title: PhoB Activates Escherichia coli O157:H7 Virulence Factors in Response to Inorganic Phosphate Limitation

status: Public on Mar 15 2014

city: Saint-Hyacinthe

first: Samuel Mohammed

last: Chekabab

state: Québec

address: 3200 Sicotte

department: microbiology pathology

institute: Umontreal

summary:
In E. coli the phosphate homeostasis is regulated by the Pst system and the two-component system PhoB/R. Pathogens like E. coli O157:H7 are responsible for many outbreaks and can be found and survive in poor inorganic phosphate (Pi) environments.
To understand global EHEC O157:H7 EDL933 strain responses to Pi-starvation, we compared the transcriptomes of EDL933 the WT strain grown in MOPS Pi rich medium and that grown in MOPS Pi poor medium, using the Affymetrix GeneChip® E. coli Genome 2.0 Array. Also we investigated the EDL933 global response to the absence of PhoB by comparing the transcriptomes of the WT strain the ΔphoB mutant both grown in Low Pi

overall_design: EDL933WT strain and its isogenic mutant ΔphoB were grown in Pi- and/or in Pi+ conditions until the OD600 reached respectively 0.55 to 0.6. Samples equal to 5.108 CFU were taken from this mid log phase and processed for transcriptomes analysis. Ten µg of RNAs were extracted and retro-transcripted. One µg of the fragmented and biotinylated cDNAs, were hybridized onto Affymetrix GeneChip® E. coli. The data were processed using the FlexArray® software; RMA normalization and the levels of transcription obtained from 3 biological replicates of each experimental condition were compared using the EB (Wright & Simon) algorithm. We then conducted comparisons between EDL933WT grown in Pi- and in Pi+ conditions (comparison A) and between EDL933WT and EDL933∆phoB strains both grown in Pi- (comparison B). The differentially expression conditions corresponded to 2-fold change (FC) cut-off and p-value < 0.05.

first: Samuel

first: Grégory

last: Jubelin

first: Charles

last: Dozois

first: Josée

last: Harel


title: Gene Expression Profiling of Prostate Benign and Malignant Tissue

status: Public on Mar 18 2014

city: Boston

first: M. Simo

last: Arredouani

state: MA

address: 330 Brookline Ave.

department: Surgery

country: USA

institute: Beth Israel Deaconess Medical Center

summary:
We profiled genome-wide gene expression of human prostate benign and malignant tissue to identify potential biomarkers and immunotherapy targets.
We stratified malignant specimens according to their TMPRSS2:ERG gene fusion status.

overall_design: Radical prostatectomy tissue samples were obtained from the Hershey Foundation Prostate Cancer Serum and Tumor Bank at our institution. Morphologic diagnosis was done by a pathologist. OCT blocks containing >30% of PCa tissue (with Gleason score of 6 or 7) were selected for RNA purification. A biopsy punch was used to select the PCa tissues from the OCT sample blocks. Benign or PCa tissues were homogenized using a TissueLyser (Qiagen) at 28 Hz for 5 min. Total RNA was isolated using Trizol reagent. RNA was quantified by NanoDrop ND-1000 spectrophotometer, and quality was evaluated with Agilent RNA 6000 NanoChip and the 2100 Bioanalyzer, with 28S/18S ratios and RIN determined by 2100 Expert software.

first: M

middle: S

first: B

last: Lu

last: Sanda


title: A gene expression atlas of early craniofacial development

city: Cincinnati

first: Rebekah

last: Karns

state: OH

address: 3333 Burnet Ave

department: Gastroenterology, Hepatology, & Nutrition

institute: Cincinnati Children's Hospital Medical Center

summary:
We present a gene expression atlas of early mouse craniofacial development. Laser capture microdissection (LCM) was used to isolate cells from the principal critical micro-regions, whose development, differentiation and signaling interactions are responsible for the construction of the mammalian face.

We examined the facial mesenchyme and adjacent neuroepithelium at E8.5, at E9.5, facial mesenchyme, olfactory placode/epidermal ectoderm, underlying neuroepithileium, and emerging mandibular and maxillary arches.  AT E10.5 we sampled the medial and lateral prominences, olfactory pit, multiple regions of the underlying neuroepithelium the mandibular and maxillary arches, and Rathke's pouch.

For these 103 samples, laser capture microdissection from serial and bioreplicated E8.5, E.9.5, and E10.5 frozen sections was used to make RNA using the ZR RNA MicroPrep kit (Zymo). Nugen RiboSpia Ovation Pico WTA System V2 was used target amplification.  We used starting total RNA of at least 2 ng.

For further details about this study contact steve.potter@cchmc.org (isolation and labeling) or bruce.aronow@cchmc.org (informatics)

overall_design: Mouse embryos were harvested at developmental stage E8.5 , E9.5, and E10.5 and using LCM, cells were captured from the major micro-regions known to be responsible for the construction of the mammalian face.  RNA was extracted, labelled, and quantified using the Mouse ST-l microarray.

first: Steve

last: Potter

first: Bruce

last: Aronow


title: Fate changes leading to multipotency of isolated mesenchymal cells [Expression: Population_vs_Clone]

status: Public on Mar 20 2014

city: La Jolla

first: Ofer

last: Shoshani

state: California

address: 9500 Gilman Drive

institute: Ludwig Institute for Cancer Research

summary: Mesenchymal populations include a fraction of cells exhibiting multipotency as well as others with limited differentiation range. It has been assumed that the mesenchymal cellular cascade is topped by a multipotent cell, which gives rise to progeny with diminishing differentiation potentials.  Here we show that cultured mesenchymal cells, a priori exhibiting a limited differentiation potential, may gain new capacities and become multipotent following single cell isolation. These fate changes were accompanied by up-regulation of differentiation promoting genes, many of which also became H4K20me1 methylated. Early events in the process included TGFβ and Wnt modulation, and down-regulation of hypoxia signaling. Indeed, hypoxic conditions inhibited the observed cell changes. Overall, cell isolation from neighboring partners caused major molecular changes and particularly, a newly established epigenetic state. It is suggested that MSCs behave non-deterministically and non-hierarchically and should therefore be defined primarily by their capacity to undergo fate changes triggered by environmental cues.

overall_design: The gene expression profile of MSC population was compared with one of its derived single cell clones

first: Dena

last: Leshkowitz

first: Hassan

last: Massalha

first: Orly

last: Ravid

first: Dov

last: Zipori


title: Fate changes leading to multipotency of isolated mesenchymal cells [Expression: Dense_vs_Sparse]

overall_design: The gene expression profile of dense and sparse MSC cultures in three sequential days after seeding was compared


title: Heme regulates the development of iron-recycling macrophages from monocytes (heme-treated BMM)

status: Public on Mar 14 2014

city: St. Louis

first: MALAY

last: HALDAR

state: MO

address: 7751 charing square lane

department: Pathology and Immunology

institute: Washington University in St. Louis

summary:
Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis.

Global gene expression pattern of bone marrow-derived macrophages generated with GM-CSF in vitro and treated with heme were compared to those treated with vehicle at 6 hours, 24 hours, and 72 hours after treatment.

overall_design: GM-CSF cultures of Spic(igfp/igfp) BM cells were treated with heme (80 µm) or vehicle after 6 days in culture. Adherent fraction of cells were harvested 6 hours, 24 hours, and 72 hours after treatment and RNA was isolated using an RNeasy mini kit (Qiagen) and submitted for amplification, labeling and hybridization. Expression values were analyzed after RMA quantile normalization using ArrayStar software (DNASTAR).

first: Malay

last: Haldar

first: Kenneth

middle: M

last: Murphy


title: Inhibiting tankyrases sensitizes KRAS mutant cancer cells to MEK inhibitors by FGFR2 feedback signaling

status: Public on Mar 06 2014

city: Cambridge

first: Joshua

last: Korn

address: 250 Mass Ave

institute: Novartis

summary:
Tankyrases (TNKS) play roles in Wnt signaling, telomere homeostasis and mitosis, offering attractive targets for anti-cancer treatment. Using unbiased combination screening in a large panel of cancer cell lines, we have identified a strong synergy between TNKS and MEK inhibitors in KRAS mutant cancer cells. Our study uncovers a novel function of TNKS in the relief of a feedback loop induced by MEK inhibition on FGFR2 signaling pathway. Moreover, dual inhibition of TNKS and MEK leads to more robust apoptosis and anti-tumor activity both in vitro and in vivo than effects observed by previously reported MEK inhibitor combinations. Altogether, our results show how a novel combination of TNKS and MEK inhibitors can be highly effective in targeting KRAS mutant cancers by suppressing a newly discovered resistance mechanism.
This experiment is designed to detect genes differentially expressed in the combination treatment compared to others

overall_design: SW480 cells were seeded in 10cm dishes and treated for 4h and 16h with DMSO, TNKS inhibitor (TNKSi : NVP-TNKS656), MEK inhibitor (MEKi : AZD6244) or the combination of both at 1uM final

first: Marie

last: Schoumacher

first: Kristen

middle: E

last: Hurov

first: Joseph

last: Lehár

first: Yan

last: Yan-Neale

first: Yuji

last: Mishina

first: Dmitriy

last: Sonkin

first: Daisy

last: Flemming

first: Michael

middle: D

last: Jones

first: Brandon

last: Antonakos

first: Vessilina

middle: G

last: Cooke

first: Janine

last: Steiger

first: Jebediah

last: Ledell

first: Mark

last: Stump

first: Williams

middle: R

last: Sellers

first: Nika

middle: N

last: Danial

first: Wenlin

last: Shao


title: Sympathetic neuropathy of the bone marrow haematopoietic stem cell niche is essential for myeloproliferative neoplasms

status: Public on Mar 12 2014

city: Madrid

first: Simón

last: Méndez-Ferrer

address: Calle Melchor Fernández Almagro, 3

country: Spain

institute: CNIC

summary: Myeloproliferative neoplasms (MPNs) are diseases caused by mutations in the haematopoietic stem cell (HSC) compartment. Most MPN patients have a common acquired mutation of Janus kinase 2 (JAK2) gene in HSCs that renders this kinase constitutively active, leading to uncontrolled cell expansion. The bone marrow (BM) microenvironment might contribute to the clinical outcomes of this common event. We previously showed that BM nestin+ mesenchymal stem cells (MSCs) innervated by sympathetic nerve fibres regulate normal HSCs. Here we demonstrate that abrogation of this regulatory circuit is essential for MPN pathogenesis. Sympathetic nerve fibres, supporting Schwann cells and nestin+ MSCs are consistently reduced in the BM of MPN patients and mice expressing the human JAK2V617F mutation in HSCs. Unexpectedly, MSC reduction is not due to differentiation but is caused by BM neural damage and Schwann cell death triggered by interleukin-1b produced by mutant HSCs. In turn, in vivo depletion of nestin+ cells or their production of CXCL12 expanded mutant HSCs and accelerated MPN progression. In contrast, administration of neuroprotective or sympathomimetic drugs prevented mutant HSC expansion. Treatment with b3-adrenergic agonists that restored the sympathetic regulation of nestin+ MSCs prevented the loss of these cells and blocked MPN progression by indirectly reducing leukaemic stem cells. Our results demonstrate that mutant HSC-driven niche damage critically contributes to disease manifestation in MPN and identify niche-forming MSCs and their neural regulation as promising therapeutic targets.

overall_design: Total RNA was isolated from BM CD45- CD31- Ter119- Nes-GFP+ cells obtained from Nes-gfp mice 10 weeks after transplantation with Mx1-cre;JAK2-V617F (n=3) or control cells (n=1). RNA was amplified using the NuGen Ovation system and hybridized to the Affymetrix MoGene 1.0 ST array.

first: Lorena

last: Arranz

first: Simon

last: Mendez-Ferrer


title: Transcriptional effects of CSB and the CSB-PGBD3 fusion protein in CSB-null UVSS1KO cells

city: Seattle

first: Lucas

middle: T

last: Gray

state: WA

address: 615 Westlake Ave N

department: Molecular Genetics

institute: Allen Institute for Brain Science

summary: Cockayne syndrome is a segmental progeria most often caused by mutations in the CSB gene encoding a SWI/SNF-like ATPase required for transcription-coupled DNA repair (TCR). Over 43 Mya before marmosets diverged from humans, a piggyBac3 (PGBD3) transposable element integrated into intron 5 of the CSB gene. As a result, primate CSB genes now generate both CSB protein and a conserved CSB-PGBD3 fusion protein in which the first 5 exons of CSB are alternatively spliced to the PGBD3 transposase. We show by microarray analysis that expression of the fusion protein alone in CSB-null UV-sensitive syndrome cells (UVSS1KO) cells induces an interferon-like response that resembles both the innate antiviral response and the prolonged interferon response normally maintained by unphosphorylated STAT1 (U-STAT1); moreover, as might be expected based on conservation of the fusion protein, this potentially cytotoxic interferon-like response is largely reversed by coexpression of functional CSB protein. Interestingly, expression of CSB and the CSB-PGBD3 fusion protein together, but neither alone, upregulates the insulin growth factor binding protein IGFBP5 and downregulates IGFBP7, suggesting that the fusion protein may also confer a metabolic advantage, perhaps in the presence of DNA damage. Finally, we show that the fusion protein binds in vitro to members of a dispersed family of 900 internally deleted piggyBac elements known as MER85s, providing a potential mechanism by which the fusion protein could exert widespread effects on gene expression. Our data suggest that the CSB-PGBD3 fusion protein is important in both health and disease, and could play a role in Cockayne syndrome.

overall_design: 12 samples total; 4 gene expression conditions in triplicate; 1 condition is a tag-only negative control

first: Arnold

last: Bailey

first: Alan

last: Weiner


title: Expression data from mouse differentiated T helper cell lineages

status: Public on Mar 26 2014

first: Chih-Chung

last: Lin

address: 660 S. Euclid Ave. Box 8118

institute: Washington University School of Medicine

summary:
Microarray data on TH cell subsets from WT C57BL/6 and Bhlhe40 KO mice
We used microarrays to detail the global programme of gene expression in polarized TH cell lineages

overall_design: Purified naïve CD4 T cells from spleen were polarized in vitro and then activated with PMA/Ionomycin prior to microarray analysis

first: Brian

last: Edelson


title: Gene expression profiling in tibial muscular dystrophy and control skeletal muscle

status: Public on Mar 11 2014

city: Helsinki

middle: Andrew

last: Screen

address: Biomedicum1, Haartmaninkatu 8

department: Dpt. of Medical Genetics

country: Finland

institute: Folkhälsan Institute of Genetics, University of Helsinki

summary: Tibial muscular dystrophy (TMD) is a late onset, autosomal dominant distal myopathy that results from mutations in the two last domains of titin. The cascade of molecular events leading from the causative Titin mutations to the preterm death of muscle cells in TMD is largely unknown. To identify these components, we used gene expression profiling of muscle biopsies from TMD patients and healthy controls.

overall_design: 5 muscle samples from 2 normal control subjects and muscle samples from 7 TMD subjects.

first: Per Harald

last: Jonson


title: Heme regulates the development of iron-recycling macrophages from monocytes

first: MALAY

last: HALDAR

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

overall_design: Refer to individual Series


title: Colon Tumor Cell Macrophage Interactions

city: Bronx

first: Leonard

middle: H

last: Augenlicht

state: NY

address: 1300 Morris Park Ave

department: Medicine and Cell Biology

institute: Albert Einstein College of Medicine

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Expression data from Neuro2a mouse neuroblastoma cell lines, anchorage dependent cells (AD) and anchorage-independent tumorspheres (AI)

status: Public on Mar 13 2014

city: Washington

first: Bi-Dar

last: Wang

state: DC

address: 2300 I street, NW

department: Pharmacology and Physiology

institute: The George Washington University Medical Center

summary:
The ability of high-risk neuroblastoma to survive unfavorable growth conditions and multimodal therapy is hypothesized to result from a phenomenon known as reversible adaptive plasticity (RAP). RAP is a novel phenomenon enabling neuroblastoma cells to transition between a proliferative anchorage dependent (AD) state and a slow growing anoikis-resistant anchorage independent (AI) state.
We used microarrays to investigate the global gene expression profiles in AD and AI cells, and to identify the differential expressed genes within signaling pathways contributing to the reversible adaptive plasticity between AD and AI cells.

overall_design: Comparison of microarray data from AD cells (n=4 independent cultures) versus AI cells (n=4 independent cultures) were performed using Partek Genomics Suite 6.5. Differentially expressed genes with an FDR ≤5% and a fold-change ≥1.5 were selected for pathway analysis.

first: Lina

last: Chakrabarti

first: Anthony

last: Sandler

first: Norman

last: Lee


title: DUX4 binding to retroelements creates promoters that are active in FSHD muscle and testis.

status: Public on Mar 19 2014

first: Stephen

last: Tapscott

state: WASHINGTON

address: 1100 Fairview N. Ave

department: Human Biology

institute: Fred Hutch Cancer Research Center

type: Expression profiling by high throughput sequencing

summary: The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues. Facioscapulohumeral muscular dystrophy (FSHD) is caused by mutations that decrease the epigenetic repression of DUX4 in somatic tissues and result in mis-expression of this transcription factor in skeletal muscle. DUX4 binds sites in the human genome that contain a double-homeobox sequence motif, including sites in unique regions of the genome as well as many sites in repetitive elements. Using ChIP-seq and RNA-seq on myoblasts transduced with DUX4 we show that DUX4 binds and activates transcription of mammalian apparent LTR-retrotransposons (MaLRs), endogenous retrovirus (ERVL and ERVK) elements, and pericentromeric satellite HSATII sequences. Some DUX4-activated MaLR and ERV elements create novel promoters for genes, long non-coding RNAs, and antisense transcripts. Many of these novel transcripts are expressed in FSHD muscle cells but not control cells, and thus might contribute to FSHD pathology. For example, HEY1, a repressor of myogenesis, is activated by DUX4 through a MaLR promoter. DUX4-bound motifs, including those in repetitive elements, show evolutionary conservation and some repeat-initiated transcripts are expressed in healthy testis, the normal expression site of DUX4, but more rarely in other somatic tissues. Testis expression patterns are known to have evolved rapidly in mammals, but the mechanisms behind this rapid change have not yet been identified: our results suggest that mobilization of MaLR and ERV elements during mammalian evolution altered germline gene expression patterns through transcriptional activation by DUX4. Our findings demonstrate a role for DUX4 and repetitive elements in mammalian germline evolution and in FSHD muscular dystrophy.

overall_design:
RNA-seq of differentiated human primary myotube cell lines for FSHD patients and control samples

Raw data not provided due to patient privacy concerns.

first: Janet

last: Young

first: Jennifer

middle: L

last: Whiddon

first: Zizhen

last: Yao

first: Bhavatharini

last: Kasinathan

first: Lauren

last: Snider

first: Linda

last: Geng

first: Judit

last: Balog

first: Rabi

last: Tawil

first: Silvere

last: van der Maarel

middle: J


title: Human meningioma culture

city: Taipei

first: Tu-Hsueh

last: Yeh

state: Taipei

address: 199, Tung-Hwa North Road

department: Neurology

country: Taiwan

institute: Chang Gung Memorial Hospital

summary: Comparison of the gene expression profiles with meningiomas of different grading.

overall_design: 24 primary meningioma cultures from surgical specimen were maintained to primary meningioma cultures.

first: T

first: Y

middle: C

last: Huang


title: Hmga2 is required for canonical WNT signaling during lung development

status: Public on Mar 07 2014

city: Nancy Cedex

first: Guillermo

last: Barreto

address: 9, Avenue de la Forêt de Haye ‐ BP 20199

department: Campus Biologie-Santé. Faculté de Médecine

country: France

institute: CNRS Director of Research

summary:
The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. Here we deciphered the role of the high mobility group AT-hook protein 2 (HMGA2) during lung development by analyzing the lung of Hmga2 deficient mice (Hmga2-/-).We found that Hmga2 is expressed in the mouse embryonic lung at the distal airways. Analysis of Hmga2-/- mice showed that Hmga2 is required for proper cell proliferation and distal epithelium differentiation during embryonic lung development. Hmga2 knockout (KO) led to enhanced canonical WNT signaling due to an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as well as a reduction of the WNT signaling antagonizing proteins GATA6 (GATA binding protein 6) and FZD2 (frizzled homolog 2).
Comparison of Hmga2-/- with Hmga2+/+ mice by Affymetrix microarray-based expression analysis of embryonic lung revealed an increased expression of genes whose products participate in cell cycle and canonical Wnt signaling.

overall_design: Affymetrix microarray transcriptome analysis of Hmga2-/- and Hmga2+/+ embryonic lung (E18.5) was performed and analyzed

first: Indrabahadur

last: Singh

first: Aditi

last: Mehta

first: Adriana

last: Contreras

first: Thomas

last: Boettger

first: Gianni

last: Carraro

first: Matthew

last: Wheeler

first: Hector

middle: A

last: Cabrera-Fuentes

first: Saverio

last: Bellusci

first: Werner

last: Seeger

last: Braun


title: Genome wide methylation profliling of pediatric glioblastomas.

status: Public on Mar 09 2014

city: Montrea

first: Simon

last: Papillon-Cavanagh

state: Quebec

address: 740 Dr Penfield

department: Human Genetics

country: Canada

institute: McGill University

type: Methylation profiling by genome tiling array

summary: Genome wide DNA methylation profiling of WT, K27M, G34R and IDH1glioblastomas

overall_design: Bisulphite converted DNA from 38 WT, 28 K27M, 17 IDH1 AND 15 G34R samples hybridised to the Illumina 450k Human Methylation Beadchip

first: Adam

last: Fontebasso

first: Jeremy

last: Schwartzentruber

first: Hamid

last: Nikbakht

first: Noha

last: Gerges

first: Pierre-Olivier

last: Fiset

first: Denise

last: Bechet

first: Damien

last: Faury

first: Nicolas

last: De Jay

first: Lori

last: Ramkissoon

first: Aoife

last: Corcoran

first: David

last: Jones

first: Dominik

last: Sturm

first: Pascal

last: Johann

first: Tadanori

last: Tomita

first: Stewart

last: Goldman

first: Mahmoud

last: Nagib

first: Anne

last: Bendel

first: Liliana

last: Goumnerova

first: Daniel

last: Bowers

first: Jeffrey

last: Leonard

first: Joshua

middle: B

last: Rubin

first: Tord

last: Alden

first: Samuel

last: Browd

first: J

last: Geyer

first: George

last: Jallo

first: Kenneth

last: Cohen

first: Nalin

last: Gupta

first: Michael

last: Prados

first: Anne-Sophie

last: Carret

first: Benjamin

last: Ellezam

first: Louis

last: Crevier

first: Almos

last: Klekner

first: Laszlo

last: Bognar

first: Peter

last: Hauser

first: Miklos

last: Garami

first: John

last: Myseros

first: Zhifeng

last: Dong

last: Siegel

first: Hayley

last: Malkin

first: Azra

last: Ligon

first: Steffen


title: A conditionally immortalized human pancreatic beta cell line

status: Public on Mar 21 2014

city: Paris

first: Raphael

last: Scharfmann

address: 24 Rue du Fg St Jacques

institute: INSERM U845, Research Center Growth and Signaling, Université Paris Descartes, Faculté de Médecine, Hôpital Cochin

type:
Expression profiling by array
Third-party reanalysis

summary: Access to an unlimited number of human pancreatic beta cells represents a major challenge in the field of diabetes to better dissect human beta cell functions and to make significant progress in drug discovery and cell replacement therapies. We previously reported the generation of the EndoC-bH1 human beta cell line that was generated by targeted oncogenesis in human fetal pancreases followed by in vivo cell differentiation in mice. Such cell line displayed many functional properties of adult beta cells. Here we devised a novel strategy to generate conditionally immortalized human beta cell lines based on CRE-mediated excision of immortalizing transgenes. The resulting EndoC-bH2 cell line can be massively amplified in vitro. Transgenes are next efficiently excised upon CRE expression leading to cell proliferation arrest and strong enhancement of beta cell specific features such as insulin expression, content and secretion. Excised EndoC-bH2 cells are close to authentic human beta cells and represent a unique tool to further study beta cell function and to understand why adult human beta cells are refractory to proliferation and how to achieve drug-dependent mobilization towards beta cell expansion.

overall_design: Expression profile of human beta cell lineEndoC-bH2 before and after excision of an immortalization cassette (SV40 LT and hTERT) is compared to human exocrine pancreas cell line SKPC and adult human islets from cadaveric donors. Three replicates were used for each sample group. The three adult human islets samples were taken from GEO series GSE40709 (GSM999550, GSM999551 and GSM999552) and normalized with H357 and SKPC cell line samples using RMA.

first: Raphaël

first: Severine

last: Pechberty

first: Yasmine

last: Hazhouz

first: Manon

last: von Bülow

first: Emilie

last: Bricout-Neveu

first: Maud

last: Grenier-Godard

first: Matthias

last: Lohmann

first: Paul

last: Czernichow

first: Philippe

last: Ravassard


title: Acute cellular injury responses in mouse renal ischemic reperfusion injury

city: Los Angeles

first: Jing

last: Liu

address: 1425 San Pablo St.

department: Department of Regenerative Medicine  & Stem Cell Biology

institute: University of Southern California

summary: Acute kidney injury (AKI) is associated with an abrupt loss of kidney function that results in significant morbidity and mortality. Considerable effort has focused around the identification of diagnostic biomarkers and the analysis of molecular events. Most studies have adopted organ-wide approaches that do not fully capture the interplay among different cell types in the pathophysiology of AKI. To extend our understanding of molecular and cellular events in AKI, we developed a mouse line that enables the identification of translational profiles in specific cell types by CRE recombinase-dependent activation of an eGFP-tagged L10a ribosomal protein subunit, and consequently, translating ribosome affinity purification (TRAP) of mRNA populations. By utilizing cell-type specific CRE-driver lines, in this study we identify distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Cell-specific translational expression profiles were uncovered 24 hours after IRI from four populations enriched for distinct anatomical and cellular subgroups: nephron, interstitial cell populations, vascular endothelium, and macrophages/monocytes by Affymetrix microarray.

overall_design: A construct containing the CAGGS promoter driving eGFP-L10a, with a loxP-site flanked triple SV40 polyA cassette between promoter and eGFP-L10a cassette was targeted into the ubiquitously active Rosa26 locus. The upstream polyA cassette is designed to block activity of the downstream eGFP-L10a cassette. CRE-dependent removal of this transcriptional block activates eGFP::L10a production within the CRE-producing cell, and all of its descendants. Mice carrying the conditional eGFP-L10a allele, referred to as L10a, were maintained in a homozygous state. L10a mice were crossed to four CRE strains to activate eGFP::L10a expression in four predominantly non-overlapping cellular compartments in the kidney. A Six2-Tet-GFP::CRE allele is active exclusively within nephron progenitors; consequently, historical labeling results in eGFP::L10a expression throughout the main body of the nephron. A Foxd1-GFP::CRE allele is active in the progenitors of many of the interstitial cell lineages including those generating mesangial and non-glomerular pericytes. In addition, Foxd1 is normally expressed in podocytes. Cdh5-CRE is reported to be active throughout the vascular endothelium, and finally, Lyz2-CRE specifically labels cells of the myeloid lineage, notably macrophages, monocytes and dendritic cells. Mice carrying any CRE allele and the L10a allele are designated generically CRE-L10a. six2-L10a, foxd1-L10a, cdh5-L10a and lyz2-L10a denote specifically mice that are compound heterozygotes for the indicated CRE driver and L10a. CRE-L10a, L10a heterozygous littermates without CRE allele, C57BL/6 wild type mice were subjected to renal bilateral warm ischemia 28 minutes followed by 24-hour reperfusion when the kidney TRAP RNA and total RNA were isolated and subjected to Affymetrix microarray. Biological triplicates for each CRE-L10a line underwent no Surgery; sham Surgery and IRI treatment.

first: Andrw

middle: P

last: McMahon

first: Michaela

last: Krautzberger


title: EcadEGFP expression in MDA-MB-134 and IPH-926

status: Public on Mar 04 2014

city: Braunschweig

first: Robert

last: Geffers

address: Inhoffenstr. 7

department: Dep. Molecular Bacteriology

country: Germany

institute: HCI - Helmholtz Centre for Infection Research

summary: This experiment aims to study transcriptional alterations induced by reconstitution of wild type E-cadherin expression in human lobular breast cancer cells harbouring deleterious, somatic CDH-1 mutations

overall_design: Two cell lines (IPH-926 and MDA-MB-134) expressing synthetic Ecad (EcadEGFP) or not (EGFP) were compared against each other. Analysis were conducted in triplicates (IPH-926) and quadruplicates (MDA-MB-134), respectively.

first: Inga

last: Karch

first: Ulrich

last: Lehmann


title: Effect of co-culture with macrophages on two colon cancer cell lines.

first: Leonard

last: Augenlicht

summary:
These data suggest that co-culture with macrophages increases expression of NDRG-1 in epithelial cell lines.  The finding is confirmed in 1 mouse epithelial cell line, and in tissue derived from mice genetically and dietetically altered to increase macrophage infiltration of the small and large intestinal epithelium.  NDRG1 is identified as a potential mediator of macrophage effects on tumorigenesis in the large and small intestine.
Array data is part of a larger study involving the effects of Vitamin D, in concert with macrophages, on intestinal homeostasis and tumorigenesis, entitled Cell autonomous and non-autonomous interactions of a western-style diet and the vitamin D receptor in intestinal homeostasis and tumorigenesis

overall_design: Cells from human colon cancer cell lines were cultured either alone, with Vitamin D3, with THP1 macrophages, or with THP1 macrophages and Vitamin D3, in a system which allowed no physical contact but exchange of soluble factors between the cell types.

first: Lidija

last: Klampfer


title: Gene-expression profiles of IFN-gamma-affected HOSE cells

city: Kyoto

first: Kaoru

last: Abiko

address: 54 Shogoin Kawaharacho, Sakyo-ku

department: Department of Gynecology and Obstetrics

country: Japan

institute: Kyoto University Graduate School of Medicine

summary: The source of IFN-γ in ovarian cancer microenvironment and its biological effect to the tumor cells is unclear. The immortalized human ovarian surface epithelial cell line, HOSE-E7/hTERT (HOSE) was treated with IFN-γ and expression microarray analysis was performed, and probes showing significantly higher values in IFN-γ-added group were termed “IFN-γ signature genes (295 probes)”.  We then applied this signature to our ovarian cancer microarray data, which included 75 ovarian cancer clinical samples, by means of ss-GSEA. IFN-γ signature score was strongly correlated to the number of infiltrating CD4-positive or CD8-positive lymphocytes in the tumors. These data suggest that the IFN-γ in the ovarian cancer microenvironment is derived from lymphocytes, and an IFN-γ-rich microenvironment is strongly correlated to a lymphocyte-rich microenvironment.

overall_design: HOSE cells were incubated in 8 separate culture dishes, 4 dishes with and 4 dishes without 500 IU/ml recombinant human IFN-γ (R&D Systems) in the culture medium for 6 hours prior to the analysis.

first: K

first: N

last: Matsumura


title: Expression data of HUVEC cells after PPARβ/δ agonist and/or hypoxia treatment

city: Tokyo

first: Tsuyoshi

last: Inoue

address: Hongo

institute: The University of Tokyo

summary:
Recently the role of PPARβ/δ in angiogenesis has been revealed, and we hypothesized that the crosstalk between hypoxia and PPARβ/δ on endothelial cells may exsist. To elucidate the interaction between two signalings, we report the comprehensive change of transcripts induced by PPARβ/δ agonist (GW501516) and/or hypoxia.
We used microarray analysis of HUVECs treated with PPARβ/δ agonist (GW501516) and/or hypoxia (1% O2) for 24-hours, and we identified a group of consistently up- or down-regulated genes.

overall_design: HUVECs were used within the first 6 passages. HUVECs were treated with PPARβ/δ agonist (GW501516) at a concentration of 100 nM and/or hypoxia (1% O2) for 24-hours. Same concentration of DMSO was used as a control sample, and as to the oxgen, normoxia was used as a control condition.

first: Takahide

last: Kohro

first: Youichiro

last: Wada

first: Akashi

last: Taguchi

first: Shogo

last: Yamamoto

first: Tatsuhiko

last: Kodama


title: D-2-Hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice

status: Public on Mar 01 2014

city: Burjassot

first: Julian

last: Carretero

state: Valencia

address: Ave. Vicent Andres Estelles s/n

department: Physiology

institute: University of Valencia

summary: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-Hydroxyglutaric aciduria  (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2- hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the  accumulation of D2-HG, we generated transgenic mice with conditionally activated IDH2R140Q and IDH2R172K alleles. Global induction of mutant IDH2 expression in adults  resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2  resulted in more pronounced phenotypes, including runting, hydrocephalus, and shortened life span—recapitulating the abnormalities observed in D2HGA patients. The  diseased hearts exhibited mitochondrial damage and glycogen accumulation with a concordant upregulation of genes involved in glycogen biosynthesis. Notably, mild  cardiac hypertrophy was also observed in nude mice implanted with IDH2R140Q expressing xenografts, suggesting that 2HG may potentially act in a paracrine fashion.  Finally, we show that silencing of IDH2R140Q in mice with an inducible transgene restores heart function by lowering 2HG levels. Together, these findings indicate that inhibitors of  mutant IDH2 may be beneficial in the treatment of D2HGA and suggest that 2HG produced by IDH mutant tumors has the potential to provoke a paraneoplastic condition.

overall_design: We have performed microarray expression profiling of hearts from IDH2 mutant and control mice.

first: Esra

last: Akbay

first: Javid

last: Moslehi

first: Camilla

last: Christensen

first: Supriya

last: Saha

first: Jeremy

last: Tchaicha

first: Shakti

last: Ramkissoon

first: Kelly

last: Stewart

first: Eiki

last: Kikuchi

first: Haikuo

last: Zhang

first: Travis

last: Cohoon

first: Stuart

last: Murray

first: Wei

first: Kazumasa

last: Uno

first: Sudeshna

last: Fisch

first: Kristen

last: Jones

first: Sushma

last: Gurumurthy

first: Camelia

last: Gliser

first: Sung

last: Choe

first: Marie

last: Keenan

first: Jaekyoung

last: Son

first: Illana

last: Stanley

first: Julie

last: Losman

last: Padera

first: Roderick

last: Bronson

first: John

last: Asara

first: Omar

last: Abdel-Wahab

first: Philip

last: Amrein

first: Amir

last: Fathi

first: Nika

last: Danial

first: Alec

last: Kimmelman

first: Andrew

last: Kung

first: Keith

last: Ligon

first: Katharine

last: Yen

first: William

last: Kaelin Jr

first: Nabeel

last: Bardeesy

first: Kwok-Kin

last: Wong


title: Tissue culture model of hypothermia

city: Tartu

first: Sten

last: Ilmjärv

state: Tartumaa

address: Ravila 19

department: Institute of Biomedicine and Translational Medicine

country: Estonia

institute: University of Tartu

summary: Therapeutic hypothermia is a clinically effective treatment for various hypoxic and ischemic conditions, but the associated molecular mechanisms remain unclear. To gain insight into hypothermia-induced transcriptional response, mouse embryonic fibroblasts were exposed to mild hypothermia (32°C) or normothermia (37°C) for increasing time periods. We aimed to identify genes with temporally near-monotonic response as the most obvious candidates for mediating the therapeutic effects of hypothermia.

overall_design: Hypothermia was compared against normothermia at seven different time-points. Hypothermic and normothermic mouse embryonic fibroblasts (MEF, in 100 mm dishes, one array per time-point) were submitted to gene expression analysis using Mouse Gene 1.0 ST GeneChip® (Affymetrix) microarrays. Differential gene expression analysis was performed with R package DEMI (http://biit.cs.ut.ee/demi/).

first: Hendrik

last: Luuk

first: Christian

last: Hundhal

first: Riin

last: Reimets

first: Margus

last: Niitsoo

first: Raivo

last: Kolde

first: Jaak

last: Vilo

first: Eero

last: Vasar


title: Gene expression profiles of T-cell acute lymphoblastic leukemia cell lines with and without chronic GSI-treatment

city: Boston

first: Jiang

last: Zhu

address: 185 Cambridge Street

institute: Massachusetts General Hospital, Harvard Medical School and Broad Institute

summary: Here we modeled T-ALL resistance to Notch inhibition, identifying ‘persister’ cells that readily expand in the presence of gamma secretase inhibitor (GSI) and the absence of Notch signaling. Rare persister cells are already present in naïve T-ALL populations, and the reversibility of the phenotype is suggestive of an epigenetic mechanism. Relative to GSI-sensitive cells, persisters activate distinct signaling and gene expression programs, and exhibit global chromatin compaction. A shRNA screen identified chromatin regulators whose depletion preferentially impairs persister cell viability, including BRD4, an acetyl-histone reader. BRD4 is up-regulated in the persisters and binds enhancers near genes with critical functions in T-ALL, including MYC and BCL2. Treatment of persisters with the BRD4 inhibitor JQ1 down-regulates these targets and induces growth arrest and apoptosis, at doses well tolerated by GSI-sensitive cells. Prompted by these findings, we examined and established the efficacy of GSI – JQ1 combination therapy against primary human leukemias in vivo. Our findings establish a role for epigenetic heterogeneity in leukemia drug resistance and suggest the potential of combination therapies that include epigenetic modulators to prevent and treat resistant disease.

overall_design: Examination of gene expression profiles in the T cell leukemia cell lines DND-41 and KOPT-K1 after chronic treatment with gamma Secretase inhibitor (Compound E, 1 uM, EMD4 Bioscience; persister) or vehicle (naïve). 2 replicates in each group.

first: Birgit

last: Knoechel

first: Bradley

last: Bernstein


title: Gene expression on in vitro T cells activated with IL-21

first: Francisco

last: Quintana

address: 77 Ave Louis Pasteur

department: Center for Neurological Diseases

institute: Harvard Medical Institute

summary:
We have analyzed the effects of IL-21 signaling on T cell activation, IL-22 production and gut inflammation
In this dataset we include the results of treating T cells with IL-21.

overall_design: Naïve CD4+ T cells (C57BL/6) were isolated, cultured in vitro +/- IL-21 and RNA was prepared

first: Ada

last: Yeste

first: Bonny

last: Patel


title: expression data of miR-21 knockdown in MCF-7

city: Galway

first: Charles

last: Spillane

state: Galway

address: University Road

department: Botany and Plant Science

country: Ireland

institute: National University of Ireland, Galway

summary:
miR-21 is overexpressed in breast cancer cells. Knock-down of miR-21 cause apoptosis and decreased cell proliferation.
To identify miR-21 regulated cancer-pathways in MCF-7 cells, we knocked-down miR-21 and performed microarray.

overall_design: RNA was harvested from MCF-7 cells 24 hours transfection of anti-control, anti-21, or untreated cells. RNA was processed and hybridized into Affymetrix whole human genome arrays in duplicates.

first: S

last: Selcuklu

first: Mark

last: Donoghue

first: H

last: Akman

first: Matheus

last: de Sousa Gomes

first: M

last: Yakicier

first: Michael

last: Kerin

first: A

last: Erson-Bensan


title: Gene expression in hTERT-RPE1 cells with overexpression of MFRP

city: Milwaukee

first: Joseph

last: Besharse

state: WI

address: 8701 Watertown Plank Rd

department: Cell Biology, Neurobiology and Anatomy,

institute: Medical College of Wisconsin

summary: Gene expression was compared between hTERT-RPE1 cells and hTERT-RPE1 cells stably overexpressing mouse MFRP with an N-terminal GFP fusion.

overall_design:
RNA was prepared from hTERT-RPE1 cells overexpressing GFP-MFRP and control cells.  Both conditions were done in triplicate.  Affymetrix GeneChip Human Genome U133Plus2.0 arrays were used to interrogate changes in gene expression.  Image data were quantified with Affymetrix Expression Console Software and normalized with Robust Multichip Analysis.

Reference:
Joseph Fogerty.  2013.  "A novel mouse mutant resembling age-related macular degeneration".  A PhD Dissertation submitted to the Graduate School of Biomedical Sciences of the Medical College of Wisconsin, Milwaukee (April 2013).


title: Expression data from control infected and H-RASG12V infected IMR90 cells.

status: Public on Feb 28 2014

city: Glasgow

first: Peter

middle: D.

last: Adams

address: Switchback Rd, Bearsden

country: United Kingdom

institute: University of Glasgow, Beatson Institute for Cancer Research

summary: Cellular senescence is a stable proliferation arrest associated with an altered secretory pathway, the Senescence-Associated Secretory Phenotype (SASP). However, cellular senescence is initiated by diverse molecular triggers, such as activated oncogenes and shortened telomeres, and is associated with varied and complex physiological endpoints, such as tumor suppression and tissue aging. The extent to which distinct triggers activate divergent modes of senescence that might be associated with different physiological endpoints is largely unknown. To begin to address this, we performed gene expression profiling to compare the senescence programs associated with two different modes of senescence, oncogene-induced senescence (OIS) and replicative senescence (RS [in part caused by shortened telomeres]). While both OIS and RS are associated with many common changes in gene expression compared to control proliferating cells, they also exhibit substantial differences. These results are discussed in light of potential physiological consequences, tumor suppression and aging.

overall_design: We used microarrays to detail the global programme of gene expression after oncogene induced senescence.

first: David

last: Nelson

first: Tony

last: McBryan


title: Peripheral blood biomarker signatures for acute kidney transplant rejection

city: La Jolla

first: Sunil

last: Kurian

state: CA

address: 10550 N Torrey Pines Road

department: Molecular and Experimental Medicine

institute: The Scripps Research Institute

summary:
In the present work, we have used whole genome expression profiling of peripheral blood samples from 51 patients with biopsy-proven acute kidney transplant rejection and 24 patients with excellent function and biopsy-proven normal transplant histology. The results demonstrate that there are 1738 probesets on the Affymetrix HG-U133 Plus 2.0 GeneChip representing 1472 unique genes which are differentially expressed in the peripheral blood during an acute kidney transplant rejection. By ranking these results we have identified minimal sets of 50 to 150 probesets with predictive classification accuracies for AR of greater than 90% established with several different prediction tools including DLDA and PAM. We have demonstrated that a subset of peripheral blood gene expression signatures can also diagnose four different subtypes of AR (Banff Borderline, IA, IB and IIA) and the top 100 ranked classifiers have greater than 89% predictive accuracy. Finally, we have demonstrated that there are gene signatures for early and late AR defined as less than or greater than one year post-transplant with greater than 86% predictive accuracies. We also confirmed that there are 439 time-independent gene classifiers for AR. Based on these results, we conclude that peripheral blood gene expression profiling can be used to diagnose AR at any time in the first 5 years post-transplant in the setting of acute kidney transplant dysfunction not caused by BK nephropathy, other infections, drug-induced nephrotoxicity or ureteral obstruction.

Keywords: kidney transplantation, peripheral blood, DNA microarrays, acute kidney rejection, biomarkers

overall_design: Microarray profiles of peripheral blood from 51 biopsy-proven acute kidney rejection (AR) and 24 well-functioning kidney transplants were randomized and compared using class comparisons, network and biological function analyses.


title: A systems biology approach for defining the molecular framework of the hematopoietic stem cell niche

city: 91400 Orsay

first: Florent

last: Dumont

state: Ile de France

address: 17 avenue des sciences

institute: Université Paris-Saclay

summary: Hematopoietic stem/progenitor cells (HSPCs) are at the basis of the hematopoietic hierarchy. Their ability to self-renew and differentiate is strictly controlled by molecular signals produced by their surrounding micorenvironments composed of stromal cells. HSPCs first emerge in the AGM (Aorta Gonads Mesonephros) region, amplify in the fetal liver (FL) and are maintained in the adult bone marrow (BM). To further characterize the molecular program of the HSPC niches, we have compared the global transcriptome of HSPC-supportive and non/less-supportive stromal clones established from the AGM, FL and BM.

overall_design: We took advantage of stromal clones established from the AGM, FL and BM and tested for their ability to support or not HSPCs ex vivo. RNA were extracted from confluent stromal cultures or sorted cells and used for hybridization of Affymetrix (mouse gene 1.0 ST) microarrays.

first: Pierre

last: Charbord

last: Durand


title: Expression data from U-2 OS osteosarcoma cell lines stably expressing an S22A-progerin mutant compared with U-2 OS expressing wt-progerin

city: Montréal

first: Mathieu

last: Vernier

address: 2900 Edouard Montpetit

department: Biochemistry

institute: Université de Montréal

summary: Disassembly of the nuclear envelope is an essential feature of mammalian cell division controlled by the phosphoryaltion of lamins via cyclin dependent kinases. This process is affected in cells expressing progerin, a lamin A allele found in patients with Hutchinson-Gilford Progeria syndrome. Progerin can inhibit cell proliferation of both normal and tumor cells and this property is largely magnified if its phosphorylation at serine 22 is inhibited by a genetic mutation to generate S22A-progerin. Surprisingly, S22A-progerin acquires the ability to trigger cellular senescence in tumor cells with mutations in the p53 and RB tumor suppression pathways suggesting a novel pathway to control the growth of malignant tumors. We used microarrays to characterize the gene expression changes induced by the S22A-progerin in comparison with the wt-progerin in U-2 OS cell line.

overall_design: U-2 OS cells were infected with a retroviral vector that express S22A-progerin or wt-progerin. After 4 days of infection, RNA was extracted from three independents replicas of each condition. Total RNA was send to Genome Quebec service for hybridization with Affymetrix microarrays.

first: Olga

last: Moiseeva

first: Frederick

last: Lessard

first: Mariana

last: Acevedo

first: Gerardo

last: Ferbeyre


title: Gene Expression Profiling in 45X Turner Syndrome patients

city: Bethesda

first: Clara

last: Cheng

address: 10 Center Drive

institute: NICHD/NIH

summary: Turner Syndrome (TS) is the most common X chromosome aneuploidy disorder in female, and the predominant karyotype is 45X, a complete loss of the second sex chromosome.  Depending on the parental origin of the single X chromosome, 45X patients can be further divided into two groups: 45Xm and 45Xp with maternal and paternal inherited X chromosome, respectively.  TS patients of 45Xm and 45Xp are found to associate with different severity in phenotype, including prevalence for cardiovascular disease.

overall_design: To study parental X chromosome impact to TS phenotype, differential gene expression in PBMC of 45Xm and 45Xp was analyzed by microarray. Gene expression for normal female 46XX was also analyzed in parallel to investigate the whole genome-wide gene expression changes between monosomy X TS patients and normal females.

first: Jian

last: Zhou

first: Carolyn

last: Bondy


title: IL-17 induces an expanded range of downstream genes in reconstituted human epidermis model

city: New York

first: Mayte

last: Suarez-Farinas

address: 1425 Madison Ave, L2-70C, Box 1077,

institute: Mount SinaiSchool of Medicine

summary:
Background: IL-17 is the defining cytokine of the Th17, Tc17, and γδ T cell populations that plays a critical role in mediating inflammation and autoimmunity. Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines with relevant contributions of IFN-γ, TNF-α, and IL-17. Despite the pivotal role IL-17 plays in psoriasis, and in contrast to the other key mediators involved in the psoriasis cytokine cascade that are capable of inducing broad effects on keratinocytes, IL-17 was demonstrated to regulate the expression of a limited number of genes in monolayer keratinocytes cultured in vitro.
Methodology/Principal Findings: Given the clinical efficacy of anti-IL-17 agents is associated with an impressive reduction in a large set of inflammatory genes, we sought a full-thickness skin model that more closely resemble in vivo epidermal architecture. Using a reconstructed human epidermis (RHE), IL-17 was able to upregulate 419 gene probes and downregulate 216 gene probes. As possible explanation for the increased gene induction in the RHE model is that CEBPβ, the transcription factor regulating IL-17-responsive genes, is expressed in differentiated KCs.
Conclusions/Significance: The genes identified in IL-17-treated RHE are likely relevant to the IL-17 effects in psoriasis, since ixekizumab (anti-IL-17A agent) strongly suppressed the “RHE” genes in psoriasis patients treated in vivo with this IL-17 antagonist.

overall_design: RHE samples were treated with IFNg, IL-22 and IL-17 and compared with control

last: Suárez-Fariñas

first: Andrea

last: Chiricozzi

first: James

last: Krueger


title: Identification of Sox3 targets in mouse neural progenitor cells

city: Adelaide

first: Nicholas

middle: Alan

last: Rogers

state: South Australia

address: MLS building Gate 8 Victoria Drive

country: Australia

institute: University of Adelaide

summary:
Sox3 has been shown to be expressed within neural progenitors of the developing mouse central nervous system. However, identification of Sox3 targets within neural progenitors has remained elusive.

Using microarrays we compared populations of in vitro derived mouse neural progenitor cells, with or without Sox3, to identify putative Sox3 neural progenitor targets.

overall_design: Mouse R1 ES cells, with or without Sox3, were differentiated into neural progenitor cells using the standard N2B27 protocols. At the fourth day of N2B27 differentiation, over two independent series, RNA was extracted from both Sox3 positive and Sox3 null populations and hybridization on a GeneChip Mouse Gene 1.0 ST Affymetrix microarrays.

first: Paul

last: Thomas


title: Expression data from whole retina of 8-week old db/db diabetic mice and lean littermates

status: Public on Feb 27 2014

city: Barcelona

first: Cristina

last: Hernández

address: Passeig Vall d'Hebron, 119-129

department: Diabetes and Metabolism

institute: Vall d'Hebron - Research Institute

summary:
Diabetic retinopathy is one of the leading causes of blindness in diabetic patients. Emerging evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy, but the underlying causes of neuronal loss are unknown.
To unravel potential mechanisms underlying early retinal neurodegeneration in diabetic retinopathy, a gene expression profiling study was undertaken to compare the gene expression in retinas of 8-week db/db diabetic mice with that of lean non-diabetic littermates.

overall_design: Retinas were obtained from 8-week db/db diabetic mice and age-matched lean non-diabetic controls. Total RNA was extracted and processed for being hybridized onto affymetrix DNA microarrays.

first: Rafael

last: Simó

first: Josep

last: Villena

first: Patrica

last: Bogdanov

first: Lidia

last: Corraliza


title: Transcriptome from circulating cells suggests dysregulated pathways associated with long-term recurrent events following first-time myocardial infarction.

city: Rochester

first: XING

last: LI

state: MN

address: 200 1st street SW

department: Health Sciences Research

institute: Mayo Clinic

summary: Whole-genome gene expression analysis has been successfully utilized to diagnose, prognosticate, and identify potential therapeutic targets for cardiovascular disease. However, the utility of this approach to identify outcome-related genes and dysregulated pathways following first-time myocardial infarction (AMI) remains unknown and may offer a novel strategy to detect affected expressome networks that predict long-term outcome.  Whole-genome microarray and targeted cytokine expression profiling on blood samples from normal cardiac function controls and first-time AMI patients within 48-hours post-MI revealed expected differential gene expression profiles enriched for inflammation and immune-response pathways in AMI patients. To determine molecular signatures at the time of AMI that could prognosticate long-term outcomes, transcriptional profiles from sub-groups of AMI patients with (n=5) or without (n=22) any recurrent events over an 18-month follow-up were compared. This analysis identified 559 differentially expressed genes. Bioinformatic analysis of this differential gene set for associated pathways revealed 1) increasing disease severity in AMI patients is associated with a decreased expression of the developmental epithelial-to-mesenchymal transition, and 2) modulation of cholesterol transport genes that include ABCA1, CETP, APOA1, and LDLR is associated with clinical outcome. In conclusion, differentially regulated genes and modulated pathways were identified that predicted recurrent cardiovascular outcomes in first-time AMI patients. This cell-based approach for risk stratification in AMI warrants a larger study to determine the role of metabolic remodeling and regenerative processes required for optimal outcomes. A validated transcriptome assay could represent a novel, non-invasive platform to anticipate modifiable pathways and therapeutic targets to optimize long-term outcome for AMI patients.

overall_design: The overall experimental design includes blood samples from 21 control and 31 myocardial infaction patient groups. Among the 31patients, 5 patients have recurrent events. Microarray were peformed on the blood samples and comparisons of control vs patient and patients with recurrent events vs patients without recurrent events were performed to identify differential genes related to disease or patients groups with recurrent events for the following bioinformatic analysis.

first: Rahul

last: Suresh

first: Xing

last: Li

first: Anca

last: Chiriac

first: Kashish

last: Goel

first: Andre

last: Terzic

first: Carmen

last: Perez-Terzic

first: Timothy

last: Nelson


title: Expression data from pDC infected with Aspergillus fumigatus

city: Sao Paulo

first: Flavio

middle: V

last: Loures

state: SP

address: Rua Deputado joaquim libanio, 216

department: Immunology

country: Brazil

institute: Universidade de Sao Paulo

summary: Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors responsible for hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2 but not Dectin-1 participates in hyphal recognition by pDCs and that Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. Thus, these structures closely resembled those of neutrophil extracellular traps (NETs).   Microarray analysis of the pDC transcriptome upon A. fumigatus infection demonstrated up-regulated expression of genes previously associated with viral infections or apoptosis. Moreover, the abundant expression of type I Interferon-encoding genes seen in CpG-stimulated pDCs was absent in the pDCs infected with A. fumigatus hyphae. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2. This interaction leads to formation of pET and triggers a distinct pattern of pDC gene expression.

overall_design: The spectrum of changes in gene expression was examined in pDCs from 3 blood donors, 2 and 4h following incubation with hyphae. Comparative controls included unstimulated and CpG-stimulated pDCs.

first: Flávio

first: Stuart

middle: M

last: Levitz

first: Charles

last: Specht


title: Fermentative and nitrate respiratory transcriptome analysis of E. coli K12 MG1655

first: Bernhard

last: Palsson

address: 9500 Gilman Dr.

institute: University of California San Diego

summary: Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during shifts in electron acceptor availability. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs), ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate > 80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Finally, based on the data we propose a feedforward with feedback trim regulatory scheme by showing extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r2 (p < 1e-6) correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. We also are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.

sample_organism: Escherichia coli str. K-12 substr. MG1655

platform_organism:
Escherichia coli
Escherichia coli K-12

overall_design:
Biological replicates were performed in triplicate for Δfnr, ΔarcA, and wild type Escherichia coli K12 MG1655 strains under both fully fermentative and nitrate respiratory conditions.
An 18 chip study with three different strains under two different culture conditions.

first: Stephen

last: Federowicz

first: Donghyuk

last: Kim

first: Byung-Kwan

last: Cho

middle: O


title: Determining the control circuitry of redox metabolism at the genome-scale

type: Genome binding/occupancy profiling by genome tiling array

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

platform_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: Refer to individual Series


title: Epigenome analysis of normal lung tissue samples

status: Public on Mar 03 2014

city: Rockville

first: Jianxin

last: Shi

state: Maryland

address: 9609 Medical Drive, 7E596

institute: NCI/NIH

summary: Genome wide DNA methylation profiling of normal lung tissue samples. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in nor mal lung tissue samples. Samples included 244 normal lung tissue samples from lung cancer patients.

overall_design:
Environment and Genetics in Lung Cancer Etiology
EAGLE; Population-based case-control study
Bisulphite converted DNA from 244 fresh-frozen primary human lung samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2. This file has 60 samples.

first: Maria

last: Landi


title: Cancer arises through reprogramming-like processes in mice

city: Houston

first: Michael

last: Green

state: TX

address: 1515 Holcombe Blvd, Unit 903

department: Lymphoma/Myeloma

institute: MD Anderson Cancer Center

summary: Gene expression data from CD22+B220+ FACS-purified splenocytes of adult wild-type, Sca1-Bcl6(floxed) and Sca1-Bcl6(Δ) knock-in CBAxC57BL/6J mice.

overall_design: The Bcl6 floxed vector was generated by inserting the mouse Bcl6–IRES-eGFP cassette flanked by loxP sites into the ClaI site of the pLy6 vector. The transgene fragment was excised from its vector by restriction digestion with NotI, purified and injected into CBAxC57BL/6J fertilized eggs. Two independent transgenic lines were generated and analyzed. Sca1-Bcl6(floxed) mice were bred to mb1-Cre mice to generate Sca1-Bcl6(Δ) mice. Splenic B220+CD22+ cells were FACS purified from wild-type, Sca1-Bcl6(floxed) and Sca1-Bcl6(Δ) mice and arrayed using Affymetrix Mouse Gene 1.0 ST arrays.

first: Isidro

last: Sánchez-García

first: Izidore

last: Lososs

first: Ash

last: Alizadeh


title: Progesterone Antagonist Therapy in a Pelizaeus-Merzbacher  Mouse Mode

status: Public on Feb 26 2014

city: Munich

first: Sven

middle: Peter

last: Wichert

state: Bavaria

address: Nussbaumstr. 7

department: Psychiatry and Psychotherapy

institute: Ludwig-Maximilians-University Munich

summary: Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disease, characterized by ataxia, intellectual disability, epilepsy and premature death. In the majority of cases, PMD is caused by duplication of PLP1 that is expressed in myelinating oligodendrocytes. Despite detailed knowledge of PLP1, there is presently no curative therapy for PMD. We used a Plp1 transgenic PMD mouse model to test the therapeutic effect of Lonaprisan, an antagonist of the nuclear progesterone receptor, in lowering Plp1 mRNA overexpression. We applied placebo-controlled Lonaprisan therapy to PMD mice for 10 weeks and performed the grid slip analysis to assess the clinical phenotype. Additionally, mRNA expression and protein accumulation as well as histological analysis of the central nervous system were performed. While Plp1 mRNA levels are increased about 1.8-fold in PMD mice compared to wildtype controls, daily Lonaprisan treatment reduced overexpression at the RNA level up to 1.5-fold, which was sufficient to significantly improve a poor motor phenotype. Electron microscopy confirmed a 25% increase in the number of myelinated axons in the corticospinal tract when compared to untreated PMD mice. Microarray analysis revealed the upregulation of pro-apoptotic genes in PMD mice that could be partially rescued by Lonaprisan treatment, which also reduced microgliosis, astrogliosis, and lymphocyte infiltration.

overall_design: We treated mice with Lonaprisan or vehicle for 10 weeks. Brains from 13 week old mice were collected and subsequently lysed for total RNA extraction. We took three biological replicates for each Treatment and Placebo.

first: Thomas

last: Prukop

first: Dirk

last: Epplen

first: Tobias

last: Nientiedt

first: Robert

last: Fledrich

first: Ruth

last: Stassart

first: Moritz

last: Rossner

first: Julia

last: Edgar

first: Hauke

last: Werner

first: Klaus-Armin

last: Nave

middle: W

last: Sereda


title: Gene profiling in CBA and BL/6 bone marrow derived dendritic cells (BMDC)

status: Public on Feb 25 2014

first: Miguel

last: Stadecker

state: MA

address: 150 Harrison Ave

institute: Tufts University School of Medicine

summary: Analysis of baseline gene expression in bone marrow derived dendritic cells (BMDC) from female CBA/J  (CBA) and C57BL/6 (BL/6) mice.  Results provide insight into strain-dependent differences in gene expression.

overall_design: CBA and BL/6 BMDCs prepared from individual mice were plated in replicate at 1x10^6 cells/ml in 48-well tissue culture plates (BD Falcon). Replicates were pooled after 4hr and total RNA was obtained by Trizol® (Invitrogen) extraction according to the manufacturer’s instructions.

first: Holly

middle: E

last: Ponichtera

first: Mara

middle: G

last: Shainheit

first: Chao-Qiang

last: Lai

first: Laurence

middle: D

last: Parnell


title: Effect of  chronic valproic acid treatment on hepatic gene expression profile in Wfs1 knockout mouse.

status: Public on Feb 20 2014

city: Tartu

first: Anton

last: Terasmaa

address: Ravila 19

department: Faculty of Medicine, Institute of Bio- and Translational Medicine

institute: University of Tartu

summary:
Aim of the present study was to compare the effect of chronic VPA treatment in wild type and Wfs1 knockout mice on hepatic gene expression profile.
Wild type, Wfs1 heterozygous and homozygous mice were treated with VPA for three months (300 mg/kg i.p. daily) and gene expression profiles in liver were evaluated using Affymetrix Mouse GeneChip 1.0 st arrays.

overall_design: male wild-type and Wfs1 mutant (+/- and -/-) mice were treated with valproic acid (300 mg/kg/day i.p.) or vehicle (saline, 10ml/kg i.p.) for 12 weeks starting from age 4 to 6 weeks. At age 16 to 18 weeks mice were killed, RNA extracted from the liver and analysed using Affymetrix Mouse Gene 1.0 ST Arrays. Expression of few genes was verified using RT-PCR. There were 8 animals in every group, 48 animals total.

first: Marite

last: Punapart

first: Mall

last: Eltermaa

last: Oflijan

first: Silva

last: Sütt

first: Anne

last: Must

first: Sulev

last: Kõks

first: Leonard

last: Schalkwyk

first: Catherine

last: Fernandes

first: Eero

last: Vasar

first: Ursel

last: Soomets


title: The effect of Sparstolonin B (SsnB) on gene expression in HCAECs

city: Columbia

first: Henry

middle: Rhodes

last: Bateman

state: SC

address: 6439 Garners Ferry Road

department: Cell Biology & Anatomy

institute: University of South Carolina

summary:
Sparstolonin B is a novel bioactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent.  SsnB has previously demonstrated anti-angiogenic properties.  In functional assays, SsnB inhibited endothelial cell tube formation (Matrigel method) and cell migration (Transwell method) in a dose-dependent manner.
We used microarrays to examine how SsnB affected the gene expression of human coronary artery endothelial cells (HCAECs), focusing in particular on pathways related to angiogenesis.

overall_design: Three plates of HCAECs were exposed to 100 micromolar SsnB and three plates of HCAECs were exposed to Vehicle Control (1:1000 dilution of DMSO).  After 24 hours, RNA was extracted for microarrays and gene expression was analyzed.

first: Jeremy

last: Barth

first: Susan

last: Lessner


title: The effect of Sparstolonin B (SsnB) on gene expression in HUVECs

summary:
Sparstolonin B is a novel bioactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent.  SsnB has previously demonstrated anti-angiogenic properties.  In functional assays, SsnB inhibited endothelial cell tube formation (Matrigel method) and cell migration (Transwell method) in a dose-dependent manner.
We used microarrays to examine how SsnB affected the gene expression of human umbilical vein endothelial cells (HUVECs), focusing in particular on pathways related to angiogenesis.

overall_design: Two plates of HUVECs were exposed to 100 micromolar SsnB and two plates of HUVECs were exposed to Vehicle Control (1:1000 dilution of DMSO).  After 24 hours, RNA was extracted for microarrays and gene expression was analyzed.


title: Gene expression data from mouse ES cell-derived primitive NSCs and definitive NSCs

city: HongKong

first: Bin

last: Wang

address: Rm 105, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, SHATIN, NT

country: China

institute: The Chinese University of Hong Kong

summary:
Primitive neural stem cells (NSCs) could be derived from pluripotent mouse embryonic stem (ES) cells, and then differentiate into definitive-type neural stem cells which resemble NSCs obtained from the central nervous system. Hence, primitive NSCs define an early stage of neural induction and provide a model to understand the mechanism that controls initial neural commitment.
In this study, we performed microarray assay to analyze the global transcriptional profiles in mouse ES cell-derived primitive and definitive NSCs and to depict the molecular changes during the multi-staged neural differentiation process.

overall_design: Primitive NSCs derived directly from ESCs in Lif (p-NSC_L), primitive NSCs that were sub-cultured in the presence of Lif and FGF (p-NSC_LF), as well as definitive NSCs derived from primitive NSCs in medium containing FGF and EGF, were collected for RNA extraction and hybridization on Affymetrix microarrays. Mouse ESCs and NSCs obtained from mouse embryonic brain (E11.5) were included for controls. For each cell type, we collected two biological replicate samples for microarray analysis.

first: Bo

last: Feng

first: Wan

middle: H

last: Tsang


title: Genome-wide expression kinetics of children with Type 1 diabetes (T1D) -associated autoantibodies or progression towards clinical T1D, compared to healthy matched controls .

city: Turku

first: Henna

last: Kallionpää

address: P.O. Box 123

department: Turku Centre for Biotechnology

institute: University of Turku

summary: To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis.

overall_design: 357 peripheral blood RNA samples from 10 autoantibody-positive children (Case) and their matched controls (Control) or alternatively 18 prediabetic children (T1DCase) and their matched controls (T1DControl) were analyzed with Affymetrix U219 gene array, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (positive for T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU). Two control children were selected for T1D cases 3, 5, 13 and 17. Case5 & T1DCase15 and  Case7 & T1DCase3 share the same matched control. Sample T1DControl7_4 was excluded from the final analysis as an outlier, resulting in 356 total Samples listed below.

first: Laura

middle: L

last: Elo

first: Juha

last: Mykkänen

first: Essi

last: Laajala

first: Matti

last: Vaarma

first: Teemu

first: Heikki

last: Hyöty

first: Jorma

last: Ilonen

first: Riitta

last: Veijola

first: Tuula

last: Simell

first: Mikael

last: Knip

first: Harri

last: Lähdesmäki

first: Olli

last: Lahesmaa

first: Isis

last: Ricaño-Ponce

first: Cisca

last: Wijmenga


title: Identification of Molecular Pathways Facilitating Glioma Cell Invasion In Situ

first: Margaret

middle: C

last: Cam

state: MD

institute: NIH

summary:
Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion.
In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC) xenograft model to explore gene expression changes in situ  in invading glioma cells compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex.

overall_design: Replicate sets of mice (n=4) were inoculated with either of two different GSC's derived from from human glioma, and each mouse had samples taken from the tumor mass, the infiltrating area and the mouse brain parenchyma, resulting in 3 samples per animal.  The tumor mass and infiltrating samples were hybridized on human U133Plus2 Arrays, whereas the infiltrating samples and mouse brain parenchyma were hybridized on mouse

first: Maggie

first: Ido

last: Nevo


title: Epigenome analysis of smoking in peripheral blood mononuclear cells (PBMC) samples

city: Iowa City

first: Robert

middle: A

last: Philibert

state: Iowa

address: MEB, 500 Newton Road, Room 2-126D

department: Psychiatry

institute: University of Iowa

summary: Genome wide DNA methylation profiling of smokers and non-smokers in PBMC samples. The Illumina Infinium 450k Human DNA methylation Beadchip v1.1  was used to obtain DNA methylation profiles across  485,577 CpGs in PBMC samples. Samples included 50 smokers and 61 non-smokers.

overall_design: Bisulfite converted DNA from the 111 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip v1.1


title: The effect of Sparstolonin B (SsnB) on gene expression

first: Henry

last: Bateman


title: Hematopoietic stem cells from mice treated with G-CSF or saline alone for 36 hours

status: Public on Feb 19 2014

city: Saint Louis

first: laura

last: schuettpelz

state: MO

address: 660 S. Euclid

institute: washington university

summary: Recent studies demonstrate that inflammatory signals regulate hematopoietic stem cells (HSCs).  Granulocyte-colony stimulating factor (G-CSF) is often induced with infection and plays a key role in the stress granulopoiesis response.  However, its effects on HSCs are less clear.  Herein, we show that treatment with G-CSF induces expansion and increased quiescence of phenotypic HSCs, but causes a marked, cell-autonomous HSC repopulating defect associated with induction of toll-like receptor (TLR) expression and signaling.  The G-CSF-mediated expansion of HSCs is reduced in mice lacking TLR2, TLR4 or the TLR signaling adaptor MyD88.  Induction of HSC quiescence is abrogated in mice lacking MyD88 or in mice treated with antibiotics to suppress intestinal flora. Finally, loss of TLR4 or germ free conditions mitigates the G-CSF-mediated HSC repopulating defect.  These data suggest that low level TLR agonist production by commensal flora contributes to the regulation of HSC function and that G-CSF negatively regulates HSCs, in part, by enhancing TLR signaling.

overall_design: RNA from KSL SLAM cells (Lineage- c-Kit+ Sca-1+ CD150+ CD48- CD41-) from bone marrow of 5-10 mice per group treated with G-CSF or saline alone was prepared using the RNA XS column kit (Machery-Nagel), amplified using the NuGen Ovation system (NuGen) and hybridized to the MoGene 1.0 ST array. This array includes 4 independent PBS control and 4 G-CSF treated groups.

first: Laura

last: Schuettpelz

first: Daniel

last: Link


title: Heme-induced inhibition of Bach1derepresses Spic.

status: Public on Mar 14 2014

city: St. Louis

first: MALAY

last: HALDAR

address: 7751 charing square lane

department: Pathology and Immunology

institute: Washington University in St. Louis

summary:
Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insight into iron homeostasis.
Bone marrow derived macrophages were generated in vitro by culturing WT and Bach1 knock out bone marrow in the presence of GM-CSF and their global gene expression pattern were compared in the presence or absence of heme at the various indicated time points after treatment.

overall_design: GMP and MPP populations were sorted from fetal liver chimeras and pooled by donor genotype. RNA was isolated using an RNAqueous-Micro Kit (Ambion) and submitted for amplification, labeling and hybridization. Expression values were analyzed after RMA quantile normalization using ArrayStar software (DNASTAR).

first: Malay

last: Haldar

first: Kenneth

last: Murphy


title: Hematopoietic stem cells from mice treated with G-CSF or saline alone for 36 hours and 7 days


title: Microarray-based DNA methylation profiling of medulloblastoma and normal cerebellum samples

city: Heidelberg

first: Peter

last: Lichter

address: Im Neuenheimer Feld 580

department: Molecular Genetics

institute: German Cancer Research Center

summary:
Robust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumor material.
Validation of patterns identified by whole-genome bisulphite sequencing in a larger cohort.

overall_design: DNA methylation profiles of 276 primary medulloblastoma and 8 normal cerebellum control samples were generated from fresh-frozen and formalin-fixed paraffin-embedded material using the Illumina 450k methylation array.

first: Volker

last: Hovestadt

first: David

middle: T

last: Jones

first: Bernhard

last: Radlwimmer

first: Stefan

last: Pfister


title: Transcriptional profiles of genes in the early stage of osteoclastogenesis

status: Public on Feb 17 2014

city: Toronto

first: Yongqiang

last: Wang

state: ON

address: 150 College St

department: Faculty of Dentistry

institute: University of Toronto

summary: Osteoclast (OC) differentiation undergoes a two-step process: commitment of hematopoietic progenitor cells to tartrate-resistant acid phosphatase (TRAcP) positive OC precursors (OCPs), and fusion of OCPs into multinucleated OCs. In order to identify transcriptional profiles of genes in the transitional phase between OC commitment and fusion in OCG, Affymetrix® Mouse Gene 1.0 ST arrays were performed on total RNA extracted from mouse (SV129/BL6 ) monocytes and pre-osteoclasts (pre-OCs), primed with macrophage colony-stimulated factor (M-CSF) or M-CSF and soluble recombinant receptor activator of NF-кB ligand (sRANKL), respectively. The analysis identified 656 RANKL-up or down-regulated in the early stage of osteoclastogenesis.

overall_design: Monocytes isolated from mouse bone marrow were stimulated with M-CSF and soluble RANKL (m + r), or M-CSF alone (m).

first: Michael

last: Glogauer


title: Reduced Expression of the Proto-oncogene Myc Increases Mouse Longevity and Enhances Healthspan

status: Public on Feb 22 2014

city: Providence

first: Jeffrey

middle: Walter

last: Hofmann

state: RI

address: 70 Ship St

department: Molecular Biology, Cell Biology and Biochemistry

institute: Brown University

summary:
MYC is a pleiotropic transcription factor that regulates numerous pathways and whose deregulation promotes cancer. Myc+/- mice have extended lifespan relative to their wild type littermates. To better understand the effects of the Myc+/- genotype on cellular processes, microarrays were performed on young (5 month) and old (24 month) Myc+/- and WT males in liver, skeletal muscle, and adipose tissues.
Microarray data were used to compare the effects of aging with the effects of the Myc+/- genotype at each age, to identify pathways enriched for differentially expressed genes, and to compare the Myc+/- gene expression signature with that from other long-lived mice.

overall_design: Male mice of each genotype (Myc+/- and wild type) were sacrificed at 5 months and 24 months of age, and tissues were harvested and snap frozen in liquid nitrogen. RNA was extracted, and pooled between 5-8 mice within each cohort, creating one pooled sample for each combination of age, genotype, and tissue. Three technical replicates were run for each sample.

first: Xiaoai

last: Zhao

first: Marco

last: De Cecco

first: Abigail

last: Peterson

first: Jayameenakshi

last: Manivannan

first: Gene

middle: B

last: Hubbard

first: Yuji

last: Ikeno

first: Yongqing

last: Zhang

first: Bin

last: Feng

first: Wenbo

last: Qi

first: Holly

last: Van Remmen

first: Richard

last: Miller

first: Rafael

last: de Cabo

first: Haiyan

last: Xu

first: Nicola

last: Neretti

first: John

last: Sedivy


title: Spheroid model system (II)

city: Uppsala

first: Mårten

last: Fryknäs

address: Akademiska sjh ingång 61

department: Medical sciencies

country: Sweden

institute: Uppsala university

summary:
Microarray based mRNA profiling was used to charactarize and compare the gene expression in cells grown as monolayer or spheroids.

Keywords: Expression profiling by array

first: Marten

last: Fryknas


title: A combined strategy of global gene expression analysis and multiplex PCR established a 13-member gene signature for the diagnosis of human hepatocellular carcinoma.

status: Public on Feb 24 2014

city: Singapore

first: Hui

last: K. Man

address: 11 Hospital Drive

department: Division of Cellular and Molecular Research

country: Singapore

institute: National Cancer Centre Singapore

summary:
Aberrant gene expression between HCC tumor tissues, histologically normal adjacent liver tissues and peripheral blood mononuclear cell (PBMC) samples from healthy individuals and patients with pancreatic carcinoma, gastric carcinoma and HCC were identified using Affymetrix gene arrays.
A 13-member HCC-specific gene signature was identified and validated via custom-designed quantitative multiplexed gene expression analysis using the GenomeLab GeXP Genetic Analysis System (GeXP).

overall_design: Peripheral blood mononuclear cell (PBMC) from healthy individuals, patients with pancreatic carcinoma, gastric carcinoma, and HCC were isolated and total RNA was extracted for Affymetrix gene microarray analysis.

first: R

last: Zhou

first: M

last: Shi

last: Chen

first: C

middle: K

last: Tan

first: L

last: London

first: H

last: Man


title: DNA methylation profiles of liver and placenta technical replicates

city: Charlestown

first: Martin

last: Aryee

address: 149 13th Street

department: Pathology

institute: Massachusetts General Hospital

summary: We profiled DNA from liver and placenta technical replicate samples on the Illumina HumanMethylation450 BeadChip array. There technical replicates represent a single liver and a single placenta sample.

overall_design: Bisulphite converted DNA was hybridized to Illumina HumanMethylation450 BeadChip arrays

middle: J

last: Irizarry


title: Gene expression changes during Type 1 diabetes pathogenesis

first: Henna

last: Kallionpää

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

Due to privacy concerns, the SNP data is not available with unrestricted access.

overall_design: Refer to individual Series

first: Laura

last: Elo

first: Juha

last: Mykkänen

first: Essi

last: Laajala

first: Matti

last: Vaarma

first: Heikki

last: Hyöty

first: Jorma

last: Ilonen

first: Riitta

last: Veijola

first: Tuula

last: Simell

first: Mikael

last: Knip

first: Harri

last: Lähdesmäki

first: Olli

last: Lahesmaa

first: Cisca

last: Wijmenga

first: Isis

last: Ricaño-Ponce


title: LNCaP prostate cancer cell lines overexpressing wild-type or GARRPR-mutant Bag-1L

status: Public on Feb 18 2014

city: Boston

last: Cato

address: 450 Brookline Ave., D728

department: Medical Oncology

institute: Dana-Farber Cancer Institute

summary: The BF-3 pocket of the androgen receptor (AR) has been identified as an allosteric modulator of the transactivation function of the AR. We now demonstrate that a duplicated GARRPR motif at the N-terminus of the cochaperone Bag-1L functions through this BF-3 domain. Amino acid exchanges in these two motifs impair binding of Bag-1L to the AR but increase the androgen-dependent activation of a subset of AR-target genes. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the receptor.

overall_design: LNCaP cells stably expressing the empty vector construct (=control), or wild-type or N-terminal GARRPR mutant Bag-1L were cultured under hormone-starvation conditions for 72 h and then treated with vehicle or 10 nM DHT for 4 h. Biological triplicate samples were analyzed for each cell line.

first: Katja

last: Jehle

first: Antje

last: Neeb

first: Claudia

last: Muhle-Goll

first: Nicole

last: Jung

first: Emmanuel

last: Smith

first: Victor

last: Buzon

first: Laia

middle: R

last: Carbó

first: Eva

last: Estébanez-Perpiñá

last: Schmitz

first: Ljiljana

last: Fruk

first: Burkhard

last: Luy

first: Yu

last: Chen

first: Marc

last: Cox

first: Stefan

last: Bräse

first: Myles

last: Brown

first: Andrew


title: Human Subperitoneal Fibroblasts and Cancer Cell Interaction Creates Microenvironment Enhancing Tumor Progression and Metastasis

city: Chiba

first: Youichi

last: Higuchi

address: 6-5-1 Kashiwanoha, Kashiwa

institute: Research Center for Innovative Oncology National Cancer Center Hospital East

summary:
Fibroblasts isolated from human colon submucosal and subperitoneal layer were stimulated by colon cancer cell line (DLD-1) cultured medium. Peritoneal invasion in colon cancer is an important prognostic factor, and the fibrosis with α-SMA was a significant pathological feature of the cancer microenvironment formed by peritoneal invasion (CMPI).
The result indicated that the gene expression of subperitoneal fibroblasts showed more various gene modification than submucosal fibroblasts. And ACTA2 expression was higher in fibroblasts from subperitoneal layer than that from submucosal layer. Together with this concordant stromal protein expression in CMPI, this in vitro model is able to reflect the special microenvironment in CMPI.

overall_design: 3 cases of human colon submucosal and subperitoneal fibroblasts were isolated, and these fibroblasts were stimulated with DLD-1 cultured medium. Total RNA were extracted from these samples and hybridized in Affymetrix microarray to compare their gene expression changes through the DLD-1 stimulation

first: Motohiro

last: Kojima

first: Mitsuru

last: Yokota

first: Genichiro

last: Ishii

first: Norio

last: Saito

first: Kazuhiko

last: Aoyagi

first: Hiroki

last: Sasaki

first: Atsushi

last: Ochiai


title: Induction of Ground-State Pluripotency by Minimal Factor Episomal-Expression in Single Cell Format

city: San Diego

first: Dave

last: Robbins

address: 3535 General Atomics Court Ste. 200

institute: Fate Therapeutics

summary:
Human pluripotent stem cells in culture are often associated with the prime state which represents a more developed state relative to the naïve state which is often associated with the inner cell mass and thought to have the potential to give rise to all cell types. We have developed a small molecule-driven cocktail FMM that maintains human pluripotent stem cells in a state similar to the naive state as defined by several properties including gene expression profile.
We used global gene expression to compare and contrast induced pluripotent stem cells -- from various starting points -- cultured in either small molecule medium FMM or conventional medium.

overall_design: Somatic cells were induced to reprogram by various methods and maintained in various culture conditions. Each culture condition was analyzed by various methods including global gene expression.

first: Bahram

last: Valamehr

first: David

first: Peter

last: Flynn


title: Mouse spleen: wild type vs leukemic

city: Charlottesville

first: R. Ariel

last: Gomez

state: VA

department: Pediatrics

institute: University of Virginia

summary:
mRNA profiling of mouse spleens comparing wild type spleens vs. spleens from mice having deletion of RBP-J in cells of the renin lineage which results in B-cell leukemia
We used microarrays to detail the global program of gene expression in wild type and the leukemic spleens which revealed upregulation of genes for cell cycle progression and B cell identity in the leukemic spleens.

overall_design: Two condition experiment: wild type vs leukemic; biological replicates: individual mice - 2 wild type, 2 mutant. One replicate per array.

first: R

first: Maria

last: Sequeira-Lopez

first: Brian

last: Belyea

first: Ellen

middle: S

last: Pentz


title: Hematopoietic stem cells from mice treated with G-CSF or saline alone for 7 days

first: laura

last: schuettpelz

summary: Recent studies demonstratethat inflammatory signals regulate hematopoietic stem cells (HSCs).  Granulocyte-colony stimulating factor (G-CSF) is often induced with infection and plays a key role in the stress granulopoiesis response.  However, its effects on HSCs are less clear.  Herein, we show that treatment with G-CSF induces expansion and increased quiescence of phenotypic HSCs, but causes a marked, cell-autonomous HSC repopulating defect associated with induction of toll-like receptor (TLR) expression and signaling.  The G-CSF-mediated expansion of HSCs is reduced in mice lacking TLR2, TLR4 or the TLR signaling adaptor MyD88.  Induction of HSC quiescence is abrogated in mice lacking MyD88 or in mice treated with antibiotics to suppress intestinal flora. Finally, loss of TLR4 or germ free conditions mitigates the G-CSF-mediated HSC repopulating defect.  These data suggest that low level TLR agonist production by commensal flora contributes to the regulation of HSC function and that G-CSF negatively regulates HSCs, in part, by enhancing TLR signaling.

overall_design: RNA from KSL SLAM cells (Lineage- c-Kit+ Sca-1+ CD150+ CD48- CD41-) from bone marrow of 5-10 mice per group treated with G-CSF or saline alone was prepared using the RNA XS column kit (Machery-Nagel), amplified using the NuGen Ovation system (NuGen) and hybridized to the MoGene 1.0 ST array. This array includes 3 independent PBS control and 3 G-CSF treated groups.

first: Laura

last: Schuettpelz

first: Daniel

last: Link


title: DNA methylation and gene expression analysis during myogenic differentiation

status: Public on Feb 15 2014

city: Fukuoka-city

first: Kohei

last: Miyata

state: Fukuoka

address: 7-45-1 Nanakuma, Jounannku

department: Obstetrics and Gynecology

institute: Fukuoka University

summary: DNA methylation has been considered to play an important role during myogenic differentiation. In terminal differentiation of myoblasts, chronological alteration of DNA methylation status was poorly understood. Using Infinium HumanMethylation450 BeadChips, we validated genome wide DNA methylation profiles of human myoblast differentiation models. To investigate correlation between DNA methylation and gene expression, we also assessed gene expression of myoblasts with GeneChip Human Genome U133 Plus 2.0 array.

overall_design:
Gene expression profiles of myoblasts (4 samples) were generated with GeneChip Human Genome U133 Plus 2.0 array (Affymetrix).
This submission represents transcriptome component of study.

first: Tomoko

last: Nakabayashi

first: Hiroshi

last: Asahara


title: Expression data from mouse ventral midbrain

city: Seoul

first: Gi Hoon

last: Son

state: select a state

address: Inchon-ro 73

department: Department of Legal Medicine

country: South Korea

institute: Korea University

summary:
The circadian nature of mood and its dysfunction in affective disorders is well recognized, but the underlying molecular mechanisms are still unclear. We showed that the circadian nuclear receptor REV-ERBa, which is associated with bipolar disorder, impacts midbrain dopamine production and mood-related behavior in mice. Genetic deletion of the Rev-erba gene or pharmacological inhibition of REV-ERBa activity in the ventral midbrain induced mania-like behavior in association with a central hyperdopaminergic state.
We used microarrays to identify differentially expressed genes in the ventral midbrains of wild-type (WT) and Rev-erba knock-out (RKO) mice.

overall_design: Male RKO and WT mice (10-15 weeks of age) were maintained in a C57BL/6J background. Mice were housed in temperature-controlled (22-23ºC) quarters under a 12-h light-dark (LD) photoperiod (lights on at 8:00 a.m.). After entrainment for >10 days under LD conditions, mice were kept in constant darkness (DD) for 2 days starting at lights-off time. On the third day, mice were sacrificed at indicated time points by cervical dislocation.

first: Gi

first: Sooyoung

last: Chung

first: Kyungjin

last: Kim


title: Array-based DNA methylation profiling in male infertility reveals allele-specific DNA methylation in PIWIL1 and PIWIL2

status: Public on Feb 16 2014

city: Kiel

first: Susanne

last: Bens

address: Arnold-Heller-Str.3 (Haus 10)

department: Institute of Human Genetics

institute: Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein

summary: Array-based DNA methylation profiling in peripheral blood leukocytes of 30 infertile men with impaired spermatogenesis as compared to 10 fertile men using the Illumina Infinium HumanMethylation 450k Bead Chip reveald 471 CpG sites (287 genes) to be differentially methylated between both groups. These CpG loci were significantly enriched for the gene ontology functions MHC class II receptor activity and piRNA binding. The latter was associated with two methylation-sensitive SNPs in the genes PIWIL1 and PIWIL2, respectivly, which showed significant allele distribution skewing in the infertile cohort. 445/471 differentially methylated CpGs were associated with SNPs, but 26 (15 genes) were not genomically templated and included the ENO1, MTA2, BRSK2 and LBX2 genes previously associated with fertility and spermatogenesis. The study identifies surrogate DNA methylation markers for idiopathic infertility in peripheral blood and suggests allele-specific DNA methylation differences at regulatory sites of genes involved in piRNA regulation to be associated with disturbed spermatogenesis.

overall_design: Bisulfite converted DNA of peripheral blood leukocytes from 30 infertile men and 10 fertile men as controls were hybridized to the Illumina Infinium HumanMethylation 450k Bead Chip.

first: Carolin

last: Friemel

first: Ole

last: Ammerpohl

first: Jana

last: Gutwein

first: Andreas

last: Schmutzler

first: Almuth

last: Caliebe

first: Monika

last: Kautza

first: Sören

last: von Otte

first: Reiner

last: Siebert