title: Ectopic expression of miR-625-3p in SW620 colorectal cancer cell lines

status: Public on Jun 09 2016

city: Aarhus

first: mads

middle: heilskov

last: rasmussen

state: Please Select

address: Brendstrupgårdsvej 21

country: Denmark

institute: Aarhus University Hospital

summary: Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Here, we have used in vitro models to show that miR-625-3p functionally induces oxPt resistance in CRC cells, and have identified signalling networks affected by miR-625-3p. The p38 MAPK activator MAP2K6 was shown to be a direct target of miR-625-3p, and, accordingly, was downregulated in patients not responding to oxPt therapy. miR-625-3p resistance could be reversed in CRC cells by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, by reducing p38 MAPK signalling using either siRNA technology, chemical inhibitors to p38 or by ectopic expression of dominant negative MAP2K6 protein we induced resistance to oxPt. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signalling as one likely mechanism a possible driving force behind of oxPt resistance.   Our study shows that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p

overall_design: Ectopic induction of miR-625-3p or scramble control shRNA were induced by independent treatment with 50 ng/mL doxycycline for 48 hours.

first: Iben

last: Lyskjær

first: Mads

last: Rasmussen

first: Claus

middle: L

last: Andersen


title: Postnatal PPARa-dependent gene expression in two-days old mouse liver

status: Public on Jun 01 2016

city: Geneva

first: Gianpaolo

last: Rando

state: GE

address: 30, quai Ernest-Ansermet

department: Molecular Biology

country: Switzerland

institute: University of Geneva

summary: Inborn errors of lipid metabolism illustrate the importance of proper milk fat oxidation in newborn mammals. In the liver, a remarkable lipid catabolic competence is present at birth; however, it is unclear how this critical trait is acquired and regulated. In this work, we found that the genes required for milk lipid catabolism are already transcribed before birth in the term fetus (E19.5) and controlled by the peroxisome-proliferator activated receptor alpha (PPARα) in mouse liver. The developmental activity of PPARα strongly regulates fatty acid oxidation genes. Two days after birth (P2), during milk suckling, PPARα-null mice develop a congenital steatosis and milk protein oxidation is de-repressed to fuel an alternative energy pathway that maintains glucose homeostasis and postnatal growth. Our results demonstrate for the first time, the developmental role of PPARα in regulating the metabolic ability to use maternal milk as fuel in the early days of life.

overall_design: Expression profile difference between PPARalpha wild-type (3 males and 3 females) and knock-out (3 males and 3 females) mouse liver in suckling mice. Two days after birth, pups were killed and their liver promptly removed and frozen in liquid nitrogen.

first: Nourhène

last: Khaled

first: Walter

last: Wahli


title: Breast cancer subtype dictates DNA methylation and ALDH1A3-mediated expression of tumor suppressor RARRES1

status: Public on Jun 06 2016

city: Halifax

first: Paola

last: Marcato

state: Nova Scotia

address: PO Box 15000

department: Pathology

country: Canada

institute: Dalhousie University

type: Methylation profiling by genome tiling array

summary: Genome wide DNA methylation profiling of cancerous and normal breast cell lines, with and without decitabine. The Illumina HumanMethylation450 beadchip array was used.

overall_design: Bisulphite converted DNA from the 36 samples were hybridised to the Illumina Human Methylation 450 bead chip array

first: Krysta

middle: M

last: Coyle

first: J

middle: P

last: Murphy

first: Dejan

last: Vidovic

first: Ahmad

last: Vaghar-Kashani

first: Cheryl

middle: A

last: Dean

first: Mohammad

last: Sultan

first: Derek

last: Clements

first: Melissa

last: Wallace

first: Margaret

last: Thomas

first: Amos

last: Hundert

first: Carman

last: Giacomantonio

first: Lucy

last: Helyer

first: Shashi

last: Gujar

first: Patrick

middle: W

last: Lee

first: Ian

middle: C

last: Weaver


title: Molecular profiling of immune activation associated with regression of melanoma metastases induced by diphencyprone

status: Public on Jun 02 2016

city: New York

first: Mayte

last: Suarez-Farinas

state: NY

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

country: USA

institute: Mount SinaiSchool of Medicine

summary: The purpose of this study was to treat cutaneous melanoma metastases with topical DPCP, and then to comprehensively study the induced immune responses associated with tumor regression.

overall_design: Six melanoma patients were sensitized to 0.4% DPCP on one of their cutaneous metastases and their right upper arm, as well on their left lower arm. Two weeks later, effective sensitization was confirmed by noting induration at the application sites, and then challenge applications were applied to the subject’s cutaneous metastases.  Also at this visit, one 0.2 mL application of 0.4% DPCP was applied to one area of non-melanoma skin, and another 0.2 mL application of 0.04% DPCP was applied to a different area of non-melanoma skin. For all patients, one of the inflamed non-melanoma sites challenged with DPCP was biopsied 3 days later.  All patients continued to receive their standard oncologic follow-up and monitoring visits.

first: James

middle: G

last: Krueger

first: Nicholas

last: Gulati


title: Expression data from human iPSC-NPC

city: Taipei City

first: Hsei-Wei

last: Wang

address: No.155, Sec.2, Linong Street

country: Taiwan

institute: National Yang Ming University

summary: Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a promising source of tailor-made cell therapy for neurological diseases. However, tumorigenicity and immunogenicity are major obstacles to translational use. Here we demonstrate epidural therapeutics of human iPSC-NPC grafts after experimental ischemic stroke to avoid surgical damage and intracerebral teratomas. We found that human iPSC-NPCs co-cultured trans-membranously with rat cortical cells subjected to oxygen-glucose deprivation, compared with human mesenchymal stem cells from bone marrow and umbilical cord Wharton's jelly, superiorly enhanced neural survival and growth as well as mitigated astrogliosis. Using comparative whole-genome microarrays and cytokine arrays, we identified a neurorestorative secretome from iPSC-NPCs and neutralization of the enriched cytokines potently abolished the neuroprotective effects in the iPSC-NPC co-cultures. Moreover, we implanted the human iPSC-NPCs epidurally using fibrin glue over the peri-infarct cortex at 7 days following permanent middle cerebral artery occlusion in adult rats. The cell-treated rats showed significant improvement in their paretic forelimb usage and grip strength from 10 days post-transplantation (dpt) onwards compared to the vehicle-treated rats, accompanied by ameliorated infarct/atrophy volumes, inflammatory infiltration and astrogliosis, as well as augmented angiogenesis, oligodendrocyte precursor cells and white matter integrity. Some iPSC-NPCs migrated into the peri-infarct cortex but poorly survived by 21 dpt. This proof-of-concept study demonstrates that a less invasive yet effective epidural delivery route of human iPSC-NPCs may promote functional remodeling of the peri-infarct brain predominantly through distinct paracrine effects.

overall_design: cDNA samples from iPSC-NPC were hybridized to the human genome U133 Plus 2.0 GeneChip arrays.


title: SNAI1 overexpression effect on MCF-10A mammary epithelial cell line (mRNA)

status: Public on May 27 2016

city: Beijing

first: Zhihua

last: Liu

address: NO.17 Nanli, Panjiayuan Road, Chaoyang District

country: China

institute: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

summary:
SNAI1 is a key transcription factor in the EMT process, that is considered as the initial step of metastasis. A lot of genes invovled in SNAI1-induced EMT may play important roles in regulating the process of metastasis.
We used microarrays to establish the gene expression in SNAI1-induced EMT process.

overall_design: MCF-10A mammary epithelial cells were transfected with either SNAI1 (L) or a control vector (C) were harvested for RNA extraction and hybridization on Affymertix microarrays. 3 biological repetitions were done for microarray analysis.

first: Yun

last: Zhan


title: Epigenomics Studies in Acute Myeloid Leukemia disease progression [enhanced RRBS-seq]

status: Public on Jun 21 2016

first: Francine

middle: E.

last: Garrett-Bakelman

address: 413 East 69th street, BRB 1426

department: Medicine

institute: Weill Cornell Medicine

type: Methylation profiling by high throughput sequencing

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

overall_design:
To determine if epigenetic heterogeneity features are linked to clinical outcome and/or genetic features, change and/or affect gene transcription during disease progression in AML, we profiled 138 paired diagnosis and relapse patient samples using Enhanced Reduced Representation Bisulfite Sequening (PMC4354670) and 14 age-matched normal bone marrow controls. Analysis was performed to define genomic loci (epialleles) which undergo epigenetic shift (PMC4242486) and these were assessed for correlation with the parameters noted.

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

There are two categories processed data files:

1. tumor versus controls (AML*_epialleles.txt.tar.gz) coming from either a diagnosis (Dx) or Relapse (Rel) subject sample - each tumor sample is compared to 14 controls, hence the gzipped folders each contain 14 files, and linked to the corresponding sample (AML_*_Dx or AML_*_Rel sample);

2. relapse vs. diagnosis tumor (AML_*_Rel_AML_*_Dx_epiallele.txt.gz) for which there is only a single gzipped file, which is linked to the corresponding relapsed tumor sample record (i.e. AML_*_Rel).

Please nothe that the AML_*_Rel_epialleles.txt.tar.gz (linked to each relapsed tumor sample) contains both AML_*_Rel_epialleles.txt.tar.gz and AML_*_Rel_AML_*_Dx_epiallele.txt.gz.

middle: E

first: Sheng

last: Li

first: Christopher

last: Mason

first: Ari

last: Melnick

first: Martin

last: Carroll

first: Michael

last: Becker

first: Richard

middle: J

last: D'Andrea

first: Peter

last: Valk

first: Lars

last: Bullinger

first: David

last: Grimwade

first: Jorge

last: Gandara

first: Caroline

last: Sheridan

first: Yaseswini

last: Neelamraju


title: Identification of TRIM24-dependent gene expression programs in prostate cancer cells.

city: Boston

first: Anna

last: Groner

state: MA

address: 450 Brookline Ave

department: Medical Oncology

institute: Dana-Farber Cancer Institute

summary: In this experiment we are exploring which genes are regulated by TRIM24 in androgen-dependent and castration-resistant prostate cancer cells.

overall_design: LNCaP and LNCaP-abl were transfected with siRNA targeting either control or TRIM24 for 48h. The cells were additionally stimulated with 10nM DHT or vehicle for 24h.

first: Jonas

last: de Tribolet-Hardy

first: Patrick

last: Tschopp

first: Lei

last: Gu

first: Jean-Philippe

last: Theurillat

first: Myles

last: Brown


title: Epigenomics Studies in Acute Myeloid Leukemia disease progression

first: Francine

last: Garrett-Bakelman

type: Expression profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Identification of proliferative and mature β-cells in the islet of Langerhans

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum Muenchen

summary:
Insulin-dependent diabetes is a complex multifactorial disorder characterized by
loss or dysfunction of β-cells. Pancreatic β-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential, thus understanding the mechanisms underlying this functional heterogeneity might allow novel regenerative approaches. Here we discovered Flattop (Fltp) as a biomarker that distinguishes proliferative from mature β-cell subpopulations with distinct molecular, physiological and ultrastructural features. Genetic lineage tracing revealed that these β-cell subpopulations react differentially to environmental changes. Upon insulin resistance Fltp- β-cells undergo compensatory proliferation, whereas Fltp-lineage+ β-cells account for islet cell hypertrophy commonly associated with cytotoxic stress. The expression of the Wnt/planar cell polarity (PCP) effector gene Fltp increases when naïve β-cells cluster together to form polarized and mature three-dimensional (3D) islet mini-organs. We show that 3D architecture and Wnt/PCP ligands are sufficient to trigger mouse and human β-cell maturation. Finally, we show that Fltp is not necessary for β-cell development, proliferation, or maturation, but is required for proper glucose-stimulated insulin secretion in mature β-cells. We conclude that 3D architecture and Wnt/PCP signaling underlie functional β-cell heterogeneity and induce β-cell maturation. The identification of Fltp as a biomarker for mature β-cells establish novel molecular underpinnings of β-cells and enable targeting of subpopulations for the regeneration of functional β-cell mass in diabetic patients.

overall_design: We performed gene expression microarray analysis on 15 samples from FACS-sorted pancreatic islet cell populations. Here we provide two of these populations, flattop-positive (n=3) and flattop-negative (n=2), as part of this bigger dataset.

first: Erik

last: Bader

first: Adriana

last: Migliorini

first: Moritz

last: Gegg

first: Noah

last: Moruzzi

first: Jantje

last: Gerdes

first: Sara

middle: S

last: Roscioni

first: Mostafa

last: Bakhti

first: Elisabeth

last: Brandl

last: Irmler

first: Michaela

last: Aichler

first: Annette

last: Feuchtinger

first: Christin

last: Leitzinger

first: Hans

last: Zischka

first: Rui

last: Wang-Sattler

last: Jastroch

first: Matthias

last: Tschöp

first: Fausto

last: Machicao

first: Harald

last: Staiger

middle: U

last: Haering

first: Helena

last: Chmelova

first: Julie

last: Chouinard

first: Nikolay

last: Oskolkov

first: Olle

last: Korsgren

first: Stephan

last: Speier

first: Heiko

last: Lickert


title: Gut microbiota directs PPARγ-driven reprogramming of the liver circadian clock by nutritional challenge

status: Public on Jun 04 2016

city: Irvine

first: Yu

last: Liu

state: California

address: UCI

department: Computer Science

institute: University of California, Irvine

summary:
The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of specific transcriptional pathways. As the gut microbiota is tightly connected to host metabolism, whose coordination is governed by the circadian clock, we explored whether gut microbes influence circadian homeostasis and how they distally control the peripheral clock in the liver. Using fecal transplant procedures we reveal that, in response to high fat diet, the gut microbiota drives PPARγ-mediated activation of newly oscillatory transcriptional programs in the liver. Moreover, antibiotics treatment prevents PPARγ-driven transcription in the liver, underscoring the essential role of gut microbes in clock reprogramming and hepatic circadian homeostasis. Thus, a specific molecular signature characterizes the influence of the gut microbiome in the liver, leading to the transcriptional rewiring of hepatic metabolism.
We used microarray to quantify the tissue specific expression level of circadian genes in terms of total RNA.

overall_design: Microarray experiments were conducted to collect tissue specific, time specific samples from mice under different fecal transplant conditions, i.e. accepting fecal transplant from donors under certain diet conditions while being fed normal diet. Results compared to previous published works.

first: Mari

last: Murakami

first: Paola

last: Tognini

first: Kristin

last: Eckel-Mahan

first: Pierre

last: Baldi

first: Paolo

last: Sassone-Corsi


title: Microarray expression data from WT and IRF4 KO Sirp-a+ DCs

status: Public on May 25 2016

city: Saint Louis

first: Carlos

middle: Gustavo

last: Briseno

state: Missouri

address: 660 S Euclid

institute: Washington University School of Medicine

summary: Cross-presentation of cell-associated antigens is carried out by classical DCs (cDCs) and monocyte-derived DCs (Mo-DCs), but whether a similar or distinct program exists for this process is unknown.  In examining this issue, we discovered that only Ly-6ChiTremL4– monocytes, but not Ly-6ChiTremL4+ monocytes, can differentiate into Zbtb46+ Mo-DCs in response to GM-CSF and IL-4. However, Ly-6ChiTremL4+ monocytes were committed to Nur77-dependent development of Ly-6CloTremL4+ monocytes.  Further, differentiation of monocytes with GM-CSF required addition of IL-4 to generate Zbtb46+ Mo-DCs that cross-presented as efficiently as CD24+ cDCs, which was accompanied by increased Batf3 and Irf4 expression.  Unlike cDCs, Mo-DCs required only IRF4, and not Batf3, for cross-presentation.  Further, Irf4–/– monocytes failed to develop into Zbtb46+ Mo-DCs, and instead developed into macrophages.  Thus, cDCs and Mo-DCs use distinct transcriptional programs for cross-presentation that may drive different antigen-processing pathways. These differences may influence development of therapeutic DC vaccines based on Mo-DCs.

overall_design:
Analysis of Sirp-a+ DCs from WT and IRF4KO DCs
Splenocytes were harvested from WT and IRF4-/- C57Bl/6 mice and Sirp-a+ DCs were sorted to >95% purity on a FacsAria Fusion

first: Kenneth

last: Murphy


title: Genes differentially expressed between Bmi1-overexpressing and empty vector control neural stem/progenitor cells

city: Darmstadt

first: Ulrike

last: Nuber

address: Schnittspahnstrasse 13

institute: TU Darmstadt

summary: Neural stem/progenitor cells were isolated from the lateral ventricle wall of 4-6 week-old CD1 mice and grown as neurospheres under low density culture conditions. Test cells were transduced with bicistronic retroviral constructs for the over-expression of Bmi1 together with eGFP, and control cells were transduced with an empty vector construct expressing eGFP only. To identify genes, which are regulated by BMI1 in neural stem/progenitor cells, the gene expression profiles of neurosphere cells over-expressing Bmi1 were compared empty vector control cells using Affymetrix Gene mouse ST1.0 arrays

overall_design: 3 independent Bmi1-overexpressing neurosphere cultures (test samples) were compared to 3 independent empty vector neurosphere cultures (control samples).

first: Falk

last: Hertwig

first: Sebastian

last: Braun


title: Expression data from early and late passages of OVDM1 cell line and the original metastatic tumor

city: BETHESDA

first: Anna

last: Roschke

address: 37 Center Dr

institute: NCI-NIH

summary:
OVDM1, a new ovarian cell line derived from a serous ovarian metastatic adenocarcinoma sample, was established by immortalization with SV40 large-T antigen and hTERT and then characterized
Expression microarrays were used for molecular profiling of early and late passages of OVDM1 cell line, as well as the original metastatic tumor.

overall_design: Total RNA was extracted from early and late passages of OVDM1 and from the metastatic tumor for hybridization on Affymetrix microarrays

first: Ester

last: Rozenblum


title: Prenatal PPARa-dependent gene expression in fetal mouse liver just before birth (E19.5)

first: Gianpaolo

last: Rando

overall_design: Expression profile difference between PPARalpha wild-type (n=6) and knock-out (n=6) mouse liver at fetal day E19.5. Term fetuses were collected by cesarean section, their liver promptly dissected and frozen in liquid nitrogen.

first: Nourhène

last: Khaled

first: Walter

last: Wahli


title: The tumor suppressor Rassf1a prevents mouse liver tumorigenesis and regulates levels of the oncogenic kinase Tbk1 and of beta tubulin gene expression in the liver

status: Public on May 31 2016

city: Duarte

first: Xiwei

last: Wu

state: CA

address: 1500 E. Duarte Rd.

department: Computational and Quantitative Medicine

institute: City of Hope National Medical Center

summary: The tumor suppressor gene RASSF1A (Ras association domain family protein 1A) coding for a microtubule stabilizing protein is epigenetically silenced in most human cancers. As a binding partner of the kinases MST1 and MST2, the mammalian orthologues of the Drosophila Hippo kinase, RASSF1A is a potential regulator of the Hippo tumor suppressor pathway. RASSF1A shares these properties with the scaffold protein SAV1. The role of this pathway in human cancer has remained enigmatic because Hippo pathway components are rarely mutated. Rassf1a homozygous knockout mice developed liver tumors. However, heterozygous deletion of Sav1 or co-deletion of Rassf1a and Sav1 produced liver tumors with much higher efficiency than single deletion of Rassf1a. Analysis of RASSF1A binding partners by mass spectrometry identified the Hippo kinases MST1, MST2 and the oncogenic IkB kinase TBK1 as the most significantly enriched RASSF1A-interacting proteins. The transcriptome of Rassf1a-/- livers was more deregulated than that of Sav1+/- livers and the transcriptome of Rassf1a-/-, Sav1+/- livers was similar to that of Rassf1a-/- mice. We found that the levels of Tbk1 protein were substantially upregulated in livers lacking Rassf1a, and at the transcript level, factors regulating Tbk1 stability, including Usp2 and Dtx4, were also dysregulated. Furthermore, transcripts of several beta tubulin isoforms were increased in the Rassf1a-deficient liver genotypes presumably reflecting a role of Rassf1a as a tubulin-binding and microtubule-stabilizing protein. Our data suggest a multifactorial role of Rassf1a in suppression of liver carcinogenesis.

overall_design: Analysis of gene expression in liver of wildtype 129 mice, Rassf1a-/- mice (RA), Sav1+/- mice (SA) and Rassf1a-/- Sav1+/- mice (RA_SA)

first: Xiaoyijng

last: Zhang

first: Cai

last: Guo

first: Arthur

middle: X

last: Li

first: Limin

last: Tsark

first: Steve

last: Vonderfecht

first: Gerd

last: Pfeifer


title: Investigating the comprehensive health effects of municipal effluents on mice using transcriptomic and metabolomic approaches

city: Nanjing

first: Yan

address: Xianlin Avenue

institute: Nanjing University

summary: Transcriptomic, metabolomic and metagenomic approaches were performed to investigate the multifaceted health effects of municipal effluents (ME) on mice. After chronic exposure for 90 days, alterations in liver gene expression, serum and urine metabolic profiles. A total of 4446 differentially expressed genes (DEGs) were identified, which related to 107 KEGG pathways. Metabolomics identified 8 and 10 differential altered metabolites (DAMs) in serum and urine, respectively. Moreover, the ME exposure also induced some perturbations of the gut microbiota, which related to co-metabolism and immune responses.

overall_design: Nine mice in each group were selected and the livers of every three mice were homogenized together to obtain a total RNA sample. Three RNA samples in the treated or control group were hybridized separately onto three arrays to compare the genomic expression between the two groups.

first: Kailong

last: Huang

first: Yongfeng

last: Deng

first: Yanping

last: Zhao


title: IRAK4_hPBMC_stimulus_compound_exp3

status: Public on May 18 2016

city: Atlanta

first: Hanjoong

last: Jo

state: GA

address: 1760 Haygood Drive, Health Sciences Research Bldg E170

department: Coulter Department of Biomedical Engineering

institute: Georgia Tech and Emory Univ

summary: The goal of this experiment is to characterize the ability of IRAK4 kinase inhibitors to block TLR7 or TLR9 induced gene transcription in human PBMCs. PBMCs from two donors were pretreated with compound for 30 minutes and stimulated with gardiquimod (TLR7 ligand) or ODN 2216 (TLR9 ligand) for 5 hrs. Compound treated gene expression profiles wil be compared to untreated.

overall_design: PBMCs from 2 independent donors were isolated, pretreated with 5 μM BMS-986126 (BMT-087965) or DMSO (vehicle) for 30 minutes at 37°C and then stimulated for 5 hours with 5 μg/ml gardiquimod. Total RNA was isolated from the cells with Qiagen RNeasy Mini Kit (Cat. # 74104). Total RNA was then treated with DNase I and cleaned up with Qiagen RNeasy MiniElute Cleanup Kit (Cat. # 74204). The RNA concentrations were determined by NanoDrop and RNA quality was evaluated using Experion (Bio-Rad). All target labeling reagents were purchased from Affymetrix (West Sacramento CA). Double-stranded cDNAs were synthesized from 1ug of total RNA through reverse transcription with an oligo-dT primer containing the T7 RNA polymerase promoter and double strand conversion using the cDNA Synthesis System. Biotin-labeled cRNA was generated from the cDNA and used to probe Human Genome U219 array, comprising of 49,293 probe sets and representing more than 20,000 human genes, using the Gene Titan MC instrument (Affymetrix, West Sacramento, CA). All cDNA and cRNA target preparation steps were processed on a Caliper GeneChip Array Station from Affymetrix. Array hybridization, washing and scanning were performed according to the manufacturer’s recommendations.

first: Carman

last: Julie


title: Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T cell blast crisis

status: Public on May 30 2016

city: Pamplona

first: Victor

last: Segura

state: Navarra

address: Avda. Pío XII, 55

department: Unit of Proteomics, Genomics and Bioinformatics

country: Spain

institute: FIMA

summary: Deregulations in transcription factors lead to abnormal development, like in leukaemias, where chromosomal abnormalities either create chimeric TFs or alter the expression of the existing ones. The characterization of the precise functions of the TFs that regulate blood formation is essential to understand how these mechanisms are altered in malignancies. We have found that Engrailed-2 becomes methylated in the progression to blast crises of T-cell phenotype in chronic myelogenous leukaemia (CML) in human samples. Subsequently we found that En2 is expressed during T-cell development in the mouse and in humans. Engrailed-2 plays an essential role in central nervous system development but it has not been shown to participate in haematopoiesis. Many TFs have been found to play essential functions both in nervous system and blood development, thus making En2 a likely candidate to be involved in haematopoiesis. We have studied haematopoiesis of wild-type vs. En2 knockout mice. To increase our understanding of the possible molecular role(s) of En2 during T cell development, we have compared by microarray analysis the gene expression patterns of En2-/- versus WT sorted DP thymocytes and also CD8+ splenocytes (the two populations in which we had detected En2 expression).

overall_design: Comparisson of global gene xpression profiling between A) CD4+CD8+ lymphocytes isolated from thymus of WT vs. ENK KO mice; and B) CD8+ lymphocytes isolated from spleens of WT vs. ENK KO mice

first: Fernando

last: Abollo-Jimenez

first: Cesar

last: Cobaleda

first: Jose

last: Martinez-Climent


title: Gene expression data from HEY cells

status: Public on May 17 2016

first: Swetha

last: Srinivasan

address: 315 ferst drive

department: Biology

institute: Georgia Institute of technology

summary:
The innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. To understand the effect of exosomal cargo released from locally stimulated cells on distal cell expression, we collected exosomes from local ovarian adenocarcinoma (HEY) cells that were either unstimulated (control-exosomes), stimulated with pIC (pIC-exosomes), or lipopolysaccharide (LPS-exosomes) for 48 hours. The three groups of exosomes were added to naïve (distal) cells and the gene expression profiles were compared between local TLR stimulation (for 6 hours) and distal stimulation mediated by exosomes at the 48-hour time point
The goal of the study was to delineate the differential effector function of TLR-exosomes based on the innate immune activation state (control-, LPS-, pIC-stimulation) of the cell of origin in vitro. We used microarrays to understand the changes in gene expression in 2 samples of local hey cells either unstimulated(control) or stimulated with poly(I:C) or LPS each. We also profiled 2 samples of distal naïve cells that were exposed to either control, LPS or poly(I:C) exosomes from local cells. Here we show that exosomes from TLR stimulated cells (TLR-exosomes) can largely recapitulate TLR activation in distal cells in vitro. We can abrogate the action-at-a-distance signaling of exosomes by UV irradiation, demonstrating that RNA is crucial for their effector function. This work definitively establishes the differential effector function for TLR-exosomes in communicating the activation state of the cell of origin.

overall_design: HEY cells were either unstimulated (Local control) or stimulated with LPS  or poly (I:C) for 6 hours and the RNA from these cells was profiled using a microarray. Exosomes were collected from local cells that were unstimulated or stimulated for 48 hours and added to distal (naive) HEY cells that were exposed to control exosomes, LPS exosomes or  pIC exosomes and then the RNA was collected for analysis by microarray. mRNA expression was captured on Affymetrix U133 Plus 2 chips. mRNA microarray data were analyzed using the Expression Console software (Affymetrix) and Bioconductor tools written in the R statistical programming language. Pre-processing of raw signal intensities and normalization was performed using GCRMA (R). Linear modelling of the transformed data was determined by using Limma in R with the Benjamini and Hochberg correction. Differentially expressed probesets were identified using a threshold 5% FDR correction and a fold change ≥ 1.4 was applied

first: Fredrik

last: Vannberg


title: Time-series Gene Expression Profiling of Childhood Acute Lymphoblastic Leukemia

status: Public on May 26 2016

city: Singapore

first: Allen Eng Juh

last: Yeoh

address: 14 Medical Drive, MD6 #09-02

department: Paediatrics

country: Singapore

institute: National University of Singapore

summary:
ALL is the most common form of childhood cancer with >80% cured with contemporary treatment protocols. Accurate risk stratification in childhood ALL is essential to avoid under- and over-treatment. Currently, we use presenting clinical, biological features, and minimal residual disease (MRD) quantitation to risk stratify patients. Although whole genome gene expression profiling (GEP) can accurately classify patients with ALL into various WHO 2008 defined subgroups, its value in predicting relapse remained to be defined. We hypothesized that global time-series GEPs of bone marrow (BM) samples at diagnosis and specific points during initial remission-induction therapy can measure the success of cytoreduction and be used for relapse prediction.
We generated time-series GEPs from 210 children with de novo ALL at diagnosis, and Day 8 of remission-induction therapy. We computed the time-series changes from diagnosis to follow-up time point of remission-induction, termed Effective Response Metric (ERM), that measures both the magnitude and direction of time-series change in multi-dimensional gene space towards the normal centroid, and we compared its ability to predict relapse against contemporary risk assignment methods including NCI criteria, cytogenetics and MRD.

overall_design: Gene expression profiling of 420 bone marrow or peripheral blood samples from 210 patiants at Day 0 and Day 8 was carried out using Affymetrix U133A or Affymetrix U133 Plus 2.0 arrays.

first: Allen Eng-Juh

first: Zhenhua

first: Difeng

last: Dong

first: Yi

last: Lu

last: Jiang

first: Jan

last: Trka

first: Ah Moy

last: Tan

first: Hai Peng

last: Lin

first: Thuan Chong

last: Quah

first: Hany

last: Ariffin

first: Limsoon

last: Wong


title: Expression data of Mesenchymal Stroma Cells (MSC)-adherent and non-adherent, human cord blood-derived, hematopoietic CD34 cells

status: Public on May 16 2016

city: Lund

first: Justyna

middle: Marta

last: Rak

state: Sverige

address: Solvegatan 19

department: Laboratory Medicine

country: Sweden

institute: Lund University

summary:
MSC-adherent hematopoietic stem and progenotir cells (HSPC) express adhesion-associated genes at higher levels than non-adherent cells while cell-cycle and differentiation-associated genes are not significantly changed between the two cell populations.
We used microarray to confirm identity of MSC-adherent and non-adherent cord blood-derived HSPCs and to exclude that cell cycle and differentiation affect adhesive capacity.

overall_design: CD34 positive cells were isolated from human cord blood (not older than 24h), expanded for 3 days and assayed for the adhesion to MSC. The adherent and non-adherent live CD34+ cells were sorted and total RNA was extracted.

first: Jonas

last: Larsson


title: SNAI1 overexpression effect on MCF-10A mammary epithelial cell line

first: Zhihua

last: Liu

type:
Expression profiling by array
Non-coding RNA profiling by array

platform_organism:
Homo sapiens
synthetic construct


title: The Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase in neurons

city: Illkirch

first: Herve

last: Moine

address: 1 rue Laurent Fries

department: Translational medicine and neurogentics

country: France

institute: CNRS

summary:
In this study, we sought to identify the mRNAs associated to FMRP protein in mouse cortical neuron using a cross linking immunoprecipitation and microarray (CLIP-microarray).
The mRNAs crosslinked at 254 nm to FMRP in mouse cortical neurons cultured 8 days in vitro (8 DIV) were immunoprecipitated with H120 anti-FMRP (Santa Cruz) and reverse transcribed to labeled cDNAs with Ovation Pico WTA system V2 (Nugen) and hybridized on Mouse Gene 1.0ST (Affymetrix)

overall_design: We analyzed total RNA (Input) and FMRP-CLIPed RNA (Clip) from 10 primary cortical neuron mouse cultures (5 Wt Input,  5 FMR1-KO Input, 5 Wt Clip, 5 FMR1-KO Clip).  Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.

first: Ricardos

last: Tabet

first: Eric

last: Flatter

first: Nicolas

last: Vitale

first: Dimitri

last: Heintz

first: Laetitia

last: Fouillen

first: Violaine

last: Alunni

first: Doulaye

last: Dembele

first: Jean-Louis

last: Mandel

first: Hervé


title: Microarray expression data from circulating blood monocytes

first: Carlos

last: Briseno

overall_design:
Analysis of Ly-6Chi TremL4– , Ly-6Chi TremL4+ and Ly-6Clo TremL4+ circulating blood monocytes
Peripheral blood was pooled from 10 WT C57Bl/6 females and monocyte subsets were sorted to >95% purity on a FacsAria Fusion

first: Malay

last: Haldar

first: Kenneth

last: Murphy


title: Distinct transcriptional programs control cross-presentation in classical- and monocyte-derived dendritic cells


title: Microarray expression data from monocytes, Mo-DCs and CD24 DCs

overall_design: Mo-DCs from WT and IRF4KO mice, BM Ly-6ChiTremL4–  and Ly-6CloTremL4+ monocytes, and WT CD24+ DCs were sorted to >95% purity on FACSAria Fusion


title: Epigenetic reprogramming of Fallopian tube fimbriae in BRCA mutation carriers defines early ovarian cancer evolution

status: Public on May 19 2016

city: Manchester

first: Sacha

last: Howell

address: Oglesby Cancer Research Centre

department: Faculty of Biology, Medicine and Health

country: United Kingdom

institute: The University of Manchester

summary: The development of non-invasive primary cancer preventive measures in humans require a thorough understanding of the initial cancer-driving molecular mechanisms. High grade serous extra-uterine M llerian cancers (HGSEMC; formerly classified as ovarian/tubal/peritoneal cancer) present at a very late stage and less than 40% of women survive 5 years. Although the recent TCGA initiatives revealed key molecular changes in established cancers, very little is known about the initial molecular alterations in cancer development. Analysis of normal tissue at extensively high risk prior to the development of any microscopic alterations is critical. BRCA1/2 mutation carriers have an up to 30   40 fold increased risk to develop ovarian cancer, preferentially HGSEMC. Despite a plethora of evidence linking mutations in BRCA1 or BRCA2 to cancer development the core components such as organ specificity (i.e. to breast and Fallopian Tube) are still missing. The Fallopian Tube of BRCA mutation carriers offers a unique opportunity to study carcinogenesis because these cancers originate only from the distal (i.e. fimbrial) end of the Fallopian Tube (which is in close proximity to the ovary), and not from the proximal end (which is close to the uterus). The ovary which is in extreme close proximity to the fimbriae provides an excellent soil for cancer cells which are likely shed from the fimbriae and once the cancer has been discovered the big bulk of tumour is usually present on the ovary and hence the majority of HGSEMC are also referred to as  ovarian cancer . To study the earliest steps of human carcinogenesis we performed epigenome-wide DNA methylation (DNAme) analyses (using the Illumina 450k DNA methylation bead-array assay assessing DNAme at ~480 000 CpG sites) in 215 microscopic normal Fallopian Tube samples of BRCA1/2 mutation carriers (n=56) and controls (n=59) who had their tubes/ovaries removed for prophylactic or other reasons, respectively (for 52 and 49 individuals respectively we analysed both fimbrial and proximal Fallopian Tubes). In order to adjust for any epigenetic effects which are not of immediate importance to the carcinogenic process, for each volunteer we analysed both the fimbrial (at risk) and the proximal (non at risk) portion of the tubes separately.

overall_design: Formalin fixed paraffin embedded (FFPE) tissue blocks were retrieved from UCL Biobank (NC09.13). Histopathological features of fimbrial and proximal section of Fallopian Tube from BRCA carriers and control cases were carefully examined. Cases negative for serous tubal intraepithelial carcinoma (STIC) lesions were chosen for DNA isolation to characterize pre-cancer epigenetic changes. For DNA isolation, a core of 3 x 0.6 mm was taken from each block representing fimbrial and proximal end of fallopian tubes from both BRCA carriers and matched control cases. The DNA was isolated using QIAamp(r) DNA FFPE Tissue Kit as per manufacturer's protocol with minor modifications (Dewaxing for 4 hours in xylene and proteinase digestion performed overnight, other procedures were as per the instructions). DNA was quantified using Nandrop and restored using the Infinium FFPE DNA Restore Kit and then 200 nanogram of DNA was bisulfite converted using the EZ DNA Methylation-Gold(tm) and subjected to methylation analysis on the Illumina Infinium Human Methylation450 BeadChip.

first: Martin

last: Widschwendter


title: Multiple levels of transcriptional regulation by PLZF in NKT cell development [human_ChIP-seq]

status: Public on May 24 2016

city: Chicago

first: Aiping

last: Mao

state: IL

address: 929 East 57th street

institute: University of Chicago

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program.
The transcription factor PLZF is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program: first, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T helper-specific transcription factor genes that in turn control T helper specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.

overall_design: Examination of PLZF binding sites in KG1a cells; Please note that raw data has been lost, and therefore was not provided.

first: Albert

last: Bendelac

first: Rebecca

last: Mathew


title: Regulation of DNA methylation landscape in human somatic cell reprogramming by miR-29 family (illumina 450K)

city: New Haven

first: Eriona

last: Hysolli

state: CT

address: 10 Amistad Street

department: Genetics

institute: Yale University

summary: Reprogramming to pluripotency after overexpression of OCT4, SOX2, KLF4 and MYC is accompanied by global genomic and epigenomic changes. Histone modification and DNA methylation states in iPSCs have been shown to be highly similar with embryonic stem cells (ESCs). However, epigenetic differences still exist between iPSCs and ESCs. In particular, aberrant DNA methylation states found in iPSCs are a major concern for using iPSCs in a clinical setting. Thus, it is critical to find factors that regulate DNA methylation states in reprogramming. Here, we found that the miR-29 family is an important epigenetic regulator during human somatic cell reprogramming. Our global DNA methylation and hydroxymethylation analysis shows that DNA demethylation is a major event mediated by miR-29a depletion during early reprogramming, and that iPSCs derived from miR-29a depletion are epigenetically closer to ESCs. Our findings uncover an important miRNA-based approach to generate clinically robust iPSCs.

overall_design: Bisulphite converted gDNAs of D551 fibroblasts transduced for 3 days with overexpression of DNMTs, TETs, TDG and OSKM or miR29a/b/c and control sponge were hybridized into Illumina Infinium HumanMethylation 450K Beadchip.

first: Yoshiaki

last: Tanaka

first: In-Hyun

last: Park


title: U937 treated with decitabine, panobinostat and valproic acid [Illumina]

status: Public on May 12 2016

city: Freiburg

first: Michael

last: Lübbert

address: Hugstetter Str. 55

institute: Medical Center - University of Freiburg

summary: We employed the AML cell line model U937 to determine the effects of single and dual treatment with the HMA decitabine and the HDACi Pano or VPA on  gene expression and DNA methylation. We noted global alterations of gene expression and a massive effect on the methylome.

overall_design: We analyzed 6 treatment conditions in triplicates summarizing to 18 samples.

first: Nadja

last: Blagitko-Dorfs

first: Pascal

last: Schlosser

first: Gabriele

last: Greve

first: Dietmar

last: Pfeifer


title: U937 treated with decitabine, panobinostat and valproic acid [Affymetrix]


title: Expression profile of diffuse large B cell lymphoma patients

city: Shanghai

first: Fan

last: YANG

address: 197, Rui Jin Er Road

institute: Shanghai Institute of Hematology

summary: To understand the biological function of GSTT1 deletion in diffuse large B cell lymphoma (DLBCL), we identified genes that are expressed differently in lymph node tissues from DLBCL patients collected at diagnosis with GSTT1 deletion (4 cases) compared to those without GSTT1 deletion (4 cases).

overall_design: Lymph node tissue of DLBCL patients were collected at diagnosis for RNA extraction and hybridization on Affymetrix microarrays. 4 cases of DLBCL samples with GSTT1 deletion and 4 cases of DLBCL samples wihtout GSTT1 deletion were used.

first: Wei-Li

last: Zhao


title: DNA microarray-mediated transcriptional profiling of avian pathogenic Escherichia coli O2 strain E058 during its infection of chicken

status: Public on May 28 2016

city: Yangzhou

first: Qingqing

last: Gao

state: Jiangsu

address: Yangzhou wenhui Road 12

department: Colledge of Veterianry medicine

institute: Yangzhou university

summary:
APEC most often infect chickens, turkeys, ducks, and other avian species, and therefore pose a significant economic burden on the poultry industry worldwide. Few studies have analyzed the genome-wide transcriptional profile of APEC during infection in vivo.
In this study, we examined the genome-wide transcriptional response of APEC O2 strain E058 in an in vivo chicken infection model to better understand the factors necessary for APEC colonization, growth, and survival in vivo. An Affymetrix multigenome DNA microarray, which contains most of the genomic open reading frames of E. coli K-12 strain MG1655, uropathogenic E. coli strain CFT073, and E. coli O157:H7 strain EDL 933, was used to profile the gene expression in APEC E058.The genes highly expressed during infection were involved in metabolism, iron acquisition or transport, virulence, response to stress, and biological regulation. Many genes encoding putative or hypothetical proteins were also strongly upregulated, implying that some undiscovered mechanism may underlie APEC pathogenesis.

overall_design: We identified the in vivo transcriptional response of APEC E058 bacteria collected directly from the blood of infected chickens. Significant differences in expression levels were detected between the in vivo expression profile and the in vitro expression profile in LB medium.

first: Song


title: Angiogenesis in the skin of SHARPIN-deficient mice with chronic proliferative dermatitis

status: Public on May 21 2016

city: Bar Harbor

first: Timothy

middle: Michael

last: Stearns

state: ME

address: 600 Main Street

department: Computational Sciences

institute: The Jackson Laboratory

summary: Angiogenesis is a common feature of pathological processes including wound healing, tumor formation, and chronic inflammation. Chronic inflammation can also be associated with dilation or proliferation of lymph vessels. We examined blood vessels and lymphatics and the expression of pro- and anti-angiogenic genes in the skin of SHARPIN-deficient mice which spontaneously develop a chronic proliferative dermatitis (cpdm). The number of blood vessels in the dermis of cpdm mice increased with age as the inflammation progressed. Lymphatics identified by labeling for LYVE1 and podoplanin were moderately dilated, but they were not increased in number. The expression of proangiogenic Vegfa, Flt1 and anti-angiogenic Sema3a mRNA was increased. VEGFA was primarily localized in keratinocytes of cpdm skin. There was also increased expression of Ece1 and Pdpn mRNA. Podoplanin was restricted to lymphatic endothelial cells in normal skin, but fibroblasts in cpdm skin also reacted with anti-podoplanin antibodies indicating that they were activated. The expression of other angiogenic and lymphangiogenic factors was not altered or decreased. These results indicate that cpdm mice may be a useful model to study the pathogenesis of angiogenesis in chronic inflammation.

overall_design: Thirty-one skin samples were taken from fifteen C57BL/KaLawRij-Sharpincpdm/Sharpincpdm RijSunJ (cpdm) and sixteen C57BL/6J (wildtype) female Mus musculus subjects at 2, 4, 6, 8, and 10 weeks of age.  Three replicates were taken per sample group, except an additional sample was taken for wildtype mice at 6 weeks of age.

first: Harm

last: HogenEsch

first: Mario

last: Sola

first: Kathleen

last: Silva

first: Victoria

last: Kennedy

first: John

last: Sundberg


title: DNA Methylation in PRDM8 is a Biomarker for Dyskeratosis Congenita

status: Public on May 23 2016

city: Aachen

first: Wolfgang

last: Wagner

address: Pauwelsstrasse 20

department: Helmholtz Institute for Biomedical Engineering

institute: RWTH Aachen University

summary: Dyskeratosis congenita (DKC) is characterized by impaired telomere maintenance and reveals clinical features of premature aging. So far, diagnosis of DKC relies particularly on telomere length screening raising the need for additional biomarkers. In this study, we analysed global DNA methylation (DNAm) profiles of DKC patients. Age-associated DNAm changes were not generally accelerated in DKC. However, we observed significant hypermethylation in the gene for PR domain containing 8 (PRDM8). Notably, the same genomic region revealed hypermethylation in aplastic anemia (AA), and Down syndrome (DS), indicating that there might be an association with premature aging syndromes. Site-specific analysis of DNAm level in PRDM8 with pyrosequencing and MassArray validated aberrant hypermethylation in 14 DKC patients and 27 AA patients. Notably, telomere length was not directly correlated with DNAm in PRDM8, indicating that the two methods are complementary. In conclusion, DNAm at PRDM8 provides a new biomarker to support diagnosis of of AA and DKC.

overall_design: DNA methylation profiles of 4 DKC samples

first: Carola

middle: I

last: Weidner

first: Qiong

last: Lin

first: Uwe

last: Gerstenmaier

first: Andrea

last: Kafie

first: Martin

last: Kirschner

first: Heiko

last: Bruns

first: Stefan

last: Balabanov

first: Arne

last: Trummer

first: Clemens

last: Stockklausner

first: Britta

last: Höchsmann

first: Hubert

last: Schrezenmeier

first: Marcin

last: Wlodarski

first: Jens

last: Panse

first: Tim

middle: H

last: Brümmendorf

first: Fabian

last: Beier


title: Quantitative comparison of DNA methylation assays for biomarker development and clinical applications

status: Public on May 20 2016

city: Vienna

first: Christoph

last: Bock

address: Lazarettgasse 14

country: Austria

institute: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences

summary: Genome-scale DNA methylation data obtained with the Infinium 450k assay. These data were used to support target selection for benchmarking of locus-specific DNA methylation assays

overall_design: 6x2 pairs of matched tumor/normal samples, 2 xenografts, and 4 pairs of treated/untreated leukemia cell lines (KG1 and KG1a)

first: Florian

last: Halbritter


title: CD73 as a therapeutic target of pancreatic neuroendocrine tumor stem cells

city: Bunkyo-ku

first: Kaoru

last: Mogushi

state: Tokyo

address: 2-1-1 Hongo

department: Intractable Disease Research Center

country: Japan

institute: Juntendo University

summary: Background: Identification and purification of cancer stem cells (CSCs) lead to new therapeutic targets; however, there has been no study to identify and isolated pancreatic neuroendocrine tumor (pNET) CSC. Therefore the clinical significance and its target remain unknown. This study aimed to identify pNET CSCs and characterize therapeutic candidate for pNET CSCs.  Methods: We isolated CSCs sorting by ALDH activity in pNET surgical section and cell lines. We verified whether these cells have the property of stemness in vivo and in vitro. Additionally in order to acquire CSC gene profile, genome-wide gene expression profiles were investigated using a microarray technique.  Results: ALDHhigh cells, but not control bulk cells, formed spheres, proliferated in hypoxia as well as normoxia and promoted cell motility, which are features of CSCs. Injection of as few as 10 ALDHhigh cells led to subcutaneous tumor formation, and 105 ALDHhigh cells established metastases but not control bulk cells in mice. Comprehensive gene expression analysis revealed that genes associated with mesenchymal stem cell, including CD73, and epithelial-mesenchymal transition (EMT) were overexpressed in ALDHhigh cells. APCP, which is CD73 inhibitor, inhibited sphere formation and cell motility in ALDHhigh cells in vitro, and tumor growth inhibition were observed in ALDHhigh cells in vivo.  Conclusions: We identified ALDHhigh cells of pNET and elucidated that they have stemness property. Furthermore we identified CD73 as a target of ALDHhigh cells. CD73 is a promising novel target of pNET CSCs.

overall_design: Human pNET cell line QGP1 was obtained from Health Science Research Resources Bank (Osaka, Japan). Comprehensive gene expression analysis in ALDHhigh pNET cells was performed to acquire the CSC gene profile. The gene expression changes in 185 probe sets were found by microarray analysis (fold-change value > 2 between ALDHhigh pNET and control cells). Genes associated with mesenchymal stem cell, including CD73 (5'-nucleotidase, ecto) and CD109, and epithelial-mesenchymal transition (EMT), including caveolin1 (CAV1) and SLUG (SNAI2) were overexpressed in ALDHhigh cells.

first: Eriko

last: Katsuta

first: Shinji

last: Tanaka

first: Shu

last: Shimada

first: Yoshimitsu

last: Akiyama

first: Arihiro

last: Aihara

first: Satoshi

last: Matsumura

first: Yusuke

last: Mitsunori

first: Daisuke

last: Ban

first: Takanori

last: Ochiai

first: Atsushi

last: Kudo

first: Hiroshi

last: Fukamachi

first: Koh

last: Nakayama

first: Shigeki

last: Arii

first: Minoru

last: Tanabe


title: Maize (Zea mays): control vs cold stress

city: Dublin

first: Mauro

last: Di Fenza

address: Belfield

country: Ireland

institute: University College Dublin

summary: Transcriptional profiling of 4 maize varieties comparing genetic root response under control temperature conditions with genetic root response under low temperature conditions

overall_design: Two-condition experiment, control vs cold stress treatment. Biological replicates: 3 control and 3 treatment per variety, independently grown and harvested. One replicate per array. Hybridization followed a two-channel loop design (direct comparison) where all the samples of interest are hybridised to each other without a reference sample.

first: Bridget

last: Hogg

first: Tommy

middle: F

last: Gallgher

first: Susanne

last: Barth


title: A  paracrine IGF1/IGF1R-PI3K signaling loop underlies resistance to CSF-1R inhibition in GBM

city: Philadelphia

first: Robert

middle: L

last: Bowman

state: PA

address: 421 Curie Blvd

department: Cancer Biology

institute: University of Pennsylvania School of Medicine

summary: Glioblastoma multiforme (GBM) is the most aggressive form of glioma, and is notorious for its terminal prognosis and lack of responsiveness to current treatment approaches. The brain tumor microenvironment (TME) represents a largely untapped reservoir of therapeutic target options in GBM. Here we have focused on the interplay between glioma cells and tumor-associated macrophages/ microglia (TAMs). TAMs accumulate in the gliomas with disease progression, and depend on colony stimulating factor 1 receptor (CSF-1R) signaling for survival. In a recent study from our laboratory, mice bearing high-grade gliomas were treated with a CSF-1R inhibitor, BLZ945 (Novartis), and tumors regressed significantly after just 7 days of treatment (PMID: 24056773). Here we investigate whether long-term treatment of high-grade gliomas with BLZ945 would result in stable management of disease in a mouse model of proneural GBM. We show that ~44% of mice survived to the trial end point (EP) with minimal disease by MRI and histology, whereas ~56% of mice showed tumor recurrence (Reb). Serial transplantation of rebound tumor cells into naïve animals re-established BLZ945 responsiveness, suggesting a role for the microenvironment in supporting recurrent disease. Indeed, RNA-seq analysis on FACS purified tumor cells and TAMs from EP and Reb tumors showed elevated PI3K signaling in Reb tumors, driven by a heterotypic paracrine interaction between TAM-derived IGF-1 and tumor cell IGF-1R. We performed combination trials to block IGF-1R or downstream PI3K signaling in rebound tumors with BLZ945 treatment, and were able to significantly prolong overall survival. Given that CSF-1R inhibitors are currently in clinical trials for multiple cancer types including for GBM, understanding the molecular mechanisms that underlie non-responsive/ resistant tumors is timely and critical.

overall_design: Tumor cells and tumor -associated macrophages (TAMs) were sorted from Vehicle, Endpoint, and Rebound tumors following BLZ945 treatment.

first: Daneila

last: Quail

first: Johanna

last: Joyce


title: Early induction of the type I interferon response in neurological forms of Gaucher disease

city: Rehovot

first: Tamar

last: Farfel-Becker

address: Weizmann Institute of sciense

country: Israel

institute: Weizmann Institute of sciense

summary: Neuroinflammation is a key phenomenon in the pathogenesis of many neurodegenerative diseases. Understanding the mechanisms by which brain inflammation is engaged and delineating the key players in the immune response and their contribution to brain pathology is of great importance for the identification of novel therapeutic targets for these devastating diseases. Gaucher disease, the most common lysosomal storage disease, is caused by mutations in the GBA1 gene and is a significant risk factor for Parkinson?s disease; in some forms of Gaucher disease, neuroinflammation is observed. An unbiased gene profile analysis was performed on a severely affected brain area of a neurological form of a Gaucher disease mouse at a pre-symptomatic stage; the mouse used for this study, the Gbaflox/flox; nestin-Cre mouse, was engineered such that GBA1 deficiency is restricted to cells of neuronal lineage, i.e., neurons and macroglia. The 10 most up-regulated genes in the ventral posteromedial/posterolateral region of the thalamus were inflammatory genes, with the gene expression signature significantly enriched in interferon signaling genes. Our results imply that the type I interferon response is involved in the development of nGD pathology, and support the notion that interferon signaling pathways play a vital role in the sterile inflammation that often occurs during chronic neurodegenerative diseases in which neuroinflammation is present.

overall_design: Neuronopathic Gaucher disease (nGD) brains were examined at 14 days, and compared to +/- littermates. 3 +/- and 3 -/- mice were analyzed.

first: Dena

last: Leshkowitz

first: Anthony

last: Futerman


title: Identification of aging-associated gene expression signatures that precede intestinal tumorigenesis

status: Public on May 03 2016

city: Kyoto

first: Yoshihisa

last: Okuchi

state: Kyoto

address: Yoshida Konoe-cho, Sakyo-ku

department: Department of Pathology and Biology of Diseases

institute: Kyoto university

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: In vivo hepatic reprogramming of myofibroblasts with AAV vectors as a therapeutic strategy for liver fibrosis

city: San Francisco

first: Milad

last: Rezvani

address: 35 Medical Center Way

department: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research

institute: University of California San Francisco

summary:
We developed in vivo reprogramming of myofibroblasts (MFs) into induced hepatocytes (MF-iHeps) using adeno-associated virus serotype 6 (AAV6) vectors expressing hepatic transcription factors in MF fate tracing (Lrat-Cre;R26R-ZsGreen) mice with carbon tetrachloride (CCl4)-induced liver fibrosis.
To determine whether MF-iHeps acquire full hepatocyte differentiation, we used microarrays to profile their global gene expression.

overall_design: We isolated MF-iHeps and primary hepatocytes (Heps) from the same mice by laser-capture microdissection (5 and 3 biological replicates, respectively) and hepatic MFs from CCl4-treated littermates isolated by fluorescence-activated cell sorting (3 biological replicates). Total RNA was extracted, transcribed, amplified and biotin labeled. Labeled cDNA targets were hybridized to GeneChip Mouse Gene 1.0 ST arrays (Affymetrix).

first: Regina

last: Español-Suñer

first: Holger

last: Willenbring


title: Expression data from oral squamous cell carcinoma cell line Cal27 after lentivirus shIL-1beta transfection

city: Guangzhou

first: Tong

last: Wu

state: Guangdong

address: Zhongshaner Road

institute: Sun Yat-sen University

summary:
Oral squamous cell carcinoma cell line Cal27 was transfected with lentiviral shIL-1beta or scrambled shRNA.
We used microarrays to detail the global program of gene expression during this process.

overall_design: IL-1beta was identified as one of the key node genes in oral carainogenesis in our preveious in vitro study. This in vivo study was designed to confirm the role of IL-1 beta and explore some more detail about the evolvment of IL-1 in malignant transformation.


title: The impact of dietary fatty acids composition on the transcriptomes of six tissues reveals specific regulation of immune related genes

city: Gothenburg

first: Leif

last: Väremo

address: Kemivägen 10

department: Biology and Biological Engineering

institute: Chalmers University of Technology

summary: Dietary polyunsaturated fatty acids (PUFA) are suggested to modulate immune function, but the effects of dietary fatty acids composition on gene expression patterns in immune organs have not been fully characterized. In the current study we investigated how dietary fatty acids composition affects the total transcriptome profile, and especially, immune related genes, in bone marrow cells (BMC) and spleen (SPL). Four tissues with metabolic function, skeletal muscle (SKM), white adipose tissue (WAT), brown adipose tissue (BAT), and liver (LIV), were investigated as a comparison. Following 8 weeks on low fat diet (LFD), high fat diet (HFD) rich in saturated fatty acids (HFD-S), or HFD rich in PUFA (HFD-P), tissue transcriptomics were analyzed by microarray and metabolic health assessed by fasting blood glucose level, HOMA-IR index, oral glucose tolerance test as well as quantification of crown-like structures in WAT. Interestingly, SKM and BMC were relatively inert to the diets, whereas the two adipose tissues (WAT and BAT) were mainly affected by HFD per se (both HFD-S and HFD-P). In particular, WAT gene expression was driven closer to that of the immune organs SPL and BMC by HFDs. Remarkably, the spleen, showed a major response to HFD-P, but not to HFD-S, whereas the LIV exhibited different responses to both of the HFDs. Further, HFD-P corrected the metabolic phenotype induced by HFD-S. Hence, the quantity and composition of dietary fatty acids affected the transcriptome in a distinct manner. Especially, PUFA prompted a specific regulation of immune related genes in the spleen. Thus, PUFA can regulate immune function by influencing gene expression.

overall_design: Mice were fed three different diets (low fat diet, high fat diet rich in saturated fatty acids and high fat diet rich in polyunsaturated fatty acids) for height weeks. Six tissues (skeletal muscle, bone marrow cells, white adipose tissue, brown adipose tissue, spleen and liver) were harvasted and analysed using microarray with 4 biological replicates per tissue and diet except for LIV/LFD and LIV/HFD-S with 5 replicates each and SPL/LFD with 3 replicates

first: Sara

last: Svahn

first: Britt

last: Gabrielsson

first: Eduard

last: Peris

first: Intawat

last: Nookaew

first: Louise

last: Grahnemo

first: Ann-Sofie

last: Sandberg

first: Ingrid

last: Wernstedt Asterholm

first: John-Olov

last: Jansson

first: Jens

last: Nielsen

first: Maria

last: Johansson


title: Expression data from young and aged murine B cell subsets

first: Michael

middle: P

last: Cancro

address: 284 JMB / 2360 Hamilton Walk

department: Pathology & Laboratory Medicine

institute: University of Pennsylvania

summary:
The origin and nature of recently discovered age-associated B cells (ABCs) is under investigation.
We used a microarray to examine the transcriptional signatures of ABCs, follicular B cells from aged mice (AFO), and follicular B cells from young mice (YFO).

overall_design: ABC, AFO, and YFO from 5 aged (22-24 mo.) and 5 young (3 mo.) C57BL/6 mice were FACS sorted as sources of RNA.

first: Yi

last: Hao

last: Paley

first: E

last: Wherry


title: Id2 is required for antiviral Th1 cell differentiation and represses Tfh cell differentiation

city: La Jolla

first: Ananda

middle: W

last: Goldrath

address: 9500 GIlman Drive.

department: Biological Sciences

institute: University of California, San Diego

summary:
Differentiation of naive CD4+ T cells into T-helper (Th) effector subsets is critical for protection against pathogens. Together, E-protein transcription factors and the inhibitor-of-DNA binding (Id) proteins are important arbiters of T cell development, but their role in the differentiation of Th1 and Tfh cells is not well understood. Th1 cells show robust Id2 expression compared to Tfh cells, and RNAi depletion of Id2 increased Tfh cell frequencies and germinal center responses, while impairing Th1 cell accumulation during viral infection. Further, Th1 cell differentiation was blocked by genetic ablation of Id2, leading to E-protein dependent accumulation of effector cells with 78% of Th1-associated genes showing diminished expression and a concurrent enrichment of the Tfh gene-expression program. The Tfh-defining transcriptional repressor Bcl6 bound to the Id2 locus inhibiting expression, providing a mechanism by which bimodal expression of Id2 in Tfh and Th1 cells can be established. Thus, Id2 is critical in enforcing the reciprocal development of Th1 and Tfh cell fates.
We used microarray to assess the changes in gene expression between Id2-sufficient and -deficient Th1 and Tfh cells.

overall_design: Id2-sufficient and -deficient SMARTA CD4+ T cells were sorted into TriZol on day 7 of LCMV infection according to expression of SLAM and CXCR5. Two replicates per sample were analyzed.

first: Laura

middle: A

last: Shaw

first: Simon

last: Belanger

first: Kyla

middle: D

last: Omilusik

first: James

last: Scott-Browne

first: J

last: Nance

first: Sunglim

last: Cho

first: John

last: Goulding

first: Li-Fan

last: Lu

first: Anna

last: Lasorella

first: Shane

last: Crotty


title: Expression data from immunophenotypic HSPCs isolated from different stages of human hematopoiesis, in vivo and in vitro

city: Los Angeles

first: Hanna

middle: Katri Annikki

last: Mikkola

address: 621 Charles E Young Drive South, 2204, Mailbox 160606

department: Molecular, Cell and Developmental Biology

institute: University of California, Los Angeles

summary:
The derivation of functional, transplantable HSCs from an pluripotent stem cells in vitro holds great promise for clinical therapies, but is unachieved. In order to achieve full functionality of HSCs, it is vital to determine the extent to which PSCs can currently be differentiated to the HSC program in vitro and identify the remaining dysregulated genetic pathways.
Microarrays were used to compare the transcritomes of ESC-derived immunophenotypic HSPCs to endogenous HSPCs from various stages of development to determine the programs important for human HSC development and function, and which programs were lacking in ESC-derived hematopoietic cells.

overall_design: CD34+CD38-CD43+CD90+ HSPCs were sorted from human placenta and embryoid bodies, and CD34+CD38-CD45+CD90+ HSPCs sorted from fetal liver and embryoid bodies co-cultured on OP9-M2 stroma, the RNA was extracted, library created and hybridized to the Affymetrix microarray

first: Diana

middle: R

last: Dou

first: Vincenzo

last: Calvanese

last: Sierra

first: Arazin

last: Minasian

first: Pamela

last: Saarikoski

first: Rajkumar

last: Sasidharan

first: Jerome

last: Zack

first: Gay

middle: M

last: Crooks

first: Zoran

last: Galic

middle: K


title: Weight gain and loss induce changes in luteal molecular signals in vervet monkeys

status: Public on May 01 2016

city: Aurora

first: Tzu Lip

last: Phang

state: CO

address: 12700 East 19th Avenue

department: Medicine

institute: University of Colorado, Denver

summary: Weight gain and loss did not significantly alter menstrual cyclicity, however, both induced alterations in the CL transcriptome

overall_design: Interventional pilot study

first: Alex

last: Polotsky

first: Andy

last: Bradford

first: Satu

last: Kuokkanen


title: Expression data from wild type and Pax6 null neural progenitors

status: Public on May 02 2016

city: Cambridge

first: Sudhir

last: Thakurela

address: 7 Divinity Avenue

institute: HSCRB

summary: Pax6 is a highly conserved transcription factor among vertebrates and is important in various aspects of the central nervous system (CNS) development. However, the gene regulatory circuitry of Pax6 underlying these functions remains elusive. We find that, following expression in neural progenitor cells, Pax6 targets many promoters embedded in an active chromatin environment. Intriguingly, many of these sites are also bound by another progenitor factor, Sox2, which cooperates with Pax6 in gene regulation. A combinatorial analysis of Pax6 binding dataset with transcriptome changes in Pax6-deficient neural progenitors reveals a dual role for Pax6, in which it activates the neuronal (ectodermal) genes while concurrently represses the mesodermal and endodermal genes thereby ensuring the unidirectionality of lineage commitment towards glutamatergic neuronal differentiation. Furthermore, Pax6 is critical for inducing activity of transcription factors that elicit neurogenesis and repress others that promote non-neuronal lineages. In addition to many established downstream effectors, Pax6 directly binds and activates a number of genes that are specifically expressed in neural progenitors but have not been previously implicated in neurogenesis. The in utero knockdown of one such gene, Ift74, during brain development impairs polarity and migration of new-born neurons. These findings demonstrate new aspects of the gene regulatory circuitry of Pax6, revealing how it functions to control neuronal development at multiple levels to ensure unidirectionality and proper execution of the neurogenic program.

overall_design: Expression profiling of wildtype and Pax6Null (Sey) neural progenitors.

first: Neha

last: Tiwari

first: Sandra

last: Schick

first: Angela

last: Garding

first: Robert

last: Ivanek

first: Benedikt

last: Berninger

first: Vijay


title: Genome-wide copy number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma

status: Public on May 07 2016

city: Omaha

first: Javeed

last: Iqbal

state: NE

address: 601 S 42nd St

institute: UNMC

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


title: Expression data from Dmp1-Cre targeted and non-targeted Cxcl12-abundant reticular (CAR) cells in mouse bone marrow

status: Public on May 14 2016

city: St. Louis

first: Daniel

middle: C

last: Link

state: MO

address: 660 South Euclid Avenue

department: Internal Medicine

institute: Washington University in St Louis

summary:
In mouse bone marrow, mesenchymal stem cells (MSC) has the potential to form osteocytes, adipocytes and cartilage. In the process of osteogenesis, MSCs differenetiate into stromal cells, such as CAR cells. Osteoblast is responsible for the formation of osteocytes and osteoblasts may be differentiated from a subset of CAR cells. Dmp1-Cre targeted CAR cells are thought to enrich for a osteoblast progenitor population.
We used microarrays to detail the gene expression profiles among Dmp1-Cre targeted and non-targeted CAR cells. Gene expression diffferences were compared to support the hypothesis that Dmp1-Cre targeted CAR cells may be enriched for osteoblast progenitors.

overall_design: Dmp1-Cre targeted and non-targeted CAR cells were FACS sorted from three mice. RNA were extracted from these sorted cells and processed for microarray using Affymetrix mogene 1.0 ST chip. Cells from one mouse represent one sample

first: Jingzhu

last: Zhang


title: Genome-wide methylation profiles of menstrual blood and vaginal fluid

city: Seoul

first: Hwan Young

last: Lee

address: 103 Daehak-ro, Jongno-gu

department: Forensic Medicine

country: South Korea

institute: Seoul National University College of Medicine

summary: The ability to predict the type of tissues or cells from molecular profiles of crime scene samples has practical implications in forensics. In order to identify body fluid-specific DNA methylation changes, genome-wide DNA methylation profiling was carried out for body fluids including menstrual blood and vaginal fluid obtained from 3 female donors aged 19, 27 and 38 years. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in bisulfite converted DNA. Samples included 3 of each vaginal fluid and menstrual bloods collected on the first, second and third days of menstrual bleeding.

overall_design: Bisulfite converted DNA from the 12 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: Hwan-Young


title: Epigenetic Pattern on the Human Y Chromosome is Evolutionarily Conserved

first: Minjie

address: 1985 Zonal Avenue

department: Department of Pharmacology and Pharmaceutical Sciences

institute: University of Southern California

summary: DNA methylation is very important for mammalian development. However, it is unclear whether the DNA methylation pattern is evolutionarily conserved. The Y-chromosome serves as a powerful tool for the study of human evolution because it is only transferred between males. In this study, based on deep-rooted pedigrees and the latest Y-chromosome phylogenetic tree, we performed epigenetic pattern analysis of Y-chromosome from 72 donors. By comparing their respective DNA methylation levels, we found that the DNA methylation pattern on the Y-chromosome was stable among family members and within haplogroups. Despite two haplogroup-specific methylation sites were found, they were both genotype-dependent. Moreover, with a remote divergence time, the African and Asian samples also had similar DNA methylation patterns. Our findings indicated that the DNA methylation pattern on Y-chromosome was conservative during human male history.

overall_design: Bisulphite converted DNA from the 74 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.

first: Caiyun

last: Yang

first: Chaochao

last: Wang


title: Global methylation analysis of development and progression of colorectal carcinoma

status: Public on May 13 2016

city: South San Francisco

first: Omar

last: Kabbarah

state: California

address: 1 DNA Way

department: Oncology Biomarker Development

institute: Genentech Inc

summary:
Colorectal tumorigenesis proceedes through well defined clinical stages assoicated with charateristic mutations. Besides genetic alterations, epi-driver genes that are aberrantly expressed in cancers in a fashion that confers a seletive growth advantage can also contribute to tumor evolution. To gain a global view of methylation patterns in normal and maliganant colorectal epithelia, we performed genome-wide DNA methylation analysis on DNAs from 48 fresh frozen CRC samples at different stages of CRC progression.
We used IlluminaHumanMethylation450 Beadchip to get  a broad view of  genome-wide DNA methylationdata  during CRC progression and identified significantly differentially methylated genes during CRC progression

overall_design: A total of 48 macro-dissected tissues including normal colon tissue, adenomas, carcinomas and metastases were collected by the Department of Pathology at the University of Virginia under the supervision of an experienced pathologist. DNA was extracted and run on IlluminaHumanMethylation450 Beadchip by Expression Analyisis.

first: Henry

last: Frierson

first: Thomas

last: Sandmann

first: Garret

last: Hampton

first: Xueping

last: Qu

first: Richard

last: Bourgon


title: Global gene expression and methylation analysis of development and progression of colorectal carcinoma


title: U937 treated with decitabine, panobinostat and valproic acid

city: Freiburg

first: Michael

last: Lübbert

address: Hugstetter Str. 55

institute: Medical Center - University of Freiburg


title: The IL4-STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p

status: Public on Apr 29 2016

city: Debrecen

first: Szilard

last: Poliska

address: Egyetem ter 1.

department: Biochemistry and Molecular Biology

country: Hungary

institute: University of Debrecen

platform_organism:
Mus musculus
synthetic construct


title: Transcriptome analysis of Largemyd and Dmdmdx/Largemyd muscles in comparison to Dmdmdx: what make them different?

status: Public on Apr 30 2016

city: Columbus

first: Camila

last: Almeida

state: OH

address: 700 Children's Drive, RB2 WA3103

department: Center for Gene therapy

institute: Nationwide Children's Hospital

summary:
Transcriptome analysis of hindlimb muscles from dystrophic mice
Muscular dystrophies (MD) are a clinically and genetically heterogeneous group of mendelian diseases. The underlying pathophysiology and phenotypic variability in each form are much more complex, suggesting the involvement of many other genes. Thus, here we studied the whole genome expression profile in muscles from three mice models for MD, at different time points: Dmdmdx, carrying a mutation in dystrophin gene, Largemyd-/- with mutation in Large and Dmdmdx/Largemyd-/- bearing both mutations. The main objective was to identify altered biological functions, contributing to the understanding of disease and to the identification of prognostic biomarkers and points for therapeutic intervention. We identified a substantial number of differentially expressed genes (DEGs) in each model, reflecting diseases' complexity. The main biological process affected in the three strains was immune system, accounting for the majority of enriched functional categories, followed by degeneration/regeneration and extracellular matrix remodeling processes.The most notable differences were in 21-day-old Dmdmdx, with a high proportion of DEGs related to regenerative capacity observed in this mouse. The new Dmdmdx/Largemyd-/- model did not show a highly different transcriptome from the parental lineages, with a profile closer to Largemyd-/-, but not bearing the same regenerative potential as Dmdmdx. This is the first report about transcriptome profile of a mouse model for congenital MD and Dmdmdx/Largemyd. By comparing the profiles studied, we conclude that  alterations in biological functions due to the dystrophic process are very similar, and that the intense regeneration in  Dmdmdx involves a large number of activated genes, not differentially expressed in the other two strains.

overall_design: We analyzed calf muscles from 5 animals of each lineage (Dmdmdx, Largemyd, Dmdmdx/Largemyd and C57Bl/6 as normal control), at three ages (21 days, 3 months and 6 months) using the Affymetrix Mouse Gene 1.0 ST platform. Array data was processed by Expression Console. No technical replicates were performed.

first: Mariz

last: Vainzof


title: Genome-wide copy number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma [gene expression]

first: Javeed

summary: We studied 277 lymphoma samples (198 FL and 79 transformed FL [tFL]) using a single-nucleotide polymorphism array to identify the secondary chromosomal abnormalities that drive the development of FL and its transformation to diffuse large B-cell lymphoma. This dataset is corresponding Gene expression data that is available for a subset of the tFL cases for Series GSE67385.

overall_design: Frozen tumor biopsies were obtained from transformed Follicular Lymphoma cases. Total RNA was extracted and processed according to the standard Affymetrix protocol and hybridization to Affymetrix HG-U133 plus 2 arrays.

first: Wing

last: Chan

first: Timothy

last: McKeithan


title: DNA methylome analyses implicate fallopian tube as the tissue of origin for high grade serous ovarian cancer [array]

status: Public on May 10 2016

first: Adam

middle: R.

last: Karpf

state: Nebraska

address: 985950 Nebraska Medical Center

department: Eppley Institute for Research in Cancer

institute: University of Nebraska Medical Center

summary:
The cell and tissue of origin of high grade serous ovarian cancer (HGSC) is controversial.  While the disease was traditionally assumed to arise from the ovarian surface epithelium (OSE), recent work supports an alternative model implicating the fallopian tube fimbriae epithelium (FTE).  We used comparative DNA methylome analyses as a means to test these two competing models, hypothesizing that the HGSC methylome should more closely resemble its tissue of origin.  Using two separate analysis methods, analysis within distinct genomic contexts, and validation studies using large-scale publically available HGSC methylome data, we consistently observed that the DNA methylome of HGSC more closely resembles FTE than OSE.   These data support the FTE origin model, and suggest DNA methylome analysis as a useful approach to examine cell/tissue lineage origin in cancer.
HGSC is the most common and lethal form of epithelial ovarian cancer (EOC).  Two distinct tissues have been hypothesized as the tissue of origin of HGSC: OSE and FTE.  We hypothesized that the DNA methylome of HGSC would more closely resemble the methylome of its tissue of origin. To test this, we profiled HGSC (n=10), OSE (n=7), and FTE (n=7) primary fresh-frozen tissues, and analyzed DNA methylome using Illumina 450K arrays (n=24) and Agilent Sure Select methyl-seq (n=7).  We compared methylomes using statistical analyses of differentially methylated CpG sites (DMC) and differentially methylated regions (DMR), and methylation within a variety of different genomic contexts, including CpG island shores.  We also analyzed methylation specifically at Homeobox (HOX) genes, due to their role in tissue specification.  We used publically available HGSC methylome data (n=628) to provide additional comparison with FTE and OSE and potential validation.  This analysis revealed that HGSC and FTE methylomes were significantly and consistently more highly conserved than were HGSC and OSE.   Pearson correlations and hierarchal clustering of genes, promoters, CpG islands, CpG island shores, and HOX genes all revealed the increased relatedness of HGSC and FTE methylomes.  In addition, two different large data sets of publically-available HGSC methylome data confirmed these relationships.   In summary, our findings support the FTE origin model for HGSC, the most common and deadly EOC subtype.  Due to its tissue-specificity and biochemical stability, interrogation of the DNA methylome appears to be a valuable approach to examine cell/tissue lineage in cancer.

overall_design: Obtained fresh-frozen high grade serous cancer (HGSC) samples (n=10) from patients undergoing surgical resection at Roswell Park Cancer Institute (RPCI) and fresh-frozen patient matched normal ovarian surface epithelial (OSE) cells (n=5) and fallopian tube epithelial (FTE) cells (n=5) from patients without malignancy. Used mechanical scraping and processing of the epithelial layer of resected ovaries and fimbriae fallopian tubes immediately after removal in the operating theater.   All samples were collected using IRB-approved protocols at RPCI. Isolated genomic DNA using the Puregene Tissue Kit (Qiagen), which includes RNAse treatment.  To eliminate potentially confounding effects due to methylation phenotype, we selected HGSC samples showing similar global methylation as FTE and OSE, as determined by LINE-1 pyrosequencing. Genomic DNA (1000ng) was bisulfite converted using EZ DNA Methylation-Direct kit (Zimo Research) following the manufacturer's protocol. Samples were hybridized to Infinium Human Methylation 450K BeadChips (Illumina) according to the manufacturer's protocol. Arrays were scanned on Iscan (Illumina).


title: Cofactors of LIM domain (CLIM) proteins modulate Wnt signaling and regulate corneal epithelial stem cell maintenance

status: Public on Apr 28 2016

city: Irvine

first: Bogi

last: Andersen

state: CA

address: 839 Health Sciences Dr.

institute: University of California, Irvine

summary: Cofactors of LIM domain proteins (CLIM1 and CLIM2) are widely expressed transcriptional cofactors that are recruited to gene regulatory regions by DNA-binding proteins, including LIM domain transcription factors. In the cornea, epithelial specific expression of a dominant negative (DN) CLIM under the Keratin 14 (K14) promoter causes blistering, inflammation, epithelial hyperplasia and neovascularization, followed by epithelial thinning and subsequent epidermal-like differentiation of the cornea epithelium. This phenotype resembles aspects of limbal stem cell deficiency, suggesting that CLIM proteins may be involved in regulating cornea stem cell maintenance. Consistent with this notion, the K14-DN-Clim cornea epithelium has fewer progenitor cells, and altered proliferation dynamics during epithelial development. Differentially regulated genes in DN-CLIM corneas include those in pathways crucial for stem cell maintenance and regulation of proliferation. In vivo ChIP-Seq experiments in the cornea epithelium show that CLIM associates with DNA regulatory elements containing binding sites for HLH and other non-LIM homeodomain factors, and that many genes that are highly expressed in the limbal epithelium, as well as genes with known roles in stem cell maintenance, are directly regulated by CLIM cofactors. DN-CLIM decreases the expression of Wnt inhibitors, including the direct target Wnt5a, causing increased Wnt signaling in the limbal region of DN-CLIM corneas. Together our results indicate that CLIMs regulate cornea stem cell maintenance by controlling Wnt activity and suggest the possibility that this pathway may be altered in limbal stem cell deficiency.

overall_design:
Postnatal day 3 (P3) littermate WT and DN-Clim whole corneas were used for Gene expression analysis (Affymetrix Mouse Gene 1.0 ST Arrays). n= 3 WT and 3 DN-Clim

This submission represents transcriptome component of study.

first: Denise

last: Stephens


title: Genome-wide DNA methylation analysis of WERI-Rb-1 (retinal 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 DNA methylation patterns following infection of the parasite Toxoplasma gondii in a clinically relevant retinal cell line over a time course of 2 hours, 6 hours and 24 hours. Parasites were washed off after 2 hours to ensure that methylation changes are truly reflective of an on-going infection, and not on-going parasite invasion.

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

last: Anderson

first: Jenefer

last: Blackwell

first: Sarra

middle: E

last: Jamieson


title: Identification of aging-associated gene expression signatures that precede intestinal tumorigenesis [mouse]

city: Kyoto

first: Yoshihisa

last: Okuchi

address: Yoshida Konoe-cho, Sakyo-ku

institute: Kyoto university

summary: Aging-associated gene expression alterations have been implicated in various cancers including colorectal cancer. We examined aging-associated gene expression signatures that precede intestinal tumorigenesis by using the expression level of fluorescent proteins (FPs) as a biomarker of a certain fraction of cells that acquire altered gene expression signatures during aging.

overall_design: We analyzed normal intestinal epithelial epithelial cells with high FP expression (n = 4), normal intestinal epithelial cells with low FP expression (n = 6), and intestinal adenomas (n = 3) from Apc mutant mice crossed with trangenic mice expressing FPs using the Affymetrix Mouse Gene 1.0 ST platform. Array data was processed by Affymetrix GeneChip Command Console, Expression Console, and Transcriptome Analysis Console softwar.

first: Y

first: M

last: Imajo

last: Matsuda


title: Microarray data of mouse primary E2A-PBX1 leukemia and preleukemia cells

city: Stanford

first: Jesus

last: Duque-Afonso

address: 265 Campus Drive

department: Pathology

institute: Stanford University

summary:
Microarray data of mouse primary E2A-PBX1 leukemias and preleukemia cells were compared to wild-type B-cell progenitor cells
Aberrant activation of signaling pathways has been linked to leukemogenesis, however, little is known about cell signaling perturbations induced by fusion transcription factors. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the chimeric fusion protein E2A-PBX1, which is present in 5-7% of pediatric and 50% of pre-B-cell receptor (preBCR+) ALL.  We describe here signaling network remodeling by E2A-PBX1 in pre-B-ALL, which results in hyperactivation of PLCγ2.  Depletion of PLCγ2 reduced proliferation of mouse and human ALLs, including E2A-PBX1 leukemias, and increased disease-free survival after secondary transplantation.  E2A-PBX1 binds and activates the transcription of its target genes ZAP70, SYK and LCK, which encode kinases upstream of PLCγ2.  Efficient shRNA-mediated depletion of the respective upstream kinases decreased cell proliferation and phosphorylated levels of PLCγ2 (pPLCγ2).  Pairwise compound knockdown of ZAP70, SYK or LCK showed additive effects on cell growth inhibition, providing a rationale for combination therapy.  Inhibition of SYK, LCK and SFK with small molecule inhibitors, including dasatinib, was highly effective in reducing pPLCγ2 and inhibiting proliferation of preBCR+ leukemias in vitro and in vivo.  Combination small molecule inhibition of SYK, LCK and SFK showed promising preclinical efficacy for preBCR+/E2A-PBX1+ leukemias.  These studies demonstrate that E2A-PBX1 induces signaling pathway perturbations upstream of PLCγ2, which render leukemias amenable to targeted therapeutic inhibition.

overall_design: We analyzed bone marrow cells from 18 mouse E2A-PBX1 leukemia mice, from 3 healthy preleukemic mice and 9 from wild-type mice using the Affymetrix Mouse Gene 1.0 ST platform.

first: Chiou-Hong

last: Lin

last: Wei

first: Jue

last: Feng

first: Kyuho

last: Han

first: Jason

last: Kurzer

first: Corina

last: Buechele

first: Stephen

last: Wong

last: Bassik

last: Cleary


title: Tissue memory of DNA methylation in iPSC of diverse somatic cells

city: Guangzhou

first: Wenyin

last: HE

address: No.63, Duobao road

institute: The third affiliated hospital of Guangzhou medical university

summary: Several studies have discussed the possibility that donor cell type may influence the epigenetics and differentiation potential of iPSCs, but it remains unclear whether iPS cells derived from different tissue sources reserve their epigenetic memory. Here, we clarify that iPSCs obtained from different tissues exhibit specific epigenetic patterns. We determined the DNA methylation profiles of 12 human cell lines, including 3 adult fibroblast cell-derived iPSC lines, 2 peripheral blood-derived mononuclear cell(PBMC)-derived iPSC lines, 2 amniotic cell-derived iPSC lines and the 5 corresponding parent cell lines. We found that the catalog of tissue-specific DNA methylation was preserved in the iPSC line as epigenetic memory during reprogramming.

overall_design: 12 human cell lines, including 2 adult fibroblast cell-derived iPSC lines, 3 peripheral blood-derived mononuclear cell(PBMC)-derived iPSC lines, 2 amniotic cell-derived iPSC lines and the 5 corresponding parental cell lines

first: Di

last: Fan

last: He

first: Xiaohua

last: Niu

first: Xiaofang

last: Sun


title: Expression data from human patients with slow or rapid Parkinson's Disease progression

status: Public on Apr 25 2016

city: Göttingen

first: Raquel

last: Pinho

address: Waldweg 33

institute: Universität Medizin Göttingen

summary:
Parkinson’s Disease is a multi-system, disabling progressive neurodegenerative condition. Clinical progression is highly heterogeneous and, thus far, there are not available biomarkers to accurately predict the rate of disease progression. Thus, identifying molecular signatures that allow discriminating between different progression rates might significantly assist the therapeutic strategy, and enable improved outcomes in clinical trials.
We performed an exploratory cross-sectional study aimed at determining whether gene expression differences in peripheral blood may be used to discriminate between patients with slow or rapid Parkinson’s disease progression

overall_design:
Based on distinct disease stages and rates of motor disease progression, 70 Parkinson's Disease patients were clinically evaluated and divided into the two groups: slow (n=35) or rapid (n=35) progression. RNA was extracted from whole blood samples of these patients. RNA quality was assessed using RIN in the two groups of patients, which displayed mean RIN values of 7.14 (rapid progressors) and 7.02 (slow progressors). From the 70 RNA samples, 3 had RIN<6 and were not included in subsequent analysis (this corresponded to 1 rapid and 2 slow progressors samples). Expression analysis included 67 array samples (34 rapid and 33 slow progressors).. Gene expression profiling was performed using RNA expression data generated by genome array plates (Affymetrix Human Genome U219 platform, HG-U219).
Patients Classification: Patients Classification: Patients were consecutively recruited from the movement disorders outpatient clinic of the Lisbon University Hospital. Neurologists with expertise in movement disorders interviewed and examined all cases. Patients were divided into two distinct groups with “Slow” or “Fast” progression, depending on the absence or presence of postural instability, respectively. Postural instability was defined by item 3.12 of the MDS-UPDRS, part III. Slow progression if scored 0 (no postural instability) and rapid progression if scored ≥ 1.
Sample Collection: Venous blood from Parkinson's Disease patients was collected in PAXgene tubes

first: Leonor

last: Guedes

first: Lilach

last: Soreq

first: Patrícia

last: Lobo

first: Tiago

last: Mestre

first: Miguel

last: Coelho

first: Mário

last: Rosa

first: Nilza

last: Gonçalves

first: Pauline

last: Wales

last: Mendes

first: Ellen

last: Gerhardt

first: Christiane

last: Fahlbusch

first: Vicenzo

last: Bonifati

first: Michael

last: Bonin

first: Gabriel

last: Miltenberger-Miltényi

first: Fran

last: Borovecki

first: Hermona

first: Joaquim

middle: J

last: Ferreira

last: Outeiro


title: RNA-Seq: assessment of transcript level analysis tools [array]

status: Public on Apr 26 2016

city: Rehovot

first: Gilgi

last: Friedlander

address: Hertzel st

institute: Weizmann Institute of Science

summary:
This study uses spiked-in transcript in order to compare various bioinformatics approaches and tools to assemble, quantify abundance and detect differentially expressed transcripts using RNA-Seq data. Mouse total RNA seq was extracted from embryonic stem cells (ES) before (designated as day 0) and four days after the addition of retinoic acid. 48 spikes were made in vitro from plasmid constructs and added to the total RNA in different concentrations (each mix has a set of different spike concentrations, see paper's method). We found that detection of differential expression at the gene level is acceptable, yet on the transcript-isofom level all tools tested were lacking accuracy and precision.
This set of microarrays was performed for the purpose of selecting unexpressed loci, to which spikes can be added

overall_design: Microarray of mouse embryonic bodies in response to Retinoic acid.  Microarrays were performed before Retinoic addition, and after 3 and 4 days.

first: Dena

last: Leshkowitz

first: Ester

last: Feldmesser

first: Ghil

last: Jona

first: Elena

last: Ainbinder

first: Yisrael

last: Parmet

first: Shirley

last: Horn-Saban


title: Pax6 occupancy and expression profiling of wild type and Pax6 null neural progenitors

first: Sudhir

last: Thakurela

address: 7 Divinity Avenue

institute: HSCRB

type: Genome binding/occupancy profiling by genome tiling array

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

overall_design: Refer to individual Series


title: The role of subclonal population of cells on tumor growth

city: Bethesda

first: Jennifer

last: Barb

state: MD

address: 12 South Drive Bldg 12A Room 2001

department: DCB

institute: NIH

summary:
In this study we activated subclonal differentiation in pancreatic adenocarcinoma cells to study the role of differentiated cells on tumor growth.
Mesenchymal pancreatic adenocarcinoma (MiaPaCa) cells differentiated into adipose and endothelial cells to assess the tumor initiation potential of the differentiated cells and molecular changes associated with cell differentiation. Epithelial (TC-2742-2) cells expressed with Ebf2 were analyzed for its tumorigenic potential and molecular changes associated with Ebf2 expression.

overall_design: MiaPaCa: Control cells were compared with differentiated Adipose and Endothelial cells. TC-2742-2: Control cells were compared with Ebf2 expressed cells

first: Sheelu

last: Varghese