title: Gene Expression in the Human Mammary Epithelium during Initiation of Lactation.

status: Public on Sep 04 2012

city: Houston

first: Mahmoud

middle: Ali

last: Mohammad

state: Texas

address: 1100 Bates St.

department: Pediatrics-Nutrition

institute: Baylor College of Medicine

summary: We have utilized the RNA isolated from breast milk fat globule (MFG) from lactating women from 6h to 42 days following delivery using the HumanHT-12 v4 Expression BeadChip (Illumina, Inc) to determine the temporal coordination of changes in gene expression in milk substrate synthesis processes. Of the 47,323 gene transcripts on the array, 16,623 transcripts were expressed. Major milk protein genes were among the most highly expressed and induced along with those involved in the metabolic and biosynthetic processes of carbohydrate and lipid. Milk fat synthesis mirrors expression of genes involved in fat synthesis, lipolysis and transport. In the lactose synthesis pathway, expression of α-lactalbumin mRNA was high already in the early milk and did not change. Lactose synthesis paralleled the induction of gene expression of proteins involved in UDP-galactose synthesis and transport.

overall_design: Serial milk samples were collected 6h following delivery, q12 h for the first 4 days and then weekly for 6 wks from 7 healthy, lean, exclusively breastfeeding women [7 x 15 = 105 samples]. RNA was isolated from the milk fat globules and utilized for microarray analyses.

first: Darryl

last: Hadsell

first: Morey

middle: W

last: Haymond


title: Expression data from electrically-altered larval Drosophila LNvs

status: Public on Sep 01 2012

city: New York

first: Marc

last: Ruben

state: NY

address: 100 Washington Square East

department: Biology

country: USA

institute: New York University

summary:
While intensely studied in the context of synaptic plasticity, the interplay between electrical activity and transcription is also relevant to circadian pacemaker neurons where ~24hr rhythms in gene expression and neural activity define the functional state of clock neurons. Here we demonstrate broad transcriptional changes in Drosophila circadian pacemaker neurons (LNvs) in response to altered electrical activity, including a large set of circadian genes.
We used microarrays to identify the global program of gene expression in purified Drosophila pacemaker neurons in response to targeted electrical manipulations

overall_design:
Drosophila larval brains (L3 stage) were dissected on the second day in constant darkness following a 12:12hr light entrainment regime. Larvae contained a Pdf-RFP transgene that labels 8 LNvs pacemaker neurons per brain, allowing purification by flow cytometry. Larvae also contained transgenes (NachBac and Kir) to specifically manipulate the electrical properties of LNvs. Brains were dissociated and LNvs purified by FACS, followed by RNA amplification and hybridization on Affymetrix microarrays.

We generated expression profiles of LNvs isolated at CT3 expressing Kir and GFP in the cyc0 mutant background. Drosophila larval brains (L3 stage) were dissected on the second day in constant darkness following a 12:12hr light entrainment regime.  Brains were dissociated and LNvs purified by FACS, followed by RNA amplification and hybridization on Affymetrix microarrays.

first: Dogukan

last: Mizrak

first: Justin

last: Blau


title: Genome-wide analysis of human macrophages stimulated with IL-4 (10ng/ml) (Illumina)

status: Public on Sep 29 2012

city: Guildford

first: Fernando

middle: O

last: Martinez Estrada

state: Surrey

address: Stag Hill

department: Faculty of Health & Medical Sciences

country: United Kingdom

institute: University of Surrey

summary: Analysis of alternative activation of macrophages at gene expression level. The study forms part of a wider study where we compare the effects of IL-4 in different human and mouse macrophages. Our results support the notion that in vitro culture conditions greatly affect the macrophage response to IL-4.

overall_design: Total RNA obtained from human monocyte derived macrophages upon exposure to 10 ng/ml of IL-4 for 48 hours.  Monocytes were induced to mature into macrophages using X Vivo 10 medium supplemented with 1% autologous serum.

last: Martinez


title: Reversal of Aberrant Cancer Methylome and Transcriptome upon Direct Reprogramming of Lung Cancer Cells [Expression]

city: Bad Nauheim

first: Jason

last: Lai

state: Hessen

address: Ludwigstrasse 43

department: Developmental Genetics

country: Germany

institute: Max Planck Institute For Heart and Lung Research

summary: Non-small cell lung cancer cell (NSCLC) lines were reprogrammed with Yamanaka's cocktail and their methylome and transcriptome were studied and characterized.

overall_design: We compared reprogrammed cells to their respective parent (2 NSCLC and 1 human lung fetal fibroblast) and used H1 as a positive control for pluripotency characteristics. The in vitro differentiated cells were also compared to the reprogrammed cells. All samples have biological triplicates except for differentiated cells.


title: Genome-wide analysis of human macrophages stimulated with IL-4 (20ng/ml) (Illumina)

overall_design: Total RNA obtained from human monocyte derived macrophages upon exposure to 20 ng/ml of IL-4 for 24 hours.  Monocytes were induced to mature into macrophages using X Vivo 10 medium supplemented with 1% autologous serum.


title: Drosophila LID RNAi gene expression profiling

status: Public on Aug 30 2012

city: Barcelona

first: David

last: Rossell

address: Baldiri Reixac 10

country: Spain

institute: IRB Barcelona

summary:
H3K4me3 is a histone modification related to gene activation. LID is a demethylase acting on this residue and therefore, it could be important for proper expression of genes in Drosophila developing tissues, such as wing imaginal discs
We used microarrays to analyse the changes in gene expression after lid depletion by RNAi, both in a wild type background and in a mutant background

overall_design: Two replicates were obtained on Nov 2010 for wild type white drosophila, GFP RNAi control and LID RNAi (on a LID mutant background).

first: Marta

last: Lloret-Llinares

last: Azorín


title: Global gene expression analysis of pluripotent cell lines and corresponding starting donor source cells

status: Public on Aug 23 2012

city: Baltimore

first: Elias

middle: Thomas

last: Zambidis

state: MD

address: 733 N. Broadway

department: Oncology

institute: Johns Hopkins School of Medicine

summary: Global gene expression analysis of induced pluripotent stem cell lines and their corresponding source cells

overall_design: Total RNA was harvested from H9 hESC (P51), non-integrated episomal CB-iPSC clones 6.2, 6.11, 6.13, (P14), 19.11, (P11), nonviral KER-iPSC clones KA.1, KA.3 (P13) nonviral FFB-iPSC: F.1, F.6 (P14) and viral fibroblast iPSC clones IMR1 (P66), IMR4 (P64). A single sample of each condition was used for this analysis.

first: T

middle: S

last: Park

first: J

last: Huo

first: A

last: Peters

first: C

middle: C

last: Talbot

first: I

middle: M

last: Kaplan

first: E

middle: T


title: Global gene expression analysis of human embryonic stem cells, adult fibroblasts , and CD34+ cord blood (CB) cells before, during, and afer their episomal induction of pluripotency

summary: Global gene expression analysis of (a) human embryonic stem cells, (b) adult fibroblasts with and without nucleofection of SOKM, and ( c ) CD34+ cord blood cells at various time points during induction of pluripotency with SOKM, with or without co-culture with bone marrow stromal cells (BMSC).

overall_design: Total RNA was harvested from adult fibroblasts, adult fibroblasts three days after nucleofection with 4F (SOKM), Day -3 unstimulated cord blood (CB) cells, Day 0 growth factor stimulated CB cells, Day +3 CB cells with or without nucleofection at Day zero and with or without Day zero to Day +3 co-culture with bone marrow stromal cells (BMSC), Day 23 CB cells nucleofected on day zero and co-cultured on BMSC from Day Zero to Day +3,  and undifferentiated H9 human embryonic stem cells. All experimental conditions repeated in three independent trials, and each replicate at each condition analyzed on an individual microarray.


title: Clinically Relevant Subsets Identified by Gene Expression Patterns Support a Revised Ontogenic Model of Wilms Tumor: A Children’s Oncology Group Study

status: Public on Aug 29 2012

city: Chicago

first: Elizaebth

middle: J

last: Perlman

state: IL

address: 2373 North Lincoln Avenue

department: Pathology

institute: Northwestern University

summary: Favorable Histology WTs (FHWT) are genetically heterogeneous and the pathogenesis for the majority is not known; therefore,  we sought to identify and characterize distinctive subsets within FHWT and to place each subset within their clinical and developmental context.

overall_design: Classification by microarray analysis : Global gene expression analysis was performed on 224 FHWT tumors using  Affymetrix U133A arrays and subsets were identified and characterized using gene set enrichment analysis, WT1, WTX, and CTNNB1 mutation status, 11p15 methylation, and 11p15 copy number.

first: Samantha

last: Gadd

first: Elizabeth


title: Fibrous stromal component in hepatocellular carcinoma reveals a cholangiocarcinoma-like gene expression trait and epithelial-mesenchymal transition.

status: Public on Aug 31 2012

city: Suwon

first: Hyun Goo

last: Woo

address: 164 Worldcup-ro Yeongtong-gu

country: South Korea

institute: Ajou University School of Medicine

summary: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. It has been shown the phenotypic overlap between HCC and CC, comprising continuous liver cancer spectrum. As a proof of concept, a recent study has demonstrated a genomic subtype of HCC expressing CC-like gene expression trait, i.e. CC-like HCC, which has revealed common genomic trait of stem cell-like property and aggressive clinical outcome. However, the histopathological characteristics of these intermediate phenotype was not fully evaluated yet. Here, we found that a variant HCC with fibrous stromal component, i.e. scirrhous HCC, has CC-like genomic features. By performing gene expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of scirrhous HCC with CC and classical HCC. We found that the scirrhous HCC express both CC-like and stem cell-like expression traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of scirrhous HCC. Over-expression of transforming growth factor β (TGF-β) signaling was also found, implying its regulatory role in the pathobiology of scirrhous HCC. Conclusion: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene expression trait in HCC. The expression of stem cell-like trait and TGF-β/EMT molecules may play pivotal roles in the aggressive phenotype of scirrhous HCC

overall_design: Gene expression profiles of HCC, CC and HCC with fibrous stroma were compared.

first: Jae

middle: Y

last: Seok

first: Deuk

first: Hyun

middle: G

first: Massimo

last: Roncalli

first: So

last: Kwon

first: Jeong

middle: E

last: Yoo

first: Ei

last: Ahn

first: Gwang

middle: I

last: Kim

first: Jin-Sub

last: Choi

first: Young

middle: B

middle: N


title: Blood transcriptome of human bacterial and influenza A pneumonia

status: Public on Aug 15 2012

city: Kingswood

first: Grant

last: Parnell

state: NSW

address: Nepean Hospital

department: Nepean Clinical School

country: Australia

institute: University of Sydney

summary: Introduction: Diagnosis of severe influenza pneumonia remains challenging because of the lack of correlation between presence of influenza virus and patient’s clinical status. We conducted gene expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure (e.g. bacterial pneumonia, non-infective systemic inflammatory response syndrome).   Methods: Whole blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene expression beadarrays. Differentially expressed genes were determined by linear mixed model analysis and over-represented biological pathways determined using GeneGo MetaCore.   Results: The gene expression profile of H1N1 influenza A pneumonia was distinctly different from bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene expression profile is characterized by up-regulation of genes from cell cycle regulation, apoptosis and DNA-damage response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene expression profile of influenza infection persisted through five days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection who subsequently developed bacterial co-infection, the influenza gene-expression signature remained unaltered, despite the presence of a super-imposed bacterial infection.   Conclusions: The whole blood expression profiling data indicates that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed up identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly.

overall_design: Daily PAXgene samples for up to 5 days for; influenza A pneumonia patients (n=8),  bacterial pneumonia patients (n=16), mixed bacterial and influenza A pneumonia patients (n=3), systemic inflammatory response patients (SIRS, n=13). Days 1 and 5 PAXgene samples for healthy control individuals

middle: P

first: Benjamin

last: Tang


title: Brain transcriptional and epigenetic associations with the autistic phenotype (expression data)

city: Cleveland

first: Matthew

last: Ginsberg

state: OH

address: 9500 Euclid Ave

department: Lerner College of Medicine

institute: Cleveland Clinic Foundation

summary: Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.

overall_design: In this set of gene expression data, 8 autism and 8 control cerebellar samples were included, as well as 6 autism and 4 control BA19 samples. Samples are labeled as R, then a number, followed by an optional letter. The number is a variable specific to the subject and brain region. A lower-case a follows technical replicates. A letter X follows biological replicates, which were performed for the two most significant outliers. cer=cerebellum; occ = occipital (BA19). Additional subject data may be obtained from the Autism Tissue Program.

middle: R

first: Robert

middle: A

last: Rubin

first: Tatiana

last: Falcone

first: Angela

middle: H

last: Ting

first: Marvin

last: Natowicz


title: Progesterone and estrogen receptors segregate into different cell subpopulations in the normal human breast

status: Public on Aug 17 2012

city: Sydney

first: Heidi

last: Hilton

address: Darcy Rd, Westmead

department: Westmead Institute for Cancer Research

summary:
Gene expression profiles of normal human mammary epithelial cell subsets enriched for luminal or myoepithelial characteristics on the basis of EpCAM and CD49f expression.
Transcription profiles were compared between luminal- and myoepithelial-enriched human MEC subsets following 3D culture from 4 individuals.
Gene expression profiles of normal human mammary epithelial cell subsets enriched for mature, luminal progenitor or bipotent progenitor-enriched characteristics on the bais of CD49f, MUC1, CD10, CD133 and Thy1 expression
Transcription profiles were compared between unsorted, mature, luminal progenitor-enriched and bipotent progenitor-enriched human MEC subsets following 3D culture from 2 individuals.

overall_design:
Four replicates of luminal-enriched human MECs and 3 replicates of myoepithelial-enriched MECs
Transcription profiles of two replicates of unsorted, mature, luminal progenitor-enriched and bipotent progenitor-enriched human MEC subsets were analysed following 3D culture


title: Brain transcriptional and epigenetic associations with the autistic phenotype

type:
Expression profiling by array
Methylation profiling by array

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

overall_design: Refer to individual Series


title: Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines (trisomy 21)

city: Paris

first: Luce

last: Dauphinot

address: 47 boulevard de l'hôpital

department: ICM

country: France

institute: INSERM U1127-CNRS UMR7225-UPMC

summary: Molecular consequences of trisomy in lymphoblastoid cell lines from patients with Down syndrome. This project analyses differentially expressed genes between humans with trisomy 21 and humans without trisomy 21.

overall_design: Total RNA obtained from human lymphoblastoid cell lines without trisomy 21 compared to cell lines from human with trisomy 21.

first: Clementine

last: Ripoll

first: Isabelle

last: Rivals

first: Emilie

last: Ait Yahya-Graison

first: Evelyne

last: Paly

first: Clothilde

last: Mircher

first: Andre

last: Ravel

first: Yann

last: Grattau

first: Henry

last: Blehaut

last: Megarbane

first: Guy

last: Dembour

first: Benedicte

last: de Freminville

first: Renaud

last: Touraine

first: Nicole

last: Creau

first: Marie-Claude

last: Potier

first: Jean-Maurice

last: Delabar


title: Role of CAMTA1 gene under drought stress

status: Public on Aug 13 2012

city: lucknow

first: samir

middle: v

last: sawant

address: rana pratap marg

department: CPMB & GE

country: India

institute: national botanical research institute

summary: The CAMTA1 mutant and Col-0 were studied under water and drought condition. The camta1 showed stunted primary root growth under osmotic stress. The expression analysis revealed drought recovery as major indicative pathway along with membrane and chloroplast related protein in  camta1 under drought stress. Large number of positively regulated genes were related to osmotic balance, transporters, AP2 and ABA. We used Affymetrix expression analysis to validate the role of CAMTA1 under drought stress.

overall_design: The RNA of Col-0 and camta1 mutant were isolated in water and drought condition.The ATH1 gene chip was used for expression analysis.

first: Neha

last: Pandey

first: Alok

last: Ranjan

first: Poonam

last: Pant

first: Samir

middle: V

last: Sawant


title: Histone acetylation and DNA demethylation of T-cells result in an anaplastic large cell lymphoma-like phenotype.

status: Public on Aug 19 2012

city: Berlin

first: Maria

last: Joosten

address: Hindenburgdamm 30

department: Instiute of Pathology

institute: Charité Berlin

summary: A characteristic feature of anaplastic large cell lymphoma (ALCL) is the significant reduction of the T-cell expression program despite its T-cell origin, a finding very similar to the loss of B-cell identity of classical Hodgkin lymphoma (cHL). Previously we demonstrated that epigenetic mechanisms are active in cHL to induce this peculiar phenotype.  The results show that combined DNA demethylation and histone acetylation of T-cell lines induce an almost complete extinction of the T-cell phenotype, including the down-regulation of essential T-cell receptor signalling pathway genes such as CD3, LCK and ZAP70, as well as an up-regulation of ALCL-characteristic genes. In contrast, combined DNA demethylation and histone acetylation of ALCL cells is not able to reconstitute their T-cell phenotype. This clearly demonstrates that similar epigenetic mechanisms are active in ALCL and cHL which are responsible for the extinction of their cell type characteristic phenotype.

overall_design: We subjected T-cell lymphoma/leukemia cell lines and ALCL cell lines (n=4, each) to epigenetic modifiers to evoke DNA demethylation and the histone acetylation. Global gene expression profiling (Affymetrix) was performed from treated and untreated cell lines which were evaluated by real-time RT-PCR and Western Blot analysis.

first: Volkhard

last: Seitz

first: Karin

last: Zimmermann

first: Erika

last: Berg

first: Dido

last: Lenze

first: Harald

last: Stein

first: Ulf

last: Leser

first: Michael

last: Hummel


title: Reversal of Aberrant Cancer Methylome and Transcriptome upon Direct Reprogramming of Lung Cancer Cells.

status: Public on Aug 27 2012

first: Jason

last: Lai

first: Dashayini

last: Mahalingam

first: ChiouMee

last: Kong

first: LingLee

last: Tay

first: Henry

last: Yang

first: Xueying

last: Wang


title: Methylphenidate exposure induces dopamine neuron loss and activation of microglia in the basal ganglia of mice

status: Public on Aug 14 2012

city: Memphis

first: Chunxu

last: Qu

state: TN

address: 262 Danny Thomas Pl

institute: St Jude Children's Research Institute

summary:
Background: Methylphenidate (MPH) a psychostimulant prescribed to manage ADHD symptoms, has been increasingly prescribed to children not meeting the strict criteria for ADHD. It has also been misused as a “cognitive enhancer” and as an alternative to other psychostimulants. Here, we investigate whether chronic or acute administration of methylphenidate in mice at either 1mg/kg or 10mg/kg dosing, affects cell number and gene expression in the basal ganglion.
Methodology/Principal findings: Through the use of stereological counting methods, we observed a significant reduction (~20%) in dopamine neuron numbers in the substantia nigra pars compacta (SNpc) following chronic administration of 10mg/kg MPH. This dosage of MPH also induced a significant increase in the number of morphologically-activated SNpc microglia. Additionally, exposure to either 1mg/kg or 10 mg/kg MPH increased the sensitivity of SNpc dopamine neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced oxidative stress. Unbiased gene screening employing Affymetrix GeneChip® HT MG-430 PM revealed changes in 115 and 54 genes in the substantia nigra (SN) of mice exposed to 1mg/kg and 10mg/kg MPH doses, respectively. Decreases in the mRNA levels of gdnf, dat1, vmat2 and th in the substantia nigra (SN) was observed with both acute and chronic dosing of 10mg/kg MPH. We also found an increase in mRNA levels of the pro-inflammatory genes il-6 and tnf-α in the striatum; although these were seen only at an acute dose of 10mg/kg and not following chronic dosing.
Conclusion: Collectively our results suggest that chronic MPH usage in mice, especially at prolonged higher doses, has long-term neurodegenerative consequences.

overall_design: drug treatment: 3 control, 3 low dose treatment, 3 high dose treatment

first: Shankar

last: Sadasivan

first: Brooks

last: Pond

first: Amar

middle: K

last: Pani

first: Yun

last: Jiao

first: Richard

last: Smeyne


title: COMPARATIVE TRANSCRIPTOMIC AND PROTEOMIC ANALYSIS OF LGR5+ve STEM CELLS AND THEIR DAUGHTERS (AFFYMETRIX ARRAYS)

city: Dresden

first: Daniel

middle: E.

last: Stange

address: Fetscherstr. 74

institute: University Clinic Dresden

summary: The identification of Lgr5 as an intestinal stem cell marker has made it possible to isolate and study primary intestinal stem cells. Applying quantitative mass spectrometry as well as transcriptomic analysis, we profiled the protein and gene changes between FACS-sorted Lgr5+ve stem cells and their immediate undifferentiated daughter cells. The overall comparison of mRNA and protein levels revealed a high level of correlation, implying that the initial control of intestinal stem cell biology occurs largely at the mRNA level. Taken together, our study presents a valuable resource for the study of intestinal stem cell biology.

overall_design: We used cell fractions of intestines from Lgr5-EGFP-ires-CreERT2 mice, expressing GFP under the control of the Lgr5 promoter. RNA was isolated from two FACS sorted cell populations, one expressing GFP at high levels (GFPbright) and the other expressing GFP at low levels (GFPdim). The gates set to sort cells for the expression profiling were the same as for the cells used for the mass spectometry analysis. cRNA from GFPbright and GFPdim cells from three different sorts (each combining three to four mice) were hybridized on Affymetrix Mouse HT MG-430 PM plate arrays.

first: Marc

last: van de Wetering

last: Volckmann

first: Jan

last: Koster

first: Hans

last: Clevers


title: COMPARATIVE TRANSCRIPTOMIC AND PROTEOMIC ANALYSIS OF LGR5+ve STEM CELLS AND THEIR DAUGHTERS


title: Gene expression in mitotic tissues of Drosophila larvae without centrosomes or too many centrosomes

status: Public on Aug 20 2012

city: Oxford

first: Janina

last: Baumbach

state: Oxfordshire

address: South Parks Road

department: Sir William Dunn School of Pathology

institute: University of Oxford

summary: Centrosome defects are a common feature of many cancers. Surprisingly, flies can proceed through the majority of development without centrosomes or with amplified centrosomes in most of their cells. It is unclear whether this is because centrosome defects do not cause many problems in Drosophila cells, or because they can adapt to cope with any problems that arise. Indeed, centrosome loss and centrosome amplification predispose fly brain cells to form tumours. Here we assess how centrosome loss or centrosome amplification perturbs cell physiology by profiling the global transcriptome of Drosophila larval brains and imaginal discs that either lack centrosomes or have too many centrosomes.

overall_design: Mitotic tissues (brains and imaginal discs) were dissected from 3rd instar Drosophila larvae of mutants lacking centrosomes (DSas-4 and DSas-6), a strain with too many centrosomes (SakOE) and two different wild type strains (w67 and OregonR). We extracted RNA from three biological replicates per strain and used it for hybridisation to Affymetrix Drosophila Genome 2.0 arrays. Per biological sample, material dissected from ten larvae was pooled. Gene expression of the mutant strains was compared to both wild type controls.

first: Mitchell

last: Levesque

first: Jordan

middle: W

last: Raff


title: Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines

status: Public on Aug 09 2012

first: Peter

last: Wilkinson

state: Ohio

address: 2103 Cornell Road

department: Pathology / Systems Biology & Bioinformatics

institute: Case Western Reserve University


title: Transcriptional profiles of sorted CD8+ and CD4+ memory T cells from CP and NP and unvaccinated control RM 7 days prior to, and 4 and 14 days after wt SIVmac239 challenge by microarray analysis.

summary: Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses.

overall_design: There are two protection outcome groups, complete protect (CP) and non-protect (NP) animals. Memory T cells (CD4+ or CD8+) were sorted for three time points, seven days pre-challenge, four days post-challenge and fourteen days post-challenge.

first: Yoshinori

last: Fukazawa

first: Haesun

last: Park

first: Mark

last: Cameron

first: Francois

last: Lefebvre

last: Lum

first: Noel

last: Coombes

first: Eisa

last: Mahyari

first: Shoko

last: Hagen

first: Jin

last: Bae

first: Marcelo

last: Delos Reyes

first: Tonya

last: Swanson

first: Alfred

last: Legasse

first: Andrew

last: Sylwester

first: Scott

last: Hansen

middle: T

last: Smith

first: Petra

last: Stafova

first: Rebecca

last: Shoemaker

first: Yuan

last: Li

first: Kelli

last: Oswald

first: Michael

last: Axthelm

first: Adrian

last: McDermott

first: Guido

last: Ferrari

first: David

middle: C

last: Montefiori

first: Paul

last: Edlefsen

last: Piatak

first: Jeffrey

middle: D

last: Lifson

first: Rafick

last: Sékaly

first: Louis

last: Picker


title: Growth factor-activated stem cell circuits and stromal signals cooperatively accelerate iPSC reprogramming of lineage-committed myeloid progenitors

first: Elias

middle: Thomas

last: Zambidis

first: T

middle: S

last: Park

first: J

last: Huo

first: A

last: Peters

first: C

last: Talbot

first: I

middle: M

last: Kaplan

first: E


title: Transcriptome analysis of a chronic in vitro model of Parkinsonism

city: Los Angeles

first: Yofre

last: Cabeza-Arvelaiz

state: California

address: 650 Charles E. Young Drive South

department: Pathology and Environmental Health Sciences

institute: University of California, Los Angeles

summary: The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND).  Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB) cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs) by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs.

overall_design: SK-N-MC cells were grown in three different conditions: media + vehicle (EtOH), media + a sublethal dose (5 nM) of rotenone, and  media + a slightly toxic dose  (50 nM) of rotenone.  Gene expression was examined at 1 and 4 weeks of rotenone treatment. Three experiments were performed, each lasting 1 and 4 weeks.  For each experiment, 5 separate dishes of vehicle-treated, and rotenone-treated cells were harvested at 1 and 4 weeks  (30 independent samples at each time point) and pooled into 3 samples (vehicle treated,and rotenone treated with 5 nM and 50 nM) at each time point for a total of 18 individual samples from all thre experiments.  Total RNA isolated from each of the 18 individual samples was used to prepared labeled cRNA and hybridized to one Genechip (Affymetrix) Human Genome array HG-U133A at the UCLA microarray core facility (http://microarray.genetics.ucla.edu/). After QC check, the data was normalized and used to assess expression indexes and fold changes (FC > 2.0, compared to vehicle-treated controls) using the model-based expression indexes (MBEI) method implemented in dCHIP, ( http://biosun1.harvard.edu/complab/dchip/), and the Signifiance Analysis of Microarrays (SAM) software for multiple test corrections. Enrichment analysis was performed by the functional annotation tools implemented in DAVID ( http://david.abcc.ncifcrf.gov), to ascertain sets of rotenone DRGs that are enriched in certain biological annotations.


title: The genomic architecture of host whole blood transcriptional response to malaria infection

city: Raleigh

first: Youssef

last: Idaghdour

state: NC

address: Gardner Hall NCSU Campus

department: Genetics

institute: NCSU

summary: Analysis of the effect of malaria infection on whole blood gene expression and uncovering regulatory effects using eQTL analysis. Testing for relashionships between genotype, expression and malaria phenotypes.

overall_design: We generated whole blood gene expression profiles and genotypes from 155 West-African children including 94 cases undergoing the symptomatic phase of blood-stage Plasmodium falciparum infection and 61 age-matched controls. PCA, analysis of covariance and eQTL analysis were performed on the data.

first: Philip

last: Awadalla


title: Profiling study of B cells from lymph nodes in miR-146a over-expression transgenic mice

status: Public on Aug 08 2012

city: CHONGQING

first: qiuye

last: guo

address: GAO TAN YAN

country: China

institute: The military medical university

summary: B cells were isolated from wild type and miR-146a transgenic mice, and analyzed using microarray assay.WT1 and WT2 were samples repeats, so were TG1 and TG2 .

overall_design: Each probe ID of a mouse transcript was ranked by fold change from up to down-regulated comparing to WT control. Sylamer miRNA seed enrichment analysis was performed with Markov correction as described (Nature Method 2008). WT vs. TG.

first: Qiuye

last: Guo

first: Jinjun

last: Zhang

first: Jingyi

last: Li

first: Gang

last: Chen

first: Qingzhu

last: Jia

first: Ying

last: Wan

first: Yuzhang

last: Wu


title: Expression data from WT (Columbia) and pifq (pif1pif3pif4pif5) mutant Arabidopsis seedlings

status: Public on Aug 02 2012

city: Albany

first: james

middle: m

last: tepperman

state: CA

address: 800 Buchanan St.

department: Plant and Microbial Biology

institute: Plant Gene Expression Center/UC Berkeley

summary: Plants respond to changes in the red:far red ratio (R:FR) of incident light. A reduction in this ratio (increase in FR) results in the Shade Avoidance Response (SAR) with associated changes in gene expression. The Phyotchrome-Interacting Factors (PIFs) are bHLH transcription factors known to be involved in the SAR. An analysis of changes in gene expression in WT and quadruple pif1pif3pif4pif5 (pifq; Leivar et al., 2008 (PMID 19920208)) mutant seedlings in response to  an increase in FR should identify primary targets of PIF signaling.

overall_design: We used microarrays to examine the SAR in WT (Columbia) and pifq mutant Arabidopsis seedlings. Arabidopsis WT and pifq mutant seeds were plated on GM medium without sucrose at room temperature. During this procedure, the seeds were routinely exposed to white light (WL) for a total of 1.5 hours after imbibition. Seeds were then stratified for 5 days at 4ºC in darkness, and then grown in WL (19 umol/m2/s, R/FR ratio of 6.48) for 2 days at 21°C (WL0 samples). Two-day-old WL-grown seedlings were then maintained in the same fluence rate of WL supplemented with far-red light (WL-FR, R/FR ratio of 0.006) for 1 (FR1), 3 (FR3) or 24 (FR24) hours before harvesting. Control seedlings were also maintained in parallel in the same fluence rate of WL for 24h (WL24) before harvesting. Three different biological replicates of each treatment were grown separately and extracted, processed, and analyzed independently.

first: Pablo

last: Leivar

first: James

last: Tepperman

first: Peter

last: Quail


title: Growth factor influence on the gene expression profile of human meibomian gland epithelial cells

status: Public on Jul 31 2012

city: Boston

first: David

last: Sullivan

state: MA

address: 20 Staniford Street

institute: Schepens Eye Research Institute

summary: Analysis of growth factor influence on immortalized human meibomian gland epithelial cells at gene expression level. Growth factors play a critical role in the proliferation and differentiation of sebaceous gland epithelial cells. Given that the meibomian gland is a large sebaceous gland, we hypothesize that growth factors exert analogous effects on human meibomian gland epithelial cells. Results provide important information of the response of human meibomian gland epithelial cells to epidermal growth factor (EGF), bovine pituitary extract (BPE), and both, such as up- or down- regulated genes involved in lipid metabolic process and cell cycle.

overall_design: Human meibomian gland epithelial cells were immortalized in our lab with a retrovirus containing telomerase reverse transcriptase (hTERT). hTERT immortalized cells (3 wells /condition / experiment) were seeded onto 6-well plates at the density of 3.76×104cells /well in SFM basal medium, SFM basal medium with epidermal growth factor (EGF; 5 ng/ml), SFM basal medium with bovine pituitary extract (BPE; 50 µg/ml), and SFM basal medium with 5ng/ml EGF plus 50 µg/ml  BPE (KGM). Total RNA was extracted from cultures in  SFM basal medium at day 2, and from cultures in SFM basal medium with BPE, basal medium with EGF, and SFM basal medium with EGF plus BPE at day 7.

first: Shaohui

last: Liu

first: Stephen

last: Richards


title: Identification of translationally deregulated proteins during inflammation

status: Public on Aug 01 2012

city: Frankfurt

first: Tobias

last: Schmid

address: Theodor-Stern-Kai 7

institute: Goethe-University Frankfurt

summary: The regulation of translation is crucial for cells to rapidly adapt to changing conditions. Although the transcriptional changes under inflammatory conditions are intensely studied, not much is known about translational changes. Therefore, this study aimed at identifying translationally deregulated targets in inflammatory settings.

overall_design: MCF-7 cells were treated for 4h with the supernatants of U937 monocytes or TPA-activated U937 monocyte-derived macrophages and subjected to polysomal fractionation using sucrose gradients. Total RNA was collected simultaneously.

first: Daniela

last: Rübsamen

first: Claudia

last: Döring

first: Martin-Leo

last: Hansmann

first: Bernhard

last: Brüne


title: Transient transfection of C28/I2 chondrocytes; the human EST DA125942 (CISTR-ACT's lncRNA) was overexpressed and siRNA-depleted

status: Public on Aug 07 2012

first: Philipp

middle: G

last: Maass

address: Robert-Rössle-Strasse 10

institute: Max Delbrück Center for Molecular Medicine

summary: The overexpression and depletion of DA125942 led to the dysregulation of essential mesenchymal and pre-chondrogenesis genes, transcripton factors and chromatin remodeling factors

overall_design: 3 replicates of each condition

first: H

last: Schulz

first: Ph


title: In vitro responses of fibroblasts from patients with TBK1 deficiency after TLR3 dependent and independent stimuli

status: Public on Jul 30 2012

city: Molndal

first: Elisabeth

last: Israelsson

address: Pepparedsleden 1

department: Translational Biology

country: Sweden

institute: AstraZeneca, IMED RIA

summary: We report here two unrelated HSE patients carrying different heterozygous mutations (D50A and G159A) in TBK1, the gene encoding TANK-binding kinase 1, a kinase at the crossroads of multiple IFN-inducing signaling pathways. Both mutant TBK1 alleles are loss-of-function, but through different mechanisms: protein instability (D50A) or a loss of kinase activity (G159A). Both are also associated with an autosomal dominant (AD) trait, but by different mechanisms: haplotype-insufficiency (D50A) or negative dominance (G159A). A defect in poly(I:C)-induced TLR3 responses can be detected in fibroblasts heterozygous for G159A, but not for D50A TBK1.

overall_design: Skin fibroblast cell lines were derived from healthy controls (n=3), patients with deficiencies for TBK1 (n=2),  TLR3 (n=2), STAT1 (n=1) and cultured for 2 or 8 hours in the presence of IFNa (105 IU/ml), IL1b (20ng/ml), or poly I:C (25ug/ml) or left unstimulated for the same length of time.

first: Melina

last: Herman

first: Michael

last: Ciancanelli

first: Yi-Hung

last: Ou

first: Lazaro

last: Lorenzo

first: Maja

last: Klaudel-Dreszler

first: Elodie

last: Pauwels

first: Vanessa

last: Sancho-Shimizu

first: Rebeca

last: Pérez de Diego

first: Avinash

last: Abhyankar

first: Yiqi

last: Guo

first: Annabelle

last: Cardon

first: Flore

last: Rozenberg

first: Pierre

last: Lebon

first: Marc

last: Tardieu

first: Edyta

last: Heropolitańska-Pliszka

first: Damien

last: Chaussabel

last: White

first: Laurent

last: Abel

first: Shen-Ying

last: Zhang

first: Jean-Laurent

last: Casanova


title: Differential Gene Expression in Patients with Mood Disorders

status: Public on Jul 26 2012

city: Oklahoma City

first: Bart

last: Frank

state: OK

institute: OMRF

summary: RNA was extracted from peripheral blood mononuclear cells (PBMC) of 24 adult healthy controls, 8 adult patients with bipolar disorder, and 21 adult patients with major depressive disorder to analyze gene expression patterns that identify biomarkers of disease and that may be correlated with fMRI data.

overall_design: Following reduction of globin transcripts, RNA from PBMC was labeled and hybridized to Illumina HT-12 v4 microarrays. Samples are designated with a unique number that is preceded by HC for healthy controls, BD for bipolar disorder, or MDD for major depressive disorder.

first: Jonathan

last: Savitz

first: Melissa

last: Bebak

first: Julie

last: Marino

first: T

last: Teague

first: Wayne

last: Drevets


title: Effects of breaking up prolonged sitting on skeletal muscle gene expression

status: Public on Jul 25 2012

city: Melbourne

first: Celine

last: Latouche

state: VICTORIA

address: 75 Commercial Road

institute: Baker IDI Heart and Diabetes Institute

summary:
Breaking up prolonged sitting has been shown to be beneficially associated with cardio-metabolic risk markers in both observational and intervention studies. We aimed to define the acute transcriptional events induced in skeletal muscle by breaks in sedentary time.
Overweight/obese adults participated in a randomized three-period, three-treatment cross-over trial in an acute setting (5 hours): seated position with no activity, seated with 2-minute bouts of light- or moderate-intensity treadmill walking every 20 minutes. Vastus lateralis biopsies were obtained in 8 of the 19 participants after each treatment and gene expression examined using microarrays validated with real-time qPCR.

overall_design: Total RNA was extracted from vastus lateralis at the 3 different experimental condition

first: Jeremy

middle: B

last: Jowett


title: Transducin-like enhancer protein 1 mediates estrogen receptor binding and transcriptional activity in breast cancer cells

status: Public on Jul 24 2012

city: Cambridge

first: Roslin

last: Russell

address: Robinson Way

institute: Cambridge Research Institute, Cancer Research UK

overall_design: TLE1 silenced breast cancer MCF-7 cell lines or control siRNA in the presence of Estrogen or a vehicle. MCF-7 cells were hormone-depleted for 3 d and treated with 100 nM estrogen (or vehicle) for 6 h. There were six biological replicates for each of the four different groups.

first: Kelly

last: Holmes

first: Jason

last: Carroll


title: Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines

status: Public on Aug 15 2012

first: Luce

last: Dauphinot

address: 47 boulevard de l'hôpital

institute: INSERM U1127-CNRS UMR7225-UPMC

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

overall_design: Refer to individual Series


title: Molecular events during the early stage of callus induction

status: Public on Jul 23 2012

city: beijing

first: Chongyi

last: XU

state: beijing

address: No.20 Nanxincun, Xiangshan

department: Center for signal transdution & metabolomics

institute: Institute of Botany, the Chinese Academy of Sciences

summary: Profiling the transcriptome of the early stage of Arabidopsis callus induction

overall_design:
variable_1 = root explants
variable_2 = aerial organ explants
variable_3 = 0 h on callus inducing medium
variable_4 = 12 h on callus inducing medium
variable_5 = 24 h on callus inducing medium
variable_6 = 48 h on callus inducing medium
variable_7 = 96 h on callus inducing medium

last: Xu

first: Ke

first: Mingzhu

last: Fan

first: Yuxin

last: Hu


title: Regulatory T cell (T reg)  function in HIV exposed seronegative (ESN) individuals

status: Public on Jul 19 2012

city: Seattle

first: Laura

last: Pattacini

state: WA

address: 1100 Fairview Ave N

department: VIDD

institute: Fred Hutchinson Cancer Research Center

summary: T reg frequency, activation and function was studied in ESN individuals. Between the subjects with a HIV-specific T cell response, we identified two groups, one, where the T regs were able to suppress T cell proliferation and one where they lacked this capability. Sorted T regs from this two groups were analysed for their expression pattern.

overall_design: Nineteen samples with CD4+ T cell response were identified, in 11 of which Tregs were unable to suppress. Due to a low number of sorted cells, samples were run only one time.

first: Jeffrey

middle: J

last: Delrow

first: M

last: McElrath

first: Jared

last: Baeten

first: Jennifer

last: Lund


title: Role of Apollon in human melanoma resistance to anti-tumor agents that activate the intrinsic or the extrinsic apoptosis pathways

status: Public on Jul 11 2012

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

country: Italy

institute: IRCSS Istituto Nazionale Tumori

summary: PURPOSE: To assess the role of Apollon in melanoma resistance to intrinsic and extrinsic pathways of apoptosis and to identify strategies to reduce its expression.    EXPERIMENTAL DESIGN: Expression of Apollon was assessed in melanoma cell lines and in surgical specimens.Gene expression profiling, mitochondrial depolarization, caspases activation and apoptosis assays were used to test the effect of Apollon silencing, by siRNA, on melanoma response to different anti-tumor agents. Levels of expression of Apollon and melanoma apoptosis were assessed after tumor treatment with the combination of MEK- and mTOR- inhibitors, or of anti-HLA class II mAbs and anti-tumor agents.    RESULTS: Melanoma cells constitutively expressed Apollon, in-vitro and in-vivo. Extent of melanoma apoptosis correlated significantly with Apollon downmodulation upon treatment with a MEK inhibitor, a BRAFV600E-specific inhibitor or the nitrosourea fotemustine. Apollon silencing enhanced melanoma apoptosis in response to the cytotoxic drugs camptothecin, celecoxib, fotemustine and temozolomide, to MEK- and BRAFV600E-specific inhibitors, and to soluble or membrane-bound TRAIL. Mechanistically, Apollon silencing in melanoma cells promoted mitochondrial depolarization, caspase-2, -8, -9 and -3 activation and alteration in the expression of genes related to different cellular functions in response to different anti-tumor agents. Treatment of melanoma cells with combination of MEK and of mTOR inhibitors, or of HLA class II antigen-specific mAb and anti-tumor agents, promoted Apollon downmodulation, associated with enhanced apoptotic responses.    CONCLUSIONS: The results suggest that Apollon is a relevant molecule in melanoma resistance to apoptosis, and that strategies aimed at downmodulating Apollon protein may improve melanoma cell death in response to anti-tumor agents that trigger the intrinsic or the extrinsic apoptosis pathways.

overall_design: The human melanoma cell line Me23682 was established in our laboratory from a surgical specimen. Cells were routinely maintained in RPMI medium 1640 (Lonza, Basel, Switzerland) supplemented with 10% FBS (Lonza) and 2 mM glutamine (Lonza). Cells were maintained at 37°C in a water-saturated atmosphere of 5% CO2 in air. 3x106 cells were seeded in 10 cm dishes; after 24 hours, cells were transfected with Apollon-specific siRNA or its unrelated control (Stealth RNAi siRNA, Invitrogen Life Technologies, Camarillo, CA) at a final concentration of 75 nmol/L and then left untreated or  treated with fotemustine (Muphoran, Italfarmaco, Milan, Italy) at 150 umol/L for 6 hours, or with  the BRAFV600E-specific inhibitor PLX4720 (Selleck Chemicals, Houston, TX) at 500 nmol/L for 8 hours, or with  the MEK inhibitor PD0325901 (Cayman Chemicals, Ann Arbor, MI) at 5 nmol/L for 8 hours. Each treatment or combination was performed in triplicate. At the end of treatment, cells were collected and RNA extracted.

first: L

first: A

last: Anichini


title: Transcriptome profiles of mouse and human monocyte and dendritic cell subsets (human data)

status: Public on Jul 12 2012

city: Singapore

first: Pavandip Singh

last: Wasan

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

department: Bioinformatics

country: Singapore

institute: Singapore Immunology Network

summary: Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized.  Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity.  Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive.  We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs.  Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets.  The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs.

overall_design: Gene expression analysis using total RNA from specific human and mouse monocyte and dendritic cell subsets purified by FACS.

first: Florent

last: Ginhoux

first: Michael

last: Poidinger

first: Pavandip

first: Muzlifah

last: Haniffa

first: Matthew

last: Collin


title: Independence of Repressive Histone Marks and Chromatin Compaction during Senescent Heterochromatic Layer Formation (mRNA)

status: Public on Jul 09 2012

first: Rafik

last: Salama

address: Li Ka Shing Centre, Robinson Way

institute: Cancer Research UK

summary: The expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into non-overlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of pre-senescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events.

overall_design: mRNA expression profiles were compared between normal growing (control) and Ras-induced senescent IMR90 cells. Each includes 5 biological replicates.

first: Masashi

last: Narita


title: Feed-forward Inhibition of Androgen Receptor Activity by Glucocorticoid Action in Human Adipocytes

status: Public on Jul 13 2012

city: Houston

first: Scott

middle: Andrew

last: Ochsner

state: TX

address: One Baylor Plaza

department: Molecular and Cellular Biology

institute: Baylor College of Medicine

summary: We compared transcriptomes of terminally differentiated mouse 3T3-L1 adipocytes [Series GSE14004] and human adipocytes to identify cell-specific differences.  Gene expression and high content analysis (HCA) data identified the androgen receptor (AR) as both expressed and functional, exclusively during early human adipocyte differentiation.  We used HCA to determine mechanisms of AR regulation and activity in human adipocytes.  We found that AR is regulated in a feed-forward fashion by glucocorticoids.

overall_design: Total RNA isolated from human subcutaneous preadipocytes differentiated for up to 14 days.

first: Sean

last: Hartig

middle: A


title: Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming

city: Brussels

first: Geert

middle: A.

last: Martens

address: Laarbeeklaan 103

department: Diabetes Research Center

country: Belgium

institute: Vrije Universiteit Brussel

summary:
Aims/hypothesis: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it.
Methods: The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was measured employing genome wide mRNA profiling. By modulation of the Delta-Notch signaling or addition of pancreatic endocrine transcription factors Myt1, MafA and Pdx1 we intended to improve the reprogramming.
Results: Ngn3 stimulates duct cells to express a focused set of genes that are abundant in islet endocrine cells and/or neural tissues. This neuro-endocrine shift, however, covers a minor fraction (5%) of the estimated genome-wide transcriptome difference between duct and islet endocrine cells. Interestingly, transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto-activation of this gene. Furthermore, pancreatic endocrine reprogramming of human duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1.
Conclusions/interpretation: The results provide further insight into the plasticity of adult human duct cells and suggest measurable routes to enhance Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy in diabetes.
We used Affymetrix HG133A and HG133B to get a comprehensive view on the reprogramming potential in vitro of human pancreatic duct cell cultures (n=3-4) at 3 and 14/20 days after ectopic adenoviral expression of murine neurogenin 3 as compared to GFP-expressing control vectors.

overall_design: The microarray analysis was performed on 3 independent samples that each contained RNA extracted from a pool of 3 independent donor pancreata. The total number of non-selected donor organs is 9. Transcripts were considered as differentially regulated by Ngn3 when 1.5 fold (LCB, unpaired P < 0.05) up- or down-regulated in AdGFP-Ngn3 versus AdGFP controls, at 3 and/or 14 dpi. Transcripts that showed differential expression between day 3 and day 14 in AdGFP-Ngn3 duct cells but not in AdGFP control cells, were also considered Ngn3-regulated

first: Harry

last: Heimberg


title: Comparison of gene expression profiles in naïve WT and Asc-null bone marrow derived dendritic cells

city: Memphis

first: Geoffrey

last: Neale

address: 262 Danny Thomas Place

department: Hartwell Center

institute: St Jude Childrens Research Hospital

summary: The adaptor protein ASC contributes to innate immunity through the assembly of caspase-1-activating inflammasome complexes. We demonstrate that ASC plays an inflammasome-independent cell-intrinsic role in adaptive immune cells. Asc-/- mice displayed defective antigen presentation by dendritic cells and lymphocyte migration due to impaired Rac-mediated actin polymerization. Genome-wide analysis showed that ASC, but not Nlrp3 or caspase-1, controls mRNA stability and expression of DOCK2, a guanine nucleotide exchange factor that mediates Rac-dependent signaling in immune cells. DOCK2-deficient dendritic cells showed similar defective antigen uptake as Asc-/- cells. Ectopic expression of DOCK2 in ASC-deficient cells restored Rac-mediated actin polymerization, antigen uptake and chemotaxis. Thus, ASC shapes adaptive immunity independently of inflammasomes by modulating DOCK2-dependent Rac activation and F-actin polymerization in dendritic cells and lymphocytes.

overall_design: Three replicates of naïve WT and three replicates of Asc-/- bone marrow derived dendritic cells were analyzed on the Affymetrix HT MG-430 PM plate array.

first: Sirish

last: Ippagunta

first: R

last: Malireddi

first: Patrick

last: Shaw

first: Thirumala-Devi

last: Kanneganti


title: Translational control: a new dimension in the regulation of Arabidopsis photomorphogenesis

city: Taipei

first: Ming-Jung

last: Liu

address: 128 Sec. 2, Academia Rd, Nankang

country: Taiwan

institute: Academia sinica

summary: The environmental “light” plays a vital role in regulating the plant growth and development. Transcriptomic profilings were widely used to examine how light regulates the changes of mRNA populations at a genome-wide scale. However, it remains unclear if translational regulation represents a new dimension of gene expression regulation in response to the light signal. Through a transcriptomic comparison of steady-state and polysome-bound mRNAs, we revealed an increased translational efficiency in de-etiolating Arabidopsis seedlings. Over 3,500 genes are subjected to translational regulation whereas only about 770 genes have increased mRNA abundances in response to the light signal. This result suggests a stronger impact of translational control over transcriptomic changes during photomorphogenesis. Genes encoding ribosomal protein are preferentially regulated at the translational level, possibly contributing to the enhancement of translation efficiency as observed. We also uncovered mRNAs regulated at the translational level share characteristics of longer half-lives and shorter cDNA length. The presence of a cis-element, TAGGGTTT, in the 5’untranslated region of a transcript renders its translational regulation by light signals. Taken together, our study revealed a previously neglected aspect of gene expression regulation during Arabidopsis photomorphogenesis. The identities and molecular signatures associated with mRNAs regulated at the translational level also offer new directions to perform mechanistic studies of light-trigged translational enhancement in Arabidopsis.

overall_design: Three biological replicates for 4-d-old etiolated seedlings with or without 0. 5 h or 4 h of white-light treatment.

first: Shu-Hsing

last: Wu


title: Transcriptome Profiling following Neuronal and Glial Expression of ALS-linked SOD1 in Drosophila

status: Public on Jul 01 2012

city: Norman

first: Emily

middle: Louise

last: Kumimoto

address: 730 Van Vleet Oval

department: Zoology

institute: University of Oklahoma

summary:
Amyotrophic Lateral Sclerosis (ALS) is generally a late onset neurodegenerative disease.  Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene accounts for approximately 20% of familial ALS and 2% of all ALS cases.  Although a number of hypothesis have been proposed to explain mutant SOD1 toxicity, the molecular mechanisms of the disease remain unclear.  SOD1 linked ALS is thought to function in a non-cell autonomous manner such that the motoneurons are critical for the onset and glia contribute to the progress of the disease.  To dissect the roles of motoneurons and glia, we used the Gal4-UAS system to determine gene expression changes following the expression of mutant human SOD1 (G85R) selectively in either motoneurons or glia, and concurrently in motoneurons and glia of flies.  We conducted a microarray on young (5 days old) and old (45 days old) flies expressing G85R in these cell types and identified a number of genes involved in a variety of processes.  The candidate genes identified by this screen may help elucidate the individual and combined contributions of motoneurons and glial cells in ALS.
We used microarrays to evaluate the transcriptional profile of 5 day old and 45 day old flies expressing mutant human SOD1 (G85R) in a tissue specific manner in motoneurons, glia, and together in motoneurons and glia and compared the expression to flies expressing wild-type drosophila SOD1 controls.

overall_design: The Gal4-UAS system was used to drive tissue expression of either mutant human SOD1 (G85R) or wild-type drosophila SOD1 (dSOD1) in flies.  Flies containing either the motoneuronal driver, D42-Gal4, the glial driver, M1B-Gal4, or the combined motoneuronal and glial drivers, D42+M1B-Gal4 were crossed to flies containing either mutant human SOD1, UAS-G85R, or wild-type drosophila SOD1, UAS-dSOD1, as a control.  Adult male progeny were collected within 24 hours after eclosion and aged to 5 (5d) and 45 (45d) days old.  Groups of 10 flies were maintained in vials of cornmeal agar food and transferred to fresh food every 5-7 days. For each Gal4-UAS line and each age, 3 biological replicates consisting of 40 whole flies were flash frozen in liquid nitrogen and used to isolate total RNA, for a total of 36 samples.

middle: L

first: Bing

last: Zhang


title: Acquired resistance to lapatinib

status: Public on Jun 30 2012

first: Prahlad

last: Ram

state: TEXAS

address: 7435 Fannin St, Unit 950

institute: UT MDACC

summary: These studies are aimed at understanding gene expression chnages in a Her2 positive breast cancer cell line that has developed acquired resistance to lapatinib. Samples include SKBR3 parental and resistant (SKBR3-R) under basal conditions and in response to 0.1 and 1uM lapatinib treatment after 24 hours.

overall_design: Pre-clinical study

first: Kakajan

last: Komurov

first: JT

last: Tseng


title: Genome-wide gene expression patterns comparing various pluripotent stem cells.

city: Minneapolis

first: Nobuaki

last: Kikyo

state: MN

department: Medicine

institute: University of Minnesota

summary: Analysis of gene expression levels of whole transcripts obtained from two WA09 ES cell cultures, two dermal fibroblast cultures, two lines each for L-iPSCs, F-iPSCs and LF-iPSCs.

overall_design: Total RNA obtained from WA09 ESCs, the dermal fibroblasts from which all iPSCs in the microarray study were derived, two F-iPSC clones, two L-iPSC clones and two LF-iPSC clones on day 100-120 were compared.

first: Hiroyuki

last: Hirai


title: Oleic acid-dependent modulation of Nitric Oxide Associated 1 protein levels regulate nitric oxide mediate signaling in plant defense.

city: LEXINGTON

first: Mihir

middle: Kumar

last: Mandal

state: KENTUCKY

address: 201 F Plant science Building

department: Plant Pathology

institute: University of Kentucky

summary:
Oleic acid-dependent modulation of Nitric Oxide Associated 1 protein levels regulate nitric oxide- mediate signaling in plant defense.
Nitric Oxide, Oleic acid, Salicylic acid, Arabidopsis, Defense

overall_design: Wild-type Col-0, mutant genotypes ssi2, ssi2 act1 and ssi2 sid2 with three  biological replicates were analyzed (one array each)

first: Pradeep

last: Kachroo

first: Aardra

middle: K


title: Gene expression in pediatric cALL

city: Halle (Saale)

first: Martin

middle: Sebastian

last: Staege

state: Sachsen-Anhalt

address: Ernst-Grube-Str. 40

department: Universitätsklinik u. Poliklinik für Kinder- u. Jugendmedizin

summary:
Common ALL (cALL) is the most frequent entity of childhood ALL and carries an early pre-B cell phenotype. Expression patterns of 25 pediatric cALL samples were analyzed by use of high-density DNA microarrays HG-U133A.
Leukemic patients’ bone marrow samples were compared to sorted B cells from cord blood of healthy donors expressing CD19 and CD10 surface antigens. Differential gene expression profiling of pediatric cALL versus non-malignant tissues enabled the
identification of aberrantly expressed genes in malignant cells, facilitating discrimination of leukemic from normal cells and possibly revealing specific disease mechanisms.
Principal component analysis clearly distinguished leukemia samples from normal controls. Significance analysis of microarrays revealed 487 genes significantly up-regulated, and 572 down-regulated genes in leukemic cells.
A comparison to previous publications investigating genetically defined subsets of cALL revealed 465 genes previously not associated with cALL.
Interestingly, terminal deoxynucleotidyl-transferase (DNTT) as well as in the context of cALL unknown genes, were found to be the strongest predictive genes for the malignant phenotype signifying the diagnostic value of our approach.

overall_design: RNA was extracted from bone marrow or peripheral blood samples form pediatric cALL patients, leukemia cell lines, and purified fetal B cells and hybridized with Affymetrix HG_U133A microarrays.

first: Stefan

last: Burdach

first: Guenther

middle: H

last: Richter


title: A Daphnane Diterpenoid Isolated from Wikstroemia polyantha induces an inflammatory response and modulates miRNA activity

status: Public on Jun 29 2012

city: Vancouver

first: Victoria

last: Svinti

address: 2350 Health Sciences Mall

country: Canada

institute: University of British Columbia

summary: MicroRNAs (miRNAs) are endogenously expressed single-stranded ~21–23 nucleotide RNAs that inhibit gene expression post-transcriptionally by binding imperfectly to elements usually within the 3′untranslated region (3′UTR) of mRNAs. Small interfering RNAs (siRNAs) mediate site-specific cleavage by binding with perfect complementarity to RNA. Here, a cell-based miRNA reporter system was developed to screen for compounds from marine and plant extracts that inhibit miRNA or siRNA activity. The daphnane diterpenoid genkwanine M (GENK) isolated from the plant Wikstroemia polyantha induces an early inflammatory response and can moderately inhibit miR-122 activity in the liver Huh-7 cell line. GENK does not alter miR-122 levels nor does it directly inhibit siRNA activity in an in vitro cleavage assay. Finally, we demonstrate that GENK can inhibit HCV infection in Huh-7 cells. In summary, the development of the cell-based miRNA sensor system should prove useful in identifying compounds that affect miRNA/siRNA activity.

overall_design: Control (no drug treatment): 1 hour and 4 hour samples, 3 replicates each; Drug-treated: 1 hour and 4 hours samples, 3 replicates each

first: Anthony

last: Khong

first: Roberto

last: Forestieri

first: David

middle: E

last: Williams

first: Brian

middle: O

last: Patrick

first: Andrea

last: Olmstead

last: Schaeffer

first: François

last: Jean

first: Michel

last: Roberge

first: Raymond

last: Andersen

first: Eric

last: Jan


title: Effect of oligomycin on transcript levels in Arabidopsis seedling cultures

status: Public on Jun 28 2012

city: Potsdam-Golm

first: Staffan

last: Persson

address: Am Mühlenberg 1

department: Institute of Molecular Plant Physiology

institute: Max Planck Institute

summary: To understand how an inhibition of the mitochondrial ATP synthase affects transcriptional programming and to identify potential candidates of the signaling machinery involved in ATP synthase deficiency responses, we used oligomycin on seedling liquid cultures. Seedlings were harvested at time points 0, 1 and 4 h after the start of oligomycin and control (EtOH) treatments. Already 1 h after addition of oligomycin a total of 102 genes were more than threefold up-regulated and 14 genes were repressed, with most of them showing persistent changes. After 4 h, 580 additional genes were more than threefold up-regulated, and 152 genes were repressed by oligomycin. Several genes for alternative NAD(P)H dehydrogenases and alternative oxidases (AOX1a, AOX1d and NDA1) were up-regulated early, and additional homologs (NDA2, NDB2, NDB4 and AOX1b) followed 4 h after the start of treatment. Several genes for subunits of complex I, complex IV and the ATP synthase were induced whereas hardly any genes encoding enzymes of glycolysis and the TCA cycle changed. Additionally, four of five hallmark genes for oxidative stress were increased by oligomycin. These genes are At2g21640 (UPOX), At1g19020, At1g05340 and At1g57630 and code for proteins of unknown function. Among oxidative stress proteins with known functions, several H2O2-responsive Glutathione-S-transferases and BCS1 (CYTOCHROME BC1 SYNTHESIS) were strongly up-regulated already after 1 h. BCS1 is induced by salicylic acid and independent of other reactive oxygen signaling (ROS) pathways, such as H2O2. The results indicate that several different ROS and defense signaling pathways were induced simultaneously by oligomycin. This is further corroborated by induction of several transcription factors of the WRKY and NAC families, which have been previously implicated in coordinating cellular defense signaling.

overall_design: Three replicates for each treatment including oligomycin and control (EtOH) samples.

first: Daniela

last: Geisler

first: Carola

last: Päpke


title: Depletion of histone deacetylase 3 antagonizes PI3K-mediated tissue overgrowth through the acetylation of histone H4 at lysine 16

status: Public on Jun 20 2012

city: Beijing

first: Wenwen

last: Lv

address: Hai Dian

institute: Tsinghua university

summary:
Histone acetylation is one of the best studied gene modifications and has been shown to be involved in numerous important biological processes. Herein，we demonstrate that Hdac3 regulates both organ and body size through the deacetylation of histone H4 at lysine 16 (H4K16ac). H4K16ac is affected by PI3K signaling cascades. Increasing H4K16ac by the depletion of Hdac3 counteracts PI3K-induced tissue overgrowth and PI3K-mediated alterations in the transcription profile.
Using microarry, we compared the transcriptional profile between flies over-expressing PI3K and flies co-expressing PI3K and Hdac3 dsRNA. The findings provide further insight into the mechanism of PI3K-mediated growth and chromatin remodeling.

overall_design: Total RNA was isolated from Drosophila wing imaginal discs using Trizol reagent and hybridized on Affymetrix microarrays. We performed microarray gene expression profiling from drosophila 3rd wing disc of en-Gal4, PI3K overexpression, HDAC3 RNAi, and PI3K overexpression + Hdac3 RNAi.

first: Wen-Wen

first: Hui-Min

last: Wei

first: Da-Liang

last: Wang

first: Jian-Quan

last: Ni

first: Fang-Lin

last: Sun


title: Comprehensive Genomic Meta-analysis Identifies Intra-Tumoral Stroma as a Predictor of Gastric Cancer Patient Survival

status: Public on Jul 05 2012

first: Wu

last: Yonghui

state: Choose your state

address: 8 College Road

institute: NCCS

summary:
Background and Aims: Gastric adenocarcinoma (gastric cancer, GC) is a major cause of global cancer mortality. Identifying molecular programs contributing to GC patient survival may improve our understanding of GC pathogenesis, highlight new prognostic factors, and reveal novel therapeutic targets. We aimed to produce a comprehensive inventory of gene expression programs expressed in primary GCs, and to identify those expression programs significantly associated with patient survival.
Methods: Using a network modeling approach, we performed a large scale meta-analysis of GC transcriptome data integrating 940 gastric transcriptomes from multiple independent patient cohorts. We analyzed a training set of 428 GCs and 163 non neoplastic gastric mucosa (‘non-malignants’), and a validation set of 288 GCs and 61 non-malignants.
Results: We identified 178 gene expression programs (modules) expressed in primary GCs, which were associated with distinct biological processes, chromosomal location patterns, cis-regulatory motifs, and clinicopathological parameters. Amongst these modules, expression of a TGF-B-signaling associated “super-module” of stroma-related genes consistently predicted patient survival in multiple GC validation cohorts. Analysis of histopathological tissue sections from gastrectomy specimens revealed that expression of this stromal module was associated with the proportion of intra-tumoral stroma (ITS). Further supporting the stromal module expression/ITS association, we found that the ITS proportion, measured directly from tissue sections, also predicted GC patient survival.
Conclusion: Stromal gene expression predicts GC patient survival in multiple independent cohorts and may be closely related to the ITS proportion, a specific morphological GC phenotype. These findings suggest that therapeutic approaches targeting pathways associated with the GC stroma may merit evaluation.

overall_design:
Profiling of 86 gastric samples (83 tumors and 3 non-malignants) on Affymetrix GeneChip U133A Array. All samples were collected with approvals from National Cancer Centre of Singapore.
Profiling of 34 gastric  tumors on Custom cDNA Microarray(30K). All samples were collected with approvals from VU University Medical Centre, Amsterdam, The Netherlands.
Profiling of 65 gastric samples (29 tumors and 36 non-malignants) on Affymetrix GeneChip Human Genome U133 set Array. All samples were collected with approvals from Leeds Institute for Molecular Medicine, St James’s University Hospital, Leeds, United Kingdom.

first: Yonghui

last: Wu

first: Patrick

last: Tan

first: Heike

last: Grabsch


title: Gene expression analysis of molecules with known function in HLA class II antigen processing and presentation in hematopoietic and (cytokine pre-treated) non-hematopoietic cells.

status: Public on Jun 19 2012

city: Leiden

first: Marieke

last: Griffioen

address: Albinusdreef 2

department: Hematology

country: Netherlands

institute: Leiden University Medical Center

summary: Gene expression analysis of molecules with known function in HLA class II antigen processing and presentation. Various hematopoietic cell types and (cytokine pre-treated) non-hematopoietic cells that are targeted in Graft-versus-Leukemia reactivity and Graft-versus-Host Disease were collected. Expression was compared between the different hematopoietic and non-hematopoietic cell types for the Invariant chain, HLA-DMA, HLA-DMB, HLA-DOA and HLA-DOB genes. The data show that the Invariant chain, HLA-DMA, HLA-DMB and HLA-DOA genes are expressed in all or the majority of cell types with HLA class II surface expression, whereas expression of the HLA-DOB gene is restricted to professional antigen presenting B-cells and mature dendritic cells.

overall_design: Total RNA was isolated from various hematopoietic cell types isolated (and cultured) from (G-CSF mobilized) peripheral blood from five different individuals and from (IFN-g pre-treated) fibroblasts cultured from skin biopsies from four different patients transplanted with allogeneic hematopoietic stem cells.

first: Anita

middle: N

last: Kremer


title: miR-200c is Aberrantly Expressed in Leiomyomas in Ethnic-Dependent Manner and Targets ZEBs, VEGFA, TIMP2 and FBLN5

status: Public on Jun 21 2012

city: Torrance

first: Tsai-Der

last: Chuang

address: 1124 WEST CARSON STREET

department: OB-GYN

institute: LA Biomed at UCLA medical center

summary: mircoRNA-200c (miR-200c) through repression of specific target genes has been associated with cellular transition, tumorigenesis and tissue fibrosis. We explored the expression and functional aspects of miR-200c in genesis of leiomyomas, benign uterine tumors with fibrotic characteristic. Gain-of function of miR-200c in isolated leiomyoma and myometrial smooth muscle cells (LSMC and MSMC) and leiomyosarcoma cell line (SKLM-S1) repressed ZEB1/ZEB2 mRNAs and proteins, with concurrent increase in E-cadherin (CDH1) and reduction in vimentin expression, phenotypic alteration and inhibition of MSMC and LSMC proliferation. We further validated TIMP2, FBLN5 and VEGFA as direct targets of miR-200c through interaction with their respective 3’UTRs, and other genes as determined by microarray analysis.

overall_design: Total RNA isolated from MSMC and LSMC following gain-of function of miR-200c was subjected to gene expression profiling using HumanHT-12 v4 Expression BeadChip (Illumina, Inc. San Diego, CA) consists of 47,000 oligonucleotide probe sets representing 28,688 transcripts.

first: Harekrushna

last: Panda

first: Xiaoping

last: Luo

first: Nasser

last: Chegini


title: The response and recovery of Arabidopsis thaliana transcriptome to phosphate starvation

status: Public on Jun 18 2012

city: No.12 Zhongguancun South Street, Haidian

first: Jun

last: Liu

state: Beijing

address: 1230 York Avenue

department: Chinese Academy of Agricultural Sciences

institute: Institute of Crop Science

type: Expression profiling by genome tiling array

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

overall_design: Refer to individual Series


title: The response and recovery of Arabidopsis thaliana transcriptome to phosphate starvation [ATH1-121501]

summary: Background: Over application of phosphate fertilizers in modern agriculture contaminates waterways and disrupts natural ecosystems. Nevertheless, this is a common practice among farmers, especially in developing countries as abundant fertilizers are believed to boost crop yields. The study of plant phosphate metabolism and its underlying genetic pathways is key to discovering methods of efficient fertilizer usage. The work presented here describes the first genome-wide resource on the molecular dynamics underpinning the response and recovery in roots and shoots of Arabidopsis thaliana to phosphate-starvation.   Results: Genome-wide profiling revealed minimal overlap between root and shoot transcriptomes suggesting two independent phosphate-starvation regulons. Novel gene expression patterns were detected for over 1000 candidates and were classified as either initial, persistent, or latent responders. Comparative analysis to AtGenExpress identified novel cohorts of genes co-regulated across multiple stimuli. The hormone ABA displayed a dominant role in regulating many phosphate-responsive candidates. Analysis of co-regulation enabled the determination of primary versus redundant members of closely related gene families with respect to phosphate-starvation. Thus, among others, we show that PHO1 acts in shoot, whereas PHO1;H1 is likely the primary regulator in root.   Conclusion: Our results uncover a much larger, staged responses to phosphate-starvation than previously described.  To our knowledge, this work describes the highest resolution of genome-wide data on plant nutrient stress to date.

overall_design: 6 Sample types, 3 replicates each

first: Nam-Hai

last: Chua

first: Jongchan

last: Woo

first: Cameron

middle: R

last: MacPherson

first: Huan

first: Takatoshi

last: Kiba

first: Matthew

last: Hannah

first: Xiu-Jie

first: Vladimir

last: Bajic


title: ATXN2-CAG42 sequesters PABPC1 into insolubility and induces FBXW8 in cerebellum of old ataxic knock-in mice

status: Public on Jul 25 2012

city: Tuebingen

first: Michael

middle: H.

last: Walter

address: Calwer Str. 7

department: Department of Medical Genetics

institute: University of Tuebingen

summary: Spinocerebellar Ataxia Type 2 (SCA2) is caused by expansion of a polyglutamine encoding triplet repeat in the human ATXN2 gene beyond (CAG)31. This is thought to mediate toxic gain-of-function by protein aggregation, and affect RNA processing, resulting in degenerative processes affecting preferentially cerebellar neurons. As a faithful animal model, we generated a knock-in mouse replacing the single CAG of murine Atxn2 with CAG42, a frequent patient genotype. This expansion size was inherited stably. The mice showed phenotypes with reduced weight and later motor incoordination. Although brain Atxn2 mRNA became elevated, soluble ATXN2 protein levels diminished over time, which might explain partial loss-of-function effects. Deficits in soluble ATXN2 protein correlated with the appearance of insoluble ATXN2, a progressive feature in cerebellum possibly reflecting toxic gains-of-function. Since in vitro ATXN2 overexpression was known to reduce levels of its protein interactor PABPC1, we studied expansion effects on PABPC1. In cortex, PABPC1 transcript, soluble and insoluble protein levels were increased. In more vulnerable cerebellum the progressive insolubility of PABPC1 was accompanied by decreased soluble protein levels, with PABPC1 mRNA showing no compensatory increase. The sequestration of PABPC1 into insolubility by ATXN2 function gains was validated in human cell culture. To understand consequences on mRNA processing, transcriptome profiles at medium and old age in three different tissues were studied and demonstrated selective induction of Fbxw8 in old cerebellum. Fbxw8 is encoded next to the Atxn2 locus and was shown in vitro to decrease the level of expanded insoluble ATXN2 protein. In conclusion, our data support the concept that expanded ATXN2 undergoes progressive insolubility and affects PABPC1 by a toxic gain-of-function mechanism with tissue-specific effects, which may be partially alleviated by the induction of FBXW8.

overall_design: Factorial design comparing Atxn2 knock-in mice with wild type littermates in three different tissues (brainstem, cerebellum, liver)

first: Ewa

last: Damrath

first: Melanie

last: Heck

first: Suzana

last: Gispert

first: Joachim

last: Nowock

first: Carola

last: Seifried

first: Udo

last: Rüb

first: Georg

last: Auburger


title: Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma

city: Lund

first: David

last: Lindgren

address: Building 404 A3, Scheelevägen 2, Medicon Village

department: Dept of Laboratory Medicine

institute: Lund University

type: Genome variation profiling by genome tiling array


title: PRMT1 interacts with leukemia fusion protein AML1-ETO for activation of transcription and transformation

city: La Jolla

first: Dong-Er

last: Zhang

address: 3855 Health Sciences Drive, Mail Stop 0815

department: Cancer Center

institute: University of California San Diego

summary: Fusion protein AML1-ETO resulted from t(8;21) translocation is highly related to leukemia development. We have previously shown that the expression of AE9a, a spliced form of AML1-ETO, can rapidly cause leukemia in mouse. To understand how AML1-ETO is involved in leukemia development, we used AE9a leukemia model to identify a novel AE9a interacting proteins PRMT1 (protein arginine methyltransferase 1) from primary leukemic cells expressing AE9a. To examine whether PRMT1 is involved in AE9a-mediated transcription regulation, genome wide gene expression analysis is carried out in hematopoietic cell line K562 (wild type or AE9a expressing) treated with (-) control siRNA or siPRMT1.

overall_design: Wild type or AE9a-expressing K562 cells with control siRNA or siPRMT1 in triplicate

first: Wei-Jong

last: Shia

first: Akiko

last: Okumura

first: Ming

last: Yan

first: Ali

last: Sarkeshik

first: Miao-Chia

last: Lo

first: Shinobu

last: Matsuura

first: Xinyang

last: Zhao

first: Stephen

middle: D

last: Nimer

first: John

last: Yates III


title: VIA of EM CD8 T cells in vaccinated monkeys

status: Public on Jun 15 2012

city: Cleveland

first: Peter

last: Wilkinson

address: 2103 Cornell Road

department: Pathology / Systems Biology & Bioinformatics

institute: Case Western Reserve University

summary: The goal of an effective AIDS vaccine is to generate immunity that will prevent HIV-1 acquisition.  Despite limited progress towards this goal, renewed optimism has followed the recent success of the RV144 vaccine trial in Thailand.  However, the lack of complete protection in this trial suggests that breakthroughs, where infection occurs despite adequate vaccination, will be a reality for many vaccine candidates.  We previously reported that neutralizing antibodies elicited by DNA prime/rAd5 boost vaccination with SIVmac239 Gag/Pol and Env provided protection against pathogenic SIVsmE660 acquisition after repeated mucosal challenge.  Here, we report that SIV-specific CD8+ T cells elicited by that vaccine lowered both peak and set-point viral loads in macaques that became infected despite vaccination.  These SIV-specific CD8+ T cells showed strong virus inhibitory activity (VIA) and displayed an effector memory (EM) phenotype.  VIA correlated with high levels of CD107a mobilization and perforin expression in SIV-specific CD8+ T cells.  Remarkably, both the frequency and the number of Gag CM9-specific public clonotypes were strongly correlated with VIA mediated by EM CD8+ T cells.  The ability to elicit such virus-specific EM CD8+ T cells might contribute substantially to an efficacious HIV/AIDS vaccine, even after breakthrough infection.

overall_design: Gag CM9-specific EM CD8+ T cells (CD28 low CD95 high tetramer+) from SIV-negative macaques at 12 wks post-DNA/rAd5 immunization were sorted by flow cytometry for microarray studies. RNA samples from strong VIA animals with (n=3) or without (n=6) CM9 peptide stimulation, along with CM9 peptide stimulated samples from weak VIA animals (n=2) were prepared using the Illumina beads station assay and hybridized to the Illumina HumanHT-12 version 4 Expression BeadChip.

first: Takuya

last: Yamamoto

first: Matthew

last: Johnson

last: Price

middle: I

last: Wolinsky

first: Jorge

last: Almeida

first: Constantinos

last: Petrovasa

first: Martha

last: Nason

first: Wendy

middle: W

last: Yeh

first: Ling

last: Shen

first: Mario

last: Roederer

first: Srinivas

middle: S

last: Rao

first: Adrian

middle: B

last: McDermott

first: Francois

last: Lefebvre

first: Gary

last: Nabel

first: Elias

last: Haddad

first: Norman

last: Letvin

first: Daniel

middle: C

last: Douek

first: Richard

last: Koup


title: Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma (gene expression)

first: David

last: Lindgren

summary: Genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma

overall_design: 131 primary bladder cancer tumor samples were analyzed on Illumina gene expression Bead Arrays.

first: Gottfrid

last: Sjodahl

first: Mattias

last: Aine

first: Martin

last: Lauss

last: Hoglund


title: Study of the role of miR-205 in prostate epithelial cells

status: Public on Jun 12 2012

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: Gene expression has been assessed on RWPE-1 cells, derived from normal prostate, upon silencing of miR-205 by an antisense locked nucleic acid.

overall_design: RWPE-1 cells were transfected in triplicate either with 100nM of an antisense locked nucleic acid targeting miR-205 (LNA-205) or a scrambled oligomer (LNA-Scr). Gene expression was assessed 72h after transfection.


title: Phosphorylated and Sumoylation-Deficient Progesterone Receptors Drive Proliferative Gene Signatures During Breast Cancer Progression (Illumina gene expression analysis)

status: Public on Jun 07 2012

first: Todd

middle: P

last: Knutson

address: 117 Pleasant St SE

department: Minnesota Supercomputing Institute

summary: Anlaysis of the differential gene expression between T47D cells expressing wild type (WT) progesterone receptor isoform B (PR) or SUMOylation-deficient PR molecules.

overall_design: Total RNA obtained from T47D breast cancer cells that express either WT PR-B or mutant PR-B (K388R, SUMO-deficient), treated with or without synthetic PR ligand R5020 for 6 h.

first: Flora

last: Fan


title: Effects of Sirt1 manipulation on gene expression in human Caco-2 cell line

city: Newcastle

first: Simon

last: Cockell

address: Framlington Place

institute: Newcastle University

summary: To compare gene expression in human intestinal cell line after Sirt1 manipulation by overexpression or targetted siRNA knockdown

overall_design: Triplicate biological replicates for Caco-2 control and Sirt1 overexpression (6 samples), duplicate biological replicates for Caco-2 control siRNA and two non-overlapping targetted Sirt1 siRNAs (6 samples)

first: Ions

middle: J

last: Laura

last: Swan


title: Lipocalin-2-mediated downregulation of Twist1 reverses the epithelial-mesenchymal transition in hepatocellular carcinoma

status: Public on Jun 01 2012

city: Daejeon

first: Sang-Yeop

last: Lee

address: 125 Gwahangno, Yuseong-gu

institute: KRIBB

summary: Elevated lipocalin-2 (Lcn2) has been observed in multiple human cancers, but its biological roles remain unclear. Our purpose in this study was to investigate whether Lcn2 is involved in hepatocellular carcinoma (HCC) development via its involvement in invasion and metastasis. Using unsupervised hierarchical clustering analysis of tissue samples, we identified preferential expression of Lcn2 (>2-fold change) in the tumor group (differentiated group) versus the non-tumor group (liver cirrhosis group). LCN2 immunoreactivity was positively correlated with TNM stage (r = 0.194, P = 0.020), but not with differentiation or recurrence of HCC. Over-expression of Lcn2 was observed in HLK-2, HKK-2, and HLK-5 HCC cells. Knock-down of Lcn2 by shRNA in HKK-2 cells was correlated with the down-regulation of E-cadherin, CK-8, CK-18, and desmoplakin I/II (DesI/II) and the up-regulation of N-cadherin, vimentin (VIM), and fibronectin (FN), which are markers of the epithelial-mesenchymal transition (EMT) associated with tumor progression. The characteristics of EMT were reversed by adenoviral transduction of Lcn2 into SH-J1 cells. EGF or TGF-β treatment resulted in downregulation of Lcn2 with a concomitant change in EMT. Stable Lcn2 expression in HCC cells reduced the expression of the transcription factor Twist1, resulting in the inhibition of cell proliferation, migration, and invasion in vitro, and suppressed tumor growth and metastatic ability in a mouse model. These findings suggest that Lcn2 can reverse the EMT in HCC through transcriptional suppression of Twist 1. Thus, Lcn2 is a candidate metastasis suppressor and a potential therapeutic target for HCC.

overall_design: Unsupervised hierarchical clustering separated the samples into two main groups: a non-tumor group (NT, n = 40) and a HCC group (HCC, n = 40), and into two subgroups: a liver cirrhosis group (LC, n = 20) and a differentiated HCC group (difHCC, n = 20). Lcn2 was one of the unique genes with a two-fold or greater difference in expression from the mean with P < 0.01 based on the t-test for hierarchical clustering analysis.

first: Yun

last: Wang

first: Goung

last: Yu

first: Mi

first: Pei

last: Hao

first: Hua

last: Li

first: In

last: Chu

first: Sang

middle: Y

first: Sun

last: Leem

first: Dae

middle: G

last: Kim


title: Whole-genome expression data from purified larval Drosophila LNv pacemaker neurons

city: New York

first: Marc

last: Ruben

state: NY

address: 100 Washington Square East

department: Biology

institute: New York University

summary: We generated whole genome expression profiles from a homogeneous population of purified pacemaker neurons (ventral Lateral Neurons, LNvs) from wild type and clock mutant Drosophila. The study identifes a group of genes whose expression is highly enriched in LNvs compared to other neurons; and a second group of genes rhythmically expressed in LNvs in a clock-dependent manner.

overall_design: Drosophila larval brains (L3 stage) were taken from a 12:12hr light entrainment regime and dissected at ZT-3 or ZT-15. Larvae contained either Pdf-Gal4:UAS-GFP transgenes or Pdf-RFP to label the 8 LNvs pacemaker neurons per brain, allowing purification by flow cytometry. Brains were dissociated and LNvs purified by FACS, followed by RNA amplification and hybridization on Affymetrix microarrays.

first: Dogukan

last: Mizrak

first: Drapeau

last: Mark

first: Justin

last: Blau


title: Fry et al Drosophila Ethanol Resistance Selection Experiment

status: Public on Jun 16 2012

city: Johnson City

first: Lev

last: Yampolsky

state: TN

address: ETSU

department: Biological Sciences

institute: East Tennessee State University

summary: Outbred D.melanogaster populations subjected to >300 generations of natural selection on either control, or 12% ethanol, or variable food (2 replicates each) and exposed, as first instar larvae, to either water control or 12% ethanol.

overall_design: Six experimental populations  were established from an outbred base population derived from flies collected in Raleigh, NC, U.S.A. in 1995.  They were selected in either control (R), ethanol (E) or variable (M) selection regimes (2 replicate populations in each) according to the following protocol. Each generation of each population was initiated by allowing 20-30 adults to lay eggs in each of 50 vials containing either standard cornmeal-molasses-agar medium (all the vials in the R populations, and half of the vials in the M populations) or medium supplemented with 12% ethanol (half of the vials in the M populations, and all of the vials in the E populations).  After 14 days, progeny from the different vials are mixed before being used to set up the next generation.  Gene expression experiment conducted after >300 generations of selection as described below.

first: James

last: Fry

first: Galina

middle: V

last: Glazko


title: c-Met regulation of tumor initiation and stemness occurs through CD44s

status: Public on May 31 2012

city: Hershey

first: Penn State

last: COM

state: PA

address: 500 University Drive

department: Genome Sciences Facility

institute: Penn State College of Medicine

summary: c-Met induces tumor initiation and stemness in HCC cells through the regulation of CD44s via AKT signaling. Over-expression of CD44s in c-Met and CD44s negative cells induce both a stemness and mesenchymal phenotype independent of c-Met.

overall_design: The down regulation of CD44s or c-Met was compared to Scrambled control to investigate the effects of CD44s or c-Met on global changes of mesenchymal or stemness markers.

first: Hien

last: Dang

first: Steven

last: Steinway

first: Wei

last: Ding

first: C

last: Rountree


title: Expression data between human degenerative and non-degenerative intervertebral discs

city: Taoyuan

first: Tsung-Ting

last: Tsai

address: No.5 Fushing St., Kweishan Township

department: Department of Orthopaedic Surgery

institute: Chang Gung Memorial Hospital

summary:
Disc Degeneration is a multifactorial disease which cause severe constant chronic pain. The development of disc degeneration could involve both genetic and environmental factors, so it's important to elucidate the difference in gene expression profiles between degenerative and non-degenerative discs from elderly patients and younger patients, respectively.
Affymetrix GeneChip Human Genome U133A Array was used to derive gene expression profiles and identified genes that would express at significantly different levels between degenerative and non-degenerative samples.

overall_design:
Human intervertebral disc tissues were harvested from elderly and younger patients with degenerative disc disease and adolescent idiopathic scoliosis, respectively, for RNA extraction and hybridization on Affymetrix microarrays.
One degenerative sample was compared to one non-degenerative sample in the same microarray run, and comparative analyses were performed in triplicate. Gene whose expression levels varied across the samples with a log ratio >0.5 or <-0.5 were selected as the genes related to disc degeneration.

first: Jong-Hwei

last: Pang