title: MINC Regulates Pervasive Transcription in Yeast and Mammals

city: Los Angeles

first: Siavash

middle: K

last: Kurdistani

address: 615 Charles E Young Dr South

department: Biological Chemistry

institute: UCLA

summary:
Purpose: We want to know whether MINC(Mot1-Ino80C-NC2) suppress pervasive transcription at both euchromatin and heterochromatin
Using next generation sequencing we show that Mot1, Ino80 chromatin remodeling complex (Ino80C), and NC2 (MINC) colocalize on chromatin and cooperate to suppress pervasive transcription in S. cerevisiae and murine embryonic stem cells (mESCs).
Conclusion: Our ChIP-Seq and  mRNA-Seq data show that MINC regulates pervasive transcription in yeast and mammals

sample_organism:
Saccharomyces cerevisiae
Mus musculus

platform_organism:
Saccharomyces cerevisiae
Mus musculus

overall_design: Here we use ChIP-seq to identify the genome-wide location of Mot1 , Ino80 and Nc2 both in yeast and mouse. Also we use anchor away and knock out in yeast and knock down in mouse to investigate the function of MINC in regulation of pervasive transcription .

first: Yong

last: Xue

first: Michael

last: Carey


title: Comparative analysis of microRNAs from Calsarcin-1 knockout vs wild-type littermates

status: Public on Jul 07 2017

city: Kiel

first: Ashraf

middle: Yusuf

last: Rangrez

address: Arnold-Heller Str. 3 (Haus 6)

country: Germany

institute: University Medical Center Kiel

summary: The present study focuses on the identification of differentially regulated microRNAs in Calsarcin-1 knockout mice, which shows dilated cardiomyopathy phenotype.

overall_design: Total RNA was isolated from hearts of Calsarcin-1 knockout and wild-type mice (4x each) was used to identify the differentially regulated microRNA between the genotypes using Illumina mouse Sentrix Beadchip platform. Differentially regulated microRNAs were identified by calculating the standard deviation differences of a given probe in Cs1-ko vs WT mice comparison.

middle: Y

first: Phillip

last: Hoppe

first: Christian

last: Kuhn

first: Elisa

last: Zille

first: Johanne

last: Frank

first: Samuel

last: Sossalla

first: Norbert

last: Frey

first: Derk


title: Transcriptional changes induced in human CD4+ cells upon ectopic expression of FOXP3

city: Montreal

first: Steven

last: Shao

state: Quebec

address: 2155 Guy Street, suite 500

country: Canada

institute: McGill University

summary:
Human CD4+CD45RA+CD25- cells were lentivirally transduced with wild-type or mutated (A384T or R397W) FOXP3, or an empty vector (EV). Transduced cells were sorted 14 days post-transduction based on GFP expression, and were restimulated with soluble anti-CD3 (30 ng/mL) and irradiated PBMCs (3x) for 14 more days. Cells were then activated with 0.5 μg/ml of phytohemagglutinin (PHA) in the presence or absence of SGF003 (8 μg/mL), and total RNA was extracted for microarray analysis. Overall, this study highlights the functional impact of TIP60 in FOXP3-driven Treg biology and provides a novel target for manipulation of human Treg activity.
This study analyzes the transcriptional changes induced by the ectopic expression of FOXP3 in human effector T cells. It also assesses the impact of the enhancement of TIP60/FOXP3 interaction using the TIP60 modifier SGF003

overall_design: Total RNA obtained from FOXP3-transduced human CD4+CD25- cells

first: Khalid

middle: B

last: Dhuban

first: Ciriaco

middle: A

last: Piccirillo


title: Bulk cell RNAseq of putatative intestinal stem cell populations

status: Public on Jul 10 2017

city: Duarte

first: John

middle: S.

last: Kaddis

state: CA

address: 1500 East Duarte Road

department: Diabetes and Cancer Discovery Science

country: USA

institute: City of Hope

type: Expression profiling by high throughput sequencing

summary: A comparative bulk cell RNA-seq analysis of diverse intestinal stem cell populations was performed, for cells expressing the following markers: Lgr5-eGFPhi, Cd166+, Cd24lo, Grp78, upper side population (SP), Bmi1, mTert, Hopx, Dclk1, a lower side population (SP)

overall_design: For each ISC population of interest, three independent mice (biological replicates) were used.  From each mouse, a marker-“positive” and a marker-“negative” population were collected, as well as a "total" population.

first: Kelley

last: Yan

first: Calvin

last: Kuo

middle: S

first: Sue

last: Grimes


title: Organoid mRNA Abundance with different treatment conditions

status: Public on Jul 06 2017

city: Salt Lake City

first: Jared

last: Rutter

state: Utah

address: 15 N Medical Drive East, Rm 4100

department: Biochemistry

institute: University of Utah

summary:
Small intestine organoids were formed from wild-type and MPC1 fl/fl mice harboring the Lger-EGFP transgene.
Organoids were treated with growth factors, drugs to modulate metabolism, or induce recombination of the Mpc1 fl/fl allele and subjected to mRNA analysis.

overall_design: Each group of smaples for comparison was composed of 3 biological replicates (labeled 1-3).


title: Single Lgr5-GFP positive cells sorted from mouse

summary: Small intestine crypts dissociated to single cells and sorted from Lgr5-EGFP mice into GFP low, mid and high populations.

overall_design: mRNA abundance for targets compared between the most stem (GFP high) and differentiating (GFP low) cells.


title: Fire salamander gene expression data from field samples in Germany

city: Braunschweig

first: Daniel

last: Goedbloed

address: Mendelssohnstrasse 4

institute: TUBS

summary: Goal of the study was to compare gene expression patterns between sites and habitats

overall_design: Salamandra salamandra tail-tip tissue was collected from different field sites, used for total RNA extraction and analyzed using an Agilent microarray

first: Till

last: Czypionka


title: Expression profiling of colorectal cancer cell lines.

city: Oslo

first: Anita

last: Sveen

address: P.O.Box 4953, Nydalen

department: Department of Molecular Oncology

country: Norway

institute: Institute for Cancer Research, Oslo University Hospital

summary: We have performed genome-wide expression analyses as part of a multi-omics study on 34 colorectal cancer cell lines. The data were used for gene expression subtyping of cell lines, gene set analyses and integration with DNA and protein level data.

overall_design: There are 34 colorectal cancer cell lines included in the study. All 34 samples were analyzed on Affymetrix Human Transcriptome 2.0 Arrays.

first: Ina

last: Eilertsen

first: Kaja

middle: C

last: Berg

first: Ragnhild

last: Lothe


title: Genome-Wide Expression Profiling of B-CLL cells vs Healthy B cells cultured in high density

city: Heidelberg

first: Selcen

last: Ozturk

address: Im Neuenheimer Feld 280

department: Molecular Genetics (B060)

institute: German Cancer Research Center (DKFZ)

summary: Aberrant expression of TNFR-1 is induced in CLL cells in the lymphoid microenvironment and stimulation of TNFR-1 increases CLL cell viability.

overall_design: Expression profiles of CLL cells and CD19-sorted B cells of healthy donors before and after being cultured for 1 day in high cell density

first: Angela

last: Schulz

first: Grischa

last: Toedt

first: Stephan

last: Stilgenbauer

first: Martina

last: Seiffert

first: Peter

last: Lichter


title: An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions

city: Exeter

first: ZhengRong

last: Yang

address: Prince of Wales Road

country: United Kingdom

institute: University of Exeter

summary: Using a library of over 1 million Y. pestis CO92 random mutants and transposon-directed insertion site sequencing, we identified 530 essential genes when the bacteria were cultured at 28oC. When the library of mutants was subsequently cultured at 37oC we identified 19 genes that were essential at 37oC but not at 28oC, including genes which encode proteins that play a role in enabling functioning of the type III secretion and in DNA replication and maintenance.

overall_design: 100 bp single end reads on an Illumina HiSeq 2500 standard mode

first: Richard

middle: W

last: Titball

first: Nicola

middle: J

last: Senior

first: Kalesh

last: Sasidharan

last: Saint

first: Andrew

middle: E

last: Scott

first: Mitali

last: Sarkar-Tyson

first: Philip

middle: M

last: Ireland

first: Helen

middle: L

last: Bullifent

first: Karen

last: Moore

first: Petra

last: Oyston

first: Timothy

middle: P

last: Atkins

first: Orkun

last: Soyer

first: Zheng

middle: R


title: Expression data of bone marrow and blood monocytes from patients with rheumatoid arthritis (RA) and osteoarthritis (OA)

status: Public on Jul 05 2017

city: Berlin

first: Biljana

last: Smiljanovic

address: Charitéplatz 1

department: Department of Rheumatology and Clinical Immunology

institute: Charité - Universitätsmedizin Berlin

summary:
Rheumatoid arthritis (RA) accompanies infiltration and activation of monocytes in inflamed joints. In this study we investigated dominant alterations of RA monocytes in bone marrow (BM), blood and inflamed joints.
CD14+ cells from BM and blood of RA and osteoarthritis (OA) patients were profiled with Affymetrix HG U133 Plus 2.0 Arrays. Detailed functional analysis was performed with reference transcriptomes of BM precursors, monocyte blood subsets, monocyte activation and mobilization. Cytometric profiling determined monocyte subsets of CD14++CD16-, CD14++CD16+ and CD14+CD16+ cells in BM, blood and synovial fluid (SF) and ELISAs quantified the release of activation markers into SF and serum.
Investigation of genes differentially expressed between RA and OA monocytes by co-expression analysis with reference transcriptomes revealed gene patterns of early myeloid precursors in RA-BM and late myeloid precursors along with reduced terminal differentiation to CD14+CD16+ monocytes in RA blood. Patterns associated with TNF/LPS stimulation were weak and more pronounced in RA blood than BM. Cytometric phenotyping of cells in BM and blood disclosed differences related to monocyte subsets and confirmed the reduced frequency of terminally differentiated CD14+CD16+ monocytes in RA blood, as suggested by transcriptome data. Monocyte activation in SF was characterized by the predominance of CD14++CD16++CD163+HLA-DR+ cells and elevated concentrations of sCD14, sCD163 and S100P.
Accelerated monocytopoiesis, BM egress and migration into inflamed joints characterise increased monocyte turnover in RA. Predominant activation in the joint suggests local and primary stimulants, which may promote also adaptive immune triggering through monocytes, thus indicating their importance for diagnostic and therapeutic strategies.

overall_design: Expression profiles of human peripheral blood (PB) and bone marrow (BM) monocytes from patients with RA and OA. Monocytes from RA and OA patients with long-lasting disease that were undergoing hip-replacement surgery were collected and processed for analyses. Functional interpretation of differential expression of genes were analyzed with conventional tools like Gene Ontology, Ingenuity pathway analysis as well as with the reference transcriptomes that portrayed (1) cells of myeloid lineage in bone marrow (GSE42519), (2) monocyte subsets in blood (GSE18565), (3) monocytes activated in vitro by various inflammatory stimuli (GSE38351) and (4) leukocytes (including monocytes as well) mobilized from bone marrow into blood by G-CSF administration (GSE7400).

first: Anna

last: Radzikowska

first: Ewa

last: Kuca-Warnawin

first: Weronika

last: Kurowska

first: Joachim

last: Grün

first: Bruno

last: Stuhlmüller

first: Marc

last: Bonin

first: Ursula

last: Schulte-Wrede

first: Till

last: Sörensen

first: Chieko

last: Kyogoku

first: Anne

last: Bruns

first: Sandra

last: Hermann

first: Sarah

last: Ohrndorf

first: Karlfried

last: Aupperle

first: Marina

last: Backhaus

first: Gerd

last: Burmester

first: Andreas

last: Radbruch

last: Grützkau

first: Wlodzimierz

last: Maslinski

first: Thomas

last: Häupl


title: Expression data from primary murine pre-osteoblasts from control and Il15ra knockout mice

city: Philadelphia

first: Emanuele

last: Loro

state: PA

address: 415 Curie Boulevard

department: Physiology

institute: University of Pennsylvania

summary: Interleukin-15 receptor alpha (IL15RA) is an important component of interleukin-15 (IL15) pro-inflammatory signaling. In addition, IL15 and IL15RA are present in the circulation and are detected in a variety of tissues where they influence physiological functions such as muscle contractility and overall metabolism. In the skeletal system, IL15RA was previously shown to be important for osteoclastogenesis. Little is known, however, about its role in osteoblast function and bone mineralization. In this study, we evaluated bone structural and mechanical properties of an Il15ra whole-body knockout mouse (Il15raKO) and used in vitro and bioinformatic analyses to understand the role IL15/IL15RA signaling on osteoblast function. We show that lack of IL15RA decreased bone mineralization in vivo and in isolated primary osteogenic cultures, suggesting a cell-autonomous effect. Il15raKO osteogenic cultures also had reduced Rankl/Opg mRNA ratio, indicating defective osteoblast/osteoclast coupling. We analyzed the transcriptome of primary pre-osteoblasts from normal and Il15raKO mice and identified 1150 genes that were differentially expressed at an FDR of 5%. Of these, 844 transcripts were upregulated and 306 were downregulated in Il15raKO cells. The largest functional clusters, highlighted using DAVID analysis, were related to metabolism, immune response, bone mineralization and morphogenesis. The transcriptome analysis was validated by qPCR of some of the most significant hits. Using bioinformatic approaches, we identified candidate genes, including Cd200 and Enpp1, that could contribute to the reduced mineralization. Silencing Il15ra using shRNA in the calvarial osteoblast MC3T3-E1 cell line decreased ENPP1 activity. Taken together, these data support that IL15RA plays a cell-autonomous role in osteoblast function and bone mineralization.

overall_design: Primary Bone Marrow Stromal Cells (BMSC) were obtained from tibiae of 10 weeks old control (B6129SF2/J) and Il15raKO (B6;129X1-Il15ratm1Ama/J) mice and differentiated for 5 days by adding 10 mM β-glycerophosphate (Sigma) and 50 µg/ml ascorbic acid to the culture medium, with daily medium changes. Samples were processed and subjected to transcriptome analysis.

first: Girish

last: Ramaswamy

first: Abhishek

last: Chandra

first: Wei

last: Tseng

first: Manoj

last: Mishra

first: Eileen

last: Shore

first: Tejvir

last: Khurana


title: The functional enhancer repertoire of human embryonic stem cells [isolated plasmid DNA-seq]

city: Vienna

first: Florian

last: Halbritter

address: Zimmermannplatz 10

country: Austria

institute: St. Anna Children's Cancer Research Institute (CCRI)

summary: We combined Self-Transcribing Active Regulatory Region Sequencing (STARR-seq) with an enrichment step using chromatin immunoprecipitation in a massively parallel reporter assay. We applied this assay, termed ChIP-STARR-seq, to normal (primed) and naive human embryonic stem cells, building up a comprehensive catalogue of functional enhancers. This database record describes the DNA-seq component from isolated plasmids.

overall_design: For each ChIP-seq library in primed hESCs: DNA-seq of plasmid libraries from primed hESCs after re-isolation from transfected cells (in dulicate) = 10 datasets in total

first: Tahsin

last: Barakat

first: Andre

middle: F

last: Rendeiro

first: Man

last: Zhang

first: Christoph

last: Bock

first: Ian

last: Chambers


title: The functional enhancer repertoire of human embryonic stem cells [STARR-RNA-seq]

summary: We combined Self-Transcribing Active Regulatory Region Sequencing (STARR-seq) with an enrichment step using chromatin immunoprecipitation in a massively parallel reporter assay. We applied this assay, termed ChIP-STARR-seq, to normal (primed) and naive human embryonic stem cells, building up a comprehensive catalogue of functional enhancers. This database record describes the STARR-RNA-seq component.

overall_design: For each ChIP-seq and BAC library:  STARR-RNA-seq datasets after transfection into primed and/or naive hESCs = 42 datasets total


title: Genome-wide gene expression analysis of human foreskin fibroblast cells infected with Toxoplasma gondii over time

city: Subiaco

first: Genevieve

last: Syn

state: Western Australia

address: 100 Roberts Road

country: Australia

institute: Telethon Kids Institute

summary: Analysis of host cell gene expression patterns following infection of the parasite Toxoplasma gondii over a time course of 2 hours, 6 hours and 24 hours. Parasites were washed off after 2 hours to ensure that gene expression changes are truly reflective of an on-going infection, and not on-going parasite invasion.

overall_design: Total RNA extracted from Toxoplasma gondii-infected cells for 2, 6 and 24 hours post-infected compared to mock-infected cells at the same time points.

first: Denise

last: Anderson

first: Jenefer

last: Blackwell

first: Sarra

last: Jamieson


title: Expression data from nonrandomized trial of vitamin D in Barrett's esophagus

city: Cleveland

first: Linda

middle: Cheng

last: Cummings

state: OH

address: 11100 Euclid Avenue Mailstop 5066

department: Medicine/Division of Gastroenterology and Liver Disease

institute: Case Western Reserve University/University Hospitals Cleveland Medical Center

summary:
Vitamin D deficiency has been associated with increased esophageal cancer risk.  Vitamin D controls many downstream regulators of cellular processes including proliferation, apoptosis, and differentiation.  We evaluated the effects of vitamin D supplementation on global gene expression in patients with Barrett's esophagus.
We used microarrays to assess global gene expression in Barrett's esophagus patients who received vitamin D supplementation.

overall_design: Patients in Arm A with Barrett's esophagus with high grade dysplasia were given vitamin D3 50,000 IU weekly for 2 weeks.  Patients in Arm B with Barrett's esophagus with low grade dysplasia or no dysplasia were given vitamin D3 50,000 IU weekly for 12 weeks.  In both arms, biopsies were obtained from two sites: Barrett's esophagus segment (IM) and normal squamous mucosa (NSQ) proximal to the segment at 2 timepoints: before (T0) and after (T1) vitamin D supplementation.

first: Patrick

last: Leahy


title: The functional enhancer repertoire of human embryonic stem cells

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
We combined Self-Transcribing Active Regulatory Region Sequencing (STARR-seq) with an enrichment step using chromatin immunoprecipitation in a massively parallel reporter assay. We applied this assay, termed ChIP-STARR-seq, to normal (primed) and naive human embryonic stem cells, building up a comprehensive catalogue of functional enhancers. For further details, please refer to the sub-series.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: A functional genomics predictive network model identifies regulators of inflammatory bowel disease: Microarray Analysis of Human Blood and Intestinal Biopsy Samples from a Phase 2b, Double-blind, Placebo-controlled Study of Ustekinumab in Crohn's Disease

city: New York

first: Eric

last: Schadt

address: 1425 Madison Avenue

institute: Icahn School of Medicine at Mount Sinai

summary: Microarray Analysis of Human Whole Blood and Intestinal Biopsy Samples from a Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Crohn’s Disease

overall_design: 329 Crohn's biopsies from multiple regions in the intestine of 87 anti TNFa refractory patients and blood samples from 204 patients at Week 0 prior to drug treatment are included in this study

first: Joshua

last: Friedman

first: Lauren

last: Peters


title: Mesenchymal Stromal Cells Derived from Human Embryonic Stem Cells, Fetal Limb and Bone Marrow Share a Common Phenotype but are Transcriptionally and Biologically Different [I]

status: Public on Jul 04 2017

city: Singapore

first: Vivek

last: Tanavde

state: Singapore

address: 30 Biopolis Street, #07-01, Matrix

department: Genome and Gene Expression Data Analysis Division

country: Singapore

institute: Bioinformatics Institute, A*STAR, Singapore

summary: Mesenchymal stromal cells (MSCs) can be obtained from several sources and the significant differences in their properties, makes it crucial to investigate the differentiation potential of MSCs from different sources to determine the optimal source of MSCs. We investigated if this biological heterogeneity in MSCs from different sources results in different mechanisms for their differentiation.  In this study, we compared the gene expression patterns of phenotypically defined MSCs derived from three ontogenically different sources: Embryonic stem cells (hES-MSCs), Fetal limb (Flb-MSCs) and Bone Marrow (BM-MSCs). Differentially expressed genes between differentiated cells and undifferentiated controls were compared across the three MSC sources. We found minimal overlap in differential gene expression (5-16%) among the three sources. Flb-MSCs were similar to BM-MSCs based on differential gene expression patterns.  Pathway analysis of the differentially expressed genes using Ingenuity Pathway Analysis (IPA) revealed a large variation in the canonical pathways leading to MSC differentiation.  The similar canonical pathways among the three sources were lineage specific.   The Flb-MSCs showed maximum overlap of canonical pathways with the BM-MSCs, indicating that the Flb-MSCs is an intermediate source between the less specialised hES-MSC source and the more specialised BM-MSC source.   The source specific pathways prove that MSCs from the three ontogenically different sources use different biological pathways to obtain similar differentiation outcomes. Thus our study advocates the understanding of biological pathways to obtain optimal sources of MSCs for various clinical applications.

overall_design: The Microarray datasets comprises of hES-MSCs differentiated into the three lineages (Adipocytes (A), Chondrocytes (C) and Osteocytes (O)) at Day 7 and Day 21 as well as their undifferentiated form that was set as the control (Basal (B0) at Day 0). The numbers of technical replicates are 6-14

first: Candida

last: Vaz

first: Betty

last: Tan


title: Mesenchymal Stromal Cells Derived from Human Embryonic Stem Cells, Fetal Limb and Bone Marrow Share a Common Phenotype but are Transcriptionally and Biologically Different [II]

overall_design: The Microarray datasets comprises of Flb-MSCs differentiated into the three lineages (Adipocytes (A), Chondrocytes (C) and Osteocytes (O)) at Day 7 and Day 14 as well as their undifferentiated form that was set as the control (Basal (B0) at Day 0). The numbers of technical replicates are 4-7.


title: Differentially expressed genes after miRNA or siRNA transfection in human cancer cell lines.

city: Chiba

first: Naohiko

last: Seki

state: Chiba

address: 1-8-1, Inohana

department: Functional Genomics

country: Japan

institute: Chiba University

summary: To identify differentially expressed genes by anti cancer treatments (microRNAs or siRNAs) in human cancer, several cell lines (lung squamous cell carcinoma, oral squamous cell carcinoma, renal cell carcinoma and prostate cancer) were subjected to Agilent whole genome microarrays.

overall_design: Human cell lines ( EBC-1, SAS, A498 and PC3) were treated with miRNAs (miR-149-5p, miR-149-3p, miR-455-5p, miR-455-3p), siRNAs (si-MMP14, si-MYO1B).

first: Yasutaka

last: Yamada


title: RNA-Seqs of WT and crwn1 crwn2 double mutant

status: Public on Jul 03 2017

city: Shanghai

first: Tongtong

last: Guo

address: 300 Feng Lin Road

department: Shanghai Institute of Plant Physiology and Ecology

country: China

institute: Chinese Academy of Sciences

summary: To address the functions of CRWN proteins, we performed RNA-seq of crwn1 crwn2 double mutant and wild-type (WT).

overall_design: 10 days seedling of crwn1 crwn2 double mutant was used with WT as a control

first: Yuda

last: Fang


title: Tocotrienol Rich Fraction (TRF) Modulates Genes Expression in Oxidative Stress-Induced Caenorhabditis elegans

city: CHERAS

first: NORALISA

last: ABDUL KARIM

state: KUALA LUMPUR

address: JALAN YAACOB LATIFF

department: CELL THERAPY CENTRE

country: Malaysia

institute: UKM MEDICAL CENTRE

summary:
The study was done to determine the effect of Tocotrienol rich fraction (TRF) on the expression of RNAs in C. elegans under oxidative stress. Apart from its antioxidant properties, tocotrienols are beneficial to health due to its neuroprotective effect, anti-carcinogenic as well as cholesterol-lowering property. It has also been demonstrated that tocotrienols play a role in regulating signal transduction of cell death pathway. However, the molecular mechanism of how tocotrienols modulate the aging pathway is still scarce.
To elucidate the molecular mechanism of lifespan extension by this antioxidant, the microarray technology is further used to analyze the changes in gene expression with TRF treatment in the present study.

overall_design: The nematodes were divided into four groups and treated accordingly: (A) control; (B) H2O2 induction (H2O2); (D) TRF treatment pre- and post- H2O2 induction (TRF+H2O2+TRF); and (F) TRF treatment (TRF). Analysis of differentially expressed genes were conducted using unpaired T-test (P-value cut off at 0.05) between two experimental conditions as followed; 1) Group A vs B; 2) Group A vs F; and 3) Group B vs D .

first: Goon

last: Jo Aan

first: Noralisa

last: Abdul Karim

first: Mohd

last: Zainudin

first: Noor

first: Suzana

last: Makpol

first: Abdul

last: Abdul Jamal

first: Wan

last: Wan Ngah


title: Repression of stress-induced LINE-1 expression protects cancer cell populations from lethal drug-exposures [ATAC-Seq]

city: South San Francisco

first: Suchit

last: Jhunjhunwala

address: 1 DNA Way, MS-444A

institute: Genentech

summary: DTP heterochromatin in genomic repeat regions protects the population from drug-induced death.

overall_design: Investigation of chromatin structure by ATACseq in 1 cell type, 6 different conditions (heterogenous parental population, drug tolerant cells derived from the heterogenous parental population, 2 subpopulations (ALDH_High and ALDH_Low) obtained from the heterogeneous parental population before or after drug treatment)

first: Charles

last: Tindell

first: Gulfem

middle: D

last: Guler

first: Marie

last: Classon


title: Transcriptional Regulation by NFATc1 in CD8+ T cells [RNA-seq]

city: Würzburg

first: Stefan

last: Klein-Hessling

address: Josef-Schneider-Str. 2

department: Institute of Pathology

institute: University of Würzburg

summary: Cytotoxic T Lymphocytes (CTLs) are effector CD8+T cells that eradicate infected and malignant cells from organism. We analyze the role of the transcription factor NFATc1 in activation and cytotoxicity of murine CD8+ T lymphocytes

overall_design: Expression profiling of CD8+ T cells (derived from the spleen of C57BL/6 mice ) by deep sequencing using Illumina HiSeq

last: Klein-Heßling

first: Matthias

last: Klein


title: Expression data from primary hepatocytes from mouse

first: Michael

last: Schupp

address: Hessische Str. 3-4

department: Institute of Pharmacology

institute: Charite Universitätsmedizin Berlin

summary:
Retinol Saturase (RetSat) is an oxidoreductase expressed at high levels in the hepatocyte fraction of liver.
We investigated the effects of RetSat depletion on gene expression in primary mouse hepatocytes.

overall_design: Hepatocytes were isolated from a male C57BL/6J mouse (wild-type, 10 weeks of age). Four hours later, cells were transfected with siRNA (Dharmacon) using Lipofectamin 2000 overnight. Medium was changed the next morning and total RNA harvested 48 hours later.

first: Mitch

last: Lazar


title: Muscle directs diurnal energy homeostasis through a myokine-dependent hormone module in Drosophila

city: College Station

first: Jason

last: Karpac

state: Texas

address: Reynolds Medical Building

department: Molecular and Cellular Medicine

institute: Texas A&M University Health Sciences Center

summary: Inter-tissue communication is critical to control organismal energy homeostasis in response to temporal changes in feeding and activity or external challenges. Muscle is emerging as a key mediator of this homeostatic control through consumption of lipids, carbohydrates, and amino acids, as well as governing systemic signaling networks. However, it remains less clear how energy substrate usage tissues, such as muscle, communicate with energy substrate storage tissues in order to adapt with diurnal changes in energy supply and demand. Using Drosophila, we show here that muscle plays a crucial physiological role in promoting systemic synthesis and accumulation of lipids in fat storage tissues through Foxo. To gain more insight into these tissue-specific changes in lipid metabolism, we generated genome-wide expression profiles from dissected thoraces (enriched in indirect flight muscle), carcass (enriched in fat body), and intestines of Act88FG4>FoxoRNAi flies and control animals.

overall_design: Intact fly thorax, carcass (with all of the eggs and intact intestines removed) and intestines were dissected in PBS from Act88FGal4>UAS-FoxoRNAi or genetically matched control flies (Act88FGal4>w1118) 10 days post-eclosion. Total RNA was extracted using Trizol reagent and used as template to generate sample libraries for RNA sequencing (using the TruSeq Stranded Total RNA Library Prep Kit). Sample libraries were sequenced using the Illumina HiSeq 2500. Sequence cluster identification, quality pre-filtering, base calling and uncertainty assessment were done in real time using Illumina's HCS 2.2.58 and RTA 1.18.64 software with default parameter settings.  Between 7 and 12 million (1X50) base pair reads were generated per library and mapped to the Drosophila genome (Release 6).

first: Xiao

last: Zhao


title: Early Transcriptome Response of Lactococcus lactis to Environmental Stresses Reveals Differentially Expressed Small Regulatory RNAs

city: Groningen

first: Anne

middle: de

last: Jong

address: Nijenborgh 7

department: Molecular Genetics

country: Netherlands

institute: university of Groningen

summary: In general, most stress response systems were activated after 5 min of exposure to a variety of stressors. In addition, many tRNAs and small non-coding RNAs were also differentially expressed.

overall_design: One strain (NCDO712), 6 stress conditions and a control condition

first: Sjoerd

last: van der Meulen

last: de Jong

first: Jan

last: Kok


title: Transcriptional Regulation by NFATc1 in CD8+ T cells [ChiP-seq]

overall_design: DNA binding of NFATc1A in CD8+ T cells (derived from the spleen of C57BL/6 mice ) was analyzed by ChIP and deep sequencing using Illumina HiSeq


title: Repression of stress-induced LINE-1 expression protects cancer cell populations from lethal drug-exposures

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


title: Experimental assay of a fitness landscape on a macroevolutionary scale

status: Public on Jul 02 2017

city: Scarborough

first: Guillaume

last: Filion

state: Ontario

address: 1265 Military Trail

department: Biological Sciences

institute: UTSC

type: Genome variation profiling by high throughput sequencing

summary: Characterization of the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here, we reconstruct the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. We find that the His3 fitness landscape is dominated by synergistic epistasis, such that the cumulative effect of amino acid substitutions causes a dramatic decline in fitness. Furthermore, in 63% of sites substitutions were strongly positive in one genetic background and strongly negative in another, with 41% of sites showing reciprocal sign epistasis. This sign epistasis, present in proportionally few genotypes, was caused by simultaneous interaction of multiple sites with demonstrating a complex multidimensional nature of the His3 fitness landscape.

overall_design: PCR amplification of mutated loci inside S. cerevisiae His3 gene.

first: Victoria

middle: O

last: Pokusaeva

first: Lorena

last: Espinar Calvo

first: Dinara

last: Usmanova

first: Lucas

last: Carey

first: Fyodor

last: Kondrashov


title: The functional enhancer repertoire of human embryonic stem cells [plasmid DNA-seq]

first: Florian

last: Halbritter

summary: We combined Self-Transcribing Active Regulatory Region Sequencing (STARR-seq) with an enrichment step using chromatin immunoprecipitation in a massively parallel reporter assay. We applied this assay, termed ChIP-STARR-seq, to normal (primed) and naive human embryonic stem cells, building up a comprehensive catalogue of functional enhancers. This database record describes the DNA-seq component from plasmid libraries prior to transfection.

overall_design: For each ChIP-seq and BAC library: DNA-seq of ChIP-STARR-seq and BAC-STARR-seq plasmid library = 12 datasets

first: Tahsin

last: Barakat

first: Andre

last: Rendeiro

first: Man

last: Zhang

first: Christoph

last: Bock

first: Ian

last: Chambers


title: Global transcriptomic changes of Plasmodium falciparum asexual parasites and late gametocytes after treatment with MMV390048 or MMV642943

status: Public on Jul 01 2017

city: Pretoria

first: LynMarie

last: Birkholtz

state: Gauteng

address: c/o Lunnon Road and Heroldt Street, Hatifeld

country: South Africa

institute: University of Pretoria

summary: Plasmodium falciparum asexual parasites and late gametocytes were treated for 24 or 48 h with MMV390048 or MMV642943 in order to understand the functional consequences of inhibiting lipid kinases

overall_design: Agilent Plasmodium falciparum DNA microarrays were performed to analyze the global transcriptomic profiles of asexual parasites and late stage gametocytes following 24 or 48 h treatment with MMV390048 or MMV642943. NF54 ring-stage ( >95% synchronicity, 6 hours post merozoite invasion) asexual parasites and mixed stage IV and V gametocytes were treated with 10 X IC50 of MMV390048 or MMV642943 for 24 or 48 h. Thereafter, parasitised erythrocytes were washed and stored at -70°C. Gametocytes were isolated from erythrocytes using Nycoprep, washed and stored at -70°C. RNA was isolated using a a combination of TriZol reagent and Qiagen RNeasy kit. RNA from each of the 10 samples labelled with Cy5 was hybridised against Cy3 labelled reference pool consisting of untreated and treated mixed asexual parasites and gametocytes. Arrays were scanned using the Axon GenePix 4000B scanner. Images were quantified and data was normalized with GenePix Pro 5.1 software.

first: Mariette

last: Botha

first: Janette

last: Reader

first: Jandeli

last: Niemand

first: Riette

last: van Biljon

first: Jessica

last: Connacher

first: Roelof

last: van Wyk

first: Lyn-Marié


title: Mesenchymal Stromal Cells Derived from Human Embryonic Stem Cells, Fetal Limb and Bone Marrow Share a Common Phenotype but are Transcriptionally and Biologically Different

first: Vivek

last: Tanavde


title: Immuno-Detection by sequencing (ID-seq) enables large-scale high- dimensional phenotyping in cells

city: Nijmegen

first: Jessie

middle: van

last: Buggenum

address: Heyendaalseweg 135

institute: Radboud University

summary: We developed a sequencing-based immunodetection method which makes it possible to multiplex measurements of many different epitopes from proteins and phosphoproteins in a high throughput setting. With these DNA-tagged antibodies and dedicated sample preparation protocol, we studied the effect of hundreds of kinase inhibitors on 70 (phospho-)proteins in primary human skin cells.

sample_organism:
Homo sapiens
synthetic construct

platform_organism:
Homo sapiens
synthetic construct

overall_design: We present an immuno-detection sequencing assay for multiplexed protein detection, based on next-generation sequencing (NGS) of barcoded DNA-tags coupled to antibodies.

last: van Buggenum

first: Klaas

last: Mulder


title: Effects of temperatures on meiotic recombination in S. cerevisiae [CGH]

city: Hangzhou

first: Daoqiong

last: Zheng

state: Zhejiang

address: 866 Yuhangtang Road

department: Institute of Microbiology

institute: College of Life Sciences, Zhejiang University

type: Genome variation profiling by genome tiling array

summary: Temperature is key for biological activities, but its role in meiotic recombination processes is less known. Here, we uncovered the patterns of meiotic recombination by monitoring the double strands DNA breaks in diploid strain ZK5 cells cultured at 14ºC, 30ºC, and 37ºC.

overall_design: Using whole genome CGH microarray, we examined meiotic DNA double strands breaks at different temperatures.

first: Ke

first: Tom

last: Petes


title: Identification of a serum-induced transcriptional signature associated with metastatic cervical cancer

city: Milwaukee

first: Martin

last: Hessner

state: WI

address: 8701 Watertown Plank Road

department: Pediatrics

institute: Medical College of Wisconsin

summary: Tumor cells that escape local tissue control can convert inflammatory cells from tumor suppressors to tumor promoters. Moreover, soluble immune-modulating factors secreted from the tumor environment can be difficult to identify in patient serum due to their low abundance. We used an alternative strategy,cell-based assay that uses PBMC “reporters” to predict biologically relevant factors in patient serum. We identified disease-specific transcriptional signatures induced by patient sera with local versus metastatic disease.

overall_design: Sera from patients with local and metastatic cervical cancer were used to induce a disease-specific transcriptional signature in cultured, healthy peripheral blood mononuclear cells (PBMCs). An empirical Bayesian method, EBarrays, was used to identify differentially expressed (DE) genes with a target false discovery rate of <5%. Ingenuity Pathway Analysis (IPA) software was used to detect the top molecular and cellular functions associated with the DE genes. IPA and in silco analysis was used to pinpoint candidate upstream regulators, including cancer-related microRNAs (miRNAs).

first: Anna

last: Palatnik

first: Shuyun

last: Ye

first: Christina

last: Kendziorski

first: Marissa

last: Iden

last: Zigman

first: Janet

last: Rader


title: Three-dimensional tumor cell growth stimulates autophagic flux and recapitulates chemotherapy resistance

city: Heidelberg

first: Emily

last: Koeneke

address: Im Neuenheimer Feld 280

institute: German Cancer Research Center (DKFZ)

summary: Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g. via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions. Here, we show that both Staticic 3D growth and 3D growth within a bioreactor system modulate key hallmarks of cancer cells, including proliferation and cell death as well as macroautophagy, a recycling pathway often activated by highly proliferative tumors to cope with metabolic stress. The autophagy-related gene expression profiles of 2D- and 3D-grown cells are substantially different, with the 3D-grown cells exhibiting an expression profile closely resembling the (patho-) physiological Statice of a tumor. Underscoring the importance of this pathway, autophagy-controlling transcription factors, such as TFEB and FOXO3, are upregulated in tumors, and 3D-grown cells have increased expression compared with cells grown in 2D conditions. Three-dimensional cultures depleted of the autophagy mediators BECN1, ATG5 or ATG7 or the transcription factor FOXO3, are more sensitive to cytotoxic treatment. Accordingly, combining cytotoxic treatment with compounds affecting late autophagic flux, such as chloroquine, renders the 3D-grown cells more susceptible to therapy and increases intracellular doxorubicin concentration to the level of 2D-grown cells. Altogether, 3D cultures are a valuable tool to study drug response of tumor cells, as these models recapitulate (patho-) physiologically relevant pathways, such as autophagy.

overall_design: Total RNA was isolated from neuroblastoma cell (BE(2)-C) cultures grown under 2D, 3D-Staticic and 3D-bioreactor conditions from three independent experiments and human neuroblastoma tissue samples chosen to resemble characteristics of BE(2)-C cells (each in triplicate)

first: Ina

last: Oehme

last: Sill

first: Inga

last: Rettig

first: Andreas

last: Schober

first: Olaf

last: Witt


title: Gene expression profiles from BMCs-expressing Genes Altered in MDS

first: Kimihito

middle: Cojin

last: Kawabata

state: NY

department: Medicine

institute: Weill-Cornell Medicine

summary:
BMCs from BMT recipient mice transplanted with BMCs-expressing EZH2-mutant were analyzed using Affymetrix GeneChip Mouse430_2
BMCs were extracted from BMT recipient mice transplanted with ABCG2-expressing BMCs and analyzed using Affymetrix GeneChip Mouse430_2

overall_design: EZH2-Mt expressing BMCs were sorted into GFP-positive and negative populations before RNA extraction. Whole BMCs were used for RNA extraction from ABCG2-expressing BMCs and compared to BMCs from control BMT mice.

first: Kawabata

last: Kimihito

first: Aburatani

last: Hiroyuki


title: PD-L1 expression and immune escape in melanoma resistance to MAPK inhibitors

city: Macquarie University

first: Helen

last: Rizos

address: 2 Technology Place

institute: Macquarie University

summary: Thirty-eight tumors from 17 patients treated with BRAF inhibitor (n=12) or combination BRAF/MEK inhibitors (n=5) with known PD-L1 expression were analyzed. RNA expression arrays were performed on all pre-treatment (PRE, n=17), early during treatment (EDT, n=8) and progression (PROG, n=13) biopsies. HLA-A/HLA-DPB1 expression was assessed by immunohistochemistry (IHC). Gene set enrichment analysis (GSEA) of PRE, EDT and PROG melanomas revealed that transcriptome signatures indicative of immune cell activation were strongly positively correlated with PD-L1 staining. In contrast, MAPK signaling and canonical Wnt/-ß-catenin activity were negatively associated with PD-L1 melanoma expression. The expression of PD-L1 and immune activation signatures did not simply reflect the degree or type of immune cell infiltration, and was not sufficient for tumor response to MAPK inhibition.

overall_design: Total RNA obtained from fresh frozen melanoma tumors treated with a BRAF inhibitor (dabrafenib or vemurafenib) or combination of dabrafenib and trametinib

first: Gulietta

last: Pupo


title: Genome-wide maps of H3K9Me3, H3K27Me and Brg1 distribution between Wild Type (Wt) and Actb-/- (KNO) Mouse Embryonic Fibroblast

city: Abu Dhabi

first: Piergiorgio

last: Percipalle

state: Abu Dhabi

address: Saadiyat Campus, Abu Dhabi

department: Biology Department, Science Division

country: United Arab Emirates

institute: New York University Abu Dhabi

summary: Using Chromatin-immunoprecipitation and NGS, we profiled the genome-wdie H3K9Me3, H3K27Me and Brg1 distribution between Wild Type (Wt) and Actb-/- (KNO) Mouse Embryonic Fibroblast

overall_design: Examination of H3K9Me3, H3K27Me and Brg1 distribution between Wild Type (Wt) and Actb-/- (KNO) Mouse Embryonic Fibroblast

first: Xin

last: Xie

first: Nizar

last: Drou

first: Ayman

last: Yousif


title: Global proteomic- and transcriptomic analyses of starvation responses reveal a central role for lipoprotein metabolism in acute starvation survival in C. elegans

city: Odense M

first: Susanne

last: Mandrup

address: Campusvej 55

department: Biochemistry and Molecular Biology

country: Denmark

institute: University of Southern Denmark

summary: The molecular mechanisms underlying the physiological and cellular response to starvation are still not fully understood. We have used quantitative proteomics and RNA-seq to examine the temporal responses to starvation in the multicellular organism C. elegans, comparing the response in both wild type animals and in animals lacking the transcription factor HLH-30. Our findings show that starvation alters the abundance of hundreds of proteins and mRNAs in a temporal manner, many of which are involved in central metabolic pathways including lipoprotein metabolism. We show that hlh-30 animals die prematurely when starved, which can be prevented by knockdown of either vit-1 or vit-5, encoding two different lipoproteins. We show that the size and number of intestinal lipid droplets under starvation are altered in hlh-30 animals, that can be rescued by knockdown of vit-1, indicating that rescue of survival of hlh-30 animals under starvation conditions is closely linked to the size and number of intestinal lipid droplets.

overall_design: hh-30 mutants and wild type Caenorhabditis elegans

first: Eva

last: B. Harvald

first: Richard

last: Sprenger

first: Kathrine

middle: B

last: Dall

first: Christer

last: Ejsing

first: Ronni

last: Nielsen

first: Alejandro

last: Murillo

first: Mark

last: Larance

first: Anton

last: Gartner

first: Angus

middle: I

last: Lamond

first: Nils

last: Færgeman


title: A common intronic variant of PARP1 confers melanoma risk and mediates melanocyte growth and senescence escape via regulation of MITF

city: Rockville

first: Jiyeon

last: Choi

state: Maryland

address: 9615 Medical Center Drive, Rm 3116

institute: NCI

type:
Expression profiling by array
SNP genotyping by SNP array
Genome variation profiling by SNP array

overall_design: Refer to individual Series


title: Genotype data from early passage UACC melanoma cell lines

type:
SNP genotyping by SNP array
Genome variation profiling by SNP array

summary: eQTL is a powerful method to detect genotype-expression correlation. To be able to identify the genes whose expression levels are correlated with melanoma-associated common variants, eQTL analysis was performed in 59 early passage melanoma cell lines

overall_design:
To perform eQTL analysis, 67 early passage melanoma cell line collected through University of Arizoan Cancer Center (UACC) were grown in culture and harvested at log phase. DNA was extracted following the protocol described below and genotypes were detected using Illumina Infinium OmniEpress array
Cancer Genome Research Laboratory at NCI (A contributor to this study).

first: Kevin

last: Brown

first: Nicholas

middle: K

last: Hayward

first: Michael

last: Gartside

first: Jeffery

last: Trent

first: Stuart

last: Macgregor

first: Matthew

middle: H

last: Law

first: Tongwu

last: Zhang


title: Human embryonic stem cells in E8 and AKIT culture medium

city: Suita

first: Kouichi

last: Hasegawa

state: Osaka

address: 6F Techno Alliance Bldg. 2-8 Yamadaoka

department: StemRIM Institute of Regeneration-Inducing Medicine

institute: Osaka University

summary: Analysis of undifferentiated KhES-1 human embryonic stem cells in growth factors-dependent (E8) and -independent (AKIT) culture medium. Results provide insight into genes differentially expressed in pluripotent states maintained by AKIT and E8 culture medium.

overall_design: Gene expression analysis of KhES-1 human ES cells mainteined in AKIT culture medum (3 replicates) compare to that in control E8 medium (3 replicates).

first: Tatsuhiko

last: Ikeda

first: Shinya

last: Yasuda


title: Transcriptional Regulation by NFATc1 in CD8+ T cells

first: Stefan

last: Klein-Hessling


title: Establishment and RNA sequencing profiling of two canine mammary gland tumors cell lines

city: Pirassununga

first: Yonara

middle: de Gouveia

last: Cordeiro

state: São Paulo

address: Duque de Caxias Norte, 255

department: Veterinary Medicine

country: Brazil

institute: University of São Paulo

summary:
Purpose: the aim of this study was to characterize cell lines derived from canine mammary gland neoplasia which could be further used for basic and applied oncology research.
Methods: samples of canine mammary carcinomas were taken to primary culture and two cell lines were well-established and described in terms of tumorigenesis, cell morphology and gene expression profile through RNA-seq analysis.
Results: Both cell lines presented spindle-shape morphology and shown common malignancies features such as invasion potential and co-expression of cytoskeleton proteins. Also, we found dysregulations in gene expression patterns between the two cell cultures as well as compared to normal mammary gland tissue.
Conclusion: transcriptomic profile of these cell lines contributed to the characterization of potential prognostic and predictive biomarkers and may enable the development of possible therapeutic molecular targets.

overall_design: 2 cell lines, 3 replicates each

first: Y

middle: G

first: H

last: Fukumasu


title: Interferon-γ Represses M2 Gene Expression in Human Macrophages by Disassembling Enhancers Bound by the Transcription Factor MAF

city: New York

first: Lionel

middle: B.

last: Ivashkiv

address: 535 East 70th Street

institute: Hospital for Special Surgery


title: Expression data from GFP- or GFP Satellite alpha-transfected human retinal pigment epithelial cell line ARPE19

city: Guangzhou

first: Lili

last: Gong

state: Guangdong

address: Jinsui Road

department: Zhongshan Ophthalmic Center

institute: Sun Yat-sen University

summary: Chromatin is divided into euchromatin and heterochromatin based on differential compaction during interphase, with heterochromatin being highly condensed, existing in transcriptional inert conformation. Embedded within heterochromatin is a group of highly repetitive DNA sequences, referred to as satellite DNAs that give rise to non-coding satellite RNAs. Satellite DNA is thought to be maintained in a transcriptionally silenced state by the repressive H3K9me3 mark. However, aberrant satellite transcription can cause heterochromatin disorganization and genome instability, which have been linked to carcinogenesis. In order to study the function of heterochromatic satellite in retinal pigmental epithelia (RPE) cell, we systematically investigated transcriptome alterations in the presence of heterochromatin destabilization induced by satellite α overexpression in APRE19 cell line, a widely used human RPE cell line.

overall_design: ARPE19 cells were transfected with GFP or GFP satellite alpha plasmid. Each transfection was performed in triplicates.GFP transfection was considered as control group.


title: Genome-wide transcriptional analysis of gene expression in leukemic cells exposed to histamine dihydrochloride

status: Public on Jun 30 2017

city: Gothenburg

first: Roberta

last: Kiffin

address: Medicinaregatan 1F

department: Sahlgrenska Cancer Center

country: Sweden

institute: University of Gothenburg

summary: Analysis of the effect on histamine dihydrochloride on the gene expression of  WT and NOX2-/- PLB cells

overall_design: Total RNA extracted from WT and NOX2-/-  PLB-985 cells cultured with or without histamine-dihydrochloride and DMSO.

first: Anna

last: Martner


title: Comparing gene expression profiles of HCmel3 mouse melanomas treated (early-during-treatment, EDT d12-d20 after ACT onset) with gp100-specific adoptive pmel-1 T cell transfer (ACT) versus non-treated control HCmel3 melanomas

city: Bonn

last: Holzel

address: Sigmund-Freud Str. 25

department: Institute of Clinical Chemistry and Clinical Pharmacology

country: Germany

institute: University Hospital Bonn

summary:
This data was also integrated with gene expression profiles from late relapse tumors (GSE40213) to compare changes from early-during-treatment to late relapse versus non-treated. These re-analyzed samples are available in this series.

In EDT samples we observed typical changes consistent with an effective anti-tumor T cell response including CD8 T cell infiltration, interferon pathway activation and downregulation of proliferation associated gene sets.

overall_design: Total RNA was isolated from excised and liquid nitrogen frozen tumors and global gene expression was performed using the Illumina Mouse WG6 v2.0 platform.

first: Julia

last: Reinhardt

first: Tobias

last: Bald

first: Dorys

last: Lopez-Ramos

first: Thomas

last: Tüting

last: Hölzel


title: Differentially expressed non-coding RNAs in mouse islets during pregnancy

city: Mölndal

first: Alex-Xianghua

last: Zhou

state: - If in U.S, Select a State -

address: Pepparedsleden 1

institute: AstraZeneca R&D Gothenburg

summary:
Pregnancy is associated with increased β-cell proliferation driven by prolactin. Long noncoding RNAs (lncRNA) are the most abundant RNA species in the mammalian genome, yet, their functional importance is mainly elusive.
This study tests the hypothesis that lncRNAs regulate β-cell proliferation in response to prolactin in the context of β-cell mass compensation in pregnancy.

overall_design: Pancreatic islets were collected from pregnant C57BL/6 female mice at gestational day 14.5 or age matched non-pregnant mice as controls. Total RNA were isolated from about 600 islets pooled from 2-4 mice. cDNA were applied to Invitrogen NCode non-coding RNA arrays in triplicates.

first: Mangala

middle: M

last: Soundarapandian

first: Björn

last: Tyrberg


title: Heterogeneity of neuroblastoma cell identity revealed by transcriptional circuitries

city: Zurich

first: Valentina

last: Boeva

address: Universitatstrasse 6

department: Computer Science

country: Switzerland

institute: ETH Zurich

summary: Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define Core Regulatory Circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 family TFs; a mixed type further deconvoluted at the single cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a novel aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

overall_design:
ChIP-seq data for neuroblastoma cell lines (H3K27ac, GATA3, HAND2, PHOX2B) and hNCC cell lines (H3K27ac); RNA-seq for neuroblastoma cell lines and hNCC cell lines.
Raw sequence data for the PDX Samples have been deposited at the EBI's European Genome-phenome Archive (EGA).

first: Boeva

last: Valentina

first: Janoueix-Lerosey

last: Isabelle


title: De novo epigenetic programs inhibit PD-1 blockade-mediated T-cell rejuvenation [WGBS]

city: memphis

first: yiping

last: fan

state: tn

address: 262 Danny Thomas Place

country: USA

institute: st jude children's hospital

type: Methylation profiling by high throughput sequencing

summary: De novo DNA methylation establishes T cell exhaustion and inhibits PD-1 blockade-mediated T-cell rejuvenation.

overall_design: Mouse antigen-specific CD8 T cells were sorted from spleens of WT and Dnmt3a cKO mice during chronic LCMV infection on day 8 and day 35 post-infection for whole genome bisulfite sequencing [WGBS] analyses. Mouse antigen-specific CD8 T cells were sorted from spleens of WT mice during chronic LCMV infection after mock or PD-L1 blockade treatment for WGBS analyses. Mouse antigen-specific CD8 T cells were sorted from WT mice during acute LCMV infection on day 35 post-infection for WGBS analysis.

first: Hazem

middle: E

last: Ghoneim

first: Yiping

last: Fan

first: Robert

last: Carter

first: Geoff

last: Neale

first: Ben

last: Youngblood


title: IFN-γ Represses M2 Gene Expression in Human Macrophages by Suppressing and Disassembling MAF-binding Enhancers [ChIP-seq]

first: Lionel

last: Ivashkiv

summary: Mechanisms by which IFN-γ activates genes to promote macrophage activation are well studied, but little is known about mechanisms and functions of IFN-γ-mediated gene repression. We used an integrated transcriptomic and epigenomic approach to analyze chromatin accessibility, histone modifications, transcription factor binding, and gene expression in IFN-γ-primed human macrophages. IFN-γ suppressed basal expression of genes corresponding to an ‘M2’-like homeostatic/reparative phenotype. IFN-γ repressed genes by suppressing the function of enhancers enriched for binding by transcription factor MAF. Mechanistically, IFN-γ ‘disassembled’ a subset of enhancers by inducing coordinate suppression of binding by MAF, lineage-determining transcription factors, and chromatin accessibility. Genes associated with MAF-binding disassembled enhancers were suppressed in rheumatoid arthritis macrophages, revealing a disease-associated ‘negative IFN-γ signature’. These results identify enhancer inactivation and disassembly as a mechanism of IFN-γ-mediated gene repression, and MAF as a regulator of the macrophage enhancer landscape that is suppressed by IFN-γ to augment macrophage activation.

overall_design: ChIP-seq analysis of epigenomic changes in human macrophages stimulated with or without IFN-γ.

first: Kyuho

last: Kang

first: Keunsoo

first: Eugenia

last: Giannopoulou

first: Yu

last: Qiao


title: De novo epigenetic programs inhibit PD-1 blockade-mediated T-cell rejuvenation

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


title: Gene expression data of CSF1R antibody-treated myeloma-associated macrophages

city: Houston

first: Qiang

last: Wang

address: 6550 FANNIN STREET

institute: HOUSTON METHODIST RESEARCH INSTITUTE

summary:
Colony-stimulating factor 1 receptor (CSF1R) signaling controls MФ differentiation and function, and blocking CSF1R exerts antitumor effects in solid tumors. We examined the effects of CSF1R blockade on multiple therapy. Our results showed that CSF1R blockade inhibited the differentiation, proliferation and survival of M2 and myeloma-associated MФs (MAMs). Microarray was used for determining CS7 effect on polarization of MAMs.
We used microarrays to detail the global programme of gene expression underlying polarizaiton of myeloma-associated macrophages by CSF1R antibody treatment and identified distinct classes of polarization-related genes during this process.

overall_design: We cultured murine bone marrow (BM)-derived monocytes from 3 C57BL/KaLwRij mice in the presence of M-CSF for 7 days to generate BM-derived Macrophages (BMDMs). Then BMDMs were cocultured with murine myeloma 5TGM1-luc cells overnight and treated with 0.5 nM anti-mouse CSF1R antibody or IgG antibody control for 3 days. After that the BMDMs were wash for 4 times to removed myeloma cells and total RNA of BMDMs was extracted with RNeasy Mini kit (Qiagen).   RNA samples were sent to CASE Comprehensive Cancer Center for quality evaluation and microarray analysis with GeneChip®Mouse Gene 2.0 ST .


title: 12plex-wheat_2012-05-The wheat grain transcriptome response to high temperature

city: evry

first: Soubigou-Taconnat

last: Ludivine

address: 2 rue gaston crémieux

department: URGV

country: France

institute: INRA

summary: 12plex_wheat_2012-05 - 12plex-wheat_2012-05 - The objective is to better understand the adaptive response of the wheat plant to an elevated mean temperature. Besides the morphological and ecophysiological responses, the changes in the expression of genes are investigated. Two genotypes (SxB49 and SxB139) are subjected to two different temperature regimes during the lag-phase of the developing grains. The profiling of the accumulation of gene transcripts throughout 12 developmental stages is carried out using a custom-designed 12x135K Roche NimbleGen gene expression microarray comprising the most recent NCBI wheat contig assembly and annotation (about 45 000 unigenes). This should permit both the identification of differentially expressed genes after heat treatment and the comparison of the behaviours of two wheat genotypes (SxB139 and SxB49).  - The effect of the temperature on the expression of genes along with the effect of genotype

overall_design: 48 dye-swap - genotype comparaison,treated vs untreated comparison

first: Ludivine

last: Taconnat

first: Said

last: Mouzeyar

first: Fouad

last: Bouzidi

first: Sandrine

last: Balzergue

first: Marie-Laure

last: Martin-Magniette


title: The Graded Response of Fur Regulon to Iron Limitation in Bacillus subtilis

city: Ithaca

first: Hualiang

last: Pi

address: 125 Wing Dr.

department: Microbiology

institute: Cornell University

summary: Bacterial cells often modulate their transcriptional profiles in response to the changes in iron availability. Ferric uptake regulator (Fur), as a global iron biosensor, plays a central role in maintaining iron homeostasis in Bacillus subtilis. Here we utilized a high affinity Fe2+ efflux transporter, Listeria monocytogenes FrvA, as an inducible genetic tool to deplete intracellular iron. We then characterized the responses of the Fur, FsrA, and PerR regulons as cells transition from iron sufficiency to deficiency. Our results indicate that the Fur regulon is derepressed in three distinct waves. First, elemental iron uptake (ywbLMN), ferric citrate uptake (ymfCDEF-yhfQ), and petrobactin uptake (yclNOPQ) systems are induced to prevent iron deficiency. Second, B. subtilis synthesizes its own siderophore bacillibactin (dhbACEBF) and turns on bacillibactin uptake (feuABC-yusV) along with flavodoxin (ykuNOP) and hydroxamate siderophore uptake (fhuBCGD-yxeB) to scavenge iron from the environment. Third, as iron levels decline further, an iron sparing response (fsrA, fbpAB, and fbpC) is induced to block the translation of nonessential iron-using proteins and permit only essential iron-dependent enzymes to utilize the limited iron. ChIP experiments demonstrate that in vivo occupancy of Fur correlates with derepression of each operon, and the graded response observed here results, at least in part, from higher affinity binding of Fur to the late induced genes. These results provide insights into the distinct roles of Fur-regulated target genes as intracellular iron levels decline.

overall_design: Experiments were done in the same genetic background WT Pspac-frvA with or without IPTG induction of FrvA at different time points for three hours.

first: Pi

last: Hualiang

first: John

last: Helmann


title: Next-generation sequencing facilitates metal homeostasis and intoxication studies

city: Boston

first: Yanhui

last: Hu

state: MA

address: 77 Avenue Louis Pasteur

department: Genetics

institute: Harvard Medical School

summary:
Purpose: Analyze transcriptome changes in response to metal treatment in wildtype and sensitized genetic backgrounds.
Methods: Zinc or manganese chloride supplementation of wildtype or mutant Drosophila S2R+ cultured cells, followed by RNA extraction.
Results: Zinc chloride supplementation induces transcriptional responses in wildtype, ia-2 mutant, and ZnT63C mutant cells.
Conclusions: Wildtype S2R+ cells have a transcriptional response to mild zinc chloride supplementation and the zinc response is greater (in degree and in number of genes) in genetically sensitized cell backgrounds that perturb zinc mobilization.

overall_design: The mRNA profiles of wild type or mutant S2R+ cells treated with 1mM ZnCl2 or MnCl2 for 24 hours, or untreated control cells, were generated by deep sequencing, in replicate, using Illumina HiSeq2000.

first: Stephanie

last: Mohr

first: Kirstin

last: Rudd

first: Wei

last: Song

first: Norbert

last: Perrimon


title: Integrated analysis of the human hematopoietic non-coding RNA landscape reveals lncRNA-stem cell signature in AML

city: Frankfurt

first: Jan-Henning

last: Klusmann

address: Theodor-Stern-Kai 7

department: Pediatric Hematology and Oncology

institute: Goehte University Frankfurt

summary: Long non-coding RNAs (lncRNAs) and miRNAs have emerged as crucial regulators of gene expression and cell fate decisions. We defined the ncRNA landscape of the human blood system to map each blood cell population by its unique lncRNA expression portrait. Exploiting co-expression of functionally related genes, we allocated cell type-specific fingerprint lncRNAs to critical regulatory circuits of the hematopoietic system. The granulocyte fingerprint gene LINC00173 was predicted to control differentiation and proliferation of myeloid cells in association with PRC2, and with this lncRNA we verified the strength of our pipeline. Following incorporation of pediatric acute myeloid leukemia (AML) samples into the landscape, we revealed an lncRNA stem cell signature shared between AML samples and healthy HSCs that predicted survival in an independent cohort of 177 AML samples. Thus, we provide a comprehensive resource for exploration of the non-coding landscape across the entire human blood hierarchy.

overall_design: Examination of H3K27me3 binding profile before and after LINC00173 knockdown.

first: Henning-Jan

last: Klusman

first: Adrian

last: Schwarzer

first: Yizhou

last: Huang

first: Dominik

last: Beck


title: IFN-γ Represses M2 Gene Expression in Human Macrophages by Suppressing and Disassembling MAF-binding Enhancers [ATAC-seq]

first: Lionel

last: Ivashkiv

overall_design: ATAC-seq analysis of epigenomic changes in human macrophages stimulated with or without IFN-γ.

first: Kyuho

last: Kang

first: Sung

last: Park

first: Keunsoo


title: JQ1 prevents BRD4 recruitment to the lytic origins of replication [Akata-Zta Brd4 ChIP-seq]

first: JJ

last: Miranda

address: 3009 Broadway

institute: Barnard College, Columbia University

summary: Lytic infection by the Epstein-Barr virus (EBV) poses numerous health risks, such as infectious mononucleosis and lymphoproliferative disorder. We demonstrate that JQ1 and other BET inhibitors block two different steps in the sequential cascade of the EBV life cycle: expression of the immediate-early gene BZLF1 and lytic genome replication. This represents a novel mode of action for antiviral drugs that may increase efficacy and decrease emergence of resistance. The ChIP-seq data below show that the BET proteins bind to both EBV lytic origins of replication.

sample_organism:
Homo sapiens
human gammaherpesvirus 4

platform_organism:
Homo sapiens
human gammaherpesvirus 4

overall_design: Brd4 ChIP-seq in latent LGNFR- and reactivated LGNFR+ Akata-ZTA cells pre-treated with acyclovir and either JQ1 or vehicle

first: K

last: Keck

first: S

middle: A

last: Moquin

first: J

middle: L


title: JQ1 prevents BRD4 recruitment to the lytic origins of replication [Akata-Zta DNA-seq]

overall_design: DNA-seq of viral DNA in latent LGNFR- and reactivated LGNFR+ Akata-ZTA cells pre-treated with acyclovir and either JQ1 or vehicle


title: A new HDV mouse model showing important features of human infection and identifying MAVS as a key player in IFN-β induction

city: Pamplona

first: Gloria

last: Gonzalez-Aseguinolaza

state: Does Not Apply

address: Av PioXII 55

department: Gene Therapy

country: Spain

institute: FIMA, CIMA

summary:
Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the absence limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented.
HDV- and HBV-replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV) (AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection. Furthermore, liver pathology, genome editing, and the activation of the innate immune response were evaluated. AAV-HDV infection initiated HDV replication in mouse hepatocytes. Genome-editing was confirmed by the presence of small and large-HDV-antigens and sequencing. Viral replication was detected for 45 days, even after the AAV-HDV vector had almost disappeared. In the presence of HBV, HDV infectious particles were detected in serum. Furthermore, as observed in patients, co-infection was associated with the reduction of HBV antigen expression and the onset of liver damage that included the up/down-regulation of genes involved in the development of liver pathologies. HDV replication induced a sustained type-I IFN response, which was significantly reduced in immunodeficient mice and almost absent in MAVS-deficient mice.
The animal model described here reproduces important characteristics of human HDV infection and provides a valuable tool for characterizing the viral infection and for developing new treatments. Furthermore, MAVS was identified as a main player in HDV detection and adaptive immunity was found to be involved in the amplification of the innate immune response.

overall_design: C57BL/6 mice received an injection of AAV-HDV, or AAV-HBV , or AAV-HBV+AAV-HDV o AAV-luc 21 days animals were sacrificed, liver isolated and RNA purified. Gene expression analysis if the first three groups was compared with the AAV-luc-terated group.

first: Lester

last: Suarez

first: Rafael

last: Aldabe

first: Xabier

last: Agirre

first: Victor

last: Segura


title: Microarray profile of osteoporosis related genes of Indian post menopausal females

status: Public on Jun 29 2017

city: Pune

first: Richa

last: Ashma

state: Maharashtra

address: Assistant Professor, Center for Advanced Studies, Department of Zoology, Savitribai Phule Pune University, Pune – 411007

country: India

institute: Savitribai Phule Pune University

summary: Osteoporosis is a multifactorial disease with genetic and strong epigenetic component. In spite of enormous candidate gene association studies, the etiology and molecular mechanism of disease is not fully known. This study is undertaken to identify new markers of osteoporosis which could be vital in diagnosis and prognosis of disease, genome-wide microarray expression approach was employed on post menopausal Indian females living in same geographical area with almost similar life-style. To validate microarray gene expression pattern, qRT-PCR was performed on top 5 genes on osteoporotic (n =32) and non-osteoporotic (n=15) post menopausal females

overall_design:
Osteoclast precursor cells were sorted from circulating monocytes of osteoporotic (n=4) and non-osteoporotic (n=4) post menopausal Asian Indian females with similar life-style and age after menopause.

doi:10.4172/2572-4916.1000185

first: Mehrunnisa

last: Raje

first: Suhas

last: Mhaske

first: Mohan

last: Wani

first: Payel

last: Ghosh


title: Identification of PAX7-induced transcriptional changes and PAX7 genomic binding during skeletal myogenic differentiation of H9 embryonic stem cells

city: Minneapolis

first: Alessandro

last: Magli

state: MN

address: 2231 6th St SE

institute: University of Minnesota

summary: Skeletal myogenic commitment of human pluripotent cells can be achieved by doxycycline-inducible expression of the transcription factor PAX7. To gain further insights on PAX7 function during this process, we performed a time course whole transcriptome analysis of differentiating H9 human embryonic stem cells from doxycycline-treated and untreated cultures. In addition, we identified the genomic binding of PAX7 in one of the selected time point (referred as PAX7+ proliferating myogenic progenitors).

overall_design: Gene expression profiling was performed on biological replicates from differentiating H9 cells at the following time points: PAX7+ mesodermal cells (day 14), PAX7+ proliferating myogenic progenitors (approximately day 23), and differentiated myocytes (differentiation stage – around day 30; 7 days in the absence of PAX7 induction). Since PAX7 expression is doxycycline inducible, we also collected uninduced control samples at the same time points (termed mesodermal cells for day 14 and proliferating cells for day 23). PAX7 genomic binding was assessed in day 23 dox-treated cultures.

first: Scott

last: Swanson

first: Rita

middle: C

last: Perlingeiro


title: Verification of predicted hotspots of Alu/Alu-mediated rearrangements in the human genome

first: James

last: Lupski

state: Texas

address: One Baylor plaza

department: MHG

institute: BCM

summary: To identify the genome-wide impact of Alu/Alu-mediated rearrangement (AAMR) on variation and human health, we have developed a bioinformatic approach to characterize Alus involved in mediating CNVs and have predicted genome-wide AAMR hotspot loci. This prediction was validated by performing molecular biological experiments on 89 samples selected by correlating AAMR hotspot genes with a database of ~54,000 chromosomal microarrays.

overall_design: A custom-designed 8x60k Agilent microarray was developed using the Agilent SureDesign website. This array is targeting 15 predicted AAMR hotspot loci. We performed hybridization against sex-matched controls on 89 DNA samples derived from blood.

first: Xiaofei

last: Song

middle: R


title: Gene expression profiling of SAS cell line transfected with siRNA targeting CYLD

city: Kumamoto

first: Satoru

last: Shinriki

state: 日本 (Japan)

address: 1-1-1, Honjo, Chuo-ku

institute: Kumamoto University

summary: Oral squamous cell carcinoma (OSCC) has a very poor prognosis due to its highly invasive nature, and 5-year survival rate has not changed apparently for the past 30 years. Although cylindromatosis (CYLD) is thought as a potent tumor suppressor, its biological and clinical significances in OSCC are largely unknown. The aim of this study was to clarify roles of CYLD in OSCC progression. Our immunohistochemical analyses revealed that CYLD expression was significantly reduced at invasive lesions in OSCC tissues whereas it was conserved in normal epithelium and carcinoma in situ. Accordingly, downregulation of CYLD by siRNA led to an acquisition of mesenchymal state and increased migratory and invasive activities in OSCC cells and HaCaT keratinocytes. Interestingly, CYLD knockdown promoted TGF-beta signaling by inducing TGF-beta receptor I (ALK5) stabilization in a cell autonomous fashion. In addition, the response to exogenous TGF-beta stimulation was enhanced by CYLD downregulation. The invasive phenotype induced by CYLD knockdown were completely blocked by an ALK5 inhibitor. Furthermore, lower CYLD expression was significantly associated with deep invasion, poor overall survival, and increased Smad3 phosphorylation which is an indicator of TGF-beta signaling activation in invasive OSCC. These findings suggest that downregulation of CYLD promotes invasion with mesenchymal transition via ALK5 stabilization in OSCC cells.

overall_design: SAS cells, an oral squamous cell carcinoma cell line, transfectd with siRNA targeting CYLD (siCYLD) or control siRNA (siCtrl) followed by treatment with ALK5 inhibitor were used for RNA extraction and hybridization on Affymetrix microarrays: siCtrl-transfected (duplicates), siCYLD-transfected  (duplicates), siCtrl-transfected with ALK5 inhibitor and siCYLD-transfected with ALK5 inhibitor

first: Hirofumi

last: Jono


title: De novo epigenetic programs inhibit PD-1 blockade-mediated T-cell rejuvenation [expression]

first: yiping

last: fan

summary:
De novo DNA methylation establishes T cell exhaustion and inhibits PD-1 blockade-mediated T-cell rejuvenation.
Expression profiling of chronically stimulated WT and Dnmt3a cKO antigen-specific CD8 T cells.

overall_design: Mouse naïve (CD44low CD62L+) and antigen-specific CD8 T cells were sorted from spleens of chronic LCMV-infected WT and Dnmt3a cKO mice at ≥ 35 days post-infection for Affymetrix gene expression analysis.

first: Hazem

last: Ghoneim

first: Yiping

last: Fan

first: Robert

last: Carter

first: Geoff

last: Neale

first: Ben

last: Youngblood


title: IFN-gamma-dependent tissue immune homeostasis is co-opted in the tumor microenvironment

first: Niroshana

last: Anandasabapathy

address: 221 Longwood Ave

department: Dermatology

institute: Brigham and Women's Hospital

summary:
Homeostatic programs maintain equilibrium between immune protection, and selftolerance. Such mechanisms impact autoimmunity and tumor formation, respectively. How tissue homeostasis is maintained, and impacts tumor surveillance is unknown. Here we identify that mononuclear phagocytes share conserved programming during homeostatic differentiation, and entry into tissue. IFNγ is necessary and sufficient to induce these transcripts, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify metastatic melanoma survival. Single-cell RNA-sequencing reveals enrichment of these modules in monocytes and DCs in human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2), a highly conserved transcript in this program is induced by IFNγ, and expressed in mononuclear phagocytes infiltrating primary melanoma. SOCS2 limits DC adaptive anti-tumoral immunity and T cell priming in vivo, indicating a critical regulatory role. Our findings link homeostasis in peripheral tissue to anti-tumoral immunity and escape, revealing coopting of tissue-specific immune development in the tumor microenvironment.
To test if IFN-gamma is not only sufficient, but also necessary to condition DC, we compared the programing of migDC isolated from the skin draining LNs of IFNgR1-/-, WT, and IL27Ra-/- mice. IL-27Ra mice were included as an additional control for IFN-gamma receptor specificity.

overall_design: 3 independent groups; 3 biological replicates per group

first: Mayte

last: Suarezfarinas

first: Ruiqi

last: Huang


title: ChIP-sequencing for histone modifications in primary human hepatocytes from three individuals heterozygous for the T2D risk haplotype at the SLC16A11 locus

city: Cambridge

first: Suzanne

last: Jacobs

address: 75 Ames Street

institute: The Broad Institute

summary: ChIP-sequencing for H3K4me1, H3K4me3, and H3K27ac was performed in primary human hepatocytes from three individuals heterozygous for the T2D risk haplotype at the SLC16A11 locus. The goal was to identify allelic skews in chromatin marks at variants at the SLC16A11 locus.

overall_design: Examination of 3 different histone modifications in 1 primary human cell type obtained from 3 individuals.

first: Victor

last: Rusu

first: Eitan

last: Hoch

first: Danielle

last: Tenen

first: Melissa

last: Gymrek

first: David

last: Altshuler

first: Stuart

last: Schreiber

first: Jose

last: Florez

first: Eric

middle: S

last: Lander


title: Wound Healing Protects Against Chemotherapy-induced Alopecia in Young Rats via Up-regulating Interleukin-1β-mediated Signaling

city: Miami

first: Tongyu

last: Wikramanayake

state: FL

address: 1600 NW 10th Avenue, RMSB 2023A

department: Dermatology and Cutaneous Surgery

institute: University of Miami Miller School of Medicine

summary: Wound healing is a complex process regulated by various cell types and a plethora of mediators. While interactions between wounded skin and the hair follicles (HFs) could induce HF neogenesis or promote wound healing, it remains unknown whether the wound healing-associated signaling milieu can be manipulated to protect against alopecia, such as chemotherapy-induced alopecia (CIA). Utilizing a well-established neonatal rat model of CIA, we show here that skin wounding protects from alopecia caused by several clinically relevant chemotherapeutic regimens, and that protection is dependent on the time of wounding and hair cycle stage. Gene expression profiling unveiled a significant increase in interleukin-1 beta (IL-1β) mediated signaling by skin wounding. Subsequently, we showed that IL-1β is sufficient and indispensable for mediating the CIA-protective effect. Administration of IL-1β alone to unwounded rats exhibited local CIA protection while IL-1β neutralization abrogated CIA protection by wounding. Mechanistically, IL-1β retarded postnatal HF morphogenesis, making HFs at the wound sites or IL-1β treated areas damage-resistant while the rats developed total alopecia elsewhere. We conclude that wound healing switches the cutaneous cytokine milieu to an IL-1β-dominated state thus retarding HF growth progression and rendering the HFs resistant to chemotherapy agents. In the future, manipulation of HF progression through interfering with the IL-1β signaling milieu may provide therapeutic benefits to a variety of conditions, from prevention of CIA to inhibition of hair growth and treatment of hirsutism.  In this experiment, we used the Rat MI-Ready array comprised of over 34,000 transcript probes for gene and alternative splice products in ENSEMBL release 37 to profile gene expression changes during acute wound healing in rat skin.  16,198 Selected rat probes were above threshold in at least one group.  3,239 significant genes were found (FDR < 0.1).

overall_design: Gene expression in rat acute wound: A 3-mm incisional wound was made on the dorsum of Long-Evans rat pups 3 days after birth.  Thirty-six hours later, skin specimens were collected from the wound sites (wound) and corresponding sites of unwounded rat pups (control). Total RNA was extracted with TriZol Reagent (Life Technologies, Grand Island, NY) and purified with the RNeasy micro kit (Qiagen), and sent to Ocean Ridge Biosciences (ORB, Palm Beach Gardens, FL) for microarray analysis using the Rat MI-Ready array from Microarrays Inc.

first: Olivera

last: Stojadinovic

first: Alexandra

last: Fricke

first: Natalie

last: Yin

first: Liang

last: Liang

first: Eleanor

last: Hinde

first: Julia

last: Escandon

first: Marjana

last: Tomic-Canic

last: Ansell

first: Ralf

last: Paus

first: Joaquin

middle: J

last: Jimenez


title: Whole genome ChIP-seq of histone H3 threonine 11 phosphorylation in Saccharomyces cerevisiae

status: Public on Jun 28 2017

city: Madrid

first: Ryan

last: Kniewel

state: Madrid

address: calle Ramiro de Maeztu, 9

department: Department of Environmental Biology

institute: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CIB-CSIC)

summary: We used ChIP-seq to determine the whole-genome enrichment of histone H3 threonine 11 phosphorylation (H3 T11ph) during Saccharomyces cerevisiae meiosis. S. cerevisiae SK1 cells were synchronized for meiotic entry and 3 and 4 hour meiotic samples were obtained. As H3 T11ph is dependent on the formation of meiotic double strand breaks (DSBs), a negative control ChIP-seq sample was obtained from a strain lacking DSBs (spo11-yf). Concurrently, ChIP-seq was carried out for histone H3 as a control for comparision.

overall_design: Ten ChIP-seq samples total were taken from the following conditions: Anti-H3 T11ph and anti-H3, 3 and 4 hours synchronous meiosis, biological replicates from wild type strain (8 samples). Anti-H3 T11ph and anti-H3, 3.5 hours synchronous meiosis single sample from spo11-Y135F DSB-negative mutant (2 samples).

first: Hajime

last: Murakami

first: Scott

last: Keeney


title: Combined epigenetic and differentiation-based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression [RNA-Seq]

city: Stockholm

first: Johan

last: Holmberg

address: Nobels väg 3

department: Department of Cell- and Molecular Biology, Ludwig Institute for Cancer Research

institute: Karolinska Institute

summary: Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging from spontaneous regression to life-threatening progression. High-risk neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem-cell transplant followed by adjuvant retinoid differentiation treatment. However, the overall survival remains low; hence, there is an urgent need for alternative therapeutic approaches. One feature of high-risk neuroblastoma is the high level of DNA methylation of putative tumor suppressors. Combining the reversibility of DNA methylation with the differentiation-promoting activity of retinoic acid (RA) could provide an alternative strategy to treat high-risk neuroblastoma. Here we show that treatment with the DNA demethylating drug 5-Aza-deoxycytidine (AZA) restores high-risk neuroblastoma sensitivity to RA. Combined systemic distribution of AZA and RA impedes tumor growth and prolongs survival. Genomewide analysis of treated tumors reveals that this combined treatment rapidly induces a HIF2α-associated hypoxia-like transcriptional response followed by an increase in neuronal gene expression and a decrease in cell-cycle gene expression. A small-molecule inhibitor of HIF2α activity diminishes the tumor response to AZA+RA treatment, indicating that the increase in HIF2α levels is a key component in tumor response to AZA+RA. The link between increased HIF2α levels and inhibited tumor growth is reflected in large neuroblastoma patient datasets. Therein, high levels of HIF2α, but not HIF1α, significantly correlate with expression of neuronal differentiation genes and better prognosis but negatively correlate with key features of high-risk tumors, such as MYCN amplification. Thus, contrary to previous studies, our findings indicate an unanticipated tumor-suppressive role for HIF2α in neuroblastoma.

overall_design: 68 samples, 3-5 samples per group, 4st treatment molecules; Ctrl (DMSO), Retinoic acid (RA), 5-Aza-deoxycytidine (AZA) and RA+AZA. 2E6 cells were injected, treatment start day 8 and tumors were collected at end point (EP; 1000 m3), day 10 or day 14.

first: Isabele

last: Westerlund

first: Yao

last: Shi

first: Konstantinos

last: Toskas

last: Fell

first: Shuijie

last: Li

first: Olga

last: Surova

first: Erik

last: Södersten

first: Per

last: Kogner

first: Ulrika

last: Nyman

first: Susanne

last: Schlisio


title: BET inhibitors block the Epstein-Barr virus lytic cycle at two distinct steps

city: New York

first: JJ

last: Miranda

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

overall_design: Refer to individual Series


title: Identification of a human airway epithelial cell subpopulation with altered biophysical, molecular, and metastatic properties

city: Los Angeles

first: Linh

middle: My

last: Tran

state: California

department: Medicine - Pulmonary & Critical Care

institute: University of Los Angeles

summary: Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant pulmonary epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of unselected cells. This enhanced migratory capacity was found to be Rac1-dependent and heritable, as evidenced by maintenance of the phenotype through multiple cell divisions continuing more than 8-weeks post-selection. The morphology of this lung epithelial subpopulation was characterized by increased cell protrusion intensity. In a murine model of micrometastatic seeding and pulmonary colonization, the motility-selected premalignant cells exhibit both enhanced survival in short term assays and enhanced outgrowth of premalignant lesions in longer term assays, thus overcoming important aspects of “metastatic inefficiency.” Overall, our findings indicate that among premalignant pulmonary epithelial cells, subpopulations with heritable motility-related biophysical properties exist, and these may explain micrometastatic seeding occurring early in the pathogenesis of lung cancer. Understanding, targeting, and preventing these critical biophysical traits and their underlying molecular mechanisms may provide a new approach to prevent metastatic behavior.

overall_design: Six different HBEC cell lines were under selection of highly migratory cells. Bioconductor limma package was utilized for identifying genes differentially expressed between selected and unselected populations.

first: Paul

last: Pagano

first: Nawal

last: Bendris

first: Sean

last: O’Byrne

first: Henry

middle: T

last: Tse

first: Shivani

last: Sharma

first: Jonathan

middle: W

last: Hoech

first: Stacy

last: Park

first: Elvira

last: Liclican

first: Zhe

last: Jing

first: Rui

first: Kostyantyn

last: Krysan

first: Manash

last: Paul

first: Yari

last: Fontebasso

first: Jill

last: Larsen

first: Shaina

last: Hakimi

first: Atsuko

last: Seki

first: Michael

last: Fishbein

first: James

last: Gimzewski

first: Dino

last: Di Carlo

first: John

middle: D

last: Minna

first: Tonya

last: Walser

first: Steven

last: Dubinett


title: Next Generation Sequencing measuring Nod-like receptors mRNA expression in intestinal epithelial cells

city: New Haven

first: Shu

last: Zhu

state: CT

address: 300 Cedar Street

institute: Yale University

summary: Intestinal epithelisal cells were obtained by EDTA isolation of ileum from WT mice followed by facs sorting (EpCAM + CD45 – 7AAD – ). Raw sequencing reads were aligned to the mouse genome (mm10) with Tophat , and gene expression levels were measured by Cufflinks .

overall_design: Ileum epithelisal cells mRNA profiles were generated by deep sequencing, in duplicate, using illumina HiSeq 2000.

first: Richard

last: Flavell


title: Antiproliferative and Apoptotic Activities of Sequence-Specific Histone Acetyltransferase Inhibitors

city: Kyoto

first: Zutao

last: Yu

state: Kyoto

address: Kyoto University Kitashirakawa-Oiwakecho, Sakyo, Department of Chemistry,  Graduate School of Science

department: Science, chemistry

institute: Kyoto University

summary: In parallel to monomeric epigenetic regulators, sequence-specific epigenetic regulators represent versatile synthetic dual-target ligands that achieve regulatory control over multi-gene networks. Development of DNA-binding domain (DBD)-HDAC inhibitors and DBD-HAT activators, which result in increased histone acetylation, has become one promising research field. However, there is no report regarding the gene regulatory pattern by sequence-specific epigenetic repressor. We report here for the first time, the synthesis of DBD-HAT inhibitors and demonstrate that these conjugates could retain their dual-target activity using predicted working model of thermal stability assay and in vitro HAT activity assay. Evaluation of antiproliferative activity in cancer cells showed that 2 (with a medium linker length of 13-atom) exhibited the highest antiproliferative activity in p53 wild-type cancer cell lines (IC50 of 1.8-2.6 uM in A549 and MV4-11 cells) and not in p53 mutant cancer cell lines. A mechanistic investigation using microarray analysis and an apoptotic assay showed that the antiproliferative effect of 2 occurred via the up-regulation of p53 target genes, and the subsequent initiation of p53-dependent apoptosis. Our research on sequence-specific dual-target epigenetic repressor offers us an alternative way to modulate HAT-governed therapeutically important genes and contributes to offer a fresh insight into antitumor therapeutics.

overall_design: Genome-wide gene expression change in A549 by treatment of 646-PIP (Comp.2 and Comp.4) were examined.

first: Hiroshi

last: Sugiyama


title: Affy MA Comparison of Porcine Esophageal Submucosal Glands (ESMGs), overlying squamous tissue, and ESMG-derived spheroids

city: Durham

first: Katherine

last: Garman

state: NC

address: 905 S LaSalle

department: Medicine

institute: Duke University

summary: Microarray analysis was used to compare the transcriptome of esophageal submucosal gland (ESMG) derived spheroids in culture relative to squamous epithelium and fresh ESMGs.

overall_design: We analyzed analyzed ESMGs, squamous tissue, and ESMG-dervied in vitro spheroids using the Affymetrix PorGene-1_0-st platform.  Three biological replicates were used for each group, no technical replicates were used.

last: von Furstenberg

first: Joy

last: Li

first: Christina

last: Stolarchuk

first: Rachel

last: Feder

first: Alexa

last: Campbell

first: Leandi

last: Kruger

first: Liara

last: Gonzalez

first: Anthony

last: Blikslager

first: Diana

last: Cardona

first: Shannon

last: McCall

first: Susan

last: Henning


title: LTR-retrotransposon control by tRNA-derived small RNA

city: Cold Spring Harbor

first: Robert

last: Martienssen

state: NY

address: 1 Bungtown Rd

department: Delbruck Bldg.

institute: Cold Spring Harbor Laboratory

type: Non-coding RNA profiling by high throughput sequencing

summary: Transposon reactivation is an inherent danger in cells that lose epigenetic silencing during developmental reprogramming. In the mouse, LTR-retrotransposons, or endogenous retroviruses (ERV), account for most novel insertions and are expressed in the absence of histone H3 Lysine 9 trimethylation in preimplantation stem cells. We found abundant, 18 nt tRNA-derived small RNA (tRF) in these cells, and ubiquitously expressed 22 nt tRFs, that include the 3' terminal CCA of mature tRNAs, and target the tRNA primer binding site (PBS) essential for ERV reverse transcription. We show that the two most active ERV families, IAP and MusD/ETn, are major targets and are strongly inhibited by tRFs in retrotransposition assays. 22 nt tRFs post-transcriptionally silence coding-competent ERVs, while 18 nt tRFs specifically interfere with reverse transcription and retrotransposon mobility. The PBS offers a unique target to specifically inhibit LTR-retrotransposons and tRF-targeting is a potentially highly conserved mechanism of small RNA-mediated transposon control.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: small RNA profiling of mouse trophoblast (TS) stem cells, embryonic stem cells (ES wild-type, Dnmt1 KO, Setdb1 inducible KO), and mouse embryonic fibroblasts, transfected HeLa cells, 3-5 replicates (a/b technical rep., integer biological rep.); H3K9m3 native ChIPseq of trophoblast stem cells (TS), 4 replicates; transposon-specific RACE of uncapped, 5' RNA ends (2x2 conditions), 2 replicates per condition; sRNA libraries of transfected HeLa cells, 3 conditions, 3 replicates each

first: Andrea

last: Schorn


title: TERRA RNA antagonizes ATRX and protects telomeres

first: Hsueh-Ping

last: Chu

address: 185 Cambridge St

department: molecular biology

institute: MGH, Harvard Medical School

summary: Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both in cis to telomeres and in trans to genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: whereas TERRA activates, ATRX represses gene expression. At telomeres, TERRA competes with telomeric DNA for ATRX binding, suppresses ATRX localization, and ensures telomeric stability. Depleting TERRA increases telomerase activity and induces telomeric pathologies, including formation of telomere-induced DNA damage foci and loss or duplication of telomeric sequences. We conclude that TERRA functions as an epigenomic modulator in trans and as an essential regulator of telomeres in cis.

overall_design:
We used CHIRT-seq to identify of TERRA interacting chromatin. We used “CHIRT,” a hybrid ChIRP and CHART method optimized for TERRA capture. Several capture probe sets were designed:  (i) TERRA antisense (TERRA-AS), to capture transcripts containing UUAGGG, and (ii) TERRA sense (TERRA-S, the reverse complement), to control for strand-specificity and further rule out DNA capture artifacts due to probe hybridization to genomic DNA rather than the intended RNA target. We sequenced two critical controls: (i) an RNaseH- control in which RNaseH was omitted in the elution step, which should preclude elution of RNA-dependent interactions; and (ii) a TERRA-S control, which would not hybridize to TERRA RNA but could pull down genomic DNA.
We analyzed RNA-seq after TERRA depletion using single-stranded antisense oligonucleotides (ASO) with locked nucleic acids (LNA) chemistry.

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