title: Gene expression of AML patient samples

city: Strassen

first: Tony

last: KAOMA

address: 1 A-B Rue Thomas Edison

department: Quantitative Biology Unit

institute: Luxembourg Institute of Health

summary: It has been hypothesized that chemotherapy resistant human acute myeloid leukemia (AML) cells are enriched in an immature phenotype, cellular quiescence and leukemic initiating cells (LICs). However, these hypotheses have never been validated completely in vivo. We have developed a physiologically relevant chemotherapeutic approach with cytosine arabinoside AraC using patient-derived xenograft (PDX) models. AraC-treated AML cells are not consistently enriched for either immature cells or quiescent cells. AraC treatment does not enrich for LICs as measured by limiting dilution in secondary transplantations. Rather chemotherapy resistant cells in vivo have high levels of reactive oxygen species (ROS) and a gene signature consistent with oxidative phosphorylation (OXPHOS). Treatment of human HIGH OXPHOS but not LOW OXPHOS AML cell lines showed chemotherapy resistance in vivo, showing that essential mitochondrial functions make significant contributions to AraC resistance in AML. Accordingly, targeting mitochondrial OXPHOS metabolism through the inhibition of mitochondrial protein synthesis, the electron transfer chain or fatty acid oxidation induced an energetic shift towards LOW OXPHOS and strongly enhanced anti-leukemic effects of AraC in AML cells. These results demonstrate that chemotherapy resistance in AML is not necessarily associated with stemness but is highly dependent on a distinct oxidative metabolism, and that the HIGH OXPHOS gene signature is a robust hallmark of the AraC response in PDX and a promising therapeutic avenue to treat AML residual disease.

overall_design: Human acute myeloid leukemia primary cells from patients were grown during 2 hours for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain gene signature specific of in vivo response to cytarabine in NSG mice.

first: Thomas

last: Farge

first: Clément

last: Larrue

first: Gwenn

last: Danet-Desnoyers

first: Martin

last: Carroll

first: Christian

last: Récher

first: Jean-Emmanuel

last: Sarry

last: Kaoma


title: microRNA cluster 106a~363 is involved in T helper 17 cell differentiation

status: Public on Jun 06 2017

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum Muenchen

summary: Combined analysis of mRNA and miRNA transcriptoms revealed a complex network regulating major immune regulatory signaling pathways

overall_design: We performed mRNA and small RNA expression microarray analysis on three T-helper populations: Th0 (control), Th2, and Th17

first: Marc

last: Kästle

last: Irmler

first: Susanne

last: Kraus-Etschmann


title: Expression data from aortic wall between myocardial infarction (MI) and non-MI group

status: Public on Jun 04 2017

city: Bangkok

first: Thidathip

last: Wongsurawat

state: Bangkok

address: 11th Flr, SiMR Bldg.,  Num. 2, Wang Lang Rd., Bangkoknoi, Siriraj hospital

country: Thailand

institute: Mahidol University

summary:
The aortic wall of patients with ischemic heart disease may have an indicative characteristic of mRNA predictive of future cardiovascular events.
We used microarrays to detail the gene expression and identified distinct classes of up-regulated and down-regulated genes.

overall_design: Ascending aortic wall punch biopsies obtained as a standard part of coronary artery bypass surgery, will be used as a novel approach to study the vessel wall of patients with atherosclerosis. A total of 37 (17 MI, 20 Non-MI) frozen aortic tissues  were embedded in TissueTek optimal cutting temperature (OCT) compound (TissueTek; Sakura Finetek USA). The embedded aortic tissues were trimmed and sectioned to a thickness of 10µm and placed on an RNase-free Polyethylene Naphthalate (PEN) membrane slide (Carl Zeiss; Germany). Haematoxylin and eosin staining (H&E) was also performed to establish the correct orientation of the embedded aortic tissue.  Each slide containing frozen aortic sections was stained with Arcturus Histogene LCM Frozen Section Staining Kit (Applied Biosystems) according to the manufacturer’s protocol to enhance the visibility of VSMCs – elongated and spindle-shaped. LCM was performed immediately upon completion of staining using the LMPC technology in MicroBeam system (PALM microlaser, Carl Zeiss). The dissected VSMCs were scraped into a microcentrifuge tube containing 100µL of ice-cold TRI Reagent® (Molecular Research Centre, USA), with 19G sterile needles and freeze down in dry ice. Total RNA was isolated from VSMCs with Tri Reagent® (Molecular Research Centre) following manufacturer’s protocol and amplified with Ovation FFPE WTA System (NuGEN Technologies).

first: Woo

middle: C

last: Cheng

first: Vladimir

last: Kuznetsov

first: Sorokin

last: Vitaly


status: Public on Jun 09 2017

city: Tokushima

first: Kensei

last: Nishida

state: Tokushima

address: 3-18-15 Kuramoto-cho

country: Japan

institute: Tokushima University Graduate school

type: Methylation profiling by genome tiling array

summary: Genome wide DNA methylation profiling of post-exercise milk product intake during interval walking training. The Illumina Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in peripheral blood samples. Samples include 24 subjects (12, placebo intake; 12, milk product intake).

overall_design: Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: Shizue

last: Masuki

first: Hiroshi

last: Nose


title: Expression data from human pancreatic tissue from healthy subjects and pancreatic ductal adenocarcinoma patients

status: Public on Jun 20 2017

city: Bergen

first: Helge

last: Ræder

address: Jonas Lies vei

country: Norway

institute: Haukeland University Hospital

summary:
CEL mutation carriers may have increased pancreatic cancer risk.
We used microarrays to detail the global programme of gene expression underlying pancreatic cancer progression in a CEL mutation carrier and non-CEL mutation pancreatic cancer patients + controls.

overall_design: We selected pancreatic specimens from four normal pancreata and four pancreata with pancreatic ductal adenocarcinoma (PDAC) including a CEL mutation carrier

last: Raeder


title: Human umbilical cordderived mesenchymal stem cells (UCMSCs) induce a global transcriptional reprogramming in cisplatindamaged human renal proximal tubular epithelial cells (RPTECs).

status: Public on Jun 19 2017

city: Bergamo

first: Marina

last: Morigi

address: Parco Scientifico Tecnologico Kilometro Rosso, via Stezzano, 87

department: Molecular Medicine

country: Italy

institute: IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy

type: Expression profiling by high throughput sequencing

summary: To gain insights into the genes involved in the protective effect of human umbilical cordderived mesenchymal stem cells (UCMSCs) on cisplatininjured human renal proximal tubular epithelial cells (RPTECs), we performed a genomewide differential gene expression analysis by Ion AmpliSeqTM Transcriptome sequencing that targets more than 20,000 human genes. Our data indicated that genes involved in the pathways related to mitochondria and energy homeostasis were strongly upregulated by stem cell treatment in respect to cells treated with cisplatin alone, possibly representing a de novo regenerative response induced by UCMSCs.

overall_design: Gene expression profiles of three RPTECs samples (Control, Cispl, and Cispl+UCMSCs) were generated by Ion AmpliSeq Transcriptome sequencing, in triplicate, using Ion Proton Sequencer.

first: Luca

last: Perico

first: Cinzia

last: Rota

first: Matteo

last: Breno

first: Caterina

last: Mele

last: Noris

first: Martino

last: Introna

first: Chiara

last: Capelli

first: Lorena

last: Longaretti

first: Daniela

last: Rottoli

first: Sara

last: Conti

first: Giuseppe

last: Remuzzi

first: Ariela

last: Benigni


title: DNA methylation analysis of B cells in Rheumatoid Arthritis

city: Barcelona

first: Antonio

last: Julià

state: Barcelona

address: c/ Baldiri Reixac nº15

department: Rheumatology Research Group

country: Spain

institute: Vall d'Hebron Hospital Research Institute

summary: This study performed a genome-wide methylation analysis of positively isolated CD19+ B cells in rheumatoid arthritis (RA) and healthy controls. The Ilumina HumanMethylation450 BeadChip was uset to obtain the methylation levels at >400,000 CpG sites. Samples include 49 RA patients and 73 healthy controls.

overall_design: Bisulphite converted DNA from the 122 samples were hybridised to the Illumina HumanMethylation450 BeadChip. Methylation levels at each CpG site were compared between RA patients and controls, as well as at a pathway-level.

last: Marsal


title: Effect of KCNJ2 overexpression on gene expression profile in human iPS cell-derived cardiomyocytes

city: Aomori

first: Yuji

last: Nakai

state: Aomori

address: 2-1-1, Yanagawa

department: Institute of Regional Innovation

institute: Hirosaki University

summary: Drug-induced cardiac arrhythmia characterized by QT prolongation and torsade de pointes has been a major reason for drug withdrawal at the late stage of clinical trials. Current preclinical testing is still insufficient to identify drugs with pro-arrhythmic risks. Human induced pluripotent stem cell-derived cardiomyocytes are a promising development in safety screening as a reproducible human model. Using the patch-clamp technique, we showed that human induced pluripotent stem cell-derived cardiomyocytes exhibited spontaneous action potentials, which represent relatively immature forms of cardiac cells. Furthermore, in some spontaneously beating cells, a hERG blocker, E4031, depolarized membrane potentials and stopped spontaneous firing, resulting in failure to evaluate drug effects on electrophysiological parameters that reflect repolarization processes. Here we show that human stem cell-derived cardiomyocytes with transduced KCNJ2 encoding the inward-rectifier potassium channel have characteristics similar to mature cardiomyocytes including responsiveness to rate changes and potassium channel blockers. Our novel strategy could allow implementation of human induced pluripotent stem cell-derived cardiomyocytes in drug safety assessment for cardiac toxicity.

overall_design: As a commercially available differentiated cardiac cell line derived from hiPS cells, iCell-CMs (Cellular Dynamics International; CDI, Madison, WI, USA) were purchased from iPS Academia Japan Inc. (Kyoto, Japan), and were thawed and cultured according to the manual provided from the company (CDI) before adenoviral infections. After pre-culture for 4-days, cells are replated to the culture substrate (collagen-coated 24-well plate). Initial plating cell numbers were 2.5 X 10^5 / well. At replating, Ad-EGFP or Ad-KCNJ2-EGFP at 100 MOI (final) were applied to the cells for 24 h to achieve adenoviral infection. The cells were then cultured for 4 days after replating, and were collected for total RNA preparation.

first: Min

last: Li

first: Yasunari

last: Kanda

first: Takashi

last: Ashihara

first: Tetsuo

last: Sasano

first: Yuko

last: Sekino

first: Tetsushi

last: Furukawa

first: Junko

last: Kurokawa


title: Clonal selection and double hit events involving tumor suppressor genes underlie relapse from chemotherapy: myeloma as a model

status: Public on Jun 01 2017

city: Indianapolis

first: Brian

last: Walker

state: IN

address: 980 W Walnut St

department: Medicine

country: USA

institute: Indiana University

summary: To elucidate the mechanisms underlying relapse from chemotherapy in multiple myeloma we performed a longitudinal study of 33 patients entered into Total Therapy protocols investigating them using gene expression profiling, high resolution copy number arrays and whole exome sequencing. The study illustrates the mechanistic importance of acquired mutations in known myeloma driver genes and the critical nature of bi-allelic inactivation events affecting tumor suppressor genes, especially TP53. The end result being resistance to apoptosis and increased proliferation rates, which drive relapse by Darwinian type clonal evolution. The number of copy number aberration changes and bi-allelic inactivation of tumor suppressor genes was increased in GEP70 high risk, consistent with genomic instability being a key feature of high risk. In conclusion, the study highlights the impact of acquired genetic events, which enhance the evolutionary fitness level of myeloma propagating cells to survive multi-agent chemotherapy and to result in relapse.

overall_design: 66 Gene expression datasets from 33 patients over two time points


title: Expression data from NMuMG-mock cells and NMuMG-MAFK cells

city: Tsukuba

first: Yukari

last: Okita

address: 1-1-1 Tnnodai

institute: University of Tsukuba

summary:
MAFK is one of small Maf transcripton factor famiy molecules. We found MAFK is highly expressed in several cancer cells and related to tumorigenesis.
Then, we established MAFK stable cell lines using NMuMG cells (mouse mammary glad epithelium) and used microarrays to examine gene expression alteration.

overall_design: RNAs from NMuMG-mock cells and MAFK stably expressing cell lines (clones 4 and 10) were hybridized on Affymetrix microarrays.

first: Hiroyuki

last: Suzuki

first: Mitsuyasu

last: Kato


title: Identification of differentially expressed transcription factors in ovarian cancer

status: Public on Jun 05 2017

city: Houston

first: Tsz-Lun

last: Yeung

state: TX

address: 1515 Holcombe Blvd. Unit 1362

department: Gynecologic Oncology and Reproductive Medicine

institute: University of Texas MD Anderson Cancer Center

summary: Ovarian cancer is the fifth most common form of cancer in women in the United States. Epithelial ovarian cancer is the most common and is highly lethal. In 2014, there will be an estimated 21,980 new cases and 14,270 deaths from ovarian cancer in the United States. No major strides have been made to improve survival over the past decade. Ovarian cancer is notable for initial chemotherapy sensitivity (>75% response rates) using combination platinum and taxane chemotherapy following debulking surgery. However, eventually, the vast majority of these women (>75-80%) will have their cancer recur within 12 to 24 months after diagnosis and will die of progressively chemotherapy-resistant diseases. Transcription factors act as master switches of various biochemical pathways by regulating gene transcription. Large number of studies demonstrated the role of transcription factors in cancer development and progression. However, transcription factors involved in the pathogenesis of ovarian cancer have not been explored thoroughly. Therefore, we propose to using transcriptome profiling to generate a transcription factor gene signature for high-grade serous ovarian cancer.

overall_design: Transcriptome profiling analyses were performed on laser microdissected epithelial tumor samples from high grade serous ovarian cancer patients and microdissected ovarian surface epithelium (HOSE) samples using the Affymetrix human genome U133 Plus 2.0 microarray

first: Samuel

last: Mok

first: Kwong-Kwok

last: Wong


title: Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in colorectal cancer cells by binding to Matrin 3 [Affymetrix Human Gene 2.0 ST]

status: Public on May 31 2017

city: Bethesda

first: Yuelin

middle: Jack

last: Zhu

state: MD

address: 9000 Rockville Pike

department: Genetics Branch, Center for Cancer Research

institute: NCI

summary: Thousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named PINCR (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a critical prosurvival function in colorectal cancer cells (CRC) in vitro and tumor growth in vivo. Targeted deletion of PINCR in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. PINCR regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including BTG2, RRM2B and GPX1. Using a novel RNA pulldown approach that utilized endogenous S1-tagged PINCR, we show that PINCR associates with the promoters of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. Our findings uncover a critical prosurvival function of a p53/PINCR/Matrin 3 axis in response to DNA damage in CRC cells.

overall_design: HCT116 p53 WT, SW48 p53 WT and RKO p53 WT cells were kept untreated or treated with Nutlin-3a and RNA samples were collected in duplicates.

first: Ritu

last: Chaudhary

first: Murugan

last: Subramanian

first: Xiao

middle: L

middle: J

first: Ashish

last: Lal


title: LMP1+SLAMF1high cells are associated with drug resistance in Epstein-Barr virus-positive Farage cells

city: SEOUL

first: Heejei

last: Yoon

state: SEOUL

address: 50 ILWON-DONG

department: SAMSUNG BIOMEDICAL RESEARCH INSTITUTE

country: South Korea

institute: SAMSUNG MEDICAL CENTER

summary: We isolated Farage cells expressing the cell surface marker SLAMF1. LMP1 and its target gene CCL22 were highly expressed in SLAMF1high Farage cells. These cells survived longer following treatment with a combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Genes associated with interferon-alpha, allograft rejection, NF-kB, STAT3 and 5 were also overexpressed in the surviving Farage cells.

overall_design: The three experimental conditions were designed: 1) Farage cells were sorted according to expression level of SLAMF1 and labeled as SLAM_high or SLAM_low.; 2) Farage cells treated with 1 μg/ml CHOP for 2 days and 3 days compared with untreated Farage cells; 3) Farage cells incubated with 1 μg/ml CHOP plus 50 ng/ml IL4 compared with 50 ng/ml IL4 alone for 2 days.  Genome-wide analysis of all cell lines were performed using the Affymetrix HuGene ST 2.0 Array Platform.  Genes with differential expression were analyzed using Statistical Analysis of Microarrays (SAM) software, and a signature of genes determined.

first: Young

middle: H

last: Ko


title: Gene expression in mouse epididymal white adipose tissue in response to short-term calorie restriction

city: Madison

first: Jamie

last: Barger

state: WI

address: 510 Charmany Drive, Suite 263

institute: LifeGen Technologies, LLC

summary:
The effect of a short-term calorie restricted diet was evaluated in epididymal white adipose tissue (WAT) in seven strains of mice
The dietary intervention was initiated at 8 weeks of age and continued until 22 weeks of age

overall_design: Tissues were collected from mice at 22 weeks of age; there were 112 microarrays used in total: for each of the 7 strains of mice, there were 8 control-fed mice and 8 calorie restricted mice (one individual mouse per microarray)


title: Waterpipe Smoking Induces Epigenetic Changes in the Small Airway Epithelium [array]

status: Public on Jun 13 2017

city: New York

first: Yael

last: Strulovici-Barel

state: NY

address: 1300 York Avenue

department: Department of Genetic Medicine

institute: Weill Cornell Medical College

summary:
Waterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use water-pipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05) representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05) change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling). Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking.
This study demonstrates that light-use waterpipe smoking in young adults is associated with a broad range of genome-wide DNA methylation-related changes of the SAE impacting a number of genes linked to pathways previously associated with cigarette smoking. Further, many of these methylation-related changes correlate with waterpipe smoking-associated changes in the SAE transcriptome. Together, these data add to the accumulating evidence that waterpipe smoking is harmful, and may lead to lung disease.

overall_design: Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk) waterpipe-only smokers.  Expression profiling on Affymetrix and methylation profiling on NimbleGen platforms.

first: Matthew

middle: S

last: Walters

first: Jacqueline

last: Salit

first: Jin-Hyun

last: Ju

first: Michelle

middle: R

last: Staudt

first: Robert

last: Kaner

first: Allison

middle: M

last: Rogalski

first: Teniola

middle: B

last: Sodeinde

first: Riyaad

last: Rahim

first: Jason

middle: G

last: Mezey

first: Ahmad

last: Almulla

first: Hisham

last: Sattar

first: Mai

last: Mahmoud

first: Ronald

last: Crystal


title: Gene expression profile (GEP) of CD34+ cells overexpressing miR-494-3p

status: Public on Jun 12 2017

city: Modena

first: Rossella

last: Manfredini

address: Via Gottardi 100

department: Life Sciences

institute: Centre for Regenerative Medicine

summary:
As recently reported by our group, we performed miRNA and gene expression profiling of CD34+ hematopoietic stem/progenitor cells (HSPCs) isolated from 42 PMF patient samples compared with 31 healthy controls. Integrative analysis of these profiles by means of Ingenuity Pathway Analysis (IPA) allowed the identification of several aberrantly regulated miRNA-mRNA target pairs organized in interaction networks. In particular, our results highlighted the up-regulation of miR-494-3p in CD34+ cells from PMF patients (Norfo R et al, Blood, 2014). Interestingly, among the most upregulated miRNAs, miR-494-3p emerges as being associated to the highest number of downregulated target mRNAs. In order to understand the biological role of miR-494-3p during the hematopoietic commitment and differentiation, we overexpressed this miRNA in cord blood (CB) derived-CD34+ cells. Cells were electroporated with either miR-494-3p miRNA mimic (mimic miR-494) or a negative control mimic (mimic Neg CTR). qRT-PCR confirmed miR-494-3p overexpression 24h and 4 days after transfection (RQ ± SEM, 512.60 ± 137.37, p<.01, and 20.63 ± 3.03, p<.01, respectively).
Immunophenotypic analysis of CD41 and CD42b megakaryocyte (MK) lineage differentiation markers, performed on serum-free megakaryocytic ultilineage culture at day 3, 5, 8, 10 and 12, demonstrated that miR-494-3p overexpression induces a significant increase in the MK fraction compared to control samples. Accordingly, morphological analysis of May-Grünwald-Giemsa stained cytospins revealed an expansion of megakaryocytic lineage in samples overexpressing miR-494-3p. These data were further confirmed by collagen-based clonogenic assays which showed a significant increase in the percentage of megakaryocytic colonies in miR-494-3p overexpressing samples compared with controls. In order to better characterize the molecular mechanisms underlying the effects of miR-494-3p on HSPCs differentiation, we performed gene expression analysis of miR-494-3p overexpressing cells 24 hours after the last nucleofection.

overall_design: Gene expression profile (GEP) was performed on total RNA derived from three independent experiments at 24h after the last nucleofection.

first: Ruggiero

last: Norfo

first: Sebastiano

last: Rontauroli

first: Valentina

last: Pennucci

first: Roberta

last: Zini

first: Samantha

last: Ruberti

first: Elisa

last: Bianchi

first: Simona

last: Salati

first: Zelia

last: Prudente

first: Chiara

last: Rossi

first: Vittorio

last: Rosti

first: Paola

last: Guglielmelli

first: Giovanni

last: Barosi

first: Alessandro

last: Vannucchi

first: Enrico

last: Tagliafico


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

first: Jamie

last: Barger

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


title: Expression data from induced mescenchymal stem cells (iMSCs), human adult fibroblasts (42 and 56-year old), and neonatal fibroblast (CRL2097).

city: Taipei

first: Pei-Lun

last: Lai

address: 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan

department: Genomic research center

country: Taiwan

institute: Acdemia Sinica

summary:
Human dermal fibroblasts are conversion into iMSCs by drug treatment, the global gene profiles of iMSCs are comparable to bone marrow MSCs.
We used microarrays to detail the global programme of gene expression in iMSCs, BMMSCs and fibroblasts.

overall_design: We generated iMSCs  that derived from 42 and 56-year old dermal fibroblasts and neonatal fibroblasts CRL2097, these three source of fibroblasts as negative control and one BMMSCs for positive control.

first: Shang-Chih

last: Yang


title: Multi-omics profiling of patients with primary Sjogren's syndrome

status: Public on May 19 2017

city: Fujisawa

first: Shinya

last: Tasaki

state: Kanagawa

address: 26-1, Muraoka-Higashi 2-chome

institute: Takeda Pharmaceutical Company Limited

summary:
Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren’s syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.

Proteomics and FACS data will be found in Synapse.
https://www.synapse.org/#!Synapse:syn8483276

overall_design: 30 pSS patients and 30 healthy volunteers were recruited and compared whole blood transcriptome

first: Hiroyoshi

last: Toyoshiba

first: Tsutomu

last: Takeuchi


title: High-risk human papillomavirus E7 affects host keratinocyte gene expression

status: Public on Jun 11 2017

city: Aurora

first: Dohun

last: Pyeon

state: CO

department: Immunology and Microbiology

institute: University of Colorado School of Medicine

summary:
To investigate the extent of gene expression dysregulation by the human papillomavirus (HPV) oncoprotein E7, we performed global gene expression analysis on normal immortalized keratinocytes from skin (NIKS),
NIKS cells maintaining the HPV16 or 18 episomes (NIKS-16, NIKS-18, respectively), and NIKS cells maintaining the HPV-16 episome deficient in E7 expression (NIKS-16ΔE7).

overall_design: NIKS cells and variants were cultured and harvested at three separate passages (n= 3). RNA was isolated and hybridized to Affymetrix chips for gene expression analysis. NIKS cells are HPV-negative control.

first: Louis

last: Cicchini


title: Parallel global gene expression and DNA methylation analyses of human papillomavirus-positive normal keratinocytes

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

overall_design: Refer to individual Series


title: High-risk human papillomavirus E7 affects host keratinocyte DNA methylation

summary:
To investigate the extent of host methylome dysregulation by the human papillomavirus (HPV) oncoprotein E7, we performed methylome array analysis on normal immortalized keratinocytes from skin (NIKS),
NIKS cells maintaining the HPV16 or 18 episomes (NIKS-16, NIKS-18, respectively), and NIKS cells maintaining the HPV-16 episome deficient in E7 expression (NIKS-16ΔE7).

overall_design: NIKS cells and variants were cultured and harvested at three separate passages (n= 3). Genomic DNA was isolated, bisultife converted and hybridized to illumina HumanMethylation 450 BeadChips for methylation analysis. NIKS cells are HPV-negative control.


title: Cytoplasmic overexpression of RNA-binding protein HuR in meningioma is a marker of poor prognosis and specific HuR knockdown decreases meningioma cell growth and resistance to hypoxia

status: Public on May 11 2017

city: Vandoeuvre-lès-Nancy

first: Sebastien

last: Hergalant

address: Faculté de Médecine. 9 avenue de la forêt de Haye

department: Bioinformatics

country: France

institute: INSERM

summary:
HuR is known to regulate mRNA stability and translatability in cytoplasm. In several human tumors, the level of HuR expression has been shown to correlate with poor disease outcome. In meningioma, however, the prognostic value and the potential pro-oncogenic properties of HuR remain obscure. To clarify these, transcriptome-wide analyses in IOMM-Lee cells were performed to pinpoint the detailed molecular consequences of HuR knockdown.
In IOMM-Lee cells, transcriptomic analyses revealed that HuR knockdown deregulated the signaling pathway of HIF1A and upregulated the expression of genes for cytoplasmic mRNA processing body assembly, poly(A)-specific ribonuclease activity, positive regulation of apoptosis, negative regulation of RNA splicing, global genome nucleotide-excision repair, and positive regulation of cell cycle arrest. Interestingly, HuR knockdown under hypoxic culture condition potentiated further the effects of HuR knockdown on cell growth, apoptosis, and HIF1A expression.

overall_design: IOMM-Lee cells transfected with either the Silencer Select Negative Control siRNA#1 (Ctrl ; n=6 ; biological replicates) or Silencer Select siRNA ELAVL1 s4608 (HuR ; n=6 ; biological replicates)

first: Guillaume

last: Gauchotte

first: Shyue-Fang

last: Battaglia-Hsu

first: Sébastien


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


title: Profiling of in vitro differentiated activated T helper cells [mRNA]

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

institute: Helmholtz Zentrum Muenchen

summary: Combined analysis of mRNA and miRNA transcriptoms revealed a complex network regulating major immune regulatory signaling pathways

overall_design: We performed mRNA and small RNA expression microarray analysis on three T-helper populations: Th0 (control), Th2, and Th17

first: Marc

last: Kästle

first: Martin

last: Irmler

first: Susanne

last: Kraus-Etschmann


title: Early Induction of NRF-2 Antioxidant Pathway by RHBDF2 Mediates More Rapid Cutaneous Healing in Mice

city: Bar Harbor

first: Vishnu

last: Hosur

state: ME

address: 600 Main Street

department: Research

institute: The Jackson Laboratory

summary:
Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. Using a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2cub/cub), which shows a regenerative phenotype, we sought to identify the underlying mechanism.
Transcriptome analyses were performed to identify early-stage pathways and biological processes that function post-wound healing in Rhbdf2cub/cub and control Rhbdf2+/+ mice.

overall_design: Two-mm through-and-through holes were punched into the ears of 4-wk-old Rhbdf2+/+ and Rhbdf2cub/cub female mice and ear pinna tissue was collected at 0h, 15 min, 2h, and 24h post-wounding (three mice per time point). A total of 23 Affymetrix Mouse Gene 1.0 ST Arrays were used for gene expression analysis. For this experiment, pairwise comparisons were used to statistically resolve gene-expression differences between genotype groups at 0h, 15 min, 2h, and 24h using the R/maanova analysis package.Differentially expressed genes were declared at an FDR q-value threshold of 0.05.

first: Lisa

last: Burzenski

first: Timothy

last: Stearns

first: Michelle

last: Farley

first: John

middle: P

last: Sundberg

first: Michael

middle: V

last: Wiles

first: Leanord

middle: D

last: Shultz


title: Genome wide STAT3 RNAi expression profiling data from Thp,Th0 and Th17 cells

status: Public on May 03 2017

first: Tarmo

last: Äijö

address: 162 5th Avenue

department: Center for Computational Biology

institute: Flatiron Institute

summary:
STAT3 is an immidiate regulator of Th17 differentiation. STAT3 difieciency downmodulate Th17 specific genes and Th17 responses. Therefore, we intend to identify genome wide targets of STAT3.
We used microarrays to profile gene expression of STAT3 regulated genes during Th17 polarization.

overall_design: Total RNA was extracted from non-targeting and STAT3 siRNA treated Thp, Th0 and Th17 cell samples from different time points. Total RNA subjected to poly-A selection and hybridization on Affymetrix microarrays.

first: Subhash

last: Tripathi

first: Riitta

last: Lahesmaa


title: KLF family members KLF4 and KLF7 regulate corneal epithelium [siKLF4-siKLF7_differentiation]

city: Irvine

first: Bogi

last: Andersen

state: CA

address: 839 Health Sciences Dr.

institute: University of California, Irvine

summary: While the regulatory landscape during stem cell differentiation has been well characterized, the shared and unique regulatory mechanisms in different ectodermally-derived epithelial cells have not been well described. Through defining the complement of super enhancers and typical enhancers in corneal epithelium for the first time, we show that regulatory regions are often shared between cell types of the same lineage, and that corneal super enhancers are already marked as potential regulatory domains in embryonic stem cells. Through the enrichment of KLF motifs in enhancers, we identified and defined a novel role for Kruppel family member KLF7 in promoting the corneal progenitor cell state, in many cases working antagonistically to corneal differentiation promoting KLF4. Our work highlights the importance of balance between proliferation and differentiation, both for proper tissue development and for homeostasis.

overall_design: pools of siRNAs were used to knockdown KLF4 or KLF7 in duplicate, with 2 scramble siRNA control cell plates. RNA was extracted and submitted for microarray.

first: Rachel

last: Herndon Klein


title: Genome-wide profiling of the functional DNA methylation landscape at base-pair resolution in human cancer types

status: Public on Jun 07 2017

city: L'Hospitalet de Llobregat

first: Manel

last: Esteller

address: Hospital Duran i Reynals Av. Gran Via s/n km, 2.7

department: PEBC

institute: IDIBELL

summary: High-resolution DNA methylation array analysis of human cancer samples and normal control tissue types.

overall_design: Array based analysis of human cancer samples and normal control tissue types

first: Holger

last: Heyn


title: Integrated data analysis reveals distinct drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

status: Public on May 04 2017

city: São Paulo

first: Caroline

middle: Moraes

last: Beltrami

state: SP

address: Rua Taguá 440

department: International Research Center - CIPE

country: Brazil

institute: A C Camargo Cancer Center

summary: Multiple joint data, including methylome, transcriptomic, BRAF V600E mutation results and clinical features, aiming to identify molecular drivers in papillary thyroid carcinomas.

overall_design: Whole DNA methylation profile was evaluated in 41 papillary thyroid cancer matched with 41 non-neoplastic adjacent tissues. In addition, an integrative analysis was performed using 34 PTC with methylome and transcriptomic data (GSE50901). The reliable gene was identified by a cross-study validation using a external database (TCGA).

first: Mateus

last: Barros-Filho

first: Mariana

last: dos Reis


title: mRNA Profiling of miR-17 family inhibition using TuD lentiviral vector in Hep3B hepatocellular carcinoma cell line [array]

city: San Diego

first: Vivek

last: Kaimal

address: 10614 Science Center Dr.

institute: Regulus Therapeutics

summary:
To functionally characterize the role of miR-17 family in HCC, lentiviral vector-based miR inhibitor TuD was used to inhibit miR-17 family of microRNAs in Hep3B cell line
Methods: Hep3B HCC cell line was acquired from American Type Culture Collection (ATCC) and miR-17 TuD or NC TuD expressing lines were generated. Microarray profiling of miR-17 TuD or NC TuD expressing samples was performed using Affymetrix HG-U133Plus2 arrays. Briefly, starting with 1 ug total RNA, amplified biotin-labeled cRNA targets were produced using the Enzo Target Labeling method. Fragmented, biotin-labeled cRNA was hybridized to the Affymetrix GeneChip® HG-U133Plus2 Genome Arrays overnight at 45C for 16 to 18 hours according to the manufacturer’s recommendations. Stain, wash (GeneChip Fluidics Station 450, EukGE-WS2v5_450 script) and scan (GCS 3000 7G with the GeneChip® AutoLoader) were performed according to the manufacturer’s recommendations. Microarray data were GC Robust Multiarray Average (GCRMA) normalized using R and the bioconductor.org package gcrma and Log2 transformed.

overall_design: Gene expression profiles for TuD expressing samples (triplicate) and NC TuD expressing samples (triplicate) were generated using Affymetrix HG-U133Plus2 microarrays

first: Xinqiang

last: Huang

first: Adam

last: Pavlicek


title: KLF family members KLF4 and KLF7 regulate corneal epithelium


title: Gene expression profiles of MM.1S cells after knockdown of HDAC3 or DNMT1

city: Tokushima

first: Takeshi

last: Harada

address: 3-18-15 Kuramoto-cho

department: Hematology, Endocrinology and Metabolism

institute: Tokushima University Graduate School of Biomedical Sciences

summary:
Previous study demonstrated that HDAC3 has a critical role in MM proliferation; however, the underlying mechanism has not yet been elucidated. We identify that HDAC3 inhibition targets DNMT1 through dual regulations. We demonstrate that knockdown of DNMT1 leads to apoptosis and significant growth inhibition in myeloma cells. HDAC3 inhibition by gene silencing or HDAC3 selective inhibitor BG45 downregulates an oncoprotein c-Myc through its acetylation. c-Myc directly regulates DNMT1 expression at its enhancer region. Furthermore, HDAC3 directly regulates the stability of DNMT1 protein through its acetylation. Pharmaceutical inhibition of HDAC3 and DNMT1 synergistically induce MM growth inhibition in in vitro and in vivo settings.
The goal of this analysis is to identify genes whose expression changes after shRNA-mediated knockdown of HDAC3 or DNMT1 using the human U133 plus 2.0 Affymetrix GeneChip in myeloma cell line (MM.1S).

overall_design: Myeloma cell line (MM.1S) was transduced with either shRNAs targeting HDAC3 (duplicate hairpins), DNMT1 (duplicate hairpins) or luciferase (control) in duplicate. The gene expression profiles of HDAC3 or DNMT1 knockdown cells were compared with that of control cells. A total of 10 RNA samples (4 HDAC3 knockdown, 4 DNMT1 knockdown, and 2 control) were analyzed.

first: Kenneth

last: Anderson


title: Gene expression in HCT116 cells after JMJD1A/1B depletion

city: Los Angeles

first: Jiong

last: Li

state: CA - California

department: School of Dentistry

institute: UCLA

summary: Using microarrays to explore the global programme of gene expression after depeltion of JMJD1A and JMJD1B

overall_design: HCT116 cells were transfected with JMJD1A and JMJD1B siRNA. 2 days post transfection the total RNA was extracted and analysed by microarray.


title: A DNA methylation atlas of the human eye and its diseases

status: Public on May 02 2017

summary: Genome-scale DNA methylation profiling using the Infinium DNA methylation BeadChip platform and samples from normal human eye and five ocular- related diseases

overall_design: DNA methylation analysis of eye samples from patient suffering ocular diseases (retinal detachment, diabetic retinopathy, glaucoma, uveal melanoma and retinoblastoma) using the Infinium DNA methylation BeadChip platform .

first: María

last: Berdasco


title: Hes1 is responsible for Notch signaling-mediated suppression of acute myeloid leukemia development

city: Tsukuba

first: Takayasu

last: Kato

state: Ibaraki

address: Tennodai 1-1-1

institute: University of Tsukuba

summary: In leukemogenesis Notch signaling can be up- and down-regulated in a context-dependent manner. Here we report that deletion of hairy and enhancer of split-1 (Hes1) promotes acute myeloid leukemia (AML) development induced by the MLL-AF9 fusion protein. Subsequently, the FMS-like tyrosine kinase 3 (FLT3) was up-regulated in mouse cells of a Hes1- or RBP-J-null background. MLL-AF9-expressing Hes1-null AML cells showed enhanced proliferation and ERK phosphorylation following FLT3 ligand stimulation. FLT3 inhibition efficiently abrogated proliferation of MLL-AF9-induced Hes1-null AML cells. Furthermore, an agonistic anti-Notch2 antibody induced apoptosis of MLL-AF9-induced AML cells in a Hes1-wild type but not a Hes1-null background. These observations demonstrate that Hes1 mediates tumor suppressive roles of Notch signaling in AML development by down-regulating FLT3 expression.

overall_design: 4 samples are analyzed,  two pairs of MLL-AF9/Hes1-/- and MLL-AF9/Hes1+/+ leukemic bone marrows.

first: Mamiko

last: Sakata-Yanagimoto

first: Hidekazu

last: Nishikii

first: Yasuyuki

last: Miyake

first: Yasuhisa

last: Yokayama

first: Yukitsugu

last: Asabe

first: Yuhei

last: Kamada

first: Naoshi

last: Obara

first: Kazumi

last: Suzukawa

first: Issay

last: Kitabayashi

first: Kazuhiko

last: Uchida

first: Hideo

last: Yagita

first: Ryoichiro

last: Kageyama

first: Shigeru

last: Chiba


title: Placental Gene Expression in Response to Histamine and Oxygen

city: London

first: Obed

last: Brew

address: St Mary's Road

country: United Kingdom

institute: University of West London

summary:
Maternal Blood histamine levels are tightly controlled in normal pregnancy. However, in specific complications of human pregnancy such as pre-eclampsia the levels of both placental and maternal blood histamine increase. Increasing blood histamine levels nonetheless, have been associated with oxidative stress, endothelial dysfunction, abnormal tissue growth, and Th1/TH2 imbalance, which are also linked to pre-eclampsia. Little is known of the molecular responses in the placenta to the prolonged exposure to increasing histamine levels in the presence of changing oxygen concentrations.
We used microarray to detail the global programme of placental gene expression in response to histamine and oxygen and identified distinct classes of regulated genes underlying the molecular functions of histamine in the placenta.

overall_design: Term (weeks 38 -40) placental micro explants from normal singleton pregnancies delivery by Elective Caesarean Sections were incubated in 8% (PL 8%) or 20% (PL 20%) oxygen for 6 days with (PL 8%-Treat or PL 20%-Treat) or without (PL 8%-Con or PL 20%-Con) histamine and aminoquanidine.

first: Mark

last: Sullivan


title: Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in colorectal cancer cells by binding to Matrin 3

city: Bethesda

first: Yuelin

last: Zhu

address: 9000 Rockville Pike

institute: NCI


title: Epigenome analysis of CHAMACOS cord blood

city: Berkeley

first: Nina

last: Holland

address: 733 University Hall

institute: University of California, Berkeley

summary: Genome wide DNA methylation profiling of CHAMACOS cord blood. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs. Methylation was assessed in 380 cord blood samples of members of the CHAMACOS cohort.

overall_design: Bisulphite converted DNA from the 380 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: Paul

last: Yousefi

first: Olivia

last: Solomon

first: Lisa

last: Barcellos

first: Brenda

last: Eskenazi


title: Postnatal monocyte maturation requires age-dependent initiation of regulatory gene programs when losing birth-associated stress tolerance

status: Public on May 01 2017

city: Bonn

first: Joachim

last: Schultze

state: NRW

address: Carl-Troll-Strasse 31

department: Genomics and Immunoregulation

institute: LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)

summary: We disprove that the impaired Myd88-dependent proinflammatory response of neonatal monocytes is a correlate for immaturity and confirm it as display of transient alarmin-mediated stress tolerization. We find a strong inducibility of TRIF-dependent genes in neonatal monocytes by LPS but a barely detectable expression at baseline.

overall_design: Isolated adult blood (AB) and cord blood (CB) monocytes were stimulated for 4h with lipopolysaccharide (LPS).

first: Thomas

last: Ulas

first: Dorothee

last: Viemann


title: Expression data from DLBCL tumor biopsies

status: Public on Apr 30 2017

city: Sunnyvale

first: Hsu-Ping

last: Kuo

address: 995 E Arques Ave

institute: Pharmacyclics

summary: Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton’s tyrosine kinase (BTK)–mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and FL lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy.

overall_design:
Gene expression in ibrutinib pretreated tumor biopsy samples from ABC-DLBCL patients was detected by U133 plus 2.0 arrays and the correlation of BCL2 expression and patient response to ibrutinib or PFS after ibrutinib treatment was analyzed. There are total 28 ABC-DLBCL samples. 17 of them are non-responders (PD+SD) and 11 of them are responders (PR+CR). For this analysis restricted to ABC-DLBCL subtype, only the ABC-DLBCL samples were used and normalized separately.

Data was processed with all subsets of DLBCL samples (60 samples) and also separately for 28 ABC-DLBCL samples ('re-analysis' samples).

The values in the sample 'characteristics' field represent:
response:
CR=complete response, PR=partial response, SD=stable disease, PD=progression disease
class:
NR=non-responder, RR=responder
subtype:
ABC=ABC-DLBCL, GCB=GCB-DLBCL, UNC=unclassified subtype
progression_free_survival_censor:
censored case = 1; event (death/progression) = 0 in the censoring variable for the progression free survival analysis

first: Scott

middle: A

last: Ezell

first: Karl

last: Schweighofer

first: Leo

middle: W

last: Cheung

first: Sidney

last: Hsieh

first: Mutiah

last: Apatira

first: Mint

last: Sirisawad

last: Eckert

first: Jeff

last: Hsu

first: Chun-Te

last: Chen

first: Darrin

last: Beaupre

first: Matthias

last: Versele

first: Betty

middle: Y

last: Chang


title: Expression data from DLBCL tumor biopsies and TMD8 cell line

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

overall_design: Refer to individual Series


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

city: Madison

first: Jamie

last: Barger

address: 510 Charmany Drive, Suite 263

institute: LifeGen Technologies, LLC

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

overall_design: Tissues were collected from mice at 22 weeks of age; there were 112 microarrays used in total: for each of the 7 strains of mice, there were 8 control-fed mice and 8 calorie restricted mice (one individual mouse per microarray)


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

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


title: Lineage specific differentiation is influenced by state of human pluripotency [mouse]

status: Public on Apr 26 2017

city: Hamilton

first: Mickie

last: Bhatia

state: Ontario

address: 1200 Main Street West

department: Stem Cell and Cancer Research Institute (SCC-RI)

country: Canada

institute: McMaster University

summary: Human pluripotent stem cells (hPSCs) have been reported in naïve and primed states. However, the ability of human PSCs to generate mature cell types is the only imperative property for translational utility. Here, we reveal that the naïve state enhances self-renewal capacity while restricting lineage differentiation in vitro to neural default fate. Gene expression analyses indicate expression of multiple lineage associated transcripts in naïve hPSCs and thus failed to predict biased functional differentiation.  Naïve hPSCs can be converted to primed allowing recovery of multilineage differentiation over long serial passage or immediately through suppression of OCT4 but not NANOG. To this end, we identified chemical inhibitors of OCT4 expression that acutely restore naïve hPSC differentiation. Our study identifies unique cell fate features and critical restrictions in human pluripotent states, and provides an approach to overcome these barriers that harness both efficient naïve hPSC growth whilst maintaining in vitro differentiation capacities essential for hPSC applications.

overall_design: Transcriptome analysis was performed on bulk culture of PSC lines in order to compare their RNA expression profile to samples of naïve and primed PSCs from the literature

first: Jong-Hee

last: Lee


title: Epigenetic minicircuitry of AML1-ETO/THAP10/MIR383 contributes t(8;21) AML leukemogenesis

city: Beijing

first: Shi

last: Long

state: Peking

address: Road One

country: China

institute: NDUT

summary: AML1-ETO is regarded as an initial event and plays a pivotal role in t(8;21) acute myeloid leukemia (AML) which is a highly heterogeneous disease. DNA methylation patterns are frequently deregulated in t(8;21) AML, though little is known of the mechanisms through which specific gene sets become aberrantly methylated. Here, We found that the promoter DNA methylation signature of t(8;21) AML blasts differs from those of normal CD34+ bone marrow cells and other AMLs. This signature contains 408 differentially methylated genes, many of which are genes involved in cancer pathway and myeloid leukemia. Database systematic survey and differential methylated regions (DMR) analysis were performed. These study demonstrated that a novel hypermethylated zinc finger containing protein-THAP10 is a target gene and can be epigenetic silenced by AML1-ETO at transcriptional level in t(8;21) AML and silencing of THAP10 by AML1-ETO predicts a poor clinical outcome. Our findings also identified that THAP10 is a bona fide target of miR-383 which can be epigenetic activated by AML1-ETO. In this study, we provided evidence that epigenetic silencing of THAP10 is the mechanistic link between AML1-ETO fusion proteins and tyrosine kinase cascades. In addition, we showed that THAP10 is a nuclear protein which inhibits myeloid proliferation inhibition and promotes differentiation both in vitro and in vivo. Altogether, our results revealed an unexpected and important link between fusion protein AML1-ETO, mir-383, THAP10 and tyrosine cascades in t(8;21) AML.

overall_design: Bisulphite converted DNA from the 12 samples were hybridised to the Illumina HumanMethylation450 BeadChip, including 5 t(8;21)-positive AML, 5 t(8;21)-negative AML M2 subtype according FAB and 2 normal bone marrow.

first: Yonghui

last: Li

first: Jinlong

last: Shi


title: The vacuolar high affinity copper transporter COPT5 participates in the copper requirement for iron signaling in Arabidopsis Thaliana

status: Public on May 30 2017

city: Burjassot

first: Angela

last: Carrió-Seguí

state: Valencia

address: Dr. Moliner 50

department: Biochemistry and Molecular Biology

institute: University of Valencia

summary: Iron and copper are important environmental nutrients for plant growth. However, the molecular mechanisms of both iron and copper signaling that integrate the two pathways remain poorly understood. The Arabidopsis thaliana high affinity copper transporter COPT5, is a tonoplast localized permease involved in copper remobilization. Here, a global expression microarray analysis of the copt5 mutant points out the induction of iron deficiency responses, including NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 4 (NRAMP4), a tonoplast-localized iron transporter.  The copper requirement in iron perception and uptake from the media becomes more evident in the double nramp3nramp4 mutant, unable to remobilize iron from vacuoles, that is highly sensitive to copper deficiency. Furthermore, COPT5 expression is altered under iron deficiency and the copt5 mutant is sensitive to iron deficiency and is unable to perceive iron in the media under copper deficiency. Noteworthy, iron deficiency post-transcriptionally restraints the copper-dependent superoxide dismutase protein levels and the subsequent activity. As a consequence of its increased iron deficiency responses, the copt5 mutant present lower levels of both copper- and iron-dependent superoxide dismutase activities. Moreover, the copt5 mutant mobilizes faster its iron storage pools and presents higher levels of iron in cotyledons and seeds. These results underline the importance of internal metal pools in the understanding of copper and iron deficiency responses and their crosstalk that are critical for governing proper plant development in response to combined metal scarcities in soils.

overall_design: 12 samples form 3 biological replicates and 4 conditions (WT+Cu; C5+Cu; Wt+BCS; C5+BCS) are analyzed. Wt is Arabidopsis thaliana columbia 0 and copt5-2 knockout mutant

last: Carrio-Segui

first: Paco

last: Romero

first: Catherine

last: Curie

first: Stéphane

last: Mari

first: Lola

last: Peñarrubia


title: Gene expression changes induced by BAY1436032 (IDH1mut inhibitor) in sorted human (CD45+) cells from bone marrow of IDH1mut patient derived xenotransplantation mice model

status: Public on May 22 2017

city: Hannover

first: Anuhar

last: Chaturvedi

address: Cral Neuberg Strasse-1

department: Hematology, Hemostasis, Oncology and Stem Cell Transplantation

institute: Hannover Medical School

summary: Mutations in the enzymes IDH1 and IDH2 have been identified in a wide variety of tumors like glioma, chondrosarcoma, thyroid cancer, lymphoma, melanoma, and in acute myeloid leukemia. Mutated IDH1/2 produces the metabolite 2-hydroxyglutarate (2HG), which interferes with epigenetic regulation of gene expression, and thus may promote tumorigenesis.

overall_design: NSG mice were transplanted with cells from a human AML patient carrying IDH1mutation. After 60-70% chimerism, mice were treated either with vehicle or with 150mg/kg/day dose of BAY1436032 perorally. Four weeks after treatment, human CD45+ cells were sorted from mouse bone marrow, from which total RNA was extracted and subjected to microarray analysis.

first: Michael

last: Heuser


title: Cord blood hematopoietic cells display altered DNA methylation patterns in preterm birth

status: Public on Apr 21 2017

city: Vancouver

first: Wendy

last: Robinson

state: BC

address: 950 W 28th Ave

department: Medical Genetics

institute: University of British Columbia

summary: Genome-wide DNA methylation was measured using the Illumina 450K array in T cells, monocytes, granulocytes and nucleated red blood cells (nRBCs) isolated from cord blood of term and extreme preterm (<31 weeks gestational age) individuals. 36 samples in total: 5 each of T cells, monocytes, granulocytes and nRBCs from term births; and 5 T cells, 4 monocytes, 4 nRBCs and 3 granulocytes from preterm births.

overall_design: Bisulphite-converted DNA from 36 cord blood cell populations sorted by a FACS protocol formally excluding erythroid lineage-specific marker CD235 in white blood cells (T cells, monocytes, granulocytes and nucleated red blood cells collected from cord blood of 5 term and 5 preterm births) were hybridized to the Illumina Infinium HumanMethylation450 BeadChip.

first: Olivia

last: de Goede

first: Pascal

last: Lavoie


title: Gene expression analysis of mouse embryonic fibroblasts reprogrammed with OSK, Esrrb and Zic3

city: Kyoto

first: Takuya

last: Yamamoto

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

department: CiRA

institute: Kyoto University

summary: We report that Zic family (Zic1/2/3) and orphan nuclear receptors family (Esrrb and Nr5a2) transcription factors (TFs) synergistically enhance the reprogramming efficiency when transduced with Oct4, Sox2 and Klf4 (OSK) into murine fibroblasts. To identify the molecular mechanisms underlying this synergy, we analyzed global gene expression at 6 days after introduction of reprogramming factors. As a result, we found that primary targets of these TFs are different when either of TFs was introduced with OSK, but a significant portion of genes including pluripotency makers such as Dppa2 was synergistically upregulated. Further analysis revealed that metabolic pathways are the important targets of these TFs for efficient reprogramming.

overall_design: Mouse embryonic fibroblasts (MEFs) introduced with 6 different combinations of TFs with triplicates

first: Masamitsu

last: Sone


title: CD8 T-cells from pSS patients and human healthy volunteers

city: Fujisawa

first: Shinya

last: Tasaki

address: 26-1, Muraoka-Higashi 2-chome

institute: Takeda Pharmaceutical Company Limited

summary: Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren’s syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.

overall_design: The peripheral CD8 T-cell subsets in four major differentiation stages, naive CD8 T-cells (TN), central memory CD8 T-cells (TCM), effector memory CD8 T-cells (TEM), terminally differentiated effector memory CD8 T-cells (TEMRA), from six pSS patients and six healthy controls were subjected to genome-wide transcriptome arrays.

first: Hiroyoshi

last: Toyoshiba

first: Tsutomu

last: Takeuchi


title: CD4 T-cells from pSS patients and human healthy volunteers

overall_design: The peripheral CD4 T-cell subsets in four major differentiation stages, naive CD4 T-cells (TN), central memory CD4 T-cells (TCM), effector memory CD4 T-cells (TEM), from six pSS patients and six healthy controls were subjected to genome-wide transcriptome arrays.


title: Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells [human]

city: Durham

first: John

last: Rawls

state: North Carolina

address: Duke University 213 Research Drive, Box 3580 DUMC CARL Building 327

institute: Duke University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We profiled genome-wide accesssible chromatin data and RNA-seq from four species (zebrafish, stickleback, mouse, and human) to identify commonly regulated genes and regulatory metods in intestinal epithelial cells (IECs).  We identify a group genes that are commonly expressed in IECs and genes that are commonly expressed along the length of the intestine in fish and mammals.  Using accessible chromatin data we identified enriched transcription factor binding site motifs In IECs and sites that are commonly accessible in IECs in all species.  Finally, we confirm the ability for these regions from multiple species to drive conserved expression in IECs using a zebrafish reporter assay.

overall_design:
Examination of expression levels and chromatin accessibility in intestinal epithelaial cells in human

Please note that RNA-Seq raw data will be made available through dbGaP (controlled access; pending submission) due to patient privacy concerns.

first: Colin

last: Lickwar

first: J

last: Camp

first: Matthew

last: Weiser

first: David

last: Kingsley

first: Terrence

last: Furey

first: Shehzad

middle: Z

last: Sheikh

middle: F


title: Expression data from hepatocytes of Tangier disease and control subjects

city: Philadelphia

first: Daniel

last: Rader

state: Pennsylvania

address: 3400 Civic Center Blvd

department: Genetics

institute: University of Pennsylvania

summary: The transcriptional effects of ABCA1 deficiency in human primary hepatocytes is not clear. We generated iPSC-derived hepatocytes from a Tangier disease patient and a matched control subject for transcriptomic profiling.

overall_design: Induced pluripotent stem cells from control and Tangier disease subjects were differentiated into hepatocytes for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain transcriptome profiles of Tangier disease hepatocytes.

first: Xin

last: Bi

first: Evanthia

middle: E

last: Pashos

first: Marina

last: Cuchel

first: Nicholas

middle: N

last: Lyssenko

first: Mayda

last: Hernandez

first: Antonino

last: Picataggi

first: James

last: McParland

first: Wenli

last: Yang

first: Ying

last: Liu

first: Ruilan

last: Yan

first: Christopher

last: Yu

first: Stephanie

middle: L

last: DerOhannessian

middle: C

last: Philips

first: Edward

last: Morrisey

first: Stephen

last: Duncan


title: Human tryptophanyl-tRNA synthetase is an IFN-gamma-inducible entry factor for Enterovirus

status: Public on Apr 16 2017

city: Hong Kong

first: Philip

last: Yeung

address: Pokfulam road

country: Hong Kong

institute: The University of Hong Kong

summary: shRNA knockdown of host gene for EV71 replication

overall_design: To identify host factor that are important for EV71 replication

first: M

first: K

last: Yuen


title: The histone demethylase KDM3A regulates the transcriptional program of the androgen receptor in prostate cancer cells

city: Oxford

first: Natasha

last: Sahgal

address: Old Road Campus

department: Ludwig Institute of Cancer Research

institute: University of Oxford

summary: To identify the genes regulated by androgen receptor (AR), we performed the profiling array analysis on the CWR22Rv1 cells and determined the differentially expressed genes upon the knockdown of AR.

overall_design: CWR22Rv1 cells were transduced with the lentiviral particles (pLKO.1 control or AR shRNA) for 48 h. Total RNA was extracted using a Total RNA Miniprep Kit (Sigma). The knockdown efficiency of AR was confirmed by qRT-PCR analysis.  RNA samples were sent to the Genomics Core Facility at University of Maryland for the quality check and processing for the Affymetrix Gene array analysis. Biological duplicate of samples were used in the  study.

last: Wilson

first: Lingling

last: Fan

first: Jianfei

last: Qi

first: Fabian

last: Filipp


title: Histone demethylase JMJD3 disrupts spectrin-dependent cytoskeleton via activation of HKDC1 to suppress Pancreatic Ductal Adenocarcinoma

first: zhangang

last: XIAO

address: the school of biomedical sciences

institute: the Chinese University of Hong Kong

summary: In this study, we established three cell lines that expressed wild type\mutant JMJD3 and the blank vector in panc-1 cells. We did the whole the mRNA expression profiling of these cell lines using affymetrix microarray kit

overall_design: Total RNA were purified from above mentioned cell lines, and the whole human mRNA expression was profiled using affymetrix microarray

first: Zhangang

first: Yangchao

last: CHEN


title: Gene expression of Th17 cells from arthritic K/BxN mice

city: Tucson

first: Hsin-Jung

last: Wu

state: AZ

address: 1656 E mabel street

department: Immunobiology

institute: University of Arizona

summary:
Th17 cells are involved in the development of many autoimmune diseases. However, recent studies have shown that in addition to the pathological Th17 effector cells located in inflammatory sites, there are also non-pathological Th17 cell types.
We examined the expression of previously reported Th17 pathogenic (red font) and non-pathogenic (blue font) genes in Th17 cells isolated from a variety tissues by microarray.

overall_design: Th17 cells marked by the expression of IL-17-eGFP were isolated from spleen, lung, and SI-LP of IL-17eGFP.K/BxN mice. We compared the fold differences of gene expression in SI-LP Th17 cells over those from spleen or lung for genes associated with pathogenic (red) and non-pathogenic (blue) Th17 cell signatures reported previously (35-37).

first: Hsin

middle: J


title: Prenatal Pesticide Exposure Interacts with a Common Polymorphism in the PON1 Gene Leading to DNA Methylation Changes

city: Antwerp (Wilrijk)

first: Ken

last: Declerck

address: Universiteitsplein 1

country: Belgium

institute: University of Antwerp

summary: Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to a cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It has been hypothesized that epigenetics might be involved. The aim of the present study was to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children.  Whole blood DNA methylation patterns in 48 children (6-11 years of age), whose mothers were occupationally unexposed or exposed to pesticides early in pregnancy, were determined by Illumina 450K methylation arrays.   A specific methylation profile was observed in prenatally pesticide exposed children carrying the PON1 192R allele. Differentially methylated genes were enriched in several neuroendocrine signaling pathways including  dopamine-DARPP32 feedback (appetite, reward pathways), corticotrophin releasing hormone signalling, nNOS, neuregulin signalling, mTOR signalling and type II diabetes mellitus signalling suggesting a possible link with the metabolic effects observed in these children. Furthermore, we were able to identify possible candidate genes which mediate the effect between pesticide exposure, leptin levels, delta BMI Z-score, and body fat percentage. In conclusion, DNA methylation may be an underlying mechanism explaining cardio-metabolic health outcomes in children that are prenatally exposed to pesticides and carrier of the PON1 192R allele.

overall_design: Bisulfite converted DNA from whole blood of 48 children were hybridised to the Illumina Infinium HumanMethylation450 BeadChip. 25 children were prenatally exposed to pesticides of which 12 were carriers of the PON1 192R allele. 23 children were unexposed to pesticides of which 12 were carriers of the PON1 192R allele.

first: Sylvie

last: Remy

first: Christine

last: Wohlfahrt-Veje

first: Katharina

middle: M

last: Main

first: Guy

last: Van Camp

first: Greet

last: Schoeters

first: Wim

last: Vanden Berghe

first: Helle

middle: R

last: Andersen


title: Epimutations as a novel cause of congenital disorders

city: New York

first: Andrew

last: Sharp

address: 1470 Madison Av

department: Genetics and Genomic Sciences

institute: Icahn School of Medicine at Mount Sinai

summary: The application of genome sequencing in patients with intellectual disability and congenital anomalies (ID/CA) typically identifies causative mutations only in a minority of cases. We hypothesized that some cases of ID/CA are caused by epigenetic aberrations that dysregulate normal genome function, and that these would be missed by conventional sequencing approaches. We performed Illumina 450k DNA methylation profiling in ~500 individuals with ID/CA, who were negative for causative mutations by microarray, exome- and/or whole genome sequencing. We screened patient methylation profiles for epimutations absent in ~1,500 controls, and validated these by bisulfite sequencing, revealing that epimutations represent large methylation changes specifically on one allele. Parental studies show that approximately half represent de novo events, a rate significantly higher than that seen in controls. We identified seven recurrent events, two of which (FMR1, MEG3) have known disease associations, validating our method for detecting pathogenic epimutations. From large-scale sequencing, population and expression studies we conclude that epimutations are: (i) Frequently associated with extreme outlier and mono-allelic gene expression, with an impact comparable to loss-of-function mutations; (ii) Generally conserved across multiple tissues within an individual, validating the use of blood DNA to study ID/CA; (iii) Can occur secondary to cis-linked regulatory mutations, providing a rationale for interpreting non-coding genetic variants; (iv) Occur sporadically with a remarkably high de novo rate, and (v) Exhibit non-Mendelian inheritance, likely being reset between generations by epigenetic reprogramming during embryogenesis. We conclude that epimutations underlie 5-10% of patients with ID/CA who are refractory to conventional mutation screening, and propose that epigenome profiling represents a promising method for the study of human disease that complements sequence-based approaches.

overall_design:
Samples were selected based on an abnormal clinical phenotype, and an absence of likely pathogenic mutations detected in previous genetic testing, including karyotype and/or array CGH, exome sequencing, or whole genome sequencing.
Illumina 450k DNA methylation profiling was performed in 489 individuals with ID/CA. In addition, we also profiled 17 mothers, 17 fathers and 97 unaffected siblings of these probands.

first: Paras

last: Garg

first: Mafalda

last: Barbosa

first: Ricky

middle: S

last: Joshi


title: JunB is essential for IL-23-dependent pathogenicity of Th17 cells.

status: Public on Apr 11 2017

city: Onna-son,Kunigami-gun

first: Hiroki

last: Ishikawa

address: 1919-1 Tancha

institute: Okinawa Institute of Science and Technology Graduate University

summary: To understand molecular mechanisms by which JunB regulates Th17 differentiation, we performed microarray analyses of JunB-deficient and control Th17 cells.

overall_design: Gene expresson profiles in WT and JunB-deficient TH0, TH17(β), TH17(23) cells.

first: Zafrul

last: Hasan

first: Shin-ichi

last: Koizumi


title: Transcriptional repression by non-canonical EED stimulation of histone deacetylase activity is required for heart maturation independently of H3K27me3 [Microarray]

status: Public on Apr 14 2017

city: Chicago

first: Yong

last: Peng

state: IL

address: 929 E 57th Street

department: Department of Chemistry

institute: University of Chicago

summary: Through H3K27me3 and H3K27ac ChIP-seq and microarray data in wile-tpye (WT) and EED-knockout (CKO) mouse cardiomyocytes, we unexpectedly uncovered a novel mechanism of PRC2-mediated gene repression. EED inactivation in the postnatal heart (EEDCKO) caused progressive, lethal dilated cardiomyopathy, with upregulation of components of the slow-twitch muscle gene program. Surprisingly, upregulation of these genes was not associated with their loss of H3K27me3, but rather with their gain of H3K27 acetylation (H3K27ac), an activating histone mark4,5. Moreover, re-expression of EED in juvenile hearts rescued heart function and normalized H3K27ac, but not H3K27me3.

overall_design: Identify the differentially expressed genes in cardiomyocytes from Wildtype (WT) and cardiac conditional EED knock-out (CKO) mice.

first: Shanshan

last: Ai

first: Fei

last: Gu

first: Qing

last: Ma

first: Yanzhu

last: Yue

first: Jinghai

last: Chen

first: Zhiqiang

last: Lin

first: Pingzhu

last: Zhou

first: Huafeng

last: Xie

first: Terence

last: Prendiville

first: Stuart

middle: H

last: Orkin

first: Da-Zhi

last: Wang

first: William

middle: T

last: Pu

first: Aibin

last: He


title: DNA methylation signature of human fetal alcohol spectrum disorder

status: Public on Apr 13 2017

first: Michael

middle: S.

last: Kobor

address: 950 West 28th Avenue

institute: Centre for Molecular Medicine and Therapeutics / University of British Columbia

summary: Prenatal alcohol exposure is the leading preventable cause of behavioural and cognitive deficits, which may affect between 2-5% of children in North America. While the underlying mechanisms of alcohol’s effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with Fetal Alcohol Spectrum Disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date. Genome-wide DNA methylation patterns of buccal epithelial cells were analyzed using the Illumina HumanMethylation450 array on a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip. After correcting for the effects of genetic background, 658 significantly differentially methylated sites between FASD cases and controls remained, with 41 displaying differences in beta greater than 5%. Furthermore, 203 differentially methylated regions containing 2 or more CpGs were also identified, overlapping with 167 different genes. The majority of differentially methylated genes were highly expressed in samples from the Allen Brain Atlas, which showed high correlations with buccal cell DNA methylation patterns. Furthermore, over-representation analysis of the up-methylated genes displayed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders. These findings suggest that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD.

overall_design: The Illumina Infinium HumanMethylation450 Beadchip was used to analyze human buccal epithelial cells from children from the NeuroDevNet cohort, assesing genome-wide DNA methylation patterns in children with fetal alcohol spectrum disorder (n=110 ) and controls (n=96) to identify a potential DNA methylation signature of FASD.

first: Elodie

last: Portales-Casamar

first: Alexandre

last: Lussier

first: Meaghan

last: Jones

first: Julia

last: MacIsaac

first: Rachel

last: Edgar

first: Sarah

last: Mah

first: Amina

last: Barhdadi

first: Sylvie

last: Provost

first: Louis-Philippe

last: Lemieux-Perreault

first: Albert

last: Chudley

first: Marie-Pierre

last: Dubé

first: Jame

last: Reynolds

first: Paul

last: Pavlidis


title: Lenaliddomide + IL21 in CLL

city: Columbus

first: Lianbo

last: Yu

state: OH

address: 1800 Cannon Drive

department: Center for Biostatistics

institute: The Ohio State University

summary: These data show distinct interactions between these two drugs on CLL cells in vitro with an ex vivo treatment

overall_design: In Vitro experiment exposing to Lenalidomide, IL-21, or combination of these in 3 patients with CLL in vitro

first: Rebekah

last: Browning

first: John

last: Byrd


title: Gene expression profiling of ligand signaling in mouse embryonic stem cells

status: Public on Apr 28 2017

city: Ottawa

first: Qiao

last: Li

address: 451 smyth road

department: Cellular and Molecular Medicine

institute: University of Ottawa

summary: Regulation of lineage specification and differentiation in embryonic stem (ES) cells can be achieved through the activation of endogenous signaling, an avenue for potential application in regenerative medicine. During vertebrate development, retinoic acid (RA) plays an important role in body axis elongation and mesoderm segmentation in that graded exposure to RA provides cells with positional identity and directs commitment to specific tissue lineages. We have previously established that bexarotene, a clinically approved rexinoid, enhances the specification and differentiation of ES cells into skeletal myocytes more effectively than RA. Profiling the transcriptomes of ES cells differentiated with bexarotene or RA permits the identification of different genetic targets and signaling pathways that may contribute to the difference of bexarotene and RA in efficiency of myogenesis. Interestingly, bexarotene induces the early expression of a myogenic progenitor marker, Meox1, while the expression of many RA targets is also enhanced by bexarotene. Several signaling molecules involved in the progression of myogenic specification and commitment are differentially regulated by bexarotene and RA, suggesting that early targets of rexinoids allow the coordinated regulation of molecular events which leads to efficient myogenic differentiation in ES cells.

overall_design: Mouse ES cells grown as embryoid bodies were treated with retinoic acid or bexarotene with untreated as control. Total RNA was isolated from undifferentiated ES cells and from untreated, RA-treated and bexarotene-treated day 7 embryoid bodies and subjected to Affymetrix GeneChip analysis. Data was normalized using GC-RMA.


title: Methylation profiling in predict recurrence hepatocellular carcinoma

city: Guangzhou

first: Yunfei

last: Yuan

state: Guangdong

address: Dongfeng Road East No.651

institute: Sun Yat-sen University Cancer Center

summary: The DNA methylation value in early-stage hepatocellular carcinoma was undetermined. The Illumina Infinium 450k Human DNA methylation Beadchip was used to identify recurrence-related abbrent CpG methylation.

overall_design: This study was performed in a total of 66 early-stage HCC samples, including 29 recurrence samples and 37 recurrence-free samples


title: Gene expression of Ewing sarcoma cell lines treated with 20S proteasome inhibitors and benzyl‐4‐piperidone compounds

status: Public on Apr 25 2017

first: Jeffrey

last: Zhao

state: NY

address: 1275 York Avenue

department: Genomics Core

institute: Memorial Sloan Kettering Cancer Center

summary: We compared the expression changes in Ewing sarcoma cell lines following treatment with 2 known 20S proteasome inhibitors versus 2 novel compounds

overall_design: Two Ewing Sarcoma cell lines (TC71 and CHP100) were treated with compounds for 6 hours.  RNA was then extracted and sent for expression analysis.  DMSO treated cells were used as controls

first: Neerav

last: Shukla

first: Marc

last: Ladanyi


title: Genome-wide methylation analysis identifies core set of hypermethylated genes in CIMP-H colorectal cancer

city: Dunedin

first: Parry

last: Guilford

address: 710 Cumberland Street

department: Biochemistry

country: New Zealand

institute: University of Otago

summary: DNA methylation was analysed using the Illumina Infinium HumanMethylation 450 Beadchip in 94 matched tissue pairs of colorectal cancer patients.

overall_design: Bisulphite converted DNA from the 192 samples were hybridised to the Illumina Infinium HumanMethylation 450 Beadchip.

first: Tyler

last: McInnes

first: Donghui

last: Zou

first: Dasari

last: Rao

first: Francesca

last: Munro

first: Vicky

last: Phillips

last: McCall

first: Michael

last: Black

first: Anthony

last: Reeve


title: Expression data from primary breast tumors

status: Public on Jun 09 2017

city: Rotterdam

first: Marcel

last: Smid

address: Dr. Molewaterplein 50

department: Medical Oncology

country: Netherlands

institute: Erasmus MC

summary:
Expression data were used to predict  the activity status of diverse pathways, which were compared to Tamoxifen response
20 M1 breast cancer patients were evaluated for the activity of transcriptomic pathways.

overall_design: Comparison of response to Tamoxifen

last: Martens

first: Wim

last: Verhaegh

first: Anja

last: van de Stolpe

first: Anieta

last: Sieuwerts


title: Expression data from young and senescent HCAECs treated with proton pump inhibitors (omeprazole and lansoprazole)

status: Public on Apr 18 2017

city: Ancona

first: Laura

last: Costarelli

address: Via Birarelli, 8

institute: INRCA - National Institute of Health & Science on Ageing

summary:
Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs, especially in older people. Although these drugs are usually considered safe, recent evidence suggests that high dose and/or long term use of PPIs may have several detrimental effects, including increased risk of adverse cardiovascular events. The impact of PPI in the aging host environment still need to be characterized. Aged tissues, including vascular tissues, accumulate senescent cells that can communicate with their environment by secreting a myriad of cytokines and growth factors. Human coronary artery endothelial cells (HCAECs) provide an excellent model system to study “in vitro” most aspects of cardiovascular function and disease related to cellular senescence. The purpose of this study is thus to investigate the in vitro effects of two well-known PPIs (Omeprazole and Lansoprazole) on endothelial gene expression in senescent e non-senescent HCAECs.
We used a cDNA microarray method to compare gene expression profiles of young and senescent HCAECs treated with omeprazole and lansoprazole.

overall_design: Young cells were cultured in medium supplemented with vehicle (CTRL) or 100μM PPIs (Omeprazole or Lansoprazole) and grown for subsequent passages until they evidenced senescence-associated phenotypes. Total mRNA was extracted and gene expression profiles were analyzed in senescent endothelial cells (P12) compared to the non-senescent cells (P6) in both untreated (CTRL) and PPI-treated groups by cDNA microarray. All experiments were performed in triplicate for each treatment group.


title: Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes and progenitors

city: Cambridge

first: Nir

last: Hacohen

state: MA

address: 415 Main Street

institute: Broad Institute

summary: Peripheral blood mononuclear cells (PBMCs) were isolated from fresh blood using Ficoll-Paque density gradient centrifugation. Single-cell suspensions were stained with different antibody cocktails designed to enrich for particular immune cell populations, which were then single cell sorted in 96-well plates.  Single cell RNA-sequencing libraries were subsequently generated for 2422 single cells using Smart-Seq2 (Picelli et al., Nature Methods, 2014). Cells were sequenced at a depth of 1-2M reads/cell.

overall_design:
The study was divided into two stages: (1) an exploratory phase, where 1140 single human blood dendritic cells and monocytes were profiled and 12 population samples; (2) a deep characterization phase, where an additional 1261 single cells and 9 population samples were profiled as part of follow-up studies.  A total of 2422 single cell and population samples were processed using Smart-Seq2 protocol (Picelli et al., Nature Methods, 2014), which allows for the generation of full-length single cell cDNA, and sequencing libraries were generated using Illumina Nextera XT DNA library preparation kit.

Please note that [1] the raw data have been submitted to dbGaP (which has controlled access mechanisms at: http://www.ncbi.nlm.nih.gov/gap; phs001294.v1.p1) due to potential privacy concerns. Please contact the submitter or dbGaP to request access to controlled-access datasets.

[2] a few samples (38) were profiled but excluded from the processed data file since they were either a bulk sample (21) or excluded due to QC (17). Therefore, there are 1,140 and 1,244 data columns in two processed data files respectively, corresponding to total 2384 samples described in the records.

first: Alexandra-Chloe

last: Villani


title: Characterization of human Fcrl4-positive B cells

city: Montpellier

first: Jerome

last: Moreaux

address: 80 Av. Augustin Fliche

department: Biological Hematology

institute: CHRU Montpellier

summary: FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, this protein is specifically expressed by memory B cells (MBCs) and is preferentially localized in subephitelial regions of lymphoid tissues. An expansion of FCRL4+ B cells has been shown in blood or other tissues in various infectious or autoimmune pathologies. In the present work, we generated and characterized in vitro FCRL4+ B cells from purified MBCs using T-dependent and/or T-independent stimulation. FCRL4+ B cells account for 17% of cells generated at day-4 of culture. Transcriptomic and phenotypic analysis of FCRL4+ cells show that they are closely related to FCRL4+ tonsillar MBCs. Interestingly, these cells highly express inhibitory receptors genes as described for exhausted FCRL4+ MBCs in the blood of HIV-viremic individuals. In agreement, in vitro generated FCRL4+ B cells show a significant underexpression of cell cycle genes with a two fold weaker number of cell division compared to FCRL4- cells. Finally, resulting from their reduced proliferation and differentiation potential, we show that FCRL4+ cells are not prone to generate plasma cells, contrary to FCRL4- cells. Given the difficulty to access to in vivo FCRL4+ cells, our in vitro model could be of major interest to study the biology of normal and pathological FCRL4+ cells.

overall_design: Gene expression profiling of human FCRL4 negative cells and FCRL4 positive cells generated in vitro from purified blood memory B cells.

first: Michel

last: Jourdan

first: Nicolas

last: Robert

first: Maïlys

last: Cren

first: Coraline

last: Thibaut

first: Christophe

last: Duperray

first: Alboukadel

last: Kassambara

first: Karin

last: Tarte

first: Bernard

last: Klein

first: Jérôme

last: Moreaux.


title: Expression data from prostate cancer cell lines

city: Hirosaki

first: Tohru

last: Yoneyama

address: 5 Zaifu-cho

department: Advanced Transplant & regenerative medicine

institute: Hirosaki University

summary:
We have investigated Perineural invasion (PNI) and epithelial-mesenchymal transition (EMT) related gene expression profiles of PC cell lines.
In this dataset, we include the expression data obtained from laminin binding O-glycan high or low androgen-independent PC cells. These data are used to obtain 70 genes that are differentially expressed in response to cell migraton signal via laminin receptors.

overall_design: 4 Total samples were analyzed. We generated the following pairwise comparisons using GeneSpring Gx Version12.6:  PC3-H vs PC3-L; LNCaP vs LNCaP-AI. Genes with an FDR≤10% and a fold-change ≥2 were selected.

first: Naoki

last: Fujita

first: Hiromichi

last: Iwamura

first: Yuki

last: Tobisawa

first: Minoru

last: Fukuda

first: Chiara

last: Ohyama


title: NR4A orphan nuclear receptor family members, NR4A2 and NR4A3, regulate neutrophil number and survival

status: Public on Apr 03 2017

city: Sheffield

first: Ian

last: Sabroe

address: Beech Hill Rd

department: Infection, Immunity and Cardiovascular Disease

institute: University of Sheffield

summary:
Defects in neutrophil number and survival are common to both hematologic disorders and chronic inflammatory diseases. At sites of inflammation, neutrophils respond to multiple signals that activate protein kinase A (PKA) signalling, which positively regulates neutrophil survival. We aimed to study the transcriptional responses to several stimuli in human neutrophils.
We used microarrays to detail the global programme of gene expression and identified distinct classes of up-regulated genes, which pointing to a key role of NR4A receptors in regulation of neutrophil lifespan and homeostasis.

overall_design: Homo sapiens neutrophil total RNA extracts were produced after 4h incubation in each specific treatment (i.e. GMCSF, hypoxia,  TLR4 agonist, PKA agonist and negative control LPS media, from the latter we also collected supernatant). These were converted to cDNA and cDNA from 5 donors was pooled prior hybridization on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array.

first: Lynne

last: Prince


title: In vitro expansion of normal and Diamond Blackfan anemia-derived peripheral blood erythroid progenitors

status: Public on Apr 04 2017

city: Little Rock

first: Jason

middle: Eli

last: Farrar

state: AR

address: 1 Children's Way, #512-10

department: Pediatrics/Hematology-Oncology

institute: University of Arkansas for Medical Sciences

summary:
The Affymetrix Human Gene 2.0 ST array was used to measure differential expression of RNA isolated from normal and Diamond Blackfan anemia (DBA) erythroid progenitors after ex vivo expansion of circulating, peripheral blood derived hematopoietic stem cells under erythroid growth conditions. The gene-level probe summaries reported in this series were computed using RMA as implemented in the Bioconductor package Oligo v1.36.1.
Diamond Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by erythroid aplasia, usually without perturbation of other hematopoietic lineages. Approximately 65% of DBA patients with autosomal dominant inheritance have heterozygous mutations or deletions in ribosomal protein (RP) genes while <1% of patients with X-linked inheritance have been identified with mutations in the transcription factor, GATA1. Erythroid cells from patients with DBA have not been well characterized and the mechanisms underlying the erythroid specific effects of either RP or GATA1 associated DBA remain unclear. We have developed an in vitro culture system to expand peripheral blood CD34+ progenitor cells from patients with DBA and differentiate them into erythroid cells. Cells from patients with RP or GATA1 mutations showed decreased proliferation and delayed erythroid differentiation compared to controls. RNA transcript analyses of erythroid cells from controls and patients with RP or GATA1 mutations showed distinctive differences, with upregulation of heme biosynthesis genes prominently in RP-mediated DBA and failure to upregulate components of the translational apparatus in GATA1-mediated DBA. Our data show that dysregulation of translational function is a common feature of DBA caused by both RP and GATA1 mutations.

overall_design: 37 samples analyzed including 10 normal CD44+/CD235+, 8 normal CD44+/235-, 5 DBA CD44+/235+, and 14 DBA CD44+/CD235- samples.

first: David

last: Bodine


title: Expression data from CIC wild type and knockout cell lines

status: Public on Apr 15 2017

city: Vancouver

first: Marco

middle: A

last: Marra

address: 675 W 10th Ave, 7th Floor

institute: Canada's Michael Smith Genome Sciences Centre

summary: Type I low-grade gliomas (LGGs), characterized by 1p/19q co-deletions and IDH1/2 mutations, show superior overall survival compared to other gliomas. Approximately 70% of cases harbour mutations in the Capicua (CIC) gene, whose product is a transcriptional repressor whose transcriptional network has yet to be extensively studied in human cells. To address this, we developed CIC knockout cell lines and used transcriptome analyses to study the consequences of CIC loss. Results were further compared to data for Type I LGGs and stomach adenocarcinomas from The Cancer Genome Atlas (TCGA). We find that CIC appears to regulate the expression of genes involved in cell-cell adhesion and nervous system development. CIC deficiency is also found to be associated with a MEK activation transcriptional signature and to act as an effector of MEK signalling. Loss of CIC may thus present a novel mechanism for the dysregulation of this and other oncogenic pathways.

overall_design: Two CIC knockout cell lines (D10 and A9) were obtained using the CRIPSR/Cas9 system and a third (D1) was obtained using the ZFN system. The parental (HEK) cell line is included, along with two CIC wild type cell lines that were submitted to the CRISPR/Cas9 process.

first: Veronique

middle: G

last: LeBlanc

first: Marlo

last: Firme

first: Jungeun

last: Song

first: Susanna

last: Chan

first: Angelica

last: Lee

first: Stephen

last: Yip

first: Suganthi

last: Chittaranjan


title: PRDM16 represses the type I Interferon response in adipocytes to promote mitochondrial and thermogenic programing

status: Public on Apr 10 2017

city: Cincinnati

first: Hee-Woong

last: Lim

state: Ohio

address: 3333 Burnet Ave. MLC 7024

department: Division of Biomedical Informatics

institute: Cincinnati Children's Hospital Medical Center

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

overall_design: Refer to individual Series


title: Epigenome analysis of PDAC cancer stem cells and non-cancer stem cells

status: Public on Apr 12 2017

city: LONDON

first: Sladana

last: Zagorac

address: Charterhouse square

institute: Barts Cancer Institute

summary: Most carcinomas, including pancreatic ductal adenocarcinoma (PDAC), are hierarchically organized with cancer stem cells (CSCs) residing at the top of the hierarchy and driving tumor progression, metastasis, and chemoresistance. Since CSCs and their more differentiated progenies (non-CSCs) share an identical genetic background, differences in epigenetics should account for the striking functional differences between these two populations of cells. Epigenetic mechanisms, such as DNA methylation, play an important role in maintaining pluripotency and regulating the differentiation of stem cells, but the role of DNA methylation in pancreatic CSCs remains unclear. Therefore, the objective of our study was to investigate the genome-wide DNA methylation profile of PDAC CSCs and to determine the importance of DNMT methyltransferases for CSC maintenance and tumorigenicity. Using high-throughput methylation analysis, we discovered that sorted CSCs have a higher level of DNA methylation, regardless of the heterogeneity or polyclonality of the CSC populations present in the tumors analyzed. Mechanistically, CSCs expressed higher DNMT1 levels than non-CSCs, and pharmacological or genetic targeting of DNMT1 in CSCs reduced their self-renewal and in vivo tumorigenic potential, highlighting DNMT1 as a potentially attractive therapeutic target.

overall_design: Bisulphite converted DNA from the 17 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2

first: Sladjana

first: Sonia

last: Alcala

first: Gustavo

last: Fernandez Bayon

first: Tony

last: Bou Kheir

first: Matthieu

last: Schoenhals

first: Anna

last: González-Neira

first: Mario

last: Fernandez Fraga

first: Alexandra

last: Aicher

first: Christopher

last: Heeschen

first: Bruno

last: Sainz Jr