title: Expression data on Treg cells isolated from wildtype mice and miR-125a deficient mice

status: Public on May 08 2015

city: Shanghai

last: Shen

address: 145 Shan  Dong  Middle Road

institute: Renji Hospital, JiaoTong University School of Medicine

summary: We found miR-125a was a key regulator that stabilizes the commitment and immunoregulatory capacity of Treg cells.To gain insights into the general functional features of miR-125a-deficient Treg cells, we performed a genome-wide gene array analysis on Treg population isolated from the spleens of 6 to 8-week-old miR-125a-deficient and WT mice

overall_design: We sorted CD4+CD25hi Treg population from the spleens of 6 to 8-week-old miR-125a-deficient and their littermate WT mice. Cells were collected and total RNA was extracted for Affymetrix GeneChip®Mouse Genome 430 2.0 Array

first: Wen

last: Pan


title: Cardioprotective signature of short-term caloric restriction

city: Toronto

first: Mansoor

last: Husain

state: Ontario

address: Room TMDT-3-910, 101 College St.

department: Toronto Gen. Hosp. Res Institute

country: Canada

institute: University Health Network

summary: OBJECTIVE: To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR).  BACKGROUND: Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we show how short-term CR protects the mouse heart from ischemia.  METHODS:  Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food over a period of 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. Prior to MI (d8), the left ventricles (LV) of AL and CR mice were collected for Western blot, DNA and microRNA (miR) analyses.  In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI.   RESULTS: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). cDNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM).  Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38).   CONCLUSIONS: Short-term CR for only 7d represents a preconditioning strategy that limits infarct size. It is associated with a unique gene and miR signature, including the activation of specific pro-survival kinases. These findings may have implications for therapeutic use of short-term CR.  .

overall_design: Male 12 wk-old C57Bl/6 mice were obtained from Charles River (Montreal, PQ, Canada) and maintained for at least 2 weeks before experimentation. Animals were randomly assigned to AL, CR and Lira groups with no initial differences in body weights. AL group mice were allowed ad libitum diet. Lira group mice were injected with Liraglutide (Glucagon-like peptide-1 agonist) at a dose of 200 µg/Kg i.p., twice daily for 7 days which is a mild weight-loss inducing dose and had access to ad libitum food and water. CR group mice were put on a Caloric restriction diet (30% less than normal ad libitum caloric intake) for 7 days to induce weight loss comparable to Lira group mice.  Mice for CR and AL were individually caged and their food intake was measured everyday between 10-11 am for 1 week to calculate the average daily food intake.  CR mice were fed 30% less than the calculated mean daily AL food consumption.  CR cages were inspected daily for any remaining food, and transferred to a new cage every day. For CR  group, pre-weighed mouse chow pellets were placed in cages between 10-11 am every day.  Body weights were recorded between 10-11 am before and after the 7 day study period. For pre-ischemic assessments, animals (n=5/group/assessment) were sacrificed on day-8 (pre-MI), hearts were immediately extracted, washed in sterile phosphate-buffered saline (PBS), with LV free walls dissected, snap frozen in liquid nitrogen and stored at -80o C.

first: Hossein

last: Noyan

first: Omar

last: El-Mounayri


title: caArray_bonda-00136: Molecular basis of age associated cytokine dysregulation in LPS stimulated macrophages

status: Public on May 06 2015

city: Rockville

first: Mervi

last: Heiskanen

state: MD

address: 9609 Medical Center Drive, 1W378

department: CBIIT

country: USA

institute: NCI

summary: Aged humans and rodents are susceptible to infection with Streptococcus pneumoniae bacteria as a result of an inability to make antibodies to capsular polysaccharides. This is partly a result of decreased production of proinflammatory cytokines and increased production of interleukin (IL)-10 by macrophages (Mphi) from aged mice. To understand the molecular basis of cytokine dysregulation in aged mouse Mphi, a microarray analysis was performed on RNA from resting and lipopolysaccharide (LPS)-stimulated Mphi from aged and control mice using the Affymetrix Mouse Genome 430 2.0 gene chip. Two-way ANOVA analysis demonstrated that at an overall P < 0.01 level, 853 genes were regulated by LPS (169 in only the young, 184 in only the aged, and 500 in both). Expression analysis of systematic explorer revealed that immune response (proinflammatory chemokines, cytokines, and their receptors) and signal transduction genes were specifically reduced in aged mouse Mphi. Accordingly, expression of Il1 and Il6 was reduced, and Il10 was increased, confirming our previous results. There was also decreased expression of interferon-gamma. Genes in the Toll-like receptor-signaling pathway leading to nuclear factor-kappaB activation were also down-regulated but IL-1 receptor-associated kinase 3, a negative regulator of this pathway, was increased in aged mice. An increase in expression of the gene for p38 mitogen-activated protein kinase (MAPK) was observed with a corresponding increase in protein expression and enzyme activity confirmed by Western blotting. Low doses of a p38 MAPK inhibitor (SB203580) enhanced proinflammatory cytokine production by Mphi and reduced IL-10 levels, indicating that increased p38 MAPK activity has a role in cytokine dysregulation in the aged mouse Mphi.

overall_design:
bonda-00136
Assay Type: Gene Expression
Provider: Affymetrix
Array Designs: Mouse430_2
Organism: Mus musculus (ncbitax)


title: Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

status: Public on May 07 2015

city: Buffalo

first: Jiho

last: Sohn

state: New York

address: 3435 Main Street, 644 Biomedical Research Building

department: Oral Biology

institute: SUNY Buffalo

summary: Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux.  In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Using a mouse model mimicking pediatric antibiotic use, we found that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide altered both host and microbiota development. Early-life PAT accelerated total mass and bone growth, and resulted in progressive changes in gut microbiome diversity, population structure, and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. While control microbiota rapidly adapted to a change in diet, PAT slowed the ecological progression, with delays lasting several months in response to the macrolide. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

overall_design: C57BL/6J mice received three antibiotic courses: at days 10-15, 28-31, and 37-40 of life, amoxicillin or tylosin.Livers were collected at age 22 weeks, RNA was extracted, and transcriptional differences were measured by microarray analysis.

first: Yael

middle: R

last: Nobel

first: Laura

middle: M

last: Cox

first: Francis

middle: F

last: Kirigin

first: Nicholas

middle: A

last: Bokulich

first: Shingo

last: Yamanishi

first: Isabel

last: Teitler

first: Jennifer

last: Chung

first: Cecily

last: Barber

first: David

middle: S

last: Goldfarb

first: Kartik

last: Raju

first: Sahar

last: Abubucker

first: Yanjiao

last: Zhou

first: Victoria

middle: E

last: Ruiz

first: Huilin

last: Li

first: Makedonka

last: Mitreva

first: Alexander

middle: V

last: Alekseyenko

first: George

last: Weinstock

first: Erica

last: Sodergren

first: Martin

middle: J

last: Blaser


title: The microRNA-200 family regulates pancreatic beta-cell survival in type 2 diabetes (Min6 cells)

city: Zuerich

first: Lennart

last: Opitz

address: Winterthurerstr. 190

country: Switzerland

institute: FGCZ Zuerich

summary:
The microRNAs miR-141 and -200c were co-overexpressed in the Min6 beta-cell line, which caused pro-apoptotic gene expression and subsquently apoptosis.
We used Affymetrix Chip analysis to address which genes are regulated upon miR-200-overexpression to define target genes of miR-200 and pro-apoptotic genes upregulated by miR-200 to induce apoptosis.

overall_design: Min6 cells were infected with a control Adenovirus or Adenovirus overexpression miR-141/200c. Cells were harvested with Trizol and RNA extraction was performed. RNA from n=3 wells was pooled for each condition and subjected to Affymetrix chip analysis

first: Bengt

last: Belgardt

first: Kashan

last: Ahmed

first: Martina

last: Spranger

first: Mathieu

last: Latreille

first: Remy

last: Denzler

first: Nadiia

last: Kondratiuk

first: Ferdinand

last: Meyen

first: Felipe

middle: N

last: Villena

first: Karolin

last: Herrmanns

first: Domenico

last: Bosco

first: Thomas

last: Rülicke

first: Markus

last: Stoffel


title: The microRNA-200 family regulates pancreatic beta-cell survival in type 2 diabetes

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

overall_design: Refer to individual Series


title: The microRNA-200 family regulates pancreatic beta-cell survival in type 2 diabetes (islet)

summary:
Islets from control and beta-cell specific miR-141/200c overexpressing mice were extracted and Affymetrix gene expression analysis performed
We used Affymetrix Chip analysis to address which genes are regulated upon miR-200-overexpression in beta-cells at the age of 6 weeks.

overall_design: Transgenic mice overexpressing miR-141/200c and control mice were subjected to islet extraction, RNA was extracted using Trizol method, and Affymetrix analysis was performed.


title: Gene Expression in mice liver after knockdown of Rab5

status: Public on May 03 2015

city: Cologne

first: Agapios

last: Sachinidis

state: NRW

address: Robert-Kochstr. 39

department: Institute of Neurophysiology

country: Germany

institute: University of Cologne

summary:
RNAi-mediated silencing of Rab5 and the consequent loss of endosomes in the mouse liver caused severe metabolic defects such as hypoglycemia, hepatomegaly, hypercholesterolemia, hyperlipidemia and glycogen accumulation.
Gene expression in mice liver after knockdown of Rab5 has been performed the Mouse Genome 430 2.0 microarrays to identify biological processes and pathways affected by Rab5.

overall_design: The mice received either PBS or lipid nanoparticles (LNPs) loaded with siRNAs agains Rab5all or Luciferase control at 1.5 mg/kg via tail vein injection. At 5 day post injection mice were sacrificed using cervical dislocation and liver tissue was harvested, snap frozen in liquid nitrogen for RNA isolation; Gene expression studies were performed applying the Mouse Genome 430 2.0 microarrays.

first: Anja

last: Zeigerer

first: Marino

last: Zerial


title: Gene expression level in normal HSCs (LKS+ cells) from different stages of AML

city: Tianjin

first: Hui

last: Cheng

address: 288 Nanjing road

country: China

institute: Institute of Hematology

summary: To investigate the molecular basis for the reversible suppression of HSCs by leukemia, we sorted the CD45.1+LKS+ population from control or leukemic mice at day 7 and day 14 for gene expression profiling analysis.

overall_design: CD45.1+LKS+ cells were sorted from leukemia and control groups at different time points. Microarray was performed at CapitalBio in Beijing. Total RNA was extracted using a Qiagen RNeasy Mini kit. We used the GeneChip Two-Cycle cDNA Synthesis Kit (Affymetrix) for cRNA amplification and labeling. RNA quality was confirmed using an Agilent 2100 bioanalyzer (Agilent Technologies). The amplified cRNA was labeled and hybridized to the Affymetrix Mouse Genome Array 430 2.0 (Affymetrix). Raw data were normalized using Microarray Analysis Software v5.0 (Affymetrix).

first: Tao


title: Identification and Targeted Inhibition of a Fibroblast Lineage Responsible for Scarring and Cancer Stroma

status: Public on May 15 2015

city: Stanford

first: Michael

last: Januszyk

state: CA

address: 257 Campus Dr.

department: Surgery

institute: Stanford University

summary: Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined due to a lack of functional subclasses. Here we reveal the presence of multiple lineages of dermal fibroblasts within the dorsal back. Genetic lineage tracing and transplantation assays demonstrate that the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation is carried out by a single, somitic-derived fibroblast lineage. Reciprocal transplantation of distinct fibroblast lineages between the dorsal back and oral cavity induced ectopic dermal architectures that mimic their place–of-origin. These studies demonstrate that intra and inter-site diversity of dermal architectures are set embryonically and maintained postnatally by distinct lineages of fibroblasts. Lineage-specific cell ablation using transgenic-mediated expression of the simian diphtheria toxin receptor in conjunction with localized administration of diphtheria toxin led to diminished connective tissue deposition in wounds and significantly reduced melanoma growth in the dorsal skin of mice. Using flow cytometry and in silico approaches, we identify CD26/DPP4 as a surface marker that allows for the isolation of this fibrogenic, scar-forming lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. The identification and prospective isolation of these lineages holds promise for translational medicine aimed at in vivo modulation of their fibrogenic behavior.

overall_design: Dermal fibroblasts were harvested for FACS from the oral dermis and cranial dermis of Wnt1Cre; R26mTmG mice, and from ventral and dorsal dermis of En1Cre; R26mTmG mice as previously described. For all microarray analysis, EPFs and ENFs where harvested from backskin of mice at 30 days of age. Positivity for GFP or RFP allowed for the separation of EPFs from ENFs and WPFs from WNFs. RNA was precipitated via chloroform-phenol extraction. Samples were processed for cleanup and concentration using Rneasy MinElute cleanup kit (cat. 74204, QIAGEN). RNA yield was typically 0.5-1 µg RNA/sorted subpopulations. RNA samples from all sorted populations were converted to cDNA using SuperScript III first strand synthesis system for RT-PCR (cat. 18080-051, Invitrogen), and hybridized to Affymetrix Mouse Genome 430 2.0 arrays. Microarrays were normalized by robust multichip average (RMA) and quantile normalization in R. Cluster analysis was performed with AutoSOME (33), using the following settings for gene expression clustering: p-value threshold of 0.05, 100 ensemble iterations, unit variance normalization of arrays, median centering of genes, and sum of squares=1 normalization for both genes and arrays.

middle: T

last: Longaker


title: The effect of BRG1 on the responsivness of IFNg Stimulated Genes

status: Public on May 01 2015

first: Rod

last: Bremner

state: ON

address: 600 University Ave

department: Lunenfeld-Tanenbaum Research Institute

institute: Mount Sinai Hospital

summary:
We studied the effect of reconstitution of BRG1 in BRG1-deficient cells on the responsivness of IFNg stimulated genes. Cells were infected with control adenovirus or BRG1-encoding virus. Cells were then left untreated or exposed to IFNg for 6 hours.
Total RNA was collected and analyzed with Illumina arrays.

overall_design: SW13 cells were infected with BRG1-encoding adenovirus or control virus. Cells were left untreated or exposed to IFNg for 6 hours

first: Mohamed

last: Abou El Hassan

first: Katherine

last: Huang


title: Gene expression profiling of cardiac-specific overexpression of TNF-α in Des-/- myocardium

status: Public on May 02 2015

city: Athens

first: Yassemi

last: Capetanaki

state: Attiki

address: Soranou Ephessiou 4

department: Basic Research

country: Greece

institute: Biomedical Research Foundation of Academy of Athens

summary: Tumor Necrosis Factor-α is greatly implicated in heart pathophysiology, while it is upregulated in the failing myocardium. A major target in TNF-α-induced heart failure is the muscle specific intermediate filament cytoskeleton, comprised by desmin. We analysed the effect of cardiac-specific overexpression of TNF-α in the Des-/- myocardium, which is a known model of dilated cardiomyopathy.

overall_design: Hearts of 3 months old mice (n=3) of Des-/- and TNFαDes-/- genotypes were used for whole genome microarray hybridization analysis.

first: Stamatis

last: Papathanasiou


title: Expression data from spontaneous highly maligant murine pre B cell lymphomas

city: München

first: Olivia

last: Prazeres da Costa

state: Bavaria

address: Trogerstr. 30

department: Medical Microbiology, Immunology and Hygiene

institute: Technische Universität München

summary:
In 20% of IRF4 deficient mice older than 150 days, spontaneous highly malignant pre B cell lymphomas emerge.  A change in the expression profile of genes involved in tumor progession and malignancy is sought for by microarray analyses.
We used microarrays to detail the global programme of gene expression underlying tumor development and identified distinct classes of up-regulated and downregulated genes in the spontaneous highly malignant pre B cell lymphoma.

overall_design: Tumor mouse cells, control mouse B cells lacking IRF4 and control wildtype mouse B cells were purified for RNA extraction and hybridization on Affymetrix microarrays.  We sought to obtain the different expression levels of genes in tumor cells vs. control cells in order to find specific tumor regulated genes.  To that end, we used cells from murine tumors, control mouse B cells lacking IRF4 from bone marrow and sorted accourding to CD19+, sIgM- (control mice IRF4 Knockout ), and control wildtype mouse B cells from bone marrow sorted accourding to CD19+, CD25+, sIgM- (control mice wildtype C57Bl6).

last: Lohoff

first: Christoph

last: Paul

first: Nadine

last: Bollig


title: Gene expression data from anti-müllerian hormone (AMH) treated mouse ovary follicles

city: Aarhus N

first: Helen

middle: Nordahl

last: Madsen

address: Brendstrupgaardsvej 100

department: Dept. Clinical Biochemistry

country: Denmark

institute: Aarhus University Hospital

summary:
Anti-müllerian hormone (AMH) has an inhibitory effect on ovarian follicle development. However, the mechanism by which AMH regulates folliculogenesis remains to be elucidated. In this study we aimed to investigate the changes in transcriptome of preantral to small antral mice follicles after culturing with AMH and thereby identify candidate genes to be involved.
This study is a repetition of a previous study (GEO accession .no.: GSE56737) at the concentration of 50 ng/mL.  The overall design are almost similar to GSE56737 except that it was performed in quadruplicate.

overall_design: Preantral to small antral follicles were collected from dissected ovaries from six to eight weeks old female C57BL/6Tac mice. Twelve hour as well as 24 hour experiments were performed in one fixed concentration of AMH and an untreated control. The experiments were performed in quadroplicate. In total 16 samples: 2 x conc. (control and 50 ng/ml AMH), 2 x time points, 4 x experiments (quadroplicate). Samples are pairwise comparable within each experiment, that is, sample 1-2 or 3-4 or 5-6 or 7-8 or 9-10 or 11-12 or 13-14 or 15-16. Data are also comparable groupwise; (1,5,9,13) vs (2,6,10,14) or (3,7,11,15) vs (4,8,12,16).

first: H

first: N

last: Tørring


title: Effects of acute Notch activation on the mammary epithelial compartment in vivo

status: Public on May 12 2015

city: Philadelphia

first: Lewis

last: Chodosh

state: Pennsylvania

address: 421 Curie Blvd

department: Cancer Biology

institute: University of Pennsylvania

summary: Notch signaling is widely implicated in mouse mammary gland development and tumorigenesis.  To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.

overall_design: Two timepoints (48h and 96h) of doxycycline induction in TetO-NICD1 (TICNX; control) and MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice with 3-4 replicates per timepoint

first: Dhruv

middle: K

last: Pant

first: Daniel

middle: L

last: Abravanel


title: Expression data from anti-müllerian hormone treated preantral/small antral mouse ovary follicles

summary: Anti-müllerian hormone (AMH) has an inhibitory effect on ovarian follicle development. However, the mechanism by which AMH regulates folliculogenesis remains to be elucidated. In this study we aimed to investigate the changes in transcriptome of preantral to small antral mice follicles after culturing with AMH and thereby identify candidate genes to be involved.

overall_design: Preantral to small antral follicles were collected from dissected ovaries from six to eight weeks old female C57BL/6Tac mice.   Twelve hour as well as 24 hour experiments were performed in two different concentrations of AMH. The experiments were performed in triplicate. In total 18 samples: 3 x conc. of AMH, 2 x time points, 3 x experiments (triplicate). Samples are comparable within each experiment, that is, sample 1-3 or 4-6 or 7-9 or 10-12 or 13-15 or 16-18.

first: Niels


title: Cross-species genomics identifies postanatal CPE as novel choroid plexus carcinoma oncogenes.

city: Memphis

first: David

last: Finkelstein

state: TN

address: 332 N. Lauderdale St.

department: Computational Biology

institute: St Jude Children's Research Hospital

summary: Choroid plexus carcinomas (CPC) are poorly understood and frequently lethal brain tumors with minimal treatment options.  Using a new mouse model of the disease and a large cohort of human CPCs [GSE60892; GSE60899], we performed a cross-species, genome-wide search for novel oncogenes within syntenic regions of chromosome gain.  TAF12, NFYC and RAD54L, co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3, were identified as oncogenes that are gained in tumors in both species and required to initiate and progress the disease in mice.  TAF12 and NFYC are transcription factors that regulate the epigenome, while RAD54L plays a central role in DNA repair.  Our data identify a group of concurrently gained, novel oncogenes that cooperate in the formation of CPC and unmask potential new avenues for therapy.

overall_design:
CPC mouse model samples of tumors derived from choroid plexus epithelium (CPE) cells that are Tp53/RB/Pten null in FVB mice. Female CD1 nude (host) mice were transfected with postanatal CPE and compared with a  medulloblastoma normal mouse embryonic,  postnatal and adult controls (loxP TP53/RB/PTEN (no Cre))
Implanted and reimplanted are from the orthotropic transplants of the primary tumor or later tumors

first: Yiai

last: Tong

first: Diana

last: Marino

first: Birgit

last: Nimmervoll

first: Kirti

last: Gupta

last: Wang

first: James

last: Dalton

middle: W

last: Ellison

first: Jinghui

last: Zhang

last: Malkin

first: Richard

last: Gilbertson


title: Treatment of C3H/HeJ grafted mice with baricitinib [prevention]

city: Iowa City

first: Ali

last: Jabbari

state: IA

address: 200 Hawkins Dr, 40025 PFP

institute: University of Iowa

summary:
The C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease.
The efficacy of topical baricitinib at treating established alopecia in the C3H/HeJ grafted model was also assessed. Microarrays were performed on skin RNA at week 0 and week 12 after starting treatment in all models.

overall_design: Baricitinib was administered in systemic form at the time of grafting. Skin samples were taken after 12 weeks.

first: Jane

last: Cerise

first: Angela

last: Christiano


title: Treatment of C3H/HeJ grafted mice with baricitinib [topical]

overall_design: Baricitinib was administered in topical form after disease establishement. Skin samples were taken at the start of treatment and after 12 weeks.


title: Comparison of Hox6 mutant and control E12.5 mouse pancreas

status: Public on Apr 30 2015

city: Ann Arbor

first: Deneen

last: Wellik

state: MI

address: 109 Zina Pitcher

department: Internal Medicine

institute: University of Michigan

summary: Hox genes are critical developmental transcription factor. We found that in mice with disrupted expression of Hoxa6, Hoxb6 and Hoxc6 there is significantly disrupted endocrine pancreas development. We used microarray analysis to probe for possible molecular mechanisms involed in Hox6 signaling in pancreas development.

overall_design: We dissected pancreata from E12.5 control and Hox6 null embryos and extracted total RNA.

first: Brian

last: Larsen


title: Transcriptomes of mesonephros- vs. ovary-derivd Gli1+ cells

status: Public on Apr 28 2015

city: RTP

first: NIEHS

last: Microarray Core

state: NC

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary: This goal of this microarray analysis is to determine whether the mesonephros-derived theca cells exhibt a different gene expression profile from that of the whole theca cell population

overall_design: The mesonephros-derived (n=3, Tamoxifen at E12.5, E14.5 and E16.5) and the neonatal ovary-derived Gli1-positive cells (n=3 Tamoxifen at P1-3 via lactating dams), were isolated from the adult ovaries of Gli1-CreERT2; Rosa-LSL-tdTomato mice at 2 months of age and were sorted by FACS

first: Chang

last: Liu

first: Humphrey

last: Yao


title: Treatment of C3H/HeJ grafted mice with baricitinib


title: Expression data from murine subcutaneous and brown adipose tissue

status: Public on Apr 27 2015

city: Mohali

first: Mahendra

last: Bishnoi

state: Punjab

address: C-127, Industrial Area, SAS Nagar, Phase 8

department: Nutrition Science and Technology

country: India

institute: National Agri-Food Biotechnology Institute

summary:
Two types of adipose tissues, white and brown, are found in mammals. Increasingly novel strategies are being proposed for the treatment of obesity and its associated complications by altering amount and/or activity of BAT using mouse models.
We used microarrays to detail the global programme of gene expression in subcutaneous white adipose tissue and brown adipose tissue.

overall_design: White adipose tissue (Subcutaneous region) and brown adipose tissue (intrascapular) were isolated from LACA mice (male, 25 ± 3g ) for RNA extraction and hybridization on Affymetrix microarrays.


title: Treatment of C3H/HeJ grafted mice with baricitinib [systemic]

overall_design: Baricitinib was administered in systemic form after disease establishment. Skin samples were taken at the start of treatment and after 12 weeks.


title: The FoxO signature in protein breakdown

status: Public on Apr 24 2015

city: Padova

first: Marco

last: Sandri

address: Viale Colombo 3

department: Department of Biomedical Science

country: Italy

institute: University of Padova

summary:
Under stress conditions mammalian cells activate compensatory mechanisms to survive and maintain cellular function. During catabolic conditions, such as low nutrients, systemic inflammation, cancer or infections, protein breakdown is enhanced and aminoacids are released from muscles to sustain liver gluconeogenesis and tissues protein synthesis. Proteolysis in muscle is orchestrated by a set of genes named atrophy-related genes. A system that is activated both in short and prolonged stress conditions is the family of Forkhead Box (Fox) O transcription factors. Here, we report that muscle-specific deletion of FoxO members resulted in protection from muscle loss because FoxO family is required for induction of autophagy-lysosome and ubiquitin-proteasome systems. Importantly, FoxOs are required for Akt activity but not for mTOR signalling underlining the concept that FoxOs are upstream mTOR for the control of protein breakdown when nutrients are lacking. Moreover, FoxO family controls the induction of critical genes belonging to several fundamental stress response pathways such as unfolded protein response, ROS detoxification and translational regulation. Finally, we identify a set of novel FoxO-dependent ubiquitin ligases including the recent discovered MUSA11 and a new one, which we named Specific of Muscle Atrophy and Regulated by Transcription (SMART). Our findings identify the critical role of FoxO in regulating a variety of genes belonging to pathways important for stress-response under catabolic conditions.
Gene expression in muscles of muscle-specific FoxO 1,3,4 knock-out mice that were fed normally or starved

overall_design:
We generated knocked-out FoxO 1,3,4 specifically in muscle by crossing FoxO1-3-4-floxed mice (FoxO1,3,4 f/f) with a transgenic line expressing Cre recombinase under the control of MLC1f promoter to generate muscle-specific FoxO1,3,4 triple knockout mice. These mice were either fed ad libitum or starved. Subsequently gene expression of the gastrocnemius muscles was analyzed.
For each of the 4 conditions (FOXO1,3,4 f/f fed or starved, FOXO1,3,4-/- fed or starved), we isolated the gastrocnemius muscles of 3 mice thus yielding 6 muscles per condition.
RNA was prepared from these muscles using the TRIzol method (Life Technologies) followed by cleanup with the RNeasy kit (QIAGEN). RNA concentration was determined by spectrophotometry and quality of the RNA was monitored using the Agilent 2100 Bioanalyzer (Agilent Technologies). RNA of the 6 muscles per condition was pooled equimolarly and used for further microarray analysis. cRNA was prepared, labelled and hybridised to Affymetrix Mouse Genome 430 2.0 Arrays using Affymetrix-supplied kits and according to standard Affymetrix protocols. Expression values were summarized using the Mas 5.0 algorithm. Genes that were up- or downregulated upon starvation compared to the fed condition were determined using Excel software. A threshold of 1.5 was used for the fold up-or downregulation consistent with the fold change that can be reliably detected with these type of arrays.

first: Reimar

last: Abraham

first: Giulia

last: Milan

first: Vanina

last: Romanello

first: Francesca

last: Pescatore

first: Andrea

last: Armani

first: Ji-Hye

last: Paik

first: Laura

last: Frasson

first: Anke

last: Seydel

last: Zhao

first: Alfred

last: Goldberg

first: Bert

last: Blaauw

first: Ronald

last: Depinho

last: Crosariol


title: Expression data from Spade/Spade mutant and wild type littermates whole ear tissue

status: Public on Apr 25 2015

city: Yokohama

first: Hisahiro

last: Yoshida

address: Tsurumi, 1-7-22

department: IMS

country: Japan

institute: RIKEN Institute

summary: Spade/Spade mutant develop the spontaneous progressive atopic dermatitis like skin inflammation at around 8-10 weeks after birth. In order to detect the pre-symptomatic events that occur in their ear tissue, we have sampled RNA from the whole ear tissue and identified the differentially expressed genes with twofolds difference in comparison with littermate wildtype ear tissue RNA samples.

overall_design: RNA from ear tissue was isolated using an RNeasy Fibrous Tissue Kit (Qiagen) and microarray analysis was performed using GeneChip mouse genome 430_2.0 array (Affymetrix). The data were analyzed by GeneSpring GX (Agilent Technologies).   The data were further analyzed by using packages in R and Bioconductor(48). Per chip normalization of datasets was performed by GCRMA package. An average intensity of two independent of duplicate for each week-wise (second-, fourth-, sixth-week) and mixture dataset was adopted in differential gene expression analysis. The differential genes were identified based on the following criteria: (i) twofold changes between wild-type and Spade (ii) false discovery rate (FDR) calculated by RankProd package with permutation number 1000 (49) for week-wise (FDR<0.05) and mixture (FDR<0.001) datasets.


title: microRNA alterations associated to early relapse in advanced stage ovarian cancer patients (validation set)

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

institute: IRCSS Istituto Nazionale Tumori

summary: A set of 45 surgical specimens has been profiled for miRNA expression to validate miRNA alterations associated to early relapse in advanced stage ovarian cancer patients.

overall_design:
Fresh frozen samples were collected from a series of consecutive patients with high-grade advanced stage ovarian cancer who underwent primary surgery at INT-Milan. After surgery all patients received postoperative platinum-based chemotherapy. All patients signed an Institutional Review Board approved consent for bio-banking, clinical data collection and molecular analysis.

Clinical codes:

Histotype: according to WHO classification guidelines

Stage: according to International Federation of Gynecological and Obstetrics (FIGO) guidelines

Grading: according to WHO classification guidelines

Debulking: NED: not evident disease; mRD: minimal residual disease; GRD: gross residual disease

Therapy code: P: Platinum without taxanes; PT: Platinum/paclitaxel

first: L


title: Effect of maple syrup extract on the liver of mice fed a high-fat diet

city: Kanagawa

first: Asuka

last: Kamei

address: LiSE 4F C-4, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki-shi

department: Project for development of food functionality assessment methods

institute: Kanagawa Academy of Science and technology

summary: The effects of the administration of maple syrup extract (MSX) on hepatic gene expression were investigated in mice fed high-fat diet.

overall_design: Male C57BL/6J mice aged 3 weeks were purchased from Charles River Japan (Kanagawa, Japan) and housed in a room maintained at 23 ± 1°C and 49 ± 16% humidity with a 12-h light/dark cycle (light 08:00–20:00; dark 20:00–08:00).  For 1 week acclimation period after purchase, all the mice were fed a low-fat diet (10 kcal% fat).  Then, they were randomly divided into three different dietary groups: the first group with the food containing fat at 10 kcal% as low-fat diet, the second group with 45 kcal% as high-fat diet, and the third with HFD plus 0.06% MSX.  The mice were fed ad libitum for 8 weeks.

first: Yuki

last: Watanabe

first: Fumika

last: Shinozaki

first: Akihito

last: Yasuoka

first: Takashi

last: Kondo

first: Tomoko

last: Ishijima

first: Tsudoi

last: Toyoda

first: Soichi

last: Arai

first: Keiko

last: Abe


title: Gene expression of murine iDCs isolated from tolerized MOG35-55-infused/MOG35-55-immunized or MOG35-55-immunized mice

status: Public on Apr 20 2015

city: Berlin

first: Pawel

last: Durek

address: Charitéplatz 1

institute: Deutsches Rheuma-Forschungszentrum

summary: Recent data from our group, demonstrate that infusion of myelin oligodendrocyte glycoprotein (MOG35-55) peptide, leads to induction of MOG35-55-specific Tregs and subsequent suppression of Experimental Autoimmune Encephalomyelitis (EAE), the mouse model of multiple sclerosis. Amelioration of EAE was accompanied by reduced MOG-specific Th1 and Th17 responses in the draining lymph nodes (dLNs). Phenotypic analysis of the dLNs of MOG-infused mice revealed a significant Treg-mediated reduction in the recruitment of 7AAD-CD3-CD19-CD11c+CD11bhighGr-1+ iDCs compared to non-infused control immunized mice. Focusing on the delineation of novel molecules/genes that are involved in the MOG-specific Treg-mediated suppression of autoimmune responses, we have isolated highly purified iDCs from MOG infused and non-infused control immunized mice.

overall_design: Gene expression profiles of iDCs isolated from tolerized or immunized mice. Affymetrix MG 430 2.0 whole genome arrays were performed in triplicates for tolerized iDCs and immunized iDCs (6 arrays in total, 5 of them were analyzed). To obtain genes significantly regulated in iDCs upon tolerization with MOG35-55, the expression profiles of iDCs isolated from tolerized or immunized mice were compared to each other. After total RNA extraction, reverse transcription, cDNA extraction, the biotinylated cRNA was transcribed, fragmented, and 15 µg cRNA hybridized to the 6 GeneChip arrays: Group1 iDCs isolated from tolerized mice, Group2 iDCs isolated from immunized mice.

first: Themis

last: Alissafi

first: Aikaterini

last: Hatzioannou

first: Marianna

last: Ioannou

first: Tim

last: Sparwasser

first: Joachim

last: Grün

first: Andreas

last: Grützkau

first: Panayotis

last: Verginis


title: Early postnatal expression data from mouse skeletal muscle stem cells

status: Public on Apr 21 2015

city: Paris

first: Sonia

last: Alonso-Martin

address: 105 bd de l'Hôpital

department: Development and stem cells

country: France

institute: Myology Research Center U974-INSERM - UPMC-Paris VI - Institut de Myologie

summary: Satellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved during early postnatal growth till acquisition of satellite cell quiescence.

overall_design:
Muscle samples were isolated from the trunk of Pax3GFP/+ mice. After digestion, GFP cells were purified via FACS and process for RNA extraction and hybridization on Affymetrix microarrays (Affymetrix Mouse Genome 430 2.0 Arrays).
The different ages selected for sample isolation were P1-P12-P28 (P, postnatal days), covering proliferant and quiescent satellite cells. The three stages were done in triplicate for P28 and 4 times for P1-P12, so 11 samples included in the microarray.

first: Anne

last: Rochat

first: Aurelién

last: de Reyniès

first: Fred

last: Relaix


title: Expression array from SIRT6WT and SIRT6KO muscle

status: Public on Apr 12 2015

city: Boston

first: Raul

last: Mostoslavsky

state: MA

address: 185 Cambridge Street, CPZN 4100

institute: Massachusetts General Hospital

summary: SIRT6 is a member of a highly conserved family of NAD+-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6- deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expres- sion of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcrip- tion factor Hif1a, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-defi- cient cells exhibit increased Hif1a activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity.

overall_design: RNA was prepared from muscle of three SIRT6 wild type and KO mice, and hybridized onto an Affymetrix GeneChip Mouse Genome 430 2.0 Array.

first: Lei

last: Zhong


title: Murine Norovirus Effect on Cells

status: Public on Apr 19 2015

city: Dunedin

first: Christopher

middle: Michael

last: Brown

address: 710 Cumberland St

department: Biochemistry

country: New Zealand

institute: University of Otago

summary: Changes in gene expression on MNV infection of RAW264.7 cells

overall_design: RAW264.7 cells were infected with MNV-1 at a multiplicity of infection of 1, or mock infected, for 12 hours

first: Chris

first: Colin

last: Davies


title: Gene expression data from 4T1 irradiated tumors treated with TGFbeta blockade

city: New York

first: Sandra

last: Demaria

address: 1300 York avenue, Room A-279

department: Radiation Oncology

institute: Weill Cornell Medicine

summary:
Accumulating data support the concept that ionizing radiation therapy (RT) has the potential to convert the tumor into an in situ, individualized vaccine; however this potential is rarely realized by RT alone. Transforming growth factor β (TGFβ) is an immunosuppressive cytokine that is activated by RT and inhibits the antigen-presenting function of dendritic cells and the differentiation of effector CD8+ T cells. Here we tested the hypothesis that TGFβ hinders the ability of RT to promote anti-tumor immunity. Development of tumor-specific immunity was examined in a pre-clinical model of metastatic breast cancer.
Mice bearing established 4T1 mouse mammary carcinoma treated with pan-isoform specific TGFβ neutralizing antibody, 1D11, showed significantly improved control of the irradiated tumor and non-irradiated metastases, but no effect in the absence of RT. Notably, whole tumor transcriptional analysis demonstrated the selective upregulation of genes associated with immune-mediated rejection only in tumors of mice treated with RT+TGFβ blockade. Mice treated with RT+TGFβ blockade exhibited cross-priming of CD8+ T cells producing IFNγ in response to three tumor-specific antigens in tumor-draining lymph nodes, which was not evident for single modality treatment.
Analysis of the immune infiltrate in mouse tumors showed a significant increase in CD4+ and CD8+ T cells only in mice treated with the combination of RT+TGFβ blockade. Depletion of CD4+ or CD8+ T cells abrogated the therapeutic benefit of RT+TGFβ blockade.
These data identify TGFβ as a master inhibitor of the ability of RT to generate an in situ tumor vaccine, which supports testing inhibition of TGFβ during radiotherapy to promote therapeutically effective anti-tumor immunity.
We used genome-wide microarray to depict main biological processes responsibles for the therapeutic benefit of the combination ofTGF-beta blockade and local radiotherapy.

overall_design: To gain a more comprehensice protrait of the effects of RT and TGFbeta blockade on gene expressionin tumors, we collected 4T1 tumors 4 days after completion of RT. Three tumors from each group were then subjected to RNA extraction and hybridization on affymetrix array.

first: Mary

middle: H

last: Barcellos-Hoff

first: Jiri

last: Zavadil

first: Claire

last: Vanpouille-Box


title: Expression data of mice cochlea treated with L-methionine and valproic acid.

status: Public on Apr 15 2015

city: Tokyo

first: Fuyuki

last: Miya

state: Tokyo

address: 35 Shinanomachi, Shinjuku-ku

department: School of Medicine

institute: Keio University

summary: Treatment of DBA/2J mice with a combination of L-methionine and valproic acid significantly attenuated progressive hearing loss. We examined gene expression in the whole cochlea of the mice. This study was aimed to detect genes of which change in expression levels were associated with attenuation of progressive hearing loss in the mice.

overall_design: DBA/2J mice at 4 weeks old (untreated_4-weeks, N=5), mice treated with control vehicle (0.1M sodium bicarbonate) for 8 weeks (Control_vehicle_12-weeks, N=5), and mice treated with L-methionine and valproic acid  (MET_and_VA_12-weeks, N=6) were analyzed.

first: Hideki

last: Mutai

first: Masato

last: Fujii

first: Tatsuhiko

last: Tsunoda

first: Tatsuo

last: Matsunaga


title: PKA-dependent Phosphorylation of A Histone Demethylase Drives Higher Order Chromatin Structures by Association with SWI/SNF Chromatin Remodeler

first: Royhan

last: Rozqie

address: Komaba, Meguro-ku

institute: The University of Tokyo

summary: The current studies show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate expression of the b1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1. Phosphorylation of JMJD1A increases its interaction with the SWI/SNF nucleosome remodeling complex and DNA-bound PPARg. This complex conferred b-adrenergic-induced JMJD1A recruitment to target sites throughout the genome. Phospho-JMJD1A also facilitated long-range chromatin looping to recruit PPARg-bound distal-enhancers, SWI/SNF, and RNA polymerase close to the Adrb1 locus to activate transcription. Mutation of the PKA-phosphorylation site on JMJD1A abolished interactions with SWI/SNF without affecting demethylase activity suggesting the two functions are independent of each other. Our results show that JMJD1A demethylase is also a signal-sensing scaffold that regulates cAMP-responsive transcription via interactions with SWI/SNF and hormone stimulated higher-order chromatin conformational changes.

overall_design: There are 3 samples analyzed. No duplication from each sample. Isoproterenol stimulation at 0hr is used as the relative to fold change in manuscript.

first: Juro

last: Sakai


title: Gene expression of distinct lung dendritic cell subsets

status: Public on Apr 02 2015

first: NIEHS

last: Microarray Core

summary:
Pulmonary dendritic cells are heterogenous cells comprise four distinct subsets including two conventional dendritic cell subsets, CD103+ and CD11bhiCD14lo cells, and two monocyte-derived dendritic cell subsets. Their functions in terms of migration and T cell activation are distinct, but genes regulating their features are to be determined.
We used microarrays to identify a select set of genes that are expressed in conventinal dendritic cells and in monocyte-derived dendriti cells.

overall_design: Four distinct lung DC subsets were purified by flow cytometry-based sorting after inhalation of lipopolusaccharide and ovalbumin.  Each subset has three replicates.

last: Nakano

first: Donald

last: Cook


title: Expression data from G0 versus G4/G5 CMP/GMP

status: Public on Apr 09 2015

city: Houston

first: Ronald

last: Depinho

address: 1400 Pressler St

institute: University of Texas MD Anderson Cancer Center

summary:
Telomere dysfunctional CMP/GMP have deregulated pathways that are associated with DNA damage signaling
We compared differentially expressed genes in the G4/G5 CMP relative to the G0 control to identify pathways that may affect CMP differentiation.

overall_design:
Bone marrow CMP and GMP cells were sorted from two paired pools of G0 TERTER/+ or G4/G5 TERTER/ER mice (5,000-20,000 cells per sample) using the Influx Cell Sorter. Every paired pool includes CMP or GMP sorted from 4 age and gender matched G0 or G4/G5 mice. RNA from the respective sorted cells was extracted using Trizol (Ambion) and profiled on 2100 Bioanalyzer (Agilent). Gene expression profiling was performed at the Sequencing and Non-coding RNA Program at MD Anderson Cancer Center. Briefly, the GeneChip® 3 IVT Express Kit (Affymetrix) was used to generate biotin-labeled cRNA, which were purified and fragmented, before target hybridization on the GeneChip® Mouse Genome 430 2.0 Array (Affymetrix) according to the manufacturer's instructions. Affymetrix raw data (CEL files) were normalized using Affymetrix Microarray Suite (MAS) version 5.0 using a TGT=100. Paired pools used in the study were:
CMP pool 1: G0-1 and G4/5-1
CMP pool 2: G0-2 and G4/G5-2
GMP pool 1: G0-1 and G4/G5-1
GMP pool 2: G0-2 and G4/G5-2

first: Simona

last: Colla

first: Derrick

last: Ong


title: Transcriptional hallmarks of heterogeneous neural stem cell niches of the subventricular zone.

status: Public on Apr 07 2015

city: Zurich

first: Kaz

last: Azim

address: Brain Research Institute

institute: Univ of Zurich

summary:
Throughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to evaluate potential heterogeneity in the NSC pool, we microdissected the dorsal and lateral SVZ at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors influenced NSC specification indicating that the fate of regionalized postnatal SVZ NSCs can be readily modified . These findings reveal functional heterogeneity of NSCs in the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts.
Microarrays of neural stem cells, early progenitors  and the tissue from subregions of the subventricular zone were compiled to screen for the full extent of heterogeneity in this region during postnatal life.

overall_design: Spatially distinct regions of the developing forebrain subventricular zone (SVZ) aged at P4, P8 and P11  were microdissected in RNAse free/sterile conditions.  Mice expressing Ascl1-EGFP in the SVZ were used to aid accurate microdissection of the dorsal and lateral wall of each of the studied time points as per our previous publications characterizing this method. As well as at the whole microdomain level, additionally, NSCs (Hes5-EGFP+/Prom1+) and early progenitors (Ascl1-EGFP+) from each microdomain were further isolated by FAC sorting methods. This was to provide a comprehensive gene expression analysis at the tissue level and at the cellular level. Generally,  1 litter was used to yield 1 'n' number of replicates. A total of 23 affymetrix analysis were performed.

first: Kasum

first: Anahi

last: Hurtado-Chong

first: Bruno

last: Fischer

first: Nitin

last: Kumar

first: Stefan

last: Zweifel

first: Verdon

last: Taylor

first: Olivier

last: Raineteau


title: Expression data for C2C12 differentiation disrupted by Lrrfip1 knockdown

status: Public on Apr 01 2015

city: Shanghai

first: Ning

last: Wei

address: 320 Yueyang RD.

institute: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

summary:
C2C12 myoblasts differentiation is a precise controlled process. Splicing of many genes changes during the differentiation process. Some muscle-specific splicing isoforms play important role in myogenesis.
We used microarrays to detail the global programme of gene expression underlying defect of lrrfip1a, a muscle specific splicing isoform of Lrrfip1.

overall_design: Differentiated C2C12 myoblasts shLUCI or shLrrfip1a were collected and extracted RNA, then hybridizated on Affymetrix. We sought to obtain the different expressed genes between shLUCI and shLrrfip1a samples.


title: Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency

status: Public on Mar 31 2015

city: Lund

first: Jonas

last: Ungerback

address: Klinikgatan 26

department: Division of Molecular Hematology

country: Sweden

institute: Lund University

summary: Ebf1 is a transcription factor with documented, and dose dependent, functions in both normal and malignant B-lymphocyte development. In order to understand more about the role of Ebf1 in malignant transformation, we have investigated the impact of reduced functional Ebf1 dose on early B-cell progenitors. Gene expression analysis in loss and gain of function analysis suggested that Ebf1 was involved in the regulation of genes of importance for DNA repair as well as cell survival. Investigation of the level of DNA damage in steady state as well as after induction of DNA damage by UV light supported that pro-B cells lacking one functional allele of Ebf1 display a reduced ability to repair DNA damage. This was correlated to a reduction in expression of Rad51 and combined analysis of published 4C and chromatin Immuno precipitation data suggested that this gene is a direct target for Ebf1. Even though the lack of one allele of Ebf1 did not result in any dramatic increase of tumor formation, we noted a dramatic increase in the formation of pro-B cell leukemia in mice carrying a combined heterozygote mutation in the Ebf1 and Pax5 genes. Even though the tumors were phenotypically similar and stable, we noted a large degree of molecular heterogeneity well in line with a mechanism involving impaired DNA repair. Our data support the idea that Ebf1 controls homologous DNA repair in a dose dependent manner and that this may explain the frequent involvement of Ebf1 in human leukemia

overall_design:
230238: Briefly, 230238 preB-cell line was infected with pMIG-Ebf1-engrailed or pMIG-control (empty vector). Cells were GFP sorted and 500.000 cells were resuspended in RLT for subsequent RNA-extraction. Analysis were perfomred in triplicate.
FL Ebf1-KO: E14.5 fetal liver (FL) Ebf1-/- were isolated and expanded expanded in vitro on OP9 stroma cells on conditions permissive for B-cell development. Expanded cells were infected with pMIG-Ebf1-ER and sorted on GFP. Cells were reseeded on OP9 stroma cells and tamoxifen was added to a final concentration of 0.1 uM. 500.000 cells were harvested and RNA extracted 0, 6, 12 and 24h. Gene expression levels were compared to 0h and analysis were performed in duplicates.
Tumor LNs: Enlarged lymphnodes from approximately 30 weeks old C57BL/6 Ebf1+/-Pax5+/-  were dissected, homogenized and live frozen. After thawing, 1 million lymphnodes cells were live sorted and  resuspended in RLT prior to RNA extraction. 8 samples were analyzed in duplicates. 1 million proB cells from wt C57BL/6 were sorted and used as controls.

first: Mahadesh

last: Prasad

last: Ungerbäck

first: Josefine

last: Åhsberg

first: Rajesh

last: Somasundaram

first: Tobias

last: Strid

first: Malin

last: Larsson

first: Robert

last: Månsson

first: Ayla

last: De Paepe

first: Henrik

last: Liljebjörn

first: Thoas

last: Fioretos

first: Jim

last: Hagman


title: Transcriptome analysis of Myotonic Dystrophy type 2 (DM2) patients.

status: Public on Apr 05 2015

first: Fabio

last: Martelli

address: via morandi 30

institute: IRCCS-Policlinico San Donato

summary:
Myotonic Dystrophy Type-2 (DM2) is an autosomal dominant disease caused by the expansion of a CCTG tetraplet repeat. It is a multisystemic disorder, affecting skeletal muscles, the heart, the eye, the central nervous system and the endocrine system.
Whole mRNAs expression was measured in the muscle of DM2 patients and compared it to controls.We identified distinct genes modulated in DM2 patients compared to controls.

overall_design: Our study included 10 DM2 and 10 control (CTR) muscle biopsies from biceps brachii. DM2 and CTR were age- and sex- matched. Most DM2 patients had myotonia and cataract, two disease hallmarks, while differences in other clinical parameters (muscle strenght, diabetes, CPK, FT3, FT4, TSH, ejection fraction) were not significant. Genes expression was assessed by Affymetrix Gene Chip Human Exon 1.0 ST Array.

first: Simona

last: Greco

first: Pasquale

last: Fasanaro

first: Alessandra

last: Perfetti

first: Giovanni

last: Meola


title: Osteoclast-secreted Cthrc1 in the coupling of bone resorption to formation

city: Obu

first: Sunao

last: Takeshita

state: Aichi

address: 35 Gengo, Morioka

department: Department of Bone and Joint Disease

institute: National Center for Geriatrics and Gerontology

summary: Bone remodeling is characterized by the sequential, local tethering of osteoclasts and osteoblasts, and is key to the maintenance of bone integrity.  While bone matrix-mobilized growth factors, such as TGF-β, are proposed to regulate remodeling, no in vivo evidence exists that an osteoclast-produced molecule is the enigmatic coupling factor.  We have identified Cthrc1, a protein secreted by mature bone-resorbing osteoclasts, that targets stromal cells so as to stimulate osteogenesis.  The expression of Cthrc1 is robustly induced when mature osteoclasts are placed on dentin or hydroxyapatite, and also by increasing extracellular calcium.  Cthrc1 expression in bone increases in a high turnover state, such as that which is induced by RANKL injections in vivo, whereas it decreases with aging or following alendronate treatment, conditions associated with suppressed bone turnover.  The targeted deletion of the Cthrc1 gene eliminates Cthrc1 expression in bone, whereas its deficiency in osteoblasts does not exert any significant effect.  Osteoclast-specific deletion of the Cthrc1 gene results in osteopenia due to reduced bone formation: it also impairs the coupling process following resorption induced by RANKL injections, with a resultant impairment of bone mass recovery.  Thus, Cthrc1 is an osteoclast-secreted “coupling factor” that regulates bone remodeling and hence, skeletal integrity.

overall_design: Total bone marrow cells were prepared from the femurs and tibias of 8-10-week-old C57BL/6 mice and cultured in the presence of M-CSF (100ng/ml) for 3 days as described previously (Takeshita et al., 2000 JBMR 15:1477-1488).  Cells were harvested with 0.02% EDTA/PBS and used as bone marrow macrophages (BMMs).  These BMMs were cultured in the presence of M-CSF (100 ng/ml) and RANKL (100ng/ml) for 2 days.  TRAP positive mononuclear cells were harvested and used as pre-osteoclasts (pOC).  These pOC cells were further cultured in the presence of M-CSF and RANKL for 2 days in normal plastic plate or on dentin slices.  After 2 days, multinucleated TRAP positive mature osteoclasts were generated as mature osteoclasts on plate (mOCp) and mature resorbing osteoclasts on dentin (mOCd), respectively.  RNAs were extracted from four different stages of osteoclast lineage cells; BMMs, pOC, mOCp and mOCd, and used for microarray analysis.

first: Hiroyuki

last: Aburatani

first: Kyoji

last: Ikeda


title: Gene and microRNA expression profiling of breast tumors from Chinese and Italian women [miRNA]

first: Matteo

last: Dugo

address: via Olgettina 60

department: Department of Medical Oncology

institute: IRCCS Ospedale San Raffaele

summary: Gene and miRNA profiles from a unique Chinese/Caucasian trans-ethnic collection of breast cancer from Shanghai (China) and Milan (Italy) were compared using an unsupervised approach that identified similar clusters of correlated features in Chinese and Caucasian datasets. Partition of gene expression data using previously published gene signatures, such as the PAM50 intrinsic gene list and the extracellular matrix (ECM) genes, revealed Chinese and Caucasian subgroups with equivalent gene and miRNA expression profiles. A significant reduction of Luminal-A tumors was observed in the Chinese series.

overall_design: Tissue samples from 78 Chinese (Han Chinese) and 97 Italian (South Europe Caucasian) consecutive primary breast tumors were subjected to gene and miRNA profiling. Tissue specimens, initially collected respectively in the Chinese and Italian hospitals, were all stored, randomly processed and analyzed in identical experimental conditions in the Italian center to minimize pre-analytical, instrumental and computational variability, enabling direct comparison of gene and miRNA profiles from the two groups.

first: Rosaria

last: Orlandi


title: Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β-cell function (Expression data from islets of control and Insm1 conditional deleted adult pancreatic islets)

first: Andranik

last: Ivanov

address: Chariteplatz 1

department: Core Unit Bioinformatics

institute: Berlin Institute of Health

summary:
The zinc finger factor Insm1 is known to regulate differentiation of pancreatic β cells during development, Here we show that Insm1 is essential for the maintenance of functionally mature pancreatic β cells in mice.
We used microarrays to analyse the global gene expression after deletion of insm1 in adult pancreatic β cells and identified functional important genes and immature islets releated genes deregulated in the mutatant islets.

overall_design: We used 8 mutant and 8 litter matched control mice for the islets preparation.

first: Shiqi

last: Jia


title: Expression data from testis of two-month-old WT and Ccnyl1 KO mice

status: Public on Mar 30 2015

city: Dallas

first: Richard

middle: Chih-Chien

last: Wang

state: Texas

address: 5323 Harry Hines Blvd

department: Dermatology

institute: UT Southwestern Medical Center

summary:
Ccnyl1 is a newly identified genes, but the founction of which remained unclear, here we used the Ccnyl1 knockout mice to finding clues for its functional roles
We used microarrays to screen the expression differences of genes in testis of WT and Ccnyl1 KO mice

overall_design: We used testis tissues from two month old mice, which were of adult age, and two mice per group

first: Zhuzhen

last: Zhang

first: Jiarui

last: Wu


title: A Novel Role for Subcutaneous Adipose Tissue in Exercise-Induced Improvements in Glucose Homeostasis.

status: Public on Apr 22 2015

first: Jonathan

last: Dreyfuss

address: 1 Joslin Pl

department: Bioinformatics & Biostatistics Core

institute: Joslin Diabetes Center

summary: Exercise training improves whole body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, training also affects other tissues including adipose tissue. To determine if exercise-induced adaptations to adipose tissue contribute to training-induced improvements in glucose homeostasis, subcutaneous white adipose tissue (scWAT) from trained or sedentary donor mice was transplanted into the visceral cavity of sedentary recipients. Remarkably, nine days post-transplantation, mice receiving trained scWAT had improved glucose tolerance and enhanced insulin sensitivity compared to mice transplanted with sedentary scWAT or sham-treated mice. Mice transplanted with trained scWAT had increased insulin-stimulated glucose uptake in tibialis anterior and soleus muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted endocrine effects. Furthermore, the deleterious effects of high-fat feeding on glucose tolerance and insulin sensitivity were completely reversed if high-fat fed recipient mice were transplanted with trained scWAT. In additional experiments, voluntary exercise training by wheel running for only 11 days resulted in profound changes in scWAT including increased expression of ∼1550 genes involved in numerous cellular functions, including metabolism. Exercise training causes adaptations to scWAT that elicit metabolic improvements in other tissues, demonstrating a previously unrecognized role for adipose tissue in the beneficial effects of exercise on systemic glucose homeostasis.

overall_design: Microarray analysis of scWAT obtained from a cohort of mice that were housed in wheel cages for 11 days compared to sedentary control mice.

first: K

middle: I

last: Stanford

first: R

last: Middelbeek

last: Townsend

first: M

middle: Y

last: Lee

first: H

last: Takahashi

last: So

last: Hitchcox

middle: R

last: Markan

last: Hellbach

last: Hirshman

first: Y

last: Tseng

first: L

last: Goodyear


title: Flow-induced Protein Kinase A / CREB pathway acts via BMP signaling to promote AGM hematopoiesis

first: Peter

middle: Geon

last: Kim

address: 360 Longwood Ave, Lc8202

department: Hematology/Oncology

institute: Dana Farber Cancer Institute

summary:
By chemical modulation of the PKA/CREB and BMP pathways in isolated AGM VE-cadherin+ cells from mid-gestation embryos, we demonstrate that PKA/CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors and is dependent on secreted BMP ligands through the type I BMP receptor.
We used microarray to document upregulation of PKA/CREB-BMP pathway as well as global BMP target upregulation upon PKA/CREB activation.

overall_design: Isolated VE+ cells from E11.5 AGM were treated with BMP4 (4ng/ml), forskolin (25uM) or both for 8 hours before RNA isolation.

middle: G

first: George

middle: Q

last: Daley


title: JARID2-associated protein network drives rapid and efficient reprogramming to pluripotency.

city: Hidaka

first: Yasushi

last: Okazaki

state: Saitama

address: 1397-1 Yamane

department: Research Center for Genomic Medicine

institute: Saitama Medical University

summary:
Somatic cell reprogramming can be achieved by cell fusion with embryonic stem cells (ESCs), nuclear transfer into oocytes, or forced expression of transcription factors essential for ESC identity. Reprogramming by transcription factors is a less efficient and slower process than that by other methods. Identification of a gene set capable of driving rapid and proper reprogramming to induced pluripotent stem cells (iPSCs) is an important issue. Here, we show that the efficiency and kinetics of iPSC reprogramming are dramatically improved by combined transduction of Jarid2, a gene highly expressed in both ESCs and oocytes and genes encoding its associated proteins. We demonstrate that forced expression of Jarid2 promotes iPSC reprogramming by suppressing the expression of Arf, a known reprogramming barrier, and that the N-terminal half of JARID2 is sufficient for such promotion. Moreover, Jarid2 accelerated retroviral transgene silencing and Nanog promoter demethylation, confirming its promoting activity. We further reveal that JARID2 physically interacts with ESRRB, SALL4A and PRDM14, and show that these JARID2-associated proteins synergistically and robustly facilitate iPSC reprogramming in a Jarid2-dependent manner. Our findings provide an insight into the important roles of Jarid2 during reprogramming, and suggest that the JARID2-associated protein network contributes to overcoming reprogramming barriers.
We used microarrays to detect the up- and down-regulated genes in MEFs transduced with Jarid2 compared to empty vector control.

overall_design: Total RNA was extracted from mouse embrionc fibroblasts (MEFs) transduced with empty vector (control) or the indicated genes at 3 days post-transduction, and two iPSC clones from MEFs transduced with OSKM plus Jarid2. Gene expression profile was analyzed by the Affymetrix GeneChip microarray system.

first: Hiroyoshi

last: Iseki

first: Yutaka

last: Nakachi

first: Tomoaki

last: Hishida

first: Yzumi

last: Yamashita-Sugahara

first: Yoko

last: Tanimoto

first: Saori

last: Iijima

first: Fumihiro

last: Sugiyama

first: Ken-ichi

last: Yagami

first: Satoru

first: Akihiko

last: Okuda


title: Promotion of pancreatic cancer metastasis by mutant p53

status: Public on Mar 28 2015

city: Glasgow

first: Owen

last: Sansom

address: Garscube Estate

country: United Kingdom

institute: Cancer Research UK Beatson Institute

summary: The TP53 transcription factor is frequently mutated at later stages of epithelial cancers, indicating a possible role in their invasion and metastasis. Importantly, in most cases rather than a simple loss of function p53 mutation, point mutations of p53 accumulate at the protein level and may have dominant negative functions. This study analyses gene expression differences between mice harbouring p53 mutation who do and do not develop metastasis.

overall_design: Samples were collected from Genetically modified mice of the genotypes indicated in the characteristics. The presence or absence of metastasis was scored and gene expression differences between the two groups measured.

first: J

last: Morton


title: Gene and microRNA expression profiling of breast tumors from Chinese and Italian women

first: Matteo

last: Dugo

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

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

overall_design: Refer to individual Series


title: DOT1L Inhibits SIRT1 and SUV39H1-Mediated H3K9 Modification to Maintain Gene Expression (array)

first: Richard

last: Koche

state: New York

institute: Memorial Sloan Kettering Cancer Center

summary:
Methylation of histone 3 on lysine 79 (H3K79) is broadly associated with active gene expression in eukaryotes, and the H3K79 methyltransferase DOT1L is indispensable for specific leukemia subtypes like those with MLL-translocations.
We found that suppression of the histone deacetylase SIRT1 rescued MLL-AF9 leukemia cells from their dependence on DOT1L. We show that upon DOT1L inhibition, SIRT1 is required for the acquisition of a repressive chromatin state consistent with facultative heterochromatin around MLL-AF9 target genes in leukemia and other genes possess an H3K79me2(hi), H3K9ac(hi), H3K9me2(low) histone modification profile in normal hematopoietic stem and progenitor cells.

overall_design: Examination of gene expression dynamics with and without drug treatment and RNA interference.

middle: P

first: Chun-Wei

last: Chen

first: Scott

middle: A

last: Armstrong


title: Tenascin C prevents acute aortic dissection in mice

status: Public on Mar 27 2015

city: Kurume

first: Hiroki

last: Aoki

state: Fukuoka

address: 67 Asahimachi

department: Cardiovascular Research Institute

institute: Kurume University

summary: Acute aortic dissection (AAD) is one of the major aortic diseases that occurs without a preceding symptom and often results in sudden death. Despite the recent advances in cardiovascular medicine, AAD remains a serious problem because its molecular pathogenesis is largely unknown.   In this paper, we report our serendipitous discovery that stress-induced expression of tenascin C (TNC), a member of matricellular proteins, is the protection mechanism of aorta to prevent AAD. The aortic wall stress imposed by the aortic stiffening and the angiotensin II infusion caused the strong induction of TNC in wild type mouse aorta without gross morphological changes. While TNC knockout mice at the baseline showed no morphological, histological or biomechanical abnormalities of aorta, deletion of TNC gene rendered the aorta susceptible to AAD upon the aortic stress. The stressed TNC-null aorta showed the loss of the tensile strength due to the insufficient expression of extracellular matrix proteins and the exaggerated proinflammatory response before the onset of AAD. Therefore, TNC works as a stress-activated molecular damper both by reinforcing the tensile strength and by limiting the excessive proinflammatory response in aorta.  Thus far, the molecular event that leads to the AAD development has been unclear because of the unpredictable nature of the AAD onset. This study sheds light on the previously unrecognized tissue protection mechanism that converts the potentially harmful stress response into the active reinforcement of the aorta, of which failure leads to the development of AAD. Although TNC is expressed in various tissues upon the mechanical and proinflammatory stimuli, its role has long been a mystery. Our data uncovered the adaptive role of TNC in aorta that must be resilient to the continuous hemodynamic and humoral stress for lifetime.

overall_design:
We used periaortic application of 0.5 M CaCl2 to the infrarenal aorta or either wild type (WT) or tenascin C knockout (TNC-KO) mice to create the mouse model for stiffened aorta and infused the mice with AngII (1 µg/min/kg) for 1 week to apply the pathological stress on aorta (Ca+AngII). Mice were then killed with an overdose of pentobarbital to obtain the tissue samples. The suprarenal aortic samples, from the level of right renal artery to 10 mm above the right renal artery, and infrarenal aortic samples, from the level of left renal artery to 10 mm below the left renal artery, were collected and kept in RNAlater (Qiagen) until the extraction of total RNA using RNeasy (Qiagen). We obtained the RNA samples from 8 mice with Ca+AngII treatment and 5 mice without Ca+AngII treatment for each genotype. We pooled the RNA samples with the identical experimental condition to perform the transcriptome analysis using Mouse Genome 430 2.0 (Affymetrix).
We obtained suprarenal aortic smooth muscle cells (ASMCs) from TNC-KO mice by enzymatic dispersion and cultured them in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum. We cultured TNC-KO ASMCs in the presence or absence of exogenous TNC (10 µg/mL) and stimulated the cells with 10 ng/mL TNF-alpha for 24 h before obtaining total RNA using RNeasy. We used 3 independent ASMC cultures without the exogenous TNC and 4 independent cultures with the exogenous TNC. We hybridized each of the RNA samples individually to Mouse Genome 430 2.0 Array (Affymetrix).

first: Taizo

last: Kimura

first: Koichi

last: Yoshimura

first: Kozoh

last: Shiraishi

first: Kyoko

last: Imanaka-Yoshida

first: Toshimichi

last: Yoshida

first: Yasuhiro

last: Ikeda

first: Kimikazu

last: Hamano

first: Michiaki

last: Hiroe

first: Kazutaka

last: Aonuma

first: Takafumi

last: Ueno

first: Tsutomu

last: Imaizumi

first: Masunori

last: Matsuzaki


title: Brain-derived neurotrophic factor contributes to the cardiogenic potential of adult resident progenitor cells in failing murine heart

status: Public on Mar 26 2015

city: Greifswald

first: Sabine

last: Ameling

address: Felix-Hausdorff.Str 8

department: Interfakultäres Institut für Genetik und Funktionelle Genomforschung

institute: Universitätsmedizin Greifswald

summary:
Aims: Resident cardiac progenitor cells show homing properties when injected into the injured but not into the healthy myocardium. The molecular background behind this difference in behavior needs to be studied to elucidate how adult progenitor cells can restore cardiac function of the damaged myocardium. Since the brain-derived neurotrophic factor (BDNF) moderates cardioprotection in injured hearts, we focused on delineating its regulatory role in the damaged myocardium.

Methods and Results: Comparative gene expression profiling of freshly isolated undifferentiated Sca-1 progenitor cells derived either from heart failure transgenic αMHC-CyclinT1/Gαq overexpressing mice or wildtype littermates revealed transcriptional variations. Bdnf expression was up-regulated 5-fold during heart failure, which was verified by qRT-PCR and confirmed at the protein level. The migratory capacity of Sca-1 cells from transgenic heart was improved by 15% in the presence of 25ng/ml BDNF. Furthermore, BDNF-mediated effects on Sca-1 cells were studied via pulsed Stable Isotope Labeling of Amino acids in Cell Culture (pSILAC) proteomics approach. After BDNF treatment, significant differences between newly synthesized proteins in Sca-1 cells isolated from control and transgenic mice were observed for CDK1, SRRT, HDGF, and MAP2K3, which are known to regulate cell cycle, survival and differentiation. Moreover, BDNF repressed the proliferation of Sca-1 cells from transgenic hearts.

Conclusion: Comparative profiling of resident Sca-1 cells revealed elevated BDNF levels in the failing heart. Exogenous BDNF (i) stimulated migration, which might improve the homing ability of Sca-1 cells derived from the failing heart and (ii) repressed the cell cycle progression suggesting its potency to ameliorate heart failure.

overall_design: Freshly isolated Sca-1 cells were derived from age-matched Cyclin T1/Gq overexpressing mice (Cyc) and their healthy counterparts (Wt) were used for comparative transcriptional profiling considering Wt as baseline condition.

first: Rasmita

last: Samal

first: Vishnu

last: Dhople

first: Praveen

last: Sappa

first: Kristin

last: Wenzel

first: Uwe

last: Völker

first: Stephan

middle: B

last: Felix

first: Elke

last: Hammer

first: Stephanie

last: Könemann


title: Transcriptional profiling of lung cancer cells transfected with Zeb1.

status: Public on Mar 25 2015

first: Chad

last: Creighton

state: TX

address: One Baylor Plaza, Mail Stop: BCM305

department: Biostatistics, Ducan Cancer Center

institute: Baylor College of Medicine

summary: To elucidate the mechanisms by which the mir-200 and the miR-183~96~182 cluster could regulate EMT and thus cellular migration, invasion and metastasis in NSCLC, we searched for common predicted targets of these microRNA families that might have a potential role in these biological processes. First we performed a cross comparison of multiple gene expression datasets from our mouse models of metastasis. We overlapped 224 genes that were elevated greater than four-folds upon Zeb1 induction in 393P cells with 210 genes that showed greater than two-fold increase in expression in the metastatic 344SQ cells compared to the non-metastatic 393P cells and 143 genes that were repressed to less than 0.5-fold in cells with exogenous expression of miR-200. This resulted in an enriched list of 45 genes that are potential miR-200 targets having a role in the process of EMT and metastasis. Next we performed an overlap of genes that were predicted targets of the miR-200 family members and the miR-183~96~182 cluster using the microRNA prediction algorithms miRanda (www.microRNA.org) and identified a list of 17 highly conserved common targets with a mirSVR score less than -6.0. The only 2 genes common in both the overlapping subsets were Zeb1 and Foxf2.

overall_design:
393P lung cancer cells with stable constitutive expression of either pCDNA vector or Zeb1 were transcriptionally profiled in triplicate cultures.
two group comparison

first: Don

last: Gibbons


title: microRNA Induction of Fatal Differentiation Programs is a Context-selective Vulnerability in Ovarian Cancer Cells

first: Michael

last: White

address: 6000 Harry Hines Blvd.

department: Cell Biology

institute: University of Texas Southwestern Medical Center


title: microRNA Induction of Fatal Differentiation Programs is a Context-selective Vulnerability in Ovarian Cancer Cells [miRNA]

summary: Analysis of microRNA (miRNA) expression in ovarian cancer cell lines and human ovarian surface epithelium (HOSE) in order to identify differentially expressed miRNAs between cancer lines and HOSE

overall_design: Total RNA was isolated from cells 72 hours after plating

first: Benjamin

last: Shields


title: Peroxisomes and mitochondria are dysfunctional in obese diabetic (db/db) mice with fatty liver

status: Public on Mar 23 2015

city: Duesseldorf

first: Birgit

last: Knebel

address: Auf'm Hennekamp 65

department: Cinical Biochemistry and Pathobiochemistry

institute: German Diabetes Center

summary:
Major causes of lipid accumulation in liver are increased import, synthesis or decreased catabolism of fatty acids. The latter is caused by dysfunction of cellular organelle controlling energy homeostasis, i.e. mitochondria. However, peroxisomes appear to be an important organelle in lipid metabolism of hepatocytes, but little is known about their role in the development of non-alcoholic fatty liver disease (NAFLD). To investigate the role of peroxisomes next to mitochondria in excessive hepatic lipid accumulation we used the leptin resistant db/db mice on C57BLKS background, a mouse model that develops hyperphagia induced diabetes with obesity and NAFLD.
We used microarrays to determine differences in hepatic gene expression in a mouse model for NAFDL (BKS.Cg-Leprdb (db/db)) and their wildtype littermates  C57BL/KSlepr+/+ (BKS) to determine the effect of persistent hepatic lipid accumulation.

overall_design: C57BL/KSlepr+/+ (BKS) and BKS.Cg-Leprdb (db/db) mice (litermates) were kept under standadized conditions with regular chow until  db/db mice develop the diabetes and obesitiy phenotype with NAFLD (14 weeks of age).

first: Jorg

last: Kotzka

first: Dirk

last: Muller-Wieland


title: Expression data from KSL and GMP cells of FLT3/ITD and FLT3/ITD-SmoM2 mice

status: Public on Mar 21 2015

city: Baltimore

first: Yiting

last: Lim

state: MD

address: 1650 Orleans Street

institute: Johns Hopkins University School of Medicine

summary:
FLT3/ITD-SmoM2 mice developed rapidly fatal myeloid leukemia compared to FLT3/ITD only mice, suggesting that overactivation of the Hedgehog signaling pathway via SmoM2 can drive myeloid disease progression
We used the Affymetrix Mouse 430_2.0 microarray to detail global gene expression responsible for disease progression in sorted bone marrow cells and found that the Hedgehog signaling pathway contributes to disease progression by enhancing FLT3 signaling

overall_design: KSL and GMP cells were FACS sorted from wild-type, FLT3/ITD and FLT3/ITD-SmoM2 bone marrow when the mice were around 3 months of age, when the FLT3/ITD-SmoM2 mice developed leukemia. RNA was extracted from the sorted cells and hybridized onto the Mouse 430_2.0 Affymetrix array.  Wild-type and FLT3/ITD mice that were used as controls were littermates of the FLT3/ITD-SmoM2 leukemic mice. Each sample consists of pooled cells from 3 mice.

first: William

last: Matsui


title: Expression data for hematopoietic stem cells (lin- sca1+ ckit+) isolated from the bone marrow of Ercc1-deficient and proficient littermates

status: Public on Mar 24 2015

city: Rotterdam

first: Jurgen

last: Haanstra

address: Dr. Molewaterplein 50

department: Hematology

country: Netherlands

institute: ErasmusMC

summary:
To identify cellular and genetic abnormalities involved in interstrand cross link repair-deficient bone marrow failure and its transformation to leukemia, we used an Ercc1 hypomorphic mouse model (Ercc1 -/d).
Gene expression profiling was done to determine which genes are differentially expressed

overall_design: LSK cells from the bone marrow of ~20 week-old  Ercc1-deficient (one knockout allele and one truncated allele (d)) and wt littermates (at least one normal Ercc1 allele) were sorted by FACS. RNA was isolated and linearly amplified before hybridisation onto the array. Gene expression in Ercc1-deficient LSK cells was compared to that of wt littermates

first: Mir Farshid

last: Alemdehy

first: Hans

last: de Looper

first: Paulina

middle: M

last: van Strien

first: Judith

last: verhagen-Oldenampsen

first: Yvette

last: Caljouw

first: Mathijs

last: Sanders

first: Remco

last: Hoogenboezem

first: Arnoud

last: de Ru

first: George

last: Janssen

middle: E

last: Smetsers

first: Marc

last: Bierings

first: Peter

last: van Veelen

first: Marieke

last: von Lindern

first: Ivo

last: Touw

first: Stefan

middle: J

last: Erkeland


title: Gene expression profiling of metastatic lung cancer cell lines

status: Public on Mar 12 2015

first: Chad

last: Creighton

summary: During malignant disease progression, the extracellular matrix (ECM) of epithelial tumors accumulates inter-molecular cross-links between collagen strands; these cross-links enhance ECM stiffness and trigger tumor cell invasion and dissemination, but the mechanisms that regulate intra-tumoral collagen maturation have not been fully defined. Using a new mouse model of metastatic lung adenocarcinoma driven by mutant K-ras expression and Cdkn1a inactivation, we showed that tumor cell invasion and metastasis are driven by high expression of lysyl hydroxylase 2 (LH2), an enzyme that hydroxylates telomeric lysine (Lys) residues on collagen.

overall_design: We interbred KrasLA1 mice, which develop non-metastatic lung adenocarcinomas at 8-10 months of age because of the expression of a somatically activated K-rasG12D allele, with Cdkn1a-/- mice, which develop sarcomas and B cell lymphomas because of depletion of p21. Cohorts were generated that had neither, either, or both mutant alleles. KrasLA1 mice that were p21-deficient (KC mice) had a shorter mean time to death than did p21-replete ones. We established cell lines from the tumors, and compared cell lines from highly metastatic tumors with those from poorly metastatic tumors.

first: Yulong

last: Chen

first: Jon

last: Kurie

first: Yiqun

last: Zhang


title: Gene expression in aortic roots of wild type versus klotho-deficient mice at 6 weeks of age

status: Public on Mar 16 2015

city: Cincinnati

first: Elaine

middle: Emily

last: Wirrig

state: Ohio

address: 240 Albert Sabin Way

department: Molecular Cardiovascular Biology

institute: Cincinnati Children's Hospital Medical Center

summary:
Klotho-deficient mice develop aortic valve annulus calcification by 6 weeks of age. Understanding the molecular basis by which aortic valve calcification is initiated will help define potential molecular targets which may be inhibited to reduce or prevent aortic valve calcification.
Changes in gene expression related to aortic valve annulus calcification were analyzed by comparing gene expression in the aortic roots from wild type versus klotho-deficient mice.

overall_design: Aortic roots, containing the aortic valve, valve annulus, and a portion of the ascending aorta were harvested from klotho-deficient and wild type mice at 6 weeks of age and analyzed by Affymetrix microarray.

first: Katherine

last: Yutzey


title: Ablation of Pten and Smad4 leads to metastatic lung carcinoma in a murine model.

summary: Lung cancer is the leading cause of cancer related death in both men and women in the United States.  Recently, Smad4 was discovered to be common somatic alteration in human squamous cell lung cancer. Our goal was to delineate the role of Smad4 in lung cancer. We have shown for the first time that the ablation of Pten and Smad4 in the murine airway epithelium harbors a metastatic proximal adeno-squamous lung cancer.

overall_design: knockout group (PTENd/d and SMAD4d/d) and control group

first: Bindu

last: Akkanti

first: Franco

last: Demayo


title: Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice

status: Public on Mar 11 2015

city: Durham

first: Pavle

last: Matak

state: North Carolina

address: 450 Research Drive, LSRC C-125

department: Pharmacology and Cancer Biology

institute: Duke University

summary: Disruption of local iron homeostasis is a common feature of neurodegenerative diseases. We focused on dopaminergic neurons, asking how iron transport proteins modulate iron homeostasis in vivo. Inactivation of the transmembrane iron exporter ferroportin had no apparent consequences. However, loss of the transferrin receptor 1, involved in iron uptake, caused profound, age-progressive neurodegeneration with features similar to Parkinson’s disease. There was gradual loss of dopaminergic projections in the striatum with subsequent death of dopaminergic neurons in the substantia nigra. After depletion of 30% of the neurons the mice developed neurobehavioral parkinsonism, with evidence of mitochondrial dysfunction and impaired mitochondrial autophagy. Molecular analysis revealed strong signatures indicative of attempted axonal regeneration, a metabolic switch to glycolysis and the unfolded protein response. We speculate that cellular iron deficiency may contribute to neurodegeneration in human patients

overall_design: Using Ribotag technology, from mouse ventral midbrain lysates, we isolated actively translated mRNA species from control and Transferrin receptor 1-null dopaminergic neurons.  Two mouse ages were used 3 wks (early neurodegeration) 10 wks (late neurodegeneration)

first: Nancy

middle: C

last: Andrews


title: MicroRNA expression profiling of human blood monocyte subsets highlights functional differences

status: Public on Mar 07 2015

city: Singapore

first: Wing-Cheong

last: Wong

address: 30 Biopolis Street #07-01

country: Singapore

institute: Bioinformatics Institute, A*STAR

summary: Identification of micro-RNAs involved in regulating differential apoptosis and migration potential of human monocyte subsets

overall_design: Comparision between freshly isolated CD14++CD16- monocytes and CD14+CD16+ monocytes from healthy human blood

first: Truong-Minh

last: Dang

first: Siew-Min

last: Ong

first: Jimiao

first: Michael

last: Poidinger

first: Francesca

last: Zolezzi

first: Siew-Cheng


title: Neuron-specific deletion of the miRNA-processing enzyme DICER induces severe but transient obesity in mice

status: Public on Mar 06 2015

city: Lausanne

first: Sylvain

last: Pradervand

address: Genopode

department: CIG

institute: UNI Lausanne

summary: Through post-transcriptional regulation of gene expression, miRNAs affect numerous regulatory pathways including those crucial for maintaining metabolic balance. Here we demonstrate that a neuronal-specific inhibition of miRNA maturation in adult mice leads to a rapid development of severe obesity, which is equally rapidly reversed. Development of obesity was associated with increased food intake and efficiency, and decreased locomotor activity. The ensuing decrease in body weight resembled a catabolic state with lowered O2-consumption and respiratory-exchange ratio. Brain transcriptome analyses in obese mice identified several obesity-related pathways including leptin, somatostatin, and nemo-like kinase signaling, as well as genes involved in feeding and appetite (e.g. Pmch, Neurotensin). A cluster of genes involved in synaptic plasticity was specifically enriched in post-obese mice that did not appear in obese mice. While other studies have identified a role for miRNAs in obesity our model is unique in that it allows for the study of processes involved in reversing obesity.

overall_design:
Tissues were collected 4 weeks and 8 weeks after induction of dicer gene knock-out. For each tissue (i.e., cortex, hypothalamus, hippocampus) a total of 3 animals per treatment and per time point was used.
Genetic modification.

first: Géraldine

last: Mang

first: Leonore

last: Wigger

first: David

last: Gatfield

first: Paul

last: Franken


title: Shp2 Signaling Suppresses Senescence in PyMT-induced Mammary Gland Cancer in Mice [Mouse430_2 array]

city: Berlin

first: Linxiang

last: Lan

address: Robert-Roessle-Str. 10

department: Cancer Research Program

institute: Max-Delbrueck-Center for Molecular Medicine

summary: In this study, we have used techniques from cell biology, biochemistry, and genetics to investigate the role of the tyrosine phosphatase Shp2 in tumor cells of MMTV-PyMT mouse mammary glands. Genetic ablation or pharmacological inhibition of Shp2 induces senescence, as determined by the activation of senescence-associated β-gal (SA-β-gal), cyclin-dependent kinase inhibitor 1B (p27), p53, and histone 3 trimethylated lysine 9 (H3K9me3). Senescence induction leads to inhibition of self-renewal of tumor cells and blockage of tumor formation and growth. A signaling cascade was identified that acts downstream of Shp2 to counter senescence: Src, Focal adhesion kinase and Map kinase inhibit senescence by activating the expression of S-phase kinase-associated protein 2 (Skp2), Aurora kinase A (Aurka), and the Notch ligand Delta-like 1 (Dll1), which block p27 and p53. Remarkably, the expression of Shp2 and of selected target genes predicts human breast cancer outcome. We conclude that therapies which rely on senescence induction by inhibiting Shp2 or controlling its target gene products may be useful in blocking breast cancer.

overall_design: Primary mammary tumor cells from MMTV-PyMT mice were cultured as mammospheres for 10 days and then treated with specific inhibitors of Notch (DAPT), MEK1 (U0126), FAK (TAE226), or Src (PP2) for another 2 days. Mammospheres were then subjected to RNA isolation. Each group contains 3 replicates.

first: Jingjing

last: Qi

first: Balázs

last: Györffy

first: Walter

last: Birchmeier


title: Mediator Med23-deficiency Enhances Neural Differentiation of Embryonic Stem Cells through Modulating BMP Signaling

status: Public on Mar 05 2015

first: Gang

last: Wang

address: Yueyang Road 320

department: Institute of Biochemistry and Cell Biology, State Key Laboratory of Cell Biology,

institute: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

summary:
Unraveling the mechanisms underlying early neural differentiation of ESCs is crucial to the cell-based therapies of neurodegenerate diseases. Neural fate acquisition is proposed to be controlled by a “default” mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of embryonic stem cells (ESCs). Unexpectedly we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23-depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of other Mediator subunit, Med1 or Med15, did not alter the neural differentiation of ESCs; and Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23-depletion attenuated the BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1 that is involved in the Bmp4 promoter-enhancer communication. Interestingly, Med23 knockdown in zebrafish embryos also enhanced the neural development at early embryogenesis, which could be reversible by coinjection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination.
We used microarrays to detail the global gene expression after MED23 knockout

overall_design: We examined the gene expression level in WT and MED23 knockout ES cells in steady culture condition.

first: Wanqu

last: Zhu

first: Xiao

last: Yao


title: ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis [expression]

city: Haining

first: Jian

last: Liu

state: Zhejiang

address: 718 East Haizhou Rd.

department: Zhejiang University - University of Edinburgh Institute

institute: Zhejiang University

summary: Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1’s expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer.

overall_design:
The microarray data includes two different ages of mouse lung samples.

The microarray for the study on late stage was did on 12-month-old wild type mouse lungs and Ptend/dSmad4d/d mouse lung tumors. This study was used to identify the significantly changed genes between lung tumors and wild type lungs.

The microarray for the study on early stage was did on 7-month-old wild type, Ptend/d and Ptend/dSmad4d/d mouse lungs. This study was used to identify the significantly changed driven genes before the lung tumor initiation and metastasis.

first: Sung

middle: N

last: Cho

first: Bindu

last: Akkanti

first: Nili

last: Jin

first: Jianqiang

last: Mao

first: Weiwen

last: Long

first: Tenghui

last: Chen

first: Yiqun

last: Zhang

first: Ximing

last: Tang

first: Ignacio

last: Wistuba

first: Chad

last: Creighton

first: Farrah

last: Kheradmand

first: Francesco

last: DeMayo


title: Shp2 Signaling Suppresses Senescence in PyMT-induced Mammary Gland Cancer in Mice

first: Linxiang

last: Lan

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

overall_design: Refer to individual Series


title: Expression data of LncRNA from the rat (Sprague-Dawley) knee articular cartilage at different developmental stages

city: Taiyuan City

first: Xiao Chun

last: Wei

state: Shanxi Shanxi

address: No.382, Wuyi Road,Taiyuan City.

department: Department of Orthopaedics

institute: the Second Hospital of Shanxi Medical University

summary:
Age as the primary rise factor could be play an important role in incidence and development of osteoarthritis. A few studies have confirmed some tissue specific lncRNA were associated with development of osteoarthritis. But if age related lncRNA would be involved in pivotal post-transcriptional gene regulation in osteoarthritis is unclear. In view of this, we have an idea that several age-related lncRNA would be screened from the rat knee cartilage at different development ages by lncRNAs Microarray analysis.
We used microarrays to detail the global programme of gene expression underlying the rat knee cartilage and identified distinct classes of age-related lncRNA during this process.

overall_design: The rat knee articular cartilage were selected at successive stages of the rat developmental for RNA extraction and hybridization on Affymetrix lncRNA arrays. We sought to obtain homogeneous populations of cartilage at each developmental stage in order to increase the temporal resolution of expression profiles. To that end, we hand-selected cartilage according to the rat developmental stages, i.e. seven time-points: newborn (T0), youth(T1), adult (T2), early-stage elderly(T3) and latter-stage elderly(T4).

first: XiaoChun

first: YongPing

last: Li


title: Expression data from Fbxl10 overexpressing 3T3-L1 cells

status: Public on Mar 04 2015

city: meguro-ku

first: Takeshi

last: Inagaki

address: 4-6-1 Komaba

institute: Univ of Tokyo

summary: Target genes of Fbxl10 during 3T3-L1 adipogenesis was analyzed

overall_design: 3T3-L1 cells overexpressing Fbxl10 using retrovirus system containing LTR promoter were differentiated and RNA was extracted at day 2 of differentiation

first: Satoshi

last: Iwasaki