title: Transcriptional profile of human epidermal keratinocytes in response to formaldehyde

first: Minsoo

last: Noh

address: 1 Gwanak-ro, Gwanak-gu

department: Pharmacy

institute: Seoul National University

summary: Formaldehyde exposure could produce a variety of dermatologic problems in humans. In human skin, formaldehyde cause irritant and allergic contact dermatitis. In this study, the genome scale transcriptional response profile of normal human keratinocytes to formaldehyde was investigated.

overall_design: The genome-wide transcriptional profiling analysis was performed in cultured human primary keratinocytes treated with the sub-cytotoxic concentration of formaldehyde in order to investigate the toxicological effect of low level exposure to formaldehyde.  Normal human keratinocytes (NHKs) were stimulated with 200 μM of formaldehyde for 24 hours and harvested for total RNA extraction and hybridization on Affymetrix microarrays.


title: Notch pathway is overexpressed and is a therapeutic target in clear cell renal cancer

status: Public on Apr 19 2016

city: Philadelphia

first: Yi-An

last: Ko

state: Pennsylvania

address: 415 curie blvd

department: Genetics & Gene Regulation

country: USA

institute: UPeenn

summary: We generated a list of Notch target genes in vivo by determining differentially expressed genes in tubules obtained from Pax8rtTA TREICNotch1 mice compared to controls.

overall_design: Mouse kidney tissue from both NICD1 and control littermates were collectred.

first: Tushar

last: Bhagat

first: Yiyu

last: Zou

first: Shizheng

last: Huang

first: Jihwan

last: Park

first: Matthew

last: Palmer

first: Caroline

last: Hu

first: Weijuan

last: Li

first: Niraj

last: Shenoy

first: Orsolya

last: Giricz

first: Yiting

last: Yu

first: Maria

last: Concepcion Izquierdo

first: Ae-Seo-Deok

first: Nishanth

last: Vallumsetla

first: Remi

last: Lawrence

first: Robert

last: Lopez

first: Masako

last: Suzuki

first: James

last: Pullman

first: A

last: Hakimi

first: John

middle: M

last: Greally

first: Bharvin

last: Patel

first: Karim

last: Benhadji

first: Kith

last: Pradhan

first: Amit

last: Verma

first: Katalin

last: Susztak


title: Genome-wide DNA methylation analysis of Romidpesin treated GCC cell lines

status: Public on May 01 2016

city: Düsseldorf

first: Daniel

last: Nettersheim

state: NRW

address: Universitätsstr. 1

department: Urology

country: Germany

institute: University Hospital Düsseldorf

summary: Illumina 450k DNA methylation microarray analysis of TCam-2, 2102EP, NCCIT and JAR cells 16 h after 10 nanomolar Romidepsin application. DMSO treated cells were used as controls. These data are part of the article 'The Histone Deacetylase Inhibitor Romidepsin is a Novel Therapeutic Option for (Cisplatin-resistant) Germ Cell Cancers' (Nettersheim et al., 2016).

overall_design: Genomic DNA was isolated by PCI extraction from TCam-2, 2102EP, NCCIT and JAR 16h after 10 nanomolar Romidepsin treatment. DMSO treated cells served as control.

first: Hubert

last: Schorle


title: Targeting Jak2-Stat5a/b signaling suppresses growth of enzalutamide-resistant prostate cancer in vitro and in vivo

city: PHILADELPHIA

first: Adam

last: Ertel

state: PA

address: 233 S 10TH ST

department: Cancer Biology

institute: Thomas Jefferson University

summary: We used cDNA microarray analysis to identify the Stat5a/b transcriptome in AR-depleted CWR22Pc cells. We sequentially depleted AR protein (AR knockdown) followed by Stat5a/b (Stat5a/b knockdown) using lentiviral shRNA in CWR22Pc cells. CWR22Pc cells were transduced with scramble shRNA (shCtrl), shAR or shStat5a/b at the start of the experiment (day 0), followed by transduction with a second lentiviral shRNA, either shCtrl or shStat5a/b, 3 days later (day 3). CWR22Pc cells were harvested on day 6 for analysis of gene expression profiles.

overall_design: CWR22Pc cells were sequentially transduced three days apart (on days 0 and 3) with 200-250 µl of lentiviral scramble control shRNA (shCtrl), shRNA-AR (shAR) or shRNA-Stat5a/b (shStat5a/b) in the presence of polybrene (1:1000) as follows: 1) shCtrl>shCtrl (control); 2) shAR>shCtrl (AR knockdown alone); 3) shStat5a/b>shCtrl (Stat5a/b knockdown alone); 4) shAR>shStat5a/b (sequential AR knockdown followed by Stat5a/b knockdown). On day 6, cells were harvested, total RNA was isolated from cells in each treatment group as non-pooled triplicates and samples were prepared for cDNA microarray analysis with Affymetrix GeneChip Human Gene 2.0 ST arrays.

first: Marja

middle: T

last: Nevalainen

first: David

last: Hoang

first: Lei

last: Gu

first: Sankar

last: Addya

first: Paolo

last: Fortina


title: Genomics of decitabine responses

status: Public on Apr 30 2016

city: Saint Louis

first: Christopher

middle: A

last: Miller

state: MO

address: 660 S Euclid Ave

department: Oncology

institute: Washington University in St Louis

type: Methylation profiling by genome tiling array

summary: Global DNA methylation was analyzed in total bone marrow cells of AML/MDS patients undergoing decitabine treatment.

overall_design: Patients with AML or MDS were treated with decitabine 20 mg/m2/day on days 1-10. Bone marrow samples were collected on day 0 and day 10. DNA was generated from total bone marrow cells, and analyzed for changes in methylation.

middle: S

last: Welch

first: Allegra

last: Petti


title: Placebo-controlled, randomized clinical trial with repeated liver biopsies: Long-term resveratrol treatment has no clear therapeutic benefit in non-alcoholic fatty liver disease

city: Aarhus

first: Kasper

last: Thorsen

address: Brendstrupgaardsvej

country: Denmark

institute: Aarhus University Hospital

summary:
Resveratrol treatment has shown beneficial effects on experimental models of non-alcoholic liver disease (NAFLD). In this pilot-size, clinical trial we teated the therapeutic potential in NAFLD patients.
We found only limited clinical effect of resveratrol treatment.

overall_design: Prospective, placebo-controlled, randomized clinical trial with two treatment arms: resveratrol 1.5 g daily (RSV) or placebo (Plc) for 6 months. Participants had baseline and end-of-trial biopsies performed.

first: Sara

last: Heebøll

first: Henning

last: Grønbæk


title: Isolated Blood Immune Cell Transcriptomics in COPD

status: Public on Apr 15 2016

city: Gaithersburg

first: Mustimbo

last: Roberts

state: MD

address: One MedImmune Way

institute: MedImmune

summary: We observed separation of COPD patients from control smokers by CD4+ T cell transcriptomics.   In contrast to CD4+ T cells, there were no transcript differences in whole blood, CD8+ T cells or  CD14+ monocytes.

overall_design: We examined transcripts of CD4+ T cells (n=79), CD8+ T cells (n=75) and CD14+ T cells (n=75) isolated from the whole blood of subjects.  The control group were smokers without COPD.  We examined differences between COPD and controls.


title: Negative control and mir-342-3p mimics-transfected RAW264.7 mouse macrophages.

status: Public on Apr 29 2016

city: Debrecen

first: Szilard

last: Poliska

address: Egyetem ter 1.

department: Biochemistry and Molecular Biology

country: Hungary

institute: University of Debrecen

summary:
RAW264.7 mouse macrophages were transfected with negative control and miR-342-3p mimics and subjected to microarray analysis 18 hours after the transfection.
We used microarray to obtain global mRNA expression data of negative control and miR-342-3p mimics-transfected RAW264.7 cells.

overall_design: RAW264.7 mouse macrophages were transfected with negative control and mir-342-3p mimics. The global mRNA expression patterns of negative control and miR-342-3p mimics-transfected RAW264.7 cells were analyzed on Affymetrix microarrays.

first: Zsolt

last: Czimmerer

first: Tamas

last: Varga

first: Mate

last: Kiss

first: Cesaré

middle: O

last: Vázquez

first: Quang

last: Doan-Xuan

first: Dominik

last: Rückerl

first: Sudhir

middle: G

last: Tattikota

first: Zsuzsanna

last: Nagy

first: Bence

last: Daniel

first: Attila

last: Horvath

first: Gergely

first: Eva

last: Varallyay

first: Matthew

middle: N

last: Poy

first: Judith

middle: E

last: Allen

last: Bacso

first: Cei

last: Abreu-Goodger

first: Laszlo


title: Comprehensive DNA methylation and gene expression profiling in differentiating human adipocytes

status: Public on Apr 13 2016

city: Wageningen

first: Myrthe

last: van den Dungen

address: Tuinlaan 5

country: Netherlands

institute: Wageningen University

summary: Genome-wide DNA methylation profiling was performed of human mesenchymal stem cells (hMSCs) differentiating into adipocytes (day 10). The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to measure DNA methylation of hMSC before differentiation (day 0) and of adipocytes at day 10 of differentiation. Our aims were to 1) measure genome-wide DNA methylation changes during adipocyte differentiation in primary hMSCs and 2) investigate the relationship between DNA methylation and gene expression regulation in a panel of 84 adipocyte-related genes.

overall_design: Bisulphite converted DNA from four independent experiments was hybridised to the Illumina Infinium 450k Human Methylation Beadchip. The first comparison was made between undifferentiated hMSCs and differentiated adipocytes at day 10. As a positive control, differentiating cells were continuously exposed to 5-Aza-2′-deoxycytidine (5-aza-dC). The second comparison was made between differentiated adipocytes at day 10 and 5-aza-dC exposed adipocytes at day 10.

middle: W

last: Van den Dungen

first: Albertinka

middle: J

last: Murk

first: Dieuwertje

last: Kok

first: Wilma

last: Steegenga


title: Genome-wide DNA methylation analysis identifies novel hypomethylated non-pericentromeric genes with potential clinical implications in ICF

status: Public on May 02 2016

city: L'Hospitalet del Llobregat

first: Sebastian

last: Moran

state: Barcelona

address: Av. Gran Via de l'Hospitalet, 199-203

department: PEBC

country: Spain

institute: IDIBELL

summary: Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are normally expressed in germ line and silenced in somatic tissues.    In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific clinical biomarkers with the aim to facilitate the identification of ICF patients.

first: Juan

last: Sandoval

first: Manel

last: Esteller


title: Expression data from HK2 proximal tubule cells transduced with shPGC-1alpha compared to cells transduced with control shRNA

status: Public on Apr 22 2016

city: Stanford

first: Amato

last: Giaccia

state: CA

address: 269 Campus Dr, CCSR South Rm 1250

department: Radiation Oncology

institute: Stanford University

summary:
To identify regulation of genes involved in lipid and glycogen metabolism by PGC-1alpha
We used whole genome expression analysis to explore the mechanism of lipid and glycogen accumulation in proximal tubule cells following suppression of PGC-1alpha expression.

overall_design: HK2 proximal tubule cell line were transduced with control (shGFP) or shPGC-1alpha shRNA.  Successfully infected cells were selected with puromycin.  Total cellular RNA was harvested 5 days after transduction, and 24 hours after puromycin selection had been ceased.

first: Edward

middle: L

last: LaGory


title: Etv inactivation effect on embryonic lung development

status: Public on Apr 28 2016

city: Madison

first: Yan

last: Zhang

state: WI

address: 425 Henry Mall Room 5240

department: Genetics

institute: UW-Madison

summary:
ETV4 and ETV5 are FGF-activated transcription factor genes. Inactivation of Etv4 and Etv5 in the lung epithelium led to prolonged branch tip growth and delayed new branch formation.
We used microarrays to detail the global programme of gene expression in embryonic day 13.5 mouse lungs and identified distinct classes of dysregulated genes affect by Etv4;5 epithelial specific knockout.

overall_design: Total mRNA obtained from three samples per group (WT and DKO). Equal mRNA from three samples per group were pooled. Affymetrix microarray transcriptome analysis of Etv4;5 knockout and control embryonic lung (E13.5) was performed and analyzed

first: John

middle: C

last: Herriges

first: Jamie

last: Verheyden

first: Zhen

first: Pengfei

last: Sui

first: Ying

last: Anderson

first: Deborah

last: Swing

first: Mark

last: Lewandoski

first: Xin

last: Sun


title: Gene expression profile of colorectal cancers with microarray

city: Kyoto

first: Masahide

last: Hamaguchi

address: 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku

department: Department of Endocrinology and Metabolism

country: Japan

institute: Kyoto Prefectural University of Medicine, Graduate School of Medical Science

summary: We have found that some tumor infiltrating lymphocytes in colorectal cancer (CRC) tumor expressed low intensity of FOXP3 with flow cytometry assays, resulting in the presence of certain amount of tumor infiltrating FOXP3lo cells in subpopulation of CRC tumor tissues. To clarify different gene expression paterns between CRC tumors with high FOXP3lo cell infiltration and without these cell infilrtraion, we performed microarray analyses with total mRNA extracted from whole tumor tissues with high FOXP3lo cell infiltration (n=2) and low FOXP3lo cell infiltration (n=2). Comparison of gene expression profiles revealed that genes involved in immune responses and inflammation were significantly up-regulated in tumor with high FOXP3lo cell infiltration.

overall_design: Total RNA from tumor tissues with high FOXP3lo cell infiltration (n=2; cOSK109, cOSK111) and low FOXP3lo cell infiltration (n=2; cOSK93, cOSK237) was isolated with RNeasy Mini Kit (Qiagen) and subjected to microarray analysis (Human Gene 2.0 ST Array, Affymetrix). Obtained raw data was normalized by the robust multi-array average algorithm (RMA) (R 2.15). Gene ontology (GO) biology process are described in 15180 genes. T-statistics was calculated by comparing these tumor types..

first: Takuro

last: Saito

first: Hiroyoshi

last: Nishikawa

first: Hisashi

last: Wada

first: Daisuke

last: Sugiyama

first: Masaki

last: Mori

first: Yuichiro

last: Doki

first: Shimon

last: Sakaguchi


title: Effect of APE1 and its acetylation on gene expression profile of lung cancer cells

city: Houston

first: Shiladitya

last: Sengupta

address: 6550 Fannin Street

institute: Houston Methodist Reserach Institute

summary:
APE1 regulates a vast majority of genes by acting as a transcriptional co-activator or as a co-repressor. It is overexpressed in diverse cancer tissues and is associated with their drug resistance. It is essential for cell proliferation. APE1 is post-translationally acetylated by HAT p300 at its N-terminal Lys 6 and 7 residues. We examined APE1 and its acetylation-dependent gene expression profile of lung cancer cells which would contribute to sustained proliferation of lung cancer cells.
We used microarry based gene expression profile analysis using affymetrix HG-U133-Plus 2 array. For differential expression testing, Linear Models for MicroArray (Limma) was used to fit linear models for analyzing designed experiments and the assessment of overall gene expression and contrast analysis comparing the experimental groups

overall_design: We used two different sets of experiments. In one set we used lung adenocarcinoma A549 cells and determined the gene expression profile of control (control siRNA transfected) and APE1-downregulated (APE1 siRNA transfected) A549 cells. Additionally, to examine the effect of acetylation of APE1, we used trichostatin A (TSA; which increases APE1's acetylation) and treated both control and APE1-downregulated cells with TSA (100 ng/ml) for 4 hrs. We compared the gene expression profile between (i) control vs. APE1 siRNA cells (this analysis will determine the genes whose expression is affected by APE1), and also between (ii) TSA-treated control vs. TSA-treated APE1 siRNA cells (this analysis will determine the genes whose expression is specifically affected by APE1's acetylation).  In another set we used normal bronchial epithelial BEAS-2B cells. In these cells we overexpressed wild type (WT) APE1 (that can be acetylated), K6R/K7R (RR) mutant APE1 (that cannot be acetylated) or N-terminal 42 amino acid deleted (ND42) mutant APE1 (that lacks the N-terminal domain of APE1 which harbors the acetylation sites). We compared the gene expression profile between (i) WT vs. RR (this analysis will determine the genes whose expression is affected by acetylable APE1), and between (ii) WT vs. ND42 (this this analysis will determine the genes whose expression is affected by full-length acetylable APE1). We have 3 biological replicates for each sample designated as 1, 2, 3 (equivalent to a,b,c).

first: Kishor

middle: K

last: Bhakat


title: PGC-1a Determines Light Damage Susceptibility of the Murine Retina

city: Basel

first: Christoph

last: Handschin

address: Spitalstrasse 41

country: Switzerland

institute: Biozentrum, University of Basel

summary: The peroxisome proliferator-activated receptor c coactivator 1 (PGC-1) proteins are key regulators of cellular bioenergetics and are accordingly expressed in tissues with a high energetic demand. For example, PGC-1a and PGC-1b control organ function of brown adipose tissue, heart, brain, liver and skeletal muscle. Surprisingly, despite their prominent role in the control of mitochondrial biogenesis and oxidative metabolism, expression and function of the PGC-1 coactivators in the retina, an organ with one of the highest energy demands per tissue weight, are completely unknown. Moreover, the molecular mechanisms that coordinate energy production with repair processes in the damaged retina remain enigmatic. In the present study, we thus investigated the expression and function of the PGC-1 coactivators in the healthy and the damaged retina. We show that PGC-1a and PGC-1b are found at high levels in different structures of the mouse retina, most prominently in the photoreceptors. Furthermore, PGC-1a knockout mice suffer from a striking deterioration in retinal morphology and function upon detrimental light exposure. Gene expression studies revealed dysregulation of all major pathways involved in retinal damage and apoptosis, repair and renewal in the PGC-1a knockouts. The light-induced increase in apoptosis in vivo in the absence of PGC-1a was substantiated in vitro, where overexpression of PGC-1a evoked strong anti-apoptotic effects. Finally, we found that retinal levels of PGC-1 expression are reduced in different mouse models for retinitis pigmentosa. We demonstrate that PGC-1a is a central coordinator of energy production and, importantly, all of the major processes involved in retinal damage and subsequent repair. Together with the observed dysregulation of PGC-1a and PGC-1b in retinitis pigmentosa mouse models, these findings thus imply that PGC-1a might be an attractive target for therapeutic approaches aimed at retinal degeneration diseases.

overall_design: We subjected wildtype and PGC-1 alpha knockout mice to 2 hrs of 15.000 lux of light and compared these to unexposed, i.e. dark exposed mice.  After exposure, the mice's eyes were removed and microarray analysis was performed.

first: Anna

last: Egger

first: Michal

last: Okoniewski


title: The genomic context and co-recruitment of SP1 affect ERRα co-activation by PGC-1α in muscle cells [array]

summary: The peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) coordinates  the transcriptional network response to promote an improved endurance capacity in  skeletal muscle, e.g. by co-activating the estrogen-related receptor α (ERRα) in the  regulation of oxidative substrate metabolism. Despite a close functional relationship,  the interaction between these two proteins has not been studied on a genomic level.  We now mapped the genome-wide binding of ERRα to DNA in skeletal muscle cell line  with elevated PGC-1α and linked the DNA recruitment to global PGC-1α target gene  regulation. We found that, surprisingly, ERRα co-activation by PGC-1α is only  observed in the minority of all PGC-1α recruitment sites. Nevertheless, a majority of  PGC-1α target gene expression is dependent on ERRα. Intriguingly, the interaction  between these two proteins is controlled by the genomic context of response elements,  in particular the relative GC and CpG content, monomeric and dimeric repeat binding  site configuration for ERRα, and adjacent recruitment of the transcription factor SP1.  These findings thus not only reveal an unprecedented insight into the regulatory  network underlying muscle cell plasticity, but also strongly link the genomic context of  DNA response elements to control transcription factor - co-regulator interactions.

overall_design: We used microarrays to detect changes in gene expression in C2C12 cells following PGC-1alpha over-expression or GFP (control) over-expression. We used 3 biological replicates for each condition. The samples were: shGFP with GFP viral infection, shGFP with PGC-1alpha viral infection, shERRa with PGC-1alpha viral infection and the ERRa inverse agonist XCT790.

first: Silvia

last: Salatino

first: Barbara

last: Kupr

first: Mario

last: Baresic

first: Erik

last: van Nimwegen


title: Gene expression profiling of MDA231 cells with alterations involving beta-oxidation pathway

status: Public on Apr 14 2016

first: Chad

last: Creighton

state: TX

address: One Baylor Plaza, Mail Stop: BCM305

department: Biostatistics, Ducan Cancer Center

institute: Baylor College of Medicine

summary: In order to confirm the role of fatty acid β-oxidation in Src regulation, we performed gene expression analysis in MDA231 cells from in vivo model treated with ETX or knockdown of CPT1 or CPT2 using shRNA. As expected, inhibition of β-oxidation showed a gene expression pattern that is opposite to the published Src regulated gene pattern. The known Src up-regulated genes are down-regulated and Src down-regulated genes are up-regulated in β-oxidation inhibited cells. Western Blotting further confirmed the gene expression pattern. Knockdown of CPT1 or CPT2 inhibited Src Y416 autophosphorylation as observed with ETX.

overall_design:
MDA231 cells were treated with ETX or knockdown of CPT1 or CPT2 using shRNA. Gene expression profiles were taken for each group and compared with control group (shRNA scramble).
Multiple group comparison [MDA231-Scramble (C), MDA231-Scramble +ETX (D), MDA231-shCPT-1 (E) and  MDA231-shCPT-2 (F)]

first: Yiqun

last: Zhang

first: Benny

last: Kaipparettu


title: DNA methylation profiles in preeclampsia and healthy control placentas

status: Public on Apr 12 2016

city: Penrith

first: Christine

last: Chiu

state: New South Wales

address: Locked Bag 1797

department: School of Medicine

country: Australia

institute: Western Sydney University

summary: Genome wide DNA methylation profiling of normal and preeclampsia placental samples. Illumina Infinium HumanMethylation450 BeadChip (450K array) was used to obtain DNA methylation profiles in placental samples. Samples included 16 samples from healthy uncomplicated pregnancies and 8 samples from pregnancies affected by preeclampsia.

overall_design: Bisulphite converted DNA from the 24 samples were hybridised to the  Illumina Infinium HumanMethylation450 BeadChip (450K array).

first: Joanne

last: Lind

first: K

middle: R

last: Yeung

first: C

first: R

last: Pidsley

first: A

last: Makris

last: Hennessy


title: Targeting metabolic symbiosis to overcome resistance to anti-angiogenic therapy

first: Gerhard

last: Christofori

address: Mattenstrasse 28

department: Department of Biomedicine

institute: University of Basel

summary: Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. In the present study, we aimed to identify resistance mechanisms to the small-molecule tyrosine kinase inhibitor nintedanib in the Py2T murine breast cancer transplantation model.  To identify differences in gene expression between short- and long-term nintedanib and untreaded FAC-sorted tumor and endothelial cells, we performed gene expression profiling by using affymetrix microarrays.

overall_design: The murine breast cancer cell line Py2T was injected into a mammary fat pad of FVB/N mice. Treatment with nintedanib was initiated when tumors reached a measurable size. After 1 week (short-term treatment) and 3 weeks of nintedanib treatment (long-term treatment), treated and untreated control (size-matched to the long-term nintedanib treatment group) tumor and endothelial cells were FAC-sorted, RNA was extracted and hybridized on Affymetrix microarrays.

first: Laura

last: Pisarsky

first: Ruben

last: Bill

first: Ryan

last: Goosen


title: Gene expression profiling of transmitochondrial cybrids (triple negative breast cancer cells in SUM159 background)

summary: We used a transmitochondrial cybrid (cybrids)-based discovery approach to identify mitochondria-regulated cancer pathways in TN BCa. Cybrids were generated under a moderately metastatic TN BCa cell line SUM159 as the common nuclear background with mitochondria from benign breast epithelium (A1N4) and moderately metastatic (SUM159) TN BCa cells. In vitro and in vivo studies suggested that even under the common moderately cancerous nuclear background, mitochondria from benign cells inhibit and metastatic cell induce cancer properties of a moderately aggressive TN BCa cell. Gene expression studies identified c-Src onco-pathway as one of the major cancer pathways altered according to the mitochondria status of the cybrids.

overall_design:
SUM159 ρ0 cells were used as nuclear donor and A1N4 and SUM 159 cells were used as mitochondrial donor cells. The two groups were profiled for gene expression using microarrays.
two group comparison (159/SUM159 vs A1/SUM159)


title: Epigenomic profiling of preterm infants reveals DNA methylation differences at sites associated with neural function

status: Public on Apr 27 2016

city: Edinburgh

first: James

last: Boardman

state: Midlothian

address: 47 Little France Crescent

department: MRC Centre for Reproductive Health

country: United Kingdom

institute: University of Edinburgh

summary: DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early life stress and life-course neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth < 32 weeks’ gestation) and healthy controls (birth > 37 weeks), and a genome-wide analysis of DNAm was performed; diffusion MRI (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components analysis was used to investigate the contribution of MRI features and key clinical variables to variance in DNAm.  Differentially methylated regions were found within 25 gene bodies and 61 promoters of protein-coding genes in preterm infants compared with controls; 10 of these are associated with neural development or function. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 principal components (PC); corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC.   Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. The differentially methylated regions identified provide several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury.

overall_design: DNA was extracted from the saliva of 36 preterm neonates 36 full term controls (>37 weeks postmenstrual age) and hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: Sarah

last: Sparrow

first: Jonathan

last: Manning

first: Jessy

last: Cartier

first: Devasuda

last: Anblagan

first: Mark

last: Bastin

first: Chinthika

last: Piyasena

first: Rozalia

last: Pataky

first: Emma

last: Moore

first: Scott

middle: I

last: Semple

first: Alastair

last: Wilkinson

first: Margaret

last: Evans

first: Amanda

last: Drake

middle: P


title: Whole blood and isolated blood cell transcriptomics in COPD

first: Mustimbo

last: Roberts

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

overall_design: Refer to individual Series


title: Whole Blood and Stimulated Whole Blood Transcriptomics in COPD.

summary: We observed no transcripts in the whole blood that distinguishes COPD patients and  control smokers.  In contrast, T cell directed stimulation of whole blood, resulted in altered transcriptomic response and separated COPD patients from control smokers.

overall_design: Performed microarrays on whole blood from 80 subjects.  Control groups were smokers with out COPD.  Compared COPD subjects to controls.  Whole blood from COPD subjects were stimulated with anti-CD3/anti-CD28 and microarray perfomed.  N=62 (stimulated) and N=64 (unstimulated


title: Oncometabolic nuclear reprogramming of cancer stemness

status: Public on Apr 08 2016

city: Oviedo

first: Agustin

middle: F

last: Fernandez

email: affernandez@hca.es, agusff@gmail.com

state: Asturias

address: Avenida de Roma s/n

department: IUOPA

institute: Oviedo University-HUCA

summary: By impairing histone demethylation and locking cells into a reprogramming-prone state, oncometabolites can partially mimic the process of induced pluripotent stem cell generation. Using a systems biology approach, combining mathematical modelling, computation, and proof-of-concept studies with live cells, we found that an oncometabolite-driven pathological version of nuclear reprogramming increases the speed and efficiency of dedifferentiating committed epithelial cells into stem-like states with only a minimal core of stemness transcription factors. Our biomathematical model, which introduces nucleosome modification and epigenetic regulation of cell differentiation genes to account for the direct effects of oncometabolites on nuclear reprogramming, demonstrates that oncometabolites markedly lower the “energy barriers” separating non-stem and stem cell attractors, diminishes the average time of nuclear reprogramming, and increases the size of the basin of attraction of the macrostate occupied by stem cells. These findings establish for the first time the concept of oncometabolic nuclear reprogramming of stemness as a novel metabolo-epigenetic mechanism for generation of cancer stem-like cells.

overall_design: Total DNA was isolated according to standard procedures from MCF10A cells with heterozygous knock-in of IDH1 dominant-negative (R132H) point mutation (HD 101-013) and MCF10A isogenic parental cells (HD PAR-058), which were obtained from Horizon Discovery (HD) Ltd., Cambridge, UK

first: Javier

last: Menendez

first: Bruna

last: Corominas-Faja

first: Elisabet

last: Cuyàs

first: María

last: García

first: Salvador

last: Fernández-Arroyo

first: Jorge

last: Joven

first: Mario

last: Fraga

first: Tomás

last: Alarcón


title: Gene expression data of whole blood of systemic juvenile idiopathic arthritis (SJIA) patients treated with canakinumab or placebo and age matched healthy controls

first: Arndt

middle: Holger

last: Brachat

state: Basel Stadt

address: Fabrikstrasse 10

department: BMD

institute: NIBR

summary:
Canakinumab is a human anti-interleukin-1 beta (IL-1 beta) monoclonal antibody neutralizing IL-1 beta. Systemic juvenile idiopathic arthritis (SJIA) is a rare, multigenic, autoinflammatory disease of unknown etiology characterized by chronic arthritis; intermittent high-spiking fever, rash, and elevated levels of acute-phase reactants. Blood samples of SJIA patients were obtained from two phase 3 clinical trials conducted by the members of the Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG) (Clinicaltrials.gov: NCT00886769 and NCT00889863). For patients, baseline and day 3 samples were analyzed for either placebo or canakinumab (Ilaris) treatment.
Clinical response was assessed at day 15 using adapted JIA American College of Rheumatology (ACR) response criteria.

overall_design: Overall, 206 samples were used in this study including 22 samples from healthy controls, 33 samples of placebo treated patients and 151 samples of canakinumab treated patients.

middle: H

first: Martin

last: Letzkus

first: Nicole

last: Hartmann

first: Alexei

last: Grom

first: Nico

last: Wulffraat

first: Hermine

last: Brunner

first: Pierre

last: Quartier

first: Riva

last: Brik

first: Liza

last: McCann

first: Huri

last: Ozdogan

first: Lidia

last: Rutkowska-Sak

first: Rayfel

last: Schneider

first: Valeria

last: Gerloni

first: Liora

last: Harel

first: Maria

last: Terreri

first: Kristin

last: Houghton

first: Rik

last: Joos

first: Daniel

last: Kingsbury

middle: M

last: Lopez-Benitez

first: Hermann

last: Gram

first: Ken

last: Abrams

first: Alberto

last: Martini

last: Lovell

first: Nanguneri

last: Nirmala

first: Nicolino

last: Ruperto


title: Whole transcript expression profiling of short-term and long-term hypoxic neural stem cells (NSCs)

status: Public on Apr 09 2016

city: Dresden

first: Lena

last: Braunschweig

address: Fetscherstr. 74

department: Neurology

institute: TU Dresden

summary:
Transcriptome analysis of murine foetal NSCs (E14) after short-term (48 hours) and long-term (13 days) hypoxic (3% oxygen) culture compared to normoxic culture (21% oxygen)
We focused on whole-transcriptome analyses using gene chip microarrays to compare expression profiles of NSCs cultured at hypoxic conditions to those of normoxic cells. Therefore, we used NSCs derived from the mesencephalon and the cortex and cultured them for short- and long-term at hypoxia/normoxia.

overall_design: We analyzed NSCs from cortex and midbrain after short- and long-term culture of hypoxia compared to normoxia.

first: Anne

last: Meyer

first: Julia

last: Jarrells

first: Alexander

last: Storch


title: High Mobility Group Box Protein 1 is Dispensable for Autophagy and Mitochondrial Quality Control in Vivo

status: Public on Apr 11 2016

city: New York

first: Robert

middle: F.

last: Schwabe

state: NY

address: 1150 St. Nicholas Avenue-412C

department: Medicine

institute: Columbia University

summary:
Gene expression of livers with hepatocyte-specific deletion of Hmgb1 was compared to control livers with floxed Hmgb1
Hmgb1-deleted livers (from mice expressing Albumin-Cre and floxed Hmgb1) and control liver (mice expressing only floxed Hmgb1)
Whole liver from 8 week old mice was used. Both groups are littermates, and have been backcrossed to C57Bl/6 five times.

overall_design:
Gene expression of mouse hepatic stellate cells was characterized
A. Livers from mice with Albumin-Cre-mediated deletion of Hmgb1  (n=4).
B. Livers from mice carrying Hmgb1 floxed alleles (n=4).

first: Peter

last: Huebener

first: Geum-Youn

last: Gwak

first: Jean-Philippe

last: Pradere

first: Catarina

last: Quinzii

first: Richard

middle: A

last: Friedman

first: Chyuang-Sheng

last: Lin

first: Chad

last: Trent

first: Ira

last: Goldberg

first: Mark

last: Czaja


title: Epigenome analysis of dnmt target sites [DKO8 cell line]

city: Los Angeles

last: Jones

state: California

address: 1441 Eastlake Ave NOR7344

institute: University of Southern California

summary: Genome wide DNA methylation profiling of target sites of dnmt3b isoforms in HCT derivative cell line DKO8. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs

overall_design: Bisulphite converted DNA from the samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: C

last: Duymich

first: P


title: Epigenome analysis of dnmt target sites


title: Epigenome analysis of dnmt target sites [3ABDKO cell line]

summary: Genome wide DNA methylation profiling of target sites of dnmt3b isoforms in HCT derivative cell line 3ABDKO followed by 5-Aza-CdR treatment. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs

first: Christopher


title: Gene expression analysis in tamoxifen resistant ER+ breast cancer cell lines

status: Public on Apr 10 2016

city: Odense C

first: Daniel

last: Elias

address: J. B. Winsløwsvej 25

department: Cancer and Inflammation Research

institute: University of Southern Denmark

summary: To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer, we performed gene array analysis and identified 366 genes with altered expression in four unique tamoxifen resistant (TamR) cell lines vs the parental tamoxifen sensitive MCF7/S0.5 cell line. Most of these genes were funcationally linked to cell proliferation, death and control gene expression, and include FYN, PRKCA, ITPR1, DPYD, DACH1, LYN, GBP1 and PRLR. Treatment with FYN specific small interfering RNA or a SRC family kinase inhibitor reduced cell growth of TamR cell lines while exerting no significant effect on MCF7/S0.5 cells. Moreover, overexpression of FYN in parental tamoxifen-sensitive MCF7/S0.5 cells resulted in reduced sensitivity to tamoxifen, demonstrating growth and survival promoting function of FYN in MCF7 cells. FYN knockdown in TamR cells led to reduced phosphorylation of 14-3-3 and CDc 25A, suggesting that FYN, by activation of of important cell cycle-associated proteins, may overcome the anti-proliferative effects of tamoxifen. Evaluation of the subcellular localization of FYN in primary breast tumors from two cohorts of endocrine-treated ER+ breast cancer patients, one with advanced disease (N = 47) and the other with early disease (N = 76), showed that in the former, plasma membrane-associated FYN expression strongly correlated with longer progression-free survival (P<0.0002). Similarly, in early breast cancer patients, membrane-associated expression of FYN in the primary breast tumor was significantly associated with increased metastasis-free (P<0.04) and overall (P<0.004) survival independent of tumor size, grade or lymph node status. Our results indicate that FYN has an important role in tamoxifen resistance, and its subcellular localization in breast tumor cells may be an important novel biomarker of response to endocrine therapy in breast cancer.

overall_design: The array included four TamR MCF7/S0.5 cell lines TamR1, TamR4, TamR7 and TamR8 and one tamoxifen sensitive MCF7/S0.5. Three biological replicates of TamR1 and TamR4 as well as 2 biological replicates of TamR7 and TamR8 was used in the study. The tamoxifen sensitive parental MCF7/S0.5 was represented by 8 biological replicates in the array.

first: Henriette

last: Hansen

first: Anne-Vibeke

last: Lænkeholm

first: Morten

last: Gjerstorff

first: Christina

last: Yde

last: Lykkesfeldt

first: Henrik

last: Ditzel


title: Chronic haloperidol effects on gene expression in mouse [array]

city: chapel hill

first: Yunjung

last: Kim

state: North Carolina

address: 120 Mason farm road

institute: UNC at Chapel Hill

summary:
We evaluate the effects of chronic administration of antipsychotic haloperidol versus placebo in male, 8-week old, C57BL/6J mice.
We used microarray to study gene expression changes after haloperidol treatment in mouse brain and liver

overall_design: We examined whole brain from 20 mice (10 haloperidol-treated mice, 10 placebo-treated mice) and liver from 18 mice (9 haloperidol-treated, 9 placebo-treated) after 30 days of haloperidol treatment with slow-release pellets.


title: CEMA, a platform to define cell states

first: William

last: Lowry

address: 621 Charles Young

institute: UCLA

summary:
gene expression database and algorithm to define cell expression modules
Using a newly-generated compendium of cell-state-specific gene expression data, we identified genes that uniquely define each cell state, including those thought to represent various developmental stages. Whereas others have performed similar analyses on tissue-specific, heterogeneous collections of public data, our focus is on single-laboratory, cell-specific data. The approach allows for more refined information than tissues, while single-laboratory data, although fewer in number, minimize artifacts arising from inter-laboratory merging. Our analysis sheds light on human cell fate through the identification of core genes that are altered over several developmental milestones, and across regional specification.  Finally, we provide an interactive, web-based application for dissemination and exploration of our results, yielding a valuable resource with a novel perspective on the development of human cells. This web service is available at www.cemagenes.com.

overall_design: For tissue derived cell types, primary cells were derived and cultured in appropriate culture medium for up to 3 weeks.  For pluripotent derived cell types, hESCs and hiPSCs were cultured under standard conditions with feeders and driven to differentiate under conditions as described previously.  For both tissue and pluripotent stem cell (PSC) derived cells, the indicated cell types were purified from mixed cultures either by expression of reporter construct (such as AFP-GFP for hepatocytes) and FACS, or by manual dissection based on morphology (such as rosettes for NPCs)(Patterson et al., 2011).  All purified cell types were judged to be pure if > 90% positive by immunostaining for at least 3 appropriate marker genes.  Many of these cell types were also assayed for appropriate function(Patterson et al., 2011).

first: Jennifer

last: Listgarten


title: Intestinal myofibroblast vs skin fibroblast

status: Public on Apr 06 2016

city: John Radcliffe hospital

first: Jenny

last: Wilding

state: Headington, Oxford

address: Weatherall institute of molecular medicine

department: oncology

institute: University of Oxford

summary:
Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumour progression. Myofibroblasts have previously mostly been distinguished from normal fibroblasts only by the expression of α smooth muscle actin (αSMA). We now identify AOC3, a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast reacting monoclonal antibody (mAb), PR2D3. The normal and tumour tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts. We have shown that the surface expression of AOC3 is sensitive to digestion by trypsin and collagenase and that anti-AOC3 antibodies can be used for FACS sorting of myofibroblasts obtained by non-enzymatic procedures. Whole genome microarray mRNA expression profiles of myofibroblasts and skin fibroblasts revealed four additional genes that are significantly expressed differentially between these two cell types; NKX2-3 and LRRC17 are expressed in myofibroblasts and SHOX2 and TBX5 in skin fibroblasts. Transforming Growth Factor β (TGFβ) substantially down-regulated AOC3 expression in myofibroblasts but not in skin fibroblasts, in which it dramatically increased the expression of αSMA. A knockdown of NKX2-3 in myofibroblasts caused a decrease of myofibroblast-related gene expression and an increased expression of the fibroblast associated gene, SHOX2, suggesting that NKX2-3 is a key mediator for maintaining myofibroblast characteristics. Our results show that colorectal myofibroblasts, as defined by the expression of AOC3, NKX2-3 and other markers, are a distinctly different cell type from TGFβ activated fibroblasts.
colorectal myofibroblast specific markers and expression profiles were sought by comparing four primary myofibroblast cultures to a panel of four  dermal and foreskin fibroblast cell lines

overall_design: Four primary myofibroblast cultures established from adult human colon compared to four skin fibroblast cell lines to identify intestinal myofibroblast specific markers

first: Walter

last: Bodmer


title: Epigenome analysis of dnmt target sites [3BK0 cell line]

first: Peter

department: Urology

summary: Genome wide DNA methylation profiling of target sites of dnmt3b isoforms in HCT derivative cell line 3BKO followed by 5-Aza-CdR treatment. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs


title: FoxA supports breast cancer growth by regulating LIPG transcription and lipid metabolism

city: Barcelona

first: Oscar

last: Reina Garcia

address: C/Baldiri Reixac 10

department: Biostatistics and Bioinformatics

institute: IRB Barcelona

summary:
The mechanisms that allow breast cancer cells to metabolically sustain growth are poorly understood. In breast cancer, FoxA1 transcription factor, along with estrogen receptor, regulates luminal cell specification and proliferation. Here we report that FoxA transcription factor family members FoxA1 and FoxA2 fuel cellular growth in breast cancer through the expression of a common target gene, namely the endothelial lipase (LIPG)
We used microarrays to detail the genes that are under de control of FoxA transcription factors in MDA231 and MCF7 breast cancer cells

overall_design: Isolated Breast cancer cells derived from non-depleted (Dox−) FoxA1 or FoxA2 MCF7 and MDA231 tumors (control groups), FoxA1- and FoxA2-depleted MCF7 and MDA231 tumors (knockdown groups) and the corresponding FoxA family-rescued tumors (rescued group) subjected to transcriptomic analysis using a GeneAtlas Human Genome U-219 Affymetrix array. Genes regulated by FoxA1 and FoxA2 were selected on the basis of the following criteria: (1) decreased expression in MCF7 and MDA231 cells upon FoxA depletion compared to control cells; and (2) increased expression in MCF7 and MDA231 FoxA-rescued cells compared to the respective FoxA-depleted population; or (1) increased expression in MCF7 and MDA231 cells upon FoxA depletion compared to control cells; and (2) decreased expression in MCF7 and MDA231 FoxA-rescued cells compared to the respective FoxA-depleted population.

first: Felipe

last: Slebe

first: Roger

last: Gomis


title: Expression data from MCF7 cells

status: Public on Apr 04 2016

city: Shang Hai

first: Yajun

last: Liang

state: Shang Hai

address: Yueyang Road 319

department: IHS

country: China

institute: CAS

summary:
MTDH was identified to be a functional gene in cancer progression. We overexpressed the gene in MCF7 cells and explored its functions in cancer stem cell maintainance.
We used microarrays to mine the genes that were regulated by MTDH after MTDH overexpression.

overall_design: The MCF7 cells that were stably trasfected with empty vector or MTDH overexpressing plasmids were used for RNA extraction and hybridization on Affymetrix microarrays. We sought to find the gene that were upregulated by MTDH.

first: Jing

last: Hu


title: Neutrophils from ARDS patients and healthy volunteers, and healthy volunteer samples treated with PI3K inhibitors

city: Stevenage

first: Glyn

last: Bradley

address: Medicines Research Centre

department: Computational Biology

institute: GSK

summary:
Rationale:  The acute respiratory distress syndrome is refractory to pharmacological intervention.  Inappropriate activation of alveolar neutrophils is believed to underpin this disease’s complex pathophysiology, yet these cells have been little studied.
Objectives:  To examine the functional and transcriptional profiles of patient blood and alveolar neutrophils compared to healthy volunteer cells, and define their sensitivity to phosphoinositide 3-kinase inhibition.
Methods:  Twenty three ventilated patients underwent bronchoalveolar lavage.  Alveolar and blood neutrophil apoptosis, phagocytosis and adhesion molecules were quantified by flow cytometry, and oxidase responses by chemiluminescence.  Cytokine and transcriptional profiling utilized multiplex and GeneChip arrays.
Measurements and Main Results:  Patient blood and alveolar neutrophils were distinct from healthy circulating cells, with increased CD11b and reduced CD62L expression, delayed apoptosis and constitutively primed oxidase responses.  Incubating control cells with disease bronchoalveolar lavage recapitulated the aberrant functional phenotype and this could be reversed by phosphoinositide 3-kinase inhibitors.  In contrast, the pro-survival phenotype of patient cells was recalcitrant to phosphoinositide 3-kinase inhibition.  RNA transcriptomic analysis revealed modified immune, cytoskeletal and cell death pathways in patient cells, aligning closely to sepsis and burns data sets but not with phosphoinositide 3-kinase signatures.
Conclusions:  Acute respiratory distress syndrome blood and alveolar neutrophils display a distinct primed, pro-survival profile and transcriptional signature.  The enhanced respiratory burst was phosphoinositide 3-kinase-dependent, but delayed apoptosis and the altered transcriptional profile were not.  These unexpected findings cast doubt over the utility of phosphoinositide 3-kinase inhibition in acute respiratory distress syndrome and highlight the importance of evaluating novel therapeutic strategies in patient-derived cells.

overall_design: 94 samples in total. The study was split in to 2 parts. PartA : PMN were isolated from ARDS patients alongside PMN from paired (i.e., age and gender-matched) HVTs. PartB: PMNs from HVTs cultured with GM-CSF and PI3K Inhibitors.

first: Mark

last: Lennon

first: Jatinder

last: Juss

first: David

last: House

first: Malcolm

last: Begg

first: Alison

last: Condliffe

first: Edwin

last: Chilvers

first: Augustin

last: Amour

first: Jurgen

last: Herre

first: Daniel

last: Storisteanu

first: Kim

last: Hoenderdos

first: Charlotte

last: Summers

first: Edith

last: Hessel


title: Gene expression profiling of xenografts and mouse embryonic fibroblasts with ectopically expressed PREX2 mutants

first: Lynda

last: Chin

address: 1515 Holcombe Blvd

department: Genomic Medicine

institute: MD Anderson Cancer Center

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: GR and ER co-activation alters the expression of differentiation genes and associates with improved ER+ breast cancer outcome

status: Public on Apr 01 2016

city: Chicago

first: Suzanne

middle: Daniela

last: Conzen

state: IL

address: 5841 S. Maryland Ave, SBRI J301, MC 2115

institute: The University of Chicago

summary:
Analysis of MCF-7 cells treated for 4h with Ethanol, Estradiol (E2), Dexamethasone (Dex), or Estradiol  + Dexamethasone (E2 + Dex)
In estrogen receptor (ER)-negative breast cancer (BC), high tumor glucocorticoid receptor (GR) expression has been associated with a relatively poor outcome. In contrast, using a meta-analysis of several genomic datasets, here we find that tumor GR mRNA expression is associated with improved ER+ relapse-free survival (RFS) (independently of progesterone receptor (PR) expression). To understand the mechanism by which GR expression is associated with a better ER+ BC outcome, the global effect of GR-mediated transcriptional activation in ER+ BC cells was studied. Analysis of GR chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in ER+/GR+ MCF-7 cells revealed that upon co-activation of GR and ER, GR chromatin association became enriched at proximal promoter regions. Furthermore, following ER activation, increased association of GR was observed at ER, FOXO, and AP1 response elements. In addition, it was determined that ER associated with GR response elements, suggesting that ER and GR interact in a complex. Co-activation of GR and ER resulted in increased expression (relative to ER activation alone) of transcripts that encode proteins promoting cellular differentiation (e.g. KDM4B, VDR) and inhibiting Wnt-signaling (IGFBP4). Finally, expression of these individual pro-differentiation genes was associated with significantly improved RFS in ER+ BC patients. Together, these data demonstrate that the co-expression and subsequent activity of tumor cell GR and ER contribute to the less aggressive natural history of early-stage BC by coordinating the altered expression of genes favoring differentiation.

overall_design: Four treatment samples (Vehicle V, Dex D, E2, or Dex+E2). Three biological replicate experiments per sample. Vehicle sample is Ethanol control.

first: Diana

last: West

first: Deng

last: Pan

first: Eva

last: Tonsing-Carter

first: Charles

last: Pierce

first: Sarah

last: Styke

first: Kathleen

last: Bowie

first: Kyle

last: Hernandez

first: Tzintzuni

last: Garcia

first: Masha

last: Kocherginsky


title: Gene expression in haematopoietic stem and progenitor cells from Gata1-EGFP reporter mouse bone marrow

city: Oxford

first: Claus

last: Nerlov

address: John Radcliffe Hospital, University of Oxford

department: MRC Molecular Haematology Unit

institute: Weatheral Institute of Molecular Medicine

summary:
Haematopoietic stem cells can differentiate into all blood cell types. In this process, cells become progressively restricted to a single cell type. The order in which differentiating cells loose lineage potential, and the prospective isolation of cells with a defined potential remains a long-standing question.

We performed gene expression analysis of haematopoietic cells from Gata1-EGFP reporter mice, leading to a model for hematopoiesis where the initial lineage decision consists of a separation of erythroid/megakaryocyte/mast cell/eosinophil potential from lymphopoietic/monocyte/neutrophil potential

overall_design: RNA was isolated from HSC EGFP-, HSC EGFP+, LMPP, CLP, preGM EGFP-, preGM EGFP+, GMP EGFP-, GMP EGFP+ and preMegE cells with the QIAGEN RNeasy Micro Kit.

first: Roy

last: Drissen

first: Natalija

last: Buza-Vidas

first: Adam

last: Mead

first: Elena

last: Mancini

first: Michael

last: Lutteropp

first: Amit

last: Grover

first: Sten

last: Jacobsen


title: Methylome-wide analysis of chronic HIV infected patients and healthy controls

status: Public on Apr 03 2016

city: La Jolla

first: Andrew

last: Gross

address: 9500 Gilman Drive #0688

institute: UCSD

summary: Current therapy has turned HIV infection into a chronic condition. Clinically, some patients suffer prematurely from ailments associated with advanced age; however, the relationship between HIV and aging is unclear. Here we have collected a large cohort of HAART treated HIV+ subjects with both recent and chronic infection and recapitulated the shared phenotype of HIV and age. To further understand this signal, we applied validated models of DNA methylation-based biological age to establish a clear link between HIV infection and molecular age advancement. We then show this result to be robust to HIV duration, cellular composition, and general methylome disorder. Finally we show a pattern of hypomethylation in HIV+ individuals at the HLA locus. Together these results lead to a much-needed better understanding of the epigenetic consequences and gerontological aspects of chronic HIV infection.

overall_design:
To determine whether HIV is associated with signs of aberrant biological aging, samples of whole blood were collected from HIV-infected, HAART-treated but otherwise healthy non-Hispanic white males (no hepatitis C co-infection, no diabetes, and strict adherence to therapy) and healthy non-Hispanic white male controls. DNA was extracted from whole blood and genome-wide methylation profiles of each sample were determined using the Illumina Infinium HumanMethylation450 BeadChip array. As a validation, a second cohort of subjects was profiled by flow-sorting cells and measuring methylation in pure-cell populations. Data were normalized and controlled for quality using standard techniques.

Please note that the following samples were excluded from the data processing by quality control steps;
METI-6
METI-7
352_CD4
381_CD4
however, their raw data was provided so that the full pipeline could be reproduced.

first: Philipp

last: Jaeger

first: Jason

last: Kreisberg

first: Katherine

last: Licon

first: Kristen

last: Jepsen

first: Mahdieh

last: Khosroheidari

first: Brenda

last: Morsey

first: Hui

last: Shen

first: Ken

last: Flagg

first: Daniel

last: Chen

first: Kang

last: Zhang

first: Howard

middle: S

last: Fox

first: Trey

last: Ideker


title: Analysis of human breast milk cells: gene expression profiles during pregnancy, lactation, involution and mastitic infection.

city: Parkville

first: christophe

last: lefevre

state: VIC

address: 1 G Royal Parade

department: Bioinformatics Division

institute: Walter Eliza Hall Institute of Medical Research

summary: The molecular processes underlying human milk production and the effects of mastitic infection are largely unknown because of limitations in obtaining tissue samples. Determination of gene expression in normal lactating women would be a significant step towards understanding why some women display poor lactation outcomes. Here we demonstrate the utility of RNA obtained directly from human milk cells to detect mammary epithelial cell (MEC)-specific gene expression. Milk cell RNA was collected from 5 time points (24 hours pre-partum during the colostrum period, mid lactation, two involution, and during a bout of mastitis) in addition to an involution series comprising three time points. Gene expression profiles were determined by use of human Affymetrix arrays. Milk cells collected during milk production showed that the most highly expressed genes were involved in milk synthesis (eg. CEL, OLAH, FOLR1, BTN1A1, ARG2), while milk cells collected during involution showed a significant down regulation of milk synthesis genes and activation of involution associated genes (eg. STAT3, NF-kB, IRF5, IRF7). Milk cells collected during mastitic infection revealed regulation of a unique set of genes specific to this disease state, whilst maintaining regulation of milk synthesis genes. Use of conventional epithelial cell markers was used to determine the population of MEC’s within each sample. This paper is the first to describe the milk cell transcriptome across the human lactation cycle and during mastitic infection, providing valuable insight into gene expression of the human mammary gland.

overall_design: Human milk sampling throughout lactation cycle and during mastitic infection.

first: Christophe

last: Lefèvre

first: Julie

last: Sharp

first: Ashalyn

last: Watt

first: Kevin

last: Nicholas


title: Highly dynamic molecular signature of macrophage subsets during sterile inflammation, resolution and tissue repair

status: Public on Apr 07 2016

city: Debrecen

first: Szilard

last: Poliska

address: Egyetem ter 1.

department: Biochemistry and Molecular Biology

institute: University of Debrecen

summary:
Tibialis anterior muscle was damaged by cardiotoxin injection and macrophage subsets were isolated and analyzed by gene expression analysis.
We used microarray to obtain global gene expression data of muscle-derived tissue macrophage subsets.

overall_design: Tissue macrophages were collected from regenerating muscle samples, Gr1+/Cx3cr1low and Gr1-/Cx3cr1high macrophage subsets were sorted. The global gene expression patterns of distinct macrophage subsets were analyzed on Affymetrix microarrays.

first: Tamas

last: Varga

first: Rémi

last: Mounier

first: Attila

last: Horvath

first: Sylvain

last: Cuvellier

first: Florent

last: Dumont

first: Szilárd

last: Póliska

first: Hamida

last: Ardjoune

first: Gaëtan

last: Juban

first: Laszlo

last: Nagy

first: Bénédicte

last: Chazaud


title: Expression data of HDAC3-deficient and sufficient medullary thymic epithelial cells (mTECs)

city: Rehovot

first: Jakub

last: Abramson

address: Herzl 234

department: Immunology

country: Israel

institute: Weizmann Institute

summary: Medullary thymic epithelial cells play essential role for induction of central self-tolerance by facilitating negative selection of self-reactive thymocytes and the generation of Foxp3+ regulatory T cells. Although studies highlighted the non-canonical NFκB pathway as the key regulator of mTEC development, comprehensive understanding of the molecular pathways regulating this process still remains incomplete. The aim of this study was to analyze the impact of Histone deacetylase 3 (HDAC3), which is highly expressed by mTECs, on mTEC development and function.  We used Affymetrix mouse 1ST arrays to analyze the impact of the Hdac3 gene on the gene expression profile of MHC-II medullary thymic epithelial cells

overall_design: Residual MHC-II low mTECs were flow-sorted from thymi isolated from HDAC3fl/fl (WT) and HDAC3fl/flFoxn1-Cre (HDAC3 cKO) 6weeks old mice. Typically, 10-30 HDAC3 cKOmice were pooled to obtain 30,000 sorted mTECs, which were then analyzed by gene expression profiling. Specifically, total RNA was extracted from ~30,000 pooled sorted cells using Trizol. Purified total RNA was then amplified using the MessageAmp RNA kit (Ambion). Biotinylated cRNA was then hybridized to Affymetrix Mouse Gene 1-ST arrays by the genomics core at the Weizmann Institute


title: R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.

city: Geneva

first: Thanos

last: Halazonetis

state: GE

address: Sciences III, 30, quai Ernest-Ansermet

department: IDepartment of Molecular Biology

institute: University of Geneva

summary: Pioneering studies within the last few years have allowed the in vitro expansion of tissue-specific adult stem cells from a variety of endoderm-derived organs, including the stomach, small intestine and colon. Here we derived organoids from mouse gallbladder tissue (gallbladder organoids), from mouse liver (including the extrahepatic biliary ducts and gallbladder; liver organoids) and from mouse small intestine tissue (intestinal organoids). RNA was prepared from these organoids and used to assay expression of 21,258 genes using Affymetrix gene expression arrays. RNA was also prepared from mouse gallbladder, liver and small intestine tissues and used to assay gene expression in these tissues. Finally, gallbladder organoids were induced to differentiate by removing R-spondin 1 and noggin from the culture media and subjected to gene expression array analysis.

overall_design: RNA was extracted from mouse gallbladder organoids, differentiated gallbladder organoids, liver organoids, small intestine organoids, gallbladder tissue, liver tissue and small intestine tissue and then used for hybridization of Affymetrix gene expression microarrays.

middle: D

first: Natalia

last: Lugli

first: Irene

last: Kamileri

first: Adrian

last: Keogh

first: Thomas

last: Malinka

first: Michalis

middle: E

last: Sarris

first: Iannis

last: Talianidis

first: Olivier

last: Schaad

first: Daniel

last: Candinas

first: Deborah

last: Stroka


title: Expression data of human tonsilar CD4 positive T cell subsets

city: Bunkyo-ku

first: Shuji

last: Sumitomo

state: Tokyo

department: Allergy and Rheumatology

institute: The University of Tokyo

summary:
Type 1 regulatory T (Tr1) cells are one of the regulatory T cell subsets that are characterized by the production of high amount of IL-10 and lack of FOXP3 expression. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue molecule and we have previously reported that LAG3 is expressed on IL-10 producing regulatory T cells. However, naturally occurring Tr1 cells in human secondary lymphoid tissue have not been detected. We identified CD4+CD25-LAG3+ T cells in human tonsil.
We compared mRNA expression of five CD4+ T cell subsets in tonsil using microarray analysis (CD4+CD25-LAG3+ T cells, CD4+CD25-CXCR5+PD-1+ follicular helper T cells (TFH), CD4+CD25+ T cells, CD4+CD25-LAG3-CD45RO+ cells and CD4+CD25-LAG3-CD45RO- cells).

overall_design: A human tonsil was obtained from a patient undergoing routine tonsillectomy, and five tonsillar CD4+ T cell subsets were sorted (each 1 x 10^5 cells). There is no biological replication.

first: Keishi

last: Fujio


title: Molecular profile of tumor-specific CD8+ T cell hypofunction in cancer

city: Mail Stop 8333

first: Jill

last: Slansky

state: CO

institute: University of Colorado School of Medicine

summary:
Comparison of genome-wide mRNA expresson between tumor-infiltrating CD8+ T cells from the tumor (hypofunctional T cells) and periphery (functional T cells)
Mechanisms of self-tolerance often result in CD8+ tumor-infiltrating lymphocytes (TIL) with a hypofunctional phenotype incapable of tumor clearance. Using a solid tumor model in mice, we found that CD8+ T cells became tolerized in less than 24 hours in an established tumor environment. To define the collective impact of pathways suppressing TIL function, we compared genome-wide mRNA expression of tumor-specific CD8+ T cells from the tumor and periphery. Notably, gene expression induced during TIL hypofunction more closely resembled self-tolerance than viral-exhaustion. Differential gene expression was refined to identify a core set of genes that defined hypofunctional TIL; these data comprise the first “molecular profile” of tumor-specific TIL that are naturally responding and represent a polyclonal repertoire. The molecular profile of TIL was further dissected to determine the extent of overlap and distinction between pathways that collectively restrict T cell functions. As suggested by the molecular profile of TIL, protein expression of inhibitory receptor LAG-3 was differentially regulated throughout prolonged late-G1/early-S phase of the cell cycle. Our data may accelerate efficient identification of combination therapies to boost anti-tumor function of TIL specifically against tumor cells.

overall_design: 4 samples, 3 biological replicates per group.

first: Katherine

last: Waugh

first: Sonia

last: Leach

first: Brandon

last: Moore

first: Tullia

last: Bruno

first: Jonathan

last: Buhrman


title: Genome-wide methylation profiles in primary intracranial germ cell tumors indicate primordial germ cell origin of germinoma

city: Chuo-ku

first: Shintaro

last: Fukushima

address: 5-1-1 Tsukiji

institute: National Cancer Center Research Institute

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

overall_design: Refer to individual Series


title: Transcriptome analysis of Escherichia coli during dGTP Starvation

city: RTP

first: NIEHS

last: Microarray Core

state: NC

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary: Our laboratory has recently discovered that E. coli cells starved for the DNA precursor dGTP are killed efficiently (dGTP starvation) in a manner similar to that described for Thymineless Death (TLD).  Conditions for specific dGTP starvation can be achieved by depriving an E. coli optA1 gpt strain of the purine nucleotide precursor hypoxanthine (Hx).  To gain insight into the mechanisms underlying dGTP starvation, we conducted genome-wide gene expression analyses on actively growing optA1 gpt strains subjected to hypoxanthine deprivation for increasing periods of time.  The data show that, upon Hx withdrawal, the optA1 gpt strain displays a diminished ability to de-repress the de novo purine biosynthesis genes, and this is likely due to internal guanine accumulation.  The impairment to fully induce the purR regulon may be a contributing factor to the lethality of dGTP starvation.  At later time points, and coinciding with cell lethality, strong induction of the SOS is observed, supporting the concept of replication stress as a final cause of death.  No evidence was observed for the participation of other stress responses, including the rpoS-mediated global stress response in the starved cells, and reinforcing the lack of feedback of replication stress into the global metabolism of the cell.  The genome-wide expression data also provide direct evidence for increased genome complexity during dGTP starvation, as a markedly increased gradient is observed for expression of genes located nearby the replication origin relative to those located towards the replication terminus.

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

overall_design: The present study was aimed at understanding the metabolic changes in dGTP-starved cells.  To do so, we designed two experiments.  The first experiment was aimed at investigating the transcriptional consequences of loss of the Hx purine source in each of the four strains (wt, optA1, gpt, and optA1 gpt).  Here, hypoxanthine was withdrawn from actively growing cells starting at OD 0.1, and periodic 2-fold dilutions were applied to keep to OD of the growing cultures below or only slightly above 0.20 (low-dilution protocol).  Samples were taken for microarray analysis at 15, 30, 45, 60, and 120 min. At each time point RNA samples were taken and analyzed for gene expression changes using the Affymetrix GeneChip E. coli Genome 2.0 Array.  This experiment was conducted three times, independently. A second experiment was aimed at following the transcriptional changes in the optA1 gpt strain during the entire 6-hour time course including the filamentation and cell death stage.  Here, we used a slightly different dilution protocol (high-dilution protocol), in which the strain was initially highly diluted (OD630 = 0.01) and further diluted at strategic points to prevent the OD to rise above 0.1.  These conditions optimize the cell death phenomenon. This experiment was also conducted three times independently.

first: Mark

last: Itsko

first: Roel

last: Schaaper


title: miR-182 and miR-10a are Key Regulators of Treg specialisation and stability during Th2 and Th1-associated Inflammation

city: Hamilton

first: Dan

last: Sturdevant

state: MT

address: 903 S 4th street

department: NIAID

institute: NIH

summary: A variety of CD4+Foxp3+ Treg cell types have been described previously, indicating molecular heterogeneity within the Foxp3+ pool of CD4+ T cells. However, the factors that shape the transcriptomic identities of different Foxp3+ Treg cells are poorly understood. To identify the molecular pathways involved, we isolated CD4+Foxp3gfp+ cells from Th1-rich or Th2-rich environments following chronic Leishmania major or Schistosoma mansoni infection, respectively. Whole genome expression profiling and next generation small RNA sequencing revealed significantly different mRNA and miRNA profiles. In-silico analyses identified miR-10a and miR-182 as ‘regulatory miRNA hubs’ in CD4+Foxp3+ cells in Th1 and Th2-environments, respectively. Using in vitro and in vivo systems we identified that IL-12/IFNg down-regulated miR-10a and its putative transcription factor, Creb. Importantly, we demonstrated that miR-10a controls a suite of genes that regulate IFNg production in Th1-Treg cells. Also, Treg cells treated with IL-4 increased miR-182 and its putative transcription factor, cMaf. Up-regulation of miR-182 mitigated IL-2 secretion, in part through repression of IL2-promoting genes, including Bach2 and Cd2ap. This study indicates that CD4+Foxp3+ cells are influenced by their environment, and that Th1 or Th2 environments promote distinct miRNA pathways, preserving Treg stability and suppressor function.

overall_design: mouse infection  vs. naïve

first: Samir

last: Kelada

first: Praveen

last: Sethupathy

first: Isobel

last: Okoye

first: Eleni

last: Kistasis

first: Stephanie

last: Czieso

first: Sandra

last: White

first: David

last: Chou

first: Craig

last: Martens

first: Stacy

last: Ricklefs

first: Kimmo

last: Virtaneva

first: Stephen

last: Porcella

first: Yasmine

last: Belkaid

first: Thomas

last: Wynn

last: Wilson


title: Escherichia coli global gene expression due ciprofloxacin challenge in human whole blood

city: Edinburgh

first: Senthil

last: Gandi

address: 49 Little France Crescent

department: Division of Infection and Pathway Medicine

institute: University of Edinburgh

summary: Treatment failures of antibiotic therapy are of major concern and can be caused by a misalignment of the antibiotic susceptibility determined in vitro with the behaviour of the pathogen in the patient. The aim of this study was to investigate the transcriptomic response of the uropathogenic strain E. coli CFT073 to antibiotic treatment in blood stream infection (BSI) models in order to understand and avoid antibiotic therapy failures in urosepsis treatments. Blood stream infection models were established by growing E. coli CFT073 in pooled human blood with and without ciprofloxacin. The antibiotic challenge was introduced at mid-logarithmic phase of growth of the organism to depict a clinical scenario. The responses were quantified by comparing to the responses at a given time point without the challenge. Global gene expression profiling of these conditions was examined using commercial DNA microarrays. The organism’s metabolic genes appeared to be regulated differently in each medium, this indicated that the bacterial growth regulation were different between the models. Bacterial growth in human serum mainly involved regulations of amino acid synthesis/utilisation such as glycine, arginine, thiamine, regulations of fimbrial proteins and bacteriophage genes. When comparing the responses to antibiotic challenge, bacteria grown in the respective medium displayed specific responses to the antibiotic challenge which were not seen in the other media. The common functions  of genes that responded to the ciprofloxacin challenge were SOS response, DNA repair, DNA replication, fimbrial genes and bacteriophage initiation. A subset of the bacteriophage genes showed similar responses between the three models. From genes that were differentially regulated, responses observed in the serum model appeared to have the highest fold changes. In this study we established new models to investigate blood stream infections. They have been used to identify previously unknown differences in the molecular response to antibiotic treatment by the uropathogenic E. coli CFT073 depending on the media. These unique responses will help to unravel the complexity of bloodstream infection and can help to improve the antibiotic therapy that is used.

overall_design: A 10 array study using total RNA recovered from bacteria that were grown in human whole blood, with and without ciprofloxacin challenge.  Arrays were performed in 5 biological replicates from each condition.

first: Johannes

last: Brennecke

first: Anning

last: Tian

first: Till

last: Bachmann


title: Escherichia coli global gene expression due ciprofloxacin challenge in laboratory medium and human serum

summary: Treatment failures of antibiotic therapy are of major concern and can be caused by a misalignment of the antibiotic susceptibility determined in vitro with the behaviour of the pathogen in the patient. The aim of this study was to investigate the transcriptomic response of the uropathogenic strain E. coli CFT073 to antibiotic treatment in blood stream infection (BSI) models in order to understand and avoid antibiotic therapy failures in urosepsis treatments. Blood stream infection models were established by growing E. coli CFT073 in pooled human serum with and without ciprofloxacin and compared to Iso-sensitest medium. The antibiotic challenge was introduced at mid-logarithmic phase of growth of the organism to depict a clinical scenario . Global gene expression profiling of these conditions was examined using commercial DNA microarrays. The organism’s metabolic genes appeared to be regulated differently in each medium, this indicated that the bacterial growth regulation were different between the models. Bacterial growth in human serum mainly involved regulations of amino acid synthesis/utilisation such as glycine, arginine, thiamine, regulations of fimbrial proteins and bacteriophage genes. When comparing the responses to antibiotic challenge, bacteria grown in the respective medium displayed specific responses to the antibiotic challenge which were not seen in the other media. The common functions  of genes that responded to the ciprofloxacin challenge were SOS response, DNA repair, DNA replication, fimbrial genes and bacteriophage initiation. A subset of the bacteriophage genes showed similar responses between the three models. From genes that were differentially regulated, responses observed in the serum model appeared to have the highest fold changes. In this study we established new models to investigate blood stream infections. They have been used to identify previously unknown differences in the molecular response to antibiotic treatment by the uropathogenic E. coli CFT073 depending on the media. These unique responses will help to unravel the complexity of bloodstream infection and can help to improve the antibiotic therapy that is used.

overall_design: A 20 array study using total RNA recovered from bacteria from bacteria that were either grown in human serum or Iso-Sensitest (IST) broth, with and without ciprofloxacin challenge.  Arrays were performed in 5 biological replicates from each condition.Upon QC checks, certain biological repeats were excluded due to poor hybridisation results.


title: Escherichia coli global gene expression due to ciprofloxacin challenge in bloodstream infection like conditions


title: Expression data from melanoma xenograft tumors originating from primary immortalized melanocytes

city: Houston

first: Lynda

last: Chin

summary: PREX2 truncating mutations occur in melanoma. We used microarray based gene expression profiling to compare expression patterns between xenografts harboring control GFP, wt PREX2 or various human relevant PREX2 mutants

overall_design: Primary xenograft tumors derived from primary immortalized melanocytes expressing indicated constructs were grown in ncr-nude mice and tumors harvested before before reaching 1.5cm size

first: Yonathan

last: Deribe

first: Chia

last: Wu


title: Estradiol facilitates functional integration of induced pluripotent stem cell-derived dopaminergic neurons into striatal neuronal circuits via activation of integrin α5β1

status: Public on Mar 31 2016

city: Stockholm

first: Kaneyasu

last: Nishimura

address: Scheeles väg 1

country: Sweden

institute: Karolinska Institutet

summary: To realize cell transplantation therapy for Parkinson's disease (PD), the grafted neurons should be integrated into the host neuronal circuit in order to restore the lost neuronal function. Here, using wheat germ agglutinin-based trans-synaptic tracing, we show that integrin α5 is selectively expressed in striatal neurons that are innervated by midbrain dopaminergic (DA) neurons from the mouse experiments. Additionally, we found that integrin α5β1 was activated by the administration of estradiol-2-benzoate (E2B) in striatal neurons of adult female rats. Importantly, we observed that the systemic administration of E2B into hemi-parkinsonian rat models facilitates the functional integration of grafted DA neurons derived from human induced pluripotent stem cells into the host striatal neuronal circuit via the activation of integrin α5β1. Finally, methamphetamine-induced abnormal rotation was recovered earlier in E2B-administrated rats than in rats that received other regimens. Our results suggest that the simultaneous administration of E2B with stem cell-derived DA progenitors can enhance the efficacy of cell transplantation therapy for PD.

overall_design: 0.5 µL of 1% WGA Alexa Fluor 488 solution was stereotactically injected into the bilateral SNpc (from the bregma: A -3.0, L ±1.2, V -4.2 and TB 0) of mouse. Two days after injection, a striatum sample was dissected from the mouse brain and dissociated into a single cell population by Accumax (Innovated Cell Technologies, Inc., CA, USA). To separate a two-cell population, Alexa Fluor 488+ cells and Alexa Fluor 488- cells were sorted using a FACSAria III cell sorter. Dead cells were identified and eliminated by 7-amino-actinomycin D (7-AAD) staining.

first: Jun

last: Takahashi


title: DNMT1 KNOCKOUT IN MURINE LIVER (methylation)

city: Copenhagen

first: Jesper

middle: B

last: Andersen

address: Ole Maaloes Vej 5

department: Biotech Research and Innovation Centre

institute: Copenhagen University

summary: Methylation profilingof isolated hepatocytes after DNMT1 knock down. DNMT1 KO versus control livers at week 4, 8 and 20.

overall_design: 18 samples analyzed

first: Snorri

last: Thorgeirsson


title: DNMT1 KNOCKOUT IN MURINE LIVER


title: Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis with no increased bleeding risk

city: Pamplona

first: Jose

last: Hermida

address: Pio XII, 55

institute: CIMA

summary:
Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts.
In WT mice, Hsp70 inducers (TRC051384, or tubastatin A) delayed thrombus formation. Remarkably, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression, higher circulating levels of activated protein C (APC) upon thrombotic stimulus and increased protection against endothelial apoptosis. Thus, Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, being especially promising in situations where there is a major bleeding hazard.

overall_design: Microarray analysis in peripheral blood cells includes eight patients with AF and stroke and eight AF subjects without stroke

first: Mikel

last: Allende

first: José


title: Influence of ATM-mediated DNA damage response on genomic variation in human induced pluripotent stem cells (Affymetrix expression)

status: Public on Mar 29 2016

city: Rochester

first: Hu

last: Li

state: MN

address: 200 First Street, Gonda Building G19-408

department: Molecular Pharmacology & Experimental Therapeutics

institute: Mayo Clinic

summary: Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors.

overall_design: We isolated RNA from Ataxia-telangiectasia (A-T) patient fibroblast derived iPS cells and A-T patient fibroblasts for hybridization to the Affymetrix gene expression microarrays.

first: Junjie

last: Lu

first: Paul

last: Lerou


title: Ingenol mebutate induces profound inflammatory and wound healing responses in uninvolved and actinic keratosis skin

city: Copenhagen N

first: Thomas

last: Litman

state: Outside the US or Canada

address: Blegdamsvej 3C

department: ISIM

institute: University of Copenhagen

summary:
We studied the transcriptomic profile of actinic keratosis (AK) skin compared to matched samples from uninvolved skin (US) before and after treatment with ingenol mebutate gel.
We found that AK has a distinct mRNA profile that separates it from uninvolved skin. In particular, numerous genes associated with epidermal development and keratinocyte differentiation, such as LCE3D, SPRR1A, PI3 and several genes in the keratin family were highly expressed in AK0 skin, but not in US0, in line with the hyperkeratosis characteristic for AK. Topical application of ingenol mebutate had a profound effect on the gene expression profile, and interestingly, many more genes were affected in US than in AK. Enrichment analysis revealed that the main responses to ingenol mebutate treatment of both US and AK were inflammatory response, response to wounding, and wound healing.

overall_design: 30 skin biopsies were analysed; 5 from each of 6 AK patients. Before initiation of treatment, baseline biopsies were taken from one AK lesion (AK0) and from uninvolved skin (US0). A third biopsy was taken after day 1 application of ingenol mebutate from one AK lesion (AK1). The fourth and fifth biopsies were obtained one day after the second topical application with ingenol mebutate from an AK lesion (AK2) and from uninvolved skin (US2), respectively.

first: John

last: Zibert

first: Maria

last: Høyer-Hansen


title: Molecular alterations in bone marrow mesenchymal stromal cells (BM-MSC) derived from acute myeloid leukemia patients (AML)

status: Public on Mar 30 2016

city: Berlin

first: Eva

middle: Kristin

last: von der Heide

address: Hindenburgdamm 30

department: Hematology

institute: Charite Berlin

summary: Genome wide methylation profiling of BM-MSC derived from AML patients in comparison to healthy donor controls using Illumina Infinium HumanMethylation450 Beadchip

overall_design: bisulfit converted genomic DNA extracted from BM-MSC samples (AML n=32) and healthy donor controls  (n=12) were hybridized onto an Illumina Infinium HumanMethylation450 Beadchip

first: Martin

last: Neumann

first: Sebastian

last: Vosberg

first: Jutta

middle: O

last: Tanchez

first: Konstandina

last: Isaakidis

first: Cornelia

last: Schlee

first: Korinna

last: Jöhrens

first: Ioannis

last: Anagnostopoulos

first: Liliana

last: Mochmann

first: Daniel

last: Nowak

first: Wolf

last: Hofmann

first: Philipp

last: Greif

first: Claudia

last: Baldus


title: Transcriptome Analysis in  Peripheral Airway Epithelium of Distinct Lung microbiome

city: new york

first: Jun-Chieh

middle: James

last: Tsay

address: 562 First Ave. NBV 7N27

department: Medicine

institute: NYU Langone Medical Center

summary:
In this study, we assessed lower airway microbiome from a cohort of patients to determine whether specific microbiome taxa correlate with with specific metabolic activities.
In a subset of 12 patients, transcriptomic expression were analyzed to compare host mucosa immune response

overall_design: We collected peripheral airway brushings from the 12 subjects whose lung microbiome were analyzed; Total RNA were obtained from the peripheral airway epithelium.

middle: J

first: Leopoldo

middle: N

last: Segal

first: William

last: Rom


title: Genome-wide methylation profiles in primary intracranial germ cell tumors indicate primordial germ cell origin of germinoma [Illumina]

first: Shintaro

last: Fukushima

summary: The pathogenesis of intracranial germ cell tumors (iGCTs) is not yet fully uncovered despite exhaustive genomic analyses. By means of a genome-wide methylation analysis, we show that pure germinoma is characterized by global DNA low methylation, a unique epigenetic feature distinct from all other subtypes of iGCTs. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, indicating the cells of origin. Unlike PGC, however, hypomethylation extends to LINE1 retrotransposon. Microdissected histologically and epigenetically distinct components of mixed-GCTs shared identical mutations in the MAPK or PI3K pathways, suggesting that the genetic alterations were likely to have occurred at the pre-implantation phase in early embryogenesis. Thus, we propose iGCTs are “Zygotoma”.

overall_design: Bisulphite converted DNA from 77 samples were hybridized to the Illumina Infinium HumanMethylation450 Beadchip


title: Expression data for HepG2 cells treated with 34 different chemicals

status: Public on Mar 28 2016

city: MASON

first: Jay

middle: Patrick

last: Tiesman

state: OH

address: PO BOX 8006

department: Global Biotechnology

institute: Procter & Gamble

summary:
This study provides an evaluation of changes in gene expression associated with treating human HEPG2 cells with 34 different chemical compounds.
Gene expression experiments studies were performed in triplicate (n=3) with the cells for each replicate treated and harvested on separate days.

overall_design: This series is part of a SuperSeries in which human toxicology-relevant cell lines were treated with three doses of 34 chemical compounds (and corresponding vehicle controls) for 6 hours.  Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported.

middle: P

first: Yuching

last: Shen

first: K

last: DeAbrew


title: Overexpression of LMO2 causes aberrant human T-cell development in vivo by three potentially distinct cellular mechanisms

status: Public on Mar 26 2016

city: Leiden

first: Martijn

last: Cordes

state: Zuid-Holland

address: Albinusdreef 2

institute: Leiden University Medical Centre

summary: LMO2 overexpressing transgenic mouse models suggest an accumulation of immature T-cell progenitors in the thymus as main pre-leukemic event. The effects of LMO2 overexpression on human T-cell development in vivo, however, are unknown. Here we report studies of a humanized mouse model transplanted with LMO2 transduced human hematopoietic stem and progenitor cells. The effects of LMO2 overexpression were confined to the T-cell lineage although initially multipotent cells were transduced. Three  effects of LMO2 on human T-cell development were observed: 1) a block at the DN/ISP stage, 2) an accumulation of CD4+CD8+ double positive CD3- cells and 3) an altered CD8/CD4 ratio with enhanced peripheral T lymphocytes

overall_design: Single stranded cDNA was synthesized from 1000 pg total RNA using the Ovation Pico WTA System V2 Module (NuGEN Technologies Inc, Leek, The Netherlands) in combination with the Encore Biotin Module (NuGEN Technologies Inc) according to the instructions of the manufacturer. Biotin labeling and fragmentation was performed and fragmented cDNA was hybridized onto Affymetrix Gene Atlas human U219 arrays.

first: Anna-Sophia

last: Wiekmeijer

first: Karin

last: Pike-Overzet

last: Brugman

first: Marja

middle: C

last: Van Eggermond

first: Edwin

middle: F

last: De Haas

first: Yunlei

last: LI

last: Oole

first: Wilfred

last: Van Ijcken

first: R

last: Egeler

first: Jules

last: Meijerink

first: Frank

last: Staal


title: Expression data for Ishikawa cells treated with 34 different chemicals

summary:
This study provides an evaluation of changes in gene expression associated with treating human Ishikawa cells with 34 different chemical compounds.
Gene expression experiments studies were performed in triplicate (n=3) with the cells for each replicate treated and harvested on separate days.


title: Expression data for MCF7 cells treated with 34 different chemicals

summary:
This study provides an evaluation of changes in gene expression associated with treating human MCF7 cells with 34 different chemical compounds.
Gene expression experiments studies were performed in triplicate (n=3) with the cells for each replicate treated and harvested on separate days.


title: Cbl family proteins are required to maintain the proteome homeostasis in mammary epithelial cells

status: Public on Mar 25 2016

city: Omaha

first: Mayumi

last: Naramura

state: NE

address: 985950 Nebraska Medical Center

department: Eppley Institute

institute: University of Nebraska Medical Center

summary:
EGFR degradation is delayed in Cbl, Cbl-b double-deficient MCF10A but EGF stimulation does not enhance their growth.
We performed a transcriptome analysis to gain insights into biological consequences of Cbl, Cbl-b loss in mammary epithelial cells.

overall_design: We compared the transcriptome of MCF10A cells expressing shRNA against Cbl and Cbl-b with control shRNA-expressing cells using Affymetrix U133 Plus 2.0. Each sample was prepared in duplicates. Data were analyzed by GSEA.

first: Chandrani

last: Mukhopadhyay


title: Expression data for HepaRG cells treated with 34 different chemicals

last: Tiesman

summary:
This study provides an evaluation of changes in gene expression associated with treating human HepaRG cells with 34 different chemical compounds.
Gene expression experiments studies were performed in triplicate (n=3) with the cells for each replicate treated and harvested on separate days.


title: In silico analyses guides selection of BET inhibitors for triple negative breast cancer treatment

status: Public on Mar 23 2016

city: Salamanca

first: Javier

last: Pérez Peña

address: C/Richard Ford Nº39, 2ºB

department: Centro Regional de Investigaciones Biomédicas

institute: Universidad de Castilla La Mancha

summary:
Triple negative breast cancer (TNBC) is an incurable disease with poor prognosis. At this moment, therapeutic options are limited to chemotherapy and no targeted agent has reached the clinical setting. Bromodomain and extraterminal (BET) inhibitors are a new family of compounds that inhibit bromodomain containing proteins affecting the expression of transcription factors (TFs), therefore modifying the expression of relevant oncogenic genes.
We decided to performed gene-set enrichment analyses to get insights into the mechanism of action of these compounds.

overall_design: We treated cells with JQ1 and extracted RNA at 12 and 24 hours.

last: Pérez-Peña

first: Alberto

last: Ocaña


title: Human toxicology-relevant cell lines treated with three doses of 34 chemical compounds

first: Jay

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

overall_design: Refer to individual Series


title: Expression data from Breast cancer subtypes

status: Public on Mar 24 2016

city: PARIS

first: Fatima

last: Mechta-Grigoriou

address: 26 rue d'Ulm

department: INSERM U830

country: France

institute: Institut Curie

overall_design: In a cohort study of primary invasive breast cancer (41 TN, 30 HER2, 29 Luminal A and 30 Luminal B) as well as 11 normal tissues samples and 14 cell lines , we obtained a tumor specimen at surgery before any patient treatment. Total RNA was extracted from all samples and the whole transcriptome was quantified with Affymetrix U133 Plus 2.0 Chips.

first: Tina

last: Gruosso

first: Yann

last: Kieffer

first: Thierry

last: Dubois