title: Gene expression architecture of mouse dorsal and tail skin reveals functional differences in inflammation and cancer: TPA time course

status: Public on Jun 01 2016

city: San Francisco

first: David

last: Quigley

state: CA

address: 1450 Third St. Room 207

department: Helen Diller Comprehensive Cancer Center

institute: UCSF

summary: Gene expression levels in normal tissues can differ substantially between individuals, due to inherited polymorphisms acting in cis or trans. Analysis of this variation across a population of genetically distinct individuals allows us to visualize a network of co-expressed genes under normal homeostatic conditions, and the consequences of perturbation by tissue damage or disease development. Here, we explore gene expression networks in normal adult skin from 470 genetically unique mice, and demonstrate the dependence of the architecture of signaling pathways on skin tissue location (dorsal or tail skin) and perturbation by induction of inflammation or tumorigenesis. Gene networks related to specific cell types, as well as signaling pathways including Sonic Hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is extensively rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.

overall_design: Time course analysis of replicate exposure to epidermal application of TPA

first: Allan

last: Balmain


title: Effects of blocking IL-17A on lung gene expression after ozone exposure in obese (db/db) mice

status: Public on May 24 2016

city: Boston

first: Stephanie

middle: A

last: Shore

state: MA

address: 665 Huntigton Av Bld1 room 307

department: Environmental Health

country: USA

institute: Harvard School of Public Health

summary: Obese mice have an augmented response to Ozone exposure (2 ppm for 3 hours and studied 24 hours later), including increase airway hyperresponsiveness and BAL inflammation when compared to WT ozone exposed mice. When IL-17A is block with systemic injected of IL-17A antibodies there is a decrease of response in the obese mice.  To determine the mechanism of action, RNA was extracted from the lungs of  IL-17A and Isotype injected ozone exposed obese mice and microarray analysis of gene expression was performed.

overall_design: Lungs were harvested from db/db mice exposed to air and ozone and injected with anti-IL-17A and isotype.

first: Joel

last: Mathews

middle: I

last: Kasahara


title: Shewanella piezotolerans WP3 wild-type strain under heat shock

status: Public on Jun 15 2016

city: Shanghai

first: Huahua

last: Jian

address: No.800 Dongchuan Road

country: China

institute: Shanghai Jiao Tong University

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

overall_design: Refer to individual Series


title: Early life stress perturbs the maturation of microglia in the developing hippocampus

status: Public on May 03 2016

city: New Haven

first: Arie

last: Kaffman

state: Connecticut

address: 300 George St. Suite 901

department: Psychiatry

institute: Yale University


title: Network Biology of the Skin [2]

status: Public on May 19 2016

overall_design: A backcross was generated using male Mus spretus and female FVB/N Hras-/- mice; female F1 hybrids were mated with male FVB/N Hras -/- or Hras -/+ mice to generate a backcross population that was either Hras +/+, +/-, or -/- as noted. Mice were aged to 8 weeks and a tail skin sample was snap frozen. This series contains only Hras +/+ and Hras +/- samples.


title: Treatment of bone marrow-derived macrophages with hFc-FNDC4 recombinant protein

status: Public on Apr 12 2016

city: Solna

first: Estelle

last: Proux-Wéra

department: Department of Biochemistry and Biophysics

country: Sweden

institute: Science for Life laboratory

summary: FNDC4 is a novel secreted factor sharing high homology with the exercise-associated myokine irisin (FNDC5). Here we report that Fndc4 is robustly upregulated in various mouse models of inflammation as well as in human inflammatory conditions. Specifically, subjects with inflammatory bowel disease show increased FNDC4 levels locally at inflamed sites of the intestine. Interestingly, administration of recombinant FNDC4 during colitis development in mice resulted in markedly reduced disease severity compared to mice injected with a control protein. Conversely, mice that lacked Fndc4 showed increased colitis severity. Analysis of binding of FNDC4 to different immune cell types revealed strong and specific binding to macrophages and monocytes. FNDC4 treatment of bone marrow-derived macrophages in vitro resulted in reduced phagocytosis, improved survival and reduced pro-inflammatory chemokine expression. Hence, treatment with FNDC4 resulted in a state of dampened macrophage activity, while enhancing their survival. Thus, we have characterized a novel factor with direct therapeutic potential in inflammatory bowel disease and possibly other inflammatory diseases.

overall_design: Bone marrow-derived macrophages were grown in growth media (DMEM, 10% FCS, 1% PenStrep and 20% L9209-media), starved for 24h in 1% FCS-DMEM and then treated for 24h in 1%FCS-DMEM with 100nM hFc-FNDC4 or hFc control protein.

first: Madeleen

last: Bosma

first: Pontus

last: Boström


title: Early life stress perturbs the maturation of microglia in the developing hippocampus [development]

summary: The goal of this project was to identify genes whose expression is modified by age in microglia isolated from the hippocampus of 14 and 28-day old control mice (i.e. normally developing mice). To accomplish this we used two independent cohorts of control mice and identified a list of 76 genes that were significantly regulated by age (p< 0.05) in both cohorts. Data for cohort 1 were extracted from gene expression of P14 and P28 control mice available in the BDS-P14-male series (GSE81036) and BDS-P28-male series (GSE81037). Data for cohort 2 are available in this series. These data are summarized also in Table S3 in Delpech J.C. et al. Early life stress perturbs the maturation of microglial cells in the developing hippocampus, Brain, Behavior and Immunity, 2016 (in preparation).

overall_design: microglial cells were isolated from the hippocampus of 14 and 28-day old control  male pups (n=6 from each group, all from differ litters) using Percoll gradient followed by FACS analysis. RNA was harvested using the he mirVana mirRNA isolation kit (Cat # AM 1560, Life technologies) and was then concentrated and Dnase treated on column using the RNA clean and contractor-5 kit (Cat# R1015, Zymo Research). Two ng of RNA were converted to cDNA using Superscript Vilo (Cat# 11754, Life Technologies), amplified with 5 rounds of PCR according to the nCounter single cell gene expression protocol and hybridized to the mouse immune panel (Cat# 150761, NanoString Technologies), and processed according to manufacturer instructions. Counts were normalized to positive controls and 5 housekeeping genes (e.g. Alas1, Gapdh, Oaz1, Polr1b, Sdha, Tbp) that were not affected by either BDS or age and showed a coefficient of variation of less than 20%. Genes were considered “present” if at least 40% of the samples showed hybridization signal that was 2 s.d. above the mean value for the negative control probes

first: Jean-Christophe

last: Delpech

first: Lan

last: Wei

first: Jin

last: Hao

first: Xiaoqing

last: Yu

first: Charlotte

last: Madore

first: Oleg

last: Butovsky


title: Expression data from adult mouse Nucleus Accumbens following prenatal infection

status: Public on Mar 01 2016

city: Zurich

first: Juliet

last: Richetto

address: Winterthurerstrasse 260

department: Institute for Pharmacology and Toxicology

country: Switzerland

institute: University of Zurich - Vetsuisse

summary:
Prenatal exposure to infectious or inflammatory insults can increase the risk of neuropsychiatric disorders with neurodevelopmental components, including schizophrenia and autism. The molecular processes underlying this pathological association are only partially understood. Here, we implemented an unbiased genome-wide transcriptional profiling of the nucleus accumbens of mice exposed to prenatal infection on GD17 compared to control subjects in order to elucidate the long term molecular signature of late prenatal infection.
We used microarray analysis to investigate the long lasting gene expression changes in a well-established mouse model that is based on maternal treatment with the viral mimic poly(I:C) during pregnancy

overall_design: C57BL/6 mice were treated with the synthetic viral mimetic poly(I:C) (5 mg/kg, i.v.) or control (saline, i.v.) solution on  gestation day 17. Offspring were subjected to cognitive and behavioral testing in adulthood, and then whole genome gene expression analysis with Affymetrix Microarray and subsequent q-PCR validation were performed on the nucleus accumbens.

first: Urs

last: Meyer

first: Marco

last: Riva

first: Annamaria

last: Cattaneo


title: Expression data from adult mouse brain regions following prenatal infection


title: Early life stress perturbs the maturation of microglia in the developing hippocampus [P14]

summary: In this study we hypothesize that early life stress perturbs the normal function of microglia in the developing hippocampus and that this effect is responsible for the ability of early life tress to disrupt normal synaptic maturation, myelination, and axonal growth in the developing hippocampus. To test this hypothesis we used the mouse immune panel from NanoString in order to identify immune-related genes whose expression is modified by BDS, a mouse model of early life stress, in microglia isolated from the hippocampus of 14-day old male pups. This project is part of a manuscript that is currently under preparation (Delpech J.C. et al. Early life stress perturbs the maturation of microglia in the developing hippocampus, Brain, Behavior and Immunity, 2016)

overall_design: microglia were isolated from the hippocampus of 14-day old control and BDS male pups (n=5 from each group, all from different litters) using Percoll gradient followed by FACS analysis. RNA was harvested using the he mirVana mirRNA isolation kit (Cat # AM 1560, Life technologies) and was then concentrated and Dnase treated on column using the RNA clean and contractor-5 kit (Cat# R1015, Zymo Research). Two ng of RNA were converted to cDNA using Superscript Vilo (Cat# 11754, Life Technologies), amplified with 5 rounds of PCR according to the nCounter single cell gene expression protocol and hybridized to the mouse immune panel (Cat# 150761, NanoString Technologies), and processed according to manufacturer instructions. Counts were normalized to positive controls and 5 housekeeping genes (e.g. Alas1, Gapdh, Oaz1, Polr1b, Sdha, Tbp) that were not affected by either BDS or age and showed a coefficient of variation of less than 20%. Genes were considered “present” if at least 40% of the samples showed hybridization signal that was 2 s.d. above the mean value for the negative control probes


title: Comparison of the DNA methylation of in vitro cultured bovine SAM-treated blastocysts and non-treated blastocysts

status: Public on Feb 02 2016

city: Quebec city

first: Habib

middle: A.

last: Shojaei Saadi

state: Quebec

address: 2440 bl hochelaga, pavillon inaf

country: Canada

institute: Laval University

type: Methylation profiling by genome tiling array

summary: Epigenetics (DNA methylation) profiling of bovine in vitro cultured expanded blastocysts (EB) comparing control non-treated expanded blastocysts with SAM-treated expanded blastocysts. S-Adenosyl methionine (SAM) is the global methyl donor providing methyl

overall_design: Two-condition experiment, bovine non-treated expanded blastocysts (pools of 10) vs bovine SAM-treated expanded blastocysts. Four biological replicates of each tissue were hybridized to four two-color arrays in a dye-balanced design.

first: H

first: D

last: Gagné

first: E

last: Fournier

first: I

last: Gilbert

first: L

middle: M

last: Baldoceda-Baldeon

first: M

last: Sirard

first: C

last: Robert


title: Network Biology of the Skin [1]

first: David

last: Quigley

overall_design: A backcross was generated using male Mus spretus and female FVB/N mice; female F1 hybrids were mated with male FVB/N mice.   Mice were aged to 8 weeks and sacrificed. Shaved dorsal skin and tail skin were snap frozen.

first: Allan

last: Balmain


title: Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid [mouse]

status: Public on Jan 27 2016

city: Wageningen

first: Guido

last: Hooiveld

address: HELIX, Stippeneng 4

department: Div. Human Nutrition & Health

country: Netherlands

institute: Wageningen University

summary:
Background: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6α-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA (INT-747) alters hepatic expression of many genes. However, no data are available on the effects of OCA in human liver. Here, we generated gene expression profiles in human precision-cut liver slices (hPCLS) after treatment with OCA.

Methods: hPCLS were incubated with OCA for 24 h. WT or FXR -/- mice received OCA or vehicle by oral gavage for 7 days.

Results: Transcriptomic analysis showed that well-known FXR target genes, including NR0B2 (SHP), ABCB11 (BSEP), SLC51A (OSTα) and SLC51B (OSTβ) and ABCB4 (MDR3), are regulated by OCA in hPCLS. Ingenuity pathway analysis confirmed that 'FXR/RXR activation' is the most significantly changed pathway upon OCA treatment. Comparison of gene expression profiles in hPCLS and mouse livers identified 18 common potential FXR targets. ChIP-sequencing in mouse liver confirmed FXR binding to IR1 sequences of Akap13, Cgnl1, Dyrk3, Pdia5, PPP1R3B and Tbx6.

Conclusions: Our study shows that hPCLS respond to OCA treatment by upregulating well-known FXR target genes, demonstrating its suitability to study FXR-mediated gene regulation. We identified 6 novel bona-fide FXR target genes in both mouse and human liver. Finally, we discuss a possible explanation for changes in HDL/LDL observed in NASH and primary biliary cirrhosis patients treated with OCA based on the genomic expression profile in hPCLS.

overall_design: Wild-type and FXR-/- mice received either a treatment with OCA (10 mg/kg/day) to pharmacologically activate FXR, or vehicle (1% methyl cellulose) daily by oral gavage for 7 days. Hereafter, mice were sacrificed and livers subjected to gene expression profiling.

first: Noortje

last: Ijssennagger

first: Aafke

middle: W

last: Janssen

first: Sander

last: Kersten

first: Saskia

last: van Mil


title: Expression data from thymic and lymph node mesenchymal stromal subsets.

status: Public on Mar 03 2016

city: Fredriksberg C

first: William

middle: Winston

last: Agace

address: Bülowsvej 27

department: National Veterinary Institute, Section for Immunology and Vaccinology

country: Denmark

institute: Technical University of Denmark

summary:
Despite their key role in immunity our understanding of primary and secondary lymphoid stromal cell heterogeneity and ontogeny remains limited. Here, using genome-wide expression profiling and phenotypic and localization studies, we identify a functionally distinct subset of BP3-PDPN+PDGFRβ+/α+CD34+ stromal adventitial cells in both lymph nodes and thymus that is located within the perivascular niche surrounding PDPN-PDGFRβ+/α-Esam-1+ITGA7+ pericytes. In re-aggregate organ grafts adult CD34+ adventitial cells gave rise to multiple thymic and lymph node mesenchymal subsets including pericytes, FRC-, MRC- and FDC-like cells, the development of which was lymphoid environment dependent. During thymic ontogeny pericytes developed from a transient population of BP3-PDPN+PDGFRβ+/α+CD34-/lo anlage-seeding progenitors that subsequently up-regulated CD34 and we provide evidence suggesting that similar embryonic progenitors give rise to lymph node mesenchymal subsets. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34+ vascular adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues.
To comprehensively study the differences and similarities between mesenchymal stromal subsets in the thymus and lymph nodes, global gene expression analysis was performed on sorted PDPN-, BP-3-PDPN+ and BP-3+PDPN+ PDGFRb+ lymph node mesenchymal cells (LNMC) as well as PDPN- and BP-3-PDPN+ PDGFRb+ thymic mesenchymal cells (TMC) from 2 w old mice by microarray.

overall_design: Total RNA was prepared from TMC and LNMC (pooled inguinal, brachial and axillary LN) subsets sorted from 3 (TMC) and 10-11 (LNMC) 2 weeks old mice per experiment. Isolated RNA from 3 individual experiments was amplified and prepared for hybridization to the Affymetrix Mouse Gene 1.1 ST Array at a genomics core facility: Center of Excellence for Fluorescent Bioanalytics (KFB, University of Regensburg, Germany)

first: Katarzyna

last: Sitnik

first: Holger

last: Weishaupt


title: Microarray analysis in Arabidopsis seedlings treated with lasalocid sodium.

status: Public on Mar 25 2016

city: Yokohama

first: Yukio

last: Kurihara

state: Kanagawa

address: 1-7-22 Suehiro-cho, Tsurumi-ku

department: CSRS

country: Japan

institute: Riken

summary: Gene expression profile in Arabidopsis seedlings treated with lasalocid sodium was compared with that in non-treated seedlings.

first: Minami

last: Matsui

first: Emiko

first: Mika

last: Kawashima


title: Defining the microglia response during the time course of chronic neurodegeneration

status: Public on Jan 13 2016

city: Easter Bush Campus

first: James

last: Vincenti

state: Midlothian

address: The Roslin Institute

department: Neurobiology Division

country: United Kingdom

institute: The Roslin Institute, The University of Edinburgh

summary: In order to study the microglia contribution in neurodegeneration more specifically we established a mouse model of prion disease in which the 79A murine prion strain was introduced by an intraperitoneal route into BALB/cJFms-EGFP/- mice, which express Enhanced Green Fluorescent Protein (EGFP) under control of the C-fms operon.  Samples were taken at time points during disease progression and histological analysis of the brain and transcriptional analysis of isolated microglia was carried out. The analysis of isolated microglia revealed a disease specific, highly pro-inflammatory signature in addition to an up-regulation of genes associated with metabolism, respiratory stress and DNA repair. This study strongly supports the growing recognition of the importance of microglia within the prion disease process and identifies the nature of the response through gene expression analysis of isolated microglia.

overall_design: Groups of gender matched BALB/cJFms-EGFP/- mice were challenged i.p. with either 0.02 ml of 0.02 w/v 79A infected or normal brain material.  The average initial age of animals at challenge was 116 days ± 2.1 SE.  Mice were culled in duplicate at 35, 100, 150 and 200 dpi.  Microglial RNA processing was handled by ARK Genomics (The Roslin Institute & R(D)SVS). The mRNA was converted to double-stranded cDNA containing biotin, using a single round of amplification, from both the poly-A 3 ́ tail and randomly using the NuGen Ovation® picoSL WTA system (NuGen, 3310) followed by the NuGen Encore® Biotin module biotin labelling process (NuGen, 4200). The cDNA samples were hybridised to Affymetrix Mouse Gene 1.1 arrays on an Affymetrix GeneTitan® Multi-Channel instrument (Affymetrix, High Wycombe, UK) incorporating the hybridisation, washing, staining and scanning stages. Annotation and quality control was performed with the Affymetrix Expression Console. Normalisation was undertaken using the robust multi-array average expression measure (Irizarry et al., 2003).  BioLayout Express3D was chosen for analysis of this dataset. The software has the ability to accommodate very large gene datasets which are viewed in a three dimensional neighbourhood with other genes based on a user defined threshold of co-expression. The capacity to handle very large datasets is integral to the software design in which the optimized graph layout and clustering algorithm are rendered within a hardware-accelerated OpenGL framework using the computer graphics processing unit and its inherent capability to handle very large numbers of calculations in a short period of time (Freeman et al., 2007).

middle: E

first: Lita

last: Murphy

first: Kathleen

last: Renault

first: Barry

last: Mccoll

first: Enrico

last: Cancellotti

first: Tom

middle: C

last: Freeman

first: Jean

last: Manson


title: Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid

first: Guido

last: Hooiveld

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Early life stress perturbs the maturation of microglial in the developing hippocampus [P28]

first: Arie

last: Kaffman

summary: In this study we hypothesize that early life stress perturbs the normal function of microglial in the developing hippocampus and that this effect is responsible for the ability of early life tress to disrupt normal synaptic maturation, myelination, and axonal growth in the developing hippocampus. To test this hypothesis we used the mouse immune panel from NanoString in order to identify immune-related genes whose expression is modified by BDS, a mouse model of early life stress, in microglia isolated from the hippocampus of 28-day old male pups. This project is part of a manuscript that is currently under preparation (Delpech J.C. et al. Early life stress perturbs the maturation of microglia in the developing hippocampus, Brain, Behavior and Immunity, 2016)

overall_design: microglial cells were isolated from the hippocampus of 28-day old control and BDS male pups (n=6 from each group, all from different litters) using Percoll gradient followed by FACS analysis. RNA was harvested using the he mirVana mirRNA isolation kit (Cat # AM 1560, Life technologies) and was then concentrated and Dnase treated on column using the RNA clean and contractor-5 kit (Cat# R1015, Zymo Research). Two ng of RNA were converted to cDNA using Superscript Vilo (Cat# 11754, Life Technologies), amplified with 5 rounds of PCR according to the nCounter single cell gene expression protocol and hybridized to the mouse immune panel (Cat# 150761, NanoString Technologies), and processed according to manufacturer instructions. Counts were normalized to positive controls and 5 housekeeping genes (e.g. Alas1, Gapdh, Oaz1, Polr1b, Sdha, Tbp) that were not affected by either BDS or age and showed a coefficient of variation of less than 20%. Genes were considered “present” if at least 40% of the samples showed hybridization signal that was 2 s.d. above the mean value for the negative control probes

first: Jean-Christophe

last: Delpech

first: Lan

last: Wei

first: Jin

last: Hao

first: Xiaoqing

last: Yu

first: Charlotte

last: Madore

first: Oleg

last: Butovsky


title: Arabidopsis thaliana: safranal-treated seedlings versus control seedlings

city: Fuchu

first: Naoya

last: Wasano

state: Tokyo

address: Saiwai-cho 3-5-8

institute: Tokyo University of Agriculture & Technology

summary: Transcriptional profiling of Arabidopsis thaliana seedlings treated with safranal, highlighting to the physiological function of plant volatile chemicals by observing early response of gene expressions in Arabidopsis seedlings.

overall_design: Two-condition experiment, safranal-treated seedlings vs. control seedlings. Biological replicates:2 control replicates, 2 safranal-treated.


title: Genome-wide analysis of sperm DNA methylation from monozygotic twin bulls

status: Public on Dec 31 2015

first: Habib

last: Shojaei Saadi

summary: Epigenetics (DNA methylation) profiling of sperm from Monozygotic (MZ) twin bull brothers comparing with each other

overall_design: Two-condition experiment, DNA methylation analysis of sperm from Monozygotic twin bull brothers which were hybridized  as dye-swap in two-color arrays in a dye-balanced design.

first: H

first: E

last: Fournier

first: C

last: Vigneault

first: P

last: Blondin

first: J

last: Bailey

last: Robert


title: Identification of circulating miRNA involved in meat yield of Korean cattle

city: Daejeon

first: Jinjong

last: Bong

address: Daehak-ro

country: South Korea

institute: NEXBIO

summary: Cattle plays an important role in providing essential nutrients through meat production. Thus, we focused on epigenetic factors associated with meat yield. To investigating circulating miRNAs that are involved with meat yield and connect biofluids and longissimus dorsi (LD) muscle in Korean cattle, we performed analyses of the carcass characteristics, miRNA array, qPCR, and bioinformatics. Carcass characteristics relative to the yield grade (YG) showed that the yield index and rib eye area were the highest, whereas the backfat thickness was the lowest for YG A (equal to high yield grade) cattle among the three YGs. miRNA array sorted the circulating miRNAs that connect biofluids and LD muscle. miRNA qPCR showed that miR-15a (r = 0.84), miR-26b (r = 0.91), and miR-29c (r = 0.92) had positive relationships with biofluids and LD muscle. In YG A cattle, miR-26b was considered to be a circulating miRNA connecting biofluids and LD muscle because the target genes of miR-26b was more involved with myogenesis. Then, miR-26b targeted genes, DIAPH3 and YOD1 were downregulated in YG A cattle. Our results suggest that miR-15a, miR-26b, and miR-29c are upregulated in biofluids and LD muscle whereas, downregulation of DIAPH3 and YOD1 in the LD muscle of finishing cattle steers.

overall_design: 29 or 30 month Korean cattle steers were classified by yield grade(YG) A, B, and C. miRNA expression patterns for exosome and LD muscle were compared among YGs.


title: Expression data from heart muscle of cardiac-specific caspase-3 and -7 knockout and wild type newborn and young mice

city: Lleida

first: Daniel

last: Sanchis

address: Av. Rovira Roure, 80

department: Basic Medical Sciences

country: Spain

institute: IRBLLEIDA - University of LLeida

summary:
Caspases, proteolytic enzymes involved in cell death could play a role independent of cell death in the developing heart
in this datasheet we include the expression data obtained from dissected heart muscle (ventricle) of wild type mice and mice knockout for caspase-3,-7

overall_design: 24 samples. genotypes: wild type and cardiac-specific conditional caspase-3 and -7 KO. Age: 1-2-day-old; 30-day-old (aprox 3 male, 3 female/genotype and age).

first: Ferran

last: Briansó

first: Ricardo

last: Gonzalo

first: Alex

last: Sánchez


title: Dual function of Jnk1 and Jnk2 in hepatocytes is essential to protect against toxic liver injury

status: Public on Jan 04 2016

first: Guido

last: Hooiveld

summary:
BACKGROUND & AIMS:
c-Jun N-terminal kinase (JNK)1 and JNK2 are expressed in hepatocytes and have overlapping and distinct functions. JNK proteins are activated, via phosphorylation, in response to acetaminophen- or CCl4-induced liver damage; the level of activation correlates with the degree of injury. SP600125, a JNK inhibitor, has been reported to block acetaminophen-induced liver injury. We investigated the role of JNK in drug-induced liver injury (DILI) in liver tissues from patients and in mice with genetic deletion of JNK in hepatocytes.

METHODS:
We studied liver sections from patients with DILI (due to acetaminophen, phenprocoumon, non-steroidal anti-inflammatory drugs or autoimmune hepatitis), or patients without acute liver failure (controls), collected from a DILI Biobank in Germany. Levels of total and activated (phosphorylated) JNK were measured by immunohistochemistry and western blotting. Mice with hepatocyte-specific deletion of Jnk1 (Jnk1Δhepa) or combination of Jnk1 and Jnk2 (JnkΔhepa), as well as Jnk1-floxed C57BL/6 (control) mice, were given injections of CCl4 (to induce fibrosis) or acetaminophen (to induce toxic liver injury). We performed gene expression microarray, and phosphoproteomic analyses to determine mechanisms of JNK activity in hepatocytes.

RESULTS:
Liver samples from DILI patients contained more activated JNK, predominantly in nuclei of hepatocytes and in immune cells, than healthy tissue. Administration of acetaminophen to JnkΔhepa mice produced a greater level of liver injury than that observed in Jnk1Δhepa or control mice, based on levels of serum markers and microscopic and histologic analysis of liver tissues. Administration of CCl4 also induced stronger hepatic injury in JnkΔhepa mice, based on increased inflammation, cell proliferation, and fibrosis progression, compared to Jnk1Δhepa or control mice. Hepatocytes from JnkΔhepa mice given acetaminophen had an increased oxidative stress response, leading to decreased activation of AMPK, total protein AMPK levels, and pJunD and subsequent necrosis. Administration of SP600125 before or with acetaminophen protected JnkΔhepa and control mice from liver injury.

CONCLUSIONS:
In hepatocytes, JNK1 and JNK2 appear to have combined effects in protecting mice from CCl4- and acetaminophen-induced liver injury. It is important to study the tissue-specific functions of both proteins, rather than just JNK1, in the onset of toxic liver injury. JNK inhibition with SP600125 shows off-target effects.

overall_design: Livers and primary hepatocytes were isolated from wild type and JNKΔhepa (Jnk1Δhepa/global Jnk2-/-) double-knockout mice and subjected to gene expression profiling.

first: Gang

last: Zhao

first: Francisco

middle: J

last: Cubero

first: Yulia

last: Nevzorova

first: Mark

middle: V

last: Boekschoten

last: Peng

first: Maximilian

last: Hatting

first: Michael

last: Müller

first: Tania

last: Roskams

first: Christian

last: Trautwein


title: Gene expression architecture of mouse dorsal and tail skin reveals functional differences in inflammation and cancer

status: Public on May 18 2016

first: David

last: Quigley

summary: Gene expression levels in normal tissues can differ substantially between individuals, due to inherited polymorphisms acting in cis or trans. Analysis of this variation across a population of genetically distinct individuals allows us to visualize a network of co-expressed genes under normal homeostatic conditions, and the consequences of perturbation by tissue damage or disease development. Here, we explore gene expression networks in normal adult skin from 470 genetically unique mice, and demonstrate the dependence of the architecture of signaling pathways on skin tissue location (dorsal or tail skin) and perturbation by induction of inflammation or tumorigenesis. Gene networks related to specific cell types, as well as signaling pathways including Sonic Hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is extensively rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression.  We present a software package for eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.

overall_design: Refer to individual Series


title: ZEB1 expression prevents DNA replication stress in cancer stem cells and delays chromosomal instability [Agilent]

city: Lyon

first: Anne

last: Wierinckx

state: select a state

address: 8, av Rockefeller

country: France

institute: University Lyon1

summary: Aberrant cell proliferation, a hallmark of most cancers, requires the escape from intrinsic antitumour barriers. Primary among these is the DNA damage response (DDR). In both cell culture-models and in early stages of tumorigenesis in vivo, activated oncogenes induce DNA replication stress and DNA double-strand breaks (DSBs), leading to DDR activation and p53-dependent apoptosis and/or senescence. The means by which tumour initiating cells, also termed cancer stem cells (CSCs), circumvent this oncosuppressive response is unknown. Here we demonstrate that the ZEB1 transcription factor provides breast CSCs with the ability to withstand an aberrant mitogenic activity. Its forced expression in human mammary epithelial cells is sufficient to alleviate DNA replicative stress and to decrease the production of reactive oxygen species, an important contributor to DDR and oncogene-induced senescence. Consistently, human breast cancer cells with endogenous ZEB1 expression show two characteristic features: low levels of DSBs and DDR markers, reflecting mitigation of the DNA replication stress, and a low p53 mutation frequency, reflecting a weak selective pressure for inactivation. Using high-throughput sequencing analysis of controlled cellular models, we further demonstrate that ZEB1 delays the onset of structural chromosomal instability (CIN), a known consequence of replicative stress and prevents the emergence of chromosome 8p deletions and 8q amplifications, two prevalent abnormalities in high grade breast cancers. Supporting these findings, ZEB1 expression discriminates human breast tumours by their copy number alterations (CNAs) and chromosome 8 aberrations. We propose that the tumorigenic potential of CSCs relies upon their unique capacity to tolerate oncogenic stimuli through the alleviation of DNA replication stress.

overall_design: Immortalized human mammary epithelial cells were infected with retrovirus expressing H-RASV12 with or without a retrovirus expressing ZEB1.

first: Anne-Pierre

last: Morel

first: Alain

last: Puisieux

first: Valérie

last: Combaret

first: Christelle

last: Lamblot

first: Christiane

last: Pinatel

first: Isabelle

last: Iacono

first: Stéphanie

last: Bréjon


title: Expression data from adult mouse Prefrontal Cortex following prenatal infection

first: Juliet

last: Richetto

summary:
Prenatal exposure to infectious or inflammatory insults can increase the risk of neuropsychiatric disorders with neurodevelopmental components, including schizophrenia and autism. The molecular processes underlying this pathological association are only partially understood. Here, we implemented an unbiased genome-wide transcriptional profiling of the prefrontal cortex of mice exposed to prenatal infection on GD17 compared to control subjects in order to elucidate the long term molecular signature of late prenatal infection.
We used microarray analysis to investigate the long lasting gene expression changes in a well-established mouse model that is based on maternal treatment with the viral mimic poly(I:C) during pregnancy

overall_design: C57BL/6 mice were treated with the synthetic viral mimetic poly(I:C) (5 mg/kg, i.v.) or control (saline, i.v.) solution on  gestation day 17. Offspring were subjected to cognitive and behavioral testing in adulthood, and then whole genome gene expression analysis with Affymetrix Microarray and subsequent q-PCR validation were performed on the prefrontal Cortex.

first: Urs

last: Meyer

first: Marco

last: Riva

first: Annamaria

last: Cattaneo


title: A weekly alternating diet between caloric restriction and medium fat protects the liver from NAFLD in middle aged C57BL/6J mice

status: Public on Oct 26 2015

first: Guido

last: Hooiveld

summary:
SCOPE: We investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet.

METHODS AND RESULTS: Nine-week-old male C57BL/6J mice received either a (i) control (C), (ii) 30E% calorie restricted (CR), (iii) MF (25E% fat), or (iv) intermittent (INT) diet, a diet alternating weekly between 40E% CR and an ad libitum MF diet until sacrifice at the age of 12 months. The metabolic, morphological, and molecular features of NAFLD were examined. The INT diet resulted in healthy metabolic and morphological features as displayed by the continuous CR diet: glucose tolerant, low hepatic triglyceride content, low plasma alanine aminotransferase. In contrast, the C- and MF-exposed mice with high body weight developed signs of NAFLD. However, the gene expression profiles of INT-exposed mice differed to those of CR-exposed mice and showed to be more similar with those of C- and MF-exposed mice with a comparable body weight.

CONCLUSIONS: Our study reveals that the INT diet maintains metabolic health and reverses the adverse effects of the MF diet, thus effectively prevents the development of NAFLD in 12-month-old male C57BL/6J mice.

overall_design: Male C57Bl/6J mice were divided to 4 dietary intervention groups: Control (AIN-93W), 30% calorie restriction (CR; AIN-93W-CR), medium fat (MF; AIN-93W-MF; 25% energy from fat) and intermittent diet (INT; weekly alternating diet between AIN-93W-MF ad lib and 40% CR of AIN-93W). We performed various measurements on metabolic parameters and gene expression analysis on the liver. This entry represents the microarray data of the liver gene expression of each mouse.

first: Fenni

last: Rusli

first: Mark

last: Boekschoten

first: Arantza

last: Zubia

first: Carolien

last: Lute

first: Wilma

last: Steegenga


title: Differentially expressed genes between WT and AtC3H17-overexpressing transgenic plants

status: Public on Dec 05 2015

city: Busan

first: Yong-Hwan

last: Moon

address: Busandaehak-ro 63Beon-gil 2, Geumjeong-gu

department: Molecular Biology

institute: Pusan National University

summary: We characterized the biological and molecular functions of AtC3H17, a unique Arabidopsis gene encoding a non-tandem CCCH zinc finger protein, in plant development. To investigate the downstream regulatory mechanisms of AtC3H17, whole genome microarray expression profiling was carried out. The experiment was designed to identify differentially expressed genes between WT and AtC3H17-overexpressing transgenic plants (AtC3H17 OXs) grown for 14 days under SD growth conditions. Interestingly, the most up-regulated genes were 12S seed storage globulin genes, CRUCIFERIN A (CRA1) and CRUCIFERIN 3 (CRU3), and seed oil-body protein genes such as OLEOSIN 1 (OLEO1) and OLEO2 in AtC3H17 OXs compared with WT. We performed quantitative RT-PCR and confirmed that transcription levels of CRU3, OLEO1, OLEO2, and 2S seed storage albumin 1 (At2S1) were higher in AtC3H17 OX seedlings than in WT seedlings.

overall_design: Differentially expressed genes between WT and AtC3H17 OX at 14 days after germination under SD conditions (8-h-light and 16-h-dark cycle) were explored in whole genome level. Two AtC3H17 OX samples were compared to WT sample as a control.

first: Dong-Hyuk

last: Woo

first: Hye-Yeon

last: Seok

first: Hee-Yeon

last: Park

first: Sun-Young

last: Lee

first: Huong

middle: T

last: Tran

first: Eun-Hye

first: Linh

last: Nguyen


title: CD8+ T cells during acute viral respiratory infection are uniquely differentiated and regulated by multiple inhibitory receptors

status: Public on Oct 01 2015

city: Nashville

first: Pengcheng

last: Lu

state: TN

address: 2200 Pierce Avenue

institute: Vanderbilt University

summary: Acute viral infection typically generates functional effector CD8+ T cells that aid in pathogen clearance. However, during acute viral lower respiratory infection (LRI), lung CD8+ T cells are functionally impaired and do not optimally control viral replication, while spleen CD8+ T cells specific for the same viral epitopes remain fully functional. To better understand the mechanisms governing lung CD8+ T cell impairment, we used flow cytometry to sort anti-viral CD8+ T cells during viral LRI.  Lung and spleen cells were stained with MHC-class I tetramers representing the immunodominant anti-viral CD8+ T cell epitope.  We then sorted to high purity: naïve CD8+ T cells, spleen epitope-specific CD8+ T cells, lung epitope-specific CD8+ cells and secondary infection lung epitope-specific CD8+ T cells.  We then performed a genome wide transcriptional analysis of these cells to characterize the gene expression profile of lung CD8+ T cell impairment.

overall_design: Epitope-specific lung and spleen CD8+ T cells were obtained using flow cytometric sorting of MHC-class I tetramer stained CD8+ T cells at day 7 after human metapneumovirus (HMPV) infection.  Tetramers were specific for the immunodominant M195 epitope (derived from the M protein of HMPV) in B6-Kb0Db0;B7.2 transgenic (B7tg) mice. Naïve CD44-CD62L+ CD8+ T cells were also obtained from the spleen.  In a separate group, mice were primed with M195 peptide-pulsed LPS-matured bone marrow-derived dendritic cells, challenged with HMPV two weeks later, and secondary M195-specific CD8+ T cells were obtained at day 7 post-challenge.

first: J

last: Erickson

first: P

last: Gilchuk

first: S

last: Joyce

first: Y

last: Shyr

last: Williams


title: Expression data from Ezh2 conditional C2 iMEFs

city: Paris Cedex 05

first: Nicolas

last: Servant

address: 26 rue d'ulm

institute: Institut Curie

summary:
Polycomb Repressive Complex 2 (PRC2) plays a key role in controlling transcriptional repression. It is thought to act at the level of the chromatin, where its enzymatic subunits Ezh1 and Ezh2 catalyse the di/tri-methylation of histone H3 on its lysine 27 (H3K27me3).
We sought to assess several parameters of PRC2-mediated transcriptional repression. To this end we performed a comparative analysis of mES and iMEF cells following deletion of Ezh2, a time-course analysis following deletion of Ezh2 in iMEFs as well as rescue experiments with Ezh1 and Ezh2 before or after deletion of Ezh2.

overall_design: In a first experiment, we performed a transcriptome analysis of mES and iMEF cells either Ezh2 WT or Ezh2-mutant. In a second experiment, we performed a time-course analysis of a clone of Ezh2-conditional iMEFs (clone C2), 0 (control), 5, 18 and 32 days after addition of Tamoxifen. In a third experiment, we analysed the transcriptome of C2 cells either i) wild-type for Ezh2, ii) in the presence of overexpressed exogenous Ezh1 or Ezh2, iii) Ezh2-mutant, and iv) with Ezh1/Ezh2 rescue either pre- or post-deletion of endogenous Ezh2.

first: Aurélie

last: Teissandier

first: Bruno

last: Zeitouni

first: Raphaël

last: Margueron


title: Sexually dimorphic characteristics of the small intestine and colon of prepubescent C57BL/6 mice

status: Public on Sep 02 2015

first: Guido

last: Hooiveld

summary: There is increasing appreciation for sexually dimorphic effects, but the molecular mechanisms underlying these effects are only partially understood. In the present study, we explored transcriptomics and epigenetic differences in the small intestine and colon of prepubescent male and female mice. In addition, the microbiota composition of the colonic luminal content has been examined. At postnatal day 14, male and female C57BL/6 mice were sacrificed and the small intestine, colon and content of luminal colon were isolated. Gene expression of both segments of the intestine was analysed by microarray analysis. DNA methylation of the promoter regions of selected sexually dimorphic genes was examined by pyrosequencing. Composition of the microbiota was explored by deep sequencing. Sexually dimorphic genes were observed in both segments of the intestine of 2-week-old mouse pups, with a stronger effect in the small intestine. Amongst the total of 349 genes displaying a sexually dimorphic effect in the small intestine and/or colon, several candidates exhibited a previously established function in the intestine (i.e. Nts, Nucb2, Alox5ap and Retnlγ). In addition, differential expression of genes linked to intestinal bowel disease (i.e. Ccr3, Ccl11 and Tnfr) and colorectal cancer development (i.e. Wt1 and Mmp25) was observed between males and females. Amongst the genes displaying significant sexually dimorphic expression, nine genes were histone-modifying enzymes, suggesting that epigenetic mechanisms might be a potential underlying regulatory mechanism. However, our results reveal no significant changes in DNA methylation of analysed CpGs within the selected differentially expressed genes. With respect to the bacterial community composition in the colon, a dominant effect of litter origin was found but no significant sex effect was detected. However, a sex effect on the dominance of specific taxa was observed. This study reveals molecular dissimilarities between males and females in the small intestine and colon of prepubescent mice, which might underlie differences in physiological functioning and in disease predisposition in the two sexes.

overall_design: Small intestine and colon were isolated from two-week old pups of dams fed a low-fat diet and subjected to gene expression profiling

first: Wilma

last: Steegenga

first: Mona

last: Mischke

first: Carolien

last: Lute

first: Michael

last: Muller

first: Torsten

last: Plosch


title: Multi-level omics analysis of gene expression in a murine model of dystrophin loss and therapeutic restoration [mRNA]

status: Public on Sep 24 2015

city: Oxford

first: Thomas

last: Roberts

address: South Parks Road

department: Department of Physiology, Anatomy and Genetics

institute: University of Oxford

summary: Duchenne muscular dystrophy (DMD) is a classical monogenic disorder, a model disease for genomic studies and a priority candidate for regenerative medicine and gene therapy. Although the genetic cause of DMD is well known, the molecular pathogenesis of disease and the response to therapy are incompletely understood. Here,we describe analyses of protein, mRNA and microRNA expression in the tibialis anterior of the mdx mouse model of DMD. Notably, 3272 proteins were quantifiable and 525 identified as differentially expressed in mdx muscle (P < 0.01). Therapeutic restoration of dystrophin by exon skipping induced widespread shifts in protein and mRNA expression towards wild-type expression levels, whereas the miRNome was largely unaffected. Comparison analyses between datasets showed that protein and mRNA ratios were only weakly correlated (r = 0.405), and identified a multitude of differentially affected cellular pathways, upstream regulators and predicted miRNA–target interactions. This study provides fundamental new insights into gene expression and regulation in dystrophic muscle.

overall_design: 3 Wt, 4 mdx and 4 Pip6e-PMO treated mdx mice

first: Henrik

last: Johansson

first: Graham

last: McClorey

first: Caroline

last: Godfrey

first: K

last: Blomberg

first: Thibault

last: Coursindel

last: Gait

first: C

last: Smith

first: Janne

last: Lehtiö

first: Samir

last: EL-Andaloussi

first: Matthew

last: Wood


title: SACL, a bHLH gene that restricts vascular cell proliferation in plants.

status: Public on Sep 01 2015

city: Valencia

first: Francisco

last: Vera-Sirera

address: Ingeniero Fausto Elio, s/n

institute: IBMCP (UPV-CSIC)

summary: The final size and arrangement of the plant vasculature requires precise adjustment of cell proliferation. In particular, radial growth of vascular bundles is to a large extent controlled by a bHLH transcription factor heterodimer formed by TARGET OF MONOPTEROS5 (TMO5) and LONESOME HIGHWAY (LHW). Excess activity of this TMO5/LHW dimer causes excessive proliferation of vascular cell divisions and thus suggests the existence of a molecular mechanism that restricts its activity in space and time. Here we show that this overproliferation phenotype is similar to acaulis5 (acl5) mutants, suggesting a role for ACL5 in controlling TMO5/LHW activity. We further identify the clade of SAC51-LIKE (SACL) bHLH transcription factors whose translation is regulated by ACL5, as inhibitors of TMO5/LHW activity. We show that SACL proteins interact with LHW impairing activation of downstream targets and alleviating the overproliferation caused by TMO5/LHW misexpression. Given that transcription of SACL genes is induced by TMO5/LHW and its upstream trigger auxin, we propose that SACL proteins represent a feedback mechanism that limits activity of this pathway and controls periclinal cell divisions.

overall_design: Three biological replicates were generated per sample. The goal of this experiment is to compare different genotypes that suppress the acl5 mutant as  Columbia-0, acl5 + pHS::SACL3 and acl5 ajax2-31, against the acl5 mutant. Every pair of samples that were compared in the same array, were also growth in the same plate. The acl5 + pHS::SACL3 seedlings (and the acl5 ones  against they are went compared) were treated to 37C degrees heat shock and then collected at the different times (30 and 210 min) after heat shock. In each comparison 1 or 2 or the replcates were reversed-labeled.

first: Bert

last: De Rybel

first: Cristina

last: Úrbez

first: Evangelos

last: Kouklas

first: Marta

last: Pesquera

first: Juan

last: Álvarez-Mahecha

first: Eugenio

middle: G

last: Minguet

first: Hannele

last: Tuominen

last: Carbonell

first: Jan

last: Borst

first: Dolf

last: Weijers

first: Miguel

last: Blázquez


title: Gene expression in luh mutant seeds in the dark: wild type (Col-0) vs. luh mutant

status: Public on Sep 27 2015

first: Nayoung

last: Lee

address: 291 Daehak-ro

department: Biological sciences

institute: KAIST

summary: Transcriptional profiling of Arabidopsis far-red light pulse treated seeds comparing luh mutant with wild type (Col-0). Seeds were imbibed within 1 hr under white light and treated far-red light pulse for 5 min followed by 12 hr dark incubation. Goal was to determine the effects of LUH as transcriptional co-regulator during seed germination process.

overall_design: Two-condition experiment, wild type vs. luh mutant. Biological replicates: 3 wild type replicates, 3 luh mutant replicates.

first: Giltsu

last: Choi


title: Clonal evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers

status: Public on Oct 11 2015

city: San Francisco

first: David

last: Quigley

address: 1450 Third St. Room 207

institute: UCSF

summary: Human tumours show a high level of clonal heterogeneity that contributes to malignant progression and metastasis, but the processes that influence the timing of metastatic dissemination of subclones are unknown.  Here, we have used whole exome sequencing of 98 matched benign, malignant, and metastatic skin tumours from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumour, but then evolve separately, acquiring an additional set of mutations during growth at distant sites. Shared mutations between primary carcinomas and their matched metastases have the distinct A>T signature of the initiating carcinogen Dimethylbanzanthracene (DMBA), but non-shared mutations are primarily G>T  or C>T substitutions, associated with oxidative stress. We found recurrent point mutations in several hundred genes, including several in the Ras (Hras, Kras, and Pik3ca) pathway. We propose that carcinogen-driven mouse tumour models can aid our understanding of the forces that shape clonal and genetic evolution of human cancers.

overall_design: Benign, primary, and metastatic DMBA/TPA-initiated tumours and matched dorsal skin from 15 FVBBX mice (Spretus x FVB F1s crossed to FVBs); 9 wild-type and 6 HrasKO mice

first: Melissa

last: McCreery

first: Allan

last: Balmain


title: Microbiota facilitates dietary heme-induced epithelial hyperproliferation and hyperplasia by breaking the mucus barrier

status: Public on Aug 03 2015

first: Guido

last: Hooiveld

summary: Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function.

overall_design: Mice were fed a Westernized high fat control diet, or the same diet supplemented with 0.5 µmol heme/g diet. One group of control and one group of heme mice received a mixture of broad spectrum Antibiotics (Abx) (ampicilin, neomycin and metronidazole) in their drinking water. After 14 days of intervention, mice were killed and gene expression was profiled in colon.

first: Noortje

last: IJssennagger

first: Clara

last: Belzer

last: Dekker

first: Michael

last: Müller

first: Michiel

last: Kleerebezem

first: Roelof

last: van der Meer


title: Exogenous isoprene modulates gene expression in unstressed Arabidopsis thaliana plants

city: East Lansing

first: Thomas

middle: D

last: Sharkey

state: MI

address: 603 Wilson Rd

department: Biochemistry and Molecular Biology

institute: Michigan State University

summary: Isoprene is a well-studied volatile hemiterpene that protects plants from abiotic stress through mechanisms that are not fully understood. The antioxidant and membrane stabilizing potential of isoprene are the two most commonly invoked mechanisms. However, isoprene also affects phenylpropanoid metabolism, suggesting an additional role as a signaling molecule. In this study, microarray based gene expression profiling reveals widespread transcriptional reprogramming of Arabidopsis thaliana plants fumigated for 24 hrs with a physiologically relevant concentration of isoprene. Functional enrichment analysis of fumigated plants revealed enhanced heat- and light-stress-responsive processes in response to isoprene. Isoprene induced a network enriched in ERF and WRKY transcription factors, which may play a role in stress tolerance. The isoprene-induced upregulation of phenylpropanoid biosynthetic genes was specifically confirmed using quantitative reverse transcription polymerase chain reaction. These results support a role for isoprene as a signaling molecule, in addition to its possible roles as an antioxidant and membrane thermoprotectant.

overall_design: Plants were held at 23 °C for 24 hours and then held at 40 °C for 24 hours, either in the presence or absence of 20 PPM isoprene during the entire 48 hours. Leaf samples were taken at the end of both 24 hour treatment periods. Each of the 4 resulting conditions was replicated 3 times.

first: Christopher

last: Harvey


title: Effect of Healthy Nordic diet on gene expression in peripheral blood mononuclear cells

status: Public on May 13 2015

city: Kuopio

first: Jussi

last: Paananen

address: Yliopistonranta 1

country: Finland

institute: University of Eastern Finland

summary: In a randomized controlled dietary intervention study we compared an isocaloric Healthy Nordic diet with the average Nordic diet for influence on peripheral blood mononuclear cells (PBMC) gene expression. We studied obese adults with features of the metabolic syndrom, n=66. There was no significant difference in age, BMI, or gene expression between the groups before the intervention. The intervention lasted for 18-24 weeks.

overall_design: Blood samples were obtained before (W0), during (W12) and after completion (W18-24) of the dietary intervention. From the samples we extracted RNA. From total RNA we prepared and hybridised biotinylated complementary RNA to GeneChip Human Gene 1.1 ST Arrays (Affymetrix Inc., Santa Clara, CA), and then washed, stained and scanned the slides using standardised protocols (Affymetrix Inc.).

first: Stine

last: Ulven


title: Deletion of Rictor in brain and fat alters peripheral clock gene expression and increases blood pressure

status: Public on Jul 05 2015

city: Schlieren

first: Elvira

last: Haas

address: Wagistrasse 12, 3rd floor

department: Division of Internal Medicine

institute: University Hospital of Zurich

summary: The mammalian target of rapamycin complex 2 (mTORC2) contains the essential protein RICTOR and is activated by growth factors. mTORC2 in adipose tissue contributes to regulating glucose and lipid metabolism. In the perivascular adipose tissue (PVAT) mTORC2 ensures normal vascular reactivity by controlling expression of inflammatory molecules. To assess whether RICTOR/mTORC2 contributes to blood pressure regulation, we applied a radiotelemetry approach in control and Rictor knockout (RictoraP2KO) mice generated by using adipocyte protein-2 gene promoter-driven CRE recombinase to delete Rictor. 24 hour mean arterial pressure (MAP) was increased in RictoraP2KO mice, and the physiologic decline in MAP during the dark period impaired. In parallel, heart rate and locomotor activity were elevated during the dark period with a pattern similar to blood pressure changes. This phenotype was associated with mild cardiomyocyte hypertrophy, decreased cardiac natriuretic peptides (NPs) and NP receptor expression in adipocytes. Moreover, clock gene expression was dampened or phase-shifted in PVAT. No differences in clock gene expression were observed in the master clock suprachiasmatic nucleus (SCN), though Rictor gene expression was also lower in brain of RictoraP2KO mice. Thus, the present study underscores the importance of RICTOR/mTORC2 for interactions between vasculature, adipocytes and brain to tune physiological outcomes such as blood pressure and locomotion.

overall_design: Gene expression in PVAT of RictoraP2KO mice was compared to controls (Rictorfl/fl) mice.

first: Katja

last: Drägert

first: Indranil

last: Bhattacharya

first: Giovanni

last: Pellegrini

first: Petra

last: Seebeck

first: Abdelhalim

last: Azzi

first: Steven

last: Brown

first: Stavroula

last: Georgiopoulou

first: Ulrike

last: Held

first: Margarete

last: Arras

first: Rok

last: Humar

middle: N

last: Hall

first: Edouard

last: Battegay


title: Comparison of the effects of five dietary fibers on mucosal transcriptional profiles, and luminal microbiota composition and SCFA concentrations in murine colon

status: Public on May 26 2015

city: Wageningen

first: Guido

last: Hooiveld

address: HELIX, Stippeneng 4

institute: Wageningen University

summary:
Consumption of diets rich in fibers has been associated with several beneficial effects on gastrointestinal health. However, detailed studies on the molecular effects of fibers in colon are limited. In this study we investigated and compared the influence of five different fibers on the mucosal transcriptome, and luminal microbiota and SCFA concentrations in murine colon. Mice were fed diets enriched with fibers that differed in carbohydrate composition, namely inulin (IN), oligofructose (FOS), arabinoxylan (AX), guar gum (GG), resistant starch (RS) or a control diet (corn starch) for 10 days. Gene expression profiling revealed the regulation of specific, but also overlapping sets of epithelial genes by each fiber, which on a functional level were mainly linked to cell cycle  and various metabolic pathways including fatty acid oxidation, tricarboxylic acid cycle, and electron transport chain. In addition, the transcription factor PPAR was predicted to be a prominent upstream regulator of these processes. Microbiota profiles were distinct per dietary fiber, but the fibers IN, FOS, AX and GG induced a common change in microbial groups. All dietary fibers, except resistant starch, increased SCFA concentrations but to a different extent. Multivariate data integration revealed strong correlations between the expression of genes involved in energy metabolism and the relative abundance of bacteria belonging to the group of Clostridium cluster XIVa, that are known butyrate producers. These findings illustrate the potential of multivariate data analysis to unravel simple relationships in complex systems.

Keywords: Expression profiling by array

overall_design: Mice received a control diet, or a diet supplemented with 10% dietary fibers for 10 days. After an overnight fast colon was removed, epithelial cells were scraped off, and subjected to gene expression profiling.

last: Lange

first: Michael

last: Müller


title: Serial gene expression analysis in locally advanced breast cancer patients who failed to respond to neoadjuvant chemotherapy

status: Public on Jun 12 2015

first: Mark

last: Magbanua

address: 1450 3rd Street, PO Box 589001

department: HemOnc

institute: UCSF/Helen Diller Familiy Comprehensive Cancer Center

summary: To elucidate candidate genes and pathways associated with poor response, we retrospectively analyzed gene expression profiles in serial biopsies from women with locally advanced breast cancer who failed to respond to anthracycline-based chemo followed by taxane in the I-SPY

overall_design: Of the 221 patients who completed neoadjuvant chemotherapy, 215 patients had surgery with 73% not achieving a pathologic complete response (pathCR). In these patients, cDNA microarray expression profiles from pretreatment biopsy (T1) were compared to those biopsy specimens obtained 24-72 hours after initiation of treatment (T2) or in tumors surgically removed after chemotherapy (TS). Paired expression data for T1vsT2 and T1vsTS were available for 29 and 39 patients with no pathCR, respectively. Paired differential expression analyses were performed via Significance Analysis of Microarrays (SAM) and differentially expressed genes were subjected to Ingenuity Pathway Analysis

first: John

last: Park

first: Sarah

last: Davis

first: Christopher

last: Haqq

first: Julia

last: Crothers

first: Laura

last: van’t Veer

first: Eduardo

last: Sosa

last: Esserman


title: Patterns of gene expression during Arabidopsis flower development from the time of initiation to maturation

status: Public on Jul 02 2015

city: Dublin

first: Pat

last: Ryan

address: College Green

country: Ireland

institute: TCD

summary: Microarray timecourse experiments conducted across flower development from initiation of floral development to anthesis of the mature flower

overall_design: 3 replicates for each of 14 timepoints collected from Arabidopsis flowers using a previously described Floral Induction System, conducted using a common reference design on two channel microarrays

first: Diarmuid

last: Ó’Maoiléidigh

first: Kamilla

last: Kwasnieska

first: Patrick

first: Hajk-George

last: Drost

first: Marcel

last: Quint

first: Frank

last: Wellmer


title: The ER-Associated Degradation Adapter Protein Sel1L Regulates Triglyceride Metabolism via Lipoprotein Lipase

status: Public on May 18 2015

last: Hooiveld

summary: Sel1L is an adaptor protein for the E3 ligase Hrd1 in the endoplasmic reticulum-associated degradation (ERAD), but its physiological role in a cell-type-specific manner remains unclear. Here we show that mice with adipocyte-specific Sel1L deficiency are resistant to diet-induced obesity and exhibit postprandial hypertriglyceridemia. Mechanistically, our data demonstrate a critical requirement of Sel1L for the secretion of lipoprotein lipase (LPL), independently of its role in Hrd1-mediated ERAD and ER homeostasis. Further biochemical analyses revealed that Sel1L physically interacts and stabilizes the LPL maturation complex consisted of LPL and lipase-maturation factor 1 (LMF1). In the absence of Sel1L, LPL is retained in the ER and prone to the formation of protein aggregates, which are degraded by autophagy-mediated degradation. The Sel1L-mediated control of LPL secretion is seen in other LPL-expressing cell types as well such as cardiac muscle and macrophages. Thus, our study reports a novel role of Sel1L in LPL secretion and systemic lipid metabolism.

overall_design: Sel1Lflox/flox mice were crossed with adiponectin promoter driven Cre mice to create adipose tissue-specific Sel1L-/- mice.  Male wildtype C57Bl/6 mice and adipose tissue-specific Sel1l-/- mice were fed a high fat diet (Research Diets D12492) for 5 weeks. Adipose tissue was excised and used for microarray analysis.

first: Haibo

last: Sha

first: Adams

last: Francisco

first: Shengyi

last: Sun

first: Nicole

last: Ehrhardt

first: Zhen

last: Xue

first: Lei

last: Liu

first: Peter

last: Lawrence

first: Frits

last: Mattijssen

first: Robert

last: Gruber

first: Muhammad

middle: S

last: Panhwar

first: J

last: Brenna

first: Hang

last: Shi

first: Bingzhong

first: Sander

last: Kersten

first: André

last: Bensadoun

first: Miklòs

last: Péterfy

first: Qiaoming

last: Long

first: Ling

last: Qi


title: Changes in polysome association of mRNA throughout growth and development in Arabidopsis thaliana (Total RNA)

city: Ikoma

first: Shotaro

last: Yamasaki

state: NARA

address: 8916-5 Takayama

department: Graduate school of bilogical science

institute: Nara institute of science and technology

summary: Translational control is a key regulatory step in the expression of genes as proteins. In plant cells, translational efficiency of mRNAs differs on different mRNA species, and the efficiency dynamically changes in various conditions. To gain a global view of translational control throughout growth and development, we performed genome-wide analysis of polysome association of mRNA over growth and leaf development in Arabidopsis thaliana by applying the mRNAs in polysome to DNA microarray. This analysis revealed that the degree of polysome association of mRNA had different levels depending on mRNA species, and the polysome association changed greatly throughout growth and development for each. In the growth stage, transcripts showed varying changes in polysome association from strongly depressed to unchanged degree, with the majority of transcripts showing dissociation from ribosomes. On the other hand, during leaf development, the polysome association of transcripts showed a normal distribution from repressed to activated mRNAs when comparing between expanding and expanded leaves. In addition, functional category analysis of the microarray data suggested that translational control has a physiological significance in plant growth and development process, especially in category of signaling and protein synthesis. Besides this, we compared changes in polysome association of mRNAs between various conditions and characterized translational controls in each. This result suggested that mRNAs translation might be controlled by complicated mechanisms for response to each condition. Our results highlight the importance of dynamic changes in mRNA translation in plant development and growth.

overall_design: Experiment using 4 developmental stages. Biological replicates: 2. Compared 2DAG and 21DAG, or Young leaves and Mature leaves.

first: Ko

last: Kato


title: Gene expression data from Lhx5 mutant mouse embryos

status: Public on Aug 14 2015

city: Heidelberg

first: Gonzalo

last: Alvarez-Bolado

address: Im Neuenheimer Feld 307

country: Germany

institute: Institute for Anatomy and Cell Biology

summary:
Lhx5 mutant mouse embryos show loss of a neuronal nucleus of the brain called the mamillary body and essential for the formation of memories. We wanted to identify the genes that are responsible for the normal development of the mammillary body.
Therefore, we used microarray experiments to identify the genes that show a changed expression in the Lhx5 mutant mammillary neuroepithelium in comparison to the wild type.

overall_design: The mammillary neuroepithelium of Lhx5 mutant und wild type embryos (Mus musculus (C57BL/6)) was dissected at a stage, where the size of the mammillary body was not yet detectable changed (E10.5) to exclude effects of the size reduction of the mammillary body in Lhx5 mutant embryos. RNA extraction and hybridization on Affymetrix  microarrays was performed to detect changes in the transcriptome that are responsible for the mutant phenotype.

first: Michael

last: Heide


title: Genes regulated in EML1 cells expressing the TEL-AML1 oncogene after 5 and 7 days of treatment with IL7 and FLT3 ligand.

city: Milan

first: Myriam

last: Alcalay

address: Via Adamello 16

department: Experimental Oncology

country: Italy

institute: European Institute of Oncology

summary:
The t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene, which functions as a transcription factor.
TEL-AML1 expression in EML1 cells results in an impairment of differentiation along the B-lymphoid lineage.

overall_design: We analyzed gene expression profiles of EML1 cells after expression of TEL-AML1


title: IL-37 protects against obesity-induced inflammation and insulin resistance

first: Guido

last: Hooiveld

summary: Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here, we report that IL-37, a newly-described antiinflammatory member of the IL-1 family, affects obesity-induced inflammation and insulin resistance. IL-37 transgenic mice (IL-37tg) did not develop an obese phenotype in response to a high-fat diet (HFD). Unlike WT mice, IL-37tg mice exhibited reduced numbers of adipose tissue macrophages and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. A short-term HFD intervention revealed that the IL-37-mediated improvement in glucose tolerance is independent of bodyweight. IL-37tg mice manifested a beneficial metabolic profile with higher circulating levels of the anti-inflammatory adipokine adiponectin. In vitro treatment of differentiating adipocytes with recombinant IL-37 reduced adipogenesis. The beneficial effects of recombinant IL-37 involved activation of AMPK signaling. In humans, steady-state IL-37 adipose tissue mRNA levels were positively correlated with insulin sensitivity, lower adipose tissue levels of leptin and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.

overall_design: Gene arrays were performed on epidydimal white adipose tissue samples from wild type and human IL37-overexpressing transgenic mice fed a high fat diet for 16 weeks.

first: Dov

middle: B

last: Ballak

first: Janna

last: van Diepen

first: Mark

last: Boekschoten

last: Müller

first: Rinke

last: Stienstra


title: Role of TBC1D4 in mouse kidneys: Identification of compensatory mechanisms in the DCT of TBC1D4-deficient mice

status: Public on Apr 10 2015

city: Zurich

first: Marianna

last: Di Chiara

state: Zurich

address: Winterthurerstrasse 190

department: Institute of Anatomy

institute: University of Zurich

summary:
In vitro studies identified TBC1D4 as an regulator of renal ion and water transporting proteins. However, TBC1D4-deficient mice did not show a defective renal salt and water homeostasis.
With microarray analysis we aimed to decipher compensatory mechanisms in TBC1D4-deficient mice which might mask the renal phenotype already on transciptomic levels.

overall_design: We used and compared mRNA of COPAS-sorted and -enriched distal convoluted tubule (DCT)-cells, known to express TBC1D4 at high levels, of 8-week old male homogenous C57/Bl6 mice of TBC1D4-deficient and wild-type mice.

first: Johannes

last: Loffing


title: Changes in polysome association of mRNA throughout growth and development in Arabidopsis thaliana

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

overall_design: Refer to individual Series


title: Phenotypical and functional characterization of human skin dermal dendritic cells and Langerhans cells.

status: Public on Aug 15 2015

city: La Jolla

first: Steven

last: Head

address: 10550 N Torrey Pines Rd

institute: The Scripps Research Institute

summary:
Cutaneous antigen presenting cells (APCs) are critical for the induction and regulation of skin immune responses. The human skin contains phenotypically and functionally distinct APCs subsets that are present at two separated locations. While CD1ahigh LCs  form a dense network in the epidermis, the CD14+ and CD1a+ APCs reside in the dermal compartment. A better understanding of the biology of human skin APC subsets is necessary for the improvement of vaccine strategies that use the skin as administration route. In particular, progress in the characterization of uptake and activatory receptors will certainly improve APC-targeting strategies in vaccination. Here we performed a detailed analysis of the expression and function of glycan-binding and pattern-recognition receptors in skin APC subsets.
Detailed analysis of the differentially expressed genes amongst both populations confirmed the exclusive expression of langerin in LCs and DC-SIGN in dermal APCs. Although several genes, such as galectin-1, -3 and -9, MGL and dectin-1 were highly abundant on both APC subpopulations, a number of glycan-binding receptors defined a cell-specific expression signature . Thus, next to langerin, Siglec-5 and L-SIGN were specific to LCs, whereas dermal APCs expressed higher levels of CLEC4A (also known as DCIR), Macrophage mannose receptor, AGR2, CLEC1A, COLEC12, MDL1, Galectin 2 and Siglec 7. Most of these glycan-binding proteins have been involved in antigen uptake, illustrating that dDC have a more specialized function in recognizing a broad repertoire of antigens for internalization than LCs. Based on these data, we can conclude that the APC subsets found in the epidermis and dermis of human skin share a significant amount of glycan-binding receptor genes, but have also unique CLRs on LC and dermal APCs illustrating that these cells may differ in their antigen recognition and uptake function.

overall_design: Human dermal APCs and LCs were purified using  MACS beads after 3 days of in vitro cell migration using CD19 and HLA-DR beads for the dermal APC sample and CD1a for the LC samples. CD19+ B cells were depleted from the dDC samples prior to RNA isolation. RNA was extracted using the Qiagen RNeasy Mini kit and used to probe the GLYCOv4 oligonucleotide array.

first: Cynthia

last: Fehres

first: Sven

last: Bruijns

first: Juan

last: Garcia-Vallejo

first: Y

last: van Kooyk


title: Identification of novel susceptibility factors in Arabidopsis towards necreotrophic fungal pathogens.

status: Public on Jan 20 2015

city: Cantoblanco

middle: Carlos

last: Oliveros

state: Madrid

address: Darwin 3

institute: CNB, CSIC

summary: Transcriptional profiles were carried out for four transcription factors and two receptor-like kinases mutants, corresponding to genes that are co-expressed in silico with the CESA7 gene in Arabidopsis. These mutants show enhanced disease susceptibility to the necrotrophic fungal pathogen Plecthosphaerella cucmerina. Several gene families of small secreted peptides, some of them with known hormone or signalling implications, were commonly up-regulated in all of the 6 genotypes, unveiling a functional implication of these secreted peptides in the defence pathway against fungi.

overall_design: Transcriptomics of 6 mutant plants, including four transcription factors and two receptor-like kinases,  were compared to their background Col-0 accession. For this porpoise, plants were grown as described and leaves from three plants of each genotype were mixed and extracted as one single replicate.  Three replicates from three different sets of plants were analysed for each genotype.

first: Albor

last: Dobón

first: Pablo

last: Vera


title: Changes in polysome association of mRNA throughout growth and development in Arabidopsis thaliana (Polysome association)

first: Shotaro

last: Yamasaki

overall_design: Experiment using two-flactionated mRNA in 4 developmental stages, Polysomal mRNA vs. total mRNA.  Biological replicates: 2. Compared 2DAG and 21DAG, or Young leaves and Mature leaves.

first: Ko

last: Kato


title: Normal mouse skin lacking Hras

status: Public on Mar 01 2015

first: David

last: Quigley

department: Helen Diller Comprehensive Cancer Center

summary: Oncogenic activating mutations in Ras genes are among the most common drivers of human disease. Treating mouse skin with the chemical carcinogen DMBA induces a characteristic mutation in Hras at codon 61. To understand how skin responds to a constitutive lack of Hras, we generated a cohort of Hras knockout mice.

overall_design: A backcross was generated using male Mus spretus and female FVB/N Hras-/- mice; female F1 hybrids were mated with male FVB/N Hras -/- or Hras -/+ mice to generate a backcross population. This series contains mice that were Hras -/-. Mice were aged to 8 weeks and a tail skin sample was snap frozen.

middle: A

first: Allan

last: Balmain


title: Nitrogen starvation and cultivar-specific leaf senescence in winter oilseed rape (Brassica napus)

status: Public on Jan 15 2015

city: Berlin

first: Reinhard

last: Kunze

state: Berlin

address: Albrecht-Thaer-Weg 6

department: Institute of Biology

institute: Freie Universität Berlin

summary: To identify marker genes that are specific for N starvation-induced leaf senescence and suitable to detect cultivar differences at early senescence stages prior to chlorophyll loss, the transcriptomes of leaves of two B. napus cultivars differing in stay-green characteristics and N efficiency were analysed four days after senescence induction by the senescence inducers N starvation, leaf shading and leaf detaching.

overall_design: Brassica napus cultivars Apex (11; N-efficient) and Capitol (12 N-inefficient) were pre-cultured in hydroponics for 28 days at optimal N supply before induction of leaf senescence by (i) N starvation, (ii) leaf shading and (iii) leaf detachment. After four days of treatment the transcriptome of leaf number 3 was determined in three separate plants (biological replicates r1 - r3).

first: Vajiheh

last: Safavi Rizi

first: Fabian

last: Koeslin-Findeklee

first: Walter

last: Horst


title: Hydrocortisone and Triiodothyronine Regulate Hyaluronate Synthesis in a Tissue–Engineered Human Dermal Equivalent through Independent Pathways

status: Public on Apr 08 2015

first: Lana

last: Schaffer

address: 10550 North Torrey Pines Road

department: DNA Array Core

institute: TSRI

summary:
Hydrocortisone (HC) and triiodothyronine (T3) have both been shown to be capable of independently inhibiting hyaluronate (HA, hyaluronic acid) synthesis in a self-assembled human dermal equivalent (human dermal matrix).
We sought to investigate the action of these two hormones in concert on extracellular matrix formation and HA inhibition in a tissue engineered human dermal matrix.

overall_design: RNA preparations were sent to CFG Microarray Core (E). Three replicate samples from each condition were used in the study. The RNA was amplified, labeled, and hybridized to the GLYCOv4 microarrays.

first: Tara

last: Pouyani


title: Expression data from proximal jejunum of WT vs. TLR2 KO mice after methotrexate (MTX) treatment

status: Public on Jan 24 2015

city: Essen

first: Elke

last: Cario

state: NRW

address: Virchowstr. 171

department: Division of Gastroenterology and Hepatology

institute: University of Duisburg-Essen, University Hospital of Essen

summary: The role of innate immunity in modulating severity of chemotherapy-induced complications is so far unclear. The aim of this study was to determine how TLR2 may influence MTX-induced mucositis in the small intestine in mice. We used microarrays to assess gene expression profiles in proximal jejunum of WT vs. TLR2 KO mice after systemic treatment with MTX.

overall_design: Mucositis was induced by i.p. injection of MTX [40mg/kg BW/d] for 4 days in WT or TLR2 knockout (KO) mice. On day 7, mice were sacrificed and RNA was extracted from proximal jejunum (n=3 mice/group) and hybridized on Affymetrix microarrays.

first: Magdalena

last: Frank


title: Microarray analysis in wild type and hy5 plants

status: Public on Jan 06 2015

city: Yokohama

first: Yukio

last: Kurihara

address: 1-7-22 Suehiro-cho, Tsurumi-ku

institute: Riken

summary: Gene expression profiles between wild type (WT) and hy5 were compared to know HY5-targets.

overall_design: Gene expression profiles between wild type (WT) and hy5 were compared to known HY5-targets.

first: Mika

last: Kawashima

first: Minami

last: Matsui


title: Inflorescence apices: rtr-2 versus wild type samples

status: Public on Dec 31 2014

city: Madrid

first: Jose M.

last: Franco-Zorrilla

address: Darwin, 3

department: Plant Molecular Genetics

institute: Centro Nacinal de Biotecnologia-CSIC

summary: Transcriptional profiling of inflorescence apices from wild type and rtr-2 mutant plants . Goal was to determine the differentially expressed genes between wild type and mutant plants in inflorescence apices.

overall_design: Two-condition experiment, rtr-2 vs. Wild type inflorescence apices. Biological replicates: 4 wild type replicates, 4 rtr-2 replicates.

first: E

last: Rojo

first: S

last: Mangano


title: DamID (LmnB1/Dam) Log2 ratios of C57Bl/6 fibroblasts and RAG2-/- pro-B cells.

status: Public on Dec 16 2014

city: Baltimore

first: Karen

last: Reddy

state: MD

address: 855 North Wolfe Street

department: Center for Epigenetics/Biological Chemistry

institute: Johns Hopkins University

type: Genome binding/occupancy profiling by genome tiling array

summary: Comparison of DamID profiles and LAD patterning across cell types reveals regions of variable LADs

overall_design: LmnB1 interactions at the nuclear periphery of C57Bl/6 pro-B cells and fibroblasts were identified by DamID in duplicate for both pro-B and fibroblasts (4 samples total). For each sample, Dam-LmnB1/Dam-only Log2 ratios of chromosomes 11 and 12 were calculated, lifted over to mm9, duplicates were normalized and averaged together.

first: Jennifer

last: Harr

first: Teresa

middle: R

last: Luperchio

first: Xianrong

last: Wong

first: Erez

last: Cohen

first: Sarah

last: Wheelan

middle: L


title: Reactive leaf volatiles act as powerful inducers of abiotic stress-related gene expression

status: Public on Dec 20 2014

city: Kobe

first: Yasuo

last: Yamauchi

state: Hyogo

address: Rokkodai 1-1, Nada

institute: Kobe University


title: Reactive leaf volatiles act as powerful inducers of abiotic stress-related gene expression [Agilent]

summary: Abiotic stresses cause serious damage to plants; therefore, plants undergo a complicated stress response through signal transduction originating from environmental stimuli. Here we show that a subset of short-chain leaf volatiles with an α,β-unsaturated carbonyl bond in their structure (reactive short-chain leaf volatiles, RSLVs) like (E)-2-hexenal and (E)-2-butenal can act as signal chemicals that strongly induce the gene expression of abiotic-related transcription factors, such as heat stress-related transcription factors (HSFA2, MBF1c) and other abiotic stress-related transcription factors (DREB2A, ZATs). RSLV-induced expression of HSFA2 and MBF1c was eliminated in HSFA1s-, known as heat stress response master regulators, knockout mutant, whereas those of DREB2A and ZATs were not, suggesting that the RSLV signaling pathway is composed of HSFA1-dependent and -independent pathways. RSLV treatment induced production of chaperon proteins, and the RSLV-treated Arabidopsis thus demonstrated enhanced abiotic stress tolerance. Because oxidative stress treatment enhanced RSLV production, we concluded that commonly found RSLVs produced by environmental stresses are powerful inducer of abiotic stress-related gene expression as oxidative stress signals.

overall_design: A four chips study of Columbia-0 following 10 µM 2E-pentenal, 3-hepten-2-one or crotonaldehydel treatment for 30 min. Datasets including acetonitrile (control) and volatiles treated samples.

first: Mikiko

last: Kunishima

first: Masaharu

last: Mizutani

first: Yukihiro

last: Sugimoto


title: lexA mutant vs Shewanella piezotolerans WP3 wild-type strain (4 C)

status: Public on Dec 01 2014

city: Shanghai

first: Huahua

last: Jian

address: No.800 Dongchuan Road

institute: Shanghai Jiao Tong University

summary: The lexA gene was deleted from WP3 genome to construct the WP3ΔlexA strain. The two strains were cultured at 4°C and the transcriptional profiles were compared.

overall_design: Three biological replicates sample and 6 technical replicates for each experiment

first: Fengping

last: Wang


title: lexA mutant vs Shewanella piezotolerans WP3 wild-type strain (20 C)

summary: The lexA gene was deleted from WP3 genome to construct the WP3ΔlexA strain. The two strains were cultured at 20°C and the transcriptional profiles were compared.


title: Cell-autonomous transformation of Lgr5-positive intestinal stem cells into gastric stem cells upon loss of transcription factor Cdx2  (AFFYMETRIX ARRAYS)

status: Public on Dec 04 2014

city: Amsterdam

first: Richard

last: Volckmann

state: Noord-Holland

address: van der Boechorststraat 6a

department: Laboratory of Experimental Oncology and Radiobiology

institute: msterdam UMC and University of Amsterdam

summary: The endodermal lining of the adult gastro-intestinal tract harbors stem cells that are responsible for the day-to-day regeneration of the epithelium. Stem cells residing in the pyloric glands of the stomach and in the small intestinal crypts differ in their differentiation program and in the gene repertoire that they express. Both types of stem cells have been shown to grow from single cells into 3D structures (organoids) in vitro. We show that single adult Lgr5-positive stem cells, isolated from small intestinal organoids, require Cdx2 to maintain their intestinal identity and are converted cell-autonomously into pyloric stem cells in the absence of this transcription factor. Clonal descendants of Cdx2null small intestinal stem cells enter the gastric differentiation program instead of producing intestinal derivatives. Conversely, forced expression of Cdx2 in gastric organoids results in their intestinalization. The intestinal genetic program is thus critically dependent on the single transcription factor encoding gene Cdx2.

overall_design: Small intestinal crypts and stomach glands were isolated from Cdx2-/fl / Lgr5-EGFP-CreERT2 mice and cultured for a week in order to generate small intestinal (SI) and stomach (Sto) in vitro organoids. The Lgr5-CreERT2 enzyme activity has been induced by overnight 4-hydroxytamoxifen induction. Tamoxifen treated and untreated Lgr5-EGFPhi SI and Sto stem cells were FACS sorted and seeded back into ENRWfg (Sto med) culture conditions in order to generate Cdx2-/fl small intestinal (Control SI), Cdx2null small intestinal (Cdx2null SI) and Cdx2-/fl stomach (Control Sto) clonal organoids. Cdx2-/fl SI organoids and Cdx2-/fl Sto organoids have been also cultured in ENR (SI med) to induce differentiation. After some passages of clonal organoid expansion, RNA was isolated from Control SI, Cdx2null SI and Control Sto Lgr5-EGFPhi FACS sorted stem cell populations and from smal intestinal and stomach organoids cultured in different conditions and hybridized on Affymetrix Mouse Gene ST 1.1 arrays.

first: Salvatore

last: Simmini

first: Jacqueline

last: Deschamps


title: Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling

status: Public on Oct 31 2014

first: Guido

last: Hooiveld

address: HELIX, Stippeneng 4

department: Div. Human Nutrition & Health

institute: Wageningen University


title: Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling [A286_GEO_LLM]

summary:
Background: Anorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer-induced anorexia is thought to be caused by an inability of food intake-regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food-intake control is likely to be mediated by altered serotonin signalling and by failure in post-transcriptional neuropeptide Y (NPY) regulation. Methods: Two tumour cachectic mouse models with different food intake behaviours were used: a C26-colon adenocarcinoma model with increased food intake and a Lewis lung carcinoma model with decreased food intake. This contrast in food intake behaviour between tumour-bearing (TB) mice in response to growth of the two different tumours was used to distinguish between processes involved in cachexia and mechanisms that might be important in food intake regulation. The hypothalamus was used for transcriptomics (affymetrix chips). Results: In both models, hypothalamic expression of orexigenic NPY was significantly higher compared with controls, suggesting that this change does not directly reflect food intake status but might be linked to negative energy balance in cachexia. Expression of genes involved in serotonin signalling showed to be different between C26-TB mice and Lewis lung carcinoma-TB mice and was inversely associated with food intake. In vitro, using hypothalamic cell lines, serotonin repressed neuronal hypothalamic NPY secretion while not affecting messenger NPY expression, suggesting that serotonin signalling can interfere with NPY synthesis, transport, or secretion.
Conclusions: Altered serotonin signalling is associated with changes in food intake behaviour in cachectic TB mice. Serotonins' inhibitory effect on food intake under cancer cachectic conditions is probably via affecting the NPY system. Therefore, serotonin regulation might be a therapeutic target to prevent the development of cancer-induced eating disorders.

overall_design: Lewis Lung tumour cells were intramuscularly inoculated 6w old male C57BL/6 mice.  Body weight and food intake were measured 3 times a week. On day 10, 14 and 17 hypothalamus was dissected and used for gene expression profiling.

first: Jvalini

last: Dwarkasing

first: Mark

last: Boekschoten

first: Josep

last: Argilès

first: Miriam

last: van Dijk

first: Silvia

last: Busquets

first: Alessandro

last: Lavianio

first: Renger

last: Witkamp

first: Klaske

last: van Norren


title: The sRNA SorY confers resistance during photooxidative stress by affecting a metabolite transporter in Rhodobacter sphaeroides

status: Public on Nov 18 2014

city: Gießen

first: Gabriele

last: Klug

address: Heinrich-Buff-Ring 26-32

department: Molecular- and Microbiology

institute: Justus-Liebig University Gießen

summary: Exposure to oxygen and light generates photooxidative stress by the bacteriochlorophyll a mediated formation of singlet oxygen (1O2) in the facultative photosynthetic bacterium Rhodobacter sphaeroides. We have identified SorY as an sRNA, which is induced under several stress conditions and confers increased resistance against 1O2. SorY by direct interaction decreases the levels of takP mRNA, encoding a TRAP-T transporter. A takP mutant shows higher resistance to 1O2 than the wild type, which is no longer affected by SorY. We present a model in which SorY reduces the metabolite flux into the TCA cycle by reducing malate import through TakP. It was previously shown that oxidative stress in bacteria leads to switch from glycolysis to the pentose phosphate cycle and to reduced activity of the tricaboxylic acid cycle. As a consequence the production of the prooxidant NADH is reduced and production of the protective NADPH is enhanced. In R. sphaeroides enzymes for glycolysis, pentose phosphate pathway, Entner–Doudoroff pathway and gluconeogenesis are induced in response to 1O2 by the alternative sigma factor RpoHII. The same is true for the sRNA SorY. By limiting malate import SorY thus contributes to the balance of the metabolic fluxes under photooxidative stress conditions. This assigns a so far unknown function to an sRNA in oxidative stress response.

overall_design: RNA samples collected from a control strain harbouring an empty vector (2.4.1pBBR) and of the SorY overexpressing strain (2.4.1pBBRSorYi) after 10 min of 1O2 stress were analyzed by two-color microarrays

first: Lennart

last: Weber


title: Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling [A358_GEO_hypocells]

city: Wageningen

overall_design: Hypothalamic neuronal cells mHypoE-46 (serotonin sensitive cells) and mHypoA-2/12 (serotonin unresponsive cells) were used to study the effect of serotonin on messenger NPY expression and NPY excretion.


title: Transcriptome analysis of transgenic plants with ectopic expression (driven by 35S promoter) of At14a-Like1 (AFL1, At3g28270) YFP fusion protein.

status: Public on Oct 17 2014

city: Taipei

first: Verslues

middle: Edwin

last: Paul

address: 128 Sec. 2, Academia Rd, Nankang, Taipei 11529 Taiwan, R.O.C.

department: Institute of Plant and Microbial Biology

country: Taiwan

institute: Academia Sinica

summary: Transcriptome analysis was used to identify genes differentially expressed in transgenic plants expressing At14a-Like1 (AFL1, At3g28270)) YFP fusion protein compared to wild type.  Transcriptome analysis was performed using seedlings grown under either control conditions or low water potential stress with the objective of identifying genes associated with the increased growth caused by AFL1 overexpression under stress.   The analysis identified 172 genes up-regulated and 525 genes down regulated in 35S:AFL1-YFP relative to wild type in control condtions.  In the stress treatment 398 genes were up regulated and 722 down regulated in 35S:AFL1-YFP plants relative to wild type.  The criteria used to identify up and down regulated genes was fold change greater than 1.5 and corrected p value ≤0.05.

overall_design: Wild type (Col-0) or transgenic Arabidopsis thaliana seedlings were germinated on agar plates and after seven days of growth, seedlings were transferred either to fresh plates of control media or to low water potential (-1.2 MPa) stress plates.  Samples were collected 10 h after transfer.

first: Kumar

middle: M

last: Nagaraj


title: Comparison of class-B GATA overexpression transcriptomes

status: Public on Oct 02 2014

city: Freising-Weihenstephan

first: Claus

last: Schwechheimer

address: WZW - Lehrstuhl Systembiologie der Pflanzen, Am Hochanger 4

institute: Claus Schwechheimer

summary:
We have used Agilent whole genome arrays (v4) to compare the gene expression changes between 10-day-old Arabidopsis wild type seedlings and AtGNLox (AT4G26150), AtGNCox (AT5G56860), AtGATA17ox (AT3G16870), BdGATA6ox (BRADI3G08240) as well as the C-terminal mutation constructs AtGNL_LLM/AAAox and AtGNC_LLM/AAAox.
Three independent biological samples were prepared for each genotype.

overall_design: Three replicate measurements of three biological samples were prepared for each genotype (1-3 or A-C). The experiment was performed in two batches; samples with replicate numbers 1-3 and A-C were prepared and hybridzed in the same respective batch.

first: Carina

last: Behringer


title: Induction of LHY expression from an alcohol-inducible promoter

status: Public on Oct 01 2014

city: Coventry

first: Nigel

middle: Paul

last: Dyer

address: Gibbet Hill Road

institute: University of Warwick

summary: The aim of the experiment was to identify transcripts that are regulated by LHY, a MYB transcription factor that functions as part of the Arabidopsis circadian clock. Transgenic plants carrying an ethanol-inducible copy ot the LHY gene (Alc::LHY) were irrigated with 6% ethanol  at ZT 17 (17 hours after dawn). Their transcriptome was compared to that of wild-type plants exposed to the same treatment at times 0, 2, 4 and 8 hours after ethanol addition.

overall_design: Duplicate experiments were carried out for both Alc::LHY and wild-type plants.

first: Isabelle

last: Carre

first: Sally

last: Adams

first: Siren

last: Veflingstad