title: Integrative Analysis of Transcriptomic and Epigenomic Data to Reveal Regulation Patterns for Osteoporosis Risk [Transcriptome]

status: Public on Oct 17 2014

city: Chang sha

first: shishi

last: min

state: Hunan

address: Lu shan  road

department: College of life sciences

institute: Hunan Normal University

summary: In this study, we analyzed transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing data simultaneously in PBMs from 5 high hip BMD subjects and 5 low hip BMD subjects. Through integrating the transcriptomic and epigenomic data, firstly we identified BMD-related genetic factors, including 9 protein coding genes and 2 miRNAs, of which 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) showed the consistent association evidence from both gene expression and methylation data, and 3 genes (TMEM55B, RNF40 and ALDOA) were confirmed in the meta-analysis of 7 GWAS samples and GEnetic Factors for OSteoporosis consortium (GEFOS-2) GWAS results. Secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status, including regulation by gene methylation, by miRNA and its methylation, by transcription factors and co-regulation by miRNA and gene methylation. In conclusion, the integration of multiple layers of omics can yield more in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology.

first: Jigang

last: Zhang

first: Lijun

last: Tan

first: Chen

last: Xu

first: Hao

last: He

first: Qing

last: Tian

first: Yu

last: Zhou

first: Chuan

last: Qiu

first: Xiang

last: Chen

first: Hong

last: Deng


title: Ataxin-2 adapts ribosomal mRNA levels and S6 phosphorylation to nutrient availability, with effects on protein synthesis and growth

status: Public on Oct 31 2014

city: Tuebingen

first: Michael

middle: H.

last: Walter

address: Calwer Str. 7

department: Department of Medical Genetics

country: Germany

institute: University of Tuebingen

summary: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder, which is caused by an unstable CAG-repeat expansion in the SCA2 gene, that encodes a polyglutamine tract (polyQ-tract) expansion in ataxin-2 protein (ATXN2). The RNA-binding protein ATXN2 interacts with the poly(A)-binding protein PABPC1, localizing to ribosomes at the rough endoplasmic reticulum or to polysomes. Under cell stress ATXN2 and PABPC1 show redistribution to stress granules where mRNAs are kept away from translation and from degradation. It is unknown whether ATXN2 associates preferentially with specific mRNAs or how it modulates their processing. Here, we investigated Atxn2 knock-out (Atxn2-/-) mouse liver, cerebellum and midbrain regarding their RNA profile, employing oligonucleotide microarrays for screening and RNA deep sequencing for validation. Modest ~1.4-fold upregulations were observed for the level of many mRNAs encoding ribosomal proteins and other translation pathway factors. Quantitative reverse transcriptase PCR and immunoblots in liver tissue confirmed these effects and demonstrated an inverse correlation also with PABPC1 mRNA and protein. ATXN2 deficiency also enhanced phosphorylation of the ribosomal protein S6, while impairing the global protein synthesis rate, suggesting a block between the enhanced translation drive and the impaired execution. Furthermore, ATXN2 overexpression and deficiency retarded cell cycle progression. ATXN2 mRNA levels showed a delayed phasic twofold increase under amino acid and serum starvation, similar to ATXN3, but different from motor neuron disease genes MAPT and SQSTM1. ATXN2 mRNA levels depended particularly on mTOR signalling. Altogether the data implicate ATXN2 in the adaptation of mRNA translation and cell growth to nutrient availability and stress.

overall_design: Factorial design comparing ataxin-2 knock-out mice with wild type littermates in three different tissues (midbrain, cerebellum, liver) and 3 different ages.

first: M

last: Fittschen

first: I

last: Lastres-Becker

first: E

last: Damrath

first: J

last: Drost

last: Klinkenberg

last: Heck

last: Azizov

last: Jendrach

first: G

last: Auburger


title: Gene expression regionalization in the outflow tract of the mouse heart

status: Public on Oct 15 2014

city: Marseille

first: Magali

address: Parc Scientifique de Luminy

department: Aix Marseille Université

country: France

institute: Institut de Biologie du Développement de Marseille

summary: Gene expression profiling of the inferior and superior wall of the distal midgestation arterial domain (outflow tract) of the wild type CD1 mouse embryonic heart

overall_design: Total RNA was recovered from dissections of the inferior and superior OFT subdomains of Mus musculus littermate embryonic hearts at day 10.5 of development (E10.5). Dissections were performed in Rnase free DEPC treated cold PBS. Seven dissected samples of each domain were pooled for total RNA extraction with RNeasy kit according to the manufacturer’s instructions (Qiagen). For a quality control measure, total RNA was checked using the Agilent BioAnalyzer System (Agilent Technologies). RNA from each source was amplified and labeled with biotin. The labeled samples were hybridized to the Affymetrix GeneChip Mouse Genome 430 2.0

last: Théveniau-Ruissy


title: Expression data from mouse adult and pups heart and hippocampal tissue.

status: Public on Oct 14 2014

city: Philadelphia

first: Junhyong

last: Kim

state: PA

address: 433 S University Avenue

department: Biology

country: USA

institute: University of Pennsylvania

summary: To assess in order to assess potential disparities in gene expression due to developmental differences we performed a comparison between hippocampus and heart tissues from rat and mouse pup (one week old) and adult (10 week old) animals.

overall_design: Using heart and hippocampal tissue from mouse  (C57BL/6) and rat (Sprague Dawley) we investigate via microarrays, gene expression divergence at the tissue level between a Brain and a Non-brain tissue. We also investigated any developement difference in gene expression between pups and adult animals. For the pups samples we used 3 biological replicates and for the adult samples we used 2 biological replicates with 2 technical replicates for each.

first: Chantal

last: Francis

first: Shreedhar

last: Natarajan

first: Miler

middle: T

last: Lee

first: Mugdha

last: Khaladkar

first: Peter

last: Buckley

first: Jai-Yoon

last: Sul

first: James

last: Eberwine


title: An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

status: Public on Oct 16 2014

city: Stanford

first: Seung

state: CA

address: 279 Campus Dr B303

department: Developmental Biology

institute: Stanford University

summary: The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene modules in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Module network analysis linked established regulators like Neurog3 to unrecognized roles in endocrine secretion and protein transport, and nominated multiple candidate regulators of pancreas development. Phenotyping mutant mice revealed that candidate regulatory genes encoding transcription factors, including Bcl11a, Etv1, Prdm16 and Runx1t1, are essential for pancreas development or glucose control. Our integrated approach provides a unique framework for identifying regulatory networks underlying pancreas development and diseases like diabetes mellitus.

overall_design: Gene expression analysis: 12 primary cell populations from wild-type pancreas and 1 cell type from a mutant background (E15 Ngn3-null cells) pancreas (in fetal and adult stage) were purified using a combination of cell surface markers and transgenic reporters. Total RNA was isolated from each cell type in at least biological triplicates, amplified and hybridized to Affymetrix Mouse 430 2.0 arrays.

first: Cecil

middle: M

last: Benitez

first: Kun

last: Qu

first: Takuya

last: Sugiyama

first: Philip

last: Pauerstein

first: Yinghua

last: Liu

first: Howard

middle: Y

last: Chang

middle: K


title: Dilution and amplification control study

summary: Mouse adult female brain’s cortex (C57BL/6, Charles River Laboratories, Inc.) was isolated and stored immediately at -80°C. Subsequently, the mRNA (15µg) was isolated using TRIzol Reagent and MicroFastTrack 2.0 Kit (Invitrogen). A Sample of 5µg was assessed on Affymetrix Mouse 430.2 array. Aliquots from the leftovers of the same cortical mRNA were diluted to single-cell RNA levels (0.1, 1, and 10 pg) and independently aRNA amplified for a total of 2 and 4 rounds and assessed on Affymetrix Mouse 430.2 arrays.

overall_design: A Sample of 5µg of mRNA was assessed on Affymetrix Mouse 430.2 array. Aliquots from the leftovers of the same cortical mRNA were diluted to single-cell RNA levels (0.1, 1, and 10 pg) and independently amplified, as described above, for a total of 2 and 4 rounds and assessed on Affymetrix Mouse 430.2 arrays.


title: Comparison of gene expression pattern between Wild-type and Setd2 knockout mESCs [Affymetrix]

city: Shanghai

first: Qiuhua

last: Huang

address: 197 ruijin road II

country: China

institute: Shanghai Institute of Hematology

summary:
SETD2/HYPB has been known as a histone H3K36 specific methyltransferase. However, its roles in physiology such as development and cellular function remain unclear. In this study, using mESCs as cellular model, we show that Setd2 mainly regulates differentiation of murine embryonic stem cells (mESCs) towards primitive endoderm. This study aimed at exploring how did Setd2 regulate primitive endoderm. differentiation.
We used microarrays to detail the global programme of gene expression controled by setd2, which is required for endoderm differentiation.

overall_design: Wild type and Setd2 knockout mESCs were selected for RNA extraction and hybridization on Affymetrix GeneChip® mouse genome 430 2.0 arrays. We sought to obtain some deregulated genes, which were required for primitive endoderm differentiation. For comparison, three biological repeats of each were performed.

first: Yuanliang

last: Zhang

first: Zhu

last: Chen

first: Qiuhuang

first: Saijuan


title: Mouse and rat cells and tissues

first: Junhyong

last: Kim

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

sample_organism:
Mus musculus
Rattus norvegicus

platform_organism:
Mus musculus
Rattus norvegicus

overall_design: Refer to individual Series


title: HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration

status: Public on Oct 10 2014

city: Lausanne

first: Tamara

last: Seredenin

address: AI2135 Station 15 EPFL

country: Switzerland

institute: EPFL


title: Expression data from Soma dissected from single-cell mouse Hippocampal neurons

summary: To assess neuronal expression divergence between mice and rats, we used the Affymetrix array platform to assay the transcriptomes of micro-dissected individual soma and pool of dendrites of hippocampal neurons in dispersed primary cell cultures from  rat and  mouse.

overall_design: Using microdissected soma and dendrites from primary cultures of hippocampal neurons of two mouse strains (C57BL/6 and Balb/c) and one rat strain (Sprague-Dawley), we investigate via microarrays, subcellular localization of mRNAs in neurons

first: Chantal

last: Francis

first: Shreedhar

last: Natarajan

first: Miler

first: Mugdha

first: Peter


title: Gene expression data from cortex of 15w old WT, R6/2, HDAC4het and R6/2::HDAC4het mice

summary: Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a glutamine rich domain. We hypothesised that it may be involved in the molecular pathogenesis of Huntington’s disease (HD), a protein folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion and transcriptional dysregulation.   We found that HDAC4 interacts with huntingtin in a polyglutamine-length dependent manner and co-localises with cytoplasmic inclusions. We show that HDAC4 reduction delayed cytoplasmic aggregate formation, restored Bdnf transcript levels and rescued neuronal and cortico-striatal synaptic function in HD mouse models. This was accompanied by an improvement in motor co-ordination, neurological phenotypes and increased lifespan. Surprisingly, HDAC4 reduction had no effect on global transcriptional dysfunction and did not modulate nuclear huntingtin aggregation.     Our results define a crucial role for cytoplasmic aggregation in the molecular pathology of HD. HDAC4 reduction presents a novel strategy for targeting huntingtin aggregation which may be amenable to small molecule therapeutics.

overall_design: mRNA expression analysis was performed by microarray in 15 weeks old WT (n=8), R6/2 (n=9), HDAC4het (n=8) and Double R6/2::HDAC4het (n=9) mice. Microarray quality control was performed using the software package provided on RACE (http://race.unil.ch).

first: Michal

last: Mielcarek

first: Christian

last: Landles

first: Andreas

last: Weiss

first: Amyaouch

last: Bradaia

last: Seredenina

first: Linda

last: Inuabasi

first: Kristian

last: Wadel

first: Crystelle

last: Touller

first: Rachel

last: Butler

first: Janette

last: Robertson

first: Sophie

middle: A

last: Franklin

first: Donna

middle: L

last: Smith

first: Paul

last: Marks

first: Erich

last: Wanker

first: Ruth

last: Luthi-Carter

first: Eric

middle: N

last: Olson

first: Herman

last: van der Putten

first: Vahri

last: Beaumont

first: Gillian

middle: P

last: Bates


title: Microarray of 3D cultured basal cells in the presence of Wnt3A

status: Public on Oct 22 2014

first: Qing Cissy

last: Yu

address: 320 Yue Yang Road

department: Institute of Biochemistry and Cell Biology

institute: Shanghai Institute of Biological Sciences

summary:
Adult stem cells have the ability to self-renew and to generate specialized cells. Self-renewal is dependent on extrinsic niche factors but few of those signals have been identified. We show that adult mammary glands contain a Wnt-responsive cell population that is enriched for stem cells. In cell culture experiments, exposure to purified Wnt protein clonally expands mammary stem cells for many generations and maintains their ability to generate functional glands in transplantation assays. We propose here that Wnt3A treated mammary stem cells retain their stemness through the regulation of its downstream target genes.
We used microarrays to detail the global gene expression pattern underlying mammary stem cells response towards Wnt3A treatment and identified distinct classes of genes during this process

overall_design: Mammary glands from 8- to 12-week-old virgin female mice were isolated and single-cell suspension was obtained. Mammary stem cell enriched population (Lin-, CD24+, CD29hi) cells were isolated using BD FACSAria. The purity of sorted population was routinely checked and ensured to be more than 95%.Total RNA from 2nd colonies passage cultured in the presence of vehicle and Wnt3A was extracted with PicoPure (Arcturs) in accordance with the manufacturer’s protocol. RNA concentration was determined with NanoDrop ND-1000, and quality was determined using the RNA 6000 Nano assay on the Agilent 2100 Bioanalyzer (Agilent Technologies). Affymetrix microarray analysis, fragmentation of RNA, labelling, hybridization to Mouse Genome 430 2.0 microarrays, and scanning were performed in accordance with the manufacturer’s protocol (Affymetrix). Total 4 samples representing two sets of replicates were analyzed.

first: Zeng

last: Yi


title: Expression data from mouse trophoblast stem cells with knock-down of Ets2

status: Public on Oct 09 2014

city: Wellington

first: Peter

last: Pfeffer

address: Kelburn Parade

department: Biological Sciences

country: New Zealand

institute: Victoria University of Wellington

summary: Mouse trophoblast stem cells were treated for 48 hours with two different stealth ds-siRNA against Elts2 and expression compared to samples treated with Invitrogen's mediumGC control and to no treatment samples.

overall_design: 3 biological repeats of each sample

first: Martyn

last: Donnison


title: aCGH data of Rb/p53 deficient mammary tumors

status: Public on Oct 07 2014

city: Guelph

first: Robert

last: Jones

address: 50 Stone Rd

department: Biomedical Sciences

country: Canada

institute: University of Guelph

type: Genome variation profiling by genome tiling array

summary: To investigate the impact of combined Rb and p53 loss in mammary tumorigenesis, we used transgenic  and viral approaches to delete Rb and p53 floxed alleles specifically in the mouse mammary epithelium.  Although MMTV-Cre (NLST) targets stem/bi-potent progenitors in the mammary gland, a subset of MMTV-Cre:Rbf/f;p53f/f mice developed non-mammary tumors. Thus, freshly isolated primary mammary epithelial cells from these animals were transplanted into the mammary fat pads of immunodeficient mice and monitored for tumor formation. In addition, primary MECs were isolated from Cre-negative Rbf/f;p53f/f mice, infected with Ad-Cre followed by orthotopic transplantation.  In all these cases, resulting tumors shared similar spindle-shape histology, expressed high levels of vimentin, a mesenchymal marker, but not E-cadherin, a luminal marker, and were classified as adeno-sacrcomatoid/spindle-cell/mesenchymal-like breast cancer. We used aCGH to detect copy number alterations associated with Rb/p53 deletion.

overall_design: Tumor DNAs from MMTV-Cre: Rbf/f;p53f/f and Ad-Cre: Rbf/f;p53f/f  conditional mutant mice are being compared to pooled tail DNAs in order to identify common alterations associated with Rb/p53 deficient tumorigenesis

first: Eldad

last: Zacksenhaus


title: Comparison of mouse naïve (CD44lo) CD8+ T cells sorted into the highest and lowest 20% with respect to CD5

status: Public on Oct 08 2014

city: Minneapolis

first: Stephen

last: Jameson

state: MN

address: 2101 6th St. SE

department: Center for Immunology

institute: University of Minnesota

summary: Lymphocytes from spleen and lymph nodes of unimmunized adult C57BL/6 mice were isolated, stained with antibodies for flow cytometry, and sorted into the CD8+ CD44lo CD5hi and CD5lo pool

middle: C

first: Ross

middle: B

last: Fulton


title: A two miRNA classifier differentiates follicular thyroid carcinomas from follicular thyroid adenomas

city: Bergen

first: Tomasz

last: Stokowy

address: Nygardsgaten 5

department: IT Division

country: Norway

institute: University of Bergen

summary: The inherent diagnostic limitations of thyroid fine needle aspiration (FNA), especially in the “indeterminate”  category, can be partially overcome by molecular analyses. We aimed at the identification of  miRNAs that could be used to improve the discrimination of indeterminate FNAs. miRNA expression profiling  was performed for 17 follicular carcinomas (FTCs) and 8 follicular adenomas (FAs). The microarray  results underwent cross-comparison using three additional microarray data sets. Candidate miRNAs were  validated by qPCR in an independent set of 32 FTCs and 46 FAs. Sixty-eight differentially expressed miRNAs  were identified. Thirteen miRNAs could be confirmed by cross comparison. A two-miRNA-classifier was  established improving the diagnostic applicability and resulted in a sensitivity of 82% and a specificity  of 49%. We present a classifier that has the potential to be successfully evaluated in cytology material  for its capability to discriminate (mutation negative) indeterminate cytologies and thereby improving  the pre-surgical diagnostics of thyroid nodules.

overall_design: miRNA expression profiling was performed for 17 follicular carcinomas (FTCs) and 8 follicular adenomas (FAs). All samples are independent, coming from different patients.

first: Markus

last: Eszlinger

first: Ralf

last: Paschke


title: Spatial Regulation of Gene Expression in Articular Cartilage Assessed by Laser Captured Microdissection and Microarray

status: Public on Oct 20 2014

city: Bethesda

first: WeiPing

last: Chen

state: MD

address: Bldg 8, Room 1A11, NIDDK/NIH

department: GCL

institute: NIDDK/NIH

summary: We used laser capture microdissection to isolate different zones of the articular cartilage from proximal tibiae of 1-week old mice, and used microarray to analyze global gene expression. Bioinformatic analysis corroborated previously known signaling pathways, such as Wnt and Bmp signaling, and implicated novel pathways, such as ephrin and integrin signaling, for spatially associated articular chondrocyte differentiation and proliferation. In addition, comparison of the spatial regulation of articular and growth plate cartilage revealed unexpected similarities between the superficial zone of the articular cartilage and the hypertrophic zone of the growth plate.

overall_design: Collecte five biological replications in three superficial, mid zone and deep zones of Articular Cartilage Assessed by Laser Captured Microdissection and Microarray(Superficial Zone vs Mid Zone vs Deep Zone)

first: Julian

last: Lui

first: Michael

last: Chau

first: Weiping

first: Crystal

middle: F

last: Cheung

first: Jeffrey

last: Hanson

first: Jaime

last: Rodriguez-Canales

first: Ola

last: Nilsson

last: Baron


title: Defining a mesenchymal progenitor niche at single cell resolution

status: Public on Oct 04 2014

first: Maya

middle: Elise

last: Kumar

address: 279 Campus Drive, room B469

department: Biochemistry

institute: Stanford University School of Medicine

summary: Most vertebrate organs are composed of epithelium surrounded by support and stromal tissues formed from mesenchyme cells, which are not generally thought to form organized progenitor pools.  Here we use clonal cell labeling with multicolor reporters to characterize individual mesenchymal progenitors in the developing mouse lung.  We observe a diversity of mesenchymal progenitor populations with different locations, movements, and lineage boundaries.  Airway smooth muscle (ASM) progenitors map exclusively to mesenchyme ahead of budding airways.  Progenitors recruited from these tip pools differentiate into ASM around airway stalks; flanking stalk mesenchyme can be induced to form an ASM niche by a lateral bud or by an airway tip plus focal Wnt signal.  Thus, mesenchymal progenitors can be organized into localized and carefully controlled domains that rival epithelial progenitor niches in regulatory sophistication.

overall_design: Mesenchyme was microdissected from e11.5 and e12.5 lung branch tips and stalks and profiled directly.  Another set of stalk dissections were cultured in either control media or media containing Wnt1.  All experiments done in duplicate.

middle: E

first: Mark

last: Krasnow


title: Expression data from mouse dissected dendrites

first: Junhyong

last: Kim

summary: Using microdissected dendrites from primary cultures of hippocampal neurons of two mouse strains (C57BL/6 and Balb/c) and one rat strain (Sprague-Dawley), we investigate via microarrays, subcellular localization of mRNAs in dendrites of neurons to assay the evolutionary differences in subcellular dendritic transcripts localization.

overall_design: To assess neuronal dendrite expression divergence between mice and rats, we used the Affymetrix array platform to assay the transcriptomes of micro-dissected individual dendrites of hippocampal neurons in dispersed primary cell cultures from Sprague-Dawley rat (9 biological replicates), C57BL/6 mouse  (14 biological replicates), and Balb/c mouse (5 biological replicates)

first: Chantal

last: Francis

first: Shreedhar

last: Natarajan

first: Miler

last: Lee

first: Mugdha

last: Khaladkar

first: Peter

last: Buckley

first: Jai-Yoon

last: Sul

first: James

last: Eberwine


title: Transcriptome profile of human dermal macrophages and monocyte-derived macrophages

city: Singapore

first: Kaibo

last: Duan

address: 8A Biomedical Grove, Immunos Building, Level 4

country: Singapore

institute: Singapore Immunology Network

summary: DC, monocyte and macrophage networks are evolutionarily conserved but the distinct subsets have been difficult to distinguish due to shared overlapping phenotypic markers between the cells. Using transcriptome microarray profiling of human and mouse mononuclear phagocyte subsets, we have distinguished human dermal DCs from monocyte-derived cells and macrophages.

overall_design: Gene Expression from total RNA from human dermal macrophages, epidermal LCs and CD14+ cells subsets purified by FACS

first: Florent

last: Ginhoux

last: Poidinger

first: Matthew

last: Collin

first: Muzlifah

last: Haniffa


title: Xenomicrobiota transplant experiment

status: Public on Oct 02 2014

city: St Louis

first: Henning

last: Seedorf

address: 4444 Forest Park Blvd

institute: Washington University

summary:
Gut microbes elicit specific changes in gene expression in the colon of mice. We colonized germ-free mice with microbial communities from the guts of humans, zebrafish and termites, human skin and tongue, soil and estuarine microbial mats.
We used microarrays to detail the differences in global gene expression in colon tissue that are caused by the different microbial communities 28 days after gavage into the germfree animal.

overall_design: Three biological replicates per group, male C57BL/6 mice (12-16 weeks old)

first: H

first: J

middle: I

last: Gordon


title: Global gene expression profile of INS1E cells, hIAPP-INS1E cells and rIAPP-INS1E cells.

status: Public on Oct 03 2014

city: Barcelona

first: Gema

last: Alcarraz-Vizán

address: Rossello 149

department: Diabetes & Obesity Laboratory

country: Spain

institute: IDIBAPS

summary:
Islet amyloid polypeptide (IAPP) is the main component of amyloid deposits in type 2 diabetic patients. Cells overexpressing the human transcript of IAPP (hIAPP) present defects in insulin secretion.
In this dataset, we include the expression data obtained from the rat pancreatic beta-cells INS1E stably transfected with human (hIAPP) or rat (rIAPP) IAPP, which lead to the overexpression of the different variants of IAPP protein. We also include INS1E cells with empty vector as control.

overall_design: 6 samples were analyzed from 3 INS1E clones stably transfected with different IAPP transcripts.

first: Anna

last: Novials


title: Upregulation of CD11A on hematopoietic stem cells denotes the loss of long-term reconstitution potential

city: Irvine

middle: Arthur

last: Inlay

address: 845 Health Sciences Rd. Gross Hall Rm. 2010

department: Molecular Biology & Biochemistry

institute: UC Irvine

type:
Expression profiling by array
Third-party reanalysis

summary: Comparison of gene expression patterns between phenotypic mouse HSCs (Lin- KIT+ SCA-1+ FLK2- CD150+ CD34-) separated into CD11A- and CD11A+ fractions. A link to our analysis of these populations can be found here (https://gexc.stanford.edu/model/1007).

overall_design: Mouse HSCs were subdivided based on expression of CD11A into positive and negative subfractions, and gene expression patterns analyzed by the Gene Expression Commons (gexc.stanford.edu)

first: John

middle: W

last: Fathman

first: Jun

last: Seita

first: Irving

last: Weissman


title: Response of the inguinal mammary gland tissue transcriptome to 17B-estradiol in 12- to 13-week-old virgin mice

status: Public on Oct 01 2014

city: Quebec

first: Ezequiel

last: Calvo

state: Quebec

address: 2705 Boul. Laurier

department: Molecular Endocrinilogy

institute: CRCHUL

summary:
Different strategies may be used to draw conclusions from the data generated by DNA microarrays in our study of the effect of estradiol (E2) on the transcriptome of the mammary gland of mice. We selected two strategies: the first one involving a classification by cellular process of regulated genes, and the second one taking advantage of gene expression profile over a time course of treatment. We also used two standardization methods, MAS5.0 and RMA, in order to assess their similarities and differences leading us to a better understanding of their impact on the results. In comparing expression patterns of regulated genes by E2, we observed that there are good similarities between gene expression profiles obtained by MAS5.0 and RMA. However, when the ratio between signal intensities of treatment and control is low, differences between data normalized by MAS 5.0 and RMA are more apparent, i.e. where the discrimination between biological and technical variability is the least obvious.

Keywords: Time course

overall_design: Mammary gland tissue samples were obtained in gonadectomized (GDX) animals treated with vehicle (control group), or injected with E2 (0.05 µg mg/mouse) at 1, 3, 6, 12, 18 and 24h prior to necropsy.

first: Denis

last: Mathon


title: IL-17A influences essential functions of the monocyte / macrophage lineage and is involved in advanced murine and human atherosclerosis

city: Eggenfelden

first: Christian

middle: Albert

last: Gleissner

address: Simonsöder Allee 20

department: Cardiology

institute: Rottal-Inn Kliniken KU

summary: Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. Interleukin-17A is a pro-inflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care.  26-weeks old apolipoprotein E-deficient (Apoe-/-) mice were fed a standard chow diet and treated either with IL-17A mAb (n=15) or irrelevant immunoglobulin (n=10) for 16 weeks. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (P=0.001) by reducing inflammatory burden and cellular infiltration (P=0.01) and improved lesion stability (P=0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, sensitization of antigen-presenting cells toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a pro-inflammatory milieu and up-regulation of molecules expressed by the IL-17A-induced macrophage subtype.   We here show for the first time that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in Apoe-/- mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte / macrophage lineage.  In addition, translational experiments underline the relevance for the human system.

overall_design: Effects of IL-17A on human monocyte-derived macrophages were assessed (n=2 per group).

last: Erbel


title: Differential gene expression analysis in motor and sensory cortex as a result of experimental autoimmune encephalomyelitis (EAE), a neuroinflammatory model for Multiple sclerosis.

city: Heidelberg - Melbourne

first: Stefan

last: Thiem

state: Victoria

address: 145 Studley Road

department: Cancer Research

country: Australia

institute: Olivia Newton-John Cancer Research Institute

summary: We performed micrarrays to investigate neuronal gene expression changes during acute inflammatory CNS axon injury using the murine myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) model. The present study was assigned to assess the direct and indirect endogenous neuronal response to spinal axonal injury in the motor and sensory cortex.

overall_design: Gene expression in motor and sensory cortex enriched tissue was assessed from four healthy and six EAE female mice. Tissue was collected from mice with paraplegia or monoplegia, with contralateral hindlimb paresis (EAE day 18-21).  The gene expression profiles of the EAE mice were compared to the motor or sensory cortex of healthy control mice, resulting in a list of differentially expressed genes in healthy and EAE mice.

last: Jonas

first: Melissa

last: Gresle

first: Helmut

last: Butzkueven

first: Victoria

last: Perreau


title: Effects of overexpressed Atoh8 on the transcriptional profile of mouse ductal cells mPAC in the absence or presence of co-expressed Neurogenin3

city: Genève

first: Jordi

last: Altirriba

address: Rue Michel-Servet 1

department: Dpts de Médecine Interne et de Physiologie cellulaire et Métabolisme

institute: Centre Médical Universitaire de Genève

summary: The basic helix-loop-helix (bHLH) transcription factors of the Drosophila’s atonal-related superfamily Neurogenin3 (Neurog3) and NeuroD1 promote endocrine differentiation in the gastrointestinal tract.  Atonal Homolog 8 (Atoh8/Math6) is a newly identified member of the atonal-related family whose expression is induced by Neurog3 and NeuroD1 in cell culture, indicating a possible role for this gene in the endocrine differentiation program downstream of these two pro-endocrine factors. Intriguingly, available experimental evidence based on a reduced number of genes suggests that Atoh8 may negatively regulate Neurog3-targeting events. In this study, we have analyzed global changes in gene expression profiles upon exogenous expression of Atoh8 alone or in combination with Neurog3 in mouse pancreatic duct (mPAC) cells. These cells activate neuroendocrine-specific gene expression in response to Neurog3 and NeuroD1 and thus serve as an optimal model to evaluate the proendocrine activity of Atoh8.  We have compared transcriptional profiles between mPAC cells treated with a recombinant adenovirus expressing Atoh8 (Ad-Atoh8) or a control adenovirus encoding B-galactosidase (Ad-Bgal), and between cells treated with Ad-Neurog3+Ad-Bgal or cells treated with Ad-Neurog3+Ad-Atoh8. The results obtained show that Atoh8 exhibits a very modest transcriptional activity in these cells thus confirming that Atoh8 does not function as a proendocrine gene. Furthermore, our data also confirm the ability of Atoh8 to block Neurog3-dependent transcriptional activation events. However, since repression is only seen for a small subset of Neurog3 gene targets, we discard a general role of Atoh8 as a negative regulator of Neurog3 pro-endocrine activity.

overall_design: mPAC cells (mouse pancreatic duct cells) were divided in 6 groups according to the treatment received: 1) non-treated (control for the infection effect), 2) treated with recombinant adenoviruses coding for β-galactosidase (control for infection with one adenovirus), 3) treated with recombinant adenoviruses coding for Atonal Homolog 8, 4) treated with recombinant adenoviruses coding for Neurogenin 3, 5) treated with recombinant adenoviruses coding for β-galactosidase and Neurogenin 3 (control for the effect of two adenoviruses, being one of them Neurogenin 3), 6) treated with recombinant adenoviruses coding for Neurogenin 3 and Atonal Homolog 8. Experiment was performed three independent times (3 independent biological replicates).

first: Miriam

last: Ejarque

first: Ramon

last: Gomis

first: Rosa

last: Gasa


title: HPL-2 in N2 (wild-type) early embryo

status: Public on Oct 11 2014

city: Santa Cruz

first: Susan

last: Strome

address: 1156 High St.

department: Molecular, Cell, and Developmental Biology

institute: UC Santa Cruz

type: Genome binding/occupancy profiling by genome tiling array

summary: ChIP-chip of HPL-2 in N2 C. elegans early embryo

overall_design: EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: N2; Developmental Stage: Early Embryo; Genotype: wild type; Sex: population predominantly Hermaphrodites perhaps with some Males; NUMBER OF REPLICATES: 3; EXPERIMENTAL FACTORS:  temperature 20

first: Jacob

last: Garrigues


title: Gene expression by cyotosolic DNA stimulation

status: Public on Sep 30 2014

city: Chicago

first: Seng-Ryong

last: Woo

state: Illinois

address: 929 E 57th street

department: Pathology

institute: University of Chicago

summary: STING molecule has been reported to be important adaptor molecule for cytosolic DNA sensing. We investigated gene expression by cytosolic DNA stimulation using bone marrow derived dendritic cells. We comparared gene expression profile between WT and STING knock out BMDCs after cytosolic DNA stimulation.

overall_design: We generated BMDCs by culturing in the presence of GM-CSF. BMDCs were stimulated by purified tumor-cell derived DNA using lipofectamine. After 7 hrs incubation, total RNA was isolated using Rneasy kit (Qiagen) and microarray was performed at genomic core facility in university of Chicago

first: SengRyong

first: Thomas

last: Gajewski


title: MMP3 treatment of SCp2 mouse mammary epithelial cells

city: Jacksonville

first: Derek

middle: Charles

last: Radisky

state: Florida

address: 4500 San Pablo Road

department: Cancer Biology

institute: Mayo Clinic

summary: Response of mouse mammary epithelial cells to treatment with  MMP3

overall_design: Cells were untreated (d1 control) or treated with MMP3 for 1-4 days (d1-4 MMP3), or washed and then allowed to recover for three additional days (d5-7 recover) then isolated for RNA.


title: Gene expression data from cortex of 9w old WT, R6/2, HDAC4het and R6/2::HDAC4het mice

city: Lausanne

first: Tamara

last: Seredenin

address: AI2135 Station 15 EPFL

institute: EPFL

summary: Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a glutamine rich domain. We hypothesised that it may be involved in the molecular pathogenesis of Huntington’s disease (HD), a protein folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion and transcriptional dysregulation.   We found that HDAC4 interacts with huntingtin in a polyglutamine-length dependent manner and co-localises with cytoplasmic inclusions. We show that HDAC4 reduction delayed cytoplasmic aggregate formation, restored Bdnf transcript levels and rescued neuronal and cortico-striatal synaptic function in HD mouse models. This was accompanied by an improvement in motor co-ordination, neurological phenotypes and increased lifespan. Surprisingly, HDAC4 reduction had no effect on global transcriptional dysfunction and did not modulate nuclear huntingtin aggregation.     Our results define a crucial role for cytoplasmic aggregation in the molecular pathology of HD. HDAC4 reduction presents a novel strategy for targeting huntingtin aggregation which may be amenable to small molecule therapeutics.

overall_design: mRNA expression analysis was performed by microarray in 9 weeks old WT (n=9), R6/2 (n=9), HDAC4het (n=9) and Double R6/2::HDAC4het (n=10) mice. Microarray quality control was performed using the software package provided on RACE (http://race.unil.ch).

first: Michal

last: Mielcarek

last: Landles

first: Andreas

last: Weiss

first: Amyaouch

last: Bradaia

last: Seredenina

first: Linda

last: Inuabasi

first: Kristian

last: Wadel

first: Crystelle

last: Touller

first: Rachel

last: Butler

first: Janette

last: Robertson

first: Sophie

last: Franklin

first: Donna

last: Smith

first: Paul

last: Marks

first: Erich

last: Wanker

first: Ruth

last: Luthi-Carter

first: Eric

last: Olson

first: Herman

last: van der Putten

first: Vahri

last: Beaumont

first: Gillian

last: Bates


title: Elevated expression of AKR1C3 leads esophageal cancer resistant to ionizing radiation via modulation of oxidative stress (TE13)

status: Public on Sep 27 2014

city: Beijing

first: Qingtao

last: Hu

address: NO.1 Beichen West Road, Chaoyang District

institute: Beijing Institute of Genomics,Chinese Academy of Sciences

summary: With the aim to elucidate the etiology of radioresistance, we explored the genetic alterations in non-radioresistant vs. resistant esophageal cancer cells acquired by long-term fractionated radiation. We found AKR1C3, an aldo-keto reductase expressed seldom in most human tissues, expressed higher in radioresistance-acquired cells. Suppression of AKR1C3 via RNAi or its chemical inhibitors restored the sensitivity of the acquired tumor cells and xenograft nude mice to ionizing radiation (IR). We also found the potential involvement of AKR1C3 in removal of cellular ROS and explain, at least partially, the acquired radioresistance by AKR1C3 overexpression.

overall_design: Genome-wide profiling of gene expression in KY170R v. KY170 and TE13R v. TE13 using Illumine Human-6 V3 microarray indicated that over 900 genes were found to be remarkably differentiated. Among them, AKR1C3, an aldo-keto reductase existing at a low level in most human tissues, attracted our attention due to its significant expression in both radioresistant cells.

first: Wei

last: Xiong

first: Jing

last: Zhao

first: Hongliang

last: Yu

first: Xiaoying

last: Li

first: Shaoqian

last: Sun

first: Yi

first: Qing

last: Xia

first: Chuanling

last: Zhang

first: Qiuchen

last: He

first: Xianshu

last: Gao

first: Lihe

first: Demin

last: Zhou


title: Transcriptional profiling of liver from wild type and PXR-null mice treated with PCN

city: Research Triangle Park

first: Christopher

last: Corton

state: NC

address: 109 TW Alexander Dr.

institute: US-EPA

summary: Many environmentally-relevant chemicals and drugs activate the nuclear receptor pregnane X receptor (PXR).  Activation of PXR can lead to increases in liver weight in part through hepatocyte replication similar to a large number of compounds that activate other nuclear receptors such as the peroxisome proliferator-activated receptor alpha and the constitutive activated receptor (CAR).  PXR controls the expression of a large battery of genes involved in xenobiotic metabolism.  Identification of genes that are accurate predictors of PXR activation would be useful in high-throughput screens to assess potential toxicity and drug-drug interactions.  Here, we identified PXR-dependent genes in the mouse liver after exposure to pregnenolone 16alpha-carbinonitrile (PCN), a chemical that is often used as a model PXR agonist.

overall_design: The animal studies were carried out at the University of Kansas Medical Center (Kansas City, KS) under federal guidelines for the use and care of laboratory animals and was approved by the KUMC Institutional Animal Care and Use Committee.  Eight-week-old adult C57BL/6 mice were purchased from Jackson Laboratories (Bar Harbor, ME).  Generation of the PXR-null mice was previously described (Staudinger et al., (2001),  Proc Natl Acad Sci USA 98:3369–3374).  PXR-null breeder pairs were engineered and backcrossed into the C57BL/6 background.  Adult male wild-type mice and PXR-null mice were maintained on standard laboratory chow and were allowed food and water ad libitum. All mice were treated once a day i.p. with either vehicle (corn oil) or PCN at 400 mg/kg/day for 4 days.  Livers were removed 24-hrs after the last dose.  Portions of the livers were rapidly snap-frozen in liquid nitrogen and stored at -70°C until analysis.  Liver gene expression analysis was performed according to the Affymetrix recommended protocol using Affymetrix Mouse Genome 430 2.0 GeneChips®. Total RNA (5 μg per sample) was labelled using the Affymetrix® One-Cycle cDNA Synthesis protocol and hybridized to arrays as described by the manufacturer (Affymetrix®, Santa Clara, CA).  Microarray hybridizations were conducted overnight at 45°C while rotating in an Affymetrix hybridization oven. After 16 hours of hybridization, the cocktail was removed and the arrays were washed and stained in an Affymetrix GeneChip® fluidics station 450 according to the Affymetrix-recommended protocol. Arrays were scanned on an Affymetrix GeneChip® scanner. Four mice per group were examined.

first: Chris


title: Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA

city: Rochester

first: Zhifu

address: 200 1st ST SW

department: HSR-BSI

summary: We aimed to identify clinically meaningful biomarkers in pulmonary carcinoid tumors (PCTs), a member of neuroendocrine neoplasms, via profiling miRNAs and mRNAs.

overall_design: Fifty-one individuals who had never smoked tobacco products and developed PCTs between 1997 and 2008 were studied. A group of 47 carcinoids tumors were analyzed; each with paired tumor-adjacent normal tissue samples (at least 5 cm away from the primary tumors). There are 24 pairs of tumor/normal samples in FF tissues, and 23 pairs of tumor/normal samples in FFPE. The expression status of 1145 miRNAs was generated by Illumina miRNA Arrays.

first: Bo

last: Deng

first: Julian

last: Molina

first: Marie

last: Aubry

first: Liang

last: Wang

first: Bruce

last: Eckloff

first: George

last: Vasmatzis

first: Ming

last: You

first: Eric

middle: D

last: Wieben

first: Jin

last: Jen

first: Dennis

last: AWigle

first: Ping

last: Yang


title: VPA alleviates neurological deficits and restores gene expression in a mouse model of Rett syndrome

city: Shinagawa-ku

first: KATSUHIDE

last: IGARASHI

state: Tokyo

department: Life Science Tokyo Advanced Research center (L-StaR)

country: Japan

institute: Hoshi University School of Pharmacy and Pharmaceutical Science

summary: Rett syndrome (RTT) is a devastating neurodevelopmental disorder that occurs once in every 10,000-15,000 live female births. Despite intensive research, no effective cure is yet available. Valproic acid (VPA) has been used widely to treat mood disorder, epilepsy, and a growing number of other disorders. In limited clinical studies, VPA has also been used to control seizure in RTT patients with promising albeit somewhat unclear efficacy. In this study we tested the effect of VPA on the neurological symptoms of RTT and discovered that short-term VPA treatment during the symptomatic period could reduce neurological symptoms in RTT mice. We found that VPA restores the expression of a subset of genes in RTT mouse brains, and these genes clustered in neurological disease and developmental disorder networks. Our data suggest that VPA could be used as a drug to alleviate RTT symptoms.

overall_design: Wild type or MeCP2KO mice received daily injections of VPA (300 mg/kg) for 2 weeks.  Each experimental condition: WT control, KO treated with VPA (KO+VPA), and KO treated with saline (KO+saline). Half brain samples were retrieved.

first: Xinyu

last: Zhao

first: Kinichi

last: Nakashima

first: Katsuhide

last: Igarashi


title: Expression of genes in E17 p57-/-  and p57+/+ hepatic mesothelial and submesothelial cells

city: Isehara

first: Akihide

last: Kamiya

state: Kanagawa

address: 143 Shimokasuya

institute: Tokai University

summary: To analyze p57 function in mouse fetal liver, we surgically isolated mesothelial and submesothelial cells from E17 p57-/- and p57+/+ livers.

overall_design: Compared gene expression in E17 p57-/- and p57+/+ hepatic mesothelial and submesothelial cells.

first: Hiromitsu

last: Nakauchi

first: Ayaka

last: Yanagida


title: Elevated expression of AKR1C3 leads esophageal cancer resistant to ionizing radiation via modulation of oxidative stress (KY170)

first: Qingtao

last: Hu

first: Wei

last: Xiong

first: Jing

first: Hongliang

last: Yu

first: Xiaoying

last: Li

first: Shaoqian

last: Sun

first: Yi

first: Qing

last: Xia

first: Chuanling

last: Zhang

first: Qiuchen

last: He

first: Xianshu

last: Gao

first: Lihe

first: Demin

last: Zhou


title: Ovarian Cancer Cell line Panel (OCCP): gene expression data.

status: Public on Sep 18 2014

city: Rotterdam

first: Marcel

last: Smid

address: Dr. Molewaterplein 50

department: Medical Oncology

country: Netherlands

institute: Erasmus MC

summary: Epithelial ovarian cancer is a very heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Rational therapeutic approaches need to account for interpatient and intratumoral heterogeneity in treatment design. Detailed characterization of in vitro models representing the different histological and molecular subtypes is therefore imperative.     Strikingly, from ~100 available ovarian cancer cell lines the origin and which subtype they represent is largely unknown. We have extensively and uniformly characterized 39 ovarian cancer cell lines (with mRNA/microRNA expression, exon sequencing, dose response curves for clinically relevant therapeutics) and obtained all available information on the clinical features and tissue of origin of the original ovarian cancer to refine the putative histological subtypes. From 39 ovarian cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type.     Three morphological subtypes (21 Epithelial, 7 Round, 12 Spindle) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes for the Spindle subtype. Clinical validation showed a clear association of the spindle-like tumors with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the morphological subtypes associated with the molecular C1-6 subtypes identified by Tothill et al. [1], Spindle clustered with C1-stromal subtype, Round with C5-mesenchymal and Epithelial with C4 subtype.    We provide a uniformly generated data resource for 39 ovarian cancer cell lines, the ovarian cancer cell line panel (OCCP). This should be the basis for selecting models to develop subtype specific treatment approaches, which is very much needed to prolong the survival of ovarian cancer patients.

overall_design: Gene expression was measured for 32 ovarian cancer cell lines using the GeneChip Human Exon 1.0 ST Array (Affymetrix). Morphological subtypes were assigned based on cell morphology, size, growth pattern and proliferation rate during culturing of the cell lines.

first: Jozien

last: Helleman

first: Corine

last: Beaufort

first: Els

last: Berns


title: mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues (gene expression)

status: Public on Sep 25 2014

city: Cambridge

first: Stephen

last: Eichhorn

state: MA

address: 9 Cambridge Center

department: Biology

institute: Whitehead Institute for Biomedical Research

summary: MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to many additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition or translational state, mRNA destabilization explains most (70% to >90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect on gene expression is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results add to the fundamental understanding of miRNAs, imply that consequential miRNA-mediated repression is largely irreversible and simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects.

overall_design: 6 samples from a variety of primary cell types

first: Huili

last: Guo

first: Sean

last: McGeary

first: Ricard

last: Rodriguez-Mias

first: Chanseok

last: Shin

first: Daehyun

last: Baek

first: Shu-hao

last: Hsu

first: Kalpana

last: Ghoshal

first: Judit

last: Villén

first: David

last: Bartel


title: Elevated expression of AKR1C3 leads esophageal cancer resistant to ionizing radiation via modulation of oxidative stress

first: Qingtao

last: Hu

first: Wei

last: Xiong

first: Jing

last: Zhao

first: Hongliang

last: Yu

first: Xiaoying

last: Li

first: Shaoqian

last: Sun

first: Yi

first: Qing

last: Xia

first: Chuanling

last: Zhang

first: Qiuchen

last: He

first: Xianshu


title: Global transcriptional profiling reveals distinct functions of thymic stromal subsets and age-related changes during thymic involution

status: Public on Sep 12 2014

city: Austin

first: Lauren

last: Ehrlich

state: TX

address: 2506 Speedway A5000

department: Molecular Biosciences

institute: The University of Texas at Austin

summary:
The thymic microenvironment is essential for proper differentiation and selection of thymocytes.Thymic involution in aged mice results in decreased T cell output and immune function. Here we use gene expression profiling of FACS sorted thymic stromal subsets to identify molecular mediators of thymocyte: stromal cell interactions, as well as gene expression changes thymic stromal subsets during early stages of thymic involution .
We used microarrays to analyze gene expression differences between thymic stromal subsets from male C57BL/6J mice 1, 3,  and 6 months of age.

overall_design: Thymic stromal subsets (cTEC, mTEClo, mTEChi, Sirpa-DC, Sirpa+DC, and fibroblasts) were isolated from two 1-, 3-, and 6- month old male C57BL/6J mice.  After enzymatic digestion of the thymi, the stromal cells were FACS purified, and RNA was extracted, amplified, labeled and hybridized to Affymetrix mouse 430 2.0 arraysarrays. Raw data were uploaded to Gene Expression Commons for normalization. Both raw CEL and normalized datasets from the 36 samples are included. A model within Gene Expression Commons has been created for analyses/comparisons of these datasets, along with previously reported thymocyte subset datasets. The model within Gene Expression Commons thus contains 6 thymic stromal populations, each from mice 1, 3, and 6 months of age, with duplicates for each datset.

first: Sanghee

last: Ki

first: Daechan

last: Park

first: Hilary

middle: J

last: Selden

first: Jun

last: Seita

first: Haewon

last: Chung

first: Jonghwan

last: Kim

first: Vishywanath

middle: R

last: Iyer


title: Expression data of isolated motor neurons from SOD1 G93A mice, after G-CSF treatment

status: Public on Sep 15 2014

city: Strasbourg

first: Alexandre

last: Henriques

address: 11 rue Humann

institute: University of Strasbourg

summary:
Gene expression changes in spinal motor neurons of the SOD1G93A-transgenic model for ALS after treatment with G-CSF.
To gain insight into the mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motor neurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment.

overall_design: A first group of SOD1G93A and WT mice was included in the study at week 11 of age when SOD1G93A mice present no signs of motor dysfunction but subtle signs of denervation detectable by electromyography. The second cohort of mice was treated with G-CSF or vehicle from week 11 to week 15. At the time of study completion, SOD1G93A mice presented clear motor impairment and motor neuron degeneration is documented. This design should provide information on genes altered in motor neurons of SOD1G93A mice from the clinically non-symptomatic to an early symptomatic stage, and give insight into genes influenced by G-CSF treatment. We sampled 300 motoneurons per mouse spinal cord by laser microdissection.

first: Stefan

last: Kastner

first: Eva

last: Handwerker

first: Claudia

last: Pitzer

first: Christian

last: Plaas

first: Friederike

last: Kirsch

first: Oliver

last: Wafzig

first: Carola

last: Krüger

first: Robert

last: Spoelgen

first: Jose-Luis

last: Gonzalez de Aguilar

first: Norbert

last: Gretz

first: Armin

last: Schneider


title: Cell type-specific requirements for iPSC reprogramming

status: Public on Sep 11 2014

city: New York

first: Matthias

last: Stadtfeld

address: 540 First Avenue Skirball Lab 4-1

institute: NYU School of Medicine

summary: The differentiated state of somatic cells provides barriers for the efficient derivation of induced pluripotent stem cells (iPSCs). To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. This revealed that inhibition of TGFβ together with activation of Wnt signaling in presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after one week of reprogramming factor expression. In contrast, hepatic progenitors and blood progenitors predominantly required only TGFβ inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner. We further demonstrate that expression of specific chromatin-modifying enzymes and reduced TGFβ/MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells.  Together, our observations define novel cell type-specific requirements for the rapid and synchronous reprogramming of somatic cells.

overall_design: For the study of reprogramming intermediates, cultures of reprogrammable MEFs at day 4 in presence of dox and compounds were harvested and stained with biotinylated anti-SSEA1 antibody (MC-480, eBioscience), followed by APC-conjugated Streptavidin and then anti-APC microbeads (Milteny Biotec) and enrichment using MACS separation columns (Milteny Biotec) according to manufacturer’s instructions. Total RNA extracted from SSEA1+ cells (>90% purity) with the RNeasy mini kit (QIAGEN) with a RIN value > 8 was subjected to transcriptional analyses with Affymetrix mouse genome 430 2.0 mRNA expression microarrays followed by bioinformatic analyses.

first: Simon

last: Vidal

first: Bhishma

last: Amlani

first: Taotao

last: Chen

first: Aristotelis

last: Tsirigos


title: Lineage reprogramming of adult mouse liver cells and B-lymphocytes to neural stem-like cells using defined factors [expression array]

status: Public on Sep 16 2014

first: Richard

middle: A

last: Young

summary: The overexpression of transcription factors Oct4, Sox2, Klf4, and c-Myc reprograms a somatic nucleus to one that is transcriptionally and epigenetically indistinguishable from an embryonic stem (ES) cell. However, it is still unclear if transcription factors can completely convert the nucleus of a differentiated cell into that of a distantly related cell type such that it maintains complete transcriptional and epigenetic reprogramming in the absence of exogenous factor expression. To test this idea, we screened a library of doxycycline-inducible vectors encoding neural stem cell (NSC)-expressed genes and found that stable, self-maintaining NSC-like cells could be induced under defined growth conditions after transduction of transcription factors. These induced NSCs (iNSCs) were characterized in the absence of exogenous factor induction and were shown to be transcriptionally, epigenetically, and functionally similar to endogenous embryonic cortical NSCs. Importantly, iNSCs could be generated from multiple adult cell types including liver cells and B-cells with genetic rearrangements.  Our results show that self-maintaining proliferative neural cells can be induced from non-ectodermal cells by expressing specific combinations of transcription factors.

overall_design: Expression analysis was performed on mouse embryonic fibroblasts (MEFs), primary-derived neural stem cells (NSCs) and induced neural stem cells (iNSCs).

first: John

last: Cassady

first: Ana

last: DAlessio

first: Rudolf

last: Jaenisch


title: The molecular basis of analgesia in congenital insensitivity to pain associated with loss of Nav1.7 function

status: Public on Sep 13 2014

city: Oxford

first: Georgios

last: Baskozos

address: Level 6, West Wing, John Radcliffe Hospital

department: NDCN

country: United Kingdom

institute: Oxford University

summary: Loss of function mutations in the SCN9a gene encoding voltage-gated  sodium channel Nav1.7 cause congenital insensitivity to pain  (CIP)  and anosmia in otherwise normal humans and mice, suggesting that this channel may be a good analgesic drug  target.  Surprisingly, potent selective antagonists of Nav1.7 are weak analgesics.  We therefore investigated whether Nav1.7 , as well as contributing to electrical signalling  may have  an additional function.     Here we report  that Nav1.7 deletion has profound effects on the sensory neuron transcriptome, leading to dysregulation  of a number of transcription factors  as well as upregulation of enkephalin precursor PENK mRNA and down regulation of CEACAM10 mRNA, a protein involved in noxious thermosensation.   PENK mRNA is transcriptionally upregulated in Nav1.7 null mutant female sensory neurons, resulting in increased enkephalin expression  in the dorsal horn of the spinal cord.   PENK expression is down-regulated  by addition of the sodium ionophore monensin, suggesting that sodium may play a role as a second messenger. Application of the opioid antagonist naloxone strongly enhances noxious peripheral input into the spinal cord,   and dramatically reduces analgesia in both male and female Nav1.7 null mutant mice, as well as in human Nav1.7 null mutants.  These data show that loss of Nav1.7 expression increases opioid drive over the lifetime of  mice and humans. They further suggest that  Nav1.7 channel blockers alone may not replicate the phenotype of null mutant humans and mice, but should be potentiated with exogenous opioids.

overall_design: RNA was extracted from Dorsal Root Ganglia tissue from Nav1.7 Knock-Out, Nav1.8 KO and Nav1.9 KO mice (n = 3) and hybridised on Affymetrix Mouse Genome 430 2.0 Array (GPL1261)

last: Wood


title: Whole-genome gene expression and splicing analysis of midbrain neurons derived from human embryonic stem cells: relevance to Parkinson's disease

status: Public on Dec 01 2014

city: London

first: Mina

last: Ryten

address: Queen Square

department: Department of Molecular Neuroscience

institute: UCL Institute of Neurology

summary:
Directed differentiation of midbrain dopaminergic neurons from human embryonic stem cells (hESCs) has galvanized much interest into their potential application in human Parkinson’s disease (PD).  We conducted genome-wide, exon-specific expression analyses at three temporally and phenotypically distinct stages of lineage restriction (pluripotent hESCs, multipotent neural precursor cells and terminally differentiated midbrain dopaminergic neurons). We compare these to expression data generated on the same platform from samples isolated from human fetal brain and from human control postmortem samples isolated from the substantia nigra. This comparison highlights the commonalities and differences between neural cells derived from hESCs and their counterparts in the human brain.

This gene expression microarray study was carried out to i) identify changes in gene expression and splicing during neural differentiation to dopaminergic neurons, and ii) determine the maturational state of hESC-derived neuronal samples particularly with regard to genes and pathways relevant to Parkinson's disease.

overall_design:
163 samples were analyzed: 5 hESC samples, 4 neural precusor samples, 3 hESC-derived neuronal samples, 94 control fetal brain samples and 57 control adult substantia nigra samples. The control fetal brain samples used in this study originated from GEO Series GSE13344. The 94 CEL files originating from GSE13344 and the 69 CEL files generated within this study were pre-processed together using RMA quantile normalization with GC background correction in Partek’s Genomics Suite v6.6 (Partek Incorporated, USA). In all subsequent analyses, the date of hybridization was included as a covariate. Both gene-level and exon-level analyses were performed.

The complete gene-level and exon-level datasets representing: (1) the hESC, neural precursor, hESC-derived neurons, and control adult substantia nigra Samples and (2) the control fetal brain Samples from Series GSE13344 (re-processed using quantile normalization), are linked below as supplementary files.

first: Rickie

last: Patani

first: Patrick

last: Lewis

first: Daniah

last: Trabzuni

first: Claire

last: Puddifoot

first: David

last: Wyllie

last: Walker

first: Colin

last: Smith

first: Giles

last: Hardingham

first: Micahel

last: Weale

last: Hardy

first: Siddharthan

last: Chandran


title: EWS-WT1 Oncogene Activates a Neuronal Reprogramming Factor ASCL1 and Mediates Partial Neural Differentiation

city: Bethesda

first: WeiPing

last: Chen

address: Bldg 8, Room 1A11, NIDDK/NIH

department: GCL

institute: NIDDK/NIH

summary: A chromosomal translocation fusion gene product EWS-WT1 is the defining genetic event in Desmoplastic Small Round Cell Tumor (DSRCT), a rare but aggressive tumor with a high rate of mortality. EWS-WT1 oncogene acts as an aberrant transcription factor that drives tumorigenesis, but the mechanism by which EWS-WT1 causes tumorigenesis is not well understood. To delineate the oncogenic mechanisms, we generated the EWS-WT1 fusion in the mouse using a gene targeting (knock-in) approach, enabling physiologic expression of EWS-WT1 under the native Ews promoter. We derived mouse embryonic fibroblasts (MEFs) and performed genome-wide expression profiling to identify transcripts directly regulated by EWS-WT1. Remarkably, expression of EWS-WT1 led to a dramatic induction of many neuronal genes. Notably, a neural reprogramming factor, ASCL1 (achaete-scute complex-like 1), was highly induced by EWS-WT1 in MEFs and in primary DSRCT. Further analysis demonstrated that EWS-WT1 directly binds to the proximal promoter region of ASCL1 and activates its transcription through multiple WT1-responsive elements. Depletion of EWS-WT1 in a DSRCT cell line resulted in severe reduction in ASCL1 expression and cell viability. Remarkably, when stimulated with neuronal induction media, cells expressing EWS-WT1 expressed neural markers and generated neurite-like projections. These results demonstrate for the first time that EWS-WT1 activates neural gene expression and is capable of directing partial neuronal differentiation, likely via ASCL1. These findings suggest that stimulating DSRCT tumor cells with biological or chemical agents that promote neural differentiation might be a useful approach to develop novel therapeutics against this incurable disease.

overall_design: mouse embryonic fibroblasts (MEFs) and performed genome-wide expression profiling to identify transcripts directly regulated by EWS-WT1 in 0 vs. 24 Hours in three replications (WT+KTS, or WT-KTS in 0, 24 H; CRE in 0 and 24H)

first: Hong-Jun

last: Kang

first: Soo

first: Jun

middle: H

last: Park

first: Marc

last: Ladanyi

first: Sean

last: Lee


title: Gene expression data from cultured mouse cortical (mCTX) neurons in different stimulation and knockdown conditions

status: Public on Sep 07 2014

city: Boston

first: Athar

middle: N.

last: Malik

address: 200 Longwood Avenue, Goldenson 405

department: Neurobiology

institute: Harvard Medical School

summary: Although the induction of C-FOS in the brain has been extensively studied for several decades to date there has been no attempt to identify the targets of C-FOS at a genome wide level, and it was not known how many genes C-FOS activates in a given cell.  To identify potential C-FOS target genes, we performed microarray analysis on RNA obtained from mouse cortical (mCTX) neurons infected with lentivirus containing either a control shRNA (targeting firefly luciferase) or c-Fos shRNA that were subsequently depolarized with 0, 1, 3, or 6 hours of KCl.

overall_design: Embryonic day 16.5 cortices from C57BL/6 mice were dissected, dissociated, plated, and subsequently grown in a cell culture incubator that maintained a temperature of 37 degrees C and a CO2 concentration of 5%.  On DIV5, lentiviral supernatant containing either a lentivirus expressing a control shRNA targeting firefly luciferase or a lentivirus expressing shRNA targeting c-Fos was applied to cultures for 6hrs with 6ug/mL polybrene.  At DIV7, mCTX neurons were silenced and stimulated with KCl for either 0, 1, 3, or 6hrs, and total RNA was purified using Trizol and the RNeasy mini kit from Qiagen.  10ug of labeled cDNA was subsequently hybridized to Affymetrix mouse genome 430 2.0 arrays with affymetrix processing.

middle: N


title: Transgenic Eµ-myc mouse lymphoma expression data for test dataset [Mouse430_2]

status: Public on Sep 10 2014

city: Durham

first: Daphne

last: Friedman

address: 101 Science Drive, Room 2121, CIEMAS Bldg

institute: Duke University Medical Center

summary: We used gene expression data from Eµ-myc mouse lymphomas to test various genomic signatures and select lymphomas for further study

overall_design: When Eµ-myc mice had evidence of lymphoma and/or ill appearance, they were humanely sacrificed and dissected.  Lymphoma tissue was obtained and flash frozen in liquid nitrogen.  Lymphoma was dissociated into a single cell suspension, and cell pellets were frozen.  Later, lymphoma tissue or cells were homogenized, and RNA was extracted.  Gene expression microarrays were performed with the isolated RNA.

first: Joseph

last: Nevins


title: Transgenic Eµ-myc mouse lymphoma expression data for training dataset

summary:
We used gene expression data from Eµ-myc mouse lymphomas to perform unsupervised analyses that identified two lymphoma subgroups.
We also used this data to develop a genomic signature to classify new lymphomas.

overall_design: When Eµ-myc mice had evidence of lymphoma and/or ill appearance, they were humanely sacrificed and dissected.  Lymphoma tissue was obtained and flash frozen in liquid nitrogen.  Later, lymphoma tissue was homogenized, and RNA was extracted.  Gene expression microarrays were performed with the isolated RNA.

first: Seiichi

last: Mori


title: Effect of Dot1l deletion on LSKs and GMPs

status: Public on Sep 08 2014

first: Scott

last: Armstrong

address: 1275 York Avenue

institute: Memorial Sloan-Kettering Cancer Center

summary:
We wanted to investigate the effects of Dot1l deletion on gene expression in LSKs and GMPs of C57/BL6 mice
Aberrant Hox gene activation is a recurrent feature in several different types of human leukemia, including leukemias with rearrangements of the mixed lineage leukemia (MLL) gene. In this study, we demonstrate that Hox gene expression is controlled by higher degree H3K79 methylation in acute myeloid leukemia (AML). We show that the deposition of progressive H3K79 methylation states at the genomic loci of critical Hox genes is dependent on the interaction of the H3K79 methyltransferase Dot1l with Af10, a protein that is found in the Dot1l complex isolated from diverse cell types. Furthermore, abrogation of the Dot1l-Af10 interaction reverses aberrant epigenetic profiles found in the leukemia epigenome and impairs the transforming ability of mechanistically distinct AML oncogenes.

overall_design: Lineage negative Sca-1 positive Kit positive (LSK) cells and granulocyte macrophage progenitors (GMPs) were sorted from Dot1 wt/wt x Mx-Cre mice or Dot1l fl/fl x Mx-Cre mice were injected with PIPC. PIPC injection induced biallelic deletion of the Dot1l allele in the Dot1l fl/fl mice but not the Dot1l wt/wt mice. The Dot1l wt/wt LSKs and GMPs were compared to the Dot1l -/- counterparts by RNA extraction and Microarrays.

first: Kathrin

last: Bernt

first: Amit

last: Sinha

first: Aniruddha

last: Deshpande


title: Assesment of gene expression upon AF10 deletion in MLL-AF9 secondary leukemia

summary: Aberrant Hox gene activation is a recurrent feature in several different types of human leukemia, including leukemias with rearrangements of the mixed lineage leukemia (MLL) gene. In this study, we demonstrate that Hox gene expression is controlled by higher degree H3K79 methylation in acute myeloid leukemia (AML). We show that the deposition of progressive H3K79 methylation states at the genomic loci of critical Hox genes is dependent on the interaction of the H3K79 methyltransferase Dot1l with Af10, a protein that is found in the Dot1l complex isolated from diverse cell types. Furthermore, abrogation of the Dot1l-Af10 interaction reverses aberrant epigenetic profiles found in the leukemia epigenome and impairs the transforming ability of mechanistically distinct AML oncogenes.

overall_design: Primary MLL-AF9 leukemias in the AF10 floxed background (homozygous) were transduced with MSCV-IRES-tdTomato (MIT) or the Cre recombinase expressing MIT vector, cells were sorted and injected into secondary recipient mice to generate Af10 floxed (MIT) or deleted (CRE) leukemias. BM cells fresly harvested from these leukemias were sorted for tdTomato expression and used for microarrays. BM cells from Hoxa9-Meis1 transduced primary leukemias were used for comparison.


title: Expression data from mouse carotid arteries in response to wire-injury

status: Public on Sep 03 2014

city: Wuhan

first: Hongliang

last: Li

state: Hubei

address: JieFang Road 238, Wuhan

department: Department of Cardiology

institute: Renmin Hospital of Wuhan University

summary:
IRF9 is ubiquitously expressed and mediates the effects of IFNs, previous study showed that IRF9 played an important role in immunity and cell fate decision. Our recent study revealed that IRF9 involved in cardiac hypertrophy, hepatic steatosis and insulin resistance. However, the function of IRF9 in VSMC and neointima formation was largely unknown. We found that IRF9 expression was significantly increased in the VSMCs of mouse carotid artery. More importantly, we generated SMC-specific IRF9 overexpression transgenic mice (IRF9 TG) and found that IRF9 TG significantly increased VSMC proliferation, migration and neointima formation compared with NTG mice in response to injury. To evaluate the underlying mechanism by which IRF9 promotes VSMC proliferation and migration after vascular injury, IRF9 TG and NTG mice were subjected to wire-injury and the carotid arteries were collected at 14 days post-injury. We combined 3-5 vessels for one sample, and 3 samples for each phenotype. Subsequently, a total of 400ng RNA was used following Affymetrix instruction and 10 ug of cRNA were hybridized for 16 hr at 45°. GeneChips were scanned using the Scanner 7G and the data was analyzed with Expression Console using Affymetrix default analysis settings and global scaling as normalization method. RMA analysis was employed to evaluate the gene expression.
We used microarrays to detect the global gene expression in the carotid arteries of smooth muscle cell specific IRF9 transgenic mice(IRF9 TG) compared with non transgenic control mice (NTG) at 14 days post-injury and identified distinct classes of altered genes.

overall_design: non-transgenic controls mice (NTG) and smooth muscle specific IRF9 transgenic mice (IRF9 TG) were subjected to wire-injury and the carotid ateries were collected at 14 days post-injury. We combine 3-5 vessels in one tube and for a single Affymetrix microarray. Total RNA was extracted and a total of 400ng RNA was used following Affymetrix instruction. 3 biological samples for each genotype.

first: Shumin

last: Zhang

first: Li-Hua Zhu

last: Zhu

first: Hou-Zao

first: Ran

first: Peng

first: Ding-Sheng

last: Jiang

first: Lu

last: Gao

first: Song

last: Tian

first: Lang

last: Wang

first: Yan

first: Pi-Xiao

first: Xiao-Fei

first: Xiao-Dong


title: Expression data from follicle associated epithelium (FAE) of small intestine in wild type  C57BL/6 mice or mice depleted with RBP-J (by VillinCre-Rbpjflox/flox)

status: Public on Sep 04 2014

city: Toyama

first: yukihiro

last: furusawa

address: Kurokawa

institute: Toyama Prefectural University

summary: To investigate the role of RBP-J in regulating epithelial cell differention in small intestine, we isolated FAE from mice depleted with RBP-J

overall_design: FAE were isolated from mice described above. Total RNA were extracted from the tissue by QIAGEN Rneasy mini kit.

first: Y

last: Furusawa

last: Obata

first: K

last: Hase


title: Genome-wide analysis of gene expression in whole blood from HIV-1 progressors and non-progressors.

status: Public on Sep 06 2014

city: Cleveland

first: Xuan

last: Xu

state: OH

address: 2109 Adelbert Rd

institute: Case Western Reserve University

summary: Expression profiling of whole blood from HIV-1 progressors and non-progressors. The comparison results showed differently expressed genes associated with disease progress.

overall_design: Total RNA obtained from whole blood from 26 patients differently numbered.

first: Chao

last: Qiu

first: Lingyan

first: Jianqing


title: miRNA profiling in the plasma of patients with in-stent restenosis (ISR)

status: Public on Sep 02 2014

city: Harbin

first: Yue

state: Heilongjiang

address: 23 Youzheng Street

department: Cardiovascular Department

institute: the First Affiliated Hospital of Harbin Medical University

summary: Studies of miRNA profiling in the plasma of patients between ISR and non-ISR

overall_design: Venous blood was collected in EDTA in the ward or the cardiac catheterization laboratory before the angiography procedure and heparin administration. Plasma was harvested by centrifugation and stored at -80°C until assayed. Identical volumes of plasma from the 6 patients with ISR and 4 patients with non-ISR were pooled to reach a final volume of 1500µL for each patient. Total RNA was extracted using miRVana isolation kit, dephosphorylated and labeled using miRNA Complete Labeling  kit. Scanning was achieved with the illumina iScan System. The result were acquired with the Genome Studio (GenomeStudioV2009.1).

first: Meijiao

last: He


title: PAX2-null progenitors define multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium

status: Public on Sep 20 2014

city: Houston

first: Frank

last: McKeon

address: 3455 Cullen Blvd

department: Biology and Biochemistry

institute: University of Houston

summary: The oviducts contain high grade serous cancer precursors, which are γ-H2AXp and p53 mutation positive. Secretory cell outgrowths (SCOUTs) are associated with older age and serous cancer. We evaluated PAX2 expression in proliferating oviductal cells, normal mucosa, SCOUTs, Walthard cell nests, STINs and HGSCs. Non-ciliated cells in normal mucosa were PAX2 positive  but became PAX2 negative in multilayered epithelium. PAX2 negative SCOUTs fell into two groups; Type I were secretory or secretory/ciliated with a “tubal” phenotype and were ALDH1 negative. Type II displayed a columnar to pseudostratified phenotype, with an EZH2,ALDH1, β-catenin, Stathmin, LEF1, RCN1 and RUNX2 expression signature . This study, for the first time, links PAX2 negative with proliferating fetal and adult oviductal cells undergoing basal and ciliated differentiation and shows that this expression state is maintained in SCOUTs, STINs and HGSCs. All three entities can demonstrate a consistent perturbation of genes involved in potential tumor suppressor gene silencing (EZH2), transcriptional regulation (LEF1), regulation of differentiation (RUNX2) calcium binding (RCN1) and oncogenesis (Stathmin). This shared expression signature between benign and neoplastic entities links normal progenitor cell expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a common pathway that could be a target of early prevention.

overall_design: 17 total samples are analyzed. 4 for TYPE 1 SCOUTs, 3 for TYPE 2 SCOUTs, 7 for paired normal epithelium, 3 for tumor

first: Gang

last: Ning

first: Christopher

middle: P

last: Crum

first: Wa

last: Xian


title: Glucocorticoid induced gene-regulation in murine bone marrow derived monocytes.

city: Muenster

first: Georg

last: Varga

address: Albert-Schweitzer-Campus 1, Gebaeude W30

department: Pediatric Rheumatology and Immunology

institute: University of Muenster

summary:
Glucocorticoids (GC) are used as first line therapies for generalized suppression of inflammation (e.g. allergies or autoimmune diseases), but their long-term use is limited by severe side effects. Our previous work has revealed that GC induced a stable anti-inflammatory phenotype in monocytes, the glucocorticoid-stimulated monocytes (GCsM) that we now exploited for targeted GC-mediated therapeutic effects.
We demonstrate that GCsM interact with T-cells in suppressing proliferation as well as cytokine release of CD8+ and especially CD4+ T-cells in vitro, and that they support generation of Foxp3+ cells.  We therefore tested their immunosuppressive potential in CD4+ T-cell-induced colitis in vivo. We found that injection of GCsM into mice with already established severe colitis abolishes the inflammation and results in significant clinical improvement within a few days. T-cells recovered from GCsM-treated mice reveal reduced secretion of pro-inflammatory cytokines IFN- or IL-17. Furthermore, accumulation of clusters of Foxp3+ CD4+ T-cells were detectable at local sites of inflammation in their colon.   Thus, GCsM are able to modify T-cell responses in vitro and in vivo and are able to down-regulate and clinically cure an established severe T-cell mediated colitis.

overall_design: Bone marrow derived monocytes where cultured 16 h with media containing M-CSF (control monocytes) or media containing M-CSF and dexamethasone (GCsM). In three independent experiments, total RNA from GCsM and control monocytes was isolated and processed for microarray hybridization.

first: Jan

last: Ehrchen

first: Anne

last: Brockhausen

first: Toni

last: Weinhage

first: Nadine

last: Nippe

first: Michael

last: Belz

first: Athanasios

last: Tsianakas

first: Matthias

last: Ross

first: Dominik

last: Bettenworth

first: Tilmann

last: Spieker

first: Marc

last: Wolf

first: Ralph

last: Lippe

first: Klaus

last: Tenbrock

first: Pieter

middle: M

last: Leenen

first: Johannes

last: Roth

first: Cord

last: Sunderkoetter


title: The Eµ-myc Mouse Model Represents Heterogeneity Across Human Aggressive B-cell Lymphomas

first: Daphne

last: Friedman

type:
Expression profiling by array
Genome variation profiling by array

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

overall_design: Refer to individual Series


title: Comparative microRNA profiling of sporadic and BRCA1 associated basal-like breast cancers

city: Randwick

first: Max

last: Yan

state: NSW

address: Prince of Wales Hospital

department: Anatomical Pathology

institute: SEALS

summary: Analysis of miRNA expression in grade 3 luminal, sporadic and BRCA1 associated basal-like breast cancers

overall_design: 44 primary grade III breast cancer (11 BRCA1 basal, 16 sporadic basal, 17 luminal) and 13 normal breast FFPE (formalin fixed, paraffin embedded) specimens, plus 7 controls and 5 cell lines were analysed. The aim of the study was to derive grade-specific miRNA signatures for sporadic and BRCA1 basal-like breast cancers, and to ascertain an immunohistochemical profile regulated by BRCA1 specific miRNAs for potential diagnostic uses.


title: Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences [30_week_Liver]

status: Public on Sep 01 2014

city: Buffalo

first: Jiho

last: Sohn

state: New York

address: 3435 Main Street, 644 Biomedical Research Building

department: Oral Biology

institute: SUNY Buffalo

summary: Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations.

overall_design: C57BL6J mice received low-dose penicillin through their drinking water (6.7 mg/L), control mice did not receive antibiotics.  All mice were started on normal chow (13.5% fat kcal). At 17 weeks of age, half of the mice were switched to high fat diet (45% fat kcal). Livers were collected at age 30 weeks, RNA was extracted, and transcriptional differences were measured by microarray analysis.

first: Laura

last: Cox

first: Shingo

last: Yamanishi

first: Alexander

middle: V

last: Alekseyenko

first: Jacqueline

last: Leung

first: Ilseung

last: Cho

first: Sungheon

middle: G

last: Kim

first: Huilin

last: Li

first: Zhan

last: Gao

first: Douglas

last: Mahana

first: Jorge

last: Zarate Rodriguez

first: Arlin

middle: B

last: Rogers

first: Nicolas

last: Robine

first: P’ng

last: Loke

first: Martin

last: Blaser


title: Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences [8_week_ileal]

overall_design: Male mice were exposed to low-dose penicillin (6.7 mg/L),  from birth. Ileums were collected at 8 weeks of age, RNA was extracted, and transcriptional differences were measured by microarray analysis.


title: Gene expression microarray data of bone marrow derived macrophages using GM-CSF(GM-BMMs) co-cultured with E0771 breast tumor cells

city: Minneapolis

first: Ying

last: Zhang

address: 117 Pleasant St S.E.

department: Minnesota Supercomputing Institute

institute: University of Minnesota

summary: E-FABP is dominately expressed in macrophages/dendritic cells. Thus E-FABP may play a siginificant role in their immune response to tumor insult. We treated mouse GM-BMMs of different genotype with E0771 breast cancer cells. Then we investigate the global gene expression in these GM-BMMs in response to tumor treatment.

overall_design: Bone marrow cells were collected from naïve C57BL/6 and E-FABP knockout mice of 6~8 week old. GM-BMMs were derived using GM-CSF (in RPMI1640 with 5%FBS) for 7 days before tumor treatment. After 18hr tumor teatment, GM-BMM total RNA was extracted using RNeasy Mini Kit (Qiagen) and subjected to mouse mRNA Gene expression by Affymetrix microarray.

first: Yuwen

first: Bing


title: Expression data from WT mice and bitransgenic Pdx1-cre/Kras*A mice bearing Pancreatic Ductal Adenocarcinoma

first: Prokopios Alexandros

last: Polyzos

address: 413 E 69th St

institute: Weill Cornell Medicine

summary:
We have carried out transcriptional profile analysis in WT MICE and bitransgenic Pdx1-cre/Kras*A MICE baring Pancreatic Ductal Adenocarcinoma
Mouse models faithfully simulating human cancer are valuable for genetic identification of potential  drug-targets but, among them, the most advantageous for practical use in subsequent preclinical  testing of candidate therapeutic regimes are those exhibiting rapid tumor development. Considering  that a KRAS mutation (predominantly in codon 12, such as KRASG12D; KRAS*) occurs with high  frequency (~90%) in cases of human pancreatic ductal adenocarcinoma (PDA)1, we sought to develop  a mouse PDA model that would exhibit high tumor incidence and short latency by ectopic  overexpression of Kras*.

overall_design: Five WT mice and 6  bitransgenic Pdx1-cre/Kras*A MICE baring Pancreatic Ductal Adenocarcinoma were used to identify key genes in the formation of panceatic malignacies

first: Dimitris

last: Stellas

first: Argyris

last: Efstratiadis


title: The DUF322 protein Asp23 of Staphylococcus aureus is membrane localized and functionally linked to cell wall stress

city: Greifswald

first: Jan

last: Pané-Farré

address: F.-L.-Jahn-Str. 15

department: Department of Microbial Physiology

summary:
With a copy number of about 25,000 molecules per cell, Asp23 is one of the most abundant proteins in Staphylococcus aureus. Asp23 has been characterized as a protein with an apparent molecular mass of 23 kDa that, following an alkaline shock, accumulates in the soluble protein fraction. Moreover, it was shown that transcription of the asp23 gene is exclusively regulated by the alternative sigma factor  B. The function of Asp23, however, has remained elusive. Sequence analysis identified Asp23 as a Pfam domain of unknown function 322 (DUF322) family member, precluding functional predictions based on its sequence.
Using fluorescence microscopy we found that Asp23 colocalizes with the staphylococcal cell membrane. Interestingly, Asp23 appeared to be excluded from sites of active cell division. We identified SAOUHSC_02443 as Asp23 membrane anchor and renamed it as AmaP (Asp23 membrane anchoring protein). To gain evidence for the function of Asp23, a deletion mutant was constructed and a comparative analysis of the wild type and mutant transcriptome was carried out. This analysis identified genes of the cell wall stress stimulon as up regulated in the asp23 mutant. Furthermore, using transmission electron microscopy of negatively stained Asp23 protein we showed that it forms large, highly flexible spiral-like complexes in vitro. In summary, we identified Asp23 as a membrane associated protein in S. aureus that forms large, elongated complexes in vitro and suggest a function for Asp23 in cell envelope homoeostasis.

platform_organism: Staphylococcus aureus subsp. aureus NCTC 8325

platform_organism: Staphylococcus aureus subsp. aureus Mu50

platform_organism: Staphylococcus aureus subsp. aureus N315

platform_organism: Staphylococcus aureus subsp. aureus MRSA252

platform_organism: Staphylococcus aureus subsp. aureus MSSA476

platform_organism: Staphylococcus aureus subsp. aureus USA300

overall_design: Sample versus pool design, pool = mixture of equal amounts of all sample RNAs analyzed, all RNAs (every strain and time point) were isolated as biological triplicates

first: Marret

last: Müller

first: Swantje

last: Reiß

first: Ulrike

last: Mäder


title: Expression data from RAW264.7 cells

city: Hangzhou

first: Bo

last: yang

state: Zhejiang

address: 866 YUHANGTANG ROAD

department: College of Pharmaceutical Sciences

institute: Zhejiang University

summary:
Hypoxia promotes macrophage polarization triggered by IL-6.In an attempt to gain speciﬁc insight into the mechanism of macrophage polarization during hypoxia.
We used microarrays to detail the global programme of gene expression and identified distinct classes of changed genes during this process.

overall_design: Four groups of RAW264.7 cells were harvested for RNA extraction and hybridization on Affymetrix microarrays (normoxia control, normoxia+IL-6,hypoxia control,hypoxia+IL-6).

first: Jun

first: Ji

last: Cao


title: Cyclin D1 Determines Androgen Dependent DNA Damage Sensing and Repair

first: Mathew

middle: Casimiro

last: Casimiro

state: United States

address: 233 South 10th St, Rm 1035

department: 233 South 10th St, Rm 1035

institute: Thomas Jefferson University

summary: Murine prostate epithelial cells (PECs) were obtained from Ccnd1-/- and Ccnd1+/+ FvB mice (2-3 months of age). RNA extracted from PECs (3 technical replicates for each group) was labeled and used to probe Affymetrix 430_2.0 arrays.

overall_design: Three control Ccnd1+/+ PECs were compared to three Ccnd1+/+ PECs.

middle: C

first: Richard

last: Pestell


title: Expression profiling of tumor cells from MYCN-driven neuroblastoma upon BRD4 or AURKA inhibition

city: Essen

first: Alexander

last: Schramm

address: Hufelandstr. 55

department: Childrens Hospital

institute: University Hospital Essen

summary: Amplification of MYCN is the most prominent genetic marker of high-stage neuroblastoma, a childhood tumor originating from the neural crest. We generated a cell line (mNB-A1) from tumors developed in transgenic mouse and treated these cells with DMSO (n=6), the BRD4-inhibitor JQ1 (n=3) or the AURKA-inhibitor MLN8237 (n=3) for 24 h.

overall_design: The expression profiles of vehicle (DMSO)-treated mNB-A1 cells were compared to JQ1- or MLN8237-treated mNB-A1 cells.

first: Johannes

last: Schulte

first: Kristina

last: Althoff


title: Expression data from adult mouse islets

city: Shanghai

first: Weiping

address: 800 Xiangyin Road

department: Pathophysiology

institute: Second Military Medical University

summary:
Zinc finger protein ZBTB20 plays a critical role in regulating insulin expression from islet beta-cells by orchestrating their gene expression profile.
We used microarrays to investigate the target gene of ZBTB20 in mouse pancreatic beta-cells.

overall_design: Adult mouse islets were harvested for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify the target genes of transcription factor ZBTB20 in beta-cells. To that end, we isolated the islets from adult beta cell-specific ZBTB20 knockout and their littermate control mice.

first: Ye


title: Gene expression profiling in mice overexpressing human wild type (WT) keratin 8 (K8) or K8 variants (G62C and R341H).

status: Public on Aug 27 2014

city: Aachen

first: Pavel

last: Strnad

address: Pauwelsstraße 30

institute: RWTH Aachen University

summary:
3 months old untreated male/female animals were used in the experiment.
We used microarray analysis to determine differential gene expression in mice livers overexpressing WT K8 and K8 variants.

overall_design: Mice liver tissues were used for RNA extraction and hybridization on Affymetrix microarrays.

first: Nurdan

last: Güldiken

first: Karlheinz

last: Holzmann


title: Expression profiling of murine MYCN-driven neuroblastomas from LSL-MYCN; Dbh-iCre mice.

summary:
Amplification of MYCN is the most prominent genetic marker of high-stage neuroblastoma, a childhood tumor originating from the neural crest.
We generated a transgenic mouse with Cre-conditional induction of MYCN in dopamine beta hydroxylase expressing cells that develops murine neuroblastomas.

overall_design:
The expression profiles of six tumors from adrenals and two tumors from superial cervical gangliae were compared to three non-malignant adrenals from wildtype mice.
These profiles of adrenals have been previously described (Molenaar et al., Nature Genetics 2012). Wild type samples are accessible at the AMC webpage: http://hgserver1.amc.nl/cgi-bin/r2/main.cgi, and accessible for registered users.


title: MMSET regulation of gene expression in t(4;14)+ myeloma

city: Chicago

first: Relja

last: Popovic

address: 303 East Superior Street

institute: Northwestern University

summary: We investigated gene expression in isogenic myeloma cell lines with or without overexpressed MMSET protein. MMSET is a histone methyltransferase which methylates lysine 36 on histone H3. Overexpression of MMSET in myeloma leads to a global increase in H3K36 methylation and concomitant decrease in H3K27 methylation. These global changes in histone methylation lead to altered gene expression.

overall_design: Total RNA was extracted from parental KMS11 cell line, NTKO cells which have the wild type MMSET allele inactivated and TKO cells which have overexpressed MMSET allele inactivated. Two different TKO clones were tested. Each sample was analyzed in triplicate.


title: Fyn-dependent prefrontal cortex gene networks in acute ethanol sensitivity

status: Public on Aug 31 2014

city: Richmond

first: Michael

last: Miles

state: VA

department: Pharmacology and Toxicology

institute: Virginia Commonwealth Univ.

summary:
Fyn kinase has been implicated in multiple behavioral responses to ethanol and in the regulation of myelin gene expression. Here we tested whether Fyn kinase modulated basal or ethanol-responsive expression of genes regulated by acute ethanol in brain regions of the mesolimbocortical dopamine pathway.
Using expression profiling, we sought to define Fyn-dependent gene networks underlying ethanol behavioral traits; with emphasis on ethanol-induced loss of righting reflex (LORR) due to the reproducible association of Fyn kinase genotype with this behavioral phenotype (Miyakawa et al., 1997, Boehm et al., 2003, Yaka et al., 2003, Boehm et al., 2004b). Our expression profiling and bioinformatics results suggest multiple Fyn-related mechanisms, especially those affecting a network of myelin-related gene expression within the medial PFC, as contributing to the sedative-hypnotic properties of ethanol. Variation in the expression of these Fyn-dependent gene networks may be critical molecular endophenotypes affecting the behavioral level of response to acute ethanol, and subsequently, the long-term risk for alcohol use disorders.

overall_design: Adult male control (B6129SF2/J) and Fyn-kinase null (B6;129S7-Fyntm1Sor/J) mice were treated with saline or ethanol (3.0 g/kg x 4 hours) and brain regions harvested by microdissection for total RNA expression profiling by Affymetrix microarrays. Samples were randomly assigned to batch groups prior to total RNA extraction, cRNA synthesis and hybridization. Each microarray represents a pooling of 3 animals and 3 arrays were analyzed per treatment group for a total of 12 arrays per brain region. Statistical and bioinformatics analysis was used to identify Fyn-dependent effects on basal and ethanol-responsive gene expression, with a particular focus on myelin-related gene expression. This series of samples includes medial prefrontal cortex (PFC).

middle: F

first: Sean

last: Farris