title: A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice [expression profiling]

status: Public on Apr 20 2017

city: Bonn

first: Dan

last: ehninger

address: Sigmund-Freud-Straße 27

institute: German Center for Neurodegenerative Diseases

summary:
Evaluation of transgenerational influence of paternal dietary methyl substrates on offspring and grand-offspring brain and behavior
Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation.
Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (MD F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. These phenomena did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.

overall_design: 6 pools of 4 mouse hippocampal cDNA each from F1 and from F2

last: Ehninger

first: Brandon

last: Pearson


title: A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice

country: Germany

type: Methylation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Dlk response to optic nerve injury

status: Public on Mar 16 2017

city: South San Francisco

first: Kevin

last: Huang

state: California

address: 1 DNA Way

department: Bioinformatics

country: USA

institute: Genentech

summary:
Expression of whole retina after optic nerve crush.

The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech.
The ID of this project in Genentech's ExpressionPlot database is PRJ0004847

overall_design: Microarray analysis of whole retina after optic nerve crush in tamoxifen-treated adult DLK conditional knockout mice with and without CreER transgene using uninjured eye as control.

first: Genentech

last: Genentech Inc


title: Comparison of gene expression changes in TSA tumors following different radiation regimens.

status: Public on Jun 09 2017

city: New York

first: Sandra

last: Demaria

state: New York

address: 1300 York avenue, Room A-279

department: Radiation Oncology

institute: Weill Cornell Medicine

summary: Radiotherapy is under investigation in the clinic for its ability to induce an in situ vaccine and enhance responses to immune checkpoint inhibitors and other immunotherapies. A variety of radiation doses and delivery schedules have been used to induce anti-tumor T cells in preclinical studies. However, the mechanisms bu which radiation induces anti-tumor T cells against poorly immunogenic tumors remain incompletely understood. In this study, we investigated changes in gene expression in mouse mammary carcinoma TSA tumors after a single dose (SD) of 20 Gy and a multi-fraction (MF) radiation regimen of 3x8Gy. To this end, TSA cells were injected into syngeneic BALB/c mice. When tumors became palpable, they were treated with local radiation therapy (RT) and harvested 4 or 24 hours later for gene expression analysis. The genome-wide microarray analysis showed key differences between SD and MF RT that may explain the differential ability of these two RT regimens to synergize with immune checkpoint inhibitors (Dewan et al., Clin Cancer Res 2009).

overall_design: To better understand why multi-fractionated (MF - 3x8Gy) radiation regimen is better at synergizing with anti-CTLA4 compared to a single dose (SD) of 20Gy, we harvested TSA tumors 4 and 24 hours after completion of RT. Three tumors from each group were then subjected to RNA extraction and hybridization on Agilent array.

first: Silvia

middle: C

last: Formenti

first: C

middle: N

last: Coleman

first: Molykutti

middle: J

last: Arankalayil

first: Claire

last: Vanpouille-Box


title: Expression data at drug-sensitive and drug-resistant phases of canine B-cell lymphoma

status: Public on Apr 01 2017

city: Bunko-ku

first: Hirotaka

last: Tomiyasu

state: Tokyo

department: Department of Veterinary Internal Medicine

country: Japan

institute: the University of Tokyo

summary: Multidrug resistance (MDR) is one of the major obstacles during the chemotherapy in lymphoma patients. Although there have been various molecules associated with acquisition of MDR phenotype in human tumor cells, MDR of tumor cells have not been successfully overcome. Canine lymphoma is thought to be a spontaneous animal model of human lymphoma because it shares many similarities with human non-Hodgkin’s lymphoma. We conducted a comprehensive analysis of changes in gene expression profiles of canine lymphoma cells by microarray analysis using tumor cell samples at drug-sensitive and drug-resistant phases in 6 dogs. It was revealed that expression of the molecules related to chemotaxis and inflammation were down regulated in MDR phases.

overall_design: We isolated RNA from tumor cell samples at drug-sensitive and drug-resistant phases of 6 dogs and detected changes in gene expression profiles between 2 phases of each dog using microarrays.

first: Miyu

last: Suenaga

first: Manabu

last: Watanabe


title: Hyponutrition during pregnancy after insemination alters the progenies’ behavior and DNA methylation of their brain

status: Public on Mar 08 2017

city: Chuoshi

first: Kunio

last: Miyake

state: Yamanashi

address: 1110 Shimokato

institute: Yamanashi University

summary: Recent epidemiological studies suggest that hyponutritional stress during fetal period increase risks of adult-onset diseases, such as type 2 diabetes and mental diseases. Rodent models have demonstrated that hyponutrition during pregnancy alters epigenetic status of neuronal genes in the fetal brains; this implicate fatal environment contributes to susceptibility to mental disorders. However, in these studies, progenies were generated with natural mating and effects of hyponutrition during egg formation have not been eliminated. Therefore, we conducted experiments in order to finely evaluate the hyponutritional effects during fatal life using in vitro fertilization. We divided three experimental groups such as control diet (CD (AIN93G)), protein-restricted diet (PR), and PR diet with supplemental folic acid (FA) and compared body weight of mother and progenies, clinical-blood biochemistry, DNA methylation and gene-expression pattern in adult brain of the progenies, behavioral phenotypes of the progenies, and DNA methylation profile in brain of the progenies. The progenies of the PR group and the FA group exhibited increased activity in the home cage, decreased contact to a novel object, and decreased social behavior compared with the CD group. Increased home-cage activity in the PR group was rescued in the FA group. The progenies of the PR group and the FA group showed different patterns of mRNA expression and genomic methylation in the brain compared with the CD group. These results suggest that hyponutrition after insemination sufficiently induced phenotypic and epigenetic changes in the progenies. In addition, supplemental nutrition to mothers should rescue the epigenetic and phenotypic changes induced with hyponutrition.

overall_design: For methylation study, there were in total 22 samples: 11 Input files (3 controls diet (CD) sammples, 4 protein-restricted diet (PR) samples, 4 PR diet with supplemental folic acid (FA) samples). In addition, gene expression profiles were analyzed to identify the effects of prenatal maternal diet and to the next generation. Four male mice of three experimental conditions (CD, PR and FA) were analyzed.

first: Tamio

last: Furuse

first: Takashi

last: Kohda

first: Hideki

last: Kaneda

first: Takae

last: Hirasawa

first: Ikuko

last: Yamada

first: Tomoko

last: Kushida

first: Misho

last: Kashimura

first: Kimio

last: Kobayashi

first: Fumitoshi

last: Ishino

first: Takeo

last: Kubota

first: Shigeharu

last: Wakana


title: MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach [SNP array]

status: Public on Apr 19 2017

city: Sao Paulo

first: Cibele

last: Masotti

state: São Paulo

address: Rua do Matao, 277.

department: Genetics and Evolutionary Biology

country: Brazil

institute: University of Sao Paulo

summary: A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals. From 46 OOM samples, which are frequently discarded during routine corrective surgeries on patients with orofacial clefts, we derived mesenchymal stem cells and correlated the individual genetic variants with gene expression from these cultured cells. Through this strategy, we detected significant cis-eQTLs (i.e., DNA variants affecting gene expression) and selected a few candidates to conduct an association study in a large Brazilian cohort (624 patients and 668 controls). This resulted in the discovery of a novel susceptibility locus for NSCL/P, rs1063588, the best eQTL for the MRPL53 gene, where evidence for association was mostly driven by the Native American ancestry component of our Brazilian sample. MRPL53 (2p13.1) encodes a 39S protein subunit of mitochondrial ribosomes and interacts with MYC, a transcription factor required for normal facial morphogenesis. Our study illustrates not only the importance of sampling admixed populations but also the relevance of measuring the functional effects of genetic variants over gene expression to dissect the complexity of disease phenotypes.

overall_design: In order to understand the genetic basis of NSCL/P susceptibility, we searched for genetic variants with regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle, OOM) of affected individuals. From OOM samples, which are frequently discarded during corrective surgeries that patients with orofacial clefts routinely undergo, we derived mesenchymal stem cells (OOMMSC), and correlated the individual genetic differences with gene expression. We obtained OOM samples from 43 NSCL/P-affected and four normal individuals, and established OOMMSC  primary cultures according to previously published protocol. DNA samples extracted from OOMMSC cell cultures were genotyped with the GeneChip Human Mapping 250K Nsp/250K Sty Arrays according to the manufactures’ protocol (Affymetrix, USA).

first: C

first: L

middle: A

last: Brito

first: M

middle: R

last: Passos-Bueno


title: Transcriptomic analysis of reovirus-induced host responses in mesenteric lymph node, lamina propria, peyer's patches, and epithelium.

status: Public on Mar 01 2017

city: Cambridge

first: Mukund

last: Varma

state: MA

address: 415 Main Street

institute: Broad Institute

summary: Analysis of reovirus-induced host responses at the level of gene expression. Results provide insights into how reovirus infection breaks tolerance to dietary antigens and promotes the development of celiac disease.

overall_design: Total RNA obtained from mouse mesenteric lymph node, lamina propria, peyer's patches, or epithelium subjected to 6 or 48 hours stimulation with Reoviruses T1L or T3D-RV compared to Sham.

first: Romain

last: Bouziat

first: Reinhard

last: Hinterleitner

first: Judy

last: Brown

first: Jennifer

middle: E

last: Stencel-Baerenwald

first: Mine

last: Ikizler

first: Toufic

last: Mayassi

first: Marlies

last: Meisel

first: Sangman

middle: M

last: Kim

first: Valentina

last: Discepolo

first: Andrea

last: Pruijssers

first: Jordan

middle: D

last: Ernest

first: Jason

last: Iskarpatyoti

first: Léa

last: Costes

first: Ian

last: Lawrence

first: Brad

last: Palanski

first: Matthew

last: Zurenski

first: Solomiia

last: Khomandiak

first: Nicole

last: McAllister

first: Pavithra

last: Aravamudhan

first: Karl

middle: W

last: Boehme

first: Fengling

last: Hu

first: Janneke

last: Samsom

first: Hans-Christian

last: Reinecker

first: Sonia

middle: S

last: Kupfer

first: Stefano

last: Guandalini

first: Carol

last: Semrad

first: Valérie

last: Abadie

first: Chaitan

last: Khosla

first: Luis

middle: B

last: Barreiro

first: Ramnik

last: Xavier

first: Aylwin

last: Ng

first: Terence

last: Dermody

first: Bana

last: Jabri


title: Genome-wide siRNA screen of genes regulating the Lipopolysaccharide-induced NF-κB and TNF-α responses in mouse macrophages

status: Public on Feb 23 2017

city: Bethesda

first: Timothy

middle: G

last: Myers

state: MD

address: 50 South Drive, Room 5509

department: Research Technologies Branch

institute: National Institute of Allergy and Infectious Diseases

summary: The mammalian innate immune system senses many bacterial stimuli through the toll-like receptor (TLR) family. Activation of the TLR4 receptor by bacterial lipopolysaccharide (LPS) is the most widely studied TLR pathway due to its central role in host responses to gram-negative bacterial infection and its contribution to endotoxemia and sepsis. Here we describe a genome-wide siRNA screen to identify genes regulating the mouse macrophage TNF-α and NF-κB responses to LPS. We include a secondary validation screen conducted with six independent siRNAs per gene to facilitate removal of off-target screen hits. We also provide microarray data from the same LPS-treated macrophage cells to facilitate downstream data analysis. These data provide a resource for analyzing gene function in the predominant pathway driving inflammatory signaling and cytokine expression in mouse macrophages.

overall_design: RAW264.7 cells were stimulated with 0 and 10 ng/ml of LPS separately for 4hrs. Two replicates for each condition.

first: Ning

last: Li

first: Samuel

last: Katz

first: Bhaskar

last: Dutta

first: Zachary

middle: L

last: Benet

first: Jing

last: Sun

first: Iain

last: Fraser


title: The EMT-activator Zeb1 is crucial for cellular plasticity and drives metastasis in pancreatic cancer

city: Lübeck

first: Hauke

last: Busch

state: Schleswig-Holstein

address: Ratzeburger Allee 160

department: Lübeck Institute of Experimental Dermatology

institute: University of Lübeck

summary: Depletion of Zeb1 in a KPC-model for pancreatic cancer affected strongly the formation of precursor lesions, tumour grading, invasion and notably metastasis during PDAC progression. In this context, EMT is important for metastasis, but there is variability and specificity (and not redundancy) in the role and function of different EMT-inducing transcription factors.

overall_design: Primary Tumor cell lines were derived in replicates from pancreatic cancer driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC-model) and also from Pdx1-Cre;Zeb1fl/fl with KrasLSL.G12D/+;Tp53LSL.R172H/+;Zeb1fl/fl mice (KPCZ, Zeb1 knockout). The tumor cell lines displayed phenotypes from mesenchymal and epithelial (designated as KPC_E, KPCZ_E or KPC_M). Two epithelial KPC cell lines and two KPCZ cell lines were treated with 5ng/ml TGFβ (KPC_E+TGFβ or  KPCZ_E+TGFβ)

first: Melanie

last: Boerries

first: Angela

last: Krebs

first: Marc

last: Stemmler

first: Thomas

last: Brabletz


title: Identification of down-stream targets of Notch signaling within the developing mosue kidney collecting ducts.

status: Public on Feb 27 2017

city: Sioux Falls

first: Kameswaran

last: Surendran

state: SD

address: 2310 East 60th Street North

department: Children's Research Center

institute: Sandord Research

summary:
Notch signaling deficient kidney collecting ducts may serve as a useful resource to identify principal cell lineage and intercalated lineage specific factors since they develop a reduced number of principal cells and an increased number of intercalated cells compared with wild type kidney collecting ducts.
We compared RNA from three E18.5 mouse kidneys per group: HoxB7Cre;RBPJf/-;Rosa+/Eyfp (Notch signaling deficient; mutant) versus RBPJf/f;Rosa+/Eyfp (wild type).

overall_design: Total RNA was extracted from three mutant and three wild type E18.5 kidneys. N=3 per group. Mutant = Notch signaling deficient collecting ducts. Wilt-type= control littermate kidneys. The sex was not determined.


title: Gene expression profiling in mouse spleen

status: Public on Feb 17 2017

city: Shanghai

first: Eugene

last: Chin

address: Yueyang Road #320

department: Institute of Health Science

country: China

institute: Shanghai Institute of Biological Sciences

summary: To understand Loxl3 gene regulation function in vivo, whole genome microarray expression profiling was used as a discovery platform to identify differential gene expressions in spleen between wild type (wt) mice and Loxl3-/- (ko) mice. Genes including cell-cell adhesion and STAT signaling pathway were identified to be differentially expressed in wt and Loxl3-/- mice.

overall_design: Total RNA from spleen of Loxl3 wild-type or knock-out mice were used for gene expression analysis.

first: Y

first: Chao

last: Huang


title: Generation of PDGFRα+ Cardioblasts from Pluripotent Stem Cells

status: Public on Feb 10 2017

city: Daejeon

first: Gou Young

last: Koh

address: 291 Daehark-ro, Yuseong-gu

country: South Korea

institute: KAIST

summary:
We uncover a novel class of cardiac lineage cells, PDGFRα+Flk1- cardioblasts (PCB), from mouse and human pluripotent stem cells (PSC) using CsAYTE, a combination of small molecules – Cyclosporin A (CsA), ROCK inhibitor Y27362, antioxidant Trolox, and ALK5 inhibitor EW7197.
To elucidate the genome-wide characteristics of PCB, microarray analysis was performed and compared with the spontaneously formed PCB, which were obtained without CsAYTE incubation (hereafter referred to as “sfPCB”), Flk1+ mesodermal precursor cells (MPC), and αMHC+ cardiomyocytes (M+CM)

overall_design: Sorting of cells was performed by flow cytometry (Flk1+ MPC at day 4.5, sfPCB and PCB at day 5.5, and M+CM at day 10.5 from PSC differentiation) and microarray analysis was performed.

first: Sung

last: Cho

first: Gou

middle: Y


title: Hypothalamic oxidative stress provokes leptin and insulin resistance [hypothlamus]

status: Public on Feb 06 2017

city: Sendai

first: Akira

last: Uruno

state: Miyagi

address: 2-1 Seiryo-cho, Aoba-ku

institute: Tohoku University Graduate School of Medicine

summary: The relationship between loss of hypothalamic function and onset of diabetes mellitus remains elusive. Therefore, we generated a targeted oxidative-stress murine model utilizing conditional knockout of selenocysteine-tRNA (Trsp) using rat insulin promoter-driven-Cre (RIP-Cre). These Trsp-knockout (TrspRIPKO) mice exhibit deletion of Trsp in both hypothalamic cells and pancreatic β-cells leading to increased hypothalamic oxidative stress and severe insulin resistance. Leptin signals were suppressed and numbers of proopiomelanocortin-positive neurons in the hypothalamus were decreased. In contrast, a Trsp-knockout mouse (TrspIns1KO) expressing Cre specifically in pancreatic β-cells, but not in the hypothalamus, did not display insulin and leptin resistance, demonstrating a critical role of the hypothalamus in the onset of diabetes mellitus. Nrf2 (NF-E2-related-factor-2) regulates antioxidant gene expression. Gene-driven increase in Nrf2 signaling suppressed hypothalamic oxidative stress and improved insulin and leptin resistance in TrspRIPKO mice. Thus, Nrf2 harbors the potential to prevent the onset of diabetic mellitus by reducing hypothalamic oxidative damage.

overall_design: Gene expression in the hypothalamus of TrspFlox/Flox (TrspFF), TrspFlox/Flox::RIP-Cre (Trsp-RIPKO) and TrspFlox/Flox::Ins1-Cre (Trsp-Ins1KO) mice. The conditional knockout of Trsp exhibits elevation of oxidative stress.

first: Yoko

last: Yagishita

first: Toshiaki

last: Fukutomi

first: Ritsumi

last: Saito

first: Daisuke

last: Saigusa

first: Jingbo

last: Pi

first: Akiyoshi

last: Fukamizu

first: Fumihiro

last: Sugiyama

first: Satoru

last: Takahashi

first: Masayuki

last: Yamamoto


title: Early temporal transcriptome responses of the bovine mid-cycle corpus luteum to prostaglandin F2 alpha indicates cytokine activation

status: Public on Jan 26 2017

city: Beaverton

first: Heather

last: Talbott

state: OR

address: L584 ONPRC (Room 2128), 505 NW 185th Ave

department: Division of Reproductive & Developmental Sciences

institute: OHSU, ONPRC

summary: In ruminants, prostaglandin F2alpha (PGF2α)-mediated luteolysis is essential for resumption of the estrous cycle and is a target for improving fertility.  To deduce the early PGF2α-provoked signaling elicited in the corpus luteum a time-course from 0.5–4 h was performed on cows at mid-cycle.  A microarray-determined transcriptome was established and analyzed by Ingenuity Pathway Analysis (IPA).  Self-organizing map analysis grouped differentially expressed transcripts into ten mRNA expression patterns indicative of signaling cascades. Classic PGF2α signaling (cyclic adenosine monophosphate, mitogen-activated protein kinases) and cytokine signaling (nuclear factor κB, interleukin) were both predicted by IPA after PGF2α administration.  Comparison with two analogous datasets revealed a conserved group of 124 transcripts similarly changed in each dataset, which also predicted cytokine signaling.  Elevated levels of cytokine transcripts after PGF2α and IPA-predicted activation of cytokine pathways demonstrate the importance of inflammatory reactions early in PGF2α -mediated luteolysis.

overall_design: Adult cows at midcycle were grouped (3 cows/group) into four PGF2α treatment times of: 0.5, 1, 2, and 4 h, and a saline control.  Corpus luteum RNA was analyzed by Affymetrix microarray.

first: Xiaoying

last: Hou

first: Fang

last: Qiu

first: Chittibabu

last: Guda

last: Yu

first: Robert

last: Cushman

first: Jennifer

last: Wood

first: Andrea

last: Cupp

first: John

last: Davis


title: Hypothalamic oxidative stress provokes leptin and insulin resistance

first: Akira

last: Uruno


title: Transcriptome analysis of samples from patients with endometriosis

status: Public on Feb 03 2017

city: Moscow

first: Maria

middle: Vladimirovna

last: Suntsova

address: Miklukho-Maklaya, 16/10

department: Department of Genetics and Postgenomic Technologies

country: Russia

institute: M.M. Shemyakin and Yu.A. Ovchinnikov  Institute of  bioorganic chemistry of the Russian Academy of Sciences

summary: The aim of this research was to explore activation/deactivation of signaling pathways in endometrium samples from patients with endometriosis.

overall_design: Samples of endometriosis, ovary cysts and cervical endometrium were obtained during surgical procedures. Tissues were placed in RNAlater solution immediately after removal and stored at -20°C.

first: Elena

last: Ilnitskaya

first: Yana

last: Aznaurova

first: Ivan

last: Petrov

first: Maksim

last: Sorokin

first: Anton

last: Buzdin

first: Assia

last: Stepanian

first: Leila

middle: V

last: Adamyan


title: Expression data from heart tissues of minipig with myocardial infarction and treated or untreated with myoblast transplantation

status: Public on Jan 28 2017

first: Zhenzhen

last: Zhan

address: Jimo Road 150

department: Research Center for Translational Medicine

institute: Shanghai East Hospital, Tongji University School of Medicine,

summary:
Myocardial infarction (MI) is a highly prevalent cardiac emergency, which results in adverse left ventricular remodeling exacerbating progressive heart failure. Inflammation in post-MI is necessary for myocyte repair and wound healing. However, it is also a key component of subsequent heart failure pathology.
Myoblasts transplantation after MI have been fulfilled a good effect on cardiac repair, but the occasion, complications of transplantation, and the underlying mechanisms have not been fully elucidated. Here, we found that myoblast transplantation decreased the expression of many pro-inflammatory genes and the activation of inflammation-related signal pathway in heart tissue of pig post MI, which mainly contributed to the improved heart function and attenuated damage of myocardial cells.

overall_design: We constructed a minipig surgical model of myocardial infarction. Myoblasts were intramyocardially injected into the infarct and border zone of heart. The infarct and border zone heart tissues from minipigs treated with myoblast transplantation or untreated control (one sample for every group) were submitted for gene expression array analysis.

first: Bo

last: Wang

first: Likui

last: Zhang

first: Hao

last: Cao

first: Huimin

last: Fan

first: Zhongmin

last: Liu


title: Hypothalamic oxidative stress provokes leptin and insulin resistance [Islets]

overall_design: Gene expression in the pancreatic islets of TrspFlox/Flox (TrspFF), TrspFlox/Flox::RIP-Cre (Trsp-RIPKO) and TrspFlox/Flox::Ins1-Cre (Trsp-Ins1KO) mice. The conditional knockout of Trsp exhibits elevation of oxidative stress.

first: Yoko

last: Yagishita

first: Toshiaki

last: Fukutomi

first: Ritsumi

last: Saito

first: Daisuke

last: Saigusa

first: Jingbo

last: Pi

first: Akiyoshi

last: Fukamizu

first: Fumihiro

last: Sugiyama

first: Satoru

last: Takahashi

first: Masayuki

last: Yamamoto


title: Genome wide analysis of rat renal gene expression at two different time points during hyperoxaluria development

status: Public on Jan 06 2017

city: Gainesville

first: Sunil

last: Joshi

state: Florida

address: 1600 S W Archer Road

department: Pathology, Immunology and Laboratory Medicine

institute: University of Florida

summary: We are testing the ability of spironolactone as a NADPH oxidase inhibitor during an induced dietary oxalate overload by Ethylene Glycol in Sprague Dawley rats at two different time points. We looked into the development of hyperoxaluria and crystal deposition at two different time points and into differences between hyperoxaluria and crystal induced alterations in the kidneys. Eventually, we are expecting to see the role of spironolactone as an inhibitor of NADPH oxidase which is involved in the production of reactive oxygen species (ROS) which leads to oxidative stress in the living organisms leading to a plethora of vascular diseases, hypertension, and kidney diseases.

overall_design: In the present study male rats were divided into three groups. Rats in Group 1 were fed normal diet which was used as control (C), Group 2 were fed normal diet supplemented with 1.25% Ethylene Glycol (EG) and Group 3 were fed diet supplemented with 1.25% EG and 15 mg/kg/day spironolactone (ES). All the three groups were further divided into two sub groups (Day 14 and Day 28).  So there were 3 treatments (Control, EG and ES) and 2 sub-groups, so a total of 6 samples. We had 4 replications of these. Therefore we had a total of 6 x 4 = 24 samples for the microarrays. First 12 samples are from day 14 and the next 12 samples are from day 28

first: Saeed

last: Khan


title: Comparison of gene expression profiles between wild-type and Dock8-deficient CD4+ T cells

status: Public on Dec 01 2016

city: Fukuoka

first: Takehito

last: Uruno

address: 3-1-1 Maidashi, Higashi-ku

department: Department of Immunobiology and Neuroscience

institute: Medical Institute of Bioregulation, Kyushu University

summary: To examine the effect of DOCK8 deficiency on  helper T cell differentiation, we employed microarray expression profiling and found that 850 genes were expressed at higher levels in Dock8–/– AND CD4+ T cells than Dock8+/– controls after antigen stimulation.

overall_design: CD4+T cells  from Dock8+/– and  Dock8–/– AND Tg h mice were stimulated with cognate antigen for 24 h in vitro, and their gene expression profiles were compared.

first: Yoshinori

last: Fukui

first: Kazuhiko

last: Yamamura


title: LncRNAs and mRNAs changes in border zone of myocardial infarction in rats

status: Public on Dec 02 2016

city: Shenyang

first: Meng

middle: Qing

last: kun

state: LiaoNing

address: No.36;Sanhao Street;Heping District

department: Cardiology

institute: Shengjing-hospital of China Medical University

summary:
Comparison of both LncRNAs and mRNAs expression in the border zone of the myocardial infarction rats and the sham operation rats
Border zone (BZ) of the myocardial infarction is critical to patients. Current treatments of myocardial infarction are primarily aimed to save the dying myocardial cell in the border zone. During myocardial infarction, certain changes in BZ, e.g, apoptosis, fibrosis, inflammation, etc, played an important role in deciding the survival. Impairment and recovery of BZ has been linked to gene expression changes. The aim of our study was to obtain a global expression profile of lncRNAs and mRNAs of the border zone in Wistar rats myocardial infarction, and identify the changes during myocardial infarction.

overall_design: 3 male rats were used to set up myocardial infarction model by ligation of LAD, and 3 rats were sham-operated. Border zone tissue of myocardial infarction was determined by TTC&EB double stain, then was send to further microarry analysis.

middle: Q

last: Kun

first: Sun

middle: Z

last: Jun


title: mRNA expression profiling in myocardial tissue by caloric restriction initiated in different aged mice

status: Public on Nov 17 2016

city: Nanjing

first: yunlu

last: sheng

state: Jiangsu

address: 300 Guangzhou Road

department: Department of Gerotology

institute: The First Hospital Affiliated to Nanjing Medical University

summary: The pathway analysis of differentially expressed genes (DEGs) demonstrated that some altered pathways, such as p53, cell cycle, and TGFb signaling pathways were closely associated with cardiac aging. Notably, FOXO signaling pathway revealed significant differences between CR initiated in different aged mice

overall_design: In this study, 6 samples from young, middle-aged, and old mice with or without caloric restriction (CR) were used to acquire the mRNA expression profiling thus to elucidate the possible molecular pathways underlying the observed different effects of CR on cardiac aging.

first: Yunlu

last: Sheng

first: Min

last: Huang


title: mRNA and miRNA expression profiling in myocardial tissue by caloric restriction initiated in different aged mice

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

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

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus

overall_design: Refer to individual Series


title: Gene expression analysis in mouse podocytes expressing shRNA directed against the long noncoding RNA Tug1

status: Public on Oct 24 2016

city: Houston

first: Shawn

middle: Samson

last: Badal

state: TX

address: 2121 W. Holcombe Blvd

department: Nephrology

institute: MD Anderson Cancer Center

summary: We generated two mouse podocyte cell lines stably transduced with either a shControl lentiviral construct or a shRNA lentiviral construct designed to target Tug1 RNA to investigate the consequences on the gene expression profile of Tug1 knockdown in differentiated mouse podocytes

overall_design: RNA from 2 biological repliactes of shControl podocytes, 2 biological replicates of independent shTug1 clones (shTug1 Clone 2 and shTug1 Clone 3)  were harvested after 10 days of podocyte differentiation and submitted for microarray analysis on the Agilent Mouse 4x44K gene expression arrays.

first: Farhad

last: Danesh

first: Jianyin

last: Long


title: Transcriptome analysis of T. reesei CBS999.97, backcrossed female fertile strains in QM6a genetic background and QM6a upon growth on cellulose

status: Public on Nov 04 2016

city: Vienna

first: Monika

last: Schmoll

address: Djerassiplatz 1

department: Centre of Microbiology and Environmental Systems Science

country: Austria

institute: University of Vienna

summary: The aim of this study was to evaluate changes in the transcriptome in the mentioned strains upon growth on cellulose

overall_design: Strains of this study were grown on Mandels Andreotti Minimal Medium with 1 % w/v microcrystalline cellulose as sole carbon source in  constant darkness for 72 hours; 2 biological replicates were included

first: Doris

last: Tisch


title: Master Regulators of oncogenic KRAS response in Pancreatic Cancer

status: Public on Nov 16 2016

first: Ines

last: de Santiago

state: - Select -

address: Robinson Way

department: CRUK

country: United Kingdom

institute: University of Cambridge

summary: We derived a transcriptional signature of oncogenic KRAS by using the KF508 murine pancreatic ductal cell line with an inducible Lox-Stop-Lox (LSL) cassette in front of the KRASG12D oncogene to regulate transcription. This dataset allowed us to study the differential expression profile after oncogenic KRAS induction in mouse.

overall_design: Total RNA was extracted from six sets of mock and cre treated ductal cells using Qiagen RNeasy kit. The RNA was labelled and hybridized. This experiment was carried out on 2 Illumina Mousev2 BeadChips using 24 arrays (1 samples per Bead-Chip).

first: Shivan

last: Sivakumar

first: Leon

last: Chlon

first: Florian

last: Markowetz


title: Expression data of Met-low and Met-high B16-F10 malignant melanoma cells

status: Public on Sep 25 2016

city: Kanazawa

first: Kunio

last: Matsumoto

address: Kakuma

institute: Kanaawa University

summary: B16-F10 malignant mouse melanoma cells have been frequently used as highly metastatic cells. Based on heterogenous cell surface expression of Met/HGF (hepatocyte growth factor) receptor in B16-F10 cells, the cells were divided into Met-low and Met-high cells by flow cytometry and these populations were subjected to microarray analysis. Met-low and Met-high cells showed different expression profiles in genes involved characteristics of tumors, including stem cell maintenance, pigmentation, and angiogenesis.

overall_design: Total RNA was prepared respectively from Met-low and Met-high cells cultured for 3 days after cell sorting. RNA samples (n=2 for each groups) were subjected to microarray analysis, using the Whole Mouse Genome (44,000) Oligo Microarray (Agilent Technologies).

first: Eri

last: Adachi

first: Katsuya

last: Sakai

first: Takumi

last: Nishiuchi


title: Transcript profiling in splenic red pulp macrophages from SIRPa-KO mice and WT mice

status: Public on Nov 22 2016

first: Zhen

last: Zhou

address: 22th,Hankou Road

department: School of Lifesciences

institute: Nanjing University

summary: To compare the splenic macrophages between SIRPα-knockout mice and WT mice, we performed a complete transcript profiling of the splenic red pulp macrophages from SIRPα-KO mice compared to WT mice using mRNA microarray as a discovery platform. SIRPα-KO mice and WT mice were kept under the same condition. Macrophages were isolated from spleen red pulp of SIRPα-KO mice and WT mice. RNA was then isolated from the same number of freshly isolated macrophages.

overall_design: In each group, 5 mice were used. Splenic red pulp macrophages isolated from 5 SIRPα-KO or 5 WT mice were mixed before RNA extraction.

first: Ke

last: Zen


title: Characterization of functional reprogramming during osteoclast development using quantitative proteomics and mRNA profiling

status: Public on Oct 12 2016

first: Timothy

last: Myers

address: 50 South Drive, Room 5509

institute: National Institute of Allergy and Infectious Diseases

summary: The innate immune system is the organism’s first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level. In addition to forming macrophages and dendritic cells, monocytes in adult peripheral blood retain the ability to develop into osteoclasts, mature bone-resorbing cells. The extensive morphological and functional transformations that occur during osteoclast differentiation require substantial reprogramming of gene and protein expression. Here we employ -omic-scale technologies to examine in detail the molecular changes at discrete developmental stages in this process (precursor cells, intermediate osteoclasts, and multinuclear osteoclasts), quantitatively comparing their transcriptomes and proteomes.

overall_design: osteoclast precursor cells , intermediate osteoclasts, and multinuclear osteoclasts isolated after 5 days in culture, 4 replicates of each condition

first: Eunkyung

last: An

first: Manikandan

last: Narayanan

first: Nathan

middle: P

last: Manes

first: Aleksandra

last: Nita-Lazar


title: Investigation of ripk3-dependent IAV-induced genes

status: Public on Oct 14 2016

city: Philadelphia

first: Sid

last: Balachandran

state: PA

address: 333 Cottman Ave

institute: Fox Chase Cancer Center

summary:
Ripk3-deficient fibroblasts and lung epithelial cells are resistant to influenza-induced cell deaths. However, Ripk3 is required for protection against influenza infection in vivo.
Here, we examine the influenza-regulated gene expressions between wild type and knock out MEFs as well as an involvement of kinase activity if any.

overall_design: Ripk3-/- or Ripk3+/+ MEFs treated with inhibitor of RIPK3 infected with PR8-ΔNS1 virus

first: Shoko

last: Nogusa


title: Treg cell gene expression signature in B16 melanoma

status: Public on Oct 31 2016

city: Heidelberg

first: Markus

last: Feuerer

state: Baden-Württemberg

address: Im Neuenheimer Feld 280

department: Tumor Immunology

institute: DKFZ

summary: Gene expression signature of Treg cells in B16 melanoma was measured and compared to B16-infiltrating CD4+ Tconv cells and CD8+ T cells as well as splenic Treg cells, CD4+ Tconv cells and CD8+ T cells.

overall_design: We isolated regulatory and conventional CD4+ T cells as well as CD8+ T cells from B16 melanoma and spleen of mice. Cells were isolated, pooled and target cells were purified by FACS. RNA was extracted and gene expression measured.

first: Ann-Cathrin

last: Hofer


title: In vivo correction of anemia in thalassemic mice by gammaPNA-mediated gene editing with stem cell factor treatment and nanoparticle delivery

status: Public on Sep 15 2016

city: West Haven

first: Francesc

last: Lopez

state: CT

department: Department of Genetics

institute: Yale University

summary: CD117+ (c KIT) and CD117- cells were isolated from mouse bone marrow and there gene expression profile was performed to observe up regulation as well as down regulation of genes. It has been noticed that CD117+ cells has many upregaulted DNA repair genes as compare to cd117- population.

overall_design: Total RNA obtained from isolated CD117+ and CD117-  cells from transgenic mice bone marrow

first: Peter

last: Glazer

first: Raman

last: Bahal


title: Glucocorticoid-regulated circadian expression genes in spinal cord of nerve-injured mice

status: Public on Jan 01 2017

first: Satoru

last: Koyanagi

state: Fukuoka

department: Pharmaceutics

institute: Kyushu University

summary: We prepared adrenalectomized (ADX) and sham-operated (sham) mice kept under a light-controlled room (ZT, zeitgeber time; ZT0, light on; ZT12, light off), and thereafter their sciatic nerve was partially ligated; mice undergone  partial sciatic nerve ligation (PSL) was used as an animal model of neuropathic pain. To screen pain-related genes whose spinal expression exhibits circadian oscillation in a glucocorticoid-dependent manner, we performed   oligonucleotide microarray analyses using RNA isolated from the spinal cords of sham-PSL mice or ADX-PSL mice at ZT10 and ZT22 when circulating glucocorticoid levels in sham-PSL mice peaked and declined, respectively

overall_design: Samples were corrected from spinal cords of sham-PSL mice or ADX-PSL mice at ZT10 and ZT22 when circulating glucocorticoid levels in sham-PSL mice peaked and declined, respectively

first: Naoki

last: Kusunose

first: Naoya

last: Matsunaga

first: Shigehiro

last: Ohdo


title: Expression data from elicitor-treated Arabidopsis seedling roots [25min]

status: Public on Sep 23 2016

city: Berkeley

first: Clarice

last: de Azevedo Souza

state: CA

address: 2151 Berkeley Way

department: Department of Plant and Microbial Biology

institute: University of California, Berkeley

summary:
Plants can perceive the presence of pathogens at the cell surface and plant damage-derived molecules via recognition of conserved microbial molecules, named pathogen- or microbe-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). Well-studied examples of PAMPs are chito-oligomers, breakdown products of fungal cell walls and insect exoskeletons.  Pectin-derived oligogalacturonides (OGs) are well-characterized DAMPs. Both PAMPs nd DAMPs are capable of activating plant immunity, generating changes in gene expression that lead to increased production of defense compounds and proteins; thus, equipping the plant cell to defend itself.
We used microarrays to assess the gene expression changes that follow 25min after elicitor treatment.

overall_design: RNA was extracted from roots of seedlings treated with cellobiose, chito-oligomers, OGs or a no-elicitor control, for 25 min using Trizol LS (Invitrogen) according to the manufacturer's recommendations. RNA integrity was checked with an Agilent 2100 BioAnalyzer. An aliquot from each RNA sample was used as a template to make cDNA, which was assessed by qRT-PCR to confirm that samples had the expected WRKY30 expression profile at 25 min. Samples were then analyzed for gene expression with Affymetrix GeneChip Arabidopsis ATH1 Genome Arrays, using standard Affymetrix reagents and protocols at the QB3-Functional Genomics Lab at the University of California, Berkeley. Samples from three biological replicas for each treatment were analyzed. A total of 24 chips were used (4 treatments x 2 time points x 3 biological replicates). Microarray data were analyzed using the GCRMA algorithm as described previously (Fletcher et al., 2011); ratios of normalized probe set intensity values were calculated for each sample pair (in which M value = log2 [elicitor/control]) and then averaged among the three replicates.

first: Shundai

last: Li

first: Andrew

last: Lin

first: Freddy

last: Boutrot

first: Guido

last: Grossman

first: Cyril

last: Zipfel

first: Shauna

middle: C

last: Somerville


title: Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment

status: Public on Sep 09 2016

first: Tamotsu

last: Sekinaka

address: 4-1 Seiryo-machi, Aobaku

department: Institute of Development, Aging and Cancer

institute: Tohoku University

summary: Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs.

overall_design: Total RNA (100 ng) from each sample was analyzed. Samples were prepared using the Agilent Low Input Quick Amp Labeling Kit; probes were hybridized onto the Agilent Whole Mouse Genome Oligo DNA Microarray kit Ver 2.0 (Agilent) according to the manufacturer’s instructions. The microarrays were scanned using the Agilent DNA microarray scanner (Agilent). Each cell-type was analyzed in three biological replicate.

first: Yohei

last: Hayashi

first: Toshiaki

last: Noce

first: Hitoshi

last: Niwa

first: Yasuhisa

last: Matsui


title: Expression data from elicitor-treated Arabidopsis seedling roots [3h]

summary:
Plants can perceive the presence of pathogens at the cell surface and plant damage-derived molecules via recognition of conserved microbial molecules, named pathogen- or microbe-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). Well-studied examples of PAMPs are chito-oligomers, breakdown products of fungal cell walls and insect exoskeletons.  Pectin-derived oligogalacturonides (OGs) are well-characterized DAMPs. Both PAMPs nd DAMPs are capable of activating plant immunity, generating changes in gene expression that lead to increased production of defense compounds and proteins; thus, equipping the plant cell to defend itself.
We used microarrays to assess the gene expression changes that follow 3h after elicitor treatment.

overall_design: RNA was extracted from roots of seedlings treated with cellobiose, chito-oligomers, OGs or a no-elicitor control, for 3 hours using Trizol LS (Invitrogen) according to the manufacturer's recommendations. RNA integrity was checked with an Agilent 2100 BioAnalyzer. An aliquot from each RNA sample was used as a template to make cDNA, which was assessed by qRT-PCR to confirm that samples had the expected WRKY30 expression profile at 3 hours post-treatment. Samples were then analyzed for gene expression with Affymetrix GeneChip Arabidopsis ATH1 Genome Arrays, using standard Affymetrix reagents and protocols at the QB3-Functional Genomics Lab at the University of California, Berkeley. Samples from three biological replicas for each treatment were analyzed. A total of 24 chips were used (4 treatments x 2 time points x 3 biological replicates). Microarray data were analyzed using the GCRMA algorithm as described previously (Fletcher et al., 2011); ratios of normalized probe set intensity values were calculated for each sample pair (in which M value = log2 [elicitor/control]) and then averaged among the three replicates.


title: Irf3 phenotyping

status: Public on Nov 02 2016

city: Braunschweig

first: Robert

last: Geffers

address: Inhoffenstr. 7

department: Dep. Molecular Bacteriology

institute: HCI - Helmholtz Centre for Infection Research

summary: The interferon regulatory factors IRF3 and IRF7 are key players in the regulation of type I and III IFN genes. In this study, we analyzed the role of IRF3 and IRF7 for the host response to influenza A virus infections in Irf3-/-, Irf7-/- and Irf3-/-Irf7-/- knock-out mice.

overall_design: The KO and WT mice were intranasally infected with PR8M virus or PBS for mock controls. Lungs were collected at indicated time points post infection (d3) . Total RNA from these lungs were used for microarray analysis.

first: K

last: Schughardt

first: B

last: Hatesuer

first: R

first: H

last: Hoang

first: E

last: Wilk


title: Expression data from elicitor-treated Arabidopsis seedling roots

first: Clarice

last: de Azevedo Souza


title: Cardiac aldosterone regulated genes in mice

status: Public on Sep 08 2016

city: Ottawa

first: Smail

last: Messaoudi

state: Ontario

address: 451 smyth road

department: BMI

country: Canada

institute: University of Ottawa

summary: Aldosterone excess is involved in cardiac diseases. The mechanisms are still unclears.  Mice  were treated for 7 days with aldosterone and a whole genome microarray analysis was performed.

overall_design: Two-group experiment: Untreated mice (Ctrl), mice + aldosterone treatment (Aldo). One comparisons: Ctrl vs Aldo

first: Veronique

last: Pelloux


title: RIPK3 restricts myeloid leukemogenesis by promoting cell death and differentiation of leukemia initiating cells

status: Public on Aug 22 2016

city: München

first: Sebastian

last: Mueller

address: Ismaninger Strasse 22

department: Institut für Molekulare Onkologie und Funktionelle Genomik

institute: Klinikum rechts der Isar

summary:
Examination of gene expression patterns in lineage negative FLT3-ITD– and pMIG-transduced BM cells via microarray study.
We performed a global mRNA profiling analysis of murine Lin– FLT3-ITD+ cells compared to empty-vector controls, purified 48h after transduction. We examined association patterns of FLT3-ITD and pMIG cells and identified a specific gene expression signature associated with FLT3-ITD signalling.

overall_design: Total RNA obtained from isolated lineage negative BM cells subjected to 48h of FLT3-ITD signalling compared to empty vector control.

first: U

last: Höckendorf

first: M

last: Yabal

first: T

last: Herold

last: Munkhbaatar

first: S

last: Rott

last: Jilg

first: J

last: Kauschinger

first: G

last: Magnani

first: F

last: Reisinger

last: Heuser

last: Kreipe

last: Sotlar

last: Engleitner

last: Rad

first: W

last: Weichert

first: C

last: Peschel

last: Ruland

last: Heikenwalder

last: Spiekermann

last: Slotta

first: O

last: Groß

first: P

middle: J

last: Jost


title: Circadian gene expression profile of pancreatic islets from C57BL6 mice fed on rodent chow diet collected at 4hr intervals around the clock

status: Public on Sep 01 2016

city: Rochester

first: Aleksey

last: Matveyenko

state: MN

address: 200 First St SW

department: Physiology and Biomedical Engineering

institute: Mayo Clinic

summary: Comparison of pancreatic islet transcriptome at 4hr intervals around the clock helps to identify genes that are cycling under the control of the circadian clock. We used Agilent microarrays to analyze pancreatic islet transcriptome at different time points across the circadian cycle.

overall_design: Pancreatic islets were isloated at ZT0, ZT4, ZT8, ZT12, ZT16, and ZT20 (ZT0 corresponds to lights on - 06:00hr and ZT12 corresponds to lights off - 18:00hr in a 12hr light, 12hr dark cycle). Pooled RNA samples, 3-5 mice per group, were used for the array.

first: Kuntol

last: Rakshit


title: Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity

status: Public on Aug 12 2016

city: 89 Beaumont ave

first: Dimitry

last: Krementsov

state: VT

address: 312C Rowell bldg, 106 Carrigan drive

department: BHSC

institute: University of Vermont

summary: Regulation of gene expression in immune cells is known to be under genetic control, and likely contributes to susceptibility to autoimmune diseases, such as multiple sclerosis (MS). How this occurs in concert across multiple immune cell types is poorly understood. Using a mouse model that harnesses the genetic diversity of wild-derived mice, more accurately reflecting genetically diverse human populations, we provide an extensive characterization of the genetic regulation of gene expression in five different naïve immune cell types relevant to MS. The immune cell transcriptome is shown to be under profound genetic control, exhibiting diverse patterns: global, cell-specific, and sex-specific. Bioinformatic analysis of the genetically-controlled transcript networks reveals reduced cell type-specificity and inflammatory activity in wild-derived PWD/PhJ mice, compared with the conventional laboratory strain C57BL/6J. Additionally, candidate MS-GWAS genes were significantly enriched among transcripts overrepresented in C57BL/6J cells compared to PWD. These expression level differences correlate with robust differences in susceptibility to experimental autoimmune encephalomyelitis, the principal model of MS, and skewing of the encephalitogenic T cell responses. Taken together, our results provide functional insights into the genetic regulation of the immune transcriptome, and shed light on how this in turn contributes to susceptibility to autoimmune disease.

overall_design: Gene expression in 5 different immune cell types from male and female C57BL/6J and PWD/PhJ mice; 3 biological replicates (each representing a pool of 3 independent mice) were used

middle: N

first: Cory

last: Teuscher


title: Development of gene expression signatures after knocking down of miR-132 in zebrafish

status: Public on Aug 09 2016

city: Shanghai

first: Jiu-lin

last: Du

address: 320 Yueyang Road

institute: Institute of Neuroscience

summary: To further development of the gene expression, we have employed whole genome microarray expression profiling as a discovery platform to identify genes that are regulated in miR-132 knockdown zebrafish. Zebrafish larvae were injected with Control MO or miR-132 MO at one-cell stage. Then the upregulated genes are combined to the miRNA prediction alagorithm. 21 genes were picked up and verifed by luciferase assay.

overall_design: The total RNA was extracted from 3 dpf zebrafish injected with 8 ng control or miR-132 MO MO. The RNA was applied for the microarray gene proliling

first: Bing

last: Xu


title: Extracellular matrix protein Matrilin-4 regulates HSC stress response

status: Public on Aug 17 2016

first: Hannah

last: Uckelmann

department: Stem Cells and Cancer

institute: German Cancer Research Center (DKFZ)

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

overall_design: Refer to individual Series


title: Comparative gene profiling study: Pak1 deficient mouse breast cancer cells vs Pak1 wt breast cancer cells

status: Public on Jul 23 2016

city: Tlalnepantla

first: Luis

middle: E.

last: Arias-Romero

address: Avenida de los Barrios #1

country: Mexico

institute: UBIMED

summary: To identify differentially regulated genes between wild-type and Pak1 deficient mouse breast cancer cells, we performed a comparative gene profiling study by using mouse whole genome arrays.

overall_design: We compared the gene expression profiles of Her2 positive : Pak1 deficient cells vs Her2 positive : Pak1 wild type cells. All the experiments were performed in duplicate using tumor derived cells from two different tumors per group.

middle: E

first: Jonathan

last: Chernoff


title: Gene expression analysis of PBS or IFNalpha treated wt hematopoietic stem cells (HSC)

summary: This study aimed at identifying the differences in expression levels between HSCs isolated from PBS or IFNa treated mice to determine the mechanism of activation of HSCs by IFNa.

overall_design: mRNA expression was analyzed from wt HSCs  isolated 16h post PBS/IFNa injection. 3 biological replicates were used per group.


title: Gene transcription profiles of spleen dentritic cells in mice infected with Schistosoma japonicum in N day, 28 day, 63 day

status: Public on Mar 31 2016

city: Whuhan

first: Lin

last: Chen

address: 185 Donghu Road

institute: Whuhan

summary: To explore the biological function of dentritic cells, the whole  expression profile microarray was adopted to investigate genes of N,28-day, 63-d dentrtic cells how to develop a role of immune regulation besides a gene expression map.

overall_design: In mice infected with Schistosoma japonicum, N-day, 28-day, 63-day spleen dentritic cells were sorted by flow cytometry, then RNA of the 3 timepoints was extracted for Agilent macroaary experiment.

first: Li

last: He


title: Type-I interferon inducible genes 26 weeks after mCMV infection in Siglec-H wt and Siglec-H ko mice and their non infected controls

status: Public on Mar 16 2016

city: Erlangen

first: Heike

last: Schmitt

address: Staudtstraße 5

department: Biology

institute: Friedrich Alexander University

summary: Type I interferons are critical anti-viral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The secretion of type I interferon of pDCs is modulated by Siglec-H, a DAP12 associated receptor on pDCs. We showed that Siglec-H deficient pDCs produce more of the type I interferon IFN-α in vitro and that Siglec-H ko mice produce more IFN-α after murine cytomegalovirus (mCMV) infection in vivo, leading to efficient clearance of the virus. Furthermore, ageing Siglec-H ko mice showed a mild form of systemic autoimmunity. In contrast, Siglec-H ko mice developed a severe form of systemic lupus-like autoimmune disease with strong kidney nephritis several weeks after a single mCMV infection. This induction of systemic autoimmune disease after virus infection in Siglec-H ko mice was accompanied by a type I interferon signature and fully dependent on type I interferon signaling. These results show that Siglec-H normally serves as modulator of type I interferon responses after infection with a persistent virus and thereby prevents induction of autoimmune disease.

overall_design: For microarray experiments gene expression profiles of total splenic cells from two wt and Siglec-H ko mice 26 weeks after infection with luciferase expressing murine Cytomegalovirus (5x105 pfu) or from two uninfected wt and Siglec-H ko control mice were analyzed

first: Sabrina

last: Sell

first: Julia

last: Koch

first: Sophia

last: Sonnewald

first: Christoph

last: Daniel

first: Thomas

middle: H

last: Winkler

first: Lars

last: Nitschke


title: Cell cycle regulatory mechanisms in skeletal muscle cells

status: Public on Jul 21 2016

city: Singapore

first: Vinay

middle: Kumar

last: Rao

address: 2 Medical drive

department: Physiology

country: Singapore

institute: NUS

summary: Genome wide gene expression analysis in G9a knockdown myoblasts

overall_design: Illumina WG-6 v2.0 arrays were hybridized with RNA from scrambled control and siG9a myoblasts to determine the gene expression profile murine skeletal myoblasts. All hybridizations were done in biological duplicates

middle: K

first: Shilpa

middle: R

last: Shankar

first: Ow

last: Rong

first: Narendra

last: Bharathy

first: Jayapal

last: Manikandan

first: Reshma

last: Taneja


title: Comparison of gene expression by microarray in diabetes antigen specific (NRP-V7), LCMV antigen specific (GP33), and  CD8+ T cells of similar phenotype from NOD mice

status: Public on Mar 17 2016

city: New Haven

first: Hailong

last: Meng

address: 300 George Str

summary: Type 1 diabetes mellitus (T1D) is caused by killing of insulin producing β cells by CD8+T cells. The disease progression accelerates as glucose tolerance deteriorates suggesting that acquired factors contribute. To identify how environmental factors may lead to the expansion and pathogenicity of the diabetogenic T cells, we analyzed diabetogenic NRP-V7-reactive CD8+ T cells that recognize a peptide from the diabetes antigen IGRP in prediabetic NOD mice.  There was an increase in the frequency of the NRP-V7-reactive cells coinciding with the time of glucose intolerance. The T cells persisted in hyperglycemic NOD mice maintained with an insulin pellet despite destruction of beta cells. We compared gene expression in the NRP-V7-reactive T cells to others that shared their phenotype but not selected for reactivity to diabetes antigens viral antigen reactive cells. Compared to these other cells, the NRP-V7-reactive cells exhibited gene expression of  memory precursor effector cells. They had reduced cellular proliferation and were less dependent on oxidative phosphorylation. When prediabetic NOD mice were treated with 2DG to block aerobic glycolysis, there was a reduction in the diabetes antigen vs other cells of similar phenotype and loss of lymphoid cells infiltrating the islets. In addition, treatment of NOD mice with 2DG resulted in improved cell granularity. These findings identify a link between metabolic disturbances and autoreactive T cells that promotes development of autoimmune diabetes.

overall_design: To distinguish the features of the autoreactive, viral antigen reactive CD8+ T cells from other cells in NOD mice that share the phenotype of these cells, we sorted CD8+ T cells that showed high expression of CD44, PD-1, CXCR3, and low expression of CD62L, and compared gene expression by microarray to the gp33 and NRP-V7 tetramer+ CD8+ T cells, sorted from the spleens mesenteric and pancreatic lymph nodes.

first: Justin

middle: W

last: Garyu

first: Mohamed

last: Uduman

first: Kevan

last: Herold

first: Steven

last: Kleinstein


title: Time course of gene expression signatures for Tet3 induced neurons

status: Public on Mar 03 2016

city: Beijing

first: Juan

last: Zhang

address: Beijing 100101, China

department: Institute of Zoology

institute: Chinese Academy of Sciences

summary: To further investigate the gene expression at different courses in MEFs and Tet3 induced neurons, we have employed whole genome microarray expression profiling as a discovery platform to identify the expression level of specific genes, such as neuronal specific genes, fibrobalst specific genes.

overall_design: The gene expression in mouse embryonic fibroblasts and Tet3 induced neurons at 1, 3, 5, 7 dpi.

first: Jianwei

last: Jiao


title: Mouse Primary Cultured Hepatocytes:  Control vs SQ1 or Pravastatin treatment.

status: Public on May 20 2016

city: Detroit

last: Kocarek

state: MI

address: 6135 Woodward Ave

department: Institute of Environmental Health Sciences

institute: Wayne State University

summary: Transcriptional profiling of mouse primary cultured hepatocytes comparing control (untreated), SQ1, and Pravastatin treated hepatocytes.

overall_design: Control (untreated) versus SQ1 or Pravastatin treated primary hepatocytes. Biological replicates: 8 control replicates, 8 treated replicates. 4 each using dye swap design.

first: T

middle: A


title: SIRT1 negatively regulates the differentiation of IL-9-producing CD4+T cells

status: Public on Jun 14 2016

city: SHANGHAI

first: Guangwei

last: Liu

state: SHANGHAI

address: DONGANROAD 130

department: Immunity

institute: Fudan University

summary: Distinct metabolic programs support the differentiation of CD4+T cells into their separate lineages. In this study, we investigated metabolic mechanisms underlying the differentiation of IL-9 producing-CD4+T cells (TH9) in allergic airway inflammation and cancerous tumors. We found here that SIRT1 negatively regulates TH9 differentiation. A deficiency of SIRT1 induced by either conditional deletion in mouse CD4+T cells or the use of small interfering RNA (siRNA) in mouse or human T cells increased IL-9 production, whereas ectopic SIRT1 expression inhibited it. Notably, SIRT1-inhibited the differentiation of TH9 cells that regulated anti-tumor immunity and allergic pulmonary inflammation. Glycolytic activation through the mTOR-hypoxia-inducible factor-1α (HIF1α) pathway was required for the differentiation of the TH9 cells that confer protection against tumors and are involved in allergic airway inflammation. Our results define the essential features of a SIRT1-mTOR-HIF1α signaling-coupled glycolytic pathway in inducing TH9 cell differentiation, with implications for metabolic reprogramming as an immunotherapeutic approach.

overall_design: Lymphocytes were isolated from the spleen and lymph nodes of mice and sorted on a FACSAria II (Becton Dickinson). The sorted naïve T cells (CD4+TCR+CD62Lhi CD44lo) from WT or SIRT1flox/flox-CD4-Cre mice were used for in vitro culture. T cells were activated with 2 ug/ml anti-CD3 (2C11; Bio X Cell), 2 ug/ml anti-CD28 (37.51; Bio X Cell) and 100 U/ml human IL-2. For TH9 cell differentiation, cultures were supplemented with 10 ng/ml IL-4 (R&D system), 2 ng/ml TGFβ1 (R&D system). After 5-6 d culture, differentiated T cells were collected and for microarray assay.

first: Yu

last: Wang

first: Yujing

last: Bi

first: Chen

last: Xi

first: Chunxiao

last: Li

first: Yan

first: Zhengguo

first: Jian

first: Yun

last: Lu

first: Huanrong

first: Huilin

last: Shu

first: Hui

last: Yang


title: Transcriptional response induced by enteropathogenic Escherichia coli (EPEC) in mouse intestinal epithelial cells in vivo

status: Public on Apr 20 2016

city: Aachen

first: Mathias

last: Hornef

address: Pauwelstr. 30

department: Institute for Medical Microbiology

institute: University Hospital RWTH Aachen

summary: In order to identify genes that were differentally regulated upon oral infection with EPEC, we isolated 8 days post-infection intestinal epithelial cells (IECs) from the small intestine of C57BL/6 neonate mice that were left untreated or orally infected with 5x104 WT EPEC E2348/69 or with 5x104 of the isogenic mutant ΔescV on their first day of life.

overall_design: RNA from small intestinal epithelial cells isolated 8 days post-infection from newborn mice orally infected at birth with WT EPEC, ΔescV or left untreated. Each sample corresponds to one animal; 4 or 6 animals from 2 or 3 different litters were used per group. Single color array

first: Aline

last: Dupont


title: Gene expression analysis of transplanted wt and Matn4-/- hematopoietic stem cells (HSC)

city: Heidelberg

first: Hannah

last: Uckelmann

address: Im Neuenheimer Feld 280

summary: This study aimed at identifying the differences in expression levels between wt and Mant4-/- HSCs after transplantation, to determine the mechanism through which Mant4-/- gain a proliferative advantage.

overall_design: mRNA expression was analyzed from Matn4-/- and wt HSCs  isolated 4 weeks after transplantation into lethally irradiated recipients. 3 biological replicates were used per group.


title: Expression data from squalestatin 1- or pravastatin-treated primary cultured mouse and rat hepatocytes.

first: Thomas

sample_organism:
Mus musculus
Rattus norvegicus

platform_organism:
Mus musculus
Rattus norvegicus


title: Hepatic transcriptome of mice fed high fat diets containing palm or linseed oil

status: Public on May 18 2016

city: Villenave d'Ornon

first: Pascal

middle: GP

last: Martin

address: 71 avenue Edouard Bourlaux

department: UMR1332 BFP

country: France

institute: INRAE

summary: The beneficial effects of dietary long-chain (LC) n-3 polyunsaturated fatty acids (PUFA) in the prevention and/or treatment of some metabolic disorders result largely from their capacity to regulate the transcription level of many genes involved in metabolic and physiological homeostasis, especially in the liver. In this respect, they are known to bind and activate the Peroxisome Proliferator-Activated Receptor alpha (PPARalpha). The precursor of LC-PUFA, a-linoleic acid (ALA, C18:3 n-3) share some beneficial metabolic effects with its LC derivatives, however its role in gene regulation is poorly documented. Here, we analysed the hepatic transcriptome of mice fed for 5 weeks diets rich in either saturated FA from palm oil (PALM group) or ALA from linseed oil (LIN group). This modification of dietary fatty acid composition in a context of a high fat diet had a subtle but significant effect on the hepatic transcriptome. We identified mainly a group of genes that were upregulated in the LIN vs the PALM group and that include several well-known PPARalpha target genes involved in lipid and xenobiotic metabolism.

overall_design: Liver gene expression was measured in male C57BL/6J mice fed during 5 weeks a high fat diet (51% energy from fat) containing palm oil, rich in saturated fatty acids (n=10) or linseed oil, rich in 18:3 n-3 (n=8)

middle: G

first: Najoua

last: Guelzim

first: Frédéric

last: Lasserre

first: Yannick

last: Lippi

first: Dominique

last: Hermier


title: Progression from low- to high-grade astrocytoma is characterized by transcriptomal heterogeneity and genomic number copy alterations (part 2)

status: Public on Feb 01 2016

city: Chapel HIll

first: Ryan

last: Miller

state: North Carolina

department: Pathology

institute: University of North Carolina

summary: We used genetically-engineered mice (GEM) to target constitutive RTK effector pathway (KrasG12D and/or Pten deletion) mutations in G1/S checkpoint-defective adult mouse astrocytes.  Genetic lineage tracing showed that these mutations potentiated tumor initiation in cortical, diencephalic, brainstem, and olfactory bulb astrocytes, producing low-grade astrocytomas (LGA).  LGA lacked copy number abnormalities (CNA), but showed oncogenic driver- and astrocyte location-specific transcriptome profiles, suggesting that both driver mutations and cellular origin contribute to LGA genomic heterogeneity.  Progression to high-grade astrocytomas (HGA) occurred stochastically, in part through location-specific acquisition of CNA.  HGA transcriptomes were heterogeneous and consisted of three subtypes that were also evident in GEM HGA with different oncogenic drivers and cellular origins.  HGA subtypes expressing immune/invasion, proliferation, and neuronal genes mimicked human mesenchymal, proneural, and neural GBM, respectively.  HGA subtypes also expressed distinct neural lineage signatures and were correlated with astrocyte location, but not oncogenic driver mutations.  These results suggest that oncogenic drivers influence LGA subtype and that regional astrocyte identity and progression-acquired CNA contribute strongly to HGA transcriptomal heterogeneity.  Defining tumor-initiating and progression-acquired mutations and the cells in which they occur would facilitate molecular classification and development of molecularly targeted strategies to manage GBM.

overall_design: Microarray analysis was completed for 43 high-grade astrocytoma, consisting of 3 genotypes.  HGA transcriptomes were heterogeneous and consisted of three subtypes that were also evident in gentically engineered mice HGA with different oncogenic drivers and cellular origins (see manuscript).  HGA subtypes expressing immune/invasion, proliferation, and neuronal genes mimicked human mesenchymal, proneural, and neural GBM, respectively.  HGA subtypes also expressed distinct neural lineage signatures and were correlated with astrocyte location, but not oncogenic driver mutations.  These results suggest that oncogenic drivers influence LGA subtype and that regional astrocyte identity and progression-acquired CNA contribute strongly to HGA transcriptomal heterogeneity.

first: Mark

last: Vitucci

first: Christopher


title: Cortex PS2 APP transgenic mice

status: Public on Jan 26 2016

city: South San Francisco

first: Brad

last: Friedman

address: 1 DNA Way

department: Bioinformatics

institute: Genentech, Inc.

summary:
Gene Expression profiles from whole cortical tissue from the PS2APP transgenic mouse model of Alzheimer's disease will reflect the cellular alterations, including the pathological drivers and the compensatory mechanisms of neurodegeneration when compared to wild-type control animals.
The "SAMID" sample characteristic is a sample identifier internal to Genentech.
The ID of this project in Genentech's ExpressionPlot database is PRJ0006684

Keywords: Expression profiling by array

overall_design: 5 Male transgenic and 5 Male wild-type mice were perfused and sacrificed at 3 months (earliest behavioral changes), 7 months (inflammation and plaque pathology), or 13 months (spreading synapse loss) of age. Hemicortices were subdissected and flash frozen prior to RNA extraction using the RNeasy Lipid Tissue extraction kit with on-column Dnase digestion.

first: Ben

last: Lauffer

first: David

last: Hansen


title: Development of gene expression signatures for identifying novel factors that can overcome age-associated reprogramming barriers

city: Daejeon

first: Yee Sook

last: Cho

address: 125 Gwahak-ro

institute: Korea Research Institute of Bioscience and Biotechnology

summary: To investigate the molecular features underlying senescence and rejuvenation during aged cell reprogramming and identify novel factors that can overcome age-associated barriers, we compared gene expression for reprogramming intermediates on D8 of tail-tip fibroblasts (TTFs) from young Wild Type (WT), old WT, and old p16 knockout (KO) mice.

overall_design: We collected TTFs from young WT, old WT, and old p16 KO mice and reprogrammed the cells by introducing four reprogramming factors, including Oct4, Sox2, Klf4, and c-Myc. Gene expression of reprogramming intermediates on D8 were compared. Two independent experiments were performed using different mice donors for each experiment.

first: Myung

last: Son

first: Youjeong

last: Kwon

first: Taekwon

first: Yee

middle: S


title: The alarmin IL-33 amplifies an immune response in the degenerating retina

status: Public on Dec 17 2015

last: McCreary

state: California

address: 1 DNA Way, MS 93

institute: Genentech

summary: ST2 heterodimerizes with IL-1RAcp to form the receptor for IL-33, which is primarily associated with allergic inflammation by inducing Th2 responses. Recently, however, IL-33 was found to be expressed in the central nervous system and in retinal Muller cells which imply functions, as yet undescribed, beyond Th2 mediated inflammation. Muller cells support the health of the retina and photoreceptors and are also involved in inflammation in retinal degeneration. It is not known how IL-33/ST2 functions in this capacity. We recently found that ST2 ko mice are protected from CLE-induced photoreceptor loss, implying a detrimental effect of IL33/ST2 in CLE. We wish to perform microarray analysis using WT and ST2 KO mice in CLE model to better understand the mechanism by which IL-33/ST2 regulates retinal degeneration.

overall_design: CLE (Constant Light Exposure) is a model of retinal damage/degeneration in mice. Mice are exposed to bright light 24 hours a day for a period of time which damages retina photoreceptors. This damage is assessed by histology, optical coherence tomography (OCT), which measures retina thickness in vivo. In this experiment, the WT and ST2 KO mice (5 mice per genotype per time point) will be exposed to 1200-lux constant light for 0, 3, 10 days. The retinal RNA will be isolated and analyzed for differential gene expression by microarray.

first: Hongkang

last: Xi

first: Kenneth

last: Katschke Jr

first: Yun

last: Li

first: Tom

last: Truong

first: Wyne

last: Lee

first: Lauri

last: Diehl

first: Linda

last: Rangell

first: Jianhua

last: Tao

first: Rommel

last: Arceo

first: Jeffrey

last: Eastham-Anderson

first: Jason

last: Hackney

first: Antonio

last: Iglesias

first: Javier

last: Cote-Sierra

first: Justin

last: Elstrott

first: Robby

middle: M

last: Weimer

first: Menno

last: van Lookeren Campagne


title: Progression from low- to high-grade astrocytoma is characterized by transcriptomal heterogeneity and genomic number copy alterations

first: Ryan

last: Miller

type: Genome variation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Development of gene sets after deleting Rb in p53 null background primary prostate cells [Rb only]

status: Public on Dec 31 2015

city: Kanazawa

first: Takumi

last: Nishiuchi

address: 13-1 Takaramachi

institute: Kanazawa University

summary: Our findings suggested that cytokines were upregulated in p53 null primary prostate cells after deleting Rb. Rb deletion is important for prostate cancer progression.

overall_design: p53-/- Rbf/f vs p53-/- Rb∆f/∆f primary prostate cells.Three independent experiments were performed.

first: Mohammed

last: Salah

first: Chiaki

last: Takahashi


title: Influenza H3N2 infection of the Collaborative Cross founder strains reveals highly divergent host responses and identifies a unique phenotype in CAST/EiJ mice

city: Braunschweig

first: Robert

last: Geffers

address: Inhoffenstr. 7

institute: HCI - Helmholtz Centre for Infection Research


title: Gene expression analysis to identify Runx1 target genes in GMP

status: Public on Jul 01 2016

city: Hamburg

first: Kira

last: Behrens

address: Martinistrasse 52

institute: Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology

summary: Disrupting mutations of the RUNX1 gene are found in 10% of patients with myelodysplasia (MDS) and 30% of patients with acute myeloid leukemia (AML). Previous studies have revealed an increase in hematopoietic stem cells (HSCs) and multipotent progenitor (MPP) cells in conditional Runx1-knockout (KO) mice, but the molecular mechanism is unresolved. We investigated the myeloid progenitor (MP) compartment in KO mice, arguing that disruptions at the HSC/MPP level may be amplified in downstream cells. We demonstrate that the MP compartment is increased more than fivefold in Runx1 KO mice, with a prominent skewing toward megakaryocyte (Meg) progenitors. Runx1- deficient granulocyte-macrophage progenitors are characterized by increased cloning capacity, impaired development into mature cells, and HSC and Meg transcription signatures. An HSC/MPP subpopulation expressing Meg markers was also increased in Runx1-deficient mice. Rescue experiments coupled with transcriptome analysis and Runx1 DNA-binding assays demonstrated that commitment is marked by Runx1 suppression of genes encoding adherence and motility proteins (Tek, Jam3, Plxnc1, Pcdh7, and Selp) that support HSC–Meg interactions with the BM niche. In vitro assays confirmed that enforced Tek expression in HSCs/MPPs increases Meg output. Interestingly, besides this key repressor function of Runx1 to control lineage decisions and cell numbers in progenitors, our study also revealed a critical activating function in erythroblast differentiation, in addition to its known importance in Meg and granulocyte/monocyte (G/M) maturation. Thus both repressor and activator functions of Runx1 at multiple hematopoietic stages and lineages likely contribute to the tumor suppressor activity in MDS and AML.

overall_design: GMP were isolated either from Runx1+/+-Tg(vav-Cre) and Runx1fl/fl-Tg(vav-Cre) mice or from mice transplanted with Runx1fl/fl-Tg(vav-Cre) progenitors engineered to express GFP with RUNX1-ERt2 or ERt2. RUNX1-ERt2 activity was induced by i.p. injection of tamoxifen on 3 consecutive days prior to GMP isolation.

first: Carol

last: Stocking


title: Identification of endothelial genes co-regulated upon endothelial Evi/Wls and Rspo3 deletion

status: Public on Feb 03 2016

first: Hellmut

last: Augustin

institute: German Cancer Center (DKFZ)

summary: Inducible endothelial Rspo3 deletion resulted in perturbed developmental and tumor vascular remodeling. Rspo3-iECKO mice strikingly phenocopied the non-canonical WNT signaling-induced vascular defects of mice deleted for the WNT secretion factor Evi/Wls. An endothelial screen for RSPO3 and EVI/WLS co-regulated genes identified novel target genes, which could be linked to WNT/Ca2+/NFAT signaling. In summary, the study identifies endothelial RSPO3-driven non canonical WNT/Ca2+/NFAT signaling as critical maintenance pathway of the remodeling vasculature.

overall_design: 10 samples (2 replicates Rspo3-WT; 3 replicates Rspo3-iECKO; 3 replicates Evi-WT; 2 replicates Evi-iECKO)

first: Beate

last: Scholz

first: Claudia

last: Korn


title: Gene expression profile of the V/SVZ and the CP at E16

status: Public on Jan 01 2016

city: Tokyo

first: Itsuki

last: Ajioka

address: 1-5-45 Yushima, Bunkyo-ku

department: Center for Brain Integration Research

institute: Tokyo Medical and Dental University

summary: Cell differentiation and proliferation are mutually exclusive. Although differentiating neurons are recognized as post-mitotic non-dividing cells, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons proliferate and form tumor. Here, we found that the acute inactivation of all Rb family in differentiating cortical excitatory neurons caused radial migration defect and S-phase progression but not cell division, whereas that in cortical progenitors caused the cell division of the differentiating neurons generated from Rb –/–; p107 –/–; p130 –/– (Rb-TKO) progenitors. Genome-wide DNA methylation analysis revealed that proximal promoters tended to become methylated during differentiation in vivo. DNA demethylation by DNA methyltransferase inhibitor allowed the acutely inactivated Rb-TKO differentiating neurons to undergo G2/M-phase progression. Our finding illustrate that cortical excitatory neurons epigenetically lose their proliferative potency after neurogenesis.

overall_design: 4 samples of the V/SVZ (ventricular/subventricular zone) tissue and 4 samples of the CP (cortical plate) tissue

first: Mio

last: Oshikawa


title: Influenza H3N2 infection of the Collaborative Cross founder strains reveals highly divergent host responses and identifies a unique phenotype in CAST/EiJ mice (blood)

summary: To determine if genetic background can modulate severity of an infection, we studied the host responses to influenza infections in the eight genetically highly diverse Collaborative Cross (CC) founder mice.

overall_design: The CC founder (C57BL/6J, 129S1/SvlmJ, CAST/EiJ, PWK/PhJ) were intranasally infected with influenza A/HK/01/68 (H3N2) with 20μl virus solution (1x101 ffu) or mock infected (with PBS). After infection lung was collected at different time points (mock_d3), d3, d5).

first: K

last: Schughardt

first: H

last: Kollmus

first: R


title: Effects of Triclosan exposition on fetal hypothalamic transcriptomics

status: Public on Feb 29 2016

city: Utrecht

first: Maria

middle: Belen

last: Rabaglino

address: Yalelaan 7

department: Population Health Science

country: Netherlands

institute: Utrecht University

summary: Triclosan (TCS), an antibacterial compound commonly added to personal care products, could be an endocrine disruptor at low doses. Although TCS has been shown to alter fetal physiology, its effects in the developing fetal brain are unknown. The objective of this study was to use transcriptomics and systems analysis to determine significantly altered biological processes in the late gestation ovine fetal hypothalamus after direct or indirect exposure to low doses of TCS. We found that short-term infusion of TCS induces vigorous changes in the fetal hypothalamic transcriptomics, which are mainly related to food intake pathways and metabolism.

overall_design: For direct TCS exposure, chronically catheterized late gestation fetal sheep were infused with vehicle (n=4) or TCS (250 μg/day; n=4) iv. For indirect TCS exposure, TCS (100 μg/kg/day; n=3) or vehicle (n=3) was infused into the maternal circulation. Fetal hypothalami were collected after 2 days of infusion, and gene expression was measured using Agilent 15k ovine microarrays.

middle: B

first: Eileen

middle: I

last: Chang

first: Elaine

last: Richards

first: Margaret

middle: O

last: James

first: Maureen

last: Keller-Wood

first: Charles

last: Wood


title: Core pathway mutations induce de-differentiation of murine astrocytes into glioblastoma stem cells that are sensitive to radiation but resistant to temozolomide.

status: Public on Jan 31 2016

first: Ryan

last: Miller

summary:
BACKGROUND:

Glioma stem cells (GSCs) from human glioblastomas (GBMs) are resistant to radiation and chemotherapy and may drive recurrence. Treatment efficacy may depend on GSCs, expression of DNA repair enzymes such as methylguanine methyltransferase (MGMT), or transcriptome subtype.

METHODS:

To model genetic alterations in human GBM core signaling pathways, we induced Rb knockout, Kras activation, and Pten deletion mutations in cortical murine astrocytes. Neurosphere culture, differentiation, and orthotopic transplantation assays were used to assess whether these mutations induced de-differentiation into GSCs. Genome-wide chromatin landscape alterations and expression profiles were examined by formaldehyde-assisted isolation of regulatory elements (FAIRE) seq and RNA-seq. Radiation and temozolomide efficacy were examined in vitro and in an allograft model in vivo. Effects of radiation on transcriptome subtype were examined by microarray expression profiling.

RESULTS:

Cultured triple mutant astrocytes gained unlimited self-renewal and multilineage differentiation capacity. These cells harbored significantly altered chromatin landscapes that were associated with downregulation of astrocyte- and upregulation of stem cell-associated genes, particularly the Hoxa locus of embryonic transcription factors. Triple-mutant astrocytes formed serially transplantable glioblastoma allografts that were sensitive to radiation but expressed MGMT and were resistant to temozolomide. Radiation induced a shift in transcriptome subtype of GBM allografts from proneural to mesenchymal.

CONCLUSION:

A defined set of core signaling pathway mutations induces de-differentiation of cortical murine astrocytes into GSCs with altered chromatin landscapes and transcriptomes. This non-germline genetically engineered mouse model mimics human proneural GBM on histopathological, molecular, and treatment response levels. It may be useful for dissecting the mechanisms of treatment resistance and developing more effective therapies.

overall_design:
Conditional Rb knockout (T), Kras activation (R), and Pten deletion (P) mutations were induced in cortical murine astrocytes from C57BL/6 mice to model genetic alterations in the core signaling pathways of human GBM.  Primary astrocytes were cultured as previously described. Briefly, cells were selectively harvested from the cortices of T, TR, and TRP postnatal day 1-4 pups, dissociated by trituration in trypsin, and incubated at 37°C for 20 minutes.  Cells were pelleted, resuspended, and cultured in DMEM supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin (complete media).  At 50% confluence, cells were infected with a recombinant adenoviral vector expressing Cre recombinase from the constitutive cytomegalovirus promoter (Ad5CMVCre, University of Iowa Gene Transfer Vector Core) at an MOI of 50 for 6 hours in complete media.3  Following infection, cells were rinsed in PBS and serially cultured in complete media at 37°C in 5% CO2 for up to 60 passages.  Efficacy of radiation and temozolomide was examined in an orthotopic allograft model of proneural GBM and expression profiling was used to examine the effects of radiation on transcriptomal subtype.  To evaluate the effects of treatment, syngeneic C57BL/6 mice were injected with 10^5  TRP astrocytes.  Tumors were established for six days and mice (9-12 per group) were randomized to treatment with temozolomide (100 mg/kg q.d. via intraperitoneal injection on days 6-10), radiation (5 Gy on days 6, 8, and 10), or both.  Animals were monitored by an observer blinded to treatment group and sacrificed upon development of neurological symptoms, at which point mice were sacrificed, tumors macrodissected, and flash frozen.  Survival was evaluated by the Kaplan-Meier method and effects of treatment compared by log-rank tests.

Microarray analysis was completed for 37 high-grade astrocytoma allografts that were either untreated or radiation treated.

first: Mark

last: Vitucci

first: Christopher


title: Influenza H3N2 infection of the Collaborative Cross founder strains reveals highly divergent host responses and identifies a unique phenotype in CAST/EiJ mice (lung)

first: Robert

last: Geffers

department: Dep. Molecular Bacteriology


title: Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival

status: Public on Nov 23 2015

city: St. Louis

first: Jinsheng

last: Yu

state: MO

address: 660 S. Euclid Ave.

department: Genetics

institute: Washington University School of Medicine

summary:
Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing identified multiple SI stem cell populations, marked by Lgr5, Bmi1 or HopX expression, that contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.
Intestines were harvested 3 h post-etoposide injection, flushed with PBS, and then flushed with ice-cold Methacarn (60% methanol, 30% chloroform, 10% acetic acid) to fix the tissue while preserving RNA integrity. Fixed intestines were rinsed with 70% ethanol, embedded in 2% agar followed by paraffin embedding. Sections were deparrafinized and dehydrated through xylene and an increasing gradient of ethanol. Laser capture microdissection was performed using the Acturus PixCell IIe, with the following settings: spot size power 80, duration 1 ms, repeat 0.2 s, target 0.150 V, current 1.82 mA. RNA was isolated from the CapSure HS LCM Caps (Applied Biosystem) using the PicoPure RNA Isolation kit (Applied Biosystems). All RNA samples were treated with DNaseI (Qiagen).

overall_design: Four biological replicates were used for each of the following treatments: Fasted Etoposide, Fed Etoposide.  Each group had 2 male and 2 females samples. 4-6 week old Lgr5EGFP-IRES-CreERT2/+ mice were dosed with 80mg/kg etoposide (i.v.).

first: Helen

last: Piwnica-Worms

first: David

first: Kelsey

middle: L

last: Tinkum


title: Gene expression profiling of thymocytes from conditional knock-out mice (FoxN1-Cre mediated KO of Gpr177)

status: Public on Nov 01 2015

first: Fabian

last: Brunk

institute: German Cancer Research Center

summary: Comparative gene expression profiling of thymocytes at the DP, CD4 SP and CD8 SP stage derived from FoxN1-Gpr177 mice (FoxN1-Cre mediated deletion of (Exon3 of) Gpr177/Wtls) or C57Bl/6N mice as comparison. Objective was to test the influence of TEC-secreted Wnt ligands on the transcriptome of thymocytes at the respective developmental stages.

overall_design: Total RNA extracted from FACS-sorted primary mouse thymocytes. CD4/8 double positive (DP) thymocytes,  CD4 single positive (CD4 SP) thymocytes and CD8 single positive (CD8 SP) thymocytes were FACS-sorted from conditional knock-out mice (FoxN1-Gpr177) and C57Bl/6N mice as comparison.

first: Bruno

last: Kyewski


title: Proteomic evaluation of the hepatocyte secretome identifies Fetuin B as a factor linking steatosis to impaired glucose metabolism

status: Public on Oct 22 2015

city: Clayton

first: Matthew

last: Watt

state: VIC

address: Monash University

department: Department of Physiology

country: Australia

institute: Faculty of Medicine, Nursing and Health Sciences

summary: The experiment examined the changes in gene expression in heptocytes isolated from mice with normal (non-fatty) livers or mice with simple steatosis induced by short-term high-fat feeding (6 weeks)

overall_design: Four biological replicates of RNA samples from isolated hepatocytes derived from C57Bl/6 mice fed a high fat diet (HFD) are compared to four biological replicates of RNA samples from isolated hepatocytes of C57Bl/6 mice fed a normal diet (chow)

first: Ruth

last: Meex


title: Genome-wide analysis of  TRA (tissue restricted antigen)-specific co-expression groups  in mouse medullary thymic epithelial cells (mTECs)

status: Public on Oct 28 2015

first: Kristin

last: Rattay

summary: Analysis of gene co-expression patterns in TRA-specific medullary thymic epithelial cell (mTEC) subsets. The whole genome gene signatures of purified mTEC subsets respectively positive for the TRAs Gp2, Pdpn, Cea1, Gad1, Ins2, Tspan8 were compared to their corresponding TRA-negative mTEC subset control. Results provide the enriched and depleted gene expressions in the different subsets.

overall_design: Total RNA obtained from FACS isolated mTECs positive for the respective TRAs were compared to their TRA-negative mTEC subsets using specific antibodies (Pdpn, Gp2, Cea1, Tspan8) or reporter mice (Gad1, Ins2).


title: Characterization of polysome enriched mRNAs following insulin treatment

status: Public on Oct 01 2015

city: Milan

first: Daniela

last: Brina

address: Via Sforza 35

country: Italy

institute: INGM

summary: To characterize RNA distribution on total and polysomal fractions of hepatocytes, we have employed whole genome microarray expression profiling as a discovery platform to identify differentially abundant mRNAs on polysomes.

overall_design: Insulin induced gene expression in Aml12 hepatocytes were measured at 1 hours after treatment (100 mM). Four replicate experiments were performed.

first: Gabriella

last: Viero

first: Toma

last: Tebaldi


title: Gene Expression Profiling of Murine Melanomas Exhibiting Differential Tumorigenicities

status: Public on Sep 29 2015

city: Hampden-Sydney

first: Kristian

middle: Michael

last: Hargadon

state: VA

address: Brown Student Center, Box 837

institute: Hampden-Sydney College

summary: The goal of this study was to compare the gene expression profiles of a highly versus poorly tumorigenic murine melanoma.  B16-F1 is a well-characterized murine melanoma cell line that grows progressively in hosts, both as primary tumors in subcutaneous tissue and as metastatic lesions in internal organs.  D5.1G4 is a chemically mutated variant of B16 melanoma that grows with significantly slower kinetics than its wild-type counterpart.  Whole genome expression microarray analysis of RNA isolated from these murine melanoma lines was performed to provide insights into factors that regulate the growth and metastasis of these tumors, which are useful models for investigating in a murine system the outgrowth, progression, and control of a cancer type that is prevalent in humans worldwide.

overall_design: B16-F1 or D5.1G4 melanoma cells were cultured for 24 hours before isolating RNA for whole genome expression analysis using the Agilent Mouse 4x44K Gene Expression Microarray v2 (Agilent Design ID 026655).  Samples were run in replicates of three.  D5.1G4 melanoma served as the reference sample, and genes expressed at 2-fold higher or lower levels in B16-F1 (with a p value ≤ 0.05) were defined as genes exhibiting differential expression between the two tumors with statistical significance.


title: Puberty-specific promotion of mammary tumorigenesis by a high animal fat diet

status: Public on Oct 14 2015

city: Chapel Hill

first: Melissa

last: Troester

state: NC

address: 2104H McGavran-Greenberg 135 Dauer Drive Campus Box 7435 27599-7435

department: Center for Environmental Health Sciences Integrated Sciences Facility Corencer Center

institute: University of North Carolina at Chapel Hill

summary: Gene expression for genes differentially expressed between early vs. late tumor onset and high fat diet (HFD) vs. low fat diet (LFD) in mice.

overall_design: 2 class analysis of early vs late tumor onset samples; 5 LFD late tumor onset, 3 HFD early tumor onset, 6 HFD late tumor onset, 4 LFD-HFD late tumor onset, 3 HFD-LFD early tumor onset, 3 HFD-LFD late tumor onset

first: Rich

last: Schwartz

first: Sandy

last: Haslam


title: Adenoviral vector vaccination induces a conserved program of CD8+ T cell memory differentiation in mouse and man

status: Public on Sep 23 2015

city: Oxford

first: Timothy

last: Hinks

state: United Kingdom

address: John Radcliffe Hospital, Headley Way, Oxford

department: NDM Experimental Medicine - New College

institute: University of  Oxford

summary: Following exposure to vaccines, antigen-specific CD8+ T-cell responses develop as long-term memory pools. Novel vaccine strategies based on adenoviral vectors, e.g. those developed for HCV, are able to induce and sustain substantial CD8+ T-cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T-cell memory pools induced  by an adenoviral vector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include up-regulation of homing receptors, and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet (TBX21). In humans, a novel adenovirus vaccine induced similar CMV-like phenotypes and underlying transcription factor regulation. These data clarify the core features of CD8+ T-cell memory following vaccination with adenovirus vectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.

overall_design: Total RNA was extracted from sorted memory CD8 T cells induce by CMV and adenoviral vectors, and naïve CD8 cells

first: Beatrice

last: Bolinger

first: Stuart

last: Sims

first: Leo

last: Swadling

first: Geraldine

last: O’Hara

first: Catherine

last: de Lara

first: Dilair

last: Baban

first: Natasha

last: Saghal

first: Lian

middle: N

last: Lee

first: Emanuele

last: Marchi

first: Mark

last: Davis

first: Evan

last: Newell

first: Stefania

last: Capone

first: Antonella

last: Folgori

first: Ellie

last: Barnes

first: Paul

last: Klenerman