title: Hypothalamic gene expression profiles from diet-induced obese mice after Celastrol or Withaferin A treatments

city: Daegu

first: Jaemin

last: Lee

state: Select One

address: 333 Techno Jungang Daero, Hyeonpung-Myeon, Dalseong-Gun

department: New Biology

institute: DGIST

summary: Obesity is characterized by central leptin resistance. Celastrol has been identified to reduce leptin resistance in diet-induced obese and leptin resistant mice. Current microarray data provide the hypothalamic gene expression profiles from mice treated with Celastrol or Withaferin A.

overall_design: Expression profiles from mice treated with Celastrol or Withaferin A

first: Umut

last: Ozcan


title: Chronic inflammation and carcinogenesis caused by intestinal specific ablation of integrin alpha6 beta4

status: Public on Jul 07 2016

city: Illkirch

first: Doulaye

last: Dembele

address: 1 rue Laurent Fries

department: Biopuces

country: France

institute: IGBMC

summary: Inflammatory bowel diseases (IBD) in humans are characterized by chronic inflammation and gastrointestinal tissue damage, caused by a combination of genetic and environmental factors. It has been largely documented that IBD frequently lead to colorectal cancers (CRC). The identification of causative factors of IBD is thus essential to understand CRC progression and develop therapeutical approaches. Models have been described in which molecular alterations are combined with inflammatory treatments in order to recapitulate IBD-associated CRC. Here, we describe a mouse line, α6fl/fl Villin-Cre, in which inactivation of the gene encoding the integrin alpha-6 subunit (ITGA6) specifically in the intestinal mucosa results into chronic inflammation and intestinal carcinogenesis. In these mice, the loss of integrin alpha-6 beta-4, a receptor mediating the attachment of epithelial cells to laminins, leads to epithelial detachment, hyperplasia, chronic inflammation, rectal prolapses, and ultimately adenocarcinomas. Alterations of differentiation affecting mucus secreting (goblet) cells as well as changes in expression of essential intestinal transcription factors were detected. Thus alpha-6 beta-4 integrin is a key factor for the maintenance of intestinal integrity and its loss may represent a risk factor for tumor progression associated with IBD.

overall_design: Transcriptome analysis of RNA from normal versus inflamed and carcinomatous rectal mucosa of α6 integrin deficient intestinal epithelium mice was performed. RNAs were prepared from 5 adenocarcinomas, which were macrodissected from the rectal prolapses and 4 flanking inflamed rectal mucosa of 53-80 week-old α6fl/fl Villin-Cre mice. RNAs from normal rectal mucosa were obtained by rectum scraping from 4 matched control animals. The transcriptome analysis was performed using the Affymetrix Mouse Gene 1.0 ST arrays. Images were processed using affymetrix GeneChip® Command Console® Software (AGCC) (version 2.0) and numerical value were generated using Affymetrix Expression Console™ Software (version 1.1).

first: Adele

last: De Arcangelis

first: Elisabeth

last: Georges-Labouesse


title: Analysis of Mast Cells in Hermansky-Pudlak Syndrome Type-1

status: Public on Jul 01 2016

city: Bethesda

first: Arnold

last: Kirshenbaum

state: Maryland

address: 10 Center Drive

department: NIAID

country: USA

institute: NIH

summary:
The near-normalization of constitutive cytokine and matrix release following rescue by HPS1 transduction of HPM cells suggests that HPS-1 HuMCs may contribute to pulmonary fibrosis and constitute a target for therapeutic intervention.
Microarray analysis of HPS-1 HuMCs and non-transduced HPM cells confirmed upregulation of differentially expressed genes involved in fibrogenesis and degranulation.

overall_design: Six HPS-1 patients and five healthy controls were studied following informed consent. One typical HPS-1 HuMC culture at 5-6 weeks was eventually overgrown by a population of smaller, rapidly dividing cells. Analysis of differential gene expression from 8 wk old control and HPS-1 HuMCs and HPM cells was performed using cDNA generated from cultured cells.

first: Maarten

last: Leerkes

first: Avanti

last: Desai


title: MEIS2 is a novel oncogenic partner in AML1-ETO positive AML [Affymetrix]

status: Public on Jul 04 2016

city: Ulm

first: Medhanie

middle: Assmelash

last: Mulaw

address: Albert-Einstein-Allee 11

country: Germany

institute: University of Ulm

summary: MEIS2 collaborates with AML1-ETO in inducing acute myeloid leukemia in a murine bone marrow transplantation model

overall_design:
We compared Gene expression profile (GEP) of murine bone marrow cells transduced with GFP, AML1-ETO, MEIS2, and AML1-ETO/MEIS2. Data from MEIS1 and AML1-ETO/MEIS1 is also included.
Mouse bone marrow cells were kept in culture for 48hrs after retroviral transduction. GFP positive cells were then sorted and cells were kept for further 24 hours in culture before microarray analysis.

middle: A


title: Expression data from  15h-grown E. coli

city: Hangzhou

first: Yue

last: Pu

address: 38 Zheda Road

country: China

institute: Zhejiang University

summary:
The production of lycopene in E. coli can be improved by mutated CRP.CRP is a well-known global transcription factor regulating the expression of more than 400 genes that belong to different functional groups of E. coli. During the accumulation of lycopene in E. coli, the engineered CRP alters the expression level of many genes, such as the genes belong to lycopene production pathway, which leads to the improved lycopene production.
We used microarrays to detail the gene expression under the condition of engineered CRP and identified distinct classes of up-regulated and down-regulated genes.

overall_design: E. coli growed for 15h was selected for RNA extraction and hybridization on Affymetrix microarrays. As we know that the biggest difference in lycopene production was at 15h during cultivation, so we chose 15h as the time-point.


title: Genome-wide DNA methylation study of hip and knee osteoarthritic and healthy cartilage reveals embryonic organ and skeletal system morphogenesis as major pathways involved in osteoarthritis

city: St. John's

first: Guangju

last: Zhai

state: NL

address: 300 Prince Philip Drive

department: Genetics, Medicine

country: Canada

institute: Memorial University of Newfoundland

type: Methylation profiling by genome tiling array

summary: Cartilage samples were collected from hip or knee joint replacement patients either due to primary OA or hip fractures as controls. DNA was extracted from the collected cartilage and assayed by Illumina Infinium HumanMethylation450 BeadChip array, which allows for the analysis of >480,000 CpG sites.

overall_design: Bisulphite converted DNA from 5 hip osteoarthritic, 6 knee osteoarthritic and 7 hip healhty cartilage samples were hybridised to the Illumina Infinium HumanMethylation450 BeadChip array

first: Erfan

last: Aref-Eshghi

first: Yuhua

last: Zhang

first: Ming

last: Liu

first: Patricia

middle: E

last: Harper

first: Glynn

last: Martin

first: Andrew

last: Furey

first: Roger

last: Green

first: Guang

last: Sun

first: Proton

last: Rahman


title: Transcription Factor TLX1 Controls Retinoic Acid Signaling to Ensure Spleen Development [Microarray Expression]

city: Milano

first: Andrea

last: Brendolan

address: Via Olgettina 60

department: Experimental Oncology

country: Italy

institute: San Raffaele Scientific Institute

summary: The molecular mechanisms underlying asplenia, a condition often associated with overwhelming infections remain largely unknown. During spleen development, the transcription factor TLX1 controls morphogenesis and organ expansion, and loss of it causes spleen agenesis. However, the downstream signaling pathways that are deregulated in the absence of TLX1 are mostly unknown. Herein, we demonstrate that loss of Tlx1 in the splenic mesenchyme causes increased retinoic acid (RA) signaling. Increased RA activity causes premature differentiation of the splenic mesenchyme and reduced vasculogenesis of the splenic anlage. Moreover, excess or deficiency in RA signaling, as observed in Cyp26b1 or Rdh10 mutants respectively, also results in spleen growth arrest. Genome-wide analysis revealed that TLX1 binds RA-associated genes through the AP-1 site and cooperates with the AP-1 family transcription factors to regulate transcription. Pharmacological inhibition of RA signaling partially rescues the spleen defect. These findings establish the critical role of TLX1 in controlling RA metabolism, and provide novel mechanistic insights into the molecular determinants underlying congenital asplenia.

overall_design: Samples: 3 replicates of E13.5 spleens from Tlx1 heterozygous embryos were compared to 3 replicates of E13.5 spleens from Tlx1 homozygous embryos

first: Giovanni

last: Tonon


title: TGFbRII-Eomes in CD4 T cells during chronic viral infection

status: Public on Jun 30 2016

city: San Diego

first: Gavin

last: Lewis

state: Ca

address: 3210 Merryfield Row

department: Immunology

institute: Janssen R&D

summary:
Transcriptome analysis of CD4+ PD1+ T cells during LCMV CL13 infection
Gene expression in WT and ERt2-cre;TGFbRII flox virus specific CD4 T cells

overall_design: Mixed chimeras of WT:ERt2cre+TGFbRII flox/flox were infected 9 days with LCMV and splenic CD4+ PD1+CD49d+ Cd8a- T cells sorted from each compartment by congenic marker

first: Elina

last: Zuniga


title: DNA methylation profiles of human blood samples from older Tsimane, Caucasians, and Hispanics

status: Public on Jul 13 2016

city: Los Angeles

first: Steve

last: Horvath

state: CA

address: 695 Charles E. Young Drive South, Box 708822

department: Human Genetics

institute: University of California, Los Angeles

summary:
Human DNA methylation Beadchip v1.2 was used to profile n=310  whole blood samples.
The main goal of the study was to measure the epigenetic age (also known as DNA methylation age) of different ethnic groups. Here we focus on subjects older than 35. Groups include Tsimane Indians, Hispanics, and Caucasian samples. To measure DNA methylation age, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928.

overall_design: We analyzed whole blood samples from 235 Caucasians, 38 Hispanics, and 37 Tsimane Indians.

first: Michael

last: Gurven


title: Genome-wide methylation analysis of esophageal squamous cell carcinoma using Infinium HumanMethylation 450 BeadChip

city: Chuo-ku

first: Satoshi

last: Yamashita

state: Tokyo

address: Tsukiji 5-1-1

country: Japan

institute: National Cancer Center Research Institute

summary: DNA methylation in esophageal squamous cell carcinoma (ESCC)

overall_design: A picture of epigenetic alterations in ESCCs was characterized.

first: Takamasa

last: Takahashi

first: Takayoshi

last: Kishino

first: Hidetsugu

last: Nakazato

first: Hideyuki

last: Takeshima

first: Toshikazu

last: Ushijima


title: Trans-resveratrol induces a potential anti-lipogenic effect in lipopolysaccharide-stimulated enterocytes

city: Pamplona

first: Fermin

middle: I

last: Milagro

state: Navarra

address: c/ Irunlarrea 1

department: Centre for Nutrition Research

country: Spain

institute: University of Navarra

summary: Background: Resveratrol has been demonstrated to exert pleiotropic health beneficial effects. Among the various mechanisms of action antioxidant, anti-inflammatory, cardio- and cancer-protective outcomes have been reported. Particularly, an important function of this natural compound against atherosclerosis has been postulated and the action of resveratrol on lipids and lipoprotein levels seems to be of relevance in this pathology, but also for other metabolic diseases. Accordingly, taking into consideration the straight contact of resveratrol with the intestine, this study aimed to gain insights into the protective effects of trans-resveratrol on enterocyte physiology and metabolism in proinflammatory conditions. For this purpose, a DNA microarray analysis was conducted in Caco-2 cells where global gene expression profile at intestinal level was screened. Cells were pretreated with 50 μΜ of trans-resveratrol and, subsequently, lipopolysaccharide (LPS) was added for 48 h.   Results: The microarray analysis revealed 121 genes differentially expressed between resveratrol-treated and non-treated cells (B> 0). Four genes, inhibitor of DNA binding 1(ID1), histidine-rich glycoprotein (HRG), NADPH oxidase (NOX1) and sprouty homolog 1 (SPRY), were upregulated by LPS treatment, but significantly downregulated with trans-resveratrol pretreatment (padj< 0.05). Moreover, genes implicated in pathways related to lipid metabolism, such as synthesis of lipids (z-score= -1.195) and concentration of cholesterol (z-score= -0.109), were markedly downregulated by trans-resveratrol. Other genes implicated in lipid metabolism, but also in cell death and survival function, such as transcription factors Krüppel-like factor 5 (KLF5) and amphiregulin (AREG), were also significantly inhibited by trans-resveratrol pretreatment. RT-qPCR-data confirmed the microarray results. Special mention deserves acyl-CoA synthetase long-chain family member 3 (ACSL3) and endothelial lipase (LIPG), which were downregulated by the stilbene and have been previously associated with fatty acid synthesis and obesity in other tissues.   Conclusions: This study envisages that trans-resveratrol might exert important anti-lipogenic effect at intestinal level under proinflammatory conditions, which have not been previously described.

overall_design: The experiment was conducte in Caco-2 cells. There were three experimental groups (n=5), Caco-2 cells stimulated with lipopolysaccharides (LPS), Caco-2 cells stimulated with LPS and pre-treated with trans-resveratrol (LPS+RSV) and non-treated Caco-2 cells.

first: Usune

last: Etxeberria

first: Victor

last: Segura

first: J

last: Martínez

first: Rosa

last: Castilla-Madrigal

first: M

middle: P

last: Lostao


title: CpG island methylation profile in non-invasive oral rinse samples is predictive of oral and pharyngeal carcinoma

city: Cincinnati

first: Scott

middle: M

last: Langevin

state: OH

address: 160 Panzeca Way, ML0056

department: Department of Environmental Health

institute: University of Cincinnati College of Medicine

summary: Epigenome-wide association study (EWAS) of oral rinse samples from a case-control study of 154 cases and 72 controls. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in oral rinse samples.

overall_design: Bisulphite converted DNA from the 226 oral rinse samples were hybridized to the Illumina Infinium HumanMethylation450 Beadchip

first: S

first: K

middle: T

last: Kelsey


title: DNA methylation profiles of human saliva

first: Steve

summary:
Human DNA methylation Beadchip v1.2 was used to analyze n=259 human saliva samples from Caucasians (non-Hispanic whites) and Hispanics collected from the PEG study (directed by Dr Beate Ritz).
The main goal of the study was to measure the epigenetic age (also known as DNA methylation age) of saliva. To measure DNA methylation age, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928.

overall_design:
The data set contains men and women of two ethnic backgrounds: Hispanics and Caucasians.

Sex: Indicates whether the sample came from a female or male human subject.

Age: Chronological age at the time of the DNA sample collection.

Ethnicity: Two values: Hispanic (living in the US) and Caucasian (living in the US).

first: Beate

last: Ritz


title: Deregulation of the pRb-E2F4 axis alters epidermal homeostasis and favors tumor development

status: Public on Jul 09 2016

city: Madrid

first: Monica

last: Martinez-Fernandez

address: Avda Complutense 40

institute: CIEMAT

summary: E2F/RB activity is altered in most human tumors. The retinoblastoma family of proteins plays a key role in regulating the progression of the cell cycle from the G1 to S phases. This is achieved through negative regulation of E2F transcription factors, important positive regulators of cell cycle entry. E2F family members are divided in two groups: activators (E2F1-E2F3a) and repressors (E2F3b-E2F8). E2F4 accounts for a large part of the E2F activity and is a main E2F repressor member in vivo. Perturbations in the balance from quiescence towards proliferation contribute to increased mitotic gene expression levels frequently observed in cancer. We have previously reported that combined Rb1-Rbl1 and Rb1-E2F1 ablation in epidermis produces important alterations in epidermal proliferation and differentiation, leading to tumor development. However, the possible roles of E2F4 in this context are still to be determined. Here we show the absence of any discernible phenotype in the skin of mice lacking of E2F4. In contrast, the inducible loss of Rb1 in the epidermis of E2F4-null mice produced multiple skin abnormalities including altered differentiation and proliferation, spontaneous wounds, carcinoma in situ development and stem cell perturbations. All these phenotypic alterations are associated with extensive gene expression changes, the induction of c-myc and the Akt activation. Moreover, the whole transcriptome analyses in comparison with previous models generated also revealed extensive changes in multiple repressive complexes and in transcription factor activity. These results point to E2F4 as a master regulator in multiple steps of epidermal homeostasis in Rb1 absence.

overall_design: Gene expression was compared between skin from transgenic Rbf/f;K14creERTM, Rbf/f;K14creERTM;E2F1-/-, Rbf/f;K14creERTM;E2F4-/- and Rbf/f, E2F4-/- mice. All mice were treated with tamoxifen.

first: Clotilde

last: Costa

first: Mirentxu

last: Santos

first: Mónica

last: Martínez-Fernández

first: Corina

last: Lorz

first: Sara

last: Lázaro

first: Jesús

last: Paramio


title: Effect of YAP overexpression on HuCCT1 cholangiocarcinoma cell line transcriptome (YAPS94A)

city: Basel

first: Yann

last: Abraham

address: Postfach

department: NIBR/DMP

country: Switzerland

institute: Novartis Pharma AG

summary:
The YAP pathway in regulating organ size by integrating external signals to control the expression of genes involved in cell proliferation. YAP is known to be involved in tumorigenesis in several tissues, yet its role in cholangiocarcinoma is not established
We used microarrays to assess the role of YAP pathway in cholangiocarcinoma either by overexpressing a constitutively active YAP1 mutant, or by downregulating YAP1 expression using shRNA

overall_design: HuCCT1 cells where transfected with either an empty vector or a vector overexpressing the constitutively active YAP1 S127A; cells were harvested, RNA was collected and analyzed using microarray

first: Patricia

last: Marti

first: Tanja

last: Blumer

first: Michael

last: Dill

first: Claudia

last: Stein

first: Philippe

last: Megel

first: Giorgia

last: Jurisic

first: Zuzanna

last: Makowska

first: Monika

last: Pikiolek

first: Vanessa

last: Orsini

last: Agarinis

first: Luigi

last: Tornillo

first: Tewis

last: Bouwmeester

first: Heinz

last: Ruffner

first: Andreas

last: Bauer

first: Tobias

last: Schmelzle

first: Christian

last: Parker

last: Terracciano

first: Markus

middle: H

last: Heim

first: Jan

middle: S

last: Tchorz


title: The landscape of pharmacogenomic interactions in human cancer

status: Public on Jul 05 2016

city: L'Hospitalet del Llobregat

first: Sebastian

last: Moran

state: Barcelona

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

department: PEBC

institute: IDIBELL

summary: Systematic studies of the cancer genome are providing unprecedented insights into the molecular nature of human cancer. Using this information to guide the development and application of therapies in the clinic remains challenging. Here we report how cancer driving alterations detected in 11,215 tumors and 29 different tissues (integrating multiple omics) correlate with response to 265 compounds profiled in 1,001 cancer cell lines. We find that cell lines faithfully resemble tumours on the domain of these alterations, and numerous examples of altered genes and pathways conferring drug sensitivity and resistance. Significantly, logic-based modeling improves our ability to identify drug sensitive sub-types and machine-learning methods enable us to investigate the predictive ability of the different data-omics. We provide a comprehensive analysis of how somatic alterations identified from the large-scale analysis of primary tumors impact on drug response. This represents a rich resource to help identify therapeutic options for selected cancer populations.

overall_design:
DNA was quantified by Quant-iT PicoGreen dsDNA Reagent (Invitrogen) and the integrity was analyzed in a 1.3% agarose gel. Bisulfite conversion of 600 ng of each sample was perform according to the manufacturer's recommendation for Illumina Infinium Assay. Effective bisulphite conversion was checked for three controls that were converted simultaneously with the samples. 4 ul of bisulfite converted DNA were used to hybridize on Infinium HumanMethylation 450 BeadChip, following Illumina Infinium HD Methylation protocol. Chip analysis was performed using Illumina HiScan SQ fluorescent scanner. The intensities of the images are extracted using GenomeStudio (2011.2) Methylation module (1.8.5) software. Methylation score of each CpG is represented as beta value.
The cell lines are not treated with any drug or coumpound.

first: Holger

last: Heyn

first: Manel

last: Esteller


title: Biomarkers of dietary energy restriction in women at increased risk of breast cancer

city: Carrington Crescent

first: Andrew

last: Sims

state: Edinburgh

address: Systems Medicine Building

department: Institute of Genetics and Molecular Medicine

country: United Kingdom

institute: University of Edinburgh

summary:
Dietary energy restriction (DER) reduces risk of spontaneous mammary cancer in rodents. In humans, DER in premenopausal years seems to reduce risk of postmenopausal breast cancer. Markers of DER are required to develop acceptable DER regimens for breast cancer prevention. We therefore examined markers of DER in the breast, adipose tissue, and serum. Nineteen overweight or obese women at moderately increased risk of breast cancer (lifetime risk, 1 in 6 to 1 in 3) ages between 35 and 45 were randomly allocated to DER [liquid diet, 3,656 kJ/d (864 kcal/d); n = 10] or asked to continue their normal eating patterns (n = 9) for one menstrual cycle. Biopsies of the breast and abdominal fat were taken before and after the intervention. RNA was extracted from whole tissues and breast epithelium (by laser capture microdissection) and hybridized to Affymetrix GeneChips. Longitudinal plasma and urine samples were collected before and after intervention, and metabolic profiles were generated using gas chromatography-mass spectrometry. DER was associated with significant reductions in weight [-7.0 (+/-2.3) kg] and in alterations of serum biomarkers of breast cancer risk (insulin, leptin, total and low-density lipoprotein cholesterol, and triglycerides). In both abdominal and breast tissues, as well as isolated breast epithelial cells, genes involved in glycolytic and lipid synthesis pathways (including stearoyl-CoA desaturase, fatty acid desaturase, and aldolase C) were significantly down-regulated. We conclude that reduced expressions of genes in the lipid metabolism and glycolytic pathways are detectable in breast tissue following DER, and these may represent targets for DER mimetics as effective chemoprophylactic agents
Transcriptomic and Metabolomic intervention study of continuous energy restriction in 19 participants

overall_design: 10 Participants were randomised to DER, 9 to control. Samples were taken before DER and once menstrual cycle later from adopsie fat and breast tissue

first: Kai

middle: R

last: Ong

first: Michelle

last: Harvie

first: Mary

last: Chapman

first: Warwick

middle: B

last: Dunn

first: David

last: Broadhurst

first: Royston

last: Goodacre

last: Wilson

first: Nicola

last: Thomas

first: Robert

last: Clarke

first: Anthony

last: Howell


title: ER stress and LIP expression array

status: Public on Jul 08 2016

city: Rehovot

first: Rina

last: Wassermann Dozorets

address: Herzl St 234

department: Molecular Genetics

country: Israel

institute: Weizmann Institute of Science

summary: The main goal of this study was to identify genes involved in augmentation of ER stress-triggered cell death by C/EBPβ LIP transcription factor.

overall_design: Three independent experiments were performed, each experiment included control and 5 different treatments.

first: Menachem

last: Rubinstein


title: Pathologic Immune Pathways in Psoriasis are Rapidly Attenuated by Tofacitinib Treatment: A Randomized Phase 2 Study in Patients with Moderate to Severe Psoriasis

city: New York

first: Mayte

last: Suarez-Farinas

state: NY

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

institute: Mount SinaiSchool of Medicine

summary: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to elucidate the molecular mechanisms underlying the clinical efficacy of tofacitinib in patients with psoriasis. Twelve patients with plaque psoriasis were randomized (3:1) to receive 10 mg of tofacitinib or placebo twice daily for 12 weeks. Biopsy specimens were taken from nonlesional (baseline) and lesional (baseline, days 1 and 3, and weeks 1, 2, 4, and 12) skin. Biopsy specimens were examined for psoriatic epidermal features (thickness, Ki67+ keratinocytes and keratin 16 [KRT16] mRNA expression, and phosphorylated signal transducer and activator of transcription [pSTAT]+ nuclei) and T-cell and dendritic cell (DC) subsets by using immunohistochemistry, and mRNA transcripts were quantified by using a microarray. In lesional skin keratinocyte pSTAT1 and pSTAT3 staining was increased at baseline but reduced after 1 day of tofacitinib (baseline, median of 1290 pSTAT1+ cells/?m2; day 1, median of 332 pSTAT1+ cells/?m2; and nonlesional, median of 155 pSTAT1+ cells/?m2). Epidermal thickness and KRT16 mRNA expression were significantly and progressively reduced after days 1 and 3 of tofacitinib administration, respectively (eg, KRT16 decreased 2.74-fold, day 3 vs baseline, P = .016). Decreases in DC and T-cell numbers were observed after weeks 1 and 2, respectively. At week 4, significant decreases in IL-23/TH17 pathways were observed that persisted through week 12. Improvements in clinical and histologic features were strongly associated with changes in expression of psoriasis-related genes and reduction in IL-17 gene expression. Tofacitinib has a multitiered response in patients with psoriasis: (1) rapid attenuation of keratinocyte Janus kinase/STAT signaling; (2) removal of keratinocyte-induced cytokine signaling, leading to reductions in pathologic DC and T-cell numbers to nonlesional levels; and (3) inhibition of the IL-23/TH17 pathway.

overall_design: Twelve patients with plaque psoriasis were randomized (3:1) to receive tofacitinib 10 mg or placebo twice daily for 12 weeks. Biopsies were taken from lesional and non-lesional skin at baseline, and from lesional skin on Day 1, Day 3, and Weeks 1, 2, 4 and 12. Biopsies were examined for psoriatic epidermal features (thickness; Ki67+ keratinocytes, keratin 16 [KRT16] mRNA expression; phosphoSTAT [pSTAT] + nuclei) and T-cell and dendritic cell (DC) subsets using immunohistochemistry. mRNA transcripts were quantified by microarray.

first: James

last: Krueger

first: Maryann

last: Whitley


title: Reprogramming-associated aberrant DNA methylation determines hematopoietic differentiation capacity of human induced pluripotent stem cells [iPSCs_methylation 2]

status: Public on Jun 29 2016

city: Kyoto

first: Yoshinori

last: Yoshida

address: 53, Kawahara-cho, Shogoin, Sakyo-ku

institute: Kyoto University

summary: The variation among induced pluripotent stem cells (iPSCs) in their differentiation capacity to specific lineages is frequently attributed to somatic memory. In this study, we compared hematopoietic differentiation capacity of 35 human iPSC lines derived from four different tissues and four embryonic stem cell lines. The analysis revealed that hematopoietic commitment capacity (PSCs to hematopoietic precursors) is correlated with the expression level of the IGF2 gene independent of the iPSC origins. In contrast, maturation capacity (hematopoietic precursors to mature blood) is affected by iPSC origin; blood-derived iPSCs showed the highest capacity. However, some fibroblast-derived iPSCs showed higher capacity than blood-derived clones. Tracking of DNA methylation changes during reprogramming reveals that maturation capacity is highly associated with aberrant DNA methylation acquired during reprogramming, rather than the types of iPSC origins. These data demonstrated that variations in the hematopoietic differentiation capacity of iPSCs are not attributable to somatic memories of their origins.

overall_design: Bisulfite-converted genomic DNA lysates from human induced pluripotent stem cells derived from dermal fibroblasts, peripheral T cells, cord blood, and dental pulp cells were hybridized to the Illumina HumanMethylation450 BeadChip.

first: Masatoshi

last: Nishizawa

first: Akira

last: Watanabe

first: Shinya

last: Yamanaka


title: Energy restriction in women at increased risk of breast cancer

first: Andrew

last: Sims

summary:
This SuperSeries is composed of the SubSeries listed below.
Gene expression profiling of continuous or intermittent energy restriction in women at increased risk of breast cancer

overall_design: Refer to individual Series


title: Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-treated diabetic mice

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

institute: Helmholtz Zentrum Muenchen

summary:
Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), is generally used to treat hyperlipidemia. Clinical trials on patients suffering from type 2 diabetes indicated that BEZ also has beneficial effects on glucose metabolism, but the underlying mechanisms remain elusive. Much less is known about the function of BEZ in type 1 diabetes.
Here, we show that BEZ treatment markedly improves hyperglycemia, glucose and insulin tolerance in streptozotocin (STZ)-treated mice, an insulin-deficient mouse model of type 1 diabetes presenting with very high blood glucose levels. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Our data demonstrate a beneficial effect of BEZ treatment on STZ mice reducing diabetes and suggest that BEZ ameliorates impaired glucose metabolism possibly via augmented hepatic mitochondrial performance, improved insulin sensitivity and metabolic flexibility.

overall_design: We performed gene expression microarray analysis on liver tissue derived from streptozotocin-treated mice treated with bezafibrate in addition.

first: Andras

last: Franko

first: Peter

last: Huypens

first: Susanne

last: Neschen

first: Martin

last: Irmler

first: Jan

last: Rozman

first: Birgit

last: Rathkolb

first: Frauke

last: Neff

first: Cornelia

last: Prehn

first: Guillaume

last: Dubois

first: Martina

last: Baumann

first: Rebecca

last: Massinger

first: Daniel

last: Gradinger

first: Gerhard

middle: K

last: Przemeck

last: Repp

first: Michaela

last: Aichler

first: Annette

last: Feuchtinger

first: Philipp

last: Schommers

first: Oliver

last: Stöhr

first: Carmen

last: Sanchez-Lasheras

first: Jerzy

last: Adamski

first: Andreas

last: Peter

first: Holger

last: Prokisch

first: Axel

last: Walch

first: Helmut

last: Fuchs

first: Eckhard

last: Wolf

first: Markus

last: Schubert

first: Rudolf

middle: J

last: Wiesner

last: Hrabĕ de Angelis


title: Intermittent energy restriction in overweight women at increased risk of breast cancer

first: Andrew

last: Sims

summary:
Lymphocyte and breast tissue samples from overweight woman at increased risk of breast cancer before and after 1 month of intermittant energy restriction
Introduction  Observational studies indicate that weight loss and energy restriction reduce breast cancer risk. Intermittent energy restriction (IER) reduces weight as well as, or more than continuous energy restriction (CER), but its effect on the breast and systemic metabolism as indicators of breast cancer risk are not known.  Methods  We assessed the effect of IER ( 2 days of 65% energy restriction) for one menstrual cycle on the breast (breast gene expression and fat cell size) and systemic metabolism (insulin resistance, lipids, serum and urine metabolites) in 23 overweight premenopausal women at high risk of breast cancer.   Unsupervised hierarchical analysis selected 100 genes with the highest variance between pre and post IER biopsies in 20 subjects, whilst mass spectrometry  was used to assess corresponding changes in serum (LCMS) and urine metabolites (GCMS) in 23 subjects in the restricted and unrestricted days of the IER.   Results Women lost on average 4.8% (± 2.0) of body weight and 8.0% (± 5.0) of body fat. Insulin resistance (HOMA) was reduced by 29.8% (±17.8) on the restricted days and by 11%(±34) on the unrestricted days of the IER. Over 250 serum and urine metabolites significantly increased or decreased during the two  restricted days and most returned to normal after the subsequent five day period . In the breast tissue, approximately half (In 11) of the subjects displayed down regulation of several metabolic pathways including lipid synthesis, growth factors and hormones, whilst epithelial genes including milk proteins, secretoglobulins and mucins were up-regulated and several metabolic pathways down-regulated including lipid synthesis, growth factors and hormones. In the other nine subjects there was no appreciable effect of IER on the breast. CorrespondingThe gene changes were not seen in peripheral blood lymphocytes, and there was no reduction in breast fat cell size. The two groups defined by change in gene expression or lack of it did not differ in the degree of weight or fat loss, other systemic metabolic markers,  or histological assessment of the biopsies.    Conclusion  We conclude that breasts vary in response to short-term IER, the mechanism of which requires further investigation. Trial registration ISRCTN77916487

first: Michelle

last: Harvie

first: Mary

last: Pennington

first: Katherine

last: Spence

first: Adam

last: Mitchell

first: Robert

last: Clarke

last: Vaughan

first: J

middle: W

last: Allwood

first: Yuan

last: Xu

first: Nicolas

last: Rattray

first: Royston

last: Goodacre

first: D

middle: G

last: Evans

first: Ellen

first: Debbie

last: McMullen

first: Anthony

last: Howell


title: Reprogramming-associated aberrant DNA methylation determines hematopoietic differentiation capacity of human induced pluripotent stem cells [iPSCs_methylation]

first: Yoshinori

last: Yoshida

overall_design: Bisulfite-converted genomic DNA lysates from induced pluripotent stem cells were hybridized to Illumina HumanMethylation450 BeadChip.

first: Masatoshi

last: Nishizawa

first: Akira

last: Watanabe

first: Shinya

last: Yamanaka


title: Characterization of the molecular signature associated with the ablation of integrin α6 in IECs in the α6ΔIEC-TAM mouse model

city: Illkirch

first: Doulaye

last: Dembele

address: 1 rue Laurent Fries

institute: IGBMC

summary:
Transcriptome analysis of mRNAs extracted from the rectal mucosa of WT and  α6ΔIEC-TAM mice, 15 days after tamoxifen treatment
Inflammatory bowel diseases (IBD) in humans are characterized by chronic inflammation and gastrointestinal tissue damage, caused by a combination of genetic and environmental factors. We show that the specific ablation of integrin α6 in intestinal epithelial cells (IECs) results in spontaneous colorectal inflammation in mice. In order to characterize the earlier molecular signature involved in the onset of inflammation,  we performed Affymetrix microarrays and compare control versus α6ΔIEC-TAM transcriptomes after tamoxifen treatment.

overall_design: RNAs were prepared from rectal mucosa of 3 control mice treated with tamoxifen, 4 mutant mice treated with tamoxifen and 4 mutant mice treated with NaCl. The transcriptome analysis was performed using the Affymetrix Mouse Gene 1.0 ST arrays. Images were processed using affymetrix GeneChip® Command Console® Software (AGCC) (version 2.0) and numerical values were generated using Affymetrix Expression Console™ Software (version 1.1).

first: Hussein

last: Hamade

first: Adele

last: De Arcangelis

first: Elisabeth

last: Georges-Labouesse


title: 17-DMAG treatment in primary CLL B cells

city: Columbus

first: Lianbo

last: Yu

address: 1800 Cannon Drive

department: Center for Biostatistics

institute: The Ohio State University

summary:
We used microarrays to analyze gene expression following treatment of leukemic B cells with the Hsp90 inhibitor 17-DMAG.
Gene expression profiling reveals the role of SOCS3 in cytokine signaling in CLL

overall_design: Primary cells from CLL patients were isolated and treated in vitro with 17-DMAG. Cells were collected for viability, gene expression analysis and cell signaling and migration assays.

first: Erin

last: Hertlein


title: Celastrol treatment on mouse embryonic fibroblasts (MEFs)

city: Daegu

first: Jaemin

last: Lee

address: 333 Techno Jungang Daero, Hyeonpung-Myeon, Dalseong-Gun

country: South Korea

institute: DGIST

summary: Celastrol has been shown to sensitize leptin receptor signaling and reduce ER stress. Current microarray data provide the gene expression profile in mouse embryonic fibroblasts (MEFs) after Celastrol treatment compared with control.

overall_design: Affymetrix microarray transcriptome analysis of mouse embryonic fibroblasts (MEFs) after Celastrol treatment

first: Umut

last: Ozcan


title: IFNg+ vs IFNg- Treg

city: New Haven

first: Margarita

last: Dominguez-Villar

state: CT

address: 300 George St

department: Neurology

institute: Yale University

summary: Gene expression studies comparing IFNg+ Tregs versus IFNg- Tregs from human peripheral blood

overall_design: Ex vivo sorted Tregs (CD25highCD127neg) were stimulated for 4 hours and IFNg-secreting cells were detected by a IFNg-capture kit. The samples were resorted based on IFNg expression.

last: Dominguez-Vilar


title: Reprogramming-associated aberrant DNA methylation determines hematopoietic differentiation capacity of human induced pluripotent stem cells [PSCderived_HPCs_methylation]

overall_design: Bisulfite converted genomic DNA lysates from human pluripotent stem cell-derived hematopoietic precursor cells (CD34+CD38-CD43+ lineage marker-) were hybridized to Illumina HumanMethylation450 BeadChip.


title: Reprogramming-associated aberrant DNA methylation determines hematopoietic differentiation capacity of human induced pluripotent stem cells [parental_lines_methylation]

overall_design: Bisulfite converted genomic DNA lysates from fibroblasts, cord blood cells, peripheral blood mononuclear cells, keratinocytes, and dental pulp cells were hybridized to Illumina HumanMethylation450 BeadChip.


title: Expression data from human bronchial epithelial cells

city: Pozzuoli

first: Diego

last: Carrella

state: NAPOLI

address: Via Campi Flegrei 34

institute: TIGEM

summary:
The F508del mutation, the most frequent in cystic fibrosis (CF), impairs the maturation of the CFTR chloride channel. The F508del defect can be partially overcome at low temperature (27 °C) or with pharmacological correctors.   The rescue elicited by low temperature may involve a direct stabilization of mutant CFTR protein and/or a change in cell transcriptome that creates a more favorable proteostasis environment.
To assess the effect of low temperature on gene expression we investigated the transcriptome of bronchial epithelial cells derived from CF with F508del mutation.  Cells were kept under control conditions or incubated at 27 °C.  Microarray data indicate that hypothermia induces a profound and global change in gene expression that may be in part responsible for rescue of F508del-CFTR.

overall_design: Bronchial epithelial cells from cystic fibrosis patients homozygotes for F508del mutation were isolated.  Cells differentiated as epithelial monolayers on porous membranes (Snapwell inserts) were incubated for 24 hours at 27 °C or kept under control conditions.  Rescue of mutant CFTR channel by low temperature was checked by measuring transepithelial chloride currents with the Ussing chamber technique.  Total RNA was extracted from treated and control cells to assess changes in gene expression with microarrays.

first: Luis

last: Galietta


title: Twist1 and Slug mediate H2A.X-regulated epithelial-mesenchymal transition in breast cells

status: Public on Jun 21 2016

city: Bethesda

first: Urbain

last: Weyemi

state: MD

address: 9000 Rockville Pike

department: National Cancer Institute

institute: National Institutes of Health

summary: The epithelial-mesenchymal transition (EMT) is thought to be essential for cancer metastasis. While chromatin remodeling is involved in EMT, histone variants contribution in EMT remains poorly investigated. Recently, we showed that silencing or removal of the histone variant H2A.X induced mesenchymal-like characteristics, including activation of the EMT transcription factors, Slug and ZEB1, in human colon cancer cells. Here, we provide the evidence that H2A.X loss in human non-tumorigenic breast cell line MCF10A results in a robust EMT activation, as substantiated by a genome-wide expression analysis. Cells deficient for H2A.X exhibit enhanced migration and invasion, along with an activation of a set of mesenchymal genes and a concomitant repression of epithelial genes. In the breast model, the EMT-related transcription factor Twist1 cooperates with Slug to regulate EMT upon H2A.X loss. Of interest, H2A.X expression level tightly correlates with Twist1, and to a lesser extent with Slug in the panel of human breast cancer cell lines of the NCI-60 datasets. These new findings indicate that H2A.X is involved in the EMT processes in cells of different origins but pairing with transcription factors for EMT may be tissue specific.

overall_design: 10 samples in total including 5 replicates of parental MCF10A cells and 5 replicates of H2A.X knockout cells.

first: Christophe

last: Redon

first: Taresh

last: Sethi

first: Allison

last: Burrell

first: Parthav

last: Jailwala

first: Manjula

last: Kasoji

first: Natalie

last: Abrams

first: Anand

last: Merchant

first: William

last: Bonner


title: Human expression data from iPSCs, motor neurons derived from iPSCs and ESCs, and fetal spinal cords

status: Public on Jun 26 2016

city: Los Angeles

first: Ritchie

last: Ho

state: California

address: AHSP 8405 8700 Beverly Blvd.

institute: Cedars-Sinai Medical Center

summary:
We compare transcriptomic profiles of human induced pluripotent stem cells (iPSCs), motor neurons (MNs) in vitro differentiated from iPSCs or human ESCs containing a HB9::GFP reporter for MNs, and human fetal spinal cords.
The purpose of this comparison is to assess the extent of molecular similarities between in vitro differentiated MNs and in vivo fetal or adult spinal cord MNs. Data for adult spinal cord MNs are published from other studies: GSE3526, GSE19332, GSE20589, and GSE40438.

overall_design: Human induced pluripotent stem cells, pluripotent stem cell derived motor neurons, and fetal spinal cords for RNA extraction and hybridization on Affymetrix arrays.

first: Clive

middle: N

last: Svendsen


title: Enhanced MET signaling in mouse epidermis activates EGFR and initiates squamous carcinogenesis

last: Cataisson

address: 37 Covent drive

institute: National Cancer Institute

summary:
MET expression is elevated in a majority of human skin cancers but its contributions to pathogenesis have not been evaluated. In a mouse model of constitutive overexpression of HGF (MT-HGF), the incidence of squamous cell skin tumors induced by initiation with 7,12-dimethylbenz(a)anthracene (DMBA) followed by exposure to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is increased fivefold over control groups. Half of these tumors carry Hras1 or Kras mutations. Without DMBA initiation, tumors also erupt on MT-HGF mouse skin but only when TPA promotion is enhanced by crossing these mice with mice overexpressing cutaneous PKCα. None of these tumors have Ras mutations.  In culture, MT-HGF keratinocytes share identical MET mediated phenotypic and biochemical features with wildtype keratinocytes transformed by oncogenic RAS. In both cell types, these common features of initiated keratinocytes arise from autocrine activation of EGFR through elevated expression and release of EGFR ligands. Inhibition of EGFR ablates the initiated signature of MT-HGF keratinocytes in vitro and causes regression of MT-HGF induced tumors in vivo. Global gene expression data indicate that MT-HGF and RAS transformed keratinocytes share largely an identical profile of over 5000 mRNAs. Gene ontology analysis reveals the most affected concordant signature is enriched for functions relevant to tissue development and response to wounding, accompanied by cytokine and growth factor activity, and peptidase and endopeptidase activity previously not linked to initiated keratinocytes. Furthermore, gene co-expression analysis in skin cancer patients revealed a core RAS/MET co-expression network considerably activated in pre cancerous and cancerous lesions. Thus MET activation though EGFR contributes to human cutaneous cancers, and inhibitors could be efficacious in advanced lesions such as those seen in transplant recipient patients.
In this dataset with provide gene expression data from primary mouse keratinocytes in culture.

overall_design: 12 samples corresponding to 3 experimental conditions

first: Aleksandra

last: Michalowski


title: Gene expression in healthy and gene deficient human naïve CD4+ T cells

city: Darlinghurst

first: Stuart

last: Tangye

state: NSW

address: 384 Victoria St

country: Australia

institute: Garvan Institute of Medical Research

summary: Ascertain the effects of disease-causing gene mutations on the differentiation status of human naïve CD4+ T cells in the setting of primary immunodeficiencies. Thus, do CD4+ T cells isolated according to a naïve surface phenotype (ie CD4+CD45RA+CCR7+)  from healthy donors exhibit a similar gene expression profile as phenotpyically-matched cells isolated from individuals with defined primary immunodeficiencies caused by specific monogenic mutations.

overall_design: Naïve CD4+ T cells were isolated from PBMCs of healthy controls or from different PID patients by sort-purifying CD4+CD45RA+CD127+CD25lo cells. Memory CD4+ T cells from healthy controls were isolated as CD4+CD45RA- cells. RNA was extracted, transcribed to cDNA and then gene expression analysis determined using Affymetrix Human Gene 2.0 or Human Gene 2.1 ST microarray chips. Normalisation (robust multichip average), log2 transformation and probe set summarisation were performed for each dataset using Bioconductor packages implemented in the R statistical computing environment, version 3.1.1. Subsequent processing and analyses were carried out using GenePattern modules (available at http://pwbc.garvan.unsw.edu.au/gp/). The datasets were merged, quantile normalised, and batch corrected using the MergeColumns, NormaliseColumns and ComBat modules. Differential gene expression analysis was assessed using LimmaGP. The top 100 differentially expressed genes between normal healthy naïve and normal healthy memory T cells, as determined by LimmaGP analysis, were used to filter the combined and batch corrected dataset of naïve CD4+ T cells from 7 healthy controls and 19 PID patients, and memory CD4+ T cells from 3 healthy controls. Unsupervised clustering was performed using NMFConsensus and NMF (Brunet et al., 2004).


title: MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome [Microarray]

status: Public on Jun 27 2016

first: Antoine

last: Peters

address: Maulbeerstrasse 66

institute: Friedrich Miescher Institute for Biomedical Research (FMI)

summary: To address the impact of cellular origin on AML, we generated an inducible transgenic mouse model for MLL-AF9 driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSCs) in vitro resulted in unprecedented clonogenic growth and expression of genes involved in migration and invasion. In vivo, some LT-HSC-derived AMLs were particularly aggressive with extensive tissue infiltration, chemo-resistance and expression of genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulators Zeb1 and Tcf4 significantly reduced leukemic blast invasion. By classifying mouse and human leukemia according to Evi1/EVI1and Erg/ERG expression, reflecting aggressiveness and cell-of-origin and performing comparative transcriptomics we identified numerous EMT-related genes that were significantly associated with poor overall survival of AML patients.

overall_design: RNA from primary cells as well as doxycyclin treated cells from immortalized LT-HSC and GMP (Granulocyte macrophage progenitor) celllines was isolated for expression profiling on Affymetrix gene arrays.

first: Vaya

last: Stavropoulou

first: Susanne

last: Kaspar

first: Stephane

last: Thiry

first: Jürg

last: Schwaller


title: Reprogramming-associated aberrant DNA methylation determines hematopoietic differentiation capacity of human induced pluripotent stem cells [PSCusedfor_iPSDMRs_methylation]

first: Yoshinori

last: Yoshida

first: Masatoshi

last: Nishizawa

first: Shinya

last: Yamanaka


title: Reprogramming-associated aberrant DNA methylation determines hematopoietic differentiation capacity of human induced pluripotent stem cells [undiff_iPSESCs_methylation]

overall_design: Bisulfite converted genomic DNA lysates from induced pluripotent stem cell　and embryonic stem cell lines were hybridized to Illumina HumanMethylation450 BeadChip.


title: Expression data from KDM3A knockdown MDA-MB-231 cells

first: Cun-Yu

last: Wang

state: California(CA)

address: 10833 Le Conte Avenue

department: Division of Oral Biology and Medicine

institute: UCLA School of Dentistry

summary:
Breast cancer invasive growth, metastasis and therapeutic resistance affects the clinical ourcome. We explored the epigenetic mechanisms that control these process in breast cancer cell line, MDA-MB-231 by knocking down a lysine specific demethylase KDM3A
We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.

overall_design: Human breast cancer cell line MDA-MB-231 was infected with scramble or KDM3A shRNA. After selection, the cells were used for microarray analysis.

first: Sivakumar

last: Ramadoss

first: Gao

last: Guo


title: HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms [Affymetrix]

city: Philadelphia

first: Bin

last: Fang

address: 3400 Civic Center Blvd, Bldg 42

institute: University of Pennsylvania

summary: We address the function of HNF6 in the mouse liver metabolism and Rev-erba cistrome

overall_design: We performed microarray in mouse livers at 5pm of the day and compared between WT and HNF6-depleted livers.

first: Yuxiang

last: Zhang

first: Manashree

last: Damle


title: TGFβ contributes to impaired exercise response by suppression of mitochondrial key regulators in skeletal muscle

first: Johannes

last: Beckers

summary: substantial number of people at risk to develop type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals who performed a controlled eight weeks cycling and walking training at 80 % individual VO2max. Participants identified as non-responders in insulin sensitivity (based on Matsuda index) did not differ in pre-intervention parameters compared to high responders. The failure to increase insulin sensitivity after training correlates with impaired up-regulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1α and AMPKα2. The muscle transcriptome of the non-responders is further characterized by an activation of TGFβ and TGFβ target genes, which is associated with increases in inflammatory and macrophage markers. TGFβ1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGFβ1 signaling down-regulates the abundance of PGC1α, AMPKα2, mitochondrial transcription factor TFAM, and of mitochondrial enzymes. Thus, increased TGFβ activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity.

overall_design: We performed gene expression microarray analysis on muscle biopsies from humans before and after an eight weeks endurance training intervention

first: Anja

last: Böhm

first: Christoph

last: Hoffmann

first: Martin

last: Irmler

first: Patrick

last: Schneeweiss

first: Günter

last: Schnauder

first: Corinna

last: Sailer

first: Vera

last: Schmid

first: Jens

last: Hudemann

first: Jürgen

last: Machann

first: Fritz

last: Schick

last: Hrabĕ de Angelis

first: Harald

last: Staiger

first: Andreas

last: Fritsche

first: Norbert

last: Stefan

last: Nieß

first: Hans-Ulrich

last: Häring

first: Cora

last: Weigert


title: Trancriptional comparison of Zbtb32-deficient and -sufficient NP-specific memory B cells at day 7 of recall response [BMPC]

status: Public on Jun 10 2016

city: Tucson

first: Deepta

last: Bhattacharya

state: Arizona

address: 1656 E. Mabel Street, MRB 217

department: Department of Immunobiology

institute: University of Arizona

summary: Memory B cell responses are more rapid and of greater magnitude than are primary antibody responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of antibody recall responses. ZBTB32 is highly expressed by mouse and human memory B cells, but not by their naïve counterparts. Zbtb32-/- mice mount normal primary antibody responses to T-dependent antigens. However, Zbtb32-/- memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32-/- secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32-/- secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of antibody recall responses.

overall_design: CD45.2 wild type and Zbtb32-/- splenocytes from NP-CGG-immune donors were transferred into CD45.1 recipients and challenged with NP-CGG. CD45.2 donor NP-specific plasma cells B cells were isolated from the bone marrow 7 days later. 6 biological replicates of each genotype were performed.

first: Arijita

last: Jash


title: Sex-specific Variation in Signaling Pathways and Gene Expression Patterns in Human Leukocytes in Response to Endotoxin and Exercise

status: Public on Jun 22 2016

city: Tuebingen

first: Michael

middle: H.

last: Walter

address: Calwer Str. 7

department: Department of Medical Genetics

institute: University of Tuebingen

summary: While exercise effects on the immune system received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise.  Using a previously published microarray data set, we investigated mRNA changes induced through exhaustive exercise  (half-marathon; pre-exercise and post-exercise [30 min, 3h, 24h], whole blood culture ± LPS (1h)) with a specific focus on sex differences (women in luteal phase vs men).  Inflammation related pathways, TLRs, cytosolic DNA sensing and RIG-I like receptors were differentially activated between sexes in LPS-stimulated cultures.  Genes differentially regulated between sexes included TNIP-1, TNIP-3, IL-6, HIVEP1, CXCL3, CCR3, IL-8 and CD69, revealing a bias towards less anti-inflammatory gene regulation in women compared to men.  In addition, several genes relevant to brain function (OLIG2, TMEM106B, DDIT4, and KMO) showed differential activation between sexes.  Some of these genes (e.g., KMO in women, DDIT4 in both sexes) potentially constitute neuroprotective mechanisms. These data reveal that the exercise-induced change in gene expression might be gender and menstrual cycle phase dependent.

overall_design: Factorial design comparing LPS and control treated blood samples of male and female athletes before and after a half-marathon at different timepoints (half-marathon; pre-exercise and post-exercise [30 min, 3h, 24h])

first: Asghar

last: Abbasi

first: Rodolfo

last: de Paula Vieira

first: Felix

last: Bischof

first: Masoud

last: Movassaghi

first: Nicole

middle: C

last: Berchtold

last: Niess

first: Carl

last: Cotman

first: Hinnak

last: Northoff


title: Trancriptional comparison of Zbtb32-deficient and -sufficient polyclonal resting memory B cells

overall_design: Wild type and Zbtb32-/- resting polyclonal splenic memory B cells were purified by fluorescence activated cell sorting, RNA was extracted, and used for Affymetrix microarray analysis. 5 biological replicates of wild type and Zbtb32-/- cells were included for each cell type.


title: Expression data from Colossolactone H treated H1650 cells

city: Taipei

first: Su-Yu

last: Chen

address: No.1, Changde St., Zhongzheng Dist., Taipei City 100, Taiwan (R.O.C.)

department: Department of Clinical Laboratory Sciences and Medical Biotechnology

country: Taiwan

institute: National Taiwan University

summary:
Ganoderma colossum (Fr.) Baker, a white rot fungus distributed in tropical and subtropical forests, is a rare Ganoderma mushroom belonging to the family Ganodermataceae. In Asia, the fruiting body of G. colossum has been used as tonics or as folk medicine for a variety of illnesses, including malignant diseases. Colossolactone H (colo H) as a new compound was isolated and studied for its anticancer mechanism in human lung cancer H1650 cells.
We used microarrays to analyze the gene expression changes upon colo H treatment that helped underlying the molecular mechanism of colo H in H1650 lung cancer cells.

overall_design: The H1650 cells treated with colo H for 12 and 24 h for RNA extraction and hybridization on Affymetrix microarrays.

first: SuYu

first: Shwu-Bin

last: Lin


title: Reprogramming-associated aberrant DNA methylation determines hematopoietic differentiation capacity of human induced pluripotent stem cells

first: Yoshinori

last: Yoshida

address: 53, Kawahara-cho, Shogoin, Sakyo-ku

institute: Kyoto University

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

overall_design: Refer to individual Series


title: Mapping epigenetic changes to the host cell genome induced by Burkholderia pseudomallei reveals pathogen-specific and pathogen-generic signatures of infection

status: Public on Jun 16 2016

city: London

first: Deniz

last: Cizmeci

address: Imperial College London

institute: Imperial College London

summary: The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling. A comparison of our data with reported methylome changes in cells infected with M. tuberculosis revealed commonality of differentially methylated genes, including genes involved in T cell responses (BCL11B, FOXO1, KIF13B, PAWR, SOX4, SYK), actin cytoskeleton organisation (ACTR3, CDC42BPA, DTNBP1, FERMT2, PRKCZ, RAC1), and cytokine production (FOXP1, IRF8, MR1). Overall our findings show that pathogenic-specific and pathogen-common changes in the methylome occur following infection.

overall_design:
The human leukemic monocyte lymphoma cell line (U937, ATCC CRL-1593.2) was maintained in RPMI 1640 supplemented with 10% foetal bovine serum (FBS) at 37°C. U937 cells were differentiated to macrophage-like cells following exposure to 20 ng/ml (final concentration) of phorbol 12-myristate 13-acetate (PMA) for 48 hours at 37°C and differentiation evidenced by increased adherence to tissue culture flasks. Overnight cultures of B. pseudomallei K96243 were diluted in L-15 medium and added to differentiated U937 cells at a multiplicity of infection (MOI) of 10. Uninfected controls were overlaid with L15 medium only. The cells were then incubated at 37°C to allow infection. The cells were washed 3 times with PBS and incubated with fresh L15 medium containing 1mg/ml kanamycin to kill extracellular bacteria. At appropriate time points the cells were washed 3 times in warm PBS and lysed with 0.1% (vol/vol) Triton X-100. DNA was isolated using an AllPrep kit (Qiagen) and stored at -80ºC until required. DNA yield was measured using a Nanodrop instrument with measurements between 22.8 – 50.6 ng/ul.
Two experiments were carried out using the above procedure. In Experiment 1, DNA was collected from uninfected and infected cells at 2 hours (T2), and 4 hours (T4) post infection (2 biological replicates and 2 technical replicates from each group). In Experiment 2, DNA was collected from uninfected and infected cells at 1 hour (T1), 2 hours (T2), 3 hours (T3) and 4 hours (T4) post infection (1 sample from each group).
The DNA methylation profile was determined using the Infinium HumanMethylation450 BeadChip (450K) (Illumina Inc.) following the manufacturer’s instructions.  The data was extracted and the initial analysis was performed using GenomeStudio (2010.3) methylation module (1.8.5). Quality control checks and quantile normalisation were implemented using WateRmelon. Samples with more than 1% of sites with a detection p-value greater than 0.05 were removed as were probes with 1% of samples with a detection p-value greater than 0.05. Probes were removed if they had a bead count less than 3 in 1% of samples. Cross-hybridizing probes were removed, leaving 425496 probes for analysis.  Here we report DNA methylation profile of 18 samples (10 infected and 8 control).

first: Emma

middle: L

last: Dempster

first: Olivia

last: Champion

first: Sariqa

last: Wagley

first: Ozgur

last: Akman

first: Joann

last: Prior

first: Orkun

last: Soyer

first: Jonathan

last: Mill

first: Richard

last: Titbal


title: caArray_smith-00014: Expression profiling of acute lymphoblastic leukemia

city: Rockville

first: Mervi

last: Heiskanen

address: 9609 Medical Center Drive, 1W378

department: CBIIT

institute: NCI

summary: Target Project: Expression profiling of acute lymphoblastic leukemia samples using U133plus2 affymetrix arrays. The study was sponsored by the national cancer institute with a goal to catalog genomic changes in ALL pre and post standard therapies.

overall_design:
smith-00014
Assay Type: Gene Expression
Provider: Affymetrix
Array Designs: HG-U133_Plus_2
Organism: Homo sapiens (ncbitax)
Material Types: cell, synthetic_RNA, total_RNA


title: CXCL12 Stimulation of CXCR4-WHIM Transduced Waldenstrom's Macroglobulinemia cell line BCWM.1

city: Boston

first: Zachary

middle: Richard

last: Hunter

state: MA

address: 450 Brookline Ave, Mayer 544

institute: Dana-Farber Cancer Institute

summary:
CXCR4 cDNA transcripts were subcloned into plenti-IRES-GFP vectors, and stably transduced using a lentiviral system In addition to wild-type CXCR4, vectors with the mutations c.1013C>G  (p.Ser338*), c.932_933insT (p.Thr311fs), and c.1030_1041delinsGT (p.Ser344fs) were generated.
Cell lines were stimulated with 50nM of the CXCR4 ligand CXCL12 (SDF1A) (R&D Systems, Minneapolis MN) for two hours. RNA from each sample was extracted at baseline and at 2 hours.

overall_design: At baseline and following stimulation, RNA was extracted and processed for analysis  using Affymetrix Human Gene ST 2.0 arrays (Affymetrix, Santa Clara, CA). Data was analyzed using Oligo and Limma bioconductor packages in R using TMM normalization.

first: Steven

last: Treon


title: HT29 and GATA6

status: Public on Jun 15 2016

city: Tokyo

first: Testu

last: Akiyama

address: 1-1-1, Yayoi, Bunkyo-ku

department: Institute of Molecular and Cellular Biosciences

institute: Tokyo University


title: Epigenomics Studies in Acute Myeloid Leukemia disease progression [RNAseq]

city: New York

first: Francine

middle: E.

last: Garrett-Bakelman

address: 413 East 69th street, BRB 1426

department: Medicine

institute: Weill Cornell Medicine

type: Expression profiling by high throughput sequencing

summary: We report the DNA methylation and transcriptional molecular features of paired diagnosis and relapsed Acute Myeloid Leukemia  samples

overall_design:
To determine if epigenetic features at gene promoters can affect gene trancription during disease progression in AML, we profiled nineteen paired diagnosis and relapse AML patient samples using RNAseq and performed correlation analysis between transcriptional variance and epigenetic heterogeneity at respective gene promoters (normalized transcript counts are included in Dx_Rel_AML_RNAseq_rpkm.txt)

To determine if epigenetic features at gene promoters can affect gene trancription in AML, we profiled 96 cells from a relapsed AML case using single cell RNA-sequencing and correlated transript variance with epigenetic heterogeneity at respective gene promoters (normalized transcript counts are included in AML_130_Rel_scRNAseq_rpkm.txt)

Raw data has been deposited to  dbGaP (controlled access) due to patient privacy concerns:
http://www.ncbi.nlm.nih.gov/gap/?term=phs001027.v1.p1

middle: E

first: Sheng

last: Li

first: Christopher

last: Mason

first: Ari

last: Melnick

first: Martin

last: Carroll

first: Michael

last: Becker

last: D'Andrea

first: Peter

last: Valk

first: Lars

last: Bullinger

first: David

last: Grimwade

first: Jorge

last: Gandara

first: Caroline

last: Sheridan

first: Yaseswini

last: Neelamraju


title: Expression data from KSRP overexpression and knockdown lung cancer cell

first: Kuo-Tai

last: Hua

address: No. 1, Sec. 1, Jen-Ai Rd.

summary:
KSRP overexpressed CL1-0 cells and  KSRP depleted CL1-5 cells were used to identify genes regulated by KSRP
We used microarrays to detail the global programme of gene expression underlying metastasis and identified distinct classes of KSRP-regulated genes during this process.

overall_design: CL1-0 cells stablely depleted KSRP expressing and CL1-5 cells stably expressed KSRP-specific shRNA were analyzed compare to respective control cells

first: Min-Liang

last: Kuo


title: Genomic structure, evolution and molecular classification of acute myeloid leukemia

status: Public on Jun 08 2016

city: Berlin

address: Augustenburger Platz 1

department: Hematology, Oncology and Tumorimmunology

institute: Charité

summary: Background: Acute myeloid leukemia (AML) is driven by somatic mutations and genomic rearrangements affecting >20 genes. Many of these are recent discoveries and how this molecular heterogeneity dictates AML pathophysiology and clinical outcome remains unclear.   Methods: We sequenced 111 leukemia genes for driver mutations in 1540 AML patients with cytogenetic and clinical data. We modeled AML’s genomic structure, defining genetic interactions, patterns of temporal evolution and clinical correlations.  Results: We identified 5,236 driver mutations involving 77 loci, including hotspot mutations in MYC. We found ≥1 driver mutation in 96% patients, and ≥2 in 85%. Gene mutations implicated in age related clonal hematopoiesis (DNMT3A, ASXL1, TET2) were the earliest in AML evolution, followed by highly specific and ordered patterns of co-mutation in chromatin, transcription and splicing regulators, NPM1 and signaling genes. The patterns of co-mutation compartmentalize AML into 12 discrete molecular classes, each presenting with distinct clinical manifestation. Amongst these, mutations in chromatin and spliceosome genes demarcate a molecularly heterogeneous subgroup enriched for older AML patients currently classified as intermediate risk and results in adverse prognosis. Two- and three-way genetic interactions often implicating rare genes/mutation-hotspots, markedly redefined clinical response and long-term curability, with the NPM1:DNMT3A:FLT3ITD genotype (6% patients) identifying poor prognosis disease, whereas within the same class NPM1:DNMT3A:NRASG12/13 (3%) associated with favorable outlooks.  Conclusions:   79% of AML is molecularly classified in 12 genomic subgroups. These represent distinct molecular phylogenies, implicating complex genotypes. Delineation of higher-order genomic relationships, guide the development of personally tailored classification, prognostication and clinical protocols. Similar studies across cancer types are warranted.

overall_design: Gene expression was profiled in 46 AML samples [n=18 AML cases with MYC mutations and n=28 AML cases with MYC wild-type].


title: Expression data from human intestinal enteroids altered for Tgfbeta signaling

status: Public on Jun 17 2016

city: Portland

first: Jared

middle: Michael

last: Fischer

state: OR

address: 3181 SW Sam Jackson Park Road

department: Molecular and Medical Genetics

institute: Oregon Health and Science University

summary: We treated intestinal enteroids continuously for 6 days with or without TgfbR1/2 inhibitor (LY2109761) or Tgfb1 ligand

overall_design: Organoids were continuously treated for 6 days, then RNA was extracted and hybridized to Affymetrix Human Genome U133 plus 2.0

middle: M


title: PAX7 is a required target for microRNA-206-induced differentiation of fusion-negative rhabdomyosarcoma

city: Memphis

first: Yong-Dong

last: Wang

state: TN

address: 262 Danny Thomas Pl, MS1135

institute: St. Jude Children's Research Hospital

summary: Genes regulated by miR-206 were identified by microarray analysis in RD cells transfected with a Negative Control (NC) or miR-206 Mimic

overall_design: Human RD rhabdomyosarcoma cells were transfected with a Negative Control (NC) miRNA Mimic or a miR-206 miRNA Mimic, 48 hours post transfection RNA was extracted and hybridized on Affymetrix microarrays.

first: Mark

last: Hatley

first: Jason

middle: A

last: Hanna


title: Longitudinal study of DNA methylation during the first 5 years of life

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:
Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life.
Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects.
Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function.
Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention.

overall_design: Longitudinal study including 15 samples

first: Rocio

last: Urdinguio

first: María

middle: I

last: Torró

first: Gustavo

last: Bayón

first: Julio

last: Álvarez-Pitti

first: Agustín

last: Fernández

first: Pau

last: Redon

first: Mario

last: Fraga

first: Empar

last: Lurbe


title: Expression data of lymphoblastoid B-cell line (LCL), T-cell, dermal fibroblast (DF), and iPSCs established from them.

status: Public on Jun 03 2016

city: Sinjuku-ku, Tokyo

first: Koki

last: Fujimori

address: 35 Shinanomachi

department: Physiology

institute: Keio University

summary:
Recent studies indicated that iPSCs retain an epigenetic memory relating to their cell of origin that affected their properties and their functions as PSCs.
Then, we used microarrays to detail the global programme of gene expression reflecting the effect of cell type of origin, and carefully compared the characteristics of iPSCs from LCL, T-cell, and DF based on their expression profiles .

overall_design: We isolated RNA from LCL, T-cell, DF, and iPSC generated from them (total 12 samples) for the gene expression microarray analysis. All of the iPSC lines we used were low passage number (less than 15).

first: Toshiki

last: Tezuka

first: Wado

last: Akamatsu

first: Hideyuki

last: Okano


title: Gene expression profiles of HT29 cells in which GATA6 expression was suppressed.

first: Testu

last: Akiyama

summary: GATA6 is a zinc finger transcription factor that is required for the proliferation, development and specific gene regulation in the gastrointestinal tract. We have recently reported that GATA6-mediated induction of the intestinal stem cell marker LGR5 is required for the tumorigenicity of colon cancer cells. However, knockdown of LGR5, unlike GATA6, does not affect the proliferation of these cells under adherent conditions. Here we show that REG4, a member of the regenerating islet-derived (REG) family, is a target of GATA6. We further demonstrate that REG4 is downregulated by overexpression of miR-363, which suppresses GATA6 expression. Moreover, we show that GATA6-mediated activation of REG4 causes an acceleration of the growth of colon cancer cells under adherent conditions. These results suggest that GATA6 simultaneously activates the transcription of genes required for growth (REG4) and clonogenicity (LGR5), and the miR-363-GATA6-REG4/LGR5 pathway is critical for colorectal tumorigenesis.

overall_design: HT29 cells were transfected with a siRNA targeting GATA6.

first: K

last: Matsumura

first: Y

last: Kawasaki


title: Gene expression profiles of HT29 cells in which LGR5 expression was suppressed.

overall_design: HT29 cells were transfected with a siRNA targeting LGR5.


title: Gene expression profiles of HT29 cells in which REG4 expression was suppressed.

overall_design: HT29 cells were transfected with a siRNA targeting REG4.


title: Examination of gene expression in cerebellum and hippocampus for mouse C57BL/6J WT and nmf205-/-

city: Farmington

first: Jeffrey

last: Chuang

address: 263 Farmington Avenue

department: Computational Biology

institute: The Jackson Laboratory for Genomic Medicine

summary: Ribosome stalling during translation has recently been shown to cause neurodegeneration, yet the signaling   pathways triggered by stalled elongation complexes are unknown.  To investigate these pathways we   analyzed the brain of B6J-nmf205-/-   mice in which neuronal elongation complexes are stalled at AGA   codons due to deficiencies in a tRNA  Arg(UCU) tRNA and GTPBP2, a mammalian ribosome rescue factor.   Increased levels of phosphorylation of eIF2α (Ser51) were detected prior to neurodegeneration in these   mice and transcriptome analysis demonstrated activation of ATF4, a key transcription factor in the   integrated stress response (ISR) pathway. Genetic experiments showed that this pathway was activated by the eIF2α kinase, GCN2, in an apparent deacylated tRNA-independent fashion. Further we found that the ISR attenuates neurodegeneration in B6J-nmf205-/-   mice, underscoring the importance of cellular and stress context on the outcome of activation of this pathway.   These results demonstrate the critical interplay between translation elongation and initiation in regulating neuron survival during cellular stress.

overall_design: Examination of gene expression in cerebellum and hippocampus for 4 mice strains derived from C57BL/6J (B6J) strain. Microarray data was performed for 3 week and 5 week old mice in both cerebellum and hippocampus for B6J and B6J-nmf205-/- three replicates each. RNA-Seq data was perform on cerebellum of mice 3 weeks old, three replicates for each genotype: B6J, B6J-nmf205-/-, B6J-Gcn2-/- and B6J-nmf205-/-;Gcn2-/-.

first: Ryuta

last: Ishimura

first: Gabor

last: Nagy

first: Ivan

last: Dotu

middle: H

first: Susan

last: Ackerman


title: Whole genome transcription and DNA methylation analysis of peripheral blood mononuclear cells identified aberrant gene regulation pathways in systemic lupus erythematosus [metylation]

city: Dallas

first: yun

last: lian

state: TX

address: 5323 Harry Hines Blvd.

institute: UT Southwestern Medical Center

summary: Our study has demonstrated that significant number of differential genes in SLE was involved in IFN, TLR signaling pathways and inflammatory cytokines. The enrichment of differential genes has been associated with aberrant DNA methylation, which may be relevant to the pathogenesis of SLE. Our observations laid the groundwork for further diagnostic and mechanistic studies of SLE and LN.

overall_design: We performed whole genome transcription and DNA methylation analysis in PBMC of 30 SLE patients, including 15 with LN (SLE LN+) and 15 without LN (SLE LN-), and 25 normal controls (NC) using HumanHT-12 Beadchips and Illumina Human Methy450 chips. The serum pro-inflammatory cytokines were quantified using Bio-plex human cytokine 27-plex assay.

first: Honglin

last: Zhu

first: Wentao

last: Mi

first: Hui

last: Luo

first: Tao

last: Chen

first: Shengxi

last: Liu

first: Xiaoxia

last: Zuo

first: Quan-zhen

last: Li


title: Effect of ibuprofen on hippocampal gene expression in APP-PS1 mice

status: Public on Jun 14 2016

city: Stanford

first: Katrin

last: Andreasson

state: CA

address: 1201 Welch Road, MSLS P210

department: Neurology and Neurological Sciences

institute: Stanford University

summary:
NSAIDs (non-steroidal anti-inflammatory drugs) inhibit cyclooxygenase (COX) enzymes and prevent Alzheimer’s disease (AD) at preclinical stages in cognitively normal aging populations.  We modeled NSAID prevention of memory impairment in AD model mice to identify novel targets of NSAID action.
We found that the widely-used NSAID ibuprofen prevented early hippocampus-dependent memory deficits in APP-PS1 mice. We therefore analyzed gene expression in the hippocampus of these mice.

overall_design:
We treated male APPSwe-PS1deltaE9 mice (strain originally provided by Dr. David Borchelt and fully back-crossed to a C57BL/6J background) and their wild-type littermates with ibuprofen in chow from 3 to 6 months of age, after which we sacrificed the mice and dissected one hippocampus from each mouse for RNA isolation and microarray analysis. In each genotype-treatment group, we analyzed samples from 5 mice.
Note: In our initial analysis, we found that sample GSM1644138, Hippocampus_WT_Con_rep5, was an outlier in overall gene expression. We therefore removed this sample before performing the analysis published in PMID 27190010.

first: Nathaniel

middle: S

last: Woodling


title: Trancriptional comparison of Zbtb32-deficient and -sufficient NP-specific memory B cells at day 7 of recall response [memory B cells]

first: Deepta

last: Bhattacharya

address: 1656 E. Mabel Street, MRB 217

institute: University of Arizona

summary: Memory B cell responses are more rapid and of greater magnitude than are primary antibody responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of antibody recall responses. ZBTB32 is highly expressed by mouse and human memory B cells, but not by their naïve counterparts. Zbtb32-/- mice mount normal primary antibody responses to T-dependent antigens. However, Zbtb32-/- memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32-/- secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32-/- secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of antibody recall responses.

overall_design: CD45.2 wild type and Zbtb32-/- splenocytes from NP-CGG-immune donors were transferred into CD45.1 recipients and challenged with NP-CGG. CD45.2 donor NP-specific memory B cells were isolated from the spleen 7 days later. 5-6 biological replicates of each genotype were performed.

first: Arijita

last: Jash


title: Synovial biopsies of osteoarthritis patients

status: Public on Jun 02 2016

city: Nijmegen

first: Marieke

last: de Vries

address: Geert Groteplein 28

department: Rheumatology

country: Netherlands

institute: Radboudumc

summary:
Synovial biopsies were obtained from osteoarthritis (OA) synovium to find genes upregulated during OA.
The genes upregulated during OA can be used to identify disease characteristic genes.

overall_design: 10 microarrays of end-stage OA synovial biopsies were compared to 7 microarrays of synovial biopsies from individuals without a joint disease. Genes with >1.2-fold upregulation and P<0.05 in OA VS HC were selected from the analysis.


title: Trancriptional comparison of Zbtb32-deficient and -sufficient cells

city: Tucson

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

overall_design: Refer to individual Series


title: Identification of a novel PPARβ/δ / miR-21-3p axis in UV-induced skin inflammation [mouse mRNA]

city: Lausanne

first: Mark

last: Ibberson

address: Genopode building

department: Vital-IT

institute: SIB Swiss Institute of Bioinformatics

summary: Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPARβ/δ is known to control cutaneous repair and UV-induced cancer development. Here, we describe a novel PPARβ/δ-dependent molecular cascade involving TGFβ-1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes, and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR-21-3p reduces UV-induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA-based topical therapies for cutaneous disorders.

overall_design: 16 samples: 4 KO (Ppard-/-) and 4 WT (Ppard+/+) irradiated for 12 weeks; 4 KO and 4 WT without irradiation

first: Liliane

last: Michalik

first: Gwendoline

last: Degueurce


title: No identical 'mesenchymal stem cells' at different times and sites: Human committed progenitors of distinct origin and differentiation potential are incorporated as adventitial cells in microvessels

city: Modena

first: Enrico

last: Tagliafico

state: MO

address: Via Campi 287

department: Center for Genome Research

institute: University of Modena and Reggio Emilia

summary: A widely shared view reads that 'MSCs' are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with the ubiquitous 'pericytes.' Using stringent in vivo differentiation assays and transcriptome analysis, we show here that human cell populations from different anatomical sources, which would all be regarded as 'MSCs' based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis further reveals that muscle 'pericytes,' which are not spontaneously osteo-chondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called 'MSCs,' with important applicative implications. The data also support the view that rather than a uniform class of 'MSCs,' different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, likely of different developmental origin.

overall_design: The anatomical identity of 'mesenchymal stem cells', (MSCs) their phenotype, their distribution in the different tissues, their lineage, their physiological functions and biological properties represent one of the most controversial and confusing areas in stem cell biology. The definition of the origin, anatomy, function and biological properties of so-called MSCs  has obvious implications both for understanding their biology and for their use in potential therapies. We have previously identified a minimal surface phenotype suited not only to enrich for the archetypal human 'MSCs' in uncultured bone marrow cell suspensions, but also to correlate their ex vivo-assayed clonogenic capacity with their in situ identity and in vivo fate following tranplantation (Sacchetti et al., 2007). Stromal cell strains were established from four different tissue sources: bone marrow (BM), skeletal muscle (MU), periosteum (PE), and perinatal blood-borne cord blood (CB) cells. For all post-natal tissue sources, clonogenic cells were prospectively isolated based on a minimal surface phenotype as previously described for human BMSCs (CD34-/CD45-/CD146+); colonies of CB-derived stromal cells were established as described (Kluth et al., 2010; Kogler et al., 2004). Of note, CD146 identified a clonogenic subset in MU (presented below) and PE (data not shown), as it does in BM. Multi-clonal strains derived from growth of the originally explanted cells were then expanded under identical culture conditions; all resulting cell strains exhibited the canonical in vitro cell surface markers regarded as characteristic of 'MSCs'. In order to characterize the specificity and functional significance of the cell surface phenotype of 'MSCs' that is widely regarded as a defining feature of 'MSCs' across tissues, we performed gene expression profiling using Affimetrix technology.

first: B

last: Sacchetti

first: A

last: Funari

first: C

last: Remoli

first: G

last: Giannicola

last: Kogler

first: S

last: Liedtke

last: Cossu

first: M

last: Serafini

last: Sampaolesi

first: E

last: Tenedini

first: I

last: Saggio

first: P

last: Robey

last: Riminucci

last: Bianco


title: Pharmacologic inhibition of host phosphodiesterase-4 improves isoniazid mediated clearance of Mycobacterium tuberculosis

city: Newark

first: Selvakumar

last: Subbian

state: NJ

address: 225 Warren St, Rm# W250.Q

department: New Jersey Medical School,

institute: Rutgers Biomedical and Health Sciences, Rutgers The State University of NJ

summary:
In this study, we evaluated the PK/PD and explored the efficacy of a PDE4 inhibitor, CC-11050 in a murine model of Mtb infection.  Infected mouse lungs with or without CC-11050 treatment was also used to interrogate genome-wide transcriptional changes.
Standard aerosol infection of mice with MtbCDC1551, followed by enumeration of lung bacterial load, pathology and transcriptional changes were monitored upto 112 days post infection.

overall_design: Mice were infected with Mtb and treatment with CC11050 was started at 14 days post-infection. Uninfected mice were included as control. At 28 days  post-infection, mice from all 3 groups (uninfected, Mtb-infected untreated or CC11050 treated)  were euthanized and lung tissue was collected to isolate total RNA and used in microarray experiments. (N=4 per group)

first: Gilla

last: Kaplan


title: Novel gene-pathway identification during the development of human epicardial fat through early life

city: Nottingham

first: Hernan

middle: Pablo

last: Fainberg

address: Derby Rd

department: Division of Child Health, Obstetrics & Gynaecology

institute: The University of Nottingham

summary:
Studies in rodents and newborn humans, demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance, which also has a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants and children in order to compare the changes in gene expression with age
We used microarrays in order to compare changes between gene to gene interactions by applying systems biology molecular analytical approaches.

overall_design: All participants had congenital heart disease (CHD) and the samples were taken at the time of surgery, immediately prior to the child undergoing cardio-pulmonary bypass. Thus, we determined the global gene expression signatures of a total of 46 paediatric patients: 11 neonates (6 to 24 days old), 28 infants (40 days to 1 year old) and 7 children (2 to 7 years old). To gain insight into how temperature control and energy balance may change with age in these fat depot, we identified functional modules of co-expressed genes using several different bioinformatics approaches, including WGCNA and gene ontology analysis.

last: Ojha

first: H

middle: P

first: V

last: Wilson

last: Pelella

last: Castellanos

middle: T

last: May

last: Lotto

last: Sacks

last: Symonds

last: Budge


title: Maternal age impacts the epigenetic profile of offspring

city: Research Triangle Park

first: Zongli

last: Xu

address: 111 tw alexander Dr.

institute: NIH/NIEHS

summary: The mechanisms controlling genome methylation during human embryogenesis remain largely unknown. Here we provide evidence that maternal age at pregnancy permanently alters the epigenetic profile of offspring. We measured DNA methylation in blood at over 450,000 CpGs across the epigenome in 890 newborns.

overall_design: Bisulphite-converted DNA from the 890 samples were hybridised to the Illumina Infinium HumanMethylation450 BeadChip.

first: Jack

last: Taylor

first: Christina

last: Markunas

first: Allen

middle: J

last: Wilcox


title: Effect of resting or activated human regulatory T cells (Tregs) on human natural killer (NK) cell differentiation in vitro.

city: London

first: Aurore

last: Saudemont

address: Royal Free Campus, Pond Street

department: Anthony Nolan Research Institute

institute: University College London

summary:
Activated but not resting Tregs affect NK cell differentiation.
We used microarray analysis to study differences of gene expression of NK cell differentiation in the presence of resting or activated Tregs.

overall_design: We compared the effect of resting and activated Tregs on NK cell differentiation by using an in vitro model of NK cell differentiation from umbilical cord blood (UCB) HSC (Grzywacz et al., 2006, Luevano et al., 2014). Tregs were added from day 9 until day 12 of culture, then HSC were re-isolated using a MoFlow cell sorter.

first: Isabela

last: Pedroza-Pacheco

first: Anna

last: Domogala

first: Martha

last: Luevano

first: Nicola

last: Jackson

first: Michael

last: Blundell

first: Adrian

last: Trasher

first: Alejandro

last: Madrigal


title: Expression data from LLC-1 tumors extracted from C57Bl/6 mice following gene transfer of p19Arf and IFN-beta

status: Public on Jun 07 2016

city: SAO PAULO

first: João Paulo

middle: PORTELA

last: CATANI

state: SAO PAULO

address: 251 AV DR ARNALDO

department: CTO

country: Brazil

institute: ICESP

summary:
Gene transfer of both p19Arf and IFN-beta induces increased immunoprotection in mice after intratumoral application
Here we performed a microarray analysis to understand this process

overall_design: Mice were treated by intratumoral application of 10^8 ifu, 5 times, each 48h. Tumors were transduced with Adenovector coding for EGFP as control, for P19Arf, IFN-beta or both P19Arf+IFNbeta

first: João

last: Portela Catani

first: Bryan

last: Strauss

first: Paulo

last: Del Valle


title: Expression data from wildtype and Dicer-deficient mouse embryonic stem (ES) cells at different stages of the cell cycle.

first: Gopuraja

last: Dharmalingam

address: Faculty of Medicine, Imperial College, Hammersmith Hospital Campus

department: Epigenetics section

institute: MRC London Institute of Medical Sciences

summary:
The protein Dicer is required for microRNA (miRNA) biogenesis. Dicer-deficient cells therefore lack almost all mature, functional miRNAs. We investigated the role of miRNAs in regulation of gene expression in mouse
ES cells by analysing gene expression in either wildtype or Dicer-deficient cells grown either under asynchronous growth conditions, or cells in the early G1 phase of the cell cycle.

overall_design: RNA was extracted from three biological replicates of both wildtype and Dicer-deficient ES cells grown under asynchronous culture conditions. To obtain cells in early G1, populations (in triplicate for both cell types) were cultured in 20ng/ml demecolcine for 4 hours, then mitotic cells were isolated using the mitotic shake-off technique (Terasima & Tolmach, Experimental Cell Research (30) 1963). Mitotic cells were replated in demecolcine-free media for 2 hours, allowing them to progress in a highly synchronised manner into early G1.

first: Matthias

last: Merkenschlager

first: Bryony

last: Graham

first: Thomas

last: Carroll


title: DNA Methylation Profiling of Uniparental Disomy Subjects Provides a Map of Parental Epigenetic Bias in the Human Genome.

status: Public on Jun 01 2016

city: New York City

first: Ricky

middle: Shantilal

last: Joshi

state: NY

address: 1470 Madison Avenue

department: Genetics and Genomic Sciences

institute: Mount Sinai School of Medicine

summary: Genomic imprinting is a mechanism in which gene expression varies depending on parental origin. Imprinting occurs through differential epigenetic marks on the two parental alleles, with most imprinted loci marked by the presence of differentially methylated regions (DMRs). To identify sites of parental epigenetic bias, here we have profiled DNA methylation patterns in a cohort of 57 individuals with uniparental disomy (UPD) for 19 different chromosomes, defining imprinted DMRs as sites where the maternal and paternal methylation levels diverge significantly from the biparental mean. Using this approach we identified 77 DMRs, including nearly all those described in previous studies, in addition to 34 DMRs not previously reported. These include a DMR at TUBGCP5 within the recurrent 15q11.2 microdeletion region, suggesting potential parent-of-origin effects associated with this genomic disorder. We also observed a modest parental bias in DNA methylation levels at every CpG analyzed across ∼1.9 Mb of the 15q11-q13 Prader-Willi/Angelman syndrome region, demonstrating that the influence of imprinting is not limited to individual regulatory elements such as CpG islands, but can extend across entire chromosomal domains. Using RNA-seq data, we detected signatures consistent with imprinted expression associated with nine novel DMRs. Finally, using a population sample of 4,004 blood methylomes, we define patterns of epigenetic variation at DMRs, identifying rare individuals with global gain or loss of methylation across multiple imprinted loci. Our data provide a detailed map of parental epigenetic bias in the human genome, providing insights into potential parent-of-origin effects.

overall_design: 66 UPD samples analyzed in total, From each individual, whole bllod DNA was extracted and global DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.

first: Paras

last: Garg

first: Corey

last: Watson

first: Andrew

last: Sharp