title: Comparison of gene expression in ventral prostates of 12 week old AR-E231G mice with AR-T857A mice

city: Adelaide

first: Vanessa

last: Thompson

state: SA

address: Frome Rd

institute: Hanson Institute / University of Adelaide

summary: The androgen receptor (AR) is an androgen-activated nuclear receptor.  The androgen signaling axis is critical in all stages of prostate cancer, although the mechanism by which it contributes to tumorigenesis remains unclear. Mutations in the AR have been detected in prostate tumors; one such mutant, E231G, exhibits increased ligand sensitivity in the presence of specific cofactors.  Mice with prostate-specific expression of AR-E231G invariably develop prostatic intraepithelial neoplasia (PIN) by 12 weeks, and metastatic prostate cancer by 52 weeks.  To determine a potential mechanism of AR-driven tumorigenesis in AR-E231G mice, we compared gene expression profiles in prostates of 12 week old AR-E231G mice with another AR-variant mouse strain (AR-T857A) that does not develop tumors.  Pathway classification of the 132 candidate genes differentially expressed in AR-E231G mouse prostates compared to AR-T857A mouse prostates revealed enrichment for groups important in prostate cancer, including “cancer,” “fatty acid metabolism” and “cell cycle” pathways.  Two genes significantly upregulated in the AR-E231G model were Adm and Cited1.  siRNA suppression of ADM and CITED1 expression by up to 63% and 79%, respectively, in LNCaP human prostate cancer cells, resulted in an approximate 1.8-fold increase in cell death.  Cell proliferation was reduced by 35% when CITED1 mRNA expression was suppressed, but not significantly altered by ADM suppression.  A gene signature set derived from this model was able to distinguish between primary Gleason grade 3 and Gleason grade 4 tumors (p=0.04237), and between human non-malignant and cancerous prostate in a test (p=0.02352) and validation cohort (p=7.53x10-9), highlighting the relevance of the AR-E231G model to the human disease.

overall_design: RNA was extracted from ventral prostate tissue from 12-week old AR-E231G and AR-T857A mice in FVB background.  Pooled RNA from 3 mice per genotype were extracted using the RNeasy kit (Qiagen, Germantown, MD, USA), and 10 µg RNA was hybridized to a total of 2 Affymetrix Mouse Genome 430 2.0 chip® microarrays.  Microarray data was normalized by Robust Multiarray Averaging.  Probes with expression changes were identified using a fold-change cut-off of log1.5.  Normalized microarray data was analysed using Ingenuity Pathways Analysis (IPA, Redwood City, CA, USA).

first: Tanya

middle: K

last: Day

first: Lisa

last: Butler

first: Wayne

last: Tilley

first: Norman

last: Greenberg

first: Howard

last: Scher


title: Comparison of the transcriptome of TEL-JAK2- versus activated NOTCH1 (ICN1)-induced T cell acute lymphoblastic leukemias (mouse)

status: Public on Sep 28 2013

city: Orsay

first: Jacques

last: GHYSDAEL

address: Centre Universitaire, Bat 110

country: France

institute: Institut Curie

summary: The TEL-JAK2 fusion oncogene and the ICN1 activated allele of NOTCH1 are the result of specific chromosomal translocations in T cell acute lymphoblastic leukemia (T-ALL). Mouse models of these diseases (TEL-JAK2 transgenic mice; Carron C.  et al. Blood (2000); a bone marrow transplantation model for ICN1-induced T-ALL) were used  to compare the transcriptional program specific to each oncoprotein in mouse models of these leukemias. Tumor load was >50% leukemic cells in all selected organs.

overall_design: Leukemic cells were collected from the thymus of terminally-ill TEL-JAK2 leukemic mice and bone marrow of terminally-ill ICN1 leukemic mice. RNA was extracted from each sample and processed for hybridization to Affymetrix arrays.

first: J

last: Ghysdael


title: Combined targeting of JAK2 and Bcl-xL/Bcl-2 as a novel curative treatment for malignancies expressing mutant JAK2 and overcoming acquired resistance to single agent JAK2 inhibitors

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

overall_design: Refer to individual Series


title: Natural cardiogenesis-based template predicts cardiogenic potential of induced pluripotent stem cell lines

status: Public on Sep 23 2013

city: Rochester

first: XING

last: LI

state: MN

address: 200 1st street SW

department: Health Sciences Research

country: USA

institute: Mayo Clinic

summary:
Rationale: Cardiac development is a complex process that results in the first integrated, multi-lineage embryonic tissue. Imperfect developmental progression leads to congenital heart disease, the most common birth defect with developmental corruption affecting more than 1% of all live births. Interrogation of individual genes has provided the backbone for cardiac developmental biology, yet a comprehensive transcriptome derived from natural cardiogenesis is required to establish an unbiased roadmap to gauge innate developmental milestones necessary for stem cell-based differentiation and in vitro disease modeling.

Objective: Apply the contextual expression database of spatial-temporal cardiac structures (published in another manuscript by Li X. from the same group) to diagnose and predict cardiogenic outcomes from individual pluripotent stem cell lines.

Methods and Results: Stage-specific cardiac structures were dissected from eight distinctive embryonic time points to produce a genome-wide expressome analysis across the spectrum of early to late cardiogenesis. Hierarchical clustering of the time course dataset demonstrated discrete gene expression profiles during natural embryonic development. In reference to the native cardiogenic expression roadmap, disruptive iPSC-derived cardiac expression profiles were revealed from pro-cardiogenic 3-factor (SOX2, OCT4, KLF4) compared to non-cardiogenic 4-factor (addition of c-MYC) reprogramming regimens upon stage-specific differentiation. Expression of cardiac-related genes from 3F-iPSC differentiated in vitro at day 0, 5, and 11 recapitulated expression of natural embryos at days 0, E7.5-E8.5, and E14.5-E18.5, respectively. In contrast, 4F-iPSC demonstrated variable gastrulation gene expression profiles beginning at day 5 of differentiation. Differential gene expression within the pluripotent ground state between the archetypical high cardiogenic potential of embryonic stem cells recapitulated in 3F-iPSC vs. the low cardiogenic potential of 4F-iPSC revealed 23 distinguishing candidate genes. Upon subsequent differentiation, cell line-specific gene expression differences were magnified to 399 genes at day 5 and 726 genes at day 11. A confirmed panel of 20 genes, differentially expressed between high and low cardiogenic cell lines, was transformed into a predictive score that was sufficient to correctly rank independent iPSC lines according to cardiogenic potential.

Conclusions: Transcriptome analysis attuned to the embryonic developing heart provides a robust platform to probe coordinated cardiac specification and maturation from stem cell-based cardiogenesis model systems. Based on this genome-wide expressome roadmap, a panel of pre-cardiac genes was extracted that allowed differential prognosis of cardiogenic competency from individual reprogrammed cell lines at the pluripotent state.

overall_design:
The overall experimental design includes 3 time points (Day0, Day5, Day11) and 3 different stem cell lines: R1 embryonic stem cells (ESCs), H9 induced pluripotent stem cells (H9-iPSCs) generated/reprogrammed by 3 transcription factors (called 3F-iPSCs), and 19BL induced pluripotent stem cells (19BL-iPSCs) generated/reprogrammed by 4 transcription factors (called 4F-iPSC). At each time point, each cell line has 3 biological replicates. In total, there are 27 samples.
R1-embryonic stem cells (R1-ESCs): Day0 undifferentiated ESCs - 3 biological replicates, Differentiated for 5 days (Day5) - 3 biological replicates, Differentiated for 11 days (Day11) - 3 biological replicates.
3F-iPSC (H9 iPSCs): Day 0 undifferentiated - 3 biological replicates, Differentiated for 5 days (Day5) - 3 biological replicates, Differentiated for 11 days (Day11) - 3 biological replicates.
4F-iPSC (19BL-iPSCs): Day0 undifferentiated - 3 biological replicates, Differentiated for 5 days (Day5) - 3 biological replicates, Differentiated for 11 days (Day11) - 3 biological replicates.

first: Almudena

last: Martinez-Fernandez

first: Xing

last: Li

first: Katherine

middle: A

last: Hartjes

first: Andre

last: Terzic

first: Timothy

middle: J

last: Nelson


title: Expression data from non-pigmented and pigmented mouse melanocytes

status: Public on Sep 21 2013

city: Boston

first: Irit

last: Adini

state: MA

address: 1 balckfan circle

department: Vascular Biology Department

institute: Boston Children's Hospital

summary:
Immortalized, amelanotic melanocytes isolted from skin of Balb/c express enzymatically-inactive tyrosinase due to a homozygous point mutation (TGT->TCT) in tyrosinase gene, resulting in a lack of melanin . To serve as a control cell line, pigmentation was restored in these cells by correcting the point mutation using an RNA-DNA oligonucleotide (kingly gift from Dr. Alexeev  Y. Vitali).
We used microarray to detail the effect of tyrosinase mutation on gene expression in normal versus mutant melanocytes.

overall_design: Pigmented and non-pigmented melanocytes were grown for RNA extraction and hybridization on Affymetrix microarrays. We used both normal and mutant melanocyte in order to obtain expression profiles. We then examined variances in gene expression between the two cell lines.

first: Robert

last: D'Amato


title: Transcriptional responses of murine macrophages to the adenylate cyclase toxin of Bordetella pertussis

status: Public on Sep 22 2013

city: Edinburgh

first: Nigel

last: Binns

address: The Chancellor's Building, 49 Little France Crescent

department: Division of Pathway Medicine

country: United Kingdom

institute: The University of Edinburgh

summary: Three different recombinant forms of CyaA were used to investigate transcriptional responses of murine bone marrow-derived macrophages (BMDMs) using Affymetrix Mouse Genome Genechips. These forms were enzymically active, invasive CyaA, nonenzymically active, invasive CyaA (CyaA*) and non-enzymically active, non-invasive CyaA (proCyaA*). BMMs, treated with 20 ng/ml of CyaA for 24 h, showed over 1000 significant changes in gene transcription compared with control cells. CyaA caused an increase in transcription of many inflammatory genes and genes associated with various signalling cascades such as those involved in cyclic AMP-dependent protein kinase A signalling. Most strikingly, CyaA caused down-regulation of numerous genes involved in cell proliferation. CyaA* at 20 ng/ml significantly up-regulated the transcription of only twelve genes after 24 h whereas proCyaA* at this concentration significantly increased the transcription of only two genes.

overall_design: The effect of administration of three different recombinant forms of pertussis toxin to mouse bone marrow derived macrophages are compared with a vehicle only contol 24 hours after treatment in technical triplicate measurements

first: Gordon

middle: Y

last: Cheung


title: A mechanistic study on the metastasis inducing function of FUS-CHOP fusion protein in liposarcoma

status: Public on Sep 20 2013

city: Heidelberg

first: Nitin

last: Patil

state: BW

address: Im Neuenheimer Feld 280

department: Molecular Oncology of Solid Tumors

country: Germany

institute: German Cancer Research Centre (DKFZ)

summary:
Identification of differential gene regulation pattern in human liposarcoma
The FUS-CHOP fusion protein has been found to be instrumental for specific oncogenic processes in liposarcoma, but its ability to induce metastasis and the underlying mechanisms by which this can be achieved remain unknown. In order to dissect its functional role in this context, we stably overexpressed this protein in SW872 liposarcoma and HT1080 fibrosarcoma cell lines, and were able to demonstrate that forced expression of FUS-CHOP significantly increases migration and invasion, as well as enhance lung and liver metastasis in the in vivo chicken chorioallantoic membrane (CAM) model, that is proliferation independent. Additionally, FUS-CHOP enhances the expression of matrix-metalloproteinases -2 and -9, and transactivates their promoters in vitro. Mutational analysis showed that C/EBP-β- (-769/-755), NF-κB (-525/-516) and CREB/AP-1 (-218/-207) sites were important for MMP-2, and NF-κB (-604/-598), AP-1 (-539/-532) and AP-1 (-81/-72) for MMP-9 transactivation. Moreover, a direct in vivo interaction of FUS-CHOP was observed in case of the MMP-2 promoter within region (-769/-207). siRNA data revealed that MMP-2 expression is essential in the FUS-CHOP induced metastatic phenotype. MMP-2-mRNA and protein expression correlated significantly with FUS-CHOP positivity in 31 resected patient liposarcoma tissues. We have for the first time provided substantial evidence for the FUS-CHOP oncoprotein as an inducer of metastasis that is due to the transcriptional induction of specific tumor-associated proteases. Insights gained from this study not only support a deeper understanding of the mechanistic properties of FUS-CHOP, but also open up new avenues for targeted therapy.

overall_design: 3 liposarcoma tumor samples, 3 corresponding normal samples, one sample replicated

first: Oliver

last: Heil


title: The AP-1 Transcription Factor c-Jun Prevents Stress-Imposed Maladaptive Remodeling of the Heart

status: Public on Sep 19 2013

city: Singapore

first: Julius

last: Müller

address: 61 Biopolis Drive

department: IMCB

country: Singapore

institute: A*Star Singapore

summary:
Systemic hypertension increases cardiac workload and subsequently induces signaling networks in heart that underlie myocyte growth (hypertrophic response) through expansion of sarcomeres with the aim to increase contractility. However, conditions of increased workload can induce both adaptive and maladaptive growth of heart muscle. Previous studies implicate two members of the AP-1 transcription factor family, junD and fra-1, in regulation of heart growth during hypertrophic response. In this study, we investigate the function of the AP-1 transcription factors, c-jun and c-fos, in heart growth. Using pressure overload-induced cardiac hypertrophy in mice and targeted deletion of Jun or Fos in cardiomyocytes, we show that c-jun is required for adaptive cardiac hyphertrophy, while c-fos is dispensable in this context. c-jun promotes expression of sarcomere proteins and suppresses expression of extracellular matrix proteins. Capacity of cardiac muscle to contract depends on organization of principal thick and thin filaments, myosin and actin, within the sarcomere. In line with decreased expression of sarcomere-associated proteins, Jun-deficient cardiomyocytes present disarrangement of filaments in sarcomeres and actin cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to pressure overload display pronounced fibrosis and increased myocyte apoptosis finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos is required to induce a transcriptional program aimed at adapting heart growth upon increased workload.
Microarrays were used to identify specific genes that might be globally affected in the absence of c-jun in cardiomyocytes.

overall_design: Total RNA was extracted from the hearts of 10 weeks old Junf/f (n=2) and Jun delta mu (n=2) mice using TRIzol Reagent.

first: Renata

last: Windak

first: Allison

last: Felley

first: Alexander

last: Akhmedov

first: Erwin

middle: F

last: Wagner

first: Thierry

last: Pedrazzini

first: Grzegorz

last: Sumara

first: Romeo

last: Ricci


title: The identification and tumorigenecity of neuronal progenitors in developing cerebellum

status: Public on Sep 13 2013

city: Philadelphia

first: Zeng-jie

last: Yang

state: Pennsylvania

address: 333  Cottman Avenue

department: Cancer Biology Program

institute: Fox Chase Cancer Center

summary: It is generally believed that cerebellar granule neurons originate exclusively from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here we identify a rare population of neuronal progenitors in the developing cerebellum that expresses Nestin. Although Nestin is widely considered a marker for multipotent stem cells, these Nestin-expressing progenitors (NEPs) are committed to the granule neuron lineage. Unlike conventional GNPs, which reside in the outer EGL and proliferate extensively, NEPs reside in the deep part of the EGL and are quiescent. Expression profiling reveals that NEPs are distinct from GNPs, and in particular, express markedly reduced levels of genes associated with DNA repair. Consistent with this, upon aberrant activation of Sonic hedgehog (Shh) signaling, NEPs exhibit more severe genomic instability and give rise to tumors more efficiently than GNPs. These studies identify a novel progenitor for cerebellar granule neurons and a novel cell of origin for medulloblastoma.

overall_design: 4 samples of Nestin expressing progenitors (NEPs), 4 samples of Math1 positive cells (GNPs) and 3 samples of Neural stem cells (CD133+ NSCs) were used for microarray analysis to determine the distinct genetic profile of NEPs. 4 samples of NEP-derived tumor and 4 samples of GNP-derived tumor were used to determine the similarity of those tumors by microarray analysis.

first: Peng

last: Li


title: Gene expression in mouse liver in response to short-term calorie restriction

status: Public on Sep 26 2013

city: Madison

first: Jamie

last: Barger

state: WI

address: 510 Charmany Drive, Suite 263

institute: LifeGen Technologies, LLC

summary:
The effect of a short-term calorie restricted diet was evaluated in six strains of mice
The dietary intervention was initiated at 8 weeks of age and continued until 22 weeks of age

overall_design: Tissues were collected from mice at 22 weeks of age; there were 96 microarrays used in total: for each of the 6 strains of mice, there were 8 control-fed mice and 8 calorie restricted mice (one individual mouse per microarray)

middle: L


title: Expression Data For BRD4 Inhibition

city: New York

first: Ping

last: Chi

state: NY

address: 417 East 68th Street

department: Human Oncology and Pathogenesis Program

institute: Memorial Sloan Kettering Cancer Center

summary: BRD4 Inhibition of spindle cell malignant peripheral nerve sheath tumor (sMPNST) tumor cells

overall_design: Cells were treated with Brd4 shRNA (3 days) or 500 nM JQ1 (2 days) before RNA isolation

first: Amish

last: Patel

first: Lu

middle: Q

last: Le


title: PDL2+, PDL2- and LPS treated PDL2- WT bone-marrow derived murine DCs

status: Public on Sep 17 2013

city: New Haven

first: Ruoyi

last: Jiang

state: CT

address: 300 Cedar Street

department: Immunobiology

institute: Yale School of Medicine

summary:
Cultured BMDCs were purified by FACS sorting for PDL2 surface expression and stimulated with LPS at 100 ng/mL or left unstimulated.
Microarray data was used to demonstrate gene expression differences between PDL2- and PDL2+ DC populations. Microarray data was also used to show that PDL2+ mature DCs were distinct from LPS treated DCs.

overall_design: Two populations of murine DCs derived from ex vivo culture were compared.

first: Yan

last: Gao


title: An Investigation of Global Gene Expression Patterns in Glaucoma and Ocular Hypertension Derived Optic Nerve Heads

status: Public on Sep 27 2013

city: Iowa City

first: Dina

last: Ahram

state: Iowa

address: 375 Newton road

department: Genetics/Opthalmology

institute: UIOWA

summary:
Purpose: The optic nerve head (ONH) is the likely site of initial damage in the glaucomatous eye. Despite the recognition of elevated intraocular pressure (IOP) as a leading risk factor for the development of glaucoma, ocular hypertension (OHT) eyes displaying consistently elevated IOP do not experience ONH damage. This study aims to identify global gene expression variations in glaucomatous ONHs and their relationship to those identified in OHT derived ONHs in order to improve our understanding of IOP-induced ONH damage.

Methods: (N=6) ONHs were collected from clinically confirmed glaucoma, OHT and age-matched control donor eyes. Total RNA extracted from ONHs was reverse transcribed and assayed using the Affymetrix Human Exon 1.0 ST array. Differentially expressed genes in glaucoma versus control and OHT derived ONHs were identified using an ANOVA analysis with a 1.25 fold change limit and P-value < 0.05. Quantitative RT-PCR was performed to validate selected differentially expressed genes.

Results: Microarray analysis revealed 149 under under-expressed genes in POAG versus control ONHs, many of which are involved in ion transport, axonogenesis and macromolecule catabolic processes. 297 genes were over expressed in OHT versus glaucoma derived ONHs. Mediators of oxidation-reduction and chemical homeostasis were among the most prominent gene groups identified. The over expression of prostaglandin-endoperoxide synthase 2, integrin, beta-like 1 and fibulin 5 in glaucomatous ONHs was confirmed by qRT-PCR.

Conclusions: Our data demonstrates marked alteration in global gene expression patterns in the glaucomatous ONH, likely due to extensive tissue injury. The observed overlapping of several differentially expressed genes in glaucoma and OHT derived ONHs suggests the induction of common mechanisms in response to elevated IOP. Preferential over-expression of certain gene groups in OHT but not glaucoma derived ONHs may confer possible protection against IOP-induced ONH damage, which remains to be investigated in future studies.

overall_design: (N=6) Glaucoma, ocular hypertension and age-matched control ONHs were assayed to investigate and compare global gene expression patterns in each sample group.

first: Amy

middle: C

last: Cook

first: Kwon

middle: H

last: Young

first: Markus

last: Kuehn


title: Gene expression profiling of primary mouse embryonic palatal mesenchymal cells in Tgfbr2 mutant mouse models

status: Public on Oct 01 2013

city: Oklahoma City

first: Richard

last: Pelikan

state: Oklahoma

address: 825 NE 13th St

department: Genes & Human Disease Research Program

institute: Oklahoma Medical Research Foundation

summary: The overall goal of this project is to investigate the role of TGF-beta signaling in regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of primary mouse embryonic palatal mesenchymal (MEPM) cells from wild type mice as well as those with a neural crest specific conditional inactivation of the Tgfbr2 gene. The latter mice provide a model of cleft palate, which is among the most common congenital birth defects and observed in many syndromic conditions.

overall_design: To investigate the adverse effects of dysfunctional TGF-Beta signaling  on the cellular metabolism of palatal mesenchyme during palatogenesis, we analyzed mice with a neural crest cell-specific conditional inactivation of Tgfbr2 (Tgfbr2fl/fl;Wnt1-Cre). We performed microarray analyses of primary mouse embryonic palatal mesenchymal cells of Tgfbr2fl/fl;Wnt1-Cre mutant mice and Tgfbr2fl/fl control mice, collected at embryonic day 13.5 (n=4 per genotype) and cultured with standard media (DMEM with supplements). Cells were collected after 2 passages.

first: Jun-ichi

last: Iwata

first: Akiko

last: Suzuki

first: Yang

last: Chai


title: Expression data from adult Shh-responding astroglia cells in mice

status: Public on Sep 18 2013

city: Bethesda

first: Yanqin

state: Maryland

address: 10 Center Dr.

institute: NIH

summary:
Sonic hedgehog (Shh) signals via Gli transcription factors to promote maintenance and proliferation of neural stem cells in the adult mouse forebrain.  We have analyzed the gene expression pattern in neurogenic Shh-responding astroglia (= neural stem cells ) in the subventicular zone of the lateral ventricle and dentate gyrus of the hippocampus in comparison to the non-neurogenic Shh-responding glia (=Bergman glia) in the cerebellum to identify the genes specifically involved in neurogenic function downstream of Shh signaling.
In this dataset, we include the expression data obtained from FACS-sorted Gli1+ GFAP+ cells from microdissected SVZ, hippocampus and cerebellum. GFAP expression is based on hGFAP-GFP reporter line and Gli1 expression is lineage marked using Gli1-CreER;ROSA26-tdTomato mice.

overall_design: 15 Total samples were analyzed. We compared expression levels of SVZ vs. Cerebellum, Hippocampus vs. Cerebelllum to identify genes which had more than 4 fold change in expression levels with p < 0.01. From this  narrowed list, we compared between SVZ and Hippocampus to identify the common genes up and down regulated.  In addition, we also identified commonly expressed genes in hippocampus and SVZ at high level.

first: Cheol

last: Lee

first: Sherry

last: Ralls

first: Sohyun

last: Ahn


title: Expression data from CD-1 mouse liver samples obtained from in-vivo treatment with genotoxic carcinogens, non-genotoxic carcinogens or non-hepatocarcinogens.

status: Public on Sep 11 2013

city: Basel

first: Jonathan

last: Moggs

address: Fabrikstrasse 2

country: Switzerland

institute: Novartis

summary:
Assessing the carcinogenic potential of drug candidates is a costly procedure which requires the life-long treatment of rodents at different dose levels. A promising approach, which may to a certain degree reduce the need for animal studies in the future is toxicogenomics. The idea is to employ microarray platforms for the genome-wide expression profiling of compounds, which may facilitate the discovery of biomarker genes and provide insights in molecular mechanisms.
We profiled global mRNA expression in the liver of male and female CD-1 mice treated with genotoxic, nongenotoxic, and non-hepatocarcinogenic compounds up to two weeks.

overall_design: Diverse compounds were administrated to male and female mice CD-1 mice by oral gavage up to 14 days. In order to chose appropriate dose levels for the carcinogenic substances, the dose reported to be carcinogenic in the 2-year mouse bioassay as stated in the CPDB database (http://potency.berkeley.edu/) was used.  To ensure clearly visible changes in gene expression in response to treatment with non-hepatocarcinogens, a high dose was used for these compounds. After 3 and 14 days of treatment, respectively, the animals were anesthetized using isoflurane, exsanguinated from the heart and then subjected to necropsy. The median lobe and left lateral liver lobe were cut in cubes with 4-5 mm side length, placed in Wheaton Cryovials, snap frozen in liquid nitrogen and kept at -80°C until extraction.

first: Johannes

last: Eichner

first: Nadine

last: Kossler


title: Expression data from TNF-stimulated mouse glomeruli

city: Munich

first: Volker

last: Vielhauer

address: Ziemssenstr. 1

department: Medizinische Klinik IV, Nephrologisches Zentrum

institute: Klinikum der Universität München, Ludwig-Maximilans-University Munich

summary:
The specific contribution of the two TNF-receptors Tnfr1 and Tnfr2 to TNF-induced inflammation in the glomerulus is unknown. In mice, TNF exposure induces glomerular expression of inflammatory mediators like adhesion molecules and chemokines in vivo, and glomerular accumulation of leukocytes.
To examine Tnfr-specific inflammatory responses in intrinsic glomerular cells but not infiltrating leukocytes we performed microarray gene expression profiling on intact glomeruli isolated from wild-type and Tnfr-deficient mice following TNF exposure in vitro.

overall_design: Glomeruli were isolated from male C57BL/6J wild-type and Tnfr-deficient mice applying a magnetic bead-based isolation technique. Isolated intact glomeruli were stimulated with TNF for 12 hours in vitro for subsequent RNA extraction and hybridization on Affymetrix microarrays.

first: Anela

last: Taubitz


title: The polycomb protein Ezh2 regulates differentiation and plasticity of CD4 T helper type-1 and type-2 cells.

city: Chiba

first: Atsushi

last: Onodera

address: Chuo-ku Inohana 1-8-1

department: Immunology

country: Japan

institute: Chiba University

summary: Following antigen encounter by CD4 T cells, polarizing cytokines induce the expression of master regulators that control differentiation.  Inactivation of the histone methyltransferase Ezh2 was found to specifically enhance T-helper (Th)1 and Th2 cell differentiation and plasticity. Ezh2 directly bound and facilitated correct expression of Tbx21 and Gata3 in differentiating Th1 and Th2 cells, accompanied by substantial tri-methylation at lysine 27 of histone 3 (H3K27-Me3). In addition, Ezh2 deficiency resulted in spontaneous generation of discrete IFN-γ and Th2 cytokine-producing populations in non-polarizing cultures, and under these conditions IFN-γ  expression was largely dependent on enhanced expression of the transcription factor Eomesodermin. In vivo, Loss of Ezh2 caused increased pathology in a model of allergic asthma and resulted in progressive accumulation of memory phenotype Th2 cells.  This study establishes a functional link between Ezh2 and transcriptional regulation of lineage-specifying genes in terminally differentiated CD4 T cells.

overall_design: Wild type and Ezh2 knock out unpolarized Th cells, Th1 cells and Th2 cells are profiled for mRNA expression

first: Damon

last: Tumes

first: Akane

first: Kenta

last: Shinoda

first: Yusuke

last: Endo

first: Chiaki

last: Iwamura

first: Hiroyuki

last: Hosokawa

first: Koji

last: Tokoyoda

first: Yutaka

first: Shinichiro

last: Motohashi

first: Toshinori

last: Nakayama


title: Transcriptome-guided functional analyses reveal novel biological properties and regulatory heirarchy of human embryonic stem cell derived ventricular cardiomyocytes.

status: Public on Sep 10 2013

first: Ronald

last: Li

address: 1 Gustave Levy Pl

institute: Mount Sinai School of Medicine

summary: Profiling global gene expression of undifferentiated human embryonic stem cells, artificially derived cardiomyocytes, fetal ventricular cardiomyocytes, and adult ventricular cardiomyocytes to determine transcriptomic variation between these cell types.

overall_design: Total RNA extracted from 10 human samples representing four stages of cardiac development from undifferentiated stem cells to mature adult cardiac tissue.

first: Stephanie

middle: N

last: Rushing


title: Potentiation of regulatory T cell stability and function via a neuropilin-1:semaphorin-4a axis

status: Public on Sep 06 2013

city: Memphis

first: David

last: Finkelstein

state: TN

address: 332 N. Lauderdale St.

department: Computational Biology

institute: St Jude Children's Research Hospital

summary: Regulatory T cells (Treg) represent a critical immunoregulatory component of the immune system. The signals that maintain Treg stability and potentiate their function remain obscure. Here we show that the immune cell surface ligand semaphorin-4a (Sema4a)

overall_design: Sema treated and NRP1 knock outs were compared to untreated wild type T cell controls

first: Greg

middle: M

last: Delgoffe

first: Seng-Ryong

last: Woo

first: Meghean

middle: E

last: Tunis

last: Gravano

first: Cliff

last: Guy

first: Matthew

last: Bettini

first: Peter

last: Vogel

first: Jody

last: Bonnevier

first: Creg

last: Workman

first: Dario

last: Vignali


title: Effect of L-Proline on mouse embryonic stem cells (ESCs)

status: Public on Sep 05 2013

city: Naples

first: Gabriella

last: Minchiotti

address: Via Pietro Castellino, 111

country: Italy

institute: Institute of Genetics and Biophysics "A. Buzzati-Traverso", CNR

summary:
We found that the non-essential amino acid L-Proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells (ESCs) into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent stem cells. This embryonic stem cell-to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling of the transcriptome
We used microarrays to elucidate whether a diverse transcriptional program is the basis of the morphological and motility differences between ESCs and L- Proline treated ESCs (PiCs)

overall_design: Total RNA was extracted from Control (ESCs) and L-Proline treated mouse embryonic stem cells (PiCs) and hybridized on Affimetrix microarrays.

first: Maria

middle: R

last: Matarazzo


title: Analysis of gene expression in wildtype and Notch1 mutant retinal cells by single cell profiling

first: Karolina

last: Mizeracka

address: 77 Avenue Louis Pasteur

institute: Harvard Medical School

summary:
Loss of Notch1 in retinal progenitor cells (RPCs) during postnatal retinal development results in the overproduction of rod photoreceptors at the expense of interneurons and glia. To examine the molecular underpinnings of this observation, microarray analysis of singla retinal cells from wildtype (WT) or Notch1 conditional knockout (N1-CKO) retinas was performed. The majority of N1-CKO cells lost expression of known Notch target genes. These cells also had low levels of RPC and cell cycle genes, and robustly upregulated rod precursor genes. In addition, single WT cells, in which cell cycle marker genes were downregulated, expressed markers of both rod photoreceptors and interneurons. These results demonstrate that individual, newly postmitotic retinal cells can begin to differentiate into more than one cell type, and that this transitional state may be dependent on Notch1 signaling.
We used microarrays to examine gene expression changes that occur in single cells after the removal of Notch1 during retinal development.

overall_design: Retinas of Notch1fl/fl P0 pups were electroporated in vivo with plamids encoding Cre driven by a broadly active promoter, CAG, along with a Cre-responsive GFP reporter, also driven by CAG promoter (CALNL-GFP). For controls, the retinas of sibling Notch1fl/fl pups were electroporated with CAG:GFP. The animals were sacrificed at P3 to allow time for Notch1 to be genetically removed and downstream gene expression changes to occur. Retinas electroporated with either CAG;Cre and CALNL-GFP or CAG:GFP alone were dissected and dissociated to individual cells, which were harvested under a dissecting microscope on the basis of their GFP signal.


title: Differential Gene Expression in HIV-Infected Individuals Following ART.

city: London

first: Akul

last: Singhania

address: 1 Midland Road

institute: The Francis Crick Institute

summary:
A paired analysis of peripheral blood mononuclear cells (PBMCs) isolated before and after antiretroviral therapy (ART) from a robust number of HIV-infected patients (N=36).
Results identify a total of 4,157 DEGs following ART in HIV-infected participants and the transition from a period of active virus replication before ART to one of viral suppression

overall_design: This study evaluated PBMC gene expression in cells from 36 (4 dropped from analysis) recently HIV-infected individuals to identify differentially expressed genes following 48 weeks of ART

first: Marta

last: Massanella

first: Christopher

last: Woelk


title: PBMCs from patients with Sjögren's syndrome and healthy controls

city: Stockholm

first: Alexander

last: Espinosa

address: Visionsgatan 18

department: Dept of Medicine

country: Sweden

institute: Karolinska Institutet

summary: Sjögren's syndrome is an autoimmune disease manifesting primarily as dryness of eyes and mouth. In this study, we compared gene expression in PBMCs between age- and gender-matched patients with Sjögren's syndrome (diagnosed by ACR criteria) and healthy controls. Cells were collected in heparinized tubes and PBMCs were prepared using Ficoll.

overall_design: Eleven patients with Sjögren's syndrome and 16 healthy controls were analyzed for expression of TRIM21, IRF1, IRF2, IRF4 and IRF8.


title: Expression data for mouse embryogenesis from oocyte to newborn

city: Wuhan

first: Wenxin

last: Li

email: liwxlab@whu.edu.cn, guomx@whu.edu.cn, jinyangc13@126.com, sparkler830305@hotmail.com

state: Hubei

address: Wuhan University, Luojia Hill,Wuhan 430072,China

department: College of Life Science

country: China

institute: Wuhan Univeristy

summary:
Studies in mouse have led to enormous progress in our understanding of early human development. The identification of genes and the signaling pathways involved in mouse embryogenesis have helped us to better understand fertilization, morulation, gastrulation, organogenesis and embryonic development in mammals.
We report a detailed analysis of the global gene expression profiles from oocyte to the end of organogenesis in mouse. Our studies revealed distinct temporal regulation patterns for genes belonging to different functional categories, supporting their roles during organogenesis.

overall_design: Mouse embryos were selected at successive stage for for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogeneous populations of embryos at each developmental stage in order to increase the temporal resolution of expression profiles. To that end, we hand-selected embryos according to morphological criteria at 12 time-points from embryos to newborn

first: Xue

last: Lu

first: Cai

last: Jinyang

first: Ma

last: Jian

first: Huang

last: Zan

first: Guo

last: Mingxiong

first: Fu

last: Liezhen

first: Shi

last: Yun-Bo

first: Li

last: Wenxin


title: Microarray to find CHOP dependent genes in response to proteasome inhibition

city: Indianapolis

first: Ron

last: Wek

state: IN

address: 635 Barnhill Dr. MS4065

department: Biochemistry & Molecular Biology

institute: Indiana University School of Medicine

summary: Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switch to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study was to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate.  We find that in response to proteasome inhibition, CHOP induces the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation.  Transcriptional expression of ATF5 is directly activated by both CHOP and ATF4.   Knock-down of ATF5 increased cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have pro-apoptotic functions.  Transcriptome analyses of ATF5-dependent genes revealed targets involved in apoptosis, including, NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feed-forward loop of stress induced transcriptional regulators, each subject to transcriptional and translational control that can switch cell fate towards apoptosis.

overall_design: 8 plates (10cm)  of WT and and 8 plates (10cm) of CHOP-/- MEF cells were subject to no stress (4 each for a total of 8) or treated for 8 hours with 1uM MG132 (4 each for a total of 8).  Unstressed cells were harvested at the same time as the stressed cells

first: Brian

last: Teske

first: Michael

last: Fusakio

first: Donghui

last: Zhou

first: Jixiu

last: Shan

first: Jeanette

last: McClintick

middle: S

last: Kilberg

first: Ronald


title: Analysis of gene expression changes induced in wild-type or Atf6a-/- mice by treatment with tunicamycin for 34h

status: Public on Sep 04 2013

first: David

middle: Thomas

last: Rutkowski

state: IA

address: 51 Newton Rd.

department: Anatomy and Cell Biology

institute: University of Iowa Carver College of Medicine

summary:
Protein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a “bottom-up” approach to infer pathways in the genetic regulation of lipid metabolism by the UPR.
We used a functional genomics to link gene expression patterns taken from microarray data to the severity and persistence of ER stress, using mice lacking the UPR signaling molecule ATF6α. This approach revealed that functionally related genes clustered into a small number of distinct expression profiles, and that lipid oxidation and efflux were targets for coordinated transcriptional suppression during ER stress.Our results establish a framework for hepatic gene regulation during ER stress.

overall_design: Atf6a-/- or +/+ mice of variable age and gender were injected intraperitoneally with 1 mg/kg tunicamycin or vehicle. 3 separate mice were used in each group. 34h after injection, mice were sacrificed and total RNA was prepared from resected livers.

first: D

middle: T

first: Randal

last: Kaufman


title: Analysis of gene expression changes induced in wild-type or Atf6a-/- mice by treatment with tunicamycin for 8h

overall_design: Atf6a-/- or +/+ mice of variable age and gender were injected intraperitoneally with 2 mg/kg tunicamycin or vehicle. 3 separate mice were used in each group. 8h after injection, mice were sacrificed and total RNA was prepared from resected livers.


title: Expression data from INTS8 human mutants and controls

status: Public on Sep 01 2013

city: Rotterdam

first: Renske

last: Oegema

address: Postbus 2040

department: Clinical Genetics

country: Netherlands

institute: Erasmus MC

summary:
The Integrator Complex (IC) is responsible for the 3'-end processing of the U1/U2 major spliceosome snRNAs. Maturation of these snRNAs is essential for the proper function of the major spliceosome. Also, there is accumulating evidence that the IC is necessary for normal vertebrate development, however no association with human disease has been reported yet.
Three siblings presented with severe intellectual disability, cerebellar hypoplasia and periventricular nodular heterotopia (PNH) of unknown cause. Using whole genome sequencing (Complete Genomics), and filtering for recessive inheritance, we discovered co-segregating compound heterozygous mutations in Integrator Complex Subunit 8 (INTS8) in the three sibs. QRT-PCR showed 2-fold decreased INTS8 RNA levels and in patients’ fibroblasts lower levels of the catalytic subunits INTS4, INTS9 and INTS11 were observed on western blots, indicating that the integrity of the complex is disrupted. Northern blots showed significantly misprocessed levels of U1, U2 and U4. Pathway analysis (DAVID) of expression data (Affymetrix Gene Chip 1.0 ST exon arrays) of RNA extracted from patient fibroblasts showed enrichment of deregulated genes involved in mRNA splicing and posttranscriptional modification. Expression data of (developing) human brain structures (Allen Brain Atlas) show that expression of INTS8 peaks prenatally, especially in the ganglionic eminences, (sub)ventricular zone and hindbrain, similar to the developmental expression in mouse embryo (Emage databse). Interestingly,  neuronal precursors from these areas migrate to the cortex and are compatible to affected regions in PNH and cerebellar hypoplasia in the patients. We propose that dysfunction of the Integrator Complex, through snRNA misprocessing and spliceosomal defects, leads to severely disrupted brain development in humans.
We used RNA isolated from human cultured fibroblasts, cell-lines were obtained from 3 individuals with INTS8 mutations and from 3 unaffected individuals.
R,Oegema

overall_design: Six Affymetrix Gene Chip 1.0 ST exon arrays (patients: III.2, III.3, III.4; controls: C1, C2, C3) were rma normalized on transcript level using the R package oligo (http://www.r-project.org). Top down regulated (n=402) or up regulated (n=281) genes with p values <0.02 were analyzed for enriched gene ontology terms (goterms_BP_all) using DAVID (medium stringency)(down: 329 DAVID IDs, up: 225 DAVID IDs).

first: M

last: Fornerod

first: R

last: Schot

first: G

last: Mancini


title: Gene expression data from lymphoblastoid cell lines from participants in the Genetics of Microangiopathic Brain Injury study

status: Public on Sep 15 2013

city: Rochester

first: Stephen

last: Turner

address: 200 1st St SW

department: Internal Medicine, Nephrology, Hypertension

institute: Mayo Clinic

summary:
European-American individuals of the GENOA cohort participating in the “Genetics of Microangiopathic Brain Injury” substudy, which investigates the genetic basis of alteration in brain structure detectable by magnetic resonance imaging.
This analysis investigated the association of gene expression with age (at the time of cell transformation).

overall_design: Participants in this study are drawn from the GENOA study, a population-based study from Rochester, MN

first: Myriam

last: Fornage

first: Sharon

last: Kardia


title: MicroRNA expression in prostate cancer cells stimulated with cancer associated fibroblasts

city: Milan

first: Paolo

last: Gandellini

address: Via Amadeo 42

department: Department of Applied Research and Technological Development

institute: Fondazione IRCCS Istituto Nazionale Tumori

summary: Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. It has been demonstrated (Giannoni E et al., Cancer Res 2010) that cancer associated fibroblasts (CAF) elicit an epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, leading to enhanced tumor cell aggressiveness. Here, we investigated the involvement of microRNAs (miRNA) in such malignant tumor-stroma interplay, to identify possible tools to counteract metastasis dissemination.

overall_design: To verify whether specific miRNAs are involved in CAF-induced EMT in PCa cells, PC-3 cells were subjected to a variety of stimuli, known to induce or not the acquisition of a mesenchymal phenotype (Giannoni E et al., Cancer Res 2010; Giannoni E et al., Antioxid Redox Signal 2011) , and profiled for miRNA expression on a microarray platform. miRNA expression profiles successfully distinguished cells that underwent EMT following the stimulation with activated fibroblasts (here referred to as “mesenchymal”) from cells that did not (“epithelial”).


title: Analysis of gene expression changes induced in wild-type or Atf6a-/- mice by treatment with tunicamycin

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

overall_design: Refer to individual Series


title: IL-21 regulates miRNA expression in B-chronic lymphocytic leukemia

first: Loris

last: De Cecco

address: via Venezian 1

institute: IRCSS Istituto Nazionale Tumori

summary: B-cell chronic lymphocytic leukemia (CLL) is a common type of leukemia, characterized by the progressive accumulation of CD5+ “mature” monoclonal B lymphocytes in peripheral blood, bone marrow and lymphoid tissues. Although circulating CLL cells are non-dividing cells, prone to spontaneous apoptosis, their progressive accumulation is the result of a dynamic balance between cell death and proliferation and a high turn-over rate has been related to a poor prognosis. Indeed, CLL cells are protected from apoptosis and proliferate in specific niches within the lymphoid tissues and the bone marrow.  By gene-expression profiling we found out that IL-21 modulates the expression of several genes including cytokine and chemokine genes and genes involved in cell survival and apoptosis in CD40-activated CLL cells. To gain information of the possible mechanisms involved in the regulation of these genes we tested the possibility that IL-21 may act through specific miRNA regulation.

overall_design:
PBMCs were isolated from heparinized blood obtained from 13 untreated patients diagnosed with CLL on the basis of clinical and immunophenotypic criteria. PBMCs were isolated by Ficoll density gradient centrifugation and characterized by immunofluorescence and FACS analysis. When residual non B-cells exceeded 10%, B cells were enriched by negative selection with antibody-coated magnetic beads (CD2-beads, Dynal, Oslo, Norway) to obtain a >95% pure CD19+/CD5+ B cell population. B-CLL cells were pre-activated on adherent CD40L-transduced L cells for 48-36h and then stimulated with IL-21 or medium only for additional 18h. Total RNA was isolated from  samples using TriZol (Invitrogen) reagent.
This Series represents 9 of the 13 cases.

first: L


title: P38 signaling underlies a cell-autonomous loss of stem cell self-renewal in aged muscle

city: Boulder

first: Bradley

middle: B

last: Olwin

state: CO

address: 347 UCB

department: MCD-Biology

institute: University of Colorado

summary: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and decreased regenerative capacity, which can lead to sarcopenia and increased mortality. While the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Therefore, identification of signaling pathways affecting satellite cell function during aging may provide insights into therapeutic targets for combating sarcopenia. Here, we show that a cell-autonomous loss in self-renewal occurs via novel alterations in FGF and p38αβ MAPK signaling in old satellite cells. We further demonstrate that pharmacological manipulation of these pathways can ameliorate age-associated self-renewal defects. Thus, our data highlight an age-associated deregulation of a satellite cell homeostatic network and reveals potential therapeutic opportunities for the treatment of progressive muscle wasting.

overall_design: Satellite cells were isolated from young (3-6mo) and aged (20-25mo) adult mice; individual date files represent 2 independent pools of RNA from 4-8 mice at each timepoint.

first: Jennifer

last: Bernet


title: IL-21 controls gene expression in B-chronic lymphocytic leukemia (CLL) cells through micro-RNA regulation

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


title: Hippocampal Gene Expression in Young and Adult Mice with Memory Deficits

status: Public on Aug 30 2013

city: St. Louis

first: Harvey

last: Armbrecht

state: MO

address: #1 Jefferson Barracks Drive

department: Division of Geriatric Medicine & Department of Molecular Microbiology & Immunology

institute: St. Louis Veterans Affairs Medical Center , & Saint Louis University School of Medicine

summary:
The purpose of this study was to determine whether there were differences in gene expression in the hippocampus, a part of the brain involved in memory consolidation, between male mice with age-related memory deficits (SAMP8 mice) and control mice with no age-related memory deficits.  The senescence-accelerated mouse (SAMP8) strain exhibits decreased learning and memory and increased amyloid beta peptide (Aβ) accumulation at 12 months compared to 4 months.  To detect differences in gene expression in SAMP8 mice, we used a Control mouse that was a 50% cross between SAMP8 and CD-1 mice and which showed no memory deficits  (50% SAMP8 mouse).  We then compared gene expression in the hippocampus of 4 month and 12 month old SAMP8 and Control mice using Affymetrix gene arrays.  At 12 months, but not at 4 months, pathway analysis revealed significant differences in the Long Term Potentiation (LTP) (6 genes), Phosphatidylinositol Signaling (6 genes), and Endocytosis (10 genes) pathways.  The changes in LTP included MAPK signaling (N-ras, CREB binding protein, protein phosphatase inhibitor 1) and Ca-dependent signaling (PI receptors 1 and 2 and phospholipase C).  Changes in phosphatidylinositol signaling genes suggested altered signaling through PI3-kinase, and Western blotting revealed phosphorylation changes in AKT and 70S6K.  Changes in the Endocytosis pathway involved genes related to clathrin-mediated endocytosis (dynamin and clathrin).  Endocytosis is required for receptor recycling, is involved in Aβ metabolism, and is regulated by phosphatidylinositol signaling.  In summary, these studies demonstrate altered genes expression in three SAMP8 hippocampal pathways associated with memory formation and consolidation.  These pathways may provide new therapeutic targets in addition to targeting Aβ metabolism itself.
Global differential profiling of hippocampal gene expression (4 month and 12 month old SAMP8 and Control mice) was performed using Affymetrix GeneChip® Mouse Genome 430 2.0 Arrays.  At 12 months, but not at 4 months, pathway analysis revealed significant differences in the Long Term Potentiation (LTP) (6 genes), Phosphatidylinositol Signaling (6 genes), and Endocytosis (10 genes) pathways.  The changes in LTP included MAPK signaling (N-ras, CREB binding protein, protein phosphatase inhibitor 1) and Ca-dependent signaling (PI receptors 1 and 2 and phospholipase C).  Changes in phosphatidylinositol signaling genes suggested altered signaling through PI3-kinase, and Western blotting revealed phosphorylation changes in AKT and 70S6K.  Changes in the Endocytosis pathway involved genes related to clathrin-mediated endocytosis (dynamin and clathrin).  Endocytosis is required for receptor recycling, is involved in Aβ metabolism, and is regulated by phosphatidylinositol signaling.  In summary, these studies demonstrate altered genes expression in three SAMP8 hippocampal pathways associated with memory formation and consolidation.  These pathways may provide new therapeutic targets in addition to targeting Aβ metabolism itself.

overall_design: 2-way ANOVA (2 x 2 conditions, n=4).  First variable was age (4 and 12 months) and second variable was mouse strain (Control and SAMP8).  This results in 4 groups: Control-4 month, Control-12 month, SAMP8-4 month, and SAMP8-12 month.   Each group had 4 biological replicates (4 mice).  The ”Control” mice were a 50% backcross of the SAMP8 mice with CD-1 mice (50% SAMP8 mice).  These mice were closely related to SAMP8 mice but exhibited no memory deficits at 4 or 12 months.  The SAMP8 mice had memory deficits at 12 months but not at 4 months.

first: Akbar

last: Siddiqui


title: Co-ordinate inhibiton of autism candidate genes by topoisomerase inhibitors [array]

city: Carrboro

first: Chandri

last: Yandava

state: NC

address: 101 Renee Lynne Court

department: Carolina Institute for Developmental Disabilities

institute: University of North Carolina at Chapel Hill

summary: Topoisomerases are necessary for the expression of neurodevelopmental genes, and are mutated in some patients with autism spectrum disorder (ASD). We have studied the effects of inhibitors of Topoisomerase 1 (Top1) and Topoisomerase 2 (Top2) enzymes on mouse cortical neurons. We find that topoisomerases selectively inhibit long genes (>100kb), with little effect on all other gene expression. Using ChIPseq against RNA Polymerase II (Pol2) we show that the Top1 inhibitor topotecan blocks transcriptional elongation of long genes specifically. Many of the genes inhibited by topotecan are candidate ASD genes, leading us to propose that topoisomerase inhibition might contribute to ASD pathology.

overall_design:
9 experiments, gene expression measured by Affymetrix microarray.
1) cultured mouse cortical neurons treated with 300nM topotecan vs vehicle-treated controls
2) cultured mouse neurons treated with 1uM topotecan vs vehicle-treated controls
3) cultured mouse cortical neurons treated with 3uM ICRF-193 vs vehicle-treated controls.
4) cultured mouse cortical neurons treated with 10 uM irinotecan vs vehicle-treated controls.
5) cultured mouse cortical neurons treated with 3-1000 nM topotecan vs vehicle treated controls
6) cultured mouse cortical neurons treated with lentivirus expressing shRNA against Top1 and Top2b vs scrambled shRNA controls
7) cultured mouse cortical neurons treated with DRB vs vehicle-treated controls
8) cultured mouse cortical neurons treated with hydrogen peroxide or paraquat vs vehicle-treated controls
9) cultured mouse cortical neurons treated with topotecan with or without subsequent drug washout, vs vehicle-treated controls.

first: Ian

last: King


title: Promiscuous gene expression in human medullary thymic epithelial cell subsets

status: Public on Aug 31 2013

city: Heidelberg

first: Benedikt

last: Brors

address: Im Neuenheimer Feld 280

institute: DKFZ

summary: Different human mTEC subsets (MUC1, CEACAM5 and SGLT1) were purified by sequential enzymatic digestion (collagenase/dispase, trypsin) followed by enrichment using magnetic beads (CD45 beads, Miltenyi Biotech) and FACS sorting.   Cells of the surface phenotype CD45-, CDR2-, EpCAM+ were further subdivided into MUC1+/MUC1-, CEACAM5+/CEACAM5- and SGLT1+/SGLT1- fractions. RNA was isolated using μMACS™ SuperAmp™ protocol (Miltenyi Biotec) and hybridized to Illumina Whole-Genome Expression Beadchips. Gene expression of Antigen-positive and Antigen-negative mTEC subsets was compared.

overall_design: Total RNA was isolated from ex-vivo isolated human mTEC subsets using μMACS™ SuperAmp™ protocol (Miltenyi Biotec)

first: S

last: Pinto

first: C

last: Michel

first: H

last: Schmidt-Glenewinkel

last: Wild

first: B

last: Kyewski


title: Effect of chronic glucocorticoid (GC) treatment on neonatal mouse whole cerebellum and whole lung

city: Boston

first: Alvin

middle: T.

last: Kho

address: 320 Longwood Avenue

department: Informatics Program

institute: Boston Children's Hospital

summary: Dexamethasone (1ug/g, Dex) or vehicle (saline) injected into postnatal days 0-7 (P0 to P7) of C57BL6J mouse pups every day. Whole organ were harvested at P7.

overall_design:
Biological replicates (n = 4) per condition: whole cerebellum or whole lung, treated with dexamethasone or vehicle.
This microarray experiment was performed concurrently with the study described in PMID:19164857.  The culture and experiment designs in PMID:19164857 are identical to those in this microarray experiment.
KEYWORDS: cell type comparison, treatment comparison.

first: Vivi

last: Heine

first: David

last: Rowitch


title: Expression data from Influenza A infected mouse primary tracheal epithelial cell cultures (MTEC), from both wild-type and MAVS-/- mice

first: Stefania

last: Crotta

address: The Ridgeway

department: IR

institute: The Crick- Mill Hill Laboratories

summary: We used microarrays to detail the global programme of gene expression in response to Influenza A  (PR8) infection

overall_design: Fully differentiated MTEC cells were infected with PR8 (moi: 0.3) or mock infected and RNA was collected at 24 hours post infection

first: A

last: Wack


title: Expression data from Influenza A infected mouse primary tracheal epithelial cell cultures (MTEC), from wild-type, IFNAR1-/-, IL28Ra-/- and  IFNAR1-/- IL28Ra-/- double ko


title: Gene signature of adult mammary stem cells and mammary cancer stem cells (Affymetrix)

status: Public on Aug 29 2013

first: Claudia

last: Gaspar

address: Dr. Molenwaterplein 40, PO Box 2040

department: Experimental Pathology

institute: ErasmusMC

summary: The Wnt/beta-catenin signalling pathway plays a central role in mammary stem cell homeostasis and in breast cancer. We employed the CD29hiCD24+ cell surface antigens to identify a subpopulation of mammary CSCs from Apc1572T/+, a mouse model for metaplastic breast adenocarcinoma, a subtype of triple-negative breast cancer in man. The MaCSCs are capable of recapitulating tumorigenesis when transplanted at low multiplicities in vivo, and of forming self-renewing organoids in vitro. Expression profiling of the different subpopulations sorted from normal and neoplastic mammary tissues revealed that the normal stem cell compartment is more similar to tumor cells than to their own differentiated progenies. Accordingly, Wnt signaling was found to be activated in the subpopulation encompassing normal mammary stem cells, though to a lesser degree than in the tumor cells. By comparing normal with cancer mouse mammary compartments, we were able to derive a MaCSC-specific signature composed of human orthologous genes able to predict poor survival, relapse and distant metastasis in human breast cancer. Finally, upon intravenous injection, only MaCSCs among the different tumor cell subpopulations are able to form metastatic lesions in a broad spectrum of anatomical sites. Overall, our data indicate that constitutive Wnt signaling activation interferes with mammary stem cell homeostasis leading to metaplasia and basal-like adenocarcinomas.

overall_design: The objective was to compare the: i) expression profiles between normal adult  mammary stem cells and tumor cancer stem cells identified by Lin-CD29hiCD24+; ii) expression profile between adult stem cells and their differentiated counterparts both in normal and in tumor tissue to generate a cancer stem cell signature that can be used to compare with mammary human tumor expression data to predict survival and prognosis. To this aim five independent mammary adenocarcinomas from C57BL6/J Apc+/1572T mice and three independently isolated pools of mammary glands from C57BL6/J Apc+/+ mice were employed to sort 10,000 cells of each of the following populations: Lin-, Lin-CD29+CD24+ and Lin-CD29hiCD24+.

first: Joana

last: Monteiro

first: Wilfrid

last: Richer

first: Patrick

last: Franken

first: Andrea

last: Sacchetti

first: Rosalie

last: Joosten

first: Anouar

last: Idali

last: Brandao

first: Charles

last: Decraene

first: Riccardo

last: Fodde


title: Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia


title: Expression data from Influenza A infected mouse primary tracheal epithelial cell cultures (MTEC)

first: S


title: Gene signature of adult mammary stem cells and mammary cancer stem cells

type:
Expression profiling by RT-PCR
Expression profiling by array


title: Genome-wide analysis of differentially expressed genes and splicing isoforms in clear cell Renal Cell Carcinoma

city: Bari

first: Alessio

last: Valletti

address: Via Amendola 165/A

department: Institute of Biomembranes and Bioenergetics

institute: CNR

summary:
In this study we performed a genome wide analysis of the entire complement of mRNAs in clear cell renal cell carcinomas (ccRCC) by means of the Affymetrix Exon Array platform. The analyses were performed both at gene and exon level.
Under our parameters over 2,000 genes resulted differentially expressed, and about 250 genes resulted alternative spliced showing differential inclusion of specific cassette exons comparing tumor and non tumoral tissues.

overall_design: 20 total samples were used for exon array analysis: 10 ccRCC tumor sample (T) and their matched non-tumor (NT) kidney tissues samples. All exon array data were analyzed using Partek Genomic Suite 6.4 software (Partek). The robust multi-array average (RMA) algorithm was used for the gene- and exon-level intensity analyses. Data were ﬁltered to consider only those probe sets included in the “Core Meta-Probeset”. Lists of genes and exons with significant variation of the expression levels were generated by using a 0.01 FDR criterion as a significant cutoff. Partek list of significant exon-level probesets (FDR corrected p-value < 0.01) and exon level ANOVA test list were used to create - by an ad hoc Python script - a database of significant probesets from Exon Array experiments. To make more stringent the analysis criteria we excluded from the final exon lists all those cases in which Exon Array revealed a significant change at gene-level. This database we created has been used to explore simple exon skipping events using as reference ASPicDB single exon skipping splicing events after mapping Affymetrix probesets on ASPicDB .gtf files. A single exon from the Partek list was defined significantly skipped only if its adjacent exons were not, by using 0.01 and 0.05 p-value criterions as a significant cutoff for the “skipped” and adjacent exons, respectively.

first: Orazio

last: Palumbo

first: Massimo

last: Carella

first: Ernesto

last: Picardi

first: Margherita

last: Gigante

first: Apollonia

last: Tullo

first: Elisabetta

last: Sbisà

first: Anna

last: D'Erchia

first: Graziano

last: Pesole

first: Elena

last: Ranieri


title: MicroRNA expression of primary gastric adenocarcinoma compared to non-cancer gastric tissue

city: Seoul

first: Jae Yun

last: Lim

address: 211 Eonju-ro, Gangnam-gu

department: Medical Oncology

country: South Korea

institute: Gangnam Severance Hospital, Yonsei University

summary: Identification of the microRNA signature associated with human gastric adenocarcinoma.

overall_design: Total RNA obtained from 60 primary gastric cancer tissues and 8 surrounding non-cancer tissues was used for microarray analysis. For validation, real-time RT-PCR was performed.

first: J

last: Lee

last: Cho


title: Progesterone receptor-dependent gene signatures in the mouse mammary gland after acute progesterone treatment

status: Public on Aug 27 2013

city: Houston

first: Ashlee

middle: Renae

last: Lain

state: TX

address: One Baylor Plaza

department: Molecular and Cellular Biology

institute: Baylor College of Medicine

summary: Progesterone (P) acting through its cognate nuclear receptors (PRs) plays an essential role in driving pregnancy-associated branching morphogenesis of the mammary gland. However, the fundamental mechanisms, including global cistromic and acute genomic transcriptional responses that are required to elicit active branching morphogenesis in response to P, have not been elucidated. We used microarray analysis to identify global gene expression signatures that are acutely regulated by PRs in the mouse mammary gland after acute P treatment.

overall_design: Mammary gland gene expression data from 10-week-old ovariectomized wildtype and progesterone receptor null mice treated subcutaneously with 17β-Estradiol for 24 hours and then 17β-Estradiol plus Progesterone for 8 or 24 hours. Three replicate pools were tested with three mice per pool.

first: Chad

last: Creighton

first: Orla

last: Conneely


title: Gene expression of SKOV3 cells after no treatment or treatment with 50 microM peracetylated GlcNAc or peracetylated 4-deoxy-GlcNAc for three days

status: Public on Aug 23 2013

city: Nijmegen

first: Xander

last: van Wijk

address: Geert Grooteplein 26-28

department: Biochemistry

institute: Radboud University Nijmegen Medical Centre

summary: Heparan sulfate (HS), a long linear polysaccharide, is implicated in various steps of tumorigenesis, including angiogenesis. We successfully interfered with HS biosynthesis using a peracetylated 4-deoxy analog of the HS constituent GlcNAc and studied the compound’s metabolic fate and its effect on angiogenesis. The 4-deoxy analog was activated intracellularly into UDP-4-deoxy-GlcNAc and HS expression was inhibited up to ~96% (IC50 = 16 µM). HS chain size was reduced, without detectable incorporation of the 4-deoxy analog, likely due to reduced levels of UDP-GlcNAc and/or inhibition of glycosyltransferase activity. Comprehensive gene expression analysis revealed reduced expression of genes regulated by HS binding growth factors as FGF-2 and VEGF. Cellular binding and signaling of these angiogenic factors was inhibited. Micro-injection in zebrafish embryos strongly reduced HS biosynthesis, and angiogenesis was inhibited in both zebrafish and chicken model systems. All these data identify 4-deoxy-GlcNAc as a potent inhibitor of HS synthesis which hampers pro-angiogenic signaling and neo-vessel formation.

overall_design: 9 samples were analyzed: 3 biological replicates from untreated SKOV3 cells, 3 biological replicates from SKOV3 cells treated with peracetylated GlcNAc, 3 biological replicates from SKOV3 cells treated with peracetylated 4-deoxy-GlcNAc

first: Els

last: van de Westerlo

first: Eugene

last: Verwiel

first: Toin

last: van Kuppevelt


title: Expression data from wild-type and HMGN1 knockout mice injected with N-nitrosodiethylamine

status: Public on Aug 24 2013

city: Bethesda

first: Yuri

last: Postnikov

state: MD

address: 37 Convent Dr

institute: NIH

summary:
HMGN1 contributes to the shortened latency of liver tumorigenesis by changing a chromatin structure and expression of relevant genes
To assess the molecular mechanisms underlying accelerated tumor development in Hmgn1-/- mice, we performed the gene expression profiling of liver cells at early stages

overall_design: Expression profiles has been compared between Hmgn1+/+ and Hmgn1-/- mice livers at 4 weeks after birth and at 12 weeks after DEN or saline (control) injection at 4 weeks

middle: V

first: Nina

last: Bubunenko


title: Lung transcript expression profile after Gata5 gene deletion

status: Public on Aug 26 2013

city: Chicago

first: Bohao

last: Chen

state: IL

address: 5841 S. Maryland Ave

department: Medicine

institute: University of Chicago

summary:
Gata5 is a zinc finger transcription factor that is expressed in embryonic pulmonary mesenchyme and becomes upregulated in the lungs, gut, and bladder during postnatal development. We used microarray to comapre gene expression profiles of mouse lung between Gata5 knockout and wild type mice. We hope to identify the differentially expressed genes that affected by Gata5 gene deletion and their functional clusters or pathways.
The goal of this study is  to identify the differentially expressed genes that affected by Gata5 gene deletion and their functional clusters or pathways.

overall_design: Total RNA samples from three Gata5 KO and four wild type control mouse left lungs were extracted from the mouse lungs and profiled using Affymetrix GeneChip Mouse Genome 430 2.0 Array.

first: Julian

last: Solway

first: Chunling

last: Zhang


title: Genome-wide analysis of the miR profile in human head and neck paraganglioma vs. Jacobson's (tympanic) nerve and SH-SY5Y neuroblastoma cells

status: Public on Aug 21 2013

city: Chieti Scalo

first: Renato

last: Mariani-Costantini

state: CH

address: Via Colle dell'Ara

department: Ageing Research Center (CeSI)

institute: "G. d'Annunzio" University Foundation

summary: The aim of the study was to assess whether changes in the expression of miRs could be implicated in the modulation of the NOTCH pathway in head and neck paragangliomas. Several miRs, notably including families (miR-34s, miR-200s) that target the NOTCH signaling pathway, resulted differentially expressed in paragangliomas compared to the reference normal  tissue, i.e., Jacobson's nerve.

overall_design: Total RNA from paraganglioma samples compared to total RNA from Jacobson's nerves (normal controls, chosen because Jacobson's nerve is a frequent site of origin of tympanic paraganglioma) and from SH-SY5Y cells (chosen based on their sympathoadrenal origin).

first: Annalisa

last: Morgano

first: Andria

last: D'Orazio


title: Targeted disruption of Hotair leads to homeotic transformation and de-repression of imprinted genes [Microarray Analysis]

city: Stanford

first: Kun

last: Qu

state: CA

address: 269 Campus Dr. CCSR 2150

department: Dermatology

institute: Stanford University

summary: Long noncoding RNAs (lncRNAs) are thought to be prevalent regulators of gene expression, but the consequences of lncRNA inactivation in vivo are mostly unknown. Here we show that targeted deletion of mouse Hotair lncRNA leads to de-repression of hundreds of genes, resulting in homeotic transformation of the spine and malformation of metacarpal-carpal bones. RNA-seq and conditional inactivation reveal an ongoing requirement of Hotair to repress HoxD genes and multiple imprinted loci such as Dlk1-Meg3 and Igf2-H19. Hotair binds to both Polycomb repressive complex 2 that methylates histone H3 at lysine 27 (H3K27) and Lsd1 complex that demethylates histone H3 at lysine 4 (H3K4) in vivo. Hotair inactivation causes coordinate H3K27me3 loss and H3K4me3 gain at select target genes throughout the genome. These results reveal a shared regulatory mechanism to enforce silent chromatin state at Hox and imprinted genes via Hotair lncRNA.

overall_design: Microarray analysis was performed on triplicate samples with Affymetrix GeneChip Mouse Genome 430 2.0 Array for both wildtype and Hotair Knockout.

first: Lingjie

last: Li

first: Bo

last: Liu

first: Orly

last: Wapinski

first: Miao-Chih

last: Tsai

first: Jiajing

first: Howard

middle: Y

last: Chang


title: Expression data from open bariatric surgery patients - various adipose samples

status: Public on Aug 22 2013

city: Danville

first: George

last: Argyropoulos

state: Pa

address: 100 North Academy Ave

department: Weis Center for Research

institute: Geisinger Medical Center

summary:
Diabetes and obesity are widespread diseases with signifciant socioeconomic implications.  We used three different types of human adipose tissue (epigastric, visceral, and subcutaneous) in order to determine differences in global gene expression between these adipose depots in severely obese patients.
In this dataset, we include the expression data obtained from three types of adipose tissue; epigastric, subcutaneous, and visceral all obtained through open gastric bypass surgery.

overall_design: 18 total samples were analyzed.  Tissues were paired together to run on one genechip, with three pairs of epigastric, three pairs of subcutaneous, and three pairs of visceral were ran on nine genechips.  Comparisons of gene expression in the form of fold changes between pairs of adipose types (i.e., subcutaneous/epigastric, visceral/epigastric, and subcutaneous/visceral) were completed by Spotfire Analysis.


title: Expression data from Balb/C mice spleen tissues

status: Public on Aug 20 2013

city: Beijing

first: Bin

last: Wan

address: 18 shuangqing road, Haidian District

institute: Research centre for eco-environmental sciences, CAS

summary:
The immunotoxicity of PFOS (perfluorooctane sulfonate) were reported previously, however, the detailed toxic mechanism remain unknown. Spleen is an important immune organ that controls the differentiation and development of immune cells including T cells, B cells, and macrophages etc. the disruption of the organ may result in altered immune functions and immunotoxicity.
We used microarrays to snapshot the changes of global gene expression, and identified target genes underlying the immunotoxicity of PFOS exposure.

overall_design: 6-8 week old Balb/c female mice were exposed to 10mg/kg body weight PFOS per day for 3 weeks through intragastric administration, and then spleens were removed for RNA extraction and hybridization on Affymetrix microarrays. By comparing the gene expression of spleens with or without PFOS exposure, we sought to obtain differentially expressed genes in order to reveal the toxic mechanism of PFOS.

first: Qi-Yan

last: Lv


title: Expression data of sleeping, waking, and sleep deprived in adult heterozygous Cnp – eGFP-L10a mice

city: Madison

first: Michele

last: Bellesi

state: WI

address: 6001 Research Park Blvd

institute: University Wisconsin-Madison

summary:
Transcriptomic studies revealed that hundreds of mRNAs show differential expression in the brains of sleeping versus awake rats, mice, flies, and sparrows. Although these results have offered clues regarding the molecular consequences of sleep and sleep loss, their functional significance thus far has been limited. This is because  the previous studies pooled transcripts from all brain cells, including neurons and glia.
In the following experiment, we studied the specific effects of sleep and wake conditions on glia cells of mouse cerebral cortex using the genetically targeted translating ribosome affinity purification (TRAP) methodology. We used bacterial artificial chromosome (BAC) transgenic mice expressing EGFP tagged ribosomal protein L10a in oligodendrocytes which constitute a defined cellular population of the mouse brain. Using this approach, we could extract only the oligodendrocitic mRNAs, and only those already committed to be translated into proteins (L10a is part of the translational machinery).

overall_design: Six mice for each vigilant state group (sleep (S), waking (W), and sleep deprivation (SD)) were considered. For each animal, one forebrain sample was immediately processed. Samples were immunoprecipitated to isolate oligodendrocytes. The precipitated portion formed the bound sample (IP) containing olidodendrocytes and the remaining part formed the unbound sample (UB) containing all the remaining cell types (neurons and other glia cells). Then, both IP and UB samples were processed and RNA was extracted.

first: Martha

last: Pfister-Genskow

first: Stephanie

last: Maret

first: Sunduz

last: Keles

first: Giulio

last: Tononi

first: Chiara

last: Cirelli


title: SCFA receptor response

status: Public on Aug 25 2013

city: West Lafayette

first: Chang

last: Kim

address: 725 Harrison St

department: Comparative Pathobiology

institute: Purdue

summary: The purpose of this study was to determine the gene expression patterns of the colon of GPR41 KO and GPR43 KO mice in response to ETOH treatment

overall_design: The mice were treated with rectal injection of ETOH. 24 hours later, the colon tissues were harvested and total RNA was isolated for array experiments.

first: MyungHoo

first: Ann

last: Feil


title: Bladder cancer: analysis of miRNA-mRNA interactions

city: Berlin

first: Hellmuth-A

last: Meyer

address: Charitéplatz 1

department: Department of Urology

institute: Charite

summary: Background: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Their abilyty to affect multiple gene pathways by targeting to various mRNAs makes them to an interesting class of regulators. The interplay between miRNA and mRNA has been proposed as an important process in cancer development and progression. In this study, we analyzed miRNA -mRNA interactions in bladder urothelial carcinoma. Methodology/Principal Findings: We have developed a new algorithm which is capable of identifying altered miRNA-mRNA regulation between tissues samples without preexisting stratification of groups. Microarray expression profiling of both miRNA and mRNA from the same sample were performed using a collective of 24 urothelial carcinoma and normal bladder tissue samples. Using our approach, normal and tumor tissue samples as well as different stages of tumor progression were successfully stratified. Also, we were able to analyzed individual miRNA-mRNA interactions from each patient, focusing on different miRNA families. Conclusions: Just recently, the need for tools that allow an integrative analysis of microRNA and mRNA expression data has been addressed. With this study, we provide an algorithm that considers the special nature of miRNA induced regulation and shows good specificities and sensitivities when applied to bladder cancer expression data.

overall_design: mRNA and microRNA expression data were analyzed together to identify bladder cancer specific micoRNA-mRNA interaction

first: N

last: Hecker

first: C

last: Stephan

first: H

middle: J

last: Mollenkopf

first: K

last: Jung

first: R

last: Preissner

middle: A


title: Expression data from miR-205 knockout in Hair Follicle Stem Cells (HFSCs) of mouse skin

city: Boulder

first: Zhaojie

last: Zhang

address: 2300 Arapahoe Ave

institute: University of Colorado at Boulder

summary:
We identified 201 genes that are consistently upregulated more than 20%, and 108 genes that are consistently downregulated more than 20% in the miR-205 KO samples in two sets of biological duplicates.
We used microarrays to measure transcriptome changes upon knockout of miR-205 in hair follicle stem cells of mouse skin and identified new targets of miR-205.

overall_design: We isolated the HFSCs from WT and miR-205 KO skin at P4 and compare mRNA expression by microarray analysis

first: Dongmei

last: Wang

first: Rui

last: Yi


title: Allergen challenged CD4+ cells from allergic patients and healthy controls

status: Public on Aug 28 2013

city: Linkoping

first: Colm

middle: Eamonn

last: Nestor

address: KEF, Hälsuniversitetet

institute: Linkoping University

summary: Gene expression (Npatients = 21, Ncontrols = 21) of CD4+ T-cells failed to seperate patients with seasonal allergic rhinitis (SAR) and healthy controls in an in vitro model system in which purified PBMCs from patients and healthy controls were challenged with allergen for 7 days.

overall_design: PBMCs from 21 patients (P) and 21 healthy controls (H) were challenged with grass pollen for 7 days. Diluent challenged control samples were obtained from all subjects. CD4+ cells were purified by MACS.

first: Mikael

last: Benson


title: Adult human brain stem cells 1

status: Public on Aug 19 2013

city: Oslo

first: Wayne

middle: George

last: Murrell

address: Sognsvannsveien 20

department: Institute for Surgical Research

country: Norway

institute: Oslo University Hospital

summary: Tissue repair using cell transplantation holds popular appeal. This underlines the need to understand stem cells within the target organ. Our laboratory works on the human brain. Using neurosphere methods, we and others have only been able to passage stem/progenitors a very few times with little expansion of numbers. Now we describe an efficient method for the establishment and propagation of human brain stem cells from whatever tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency markers Sox2 and Oct4 are expressed without artificial induction. For the first time, multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells' behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient's own-derived stem cells.

overall_design:
Adult human brain stem cells from the subventricular zone were compared to those from hippocampus.
Total RNA from three adult human brain biopsy sources: 3 subventricular-derived cell lines and 3 hippocampus-derived cell lines.

first: Emily

last: Pelmero


title: Microarray using CD31+/CD41-/CD45- cells from E9.5 mouse heart tube, caudal half and yolk sac

status: Public on Aug 17 2013

city: Los Angeles

first: Atsushi

last: Nakano

state: California

address: 615 Charles E. Young Dr. South

department: MCDB/BSCRC

institute: UCLA

summary: Hematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial, and hematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a hemogenic organ akin to the dorsal aorta. Here, we examined the hemogenic activity of the developing endocardium. Mouse heart explants generated myeloid and erythroid colonies in the absence of circulation. Hemogenic activity arose from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and was transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, were expressed in and required for the hemogenic activity of the endocardium. Together, these data suggest that a subset of endocardial and yolk sac endothelial cells expressing cardiac markers serve as a de novo source for transient definitive hematopoietic progenitors.

overall_design: Two independent biological duplicates of freshly isolated mouse tissues (caudal half, heart tube, yolk sac) were sorted for CD31+/CD41-/CD45- cells.

first: Nakano

last: Haruko

last: Atsushi


title: Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner

city: Livermore

first: Gabriela

last: Loots

address: 7000 East Avenue

department: BBTD

institute: Lawrence Livermore National Laboratory

summary:
WNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emergning as key regulatory proteins with great promise as therapeutic agents for bone disorders. Until recently Sost and its paralog Sostdc1 have been described as growth factors with highly restricted expression in the adult where Sost was assumed 'osteocyte-' and Sostdc1 'kidney-' specific. Here we show that these two proteins emerged throgh ancestral genome duplication and their expression patterns have diverged to span complimentary domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme.
While Sostdc1-/- mice lack any obvious limb and skeletal defects, Sost-/- mice recapitulate the hand defects described for sclerosteosis patients. However, elevated WNT signaling in Sost-/-; Sostdc1-/- mice causes misregulation of SHH signaling, ectopic activation of Sox9 in the digit 1 field and ultimately preaxial polydactyly. In addition, we show that the syndactyly documented in Sclerosteosis is present in both Sost-/- and Sost-/-; Sostdc1-/- mice, and is driven by misregulation of Fgf8 in the AER, a region lacking Sost and Sostdc1 expression. This study highlights the complexity of WNT signaling in skeletal biology and disease and emphasizes how redundant mechanisms and non-cell autonomous effects can synergize to unveil new intricate phenotypes caused by elevated WNT signaling.

overall_design: Five arrays were analyzed, consisting of two total embryonic fore-limb RNA (experimental) and three total embryonic forelimb RNA (reference) samples at E11.5 DPC mouse (C57Bl6 strain). Embryos were not pooled to generate samples. Two to three biological replicates for limb bud samples were used. Comparisons were made between WT and double mutant (SostKOSostLKO) limb bud samples.

first: Nicole

last: Collette

first: Cristal

last: Yee

first: Deepa

last: Murugesh

first: Aimy

last: Sebastian

first: Leila

last: Taher

first: Nicholas

middle: W

last: Gale

first: Aris

last: Economides

first: Richard

last: Harland

middle: G


title: Expansion of multipotent stem cells from the adult human brain

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

overall_design: Refer to individual Series


title: Adult human brain stem cells 2

overall_design:
Grey matter and white matter: tissue, stem cells and differentiated cells compared.
Total RNA from two brain biopsy sources (grey matter, white matter) from one adult human.


title: Sequential induction of effector function, tissue migration and cell death during polyclonal activation of regulatory T-cells

status: Public on Aug 10 2013

city: Wuerzburg

first: Susanne

middle: Elma

last: Kneitz

address: Biozentrum, Am Hubland

department: Physiologigcal Chemistry

institute: University of Wuerzburg

summary: The ability of Treg-cells to produce interleukin-10 (IL-10) is important for the limitation of  inflammation at environmental interfaces like colon or lung. Under steady state conditions, however,  only few Treg-cells produce IL-10 ex vivo. To investigate the origin and fate of IL-10 producing Tregcells  we used a superagonistic mouse anti-mouse CD28 mAb (CD28SA) for polyclonal in vivo  stimulation of Treg-cells, which not only led to numeric expansion but also to a dramatic increase in IL-  10 production. IL-10 secreting Treg-cells strongly upregulated surface receptors associated with  suppressive function, and had higher but IL-10 independent, in vitro suppressive capacity than nonproducing  Treg-cells. Furthermore, polyclonally expanding Treg-cells shifted their migration receptor  pattern after activation from a lymph node-seeking to an inflammation-seeking phenotype, explaining  the preferential recruitment of IL-10 producers to sites of ongoing immune responses. Finally, we  observed that IL-10 producing Treg-cells from CD28SA stimulated mice were more apoptosis-prone in  vitro than their IL-10 negative counterparts. These findings support a model where prolonged activation  of Treg-cells results in terminal differentiation towards an IL-10 producing effector phenotype  associated with a limited lifespan, implicating built-in termination of immunosuppression.

overall_design: total samples analysed are 4

first: Daniela

last: Langenhorst

first: Tea

last: Gogishvili

first: Eliana

last: Ribechini

first: Kirsty

last: McPherson

first: Manfred

last: Lutz

first: Tim

last: Sparwasser

first: Thomas

last: Hünig


title: Profiling of glycerol- and CTX-induced models of muscle regeneration in mice

status: Public on Aug 16 2013

city: Basel

first: Sophie

last: Brachat

address: Novartis Campus

department: Muskuloskeletal

institute: Novartis Institutes For Biomedical Research

summary: Utilizing glycerol and cardiotoxin (CTX) injections in the tibialis anterior muscles of M. musculus provides models of skeletal muscle damages followed by skeletal muscle regeneration. In particular, glycerol-induced muscle regeneration is known to be associated with ectopic adipogenesis. We characterized genome-wide expression profiles of tibialis anterior muscles from wild-type mice injured by either glycerol or CTX injection. Our goal was to detect gene expression changes during the time course of glycerol-induced and CTX-induced muscle regeneration models, that can lead to ectopic adipocyte accumulation.

overall_design:
Tibialis anterior muscle of 12 week old wildtype C57BL/6J male mice injected i.m with either glycerol or CTX were collected 3, 7, 14 or 21 days after injection. 6 biological replicates were used for each time points.
Please note that a few replicate samples did not pass QC test, thus, were removed from the submission.
Unchallenged tibialis anterior muscles from a group of 5 wildtype C57BL/6J mice were also as a control. Total RNA was extracted, QCed and hybridized to Affymetrix microarrays.

first: Laura

last: Lukjanenko

first: Jérôme

middle: N

last: Feige


title: Gene expression microarray analysis on the dentate gyrus of Schnurri-2 knockout and wild-type control mice

status: Public on Aug 13 2013

city: Toyoake

first: Juzoh

last: Umemori

address: 1-98 Kutsukakecho, Dengakugakubo

institute: Fujita Health University

summary: Schnurri-2 (Shn-2), an NF-kappa B site-binding protein, tightly binds to the enhancers of major histocompatibility complex (MHC) class I genes and inflammatory cytokines, which have been shown to harbor common variant single nucleotide polymorphisms associated with schizophrenia. Shn-2 knockout mice show behavioral abnormalities that strongly resemble those of schizophrenics. We performed gene expression microarray analysis of dentate gyri from Shn-2 knockout and wild-type control mice.

overall_design: Dentate gyrus RNA isolated from six Shn-2 knockout and six control wild-type mice were compared.

first: Keizo

last: Takao


title: Gene expression microarray analysis on the medial prefrontal cortex of Schnurri-2 knockout and wild-type control mice

summary: Schnurri-2 (Shn-2), an NF-kappa B site-binding protein, tightly binds to the enhancers of major histocompatibility complex (MHC) class I genes and inflammatory cytokines, which have been shown to harbor common variant single nucleotide polymorphisms associated with schizophrenia. Shn-2 knockout mice show behavioral abnormalities that strongly resemble those of schizophrenics. We performed gene expression microarray analysis of prefrontal cortices from Shn-2 knockout and wild-type control mice.

overall_design: Prefrontal cortex RNA isolated from six Shn-2 knockout and six control wild-type mice were compared.


title: Gene expression microarray analysis on the medial prefrontal cortex and dentate gyrus of Schnurri-2 knockout and wild-type control mice


title: Head and neck paragangliomas

first: Renato

last: Mariani-Costantini

type:
Genome variation profiling by SNP array
SNP genotyping by SNP array
Non-coding RNA profiling by array


title: Exon Array Expression Profiling of HCT116 (p53null) cells transfected with wildtype p53 and 6 p53 mutants

city: Singapore

first: Bei

last: Wang

address: 8A Biomedical Grove, #03-06, Immunos

institute: Singapore Immunology Network

summary:
The tumor suppressor protein p53 functions to regulate diverse cellular processes including apoptosis, cell cycle, senescence and metabolism. Act as a master transcription factor, it can transcriptionally regulate the gene expression of many downstream target genes. p53 is frequently mutated in cancer by single nucleotide/amino acid substitutions at the DNA binding domain that result in a mutant form of p53 protein and usually loses its DNA binding and transcriptional regulation abilities.
In this study, we performed gene expression analysis using Affymetrix Exon Array ST1.0 platform to assess the transcriptome of wildtype p53 and 6 loss-of-function p53 mutants in p53null HCT116 cells.

overall_design: 8 samples were analyzed as a group. pcDNA3.1 empty construct was served as a control experiment.

first: Dandan

last: Niu

first: Liyun

last: Lai

first: Ee-Chee

last: Ren


title: Exon arrays from HT-29, MCF10A, and MDA-MB-436 cells

status: Public on Aug 06 2013

city: Charlottesville

first: Byong

middle: Ha

last: Kang

state: VA

address: 415 Lane Road, MR5-Rm. 2225

department: Department of Biomedical Engineering

institute: University of Virginia

summary: Expression data from HT-29 cells treated with IFN-γ for 24 hr, MCF10A cells, and MDA-MB-436 cells.

overall_design: Total RNA was isolated with the RNeasy Mini Kit (Qiagen). Sense-strand cDNA synthesis, terminal labeling, and hybridization were performed using Ambion WT Expression Kit (Applied Biosystems, P/N 4425209).

middle: H

first: Karin

last: Jensen

first: Jaime

last: Hatch

first: Kevin

last: Janes


title: Gene expression profile of epithelial ovarian tumor tissue of a transgenic mouse model compared to normal mouse ovary tissue

city: Urbana

first: Mary

last: Laws

address: 2001 S. Lincoln Ave.

institute: University of Illinois

summary:
The etiology of ovarian cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mouse model termed ERalpha d/d in which a conditional deletion of estrogen receptor alpha (ERalpha) gene occurred in the anterior pituitary, but ERalpha expression remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to elevated production of luteinizing hormone (LH) by this tissue. Hyperstimulation of ovarian cells by LH resulted in increased steroidogenesis, leading to high circulating levels of progesterone, testosterone and E.  The ERalpha d/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age, and by 12 months, most mice carrying these tumors died. Besides proliferating epithelial cells, these tumors also contained an expanded population of stromal cells, which express P450 aromatase suggesting that these cells acquired the ability to synthesize E. In ERalpha d/d mice, in response to the E produced by the stromal cells, the ERalpha signaling is accentuated in the ovarian epithelial cells, triggering increased ERalpha-dependent gene expression, abnormal cell proliferation, and tumorigenesis. The ERalpha d/d animal model of ovarian epithelial tumorigenesis will serve as a powerful tool for exploring the involvement of E-dependent signaling pathways in the etiology of ovarian cancer.
To identify aberrantly regulated genes in epithelial ovarian tumors, we performed gene expression profling of ovarian tumor tissue isolated from ERaplha d/d mice and normal ovary tissue isolated from ERaplha f/f control mice.

overall_design: The ERalpha d/d mouse model was created via conditional deletion of ERalpha by employing the Cre-LoxP strategy. Transgenic mice expressing Cre recombinase under the control of progesterone receptor (PR) promoter, termed PR-cre mice, were crossed with mice harboring the ‘floxed’ ERalpha gene (ERalpha f/f) to create the ERalpah d/d mice in which the ERalpha gene is deleted in cells expressing PR. Ovarian tumor tissue was isolated from ERalpha d/d mice and normal ovary tissue was isolated from ERalpha f/f mice at 5 months and 10 months of age. Tissues were snap frozen and total RNA was isolated. Total RNA was pooled from 3 mice for each sample subjected to microarray analysis.

first: Indrani

middle: C

last: Bagchi

first: Milan

middle: K


title: Chronic lymphocytic leukemia cells are activated and proliferate in response to specific Th cells

status: Public on Aug 08 2013

first: Ludvig

last: Munthe

state: Oslo

department: Institute of Clinical Medicine

institute: University of Oslo

summary:
Changes in gene expression profile of CLL cells in response to an antigen-specific Th cell clone that is specific for a Ckappa peptide of mouse Abs. Mouse anti human BCR mAbs were used to ligate BCR and deliver antigen to CLL cells.
32-45 x10e6 PBMC were incubated overnight with or without 2 μg/ml of Ms κ+IgG anti-kappa and anti-lambda mAbs. The PBMC were then cultured in presence or absence of 12.5 x10e6 T18 cells. On day 3, CLL cells were purified by negative selection using CD3 and CD14 Dynabeads (Invitrogen). RNA from CLL cells was controlled and quantified on a NanoDrop1000 (Thermo Scientific, Wilmington, DE, USA). 290ng per sample was amplified and labeled with the TotalPrep™-96 RNA Amplification Kit (Illumina, San Diego, CA, USA). Sample quality was further tested by Agilent 2100 bioanalyzer (Agilent, Santa Clara, CA, USA). 1500ng of biotin labeled cRNA was used to hybridize onto Illumina HumanWG-6 v3 Expression BeadChips. After scanning, the results were imported into Illumina GenomeStudio v. 2010.1, Gene Expression module v. 1.6.0 for quality control and data export. Analysis was performed utilizing GeneSpring GX v11 software (Agilent, Santa Clara, CA, USA). In GeneSpring GX, Logbase 2-transformed data were normalized to the 75 percentile with baseline transformation to median of all samples. Flag Information: Lower cutoff for 'Present' call: 0.8, Upper cutoff for 'Absent' call: 0.6

overall_design: Testing antigen dependent Th cell - CLL cell collaboration, effects on gene expression of CLL cells

first: Audun

last: Os

first: Simone

last: Bürgler

first: Anna

last: Parente Ribes

first: Ane

last: Funderud

first: Dong

first: Keith

middle: M

last: Thompson

first: Geir

middle: E

last: Tjønnfjord

first: Bjarne

last: Bogen