cultured mouse Th9, Th2 and Treg cells and resting versus activated Th9 cells.

overall_design: Three replicates were analyzed for each culture condition; Th9 unstim, Th2 unstim, Treg unstim, Th9 stim

first: M


title: Effect of ultradian light-dark cycles on the transcriptome of mice carying a human Per3 polymorphism

status: Public on Mar 11 2014

city: Guildford

first: Emma

last: Laing

address: Stag Hill

institute: University of Surrey

summary: In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) θ power during wakefulness and δ power during sleep, were greater in the Per35/5 mice. During recovery, the Per35/5 mice fully compensated for the SD-induced deficit in δ power, but the Per34/4 and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.-Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E. E., Koentgen, F., Dijk, D.-J., Archer, S. N. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.

overall_design:
Mice were kept under 3.5h light- 3.5 hours dark cycles and samples were collected in the 17th light cycle
Boxhill represents Per35/5 mice and Coach represents Per34/4 mice.
A total of 30 samples comprizing 30 mice

first: Daan

last: van der Veen

first: Sibah

last: Hasan

first: Raphaelle

last: Winsky-Sommerer

first: Alexandra

last: Hogeben

first: Frank

last: Koentgen

first: Derk-Jan

last: Dijk

first: Simon

middle: N

last: Archer


title: Profile analysis of endogenous and exosomal microRNAs in human colon cancer cell lines-1

first: Naoto

last: Tsuchiya

overall_design: Endogenously expression of microRNAs were analyzed by Agilent Human miRNA V3 Microarray (G4470C) using  total RNAs of human colon-derived FHC cells and human colon cancer cell lines (HCT116 cells and SW480 cells) at two independent experiments. Exosomal microRNAs were analyzed by microRNA microarray using total RNAs of exosomes from conditioned media of FHC cells, HCT116 cells, and SW480 cells at three independent experiments.As negative control of exosomal microRNAs in conditioned media, FBS-exosomal microRNAs were analyzed at four independent experiments. Exosomes were prepared by step-wise ultra-centrifugation methods. RNA was prepared by Trizol or Trizol-LS reagent (Invitrogen) and RNeasy mini spin column (Qiagen).

first: Hiroko

last: Ogata-Kawata


title: Gene expression in IL-10-deficient and wild-type mice following Citrobacter rodentium infection

status: Public on Mar 12 2014

city: La Jolla

first: Lars

last: Eckmann

address: 9500 Gilman Drive

department: Gastroenterology

institute: University of San Diego

summary: To further understand immune mechanims involved in regulating intestinal inflammation, we employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential of regulating inflammation in the absence of IL-10. Whole colon tissue from IL-10-deficient and C57BL/6 (wild-type) mice was collected 2 weeks after Citrobacter rodentium infection and from uninfected controls. Consistent with the histological and cellular analysis, expression levels of many chemokines and cytokines involved in recruiting leukocytes and promoting inflammation were, on average, lower in IL-10 deficient compared to wild-type mice after infection. An exception to this general trend was IL-27, a cytokine with both pro- and anti-inflammatory properties.

overall_design: Two weeks after Citrobacter rodentium challenge, total RNA was extracted and analyzed from whole colon tissue of infected IL-10-deficient and wild-type mice, and compared to uninfected controls. Each sample contained equal amounts of total RNA from 4-5 female mice which were pooled and used in the experiment.

first: Sara

last: Dann


title: Six2CrefSall1 E14.5 WTvsKO, Sall1CreERfSall1 E14.5 WTvsKO 100120

status: Public on Mar 24 2014

city: Kumamoto

first: Ryuichi

last: Nishinakamura

address: Honjo 2-2-1

department: IMEG

institute: Kumamoto Univ.

summary: We have employed whole genome microarray expression profiling to identify genes  regulated by Sall1 in the kidney.

overall_design: Kidneys at E14.5 were obtained from nephron progenitor-specific Sall1 deletion ( 2 sets)  and inducible Sall1 deletion 48 hrs after tamoxifen treatment (1 set).


title: Transcription profile of primordium gut organs

status: Public on Mar 25 2014

city: Tsukuba

first: Mari

last: Sekine

address: 1-1-1 Tennoudai

department: Graduate School of Life and Environmental Sciences

institute: The University of Tsukuba

summary:
Induced pluripotent stem (iPS) cells are a novel stem cell population induced from mouse and human adult somatic cells through reprogramming by transduction of defined transcription factors. Recently, researchers success in generation various cells from iPSCs. Lung progenitor cells are able to differentiate to all of the cells exist in adult lung, attract attention for regenerative medicine. It is known to present between embryonic day 9.5 from 13.5 in mice. We can realized at regenerative medicine in lung using lung progenitor cell surface markers defined by compering each endoderm primordia of organ formation.
We investigated the differences in gene expression of each endoderm organ.

overall_design: Mouse gut organs morphogenesis begin at E9.5-E11.5. The primordium lung, esophagus, stomach, and intestine at E11.5 were dissected and analysed transcription profile.

first: Takaaki

last: Noguchi


title: Transcriptome profiling of the newborn mouse lung response to acute ozone exposure

city: Denver

first: Kelsa

last: Gabehart

state: CO

address: 1400 Jackson St

department: Pediatrics

institute: National Jewish Health

summary: Ozone is a major air pollutant in highly populated areas. High levels of ambient ozone have been associated with decreased lung function and increased exacerbations of asthma in children and adults. However, the effects of ozone on the newborn’s lung are largely unknown.  This study was aimed at profiling the newborn lung response to ozone at the transcriptome level to define the impact of ozone pollutant on the developing postnatal lung. Newborn mice were exposed to ozone or filtered normal air for 3 h. Total RNA was isolated from lung tissues at 6 and 24 h after completion of exposure and was subjected to gene expression analysis using Whole Mouse Genome Gene Expression 4X44K Microarrays (G2519F-014868, Agilent Technologies). Transcriptome analysis of the postnatal lung indicated that 455 genes were down-regulated and 166 genes were up-regulated by at least 1.5 fold at 6 h post-ozone exposure (t-test, p<0.05). At 24 h post exposure, 543 genes were down-regulated and 323 genes were up-regulated in the lungs of ozone-exposed newborn mice, compared to filtered air-exposed newborn mice (t-test, p<0.05). After controlling for false discovery rate, 50 genes were significantly down-regulated and only 4 genes were up-regulated at 24 h post ozone-exposure (q<0.05). Gene ontology enrichment analysis revealed that cell cycle-associated functions including cell division/proliferation, cellular assembly and organization were the predominant pathways negatively regulated by ozone exposure. These findings suggest that elevated ozone pollution may interfere with lung development and growth in the early age.

overall_design: Three-day old BALB/c mice were exposed for 3 h to ozone (1000 parts per billion). Age-matching littermate controls were exposed for 3 h to filtered normal air. Whole lung tissue was collected 6 and 24 h after completion of exposure to ozone or filtered air and was subjected to microarray analysis.  Each time point was performed separately with its own filtered air littermate controls. Pups were cross-fostered during exposure so that all pups were with a dam during exposure. A total of 6-8 mice were initially included in each group and time point. Of these, n=4 mouse lungs were randomly selected for use in gene expression analysis.

first: Azzeddine

last: Dakhama


title: Gene expression profiles in wild-type and Jmjd3-/- embryos

status: Public on Feb 23 2014

city: Kanazawa

first: Takumi

last: Nishiuchi

address: 13-1 Takaramachi

institute: Kanazawa University

summary: Gene expression profiles were compared between wild-type and Jmjd3-/- embryos at E9.5 when mRNAs of posterior Hox genes are upregulated, because Jmjd3-/- mice embryos showed homeotic transformation. As expected, mRNAs of Hoxd10 and Hod11 were decreased in Jmjd3-/- embryos. Moreover, gene onthology (GO) analyses identified down-regulated genes (FC>1.5) in Jmjd3-/- embryos were “multicellular organismal development” and “developmental process”.

overall_design: Gene expressions in wild-type and Jmjd3-/- posterior half of embryos at E9.5 were examined. Two independent RNA samples of each genotypes were used to verify the reproducibility of the microarray analyses.

first: Chie

last: Naruse

first: Shinwa

last: Shibata

first: Kanae

last: Abe

first: Takayuki

last: Kawaguchi

first: Tomoaki

last: Kato

first: Masahide

last: Asano


title: Gene expression patterns induced by a transient switch-on of ROS production in mouse skin

status: Public on Feb 25 2014

city: Madrid

first: Javier

last: Suela

state: M

address: Faraday 7

institute: NIMGenetics

summary: Gene expression signatures induced by transient ROS production were characterized in both mouse back skin and tail epidermis samples. A transient in situ ROS production in the tissue was activated by an adapted photodynamic treatment, using methyl aminolevulinate as a metabolic precursor of endogenous Protoporphyrin IX.

overall_design: Gene expression in skin samples was measured 48 h after the photodynamic treatment. Experimental groups included: [1] Back skin control group (n=3 animals); [2] Back skin treated group (n=3 animals); [3] Tail skin control group (n=3 animals); and [4] Tail skin treated group (n=3 animals).

first: Elisa

last: Carrasco

first: Jesús

last: Espada

first: Ángeles

last: Juarranz


title: SM004 - SARS infection of C57BL6, TIMP1 and Serpine1 knock-out mice.

status: Public on Feb 20 2014

city: Seattle

first: Michael

last: Katze

address: Rosen Building 960 Republican St.

institute: University of Washington

summary: This purpose of this experiment was to investigate the transcriptional differences between C57BL6, TIMP1 and Serpine1 knock-out mice infected with SARS MA15 virus.

overall_design: Overview of Experiment: Groups of 20 week old C57BL6, TIMP1 and Serpine1 (PAI1) knock-out mice were infected with SARS MA15  virus. Infections were done at 10^4 PFU or time-matched mock infected. Time points were 4 and 7 d.p.i.  There were 2-4 animals/dose/time point. Lung samples were collected for virus load, transcriptional and proteomics analysis. Weight loss and animal survival were also monitored.

first: Ralph

last: Baric

first: Lisa

last: Gralinski

first: Lynn

last: Law

first: Jean

last: Chang


title: Effect of 12 hour sleep restriction on the transcriptome of mice carying a human Per3 polymorphism

first: Emma

last: Laing

overall_design:
Mice recievied 12 hours of sleep restriction during the 12 hours of light in the light-dark cycle
Boxhill represents Per35/5 mice and Coach represents Per34/4 mice.
A total of 48 samples comprising 24 mice

first: Daan

last: van der Veen

first: Sibah

last: Hasan

first: Raphaelle

last: Winsky-Sommerer

first: Alexandra

last: Hogeben

first: Frank

last: Koentgen

first: Derk-Jan

last: Dijk

first: Simon

last: Archer


title: SM007 - Infection with SARS MA15 of C57BL6/J mice and CXCR3 knockouts in the same strain of mice.

summary: The purpose of this experiment is to compare the host response of C57BL6/J mice to that of CXCR3 knockout mutant mice in response to SARS MA15 virus infections.

overall_design: Groups of 10 week old C57BL6 mice or CXCR3 knockout mice were infected with SARS MA15 at a dose of 10^5 PFU or mock infected. Mice were euthanized on days 2, 4 and 7 post infection to measure virus load and isolate samples for measurement of virus load, lung pathology,  and transcriptional.  Mock infected animals were also harvested at each time point. Mice were weighed every 24 hours to measure general disease progression and any mouse approaching 30% weight loss were euthanized.


title: A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism

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

overall_design: Refer to individual Series


title: Gene expression profiling of liver tissue from lean (WT) and obese (ob/ob) mice following a chronic exposure of low doses of pharmaceuticals

status: Public on Mar 04 2014

city: Rennes

first: Cedric

last: Coulouarn

address: CLCC Eugène Marquis, Rue de la Bataille Flandres Dunkerque, Bat D, 1er étage

institute: INSERM

summary:
BACKGOUND: Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can have harmful consequences for the liver, especially in the context of obesity.
OBJECTIVES: To determine whether chronic, low dose exposure to pharmaceuticals could have deleterious effects in livers of lean and obese mice.
METHODS: Lean and ob/ob male mice (5-week-old) were treated for 4 months with a mixture of 11 drugs (acetaminophen, caffeine, carbamazepine, cotinine, diclofenac, erythromycin, ibuprofen, phenazone, roxithromycin, salicylic acid and sulfamethoxazole) provided in drinking water at a concentration of 1 mg/L (for each drug). At the end of the treatment, investigations were performed in liver and plasma.
RESULTS: Some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 1 mg/L of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals indicated that expression of 8 different circadian genes was significantly modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 100-1,000 ng/L. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were confirmed in an independent study performed in female mice.
CONCLUSIONS: Chronic, low dose exposure to pharmaceuticals disturbed hepatic expression of circadian genes, especially in obese mice. Because some of the 11 drugs can be found in the drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, in particular for obese individuals exposed to these contaminants.

overall_design: C57BL/6J lean and ob/ob male mice (5-week-old) were treated for 4 months with a mixture of 11 drugs provided in drinking water at a concentration of 1 mg/L (for each drug). 4 groups were designed: untreated versus treated WT and ob/ob mice (n=6 mice per group).

first: Bernard

last: Fromenty


title: Affymetrix expression data from colon cancer patient tissues

status: Public on Feb 19 2014

city: Bethesda

first: Aaron

last: Schetter

state: MD

address: 37 Convent Drive, Building 37, Room 3050

department: Laboratory of Human Carcinogenesis

institute: National Cancer Institute

summary:
Gene expression profiling of 111 colon tissues from tumors and adjacent noncancerous tissues.
Genotypes for the rs5995355 in NCF4 are included to identify genes whose expression are associated with this genotype.

overall_design: RNA from fresh frozen colon tissues were extracted using Trizol and hybridized to Affymetrix U113A arrays

first: Brid

last: Ryan

first: Curtis

last: Harris


title: Over-expression of either MECP2_e1 or MECP2_e2 in mouse MECP2 knockout fibroblasts

status: Public on Jan 25 2014

city: Toronto

first: john

last: vincent

state: ON

address: 250 College Street

department: Neuroscience Research

institute: Centre for Addiction & Mental Health

summary:
Aim: to detect genes that are differentially transcribed in mouse MECP2 knockout fibroblasts over-expressing either of the two human MECP2 isoforms, MECP2_e1 or MECP2_e2.
Methods: mouse Mecp2tm1.1Bird knockout fibroblast cell line was stably infected by lentiviral vectors over-expressing MECP2_e1, MECP2_e2, or eGFP. RNA extracted, and used for gene expression microarray analysis

overall_design: 3 biological replicates for MECP2_e1; 3 replicates for MECP2_e2; 3 replicates for eGFP as control; 3 replicates for MECP2_e1 with 9bp insertion mutation in N-terminal

first: John

last: Vincent

first: Marija

last: Orlic-Milacic


title: Thalamus and hypothalamus response to visual input deprivation

status: Public on Jan 26 2014

city: Shanghai

first: Xiang

last: Yu

address: 320 Yue Yang Road

department: Institute of Neuroscience and State Key Laboratory of Neuroscience

institute: Chinese Academy of Sciences

summary: Analysis of thalamus and hypothalamus under conditions of visual deprivation by dark-rearing (DR). Animals subjected to DR from birth till postnatal day (P) 14. Results provide insight into the role of visual inputs in the regulation of gene expression in thalamus and hypothalamus during development.

overall_design: RNA sample was taken from thalamus and hypothalamus of 14-day-old mouse reared in standard or dark condition. Comparisons among groups were made by one-color method with normalized data from Cy3 channels for data analysis.

first: Shu-Jing

last: Li


title: Gene expression profiling of two diffuse large B-cell lymphoma (DLBCL) cell lines, DHL4 and DHL6, treated with the SYK inhibitor, R406

status: Public on Dec 31 2013

city: Boston

first: Stefano

last: Monti

state: MA

address: 72 East Concord st. E-613B

department: Medicine

institute: Boston University

summary: The two DLBCL cell lines were treated with R406 to assess the signature of SYK inhibition. In previous studies, R406 decreased the proliferation and induced apoptosis of these surface Ig+ cell lines. In the previous studies, R406 inhibited the autophosphorylation of SYK 525/526 and SYK-dependent phosphorylation of BCR signaling components such as BLNK.

overall_design: RNA samples from two DLBCL cell lines, DHL4 and DHL6, treated with R406 or vehicle (DMSO) alone for 0, 2, 6, 24 or 48 hours were profiled in triplicate on Affymetrix HT_HG-U133A chips.

first: Linfeng

last: Chen


title: microRNA profiles of activated and resting T cells and their exosomes

status: Public on Feb 27 2014

first: Fatima

last: Sanchez-Cabo

address: Melchor Fernandez Almagro

institute: CNIC

summary: Microarray analysis of exosomal and cellular miRNAs in activated and resting primary human T lymphoblasts

overall_design: Primary human T lymphoblasts were obtained from eight donors and total RNA was isolated from cells and derived exosomes before and after activation with PMA plus ionomycin.

first: Carolina

last: Villarroya-Beltri

first: María

last: Mittelbrunn

first: Fátima

last: Sánchez-Cabo

first: Francisco

last: Sánchez-Madrid


title: Commensal microbiota contributes to chronic endocarditis and arrhythmia in TAX1BP1 deficient mice.

status: Public on Feb 01 2014

city: Oita

first: Satoko

last: Nakano

address: 1-1 Idaigaoka Yufu

institute: Oita University

summary: Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules with its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mouse develops age-dependent inflammatory constitution in multiple organs including heart, liver, skin and succumb to premature heart failure. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed that the 588 transcription alterations. SAA3 (serum amyloid A3), at 1,180-fold induction (FI), CHI3L1(361-FI), HP(187-FI), IL1B(122-FI) and SPP1/OPN(101-FI) and WIF1 (Wnt inhibitory factor 1) at 11-fold decrease implied extensive inflammation and tissue degeneration at this microenvironment. Intense Saa3 staining and significant reduction of I-κBα at the same area, massive infiltration of inflammatory lymphocytes and edema formation at the peripheral areas of sinoatrial and atrioventricular node were also observed and electrocardiogram indicated atrioventricular conduction defect (elongated PQ-interval) in TAX1BP1-KO mice. Since antibiotics-induced ‘germ free’ status for three months significantly ameliorated these chronic autoimmune and altered cardiac excitation properties, we conclude that these chronic pathological conditions, as we named ‘pseudo-infective endocarditis’ were boosted by the commensal microbiota those who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation and cardiac dysfunction.

overall_design: We employed laser capture microdissection (LCM) and gene expression microarray technique to obtain the specific gene expression information of pathologic organ. Total RNAs of mitral valves from three independent tissues of 8- or 16-week age (-wk) male mice of either WT or TAX1BP1-KO mice were prepared by LCM followed by total RNA extraction kit. Then the global mRNA expression profiles were analyzed by Agilent gene expression microarray.

first: Emi

last: Ikebe

first: Yoshiyuki

last: Tsukamoto

first: Yan

last: Wang

first: Takashi

last: Matsumoto

first: Takahiro

last: Mitsui

first: Takaaki

last: Yahiro

first: Kunimitsu

last: Inoue

first: Hiroaki

last: Kawazato

first: Aiko

last: Yasuda

first: Kanako

last: Ito

first: Shigeo

last: Yokoyama

first: Yuetsu

last: Tanaka

first: Hideki

last: Hasegawa

first: Kuan-Teh

last: Jeang

first: Mitsuo

last: Hori

first: Tatsuo

last: Shimada

first: Masatsugu

last: Moriyama

first: Katsushige

last: Ono

first: Toshiaki

last: Kubota

first: Wataru

last: Fujibuchi

first: Hidekatsu

last: Iha

first: Akira

last: Nishizono


title: A global toxicogenomic analysis investigating the mechanistic differences between tobacco and marijuana smoke condensates in vitro

status: Public on Feb 06 2014

city: Ottawa

first: Andrew

last: Williams

address: 50 Columbine

institute: Health Canada

summary: Like tobacco smoking, habitual marijuana smoking causes numerous adverse pulmonary effects. However, the mechanisms of action involved, especially as compared to tobacco smoke, are still unclear. To uncover putative modes of action, this study employed a toxicogenomics approach to compare the toxicological pathways perturbed following exposure to marijuana and tobacco smoke condensate in vitro. Condensates of mainstream smoke from hand-rolled tobacco and marijuana cigarettes were similarly prepared using identical smoking conditions. Murine lung epithelial cells were exposed to low, medium and high concentrations of the smoke condensates for 6 hr. RNA was extracted immediately or after a 4-hr recovery period and hybridized to mouse whole genome microarrays. Tobacco smoke condensate (TSC) exposure was associated with changes in xenobiotic metabolism, oxidative stress, inflammation, and DNA damage response. These same pathways were also significantly affected following marijuana smoke condensate (MSC) exposure. Although the effects of the condensates were largely similar, dose-response analysis indicates that the MSC is substantially more potent than TSC. In addition, steroid biosynthesis, apoptosis, and inflammation pathways were more significantly affected following MSC exposure, whereas m-phase cell cycle pathways were more significantly affected following TSC exposure. MSC exposure also appeared to elicit more severe oxidative stress than TSC exposure, which may account for the greater cytotoxicity of MSC. This study shows that in general, MSC impacts many of the same molecular processes as TSC. However, subtle pathway differences can provide insight into the differential toxicities of the two complex mixtures.

overall_design: Murine epithelial lung cells were exposed to tobacco smoke condensates (0, 25, 50, 90 μg/ml) or marijuana smoke condensates (0, 2.5, 5, 10 μg/ml) in serum-free medium for a six hour period. Following the six-hour exposure, cells were either harvested immediately or washed with phosphate-buffered saline and incubated in fresh serum-free medium for a four hour recovery period. Total RNA was extracted from the cells and hybridized against Universal Mouse Reference RNA (Agilent Technologies Canada, Inc.) to Agilent whole mouse genome microarray slides containing 44,000 transcripts. A LOWESS normalization was applied to expression results, and statistically significant genes were identified using the R library MAANOVA. Microarray results were validated by real time RT-PCR.

first: Rebecca

last: Maertens

first: Paul

last: White

first: Carole

last: Yauk


title: Transcriptome profiling in Engrailed2 knockout mice reveals common molecular pathways associated with ASD.

status: Public on Dec 23 2013

city: Trento

first: Erik

last: Dassi

state: TN

address: Via Sommarive, 9

department: CIBIO

country: Italy

institute: University of Trento

summary: Background: Transcriptome analysis has been used in autism spectrum disorder (ASD) to unravel common pathogenic pathways based on the assumption that distinct rare genetic variants or epigenetic modifications affect common biological pathways dysregulated in ASD. To unravel recurrent ASD-related neuropathological mechanisms, we took advantage of the En2-/- mouse model and performed transcriptome profiling on cerebellar and hippocampal adult tissues.  Methods: En2-/- and WT cerebellar and hippocampal tissue from littermate mice were assessed for differential gene expression using microarray hybridization followed by RankProd analysis. To identify functional categories overrepresented in the differentially expressed genes we used the BIOBASE ExPlain system and mouse phenotype ontology database. Furthermore, we performed direct enrichment analysis of ASD associated genes from the SFARI repository in our differentially expressed genes.  Results: We found 842 differentially expressed genes in En2-/- cerebellum and 862 in the En2-/- hippocampus. Our functional analysis revealed that the molecular signature of En2-/- cerebellum and hippocampus shares convergent pathological pathways with ASD, including abnormal synaptic transmission, altered developmental processes and increased immune response. Furthermore, when directly compared to the repository of the SFARI database, our differentially expressed genes show enrichment of ASD-associated genes significantly higher than previously reported. Among the differentially expressed genes 20 were validated by quantitative PCR.  Conclusions: Our results indicate the En2-/- mouse model of ASD as an appropriate tool to investigate molecular alterations related to ASD.

overall_design: En2-/- and WT cerebellar and hippocampal tissue from 3 littermates mice for each genotype was hybridized on three replicates microarrays.

first: Paola

last: Sgadò

first: Giovanni

last: Provenzano

first: Valentina

last: Adami

first: Giulia

last: Zunino

first: Sacha

last: Genovesi

first: Simona

last: Casarosa

first: Yuri

last: Bozzi


title: Early gene expression changes in spinal cord from SOD1G93A Amyotrophic Lateral Sclerosis animal model

status: Public on Nov 21 2013

city: São Paulo

first: Gabriela

middle: Pintar

last: Oliveira

state: Outside the US or Canada

address: Dr Arnaldo Av, 455, 2nd floor

department: Neurology

country: Brazil

institute: University of Sao Paulo Medical School

summary: Amyotrophic Lateral Sclerosis (ALS) is an adult-onset and fast progression neurodegenerative disease that leads to the loss of motor neurons. Mechanisms of selective motor neuron loss in ALS are unknown. The early events occurring in the spinal cord that may contribute to motor neuron death are not described, neither astrocytes participation in the pre-symptomatic phases of the disease. In order to identify ALS early events, we performed a microarray analysis employing a whole mouse genome platform to evaluate the gene expression pattern of lumbar spinal cords of transgenic SOD1G93A mice and their littermate controls at pre-symptomatic ages of 40 and 80 days. Differentially expressed genes were identified by means of the Bioconductor packages Agi4x44Preprocess and limma. FunNet web based tool was used for analysis of over-represented pathways. Furthermore, immunolabeled astrocytes from 40 and 80 days old mice were submitted to laser microdissection and RNA was extracted for evaluation of a selected gene by qPCR. Statistical analysis has pointed to 492 differentially expressed genes (155 up and 337 down regulated) in 40 days and 1105 (433 up and 672 down) in 80 days old ALS mice. The KEGG pathways tight junction, antigen processing and presentation, oxidative phosphorylation, endocytosis, chemokine signaling pathway, ubiquitin mediated proteolysis and glutamatergic synapse were found over-represented at both 40 and 80 days pre-symptomatic ages. Ube2i gene expression was evaluated in astrocytes from both transgenic ages, being up regulated in 40 and 80 days astrocytes enriched samples. Our data points to important early molecular events occurring in pre-symptomatic phases of ALS in mouse model. Early SUMOylation process linked to astrocytes might account to non autonomous cell toxicity in ALS. Further studies on the signaling pathways presented here may provide new insights to better understand the events triggering motor neuron death in this devastating disorder.

overall_design: Whole lumbar spinal cord from SOD1G93A and Non transgenic controls from 40 and 80 days were used in the experiments. 4 biological replicates were used. A reference sample, comprised by RNA from different neonatal organs (heart, liver, kidney) were used in the hybridations

middle: P

first: Chrystian

last: Alves

first: Gerson

last: Chadi


title: Identification of renal distal convoluted tubules enriched genes

status: Public on Nov 19 2013

city: Lyon

first: Nicolas

last: Picard

address: 7 passage du Vercors

institute: CNRS

summary:
The renal distal convoluted tubule DCT is a short part of the distal nephron with specific functions transporting ions and thereby modifying Na, Ca, Mg, K balance
A transcriptomic analysis of the DCT was performed to identify specific gene expression which would implicate those genes in specific DCT function

overall_design: Fluorescent DCT (EGFP+) were sorted out from a renal tubule suspension by a COPAS (Complex Object Parametric analyser and sorter). EGFP- and the total (ALL) fractions were also sorted by COPAS. Gene expression for each fractions (EGFP+, EGFP-, ALL) was performed in 4 mice

first: NICOLAS

last: PICARD

first: JOHANNES

last: LOFFING


title: Gene expression from Prep1-ablated mice

status: Public on Jan 01 2014

city: Nuthetal

first: Timo

last: Kanzleiter

address: Arthur-Scheunert-Alle 114

department: Experimental Diabetology

institute: DIfE

summary: The homeodomain transcription factor Prep1 was previously shown to regulate insulin sensitivity. Our aim was to study the specific role of Prep1 for the regulation of energy metabolism in skeletal muscle. Muscle specific ablation of Prep1 resulted in increased expression of respiratory chain subunits. This finding was consistent with an increase in mitochondrial enzyme activity without affecting mitochondrial volume fraction as assessed by electron microscopy. Metabolic phenotyping revealed no differences in daily energy expenditure or body composition. However, during treadmill exercise challenge, Prep1 ablation resulted in a higher maximal oxidative capacity and better endurance. Elevated PGC-1α expression was identified as a cause for increased mitochondrial capacity in Prep1-ablated mice. Prep1 stabilizes p160 Mybbp1a, a known inhibitor of PGC-1α activity. Thereby, P160 protein levels were significantly lower in muscle of Prep1-ablated mice. By a ChIPseq approach, PREP1-binding sites in genes encoding mitochondrial components (e.g. Ndufs2) were identified that might be responsible for elevated OXPHOS proteins in the muscle of Prep1 nullmutants. These results suggest that Prep1 exhibits additional direct effects on regulation of mitochondrial proteins. We therefore conclude that Prep1 is a regulator of oxidative phosphorylation components via direct and indirect mechanisms.

overall_design: Consequence of Prep1 ablation in skeletal muscle was investigated in Prep1deltaSM mice and compared to Prep1 flox mice, both on C57BL/6 background. 4 mice of each genotype were used to extract RNA from the tibialis anterior muscle.

first: T


title: IFN-alpha- and IFN-gamma-regulated transcription in MEFs derived from wild type mice or littermates expressing STAT1F77A

status: Public on Jan 12 2014

city: Nottingham

first: Andreas

last: Begitt

address: Clifton Boulevard

department: School of Life Sciences

institute: University of Nottingham

summary: Transcriptional profiling of mouse primary embryonic fibroblasts (MEFs) from wild type (WT) and knockin littermates expressing STAT1F77A (KI). For both genotypes, untreated control cells were compared to cells treated with IFN-alpha or IFN-gamma.

overall_design: Two condition experiments; untreated versus IFN treated

first: Filipa

last: Antunes

first: Uwe

last: Vinkemeier

first: Mathias

last: Droescher


title: SM003 - icSARS CoV, SARS MA15 wild type and SARS BatSRBD mutant virus infections of C57BL6 mice - A time course

status: Public on Feb 15 2014

first: Michael

last: Katze

department: Microbiology

summary: This purpose of this experiment was to investigate the transcriptional differences between mice infected with icSARS CoV, SARS MA15 wild type or SARS BatSRBD viruses.

overall_design: Overview of Experiment: Groups of 20 week old C57BL6 mice were infected with icSARS CoV, Wild Type SARS MA15 or SARS BatSRBD mutant viruses. Infections were done at 10^4 PFU or 10^5 PFU or time-matched mock infected. Time points were 1, 2, 4 and 7 d.p.i.  There were 3-5 animals/dose/time point. Lung samples were collected for virus load, transcriptional and proteomics analysis. Weight loss and animal survival were also monitored.

first: Ralph

last: Baric

first: Lynn

last: Law

first: Lisa

last: Gralinski

first: Jean

last: Chang


title: Obesity primes the enhancer landscape of colon epithelium for cancer

status: Public on Jan 13 2014

city: Research Triangle Park

first: Deepak

last: Mav

state: NC

address: 2 Davis Drive

institute: Sciome LLC

summary: High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon-specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients.

overall_design:
We measured gene expression in colon epithelium from wild type mice and NAG-1 (non-steroidal anti-inflammatory drug (NSAID)-activated gene-1) transgenic mice fed either a 10% fat diet (LF) or a 60% fat diet (HF) for 20 weeks, using Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays (014868) (Agilent Technologies) following the Agilent 1-color microarray-based gene expression analysis protocol.

The ChIP-seq component of the study is included in GSE46748.

first: Ruifang

last: Li

first: Paul

middle: A

last: Wade

first: Ruchir

last: Shah


title: Dynamic analysis of gene expression and genome wide transcription factor binding during lineage-specification of multipotent progenitors [HP]

status: Public on Oct 17 2013

city: Lund

first: Shamit

last: Soneji

address: Sölvegatan 19

country: Sweden

institute: BMC

summary:
FDCPmix cells were infected with Gata, Pu1 shRNAs and microarrayed 5 days after infecton as part of a study investigating the differentiation of a multipotential cell-line to erthroid and myeloid fates.
We used the paradigmatic 'GATA-PU.1 axis’ to explore, at systems-level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIPSeq of GATA1, GATA2 and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (i)  differential complexity of sequence motifs bound by GATA1, GATA2 and PU.1; (ii) the scope and interplay of the GATA1 and GATA2 programs within, and during transitions between, different cell compartments, and the extent of their hard-wiring by DNA motifs; (iii) the potential to predict gene expression trajectories based on global associations between TF-binding data and target gene expression and (iv) how dynamic modeling of DNA-binding and gene expression data can be used to infer regulatory logic of TF circuitry.  This 'rubric' exemplifies the utility of this cross-platform resource for deconvoluting the complexity of transcriptional programs controlling stem/progenitor cell fate in hematopoiesis.

overall_design: FDCPmix cells were infected with lentivirus containing either Pu1 or Gata2 shRNAs. After 5 days cells were washed, GFP sorted and microarrayed. Controlled against empty vector.

first: Tariq

last: Enver


title: SM012 - SARS MA15 wild type, and SARS deltaORF6 mutant virus infections of C57BL6 mice - A time course

status: Public on Jan 23 2014

state: WA

summary: This purpose of this experiment was to investigate the transcriptional differences between mice infected with SARS MA15 or SARS deltaORF6 mutant viruses.

overall_design: Overview of Experiment: Groups of 20 week old C57BL6 mice were infected with wild type SARS MA15 or SARS deltaORF6 mutant viruses.  Infections were done at 10^5 PFU or time-matched mock infected.  Time points were 1, 2, 4 and 7 d.p.i.  There were 3 animals/dose/time point.  Lung samples were collected for virus load, transcriptional and proteomics analysis. Weight loss and animal survival were also monitored.


title: Dynamic analysis of gene expression and genome wide transcription factor binding during lineage-specification of multipotent progenitors [ER]

summary:
FDCPmix cells were infected with Gata1 and Pu1 ER fusion proteins and microarrayed after induction to reveal genes regulated by each factor as part of a study investigating the differentiation of a multipotential cell-line to erthroid and myeloid fates.
We used the paradigmatic 'GATA-PU.1 axis’ to explore, at systems-level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIPSeq of GATA1, GATA2 and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (i)  differential complexity of sequence motifs bound by GATA1, GATA2 and PU.1; (ii) the scope and interplay of the GATA1 and GATA2 programs within, and during transitions between, different cell compartments, and the extent of their hard-wiring by DNA motifs; (iii) the potential to predict gene expression trajectories based on global associations between TF-binding data and target gene expression and (iv) how dynamic modeling of DNA-binding and gene expression data can be used to infer regulatory logic of TF circuitry.  This 'rubric' exemplifies the utility of this cross-platform resource for deconvoluting the complexity of transcriptional programs controlling stem/progenitor cell fate in hematopoiesis.

overall_design: FDCPmix cells were inected with lentivirus containing either Gata1 or Pu1 ER fusion protein, or a empty vector. Cells were sort on GFP and tamoxifen added after a period of growth. Expression arrays were performed at the beginning, and 24hr after induction of the ER fusion construct.


title: Medullary Thymic Epitherlial Cell (mTEC) Gene Expression in MBD1 WT and KO Mice

city: San Francisco

first: Mark

middle: Stuart

last: Anderson

state: CA

address: 513 Parnassus Avenue, HSW Room  1102, Box 0540

department: Diabetes Center

institute: UCSF

summary: To explore global gene expression using microarray analysis in mTEC's isolated from MBD1 WT and MBD1 KO mice

overall_design: mTECs were sorted by flow cytometry from 30 day old MBD1 WT and KO Mice.  4 biological replicates were performed for both MBD1 WT and KO mice (1 replicate of each failed quality control and wasd removed from the analysis).

first: Mike

last: Waterfield


title: Pulmonary retention of titanium dioxide nanoparticles and biological outcomes following low dose instillation in mice

status: Public on Nov 01 2013

first: Mainul

last: Husain

address: 50 Colombine Driveway

summary: Pulmonary exposure to high doses of nanoparticles (NP) leads to well characterized lung toxicity in addition to long-term NP retention. However, pulmonary NP accumulation and toxicity following low dose exposures are not well described. In the present study we sought to: (1) investigate particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO2) and (2) determine the effects of long-term particle accumulation on pulmonary systems. Female C57BL/6 mice were exposed to rutile nano-TiO2 (primary size of 20.6 nm and surface area of 107.7 m2/g) via single intratracheal instillations of 18, 54 and 162 µg/mouse and sampled 1, 3 and 28 days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using Nanoscale Hyperspectral Microscope. DNA microarrays, pathway-specific real-time RT-PCR (qPCR) and gene-specific qPCR arrays, and tissue protein analyses were employed to characterize pulmonary responses. Hyperspectral mapping showed dose-dependent retention of nano-TiO2 in the lungs up to 28 days post-exposure time. Retention did not correlate with the extent of inflammatory neutrophil influx into the lungs. DNA microarray analysis showed altered expression of approximately 3000 genes across all treatment groups (±1.3 fold; p<0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein levels. Although the low dose exposure failed to induce observable inflammation, significant changes in the expression of genes and proteins associated with inflammation were observed. Moreover, diminished (or absent) neutrophil influx in the low and medium dose groups was correlated with negative regulation of genes associated with ion homeostasis and muscle regulation. Gene expression changes for several inflammatory mediators have previously been noted in mice exposed to the same nano-TiO2 via inhalation. Our results suggest that retention of nano-TiO2 in the absence of inflammation and effective clearance can perturb calcium and ion homeostasis, and affect smooth muscle activities over time.

overall_design: This experiment consists of three different dosages of TiO2, e.g., low (18 ug), medium (54 ug) and high (162 ug), and one control. There are 3 time points for each treatment and control group, e.g., day 1, day 3 and day 28. Each dose or time point has 5-6 biological replicates. There are total 65 samples (arrays)

first: A

middle: T

last: Saber

first: Charles

last: Guo

first: N

middle: R

last: Jacobsen

first: K

last: Jensen

first: Carole

last: Yauk

first: Andrew

last: Williams

first: U

last: Vogel

first: H

last: Wallin

first: Sabina

last: Halappanavar


title: Dynamic analysis of gene expression and genome wide transcription factor binding during lineage-specification of multipotent progenitors [PC]

summary:
Primary hematopoietic cells from mouse bone marrow were sorted and hybridised expression microarrays as part of a study investigating the differentiation of a multipotential cell-line to erthroid and myeloid fates.
We used the paradigmatic 'GATA-PU.1 axis’ to explore, at systems-level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIPSeq of GATA1, GATA2 and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (i)  differential complexity of sequence motifs bound by GATA1, GATA2 and PU.1; (ii) the scope and interplay of the GATA1 and GATA2 programs within, and during transitions between, different cell compartments, and the extent of their hard-wiring by DNA motifs; (iii) the potential to predict gene expression trajectories based on global associations between TF-binding data and target gene expression and (iv) how dynamic modeling of DNA-binding and gene expression data can be used to infer regulatory logic of TF circuitry.  This 'rubric' exemplifies the utility of this cross-platform resource for deconvoluting the complexity of transcriptional programs controlling stem/progenitor cell fate in hematopoiesis.

overall_design: Primary hematopoietic cells from mouse bone marrow sorted using the dissection as described by Pronk et al (2007,Cell Stem Cell) where lin was defined as B220, CD3, CD4, CD8, CD41, Mac1, Gr1, Ter119.


title: Gene expression in the isolated islets of 10 day old, 4 wk old, 12 wk old, and 20 wk old Non-Obese Diabetic (NOD) mice compared to healthy age matched control NOD.B10 mice

status: Public on Nov 28 2013

city: Stanford

first: Linda

last: Yip

address: 269 Campus Drive West, CCSR Building Rm. 2240

institute: Stanford University

summary: Gene expression in the islets of diseased NOD mice compared to congenic healthy NOD.B10 mice at various ages, during the progression of NOD disease.

overall_design: Islets were isolated from individual NOD and NOD.B10 mice by collagenase digestion. RNA was extracted using Trizol, combined with the RNeasy micro kit (Qiagen). RNA quality was assessed using the Agilent 2100 Bioanalyzer and the RNA 6000 Pico Reagent Kit (Agilent). Microarrays were performed using the Whole Mouse Genome Microarray Kit, 4×44K 2-color arrays (Agilent Technologies).


title: Dynamic analysis of gene expression and genome wide transcription factor binding during lineage-specification of multipotent progenitors [TC]

summary:
An expression time course experiment to investigate gene expression changes during differentiation of multipotential cells over two lineages using the model cell line FDCPmix differentiating towards erytroid and myeloid fates.
We used the paradigmatic 'GATA-PU.1 axis’ to explore, at systems-level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIPSeq of GATA1, GATA2 and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (i)  differential complexity of sequence motifs bound by GATA1, GATA2 and PU.1; (ii) the scope and interplay of the GATA1 and GATA2 programs within, and during transitions between, different cell compartments, and the extent of their hard-wiring by DNA motifs; (iii) the potential to predict gene expression trajectories based on global associations between TF-binding data and target gene expression and (iv) how dynamic modeling of DNA-binding and gene expression data can be used to infer regulatory logic of TF circuitry.  This 'rubric' exemplifies the utility of this cross-platform resource for deconvoluting the complexity of transcriptional programs controlling stem/progenitor cell fate in hematopoiesis.

overall_design: Multipotential FDCPmix cells were placed in two separate cytokine conditions and differentiated to erythroid and myeloid cells. Samples were taken at the time intervals indicated and hybridised to Agilent expression arrays. Each time point was done in triplicate.


title: SM009 - SARS infection of C57BL6, and PLAT knock-out mice.

status: Public on Feb 20 2014

city: Seattle

first: Michael

last: Katze

address: Rosen Building 960 Republican St.

institute: University of Washington

summary: This purpose of this experiment was to investigate the transcriptional differences between C57BL6, PLAT knock-out mice infected with SARS MA15 virus.

overall_design: Overview of Experiment: Groups of 20 week old C57BL6 and PLAT knock-out mice were infected with SARS MA15 virus. Infections were done at 10^5 PFU or time-matched mock infected. Time points were 4 and 7 d.p.i.  There were 2-4 animals/dose/time point. Lung samples were collected for virus load, transcriptional and proteomics analysis. Weight loss and animal survival were also monitored.

first: Ralph

last: Baric

first: Lynn

last: Law

first: Lisa

last: Gralinski

first: Jean

last: Chang


title: Microarray analysis of gene expression in mouse embryonic fibroblasts (MEFs) by addition of serum from L/MDR irradiated mice at 10 and 20 days.

city: Rokkasho

first: Takashi

last: Sugihara

state: Aomori

address: 2-121 Hacchazawa

department: Radiobiology

institute: Institute for Environmental Sciences

summary: The expression changes were detected by addition of serum form L/MDR irradiated mice at 10 and 20 days in mouse embryonic fibroblasts (MEFs).

overall_design: (Expression of MEFs by addition of serum from nonirradiated mice) vs (Expression of MEFs by addition from L/MDR irradiated mice)


title: IFN-γ-induced iNOS expression in regulatory macrophages prolongs allograft graft survival in fully immunocompetent recipients.

status: Public on Dec 21 2013

city: Bergisch-Gladbach

first: Stefan

last: Tomiuk

address: Friedrich-Ebert-Str. 68

department: Bioinformatics

institute: Miltenyi Biotec GmbH

summary: Mouse monocytes exposed to M-CSF and IFN-γ were driven to a suppressor phenotype over a seven day culture period. The resulting regulatory macrophages (M regs) expressed markers distinguishing them from M0-, M1-, and M2-polarised macrophages and monocyte-derived DCs. M regs completely suppressed polyclonal T cell proliferation through an inducibile nitric oxide synthase (iNOS)-dependent mechanism. Additionally, M regs were found to eliminate cocultured T cells in an allospecific fashion. In a heterotopic heart transplant model, a single intravenous administration of 5x10^6 donor-strain M regs prior to transplantation significantly prolonged allograft survival in fully immunocompetent recipients using both the stringent C3H-to-BALB/c and C57BL/6-to-BALB/c strain combinations; this graft-protective effect was alloantigen-specific. M regs from Nos2-deficient mice did not prolong allograft survival, proving that M reg function in vivo is iNOS-mediated and dependent on living cells. Co-treatment with 1 mg/kg/day rapamycin for 10 days post-transplant markedly enhanced the effect of M regs. In untransplanted C57BL/6 recipients, M regs of BALB/c origin were detectable for up to 2 weeks post-infusion. It is concluded that mouse M regs represent a novel, phenotypically distinct subset of tolerogenic macrophages, which resemble human M regs in their derivation, phenotype and in vitro functions.

overall_design: The dataset comprises 36 samples divided into twelve sample groups each representing a certain monocyte/macrophage subtype

first: Paloma

last: Riquelme

first: Anja

last: Kammler

first: Fred

last: Fändrich

first: Hans

last: Schlitt

first: Edward

middle: K

last: Geissler

first: James

last: Hutchinson


title: Expression data of blood (BVEC) versus lymphatic (LVEC) vascular endothelial silenced for RhoB and VEZF1

status: Public on Oct 28 2013

first: Sharon

last: Shechter

address: 99 Brookline ave.

department: Pathology

institute: Beth Israel Deaconess

summary:
RhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge.
We used microarrays to link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to RhoB/VEZF1-mediated gene regulation in primary human blood versus lymphatic endothelial cells.

overall_design: Pure populations of human primary BVECs and LVECs silenced for RhoB or VEZF1 were used for RNA extraction and hybridization on Affymetrix microarrays. We extracted these cells from human male foreskins from at least four individuals and purified them using Dynabeads associated with vascular markers (CD31 and Podoplanin).

first: Damien

last: Gerald


title: SYK Is a Critical Regulator of FLT3 In Acute Myeloid Leukemia

status: Public on Jan 15 2014

city: Cambridge

first: Gabriela

last: Alexe

address: 415 Main St.

department: Computational Biology and Bioinformatics

institute: Broad Institute

summary: Cooperative dependencies between mutant oncoproteins and wild-type proteins are critical in cancer pathogenesis and therapy resistance. Although spleen tyrosine kinase (SYK) has been implicated in hematologic malignancies, it is rarely mutated. We used kinase activity profiling to identify collaborators of SYK in acute myeloid leukemia (AML) and determined that FMS-like tyrosine kinase 3 (FLT3) is transactivated by SYK via direct binding. Highly activated SYK is predominantly found in FLT3-ITD positive AML and cooperates with FLT3-ITD to activate MYC transcriptional programs. FLT3-ITD AML cells are more vulnerable to SYK suppression than FLT3 wild-type counterparts. In a FLT3-ITD in vivo model, SYK is indispensable for myeloproliferative disease (MPD) development, and SYK overexpression promotes overt transformation to AML and resistance to FLT3-ITD-targeted therapy.

overall_design: HL-60, MOLM-14, and U937 cell lines were transduced in triplicate with a control luciferase-directed shRNA (target sequence CCTAAGGTTAAGTCGCCCTCG), and in duplicate with two SYK-directed shRNAs:  shSYK_1 (clone ID TRCN0000197257,  target sequence  GCAGCAGAACAGACATGTCAA)   and shSYK_2  (clone ID TRCN0000003163 , target sequence  GCAGGCCATCATCAGTCAGAA),  and were then selected with 1 µg/ml puromycin 48 hours post-infection. At day 5 post-infection, RNA was extracted and profiled using HT HG-U133A arrays (Affymetrix) at the Broad Institute (Cambridge, MA, USA). The computational analysis of the gene expression data was performed through the Genome Space bioinformatics platform (http://www.genomespace.org).

first: Kimberly

last: Stegmaier


title: Gene expression profiling on innervated and denervated muscles of Smad4 KO and control mice.

status: Public on Sep 17 2013

city: Padua

first: Marco

last: Sandri

address: via Orus,2

institute: VIMM (Venetian Institute of Molecular Biology)

summary:
To identify novel atrophy-related genes, which are controlled by BMP signaling, we performed gene expression profiling on innervated and 14 days denervated muscles of Smad4 knockout and control mice, focusing on genes that were differentially upregulated in denervated Smad4-/- muscles compared to controls. Among the different genes our attention was attracted by a gene that encodes for a novel f-box protein (Fbxo30) belonging to the SCF complex family of the ubiquitin ligases.
Cell size is determined by the balance between protein synthesis and degradation. This equilibrium is affected by hormones, nutrients, energy levels, mechanical stress and cytokines. Mutations that inactivate Myostatin lead to important muscle growth in animals and humans. However, the signals and pathways responsible for this hypertrophy remain largely unknown. Here we find that BMP signaling, acting through Smad1/5/8, is the fundamental hypertrophic signal. Inhibition of BMP signaling causes muscle atrophy, abolishes the hypertrophic phenotype of Myostatin knockout and strongly exacerbates the effects of denervation and fasting. BMP-Smad1/5/8 negatively regulates a novel gene (Fbxo30) that encodes an ubiquitin ligase, that is required for muscle loss. Collectively, these data identify a critical role for the BMP pathway in adult muscle maintenance, growth and atrophy.

overall_design: Gene expression profiling on innervated and 14 days denervated muscles of Smad4 knockout and control mice. Three independent experiments were performed for each experimental condition using different animals for each experiment.

first: Roberta

last: Sartori


title: profile miRNA expression in breast cancer

status: Public on Feb 01 2014

city: Barcelona

first: Andrea

last: Feliciano

address: Passeig Vall d´Hebron 119-129

institute: Vall d´Hebron Research Institute

summary: differential miRNA expression between breast tumor tissue and normal tissue

overall_design: 50 tumor samples were analyzed. As control samples,  3 pools of normal tissue (10 normal samples for each pool ) were used.

first: Josep

last: Castellvi

first: Ana

last: Artero

first: Jose

last: Leal

first: Cleofé

last: Romagosa

first: Javier

last: Hernández

first: Vicente

last: Peg

first: Angels

last: Fabra

first: Francisco

last: Vidal

first: Hiroshi

last: Kondoh

first: Santiago

last: Ramón y Cajal

first: Matilde

middle: E

last: Lleonart


title: Gene expression profiles in group G streptococci during infection and under various stress conditions

status: Public on Sep 13 2013

city: Tokyo

first: Shinya

last: Watanabe

address: 1-21-1 Toyama

department: Department of Infectious Diseases

institute: National Center for Global Health and Medicine

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

sample_organism: Streptococcus dysgalactiae subsp. equisimilis GGS_124

overall_design: Refer to individual Series


title: Gene expression profiling to identify genes that are differentially expressed between murine MHCIIlo and MHCIIhi dendritic cell subpopulations [LPS stimulation]

status: Public on Dec 22 2013

city: South San Francisco

first: Jason

last: Hackney

address: 1 DNA Way

department: Department of Bioinformatics and Computational Biology

institute: Genentech, Inc.

summary: Hematopoietic progenitors from mouse bone marrow were differentiated into dendritic cells for 5 days with GM-CSF and IL-4. On day 6, MHCIIhi and MHCIIlo BMDC subpopulations were sorted to purify by flow cytometry. RNA was extracted and processed for microarray analysis.

overall_design: Two condition experiment; Biological replicates: 5 replicates per condition.

first: Zora

last: Modrusan

first: Bryan

last: Vander Lugt

first: Aly

last: Khan

first: Smita

last: Agrawal

first: Justin

last: Lesch

first: Meijuan

last: Zhou

first: Wyne

last: Lee

first: Summer

last: Park

first: Min

last: Xu

last: DeVoss

first: Chauncey

last: Spooner

first: Cecile

last: Chalouni

first: Lelia

last: Delamarre

first: Ira

last: Mellman

first: Harinder

last: Singh