title: miRNA Expression data from human osteosarcoma (OS)

status: Public on Jul 01 2015

city: Yufu

first: Masanori

last: Kawano

address: 1-1 Idaigaoka, Hasama-machi

institute: Oita University

summary:
To explore possible oncogenic factors in OS, we used a microarray-based approach to profile changes in the expression of miRNAs in five OS cell lines and human mesenchymal stem cells (hMSCs).
We used a microarray-based approach to profile in the miRNA expression of OS

overall_design: Human OS cell lines were analyzed with genome-wide expression arrays.

first: Kazuhiro

last: Tanaka


title: Effect of type 2 diabetes on transcriptional signatures during exercise and recovery

status: Public on Jul 03 2015

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum Muenchen

summary: We performed gene expression microarray analysis of skeletal muscle biopsies from normal glucose tolerant subjects and type 2 diabetes subjects obtained during a 60 min bicycle ergometer exercise and the 180 min of recovery phase

overall_design: We analysed skeletal mucle biopsies from patients with T2D and from control subjects (n=7 each) at three time points during exercise and recovery

first: Jakob

last: Hansen

first: Martin

last: Irmler

first: Miriam

last: Hoene

first: Mika

last: Scheler

last: Hrabé de Angelis

first: Hans

middle: U

last: Häring

first: Bente

middle: K

last: Pedersen

first: Rainer

last: Lehmann

first: Peter

last: Plomgaard

first: Cora

last: Weigert


title: Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis

status: Public on Jul 28 2015

city: Nicosia

first: Panagiotis

last: Papageorgis

address: 75, Kallipoleos avenue

department: Biological Sciences

country: Cyprus

institute: University of Cyprus

summary:
IL13Rα2 overexpression promotes metastasis of basal-like breast cancers
IL13Rα2 depletion in highly metastatic breast cancer cells suppresses lung metastases formation by upregulating TP63 and decreasing their migratory potential

overall_design: MCF10CA1a (MIV) cells expressing the luciferase gene (MIV-Luc), were stably transduced with lentiviral constructs expressing either scrambled shRNA or shRNA against IL13Rα2. The two cell lines were then either mock treated  or treated with 20ng/ml IL13 for 16h followed by RNA isolation. Gene expression analysis was performed using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool.

first: Alexandros

last: Tzatsos

first: Nico

last: Ruf

first: Sam

last: Thiagalingam

first: Andreas

last: Constantinou


title: Integration analysis of three omics data using penalized regression methods: An application to bladder cancer (expression)

status: Public on Aug 04 2015

city: Madrid

first: Nuria

last: Malats

state: Madrid

address: C/ Melchor Fernández Almagro 3

country: Spain

institute: CNIO

summary: Omics data integration is becoming necessary to investigate the still unknown genomic mechanisms of complex diseases. During the integration process, many challenges arise such as data heterogeneity, the smaller number of individuals in comparison to the number of parameters, multicollinearity, and interpretation and validation of results due to their complexity and lack of knowledge about biological mechanisms. To overcome some of these issues, innovative statistical approaches are being developed. In this work, we applied penalized regression methods (LASSO and ENET) to explore relationships between common genetic variants, DNA methylation and gene expression measured in bladder tumor samples and have proposed a permutation-based method to concomitantly assess significance and correct by multiple testing with the MaxT algorithm. The overall analysis flow consisted of three steps: (1) SNPs/CpGs were selected per each gene probe within 1Mb window upstream and downstream the gene; (2) LASSO and ENET were applied to assess the association between each expression probe and the selected SNPs/CpGs in three multivariable models (SNP, CPG, and Global models, the latter integrating SNPs and CPGs); and (3) the significance of each model was assessed using the permutation-based MaxT method. We identified 48 genes whom expression levels were associated with both SNPs and GPGs. Importantly, we replicated results for 36 (75%) of them in an independent data set (TCGA). We checked the performance of the proposed method with a simulation study and further supported our results with a biological interpretation based on an enrichment analysis. The approach we propose allows reducing computational time and is flexibly and easy to implement when analyzing several omics data. Our results highlight the importance of integrating omics data by applying appropriate statistical strategies to discover new insights into the complexity of disease genetic mechanisms.

overall_design: Gene expression data were obtained from 44 tumor samples using the Affymetrix DNA Microarray Human Gene 1.0 ST Array with 32,321 probes.

first: Silvia

last: Pineda

first: Francisco

middle: X

last: Real

first: Manolis

last: Kogevinas

first: Alfredo

last: Carrato

first: Stephen

middle: J

last: Chanock

first: Núria

first: Kristel

last: Van Steen


title: MEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS/MAPK Pathway Activation in Squamous Cell Carcinoma (SCC)

status: Public on Aug 05 2015

city: Singapore

first: Chong-Lei

last: Bi

address: #12-02, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive

country: Singapore

institute: Cancer Science Institute Singapore

summary:
Genomic analyses of SCC have yet to yield significant strategies against pathway activation to improve treatment. Platinum-based chemotherapy remains the mainstay of treatment for SCC of different histotypes either as a single agent or alongside other chemotherapeutic drugs or radiotherapy; however, resistance inevitably emerges, which limits the duration of treatment response.
To elucidate mechanisms that mediate resistance to cisplatin, we compared drug-induced perturbations to gene expression between cisplatin-sensitive and -resistant SCC cells.

overall_design: Cisplatin-sensitive and -resistant SCC cells were identified through MTS assay. Gene expression profiling (Affymetrix GeneChip 1.0ST) was performed to identify putative genes and cellular pathways that may be associated with cellular response to cisplatin.

first: Chonglei

first: Li

middle: R

last: Kong


title: Integration analysis of three omics data using penalized regression methods: An application to bladder cancer

type:
Expression profiling by array
Methylation profiling by array

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

overall_design: Refer to individual Series


title: Whole genome expression profiling and analysis on high-charge and energy particle irradiated cells

status: Public on Jul 07 2015

city: Atlanta

first: Zhentian

last: Li

state: GA

address: 1510 Cliton Rd, RRC 4172

country: USA

institute: Emory University

summary: In an attempt to gain insight into the mechanism whereby irradiated cells influence the outcome of DSB repair in their non-irradiated neighbors, we performed whole genome expression profiling.

overall_design: Total of 9 samples are analyzed, including 0, 0.3 and 1.0 Gy dose groups, each with 3 biological replicates.

first: Gregory

last: Doho

first: Xuan

last: Zheng

first: Kishore

last: Jella

first: Shuyi

first: Ya

last: Wang

first: William

middle: S

last: Dynan


title: NF-κB activation impairs somatic cell reprogramming in ageing [MSCs]

city: Oviedo

first: Jose

last: Freije

state: Asturias

address: C/ Fernando Bongera s/n

department: Bioquimica y Biologia Molecular

institute: Universidad de Oviedo

summary:
Transcriptional profiling of human control and Néstor-Guillermo Progeria Syndrome (NGPS) mesenchymal stem cells (MSCs).

Somatic cell reprogramming involves rejuvenation of adult cells and relies on the ability to erase age-associated molecular marks. Accordingly, reprogramming efficiency declines with ageing, and age-associated features such as genetic instability, cell senescence or telomere shortening negatively affect this process. However, the regulatory mechanisms that constitute age-associated barriers for cell reprogramming remain largely unknown. Here, by using cells from patients with premature ageing, we demonstrate that NF-κB activation is a critical barrier for the generation of induced pluripotent stem cells (iPSCs) in ageing. We show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs generation of iPSCs by eliciting reprogramming repressors DOT1L and YY1, reinforcing cell senescence signals and down-regulating pluripotency genes. We also show that genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo Progeria Syndrome (NGPS) and Hutchinson-Gilford Progeria Syndrome (HGPS) patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo ameliorates the accelerated ageing phenotype and extends lifespan in a progeroid animal model. Collectively, our results provide evidence for a novel role of NF-κB in the control of cell fate transitions and reinforce the interest of studying age-associated molecular impairments to implement cell reprogramming methodologies, and to identify new targets of rejuvenation strategies.

overall_design: Control and NGPS MSCs were differentiated into bone in the presence or absence of sodium salicylate. Total RNA was extracted and global gene expression was analyzed.

first: Fernando

middle: G

last: Osorio

first: Clara

last: Soria-Valles

middle: M

first: Carlos

last: Lopez-Otin


title: Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

city: Seattle

first: James

middle: William

last: MacDonald

state: WA

address: 4225 Roosevelt Way NE

department: Environmental and Occupational Health Sciences

institute: University of Washington

summary: Silymarin (SM) is a popular botanical medicine with purported liver protective effects. SM displays multiple effects in animal models and in cell culture including prevention of liver disease, reduction of inflammation, oxidative stress, and proliferation. Despite a plethora of data indicating that SM impinges on multiple cellular signaling pathways important in inflammation and disease, no unifying mechanisms have been forwarded. To define how SM elicits so many biological effects, the current study presents the first comprehensive transcriptional profiling study of human hepatoma cells treated with SM. The intention of the study was to focus on the early transcriptional events that are associated with SM-induced inhibition of proliferation and inflammation. Collectively, the data demonstrate that SM causes a rapid transcriptional reprogramming of cells that initially manifests as energy stress and slowing of cellular metabolism, leading to inhibition of cell growth and inflammation.

overall_design: The effects of silymarin on liver hepatoma Huh7.5.1 cells were detected using a time course approach.

first: Erica

last: Lovelace

first: Jessica

last: Wagoner

middle: W

first: Theo

last: Bammler

first: Richard

middle: D

last: Beyer

first: Federico

last: Farin

first: Steven

last: Polyak


title: Alterations in serum microRNA in humans with alcohol use disorders impact cell proliferation and cell death pathways and predict structural and functional changes in brain [miRNA 3.0]

status: Public on Jul 31 2015

city: Syracuse

first: Frank

middle: A

last: Middleton

state: NY

address: 505 Irving Avenue

department: Neuroscience and Physiology

institute: SUNY Upstate Medical Univ

summary: We performed a global analysis of extracellular miRNAs in the serum of human subjects diagnosed with Alcohol Use Disorder (AUD) to identify robust biomarkers of early brain damage or dysfunction. This was performed in a set of 20 AUD subjects and 10 age-matched controls. They were subjected to comprehensive medical, neuropsychological and neuroimaging tests, followed by comparison of miRNA levels found in peripheral blood serum. The levels of miRNAs were quantified using two independent high-throughput methods: Affymetrix microarray and Illumina next-generation RNA-sequencing. Cross-species validation was performed using rat drinking models and mouse neural stem cell culture models, with tissue specificity of the serum miRNAs examined using additional RNA-sequencing of serum and body tissues in untreated rats. This data series includes the human miRNA 3.0 GeneChip data only but is part of a larger superseries.

overall_design: A total of 30 miRNA 3.0 GeneChips and 27 RNA-sequencing libraries were run on the same RNA samples from human subjects.

first: Cherry

last: Ignacio

last: Hicks

first: Patrick

last: Burke

first: Lambert

last: Lewis

first: Zsuzsa

last: Szombathyne-Meszaros


title: Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition

city: Rome

first: Giulia

last: Fontemaggi

address: Via Elio Chianesi, 53

country: Italy

institute: Italian National Cancer Institute Regina Elena

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


title: Affymetrix SNP array data for rhabdomyosarcoma samples

status: Public on Jun 30 2015

city: Tokyo

first: Masafumi

last: Seki

state: Tokyo

address: 7-3-1, Hongo, Bunkyo-ku

department: Department of Pediatrics

country: Japan

institute: The University of Tokyo

summary:
Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from fresh frozen tissues.
To obtain a profile of copy number alterations in RMS, we studied 65 samples in 60 RMS cases. Other data of 38 samples are deposited in GSE41263:
GSM1528059
GSM1528057
GSM1528061
GSM1528058
GSM1528054
GSM1528060
GSM1012723
GSM1012722
GSM1012746
GSM1528055
GSM1528056
GSM1530028
GSM1012751
GSM1012724
GSM1012726
GSM1012747
GSM1012725
GSM1012716
GSM1012735
GSM1012713
GSM1012736
GSM1012737
GSM1012738
GSM1012730
GSM1012739
GSM1012740
GSM1012750
GSM1012717
GSM1012718
GSM1012719
GSM1012741
GSM1012732
GSM1012715
GSM1012720
GSM1012742
GSM1012721
GSM1012743
GSM1012744

overall_design: Copy number analysis of Affymetrix 250K or Cytoscan_HD SNP arrays was performed for 27 rhabdomyosarcoma samples.

first: Riki

last: Nishimura

first: Kenichi

last: Yoshida

first: Yusuke

last: Sato

first: Seishi

last: Ogawa

first: Junko

last: Takita


title: Inefficient translation of nsrR constrains behavior of the NsrR regulon in Escherichia coli

status: Public on Jun 27 2015

city: Richardson

first: Stephen

last: Spiro

state: TX

address: 800 West Campbell Road

department: Molecular and Cell Biology

institute: University of Texas at Dallas

summary:
Investigation of whole genome gene expression level changes in a Escherichia coli MG1655 K-12 nsrR with AUG start codon compared to the wild type nsrR (with a GUG start codon) and to the control lacking the nsrR gene.
Conversion of the nsrR start codon from the wild type GUG to AUG increased the efficiency of translation and had measurable effects on the expression patterns of some NsrR regulated genes.

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

overall_design: A nine chip study using total RNA recovered from three separate cultures of Escherichia coli MG1655 K-12 AUGnsrR, three separate cultures of the WT nsrR (GUGnsrR) and three separate cultures of nsrR deletion strain. Each chip measures the expression level of 4,254 genes from Escherichia coli MG1655 K-12 with eight 60-mer probes per gene, with 2-fold technical redundancy.

first: Shivani

last: Chhabra


title: Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes [expression]

city: Stanford

first: Nidhi

last: Bhutani

state: California

address: 300 Pasteur Drive, R164 Edwards Bldg

department: Orthopaedic Surgery

institute: Stanford University

summary:
Examination of the genome-wide distribution of 5hmC in osteoarthritic chondrocytes compared to normal chondrocytes in order to elucidate the effect on OA-specific gene expression.
5hmC-sequencing was performed and data was compared with microarray gene expression data to identify genes with differential expression between normal and OA chondrocytes that are potentially under epigenetic regulation.

overall_design:
Gene expression patterns were examined by comparing the 5 normal samples to the 2 OA samples to assess the changing expression profiles between normal and OA chondrocytes.
We analyzed the changes in gene expression in OA; genes with a fold-change ≥ or ≤1.5 or 1.2, with a difference in intensity of >100 and within the lower 90% confidence bound, were selected.

first: Sarah

middle: E

last: Taylor

first: Ye

middle: H

last: Li


status: Public on Jun 12 2015

city: Goettingen

first: Jan

last: Menke

address: Robert-Koch-Strasse 40

institute: University Hospital Goettingen

type: Genome variation profiling by genome tiling array

summary: Affymetrix SNP array data for embryonal rhabdomyosarcoma in a patient with Costello syndrome

overall_design: Affymetrix SNP array was performed according to the manufacturer's directions on DNA extracted from a fresh-frozen tumor sample.

first: Silke

last: Pauli


title: Whole genome analysis of cells permissive for late gene expression of HPV-16

city: Lund

first: Stefan

last: Schwartz

address: BMC B13, Kilnikagatan 26

country: Sweden

institute: Lund university

summary:
Aim was to identify cellular factors that regulate HPV-16 late gene expression at the level of RNA processing
Cervical cancer cells permissive for HPV16 late gene expression were identified and characterized. These cells either contained a novel spliced variant of the L1 mRNAs that bypassed the suppressed HPV16 late, 5’-splice site SD3632, produced elevated levels of RNA-binding proteins SRSF1 (ASF/SF2), SRSF9 (SRp30c) and HuR that are known to regulate HPV16 late gene expression, or were shown by a gene expression array analysis to overexpress the RALYL RNA-binding protein of the hnRNP C-family. Overexpression of RALYL, or RALY and hnRNP C1 that are two other members of the hnRNP C-family, induced HPV16 late gene expression from HPV16 subgenomic plasmids and from episomal forms of the full-length HPV16 genome. Induction of HPV16 late gene expression by the hnRNP C-proteins was dependent on the HPV16 early untranslated region to which these proteins also were shown to bind in vitro, and in living cells. Our experiments revealed that hnRNP C proteins that interacted with the HPV16 early untranslated region reached out to the splicing silencer complex at HPV16 SD3632 and derepressed this splice site, thereby activating production of HPV16 spliced late L1 mRNAs. In conclusion, hnRNP C- proteins bind to the HPV16 early untranslated region and control of HPV16 late L1 mRNA splicing.

overall_design: Total cellular RNA was extracted from stable cell lines.  Samples were prepared in triplicates. C33ARSVNeo served as control cell line.

first: Soniya

last: Dhanjal

first: Anki

last: Mossberg


title: Effect of knock down of LASP-1 on luminal breast cancer cells (MCF7)

status: Public on Jun 26 2015

city: Nashville

first: Dayanidhi

last: Raman

state: TN

address: PRB436, 23rd Ave S @ Pierce

department: Cancer Biology

institute: Vanderbilt Universirty

summary:
Nuclear LASP-1 has a direct correlation with the overall survival of breast cancer patients. Gene expression analysis of MCF7 human breast cancer cells cultured in 3D-Matrigel was performed.
Up regulation of cell junction proteins, extracellular matrix proteins and down regulation of MMP 9 and 2  were observed. This corroborates well with the involvement of LASP-1 in cell migration and chemotaxis.

overall_design: Non-silencing (control) and LASP-1 knock down MCF7 cells were cultured on 3D-Matrigel, total RNA was extracted and anlyzed - 4 biological replicates each. The first biological replicate was done as a pilot. Biological replicates 2-4 were run as a second set after pilot.

first: Nichole

last: Duvall-Noelle


title: A novel small-molecule inhibitor of STAT5A/STAT5B with therapeutic potential for prostate cancer and CML

city: PHILADELPHIA

first: Adam

last: Ertel

state: PA

address: 233 S 10TH ST

institute: Thomas Jefferson University

summary: We assessed the gene expression profiles induced by both genetic and pharmacological knockdown of Stat5a/b in CML cells. Stat5 was suppressed in K562 cells by lentiviral expression of Stat5 shRNA vs. scramble control for 6 days or by treatment of the cells with IST5-002 (5 µM) for 48 h.

overall_design: K562 cells were treated with IST5-002 (5 µM) or vehicle (DMSO) for 48 h.  For Stat5 knockdown, K562 cells were infected with Stat5-shRNA lentivirus or scramble-shRNA lentivirus (as control) for 48 h followed by puromycin (2ug/ml) selection for 6 days to enrich for cells expressing Stat5 or scramble shRNA. Each group (vehicle control, IST5-002, scramble-shRNA control and Stat5-shRNA) was prepared in triplicate, and RNA samples from each group were not pooled.

first: Marja

middle: T

last: Nevalainen

first: Bruno

last: Calabretta

first: Lei

last: Gu

first: Samanta

last: Mariani

first: Paolo

last: Fortina


title: IL-2-dependent gene expression by human regulatory T cells

status: Public on Jul 09 2015

city: Miami

first: Thomas

last: Malek

state: FL

address: 1600 NW 10th Avenue

department: Microbiology/Immunology

institute: University of Miami

summary:
This study determined the genes that are differetially expressed when regulatory T cells were stimulated in vitro with IL-2
388 Affymetrix targets were found to be up or down regulated in human regulatory T cells by IL-2 by two-fold or more. Gene enrichment analyss  identified that IL-2 functions to regulate gene expression for mRNAs important for immune system processes, cell growth, cell death,  inflammatory response, cell migration, and the Jak/Stat pathway, among others. A subset of these differentially expressed genes were distinctively expressed between individual subjects.

overall_design: Human regulatory T cells (Tregs)  cells were FACS purified based on expression of CD4+ CD127-lo CD25-HI. These cells were cultured for 24 hr in media with or without IL-2 (100 u/ml). The cells were harvested, total RNA was prepared and processed to probe Affymetrix human Gene ST1.0 arrays.

first: Alberto

last: Pugliese


title: Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition [mRNA]

first: Giulia

last: Fontemaggi

summary:
Treatment of leukemia cells with 1,25-dihydroxyvitamin D3 may overcome their differentiation block and lead to the transition from myeloblasts to monocytes. To identify microRNA-mRNA networks relevant for myeloid differentiation, we profiled the expression of mRNAs and microRNAs associated to the low- and high-density ribosomal fractions in leukemic cells and in their differentiated monocytic counterpart. Intersection between mRNAs shifted across the fractions after treatment with putative target genes of modulated microRNAs showed a series of molecular networks relevant for the monocyte cell fate determination
In this dataset, we include the expression data obtained from the profiling of ribosome/polysome-associated miRNAs and mRNAs in proliferating HL60 cells and in cells induced to differentiate by 1,25-dihydroxyvitamin D3 (VitD3) treatment

overall_design: 18 total samples, 9 from control proliferating HL60 cells and 9 from VitD3-treated HL60 cells

first: Francesco

last: Fazi

first: Giovanni

last: Blandino


title: Expression data from patients of idiopathic portal hypertension

status: Public on Jun 06 2015

city: Osaka

first: Kohei

last: Kotani

address: 1-4-3, Asahimachi, Abeno-ku

institute: Graduate School of Medicine, Osaka City University

summary:
Idiopathic portal hypertension (IPH) is characterized by portal hypertension due to obstruction or stenosis of the intrahepatic peripheral portal branches. Researchers have suggested that IPH may be attributed to intrahepatic peripheral portal vein thrombosis, splenic factors, abnormal autoimmunity, and related factors, however, the etiology of IPH remains unclear.
We used microarrays to identify the functions of genes expressed in blood samples from patients with IPH.

overall_design: In order to examine the specific expression of genes in patients with IPH, we analyzed blood samples from three patients with IPH and three healthy volunteers as control using DNA microarrays.

first: Susumu

last: Shiomi


title: Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma (expression)

city: New York

first: Emily

last: Bernstein

address: 1470 Madison Avenue, 6th floor Rm 302

department: Oncological Sciences

institute: Mount Sinai School of Medicine

summary: Here we report a novel role for H2A.Z.2 (H2AFV) as a mediator of cell proliferation and sensitivity to targeted therapies in malignant melanoma. While both H2A.Z.1 and H2A.Z.2 are highly expressed in metastatic melanoma and correlate with decreased patient survival, only H2A.Z.2 deficiency results in impaired cellular proliferation of melanoma cells, which occurs via a G1/S arrest. Integrated gene expression and ChIP-seq analyses revealed that H2A.Z.2 positively regulates E2F target genes, and that such genes acquire a distinct H2A.Z occupancy signature over the promoter and gene body in metastatic melanoma cells. We further identified the BET family member BRD2 as an H2A.Z-interacting protein in melanoma cells, and demonstrate that H2A.Z.2 silencing cooperates with BET inhibition to induce cell death.

overall_design: Total RNA samples from SKmel147 melanoma cell line. Transcript levels were analyzed after control or H2AZ variant RNA interference.

first: Chiara

last: Vardabasso

first: Alexandre

last: Gaspar-Maia

first: David

last: Garcia-Valle

first: Dan

last: Hasson

first: Tobias

last: Straub

first: Sandra

last: Hake


title: Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma

type: Genome binding/occupancy profiling by high throughput sequencing

type: Expression profiling by high throughput sequencing


title: Time series expression data  following miR-9 inhibition

city: CANBERRA

first: Jiayu

last: Wen

state: ACT

address: 133 Garran Rd

department: Department of Genome Science

country: Australia

institute: John Curtin School of Medical Research, The Australian National University

summary: A high-resolution time series study of transcriptome dynamics following antimiR--mediated inhibition of miR-9  in a Hodgkin lymphoma cell-line revealed both general and miR-9 specific aspects of the miRNA--mediated post--transcriptional dynamic response.MiR-9 inhibition induced a multiphasic gene response, with an initial direct response at approximately 4 hours and multiple later responses which showed transcription factor enrichments indicative of indirect causally downstream responses, and an overall shift of gene product function from predominantly mRNA processing at early time points to translation at later time points.

overall_design: The full time course used was: 2,4,6,8,10,12,14,16,18,20,22,26,32,40,56,80,112 hours post-miR-9 inhibition. Microarrays were Affymetrix HuGene-10-st-v1.   Each LNA-antimiR treated cell sample was matched with an LNA scramble control at each time point.  This overall time schedule was divided into two independent biological replicates: one covering early time points (2 hours to 20 hours), and another covering later time points (22 hours to 112 hours).

first: Brian

last: Parker


title: Delineation of in vitro chondrogenesis of human synovial stem cells following preconditioning with decellularized matrix

status: Public on Jun 04 2015

city: Morgantown

first: Mary

last: Davis

state: WV

address: 1 Medical Center Drive

institute: West Virginia University Health Sciences Center

summary: As a tissue-specific stem cell for chondrogenesis, synovium-derived stem cells (SDSCs) are a promising cell source for cartilage repair. However, a small biopsy can only provide a limited number of cells. Cell senescence from both in vitro expansion and donor age presents a big challenge for stem cell based cartilage regeneration. Here we found that expansion on decellularized extracellular matrix (dECM) full of three-dimensional nanostructured fibers provided SDSCs with unique surface profiles, low elasticity but large volume as well as fibroblast-like shape. dECM expanded SDSCs yielded large pellets with intensive staining of type II collagen and sulfated GAGs, which was supported by both biochemical data and real-time PCR results. Our results also hint at lower levels of inflammatory genes and how they might be responsible for enhanced chondrogenic differentiation in dECM expanded SDSCs. Despite an increase of type X collagen in chondrogenically induced cells, dECM expanded cells had significantly lower potential for endochondral bone formation. Both Wnt and MAPK signals were actively involved in both expansion and chondrogenic induction of dECM expanded cells. dECM expanded human SDSCs could be a potential cell source for autologous cartilage repair

overall_design: Adult human synovial fibroblasts (4 donors, two male and two female, average 43 years old, all had no known joint disease) were grown for one passage on plastic flasks (P cells) or plastic flasks pre-coated with decellularized extracellular matrix (E cells). Aliquots were centrifuged and pellets cultured for 35 days in serum-free chondrogenic medium (P pellet or E pellet). There are no replicates.

first: Ying

last: Zhang

first: Jingting

last: Li

first: Ming

last: Pei


title: Single transcription factor conversion of human blood fate to NPCs with CNS and PNS developmental capacity

status: Public on Jun 02 2015

city: Hamilton

first: Mickie

last: Bhatia

state: Ontario

address: 1200 Main Street West

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

country: Canada

institute: McMaster University

summary: Direct cell fate conversion allows the generation of somatic cells that are otherwise difficult to obtain directly from patients. The clinical applicability of this approach depends on obtaining an initial source of somatic cells from adult patients that is easy to harvest, store, and manipulate for reprogramming. Here we have generated induced neural progenitor cells (iNPCs) from neonatal as well as peripheral blood from human adults using single factor OCT4 based reprogramming. Unlike fibroblasts that share molecular hallmarks of neural crest, direct OCT4 reprogramming of human blood could be facilitated by SMAD+GSK-3 inhibition to overcome restrictions on neural fate conversion. Blood derived (BD)-iNPCs functionally differentiate in vivo, and respond to guided differentiation in vitro to produce both glia (astrocytes and oligodendrocytes) and multiple neuronal subtypes including dopamine releasing DA neurons (CNS related) and nociceptive neurons (PNS). Furthermore, BD nociceptive neurons phenocopy chemotherapy induced neurotoxicity in a system suitable for high throughput drug screening. Our findings provide an easily accessible approach to generate human NPCs that harbor extensive developmental potential, enabling the study of clinically relevant neural diseases directly from patient cohorts.

overall_design: hFibs served as a comparison point for both Fib_iNPC_Oct4 and Fib_iNPC_Oct4_Inhibitors.  hCB_34pos served as a comparison point for BD_iNPC_Oct4 and BD_iNPC_Oct4_Inhibitors.

first: Jong-Hee

last: Lee

first: Ryan

last: Mitchell

first: Zoya

last: Shapovalova


title: Inhibition of Akt promotes immunologic memory in tumor-infiltrating lymphocytes isolated from patients with melanoma

status: Public on Jun 03 2015

city: Doha

first: Francesco

middle: Maria

last: Marincola

address: Al Nasr Tower, AL Corniche Street, PO Box 26999

country: Qatar

institute: Sidra Medical and Research Center

summary: Adoptive cell immunotherapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) can result in complete regression of advanced melanoma in some patients, but the efficacy of this potentially curative therapy is limited by poor persistence of TIL after adoptive-transfer. Pharmacologic inhibition of the serine/threonine kinase Akt has recently been shown to promote immunologic memory in viral-specific murine models, but whether this approach may enhance features of memory (e.g. long-term persistence) in TIL which are characteristically exhausted and senescent is not established. Here we show that pharmacologic inhibition of Akt enables expansion of TIL with the transcriptional, metabolic and functional properties characteristic of memory T cells. Consequently, Akt inhibition results in enhanced persistence of TIL after adoptive transfer into an immunodeficient animal model and augments antitumor immunity of CD8 T cells in a mouse model of cell-based immunotherapy for melanoma. Pharmacologic inhibition of Akt represents a novel immunometabolomic approach to enhance the persistence of anti-tumor T cells and improve the efficacy of cellbased immunotherapy for metastatic cancer.

overall_design: Human TIL from 3 patients (biological replicates) were cultured independently in triplicate (technical replicates). TIL were stimulated with agonistic CD3 (OKT3) and irradiated allogeneic feeders (200:1 ratio) with high dose IL-2 in the presence (n=12) or absence (n=12) of Akt inhibitor (1uM).


title: Impact of Gene Dosage on Gene Expression, Biological Processes and Survival in Cervical Cancer: a Genome-Wide Follow-Up Study [CytoScanHD_Array]

city: MEXICO CITY

first: INGRID

last: MEDINA MARTINEZ

state: CUAUHTEMOC

address: DR. BALMIS 148

department: MEDICINA GENOMICA

country: Mexico

institute: HOSPITAL GENERAL DE MEXICO OD

summary: The contribution of copy number (CN)-altered genes in cervical carcinogenesis is unknown owing to a lack of correlation with gene expression. We mapped CN-altered genes in 31 cervical cancers (CCs), and investigated the expression of 21,000 genes in 55 CCs using microarrays. Biological processes associated with genes deregulated by gene dosage and the relationship between gene dosage and patient survival were investigated. CN-altered genome (CN-AG) percentages varied widely among tumors from 0% to 32.2% (mean = 8.1 ± 8.9). Tumors were classified as low (mean = 0.5 ± 0.6, n = 11), medium (mean = 5.4 ± 2.4, n = 10), or high (mean = 19.2 ± 6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated by gene dosage; by contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.6% of deregulated genes in whole tumors (r2 = 0.236, p = 0.006; analysis of variance), including those in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This result suggests that the remaining genes are not deregulated directly by gene dosage but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profiles of APC/C-proteasome-dependent proteolysis and glycolysis were associated with poor patient survival, although only the first 2 correlations were statistically significant (p < 0.05, log-rank test). The data suggest that inhibitors of APC/C-dependent proteasome proteolysis and glycolysis may be useful treatments in these patients.

overall_design:
In this study 31 tumors and 25 reference controls were used for analysis of copy number alterations using the 500K microarray. The results obtained from 500K array analysis were validated in 15 of the 31 tumors with a higher density microarray (Cytoscan HD). For the analysis of gene expression 55 cervical tumors (27 of them belong to the group of 31 tumors analyzed for copy number) and 17 exocervical controls were used.

Please note that the sample R397 in the CytoScanHD_Array set corresponds to the R392 sample in the other data sets (due to an error in file name).

first: Ingrid

last: Martinez

first: Jaime

last: Berumen


title: Gene expression of human small intestine generated by biopsy specimens

status: Public on Jun 11 2015

city: Bunkyo-ku

first: Kiichiro

last: Tsuchiya

address: 1-5-45 Yushima

institute: Tokyo Medical and Dental University

summary: The entire small intestine was obseved by   balloon endoscopy. Biopsy specimens were taken from jejunum, ileum and colon, respectively.

overall_design: Four crohn disease patients and four nonIBD controls were compared.

first: Ryohei

last: Hayashi

first: Nobukatsu

last: Horita


title: Impact of Gene Dosage on Gene Expression, Biological Processes and Survival in Cervical Cancer: a Genome-Wide Follow-Up Study

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

overall_design: Refer to individual Series


title: Metabolic syndrome exercise training

status: Public on May 31 2015

city: Nijmegen

first: Fleur

last: Poelkens

state: Gelderland

address: PO Box 9101

department: Physiology

country: Netherlands

institute: Radboud University Nijmegen Medical Centre

summary: We assessed vastus lateralis muscle gene expression levels of 6 women with the metabolic syndrome before and after a 6 month exercise training program

overall_design: RNA was isolated from a vastus lateralis muscle biopsy of 12 women with the metabolic syndrome before and after a 6 month guided endurance exercise training program

first: Gerwen

last: Lammers

first: Maria

last: Hopman


title: Expression data from MDA-MB-231 cells treated with vehicle or YW3-56

status: Public on May 21 2015

city: University Park

first: Yanming

last: Wang

state: Pennsylvania

address: 454 North Frear Building

institute: The Penn State University

summary:
PAD4 is overexpressed in many cancer cells. We developed PAD inhibitors that efficiently inhibit the cancer cell growth. One inhibitor YW3-56 could efficently induce cell death of triple negative breast cancer MDA-MB-231 cells.
We used microarray to detail the global gene expression of MDA-MB-231 before and after YW3-56 treatment and identify significant up-regulated or down-regulated genes by YW3-56

overall_design: MDA-MB-231 cells were cultured and treated with vehicle (DMSO) or YW3-56. Cells were washed with PBS and harvested for RNA extraction and hybridization on Affymetrix microarry.

first: Shu

first: Pingxin


title: Effects of Integrating and Non-integrating Reprogramming Methods on Copy Number Variation and Genomic Stability of Human Induced Pluripotent Stem Cells

status: Public on Jun 08 2015

city: Guangzhou

first: Wenyin

last: HE

state: Guangdong

address: No.63, Duobao road

country: China

institute: The third affiliated hospital of Guangzhou medical university

summary: Human-induced pluripotent stem cells (iPSCs) are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC) lines, 6 iPSC lines derived using integrating vectors (“integrating iPSC lines”), 6 iPSC lines derived using non-integrating vectors (“non-integrating iPSC lines”), and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV), loss of heterozygosity (LOH) and mosaicism patterns of integrating and non-integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non-integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA database were highest in integrating iPSC lines. Different SNP calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA-integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high-resolution method to monitor genomic aberrations in iPSCs intended for clinical applications to avoid any negative effects of reprogramming or cell culture.

last: He

first: Xiaofang

last: Sun

first: Yong

last: Fan


title: The Anticancer Mechanism of the Ribonucleotide Reductase Inhibiting Drug COH29 Involves Suppression of DNA Repair

status: Public on May 08 2015

city: Duarte

first: Charles

middle: David

last: Warden

state: CA

address: 1500 East Duarte Rd

department: Department of Molecular and Cellular Biology

institute: City of Hope

summary: Mechanism of Action Study for COH29

overall_design: Compare COH29 treatment in DNA-repair deficient cell line with truncated BRCA1 (HCC1937) versus phenotypically normal cell line with exogenous WT BRCA1 expression (HCC1937+BRCA1)

first: Y

last: Yen

first: B

last: Zhou

first: C


title: Expression data from MCF7 cells treated with Neuregulin (NRG) at different times

city: Salamanca

first: Juan

middle: Carlos

last: Montero

state: Salamanca

address: Campus Miguel de Unamuno

institute: Instituto de Biología Molecular y Celular del Cáncer. CSIC-Universidad de Salamanca.

summary: To gain insights into the mechanism responsible for the protumorigenic actions of NRG we performed gene expression analyses of MCF7 cells treated with soluble NRG for 3, 6, 12 and 24 hours.

overall_design: MCF7 cells were treated with NRG for 0, 3, 6,12, 24 hours, 3 for each condition, prepared from three different experiments

first: Samuel

last: Seoane

middle: C

first: Alberto

last: Ocaña

first: Atanasio

last: Pandiella


title: Global gene expression analysis of fibroblast, dOB, osteoblast, MSC and MSC-OB

city: Kyoto

first: Kenta

last: Yamamoto

address: Kajicho 465

department: Immunology

institute: Kyoto Prefectural University of Medicine

summary:
Comparison of each cell mRNA expression pattern.
We generated osteoblasts like cell by direct reprogramming technique from human fibroblast. To confirm dOB gene expression pattern similarity to osteoblasts, we analyzed and compared the gene expression profiles of the samples by cDNA microarry. These analysis revealed that dOB are similar to osteoblats in comparative level to MSC-OB.

overall_design: 6 samples.

first: Osam

last: Mazda


title: Coordinated epigenetic remodelling occurs during early breast carcinogenesis [Expression profiling]

status: Public on May 09 2015

city: Darlinghurst

first: Warwick

middle: James

last: Locke

state: NSW

address: 384 Victoria St

department: Cancer Deparment

institute: The Garvan Institute of Medical Research

summary: Dysregulation of the epigenome is a common event in malignancy. However, deciphering the earliest cancer associated epigenetic events remains a challenge. Cancer epigenome studies to date have primarily utilised cancer cell lines or clinical samples, where it is difficult to identify the initial epigenetic lesions from those that occur over time. Here, we analysed the epigenome of normal Human Mammary Epithelial Cells (HMEC) and a matched variant cell population (vHMEC) that has escaped senescence and undergone partial carcinogenic transformation. Using this model system we sought to identify the earliest epigenetic changes that potentially occur during carcinogenesis. First we show that the transcriptome of vHMEC resembles that of basal-like breast cancer. Moreover, in vHMEC there is significant deregulation of MYC, p53, EZH2/polycomb, the Aryl Hydrocarbon Receptor (AHR) and miRNAs-143, 145, 199a and 519a at the transcriptional level. Second, we find that vHMEC exhibit genome-wide changes in DNA methylation affecting key cancer-associated pathways. Hypermethylation predominately impacted gene promoters (particularly those targeted by AHR and TP53) and polycomb associated loci, whereas hypomethylation frequently affected enhancers. Next we show that long range epigenetic deregulation occurred in vHMEC involving concordant change in chromatin modification and gene expression across ~0.5-1Mb regions. Finally, we demonstrate that the DNA methylation changes we observe in vHMECs, occur in basal-like breast cancer (notably FOXA1 hypermethylation).. Overall our results suggest that the first steps of carcinogenesis are associated with a co-ordinated deregulation of DNA methylation and chromatin modification spanning a range of genomic loci potentially targeted by key transcription factors and a corresponding deregulation of transcriptional networks.

overall_design: We sought to compare the differences in gene expression in vHMEC when compared to isogenic HMEC cells. Two time points in the vHMEC growth phase were used to assess if continual passage of vHMEC contributed to expression differences. RNA was extracted from a total of 4 HMEC (and matched vHMEC) lines.


title: CHD8 controls progestin-dependent gene expression in T47D cells

status: Public on Jun 01 2015

city: Sevilla

first: Jose

middle: C.

last: Reyes

address: Av. Américo Vespucio

department: Genome biology

institute: CABIMER

summary: CHD8 is an ATPase of the SNF2 family involved in ATP-dependent nucleosome remodeling. Our data indicate that in the presence of progestin (R5020), a progesterone receptor (PR) agonist, CHD8 is recruited to a number of PR enhancers. To correlate CHD8 binding sites with CHD8-regulated gene expression we performed a transcriptomic analysis of T47D-MTVL cells transfected with a control siRNA or a siRNA specifically targeting CHD8 and stimulated during 6h with progestin or vehicle. CHD8-dependent genes presented lower induction of up-regulated genes and lower repression of down-regulated genes, indicating that CHD8 is required for progesterone-dependent regulation of a subset of genes.

overall_design: T47D-MTVL cells were transfected with control siRNA (siCt) or siRNA against CHD8 (siCHD8), subjected to serum deprivation during 48 h and then stimulated with 10 nM R5020 (R5020) or vehicle (EtOH) for 6 h. Three independent samples were taken from each condition: SiCt_EtOH, SiCt_R5020, SiCHD8_EtOH, SiCHD8_R5020.

first: A

last: Subtil-Rodríguez

first: J


title: The cellular origin and malignant transformation of Waldenström's Macroglobulinemia [gene expression]

status: Public on May 05 2015

city: Pamplona

first: Bruno

last: Paiva

address: Av. Pio XII, 55

institute: Clinica Universidad de Navarra

summary: Although information on the molecular pathogenesis of Waldenström’s Macroglobulinemia (WM) has greatly improved in recent years, the exact cellular origin and the mechanisms behind WM transformation from IgM MGUS remain undetermined. Here, we undertook an integrative phenotypic, molecular and genomic approach to study clonal B-cells from newly-diagnosed patients with IgM MGUS (n=22), smoldering (n=17), and symptomatic WM (n=10). Through principal-component-analysis of multidimensional flow cytometry data, we demonstrated overlapping phenotypic profiles between clonal B-cells from IgM MGUS, smoldering and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between FACS-sorted clonal B-cells from the three disease stages. Interestingly, while the transcriptome of the Waldenström’s clone was highly deregulated as compared to CD25-CD22+ normal B-cells, significantly less genes were differentially expressed and specific WM pathways down-regulated while comparing the transcriptome of the Waldenström’s clone vs. its normal phenotypic counterpart: CD25+CD22+dim B-cells. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from  IgM MGUS and smoldering WM vs. symptomatic WM (18% vs. 20% and 73%, respectively; P =.008), suggesting a multistep transformation of clonal B-cells that albeit benign (i.e.: IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström’s clone.

overall_design: Normal bone marrow CD25+ B-cells, Clonal B-Cells from IgM Monoclonal Gammopathy of Undetermined Significance, and Clonal B-Cells from Waldenström's Macroglobulinemia

first: Luis

last: Corchete

first: Maria-Belen

last: Vidriales

first: Ramón

last: García-Sanz

middle: J

last: Perez

first: Maria

middle: L

last: Sánchez

first: Paloma

last: Barcena

first: Cristina

last: Jimenez

last: Sarasquete

first: Maria-Victoria

last: Mateos

first: Enrique

last: Ocio

first: Noemi

last: Puig

first: Fernando

last: Escalante

first: José

last: Hernández

first: Rebeca

last: Cuello

first: Alfonso

last: de Coca

first: Magdalena

last: Sierra

first: Maria-Carmen

last: Montes

first: Tomás

last: González-López

first: Josefina

last: Galende

first: Abelardo

last: Bárez

last: Alonso

first: Emilia

last: Pardal

last: Orfao

first: Norma

last: Gutierrez

first: Jesús

middle: F

last: San Miguel


title: Gene Dosage, Mainly 3q Amplification, Deregulates a Quarter of Genes in Cervical Cancer: It Induces Glycolysis, Anaphase-dependent Proteasome Proteolysis, and Low Survival

first: INGRID

last: MEDINA MARTINEZ

overall_design:
In this study 31 tumors and 25 reference controls were used for analysis of copy number alterations using the 500K microarray. The results obtained from 500K array analysis were validated in 15 of the 31 tumors with a higher density microarray (Cytoscan HD). For the analysis of gene expression 55 cervical tumors (27 of them belong to the group of 31 tumors analyzed for copy number) and 17 exocervical controls were used.

Please note that 59 Samples (included in the GSE29570; PMID 22357541) were re-analyzed with 13 new samples and the reanalyzed samples are indicated in the Description/Relations field.

Please note that the sample R397 in the CytoScanHD_Array set corresponds to the R392 sample in the other data sets (due to an error in file name).

first: Ingrid

middle: M

last: Martinez

first: Jaime

last: Berumen


title: Mucosal gene expression profiling in patients with inflammatory bowel disease

status: Public on May 27 2015

city: Leuven

last: Arijs

address: Herestraat 49

department: Clinical and Experimental Medicine

country: Belgium

institute: KULeuven

summary: Microarrays were used to analyze the gene expression in endoscopic-derived intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) and controls

overall_design: Mucosal biopsies were obtained at endoscopy  from the colon of 97 ulcerative colitis (UC), 8 Crohn's disease (CD) patients and 11 controls. The biopsies were taken at the most affected sites but at a distance of ulcerations. Disease activity was endoscopically assessed. Total RNA extracted from mucosal biopsies was used to analyze mRNA expression via Affymetrix Human Gene 1.0 ST arrays

first: Gert

last: De Hertogh

first: Frans

last: Schuit

first: Paul

last: Rutgeerts

first: Séverine

last: Vemeire


title: The effect of MFNG knockdown on gene expression profile of xenograft tumor derived from MDA-MB231 cells

status: Public on May 01 2015

city: Jackson

first: Keli

last: Xu

state: MS

address: 2500 N. State St.

department: Cancer Institute

institute: University of Mississippi Medical Center

summary: Mfng, a modulator of Notch signaling, is highly expressed in human claudin-low breast cancer (CLBC). To determine Mfng’s roles in CLBC pathogenesis,we knocked down Mfng in a CLBC cell line MDA-MB231, and found that Mfng knockdown altered Notch activation, decreased tumor sphere formation in vitro, and reduced tumor growth in xenograft model. To identify the potential downstream targets of Mfng during CLBC tumorigenesis, we compared the gene expression profiles between xenografts tumor derived from of MDA-MB231 cells carrying Mfng shRNA and the control vector.  Mfng, a modulator of Notch signaling, is highly expressed in human claudin-low breast cancer (CLBC). To determine Mfng’s roles in CLBC pathogenesis,we knocked down Mfng in a CLBC cell line MDA-MB231, and found that Mfng knockdown caused alteration in Notch activation, associated with decreased tumor sphere formation in vitro, as well as reduced tumor growth in xenograft model. We intend to compare gene expression profiles between xenografts of MDA-MB231 cells carrying Mfng shRNA and the control vector. This project seeks to identify potential downstream targets of Mfng in CLBC.

overall_design: MDA-MB231 cells were transfected with shRNA against MFNG. Stable cell clones with knockdown of MFNG or corresponding control were selected and injected orthotopically into SCID mice. Total RNA was then extracted from the xenograph tumors for microarray analysis.


title: A cross-comparison of technologies for the detection of microRNAs from FFPE samples of hepatoblastoma patients [microarray]

status: Public on May 03 2015

city: Dunedin

first: Aniruddha

last: Chatterjee

state: Otago

address: 270 Great king Street

department: Pathology

country: New Zealand

institute: University of Otago

summary: This work highlights similarities and differences between three platforms (next-generation sequencing, microarray and NanoString) for detecting miRNAs and compares their strengths and weaknesses.

overall_design: miRNA expression profiles were determined in 6 Hepatoblastoma FFPE samples using a microarray platform.

first: Anna

last: Leichter

first: Vicky

last: Fan

first: Peter

last: Tsai

first: Rachel

middle: V

last: Purcell

first: Michael

last: Sullivan

middle: R

last: Eccles


title: Selective inhibition of SIN3 corepressor with avermectins as a novel therapeutic strategy in triple negative breast cancer

city: Stirling

first: Kevin

last: Petrie

state: Stirling

address: Stirling

department: Biological and Environmental Sciences

country: United Kingdom

institute: University of Stirling

summary: Triple negative breast cancers (TNBC) lacking estrogen, progesterone and HER2 receptors account for 10-20% of breast cancer and are indicative of poor prognosis. The development of effective treatment strategies therefore represents a pressing unmet clinical need. We previously identified a molecularly-targeted approach to target aberrant epigenetics of TNBC using a peptide corresponding to the SIN3 interaction domain (SID) of MAD. SID peptide selectively blocked binding of SID-containing proteins to the paired α-helix (PAH2) domain of SIN3, resulting in epigenetic and transcriptional modulation of genes associated with epithelial-mesenchymal transition (EMT). To find small molecule inhibitor (SMI) mimetics of SID peptide we performed an in silico screen for PAH2 domain-binding compounds. This led to the identification of the avermectin macrocyclic lactone derivatives selamectin and ivermectin (Mectizan) as candidate compounds. Both selamectin and ivermectin phenocopied the effects of SID peptide to block SIN3-PAH2 interaction with MAD, induce expression of CDH1 and ESR1 and restore tamoxifen sensitivity in MDA-MB-231 human and MMTV-Myc mouse TNBC cells in vitro. Treatment with selamectin or ivermectin led to transcriptional modulation of genes associated with EMT and maintenance of a cancer stem cell phenotype in TNBC cells. This resulted in impairment of clonogenic self-renewal in vitro and inhibition of tumor growth and metastasis in vivo. Underlining the potential of avermectins in TNBC, pathway analysis revealed that selamectin also modulated the expression of therapeutically-targetable genes. Consistent with this, an unbiased drug screen in TNBC cells identified selamectin-induced sensitization to a number of drugs, including those targeting modulated genes.

overall_design: Sub-confluent cultures of MDA-MB-231 cells were treated with vehicle or 1µM selamectin for 24h. Experiments were performed as three independent replicates.

first: Yordan

last: Sbirkov


title: Adaptation of HepG2 Cells to a Steady-State Reduction in the Content of Protein Phosphatase 6 (PP6) Catalytic Subunit

city: Providence

first: Joan

last: Boylan

state: RI

address: 593 Eddy Street

department: Pediatrics

institute: Rhode Island Hospital

summary:
To assess the potential of PP6 as a therapeutic target in liver disorders, we attenuated expression of the PP6 catalytic subunit in HepG2 cells using lentiviral-transduced shRNA. Two PP6 knock-down (PP6KD) cell lines 18.5 and 19.5, (90% reduction of PP6-C protein content) were studied in depth.
Both proliferated at a rate similar to control cells. However, flow cytometry indicated G2/M cell cycle arrest that was accounted for by a shift of the cells from a diploid to tetraploid state. PP6KD cells did not show an increase in apoptosis, nor did they exhibit reduced viability in the presence of bleomycin. Gene expression analysis by microarray showed attenuated anti-inflammatory signaling. Genes associated with DNA replication were downregulated. Mass spectrometry-based phosphoproteomic analysis yielded 80 phosphopeptides representing 56 proteins that were significantly affected by a stable reduction in PP6-C. Proteins involved in DNA replication, DNA damage repair and pre-mRNA splicing were overrepresented among these. PP6KD cells showed intact mTOR signaling.

overall_design: To generate cell lines in which PP6-C was reduced in expression (PP6-C knock-down; PP6KD), HepG2 cells were seeded into 96-well plates and transduced with lentiviral particles (multiplicity of infection of 5) corresponding to different short hairpin RNA (shRNA) constructs targeted to the PP6-C gene (Mission shRNA; Sigma-Aldrich, St. Louis, MO). Procedures followed the manufacturer’s protocol. Cell lines were selected in 2 µg/ml puromycin and surviving colonies of cells were expanded as mass cultures in puromycin. Five individual shRNA lentiviral particle constructs were tested. Cell lines 18.5 and 19.5 (TRCN0000297274 and TRCN0000379835 Mission lentiviral designation, respectively) were chosen for further experiments. Mission TRC2 non-target shRNA control transduction particles were used for control transduction.

first: Philip

last: Gruppuso


title: Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes

status: Public on May 19 2015

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum Muenchen

summary:
Background/aims: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type‐2 diabetes, and the metabolic syndrome. We asked whether FGF21 levels differ between subjects with metabolically healthy vs. unhealthy obesity (MHO vs. MUHO) opening the possibility that FGF21 is a cross‐talker between liver and adipose tissue in MUHO. Furthermore, we studied the effects of chronic FGF21 treatment on adipocyte differentiation, lipid storage, and adipokine secretion.

Methods/study design: In 20 morbidly obese donors of abdominal subcutaneous fat biopsies discordant for their whole‐body insulin sensitivity (hereby classified as MHO or MUHO subjects), serum FGF21 was quantified. The impact of chronic FGF21 treatment on differentiation, lipid accumulation, and adipokine release was assessed in isolated preadipocytes differentiated in vitro.

Results: Serum FGF21 concentrations were more than two‐fold higher in MUHO as compared to 37 MHO subjects (457 ±378 vs. 211 ±123 pg/mL; p<0.05). FGF21 treatment of human preadipocytes for the entire differentiation period was modestly lipogenic (+15%; p<0.05), reduced the expression of key adipogenic transcription factors (PPARG and CEBPA, ‐15% and ‐40%, respectively; p<0.01 both), reduced adiponectin expression (‐20%; p<0.05), markedly reduced adiponectin release (‐60%; p<0.01), and substantially increased leptin (+60%; p<0.01) and interleukin‐6 (+50%; p<0.001) release.

Interpretation/conclusions: The hepatokine FGF21 exerts weak lipogenic and anti‐adipogenic actions and marked adiponectin‐suppressive and leptin and interleukin‐6 release‐promoting effects in human differentiating preadipocytes. Together with the higher serum concentrations in MUHO subjects, our findings reveal FGF21 as a circulating factor promoting the development of metabolically unhealthy adipocytes.

overall_design: We analysed in vitro differentiated preadipocytes from 20 human donors treated with FGF21 or control cultures.

first: Lucia

last: Berti

first: Martin

last: Irmler

first: Marty

last: Zdichavsky

first: Tobias

last: Meile

first: Anja

last: Böhm

first: Norbert

last: Stefan

first: Andreas

last: Fritsche

first: Alfred

last: Königsrainer

first: Hans

middle: U

last: Häring

last: DeAngelis

first: Harald

last: Staiger


title: Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure

city: Warsaw

first: Monika

last: Gora

address: Pawinskiego 5A

department: Genetics

country: Poland

institute: Institute of Biochemistry and Biophysics

summary:
Heart failure (HF) is the most common cause of morbidity and mortality in the developed countries, especially considering the present demographic tendencies in those populations.
We identified biologically relevant transcripts that are significantly altered in the early phase of myocardial infarction (MI) and are associated with the development of post-myocardial infarction HF.

overall_design: We collected peripheral blood samples from patients (n=111) with ST-segment elevation myocardial infarction (STEMI) at four time points (admission, discharge, 1 month after MI, and 6 months after MI). Control group comprised patients (n=46) with a stable coronary artery disease and without a history of myocardial infarction. Affymetrix HuGene 1.0 ST arrays were used to analyze mRNA levels in periperal blood mononuclear cells (PBMCs) isolated from the study and control groups. Samples from the first three time points were compared with the samples from the same patients collected 6 months after MI (stable phase) and with the control group. Additionaly, based on plasma NT-proBNP level and left ventricular ejection fraction parameters the STEMI patients were divided into HF and non-HF groups.We attempted to identify transcripts whose differential expression on the 1st day of myocardial infarction predicted which patients would develop symptoms of HF during the 6 months of follow-up. For this purpose, we compared the microarray results for samples collected on admission for the HF group versus the non-HF group.

first: Agata

last: Maciejak

first: Marek

last: Kiliszek

first: Marcin

last: Michalak

first: Dorota

last: Tulacz

first: Grzegorz

last: Opolski

first: Krzysztof

last: Matlak

first: Slawomir

last: Dobrzycki

first: Agnieszka

last: Segiet

first: Beata

last: Burzynska


title: Transcriptome profiling of Bmi1 silenced-K562 CML cell line

status: Public on May 12 2015

city: Valbonne - Sophia-Antipolis

first: Kevin

last: Lebrigand

address: 660 route des lucioles

country: France

institute: IPMC/CNRS

summary: The Bmi1 Polycomb protein is involved in the epigenetic repressive control of self renewal and survival of cancer initiating cells. In Chronic Myeloid Leukemia (CML), bmi1 expression increases gradually as the disease progresses from a chronic latent phase to a deadly blast crisis. We developped an inducible shRNA system to silence Bmi1 in the human K562 chronic myeloid leukemia (CML) cell line in order to identify new Bmi1-target genes.

overall_design: Gene profiling was performed on inducible shBmi1-K562 cells incubated without (P3-K562+shBMI1) or with doxycycline for 96h (P4-K562+shBMI1+doxycycline) using HG-U133 Plus2 Affymetrix Arrays.

first: D

last: Mary

first: J

last: Peyron

first: B

last: Mari

first: C

last: Moreilhon

first: P

last: Barbry

first: K


title: Effects of knockdown of ROCK1 and ZIPK on gene expression in cultured human vascular smooth muscle cells

status: Public on May 15 2015

city: Calgary

first: Michael

middle: Patrick

last: Walsh

state: Alberta

address: 3330 Hospital Drive NW

department: Biochemistry & Molecular Biology

institute: University of Calgary

summary: Rho-associated kinase (ROCK) and zipper-interacting protein kinase (ZIPK) have been implicated in diverse physiological functions, including smooth muscle contraction, cell proliferation, cell adhesion, apoptosis, cell migration and inflammation. Many aspects of regulation via ROCK and ZIPK, however, remain unclear. In this study, we utilized an siRNA approach to knock down ROCK1 and ZIPK in cultured human arterial smooth muscle cells. Microarray analysis was performed, using a whole-transcript expression chip, to identify changes in gene expression profiles induced by ROCK1 and ZIPK knockdown. ROCK1 knockdown affected the expression of 553 genes (355 down-regulated and 198 up-regulated), while ZIPK knockdown affected the expression of 390 genes (219 down-regulated and 171 up-regulated). A high incidence of up- and down-regulation of transcription regulator genes was observed in both ROCK1 and ZIPK knockdowns. Other markedly affected groups included transporters, kinases, peptidases, transmembrane and G protein-coupled receptors, growth factors, phosphatases and ion channels. Three microRNAs (mir-145, mir-199 and mir-622) were up-regulated by ROCK1 knockdown, whereas ZIPK knockdown had no effect on microRNA expression. 76 differentially expressed genes were common to ROCK1 and ZIPK knockdown, of which 41 were down-regulated and 26 up-regulated by both treatments, while the other 9 genes were differentially up/down-regulated. Ingenuity Pathway Analysis identified five pathways shared between the two knockdowns, which are mainly involved in cell cycle regulation. Marked differences in the effects of ROCK1 and ZIPK knockdown on the genes involved in cell cycle regulation suggested that ROCK1 and ZIPK regulate the cell cycle by different mechanisms. ROCK1, but not ZIPK knockdown significantly reduced the viability of vascular SMC. ROCK1 knockdown also affected several cytokine signaling pathways with up-regulation of 5 and down-regulation of 4 cytokine genes, in contrast to ZIPK knockdown, which affected the expression of only two cytokine genes (both down-regulated). IL-6 gene expression and secretion of IL-6 protein were up-regulated by ROCK1 knockdown, whereas ZIPK knockdown reduced IL-6 mRNA expression and IL-6 protein secretion and ROCK1 protein expression, suggesting that ROCK1 may inhibit IL-6 secretion. IL-1β mRNA and protein levels were increased in response to ROCK1 knockdown. Finally, ROCK1 but not ZIPK knockdown inhibited proliferation of vascular smooth muscle cells. We conclude that ROCK1 and ZIPK have diverse, but predominantly distinct regulatory functions in vascular smooth muscle cells.

overall_design: Human coronary artery smooth muscle cells were transfected with siRNA targeting ROCK1 or ZIPK or with negative control siRNA that does not target any gene product. 48 h later, total RNA was isolated, reverse transcribed, amplified, labeled with the Ambion WT Express kit and hybridized to Human Gene 1.0 ST arrays (Affymetrix) at 45 oC for 16 h. The probe arrays were washed and stained on an Affymetrix GeneChip Fluidics-450 and scanned on an Affymetrix GeneChip Scanner 3000 7G System. Triplicates were prepared under all three conditions for microarray analysis.

middle: P

first: Jing

last: Deng


title: Transcriptomic analysis reveals novel long non-coding RNAs critical for vertebrate development [Affymetrix]

city: La Jolla

first: Christopher

last: Benner

state: California

address: 9500 Gilman Dr. MC 0640

department: Medicine

institute: University of California, San Diego (UCSD)

summary: Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development.

overall_design: shRNA knock down of lncRNAs followed by microarray gene expression profiling

first: Leo

last: Kurian

first: Aitor

last: Aguirre

first: Juan

last: Izpisua-Belmonte


title: The cellular origin and malignant transformation of Waldenström's Macroglobulinemia

status: Public on May 06 2015

first: Bruno

last: Paiva

country: Spain

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

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

overall_design: Refer to individual Series


title: MicroRNA expression profile of PBMCs in OAD mice and control mice

city: St .Louis

first: Zhongping

last: Xu

state: mo

address: 660s euclide Ave.

department: Surgery

country: USA

institute: Washington University in St. Louis

summary:
MicroRNA expression profiling was performed in PBMCs collected from 12 C57B/6 mice at 7 and 15 days after administration of H2Kb and Isotype antibody.
Results: there was a substantial proportion of microRNAs changed over time in OAD mice compared to control mice.
Dysregulated microRNA expression in murine obliterative airway disease induced by anti-MHC I antibodies


title: Glioblastoma-initiating cells from the peritumoral tissue have an invasive phenotype that is dependent on Rac and RhoA activation and downregulation of cytoplasmic p27.

status: Public on May 13 2015

first: Victor

last: Segura

state: Navarra

address: Avda. Pío XII, 55

department: Unit of Proteomics, Genomics and Bioinformatics

institute: FIMA

summary: The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts therapeutic access and surgical resection. Therefore, effective anti-invasive strategies of GBM cells can be key to increase the efficacy of chemotherapy against this devastating disease. As cancer stem or initiating cells are considered to retain the tumorigenic potential in a number of tumors including glioblastoma, we studied the invasion capabilities of glioblastoma initiating cells (GICs) that were isolated from the peritumoral (PT) tissue, which surrounds the tumor mass (TM) and remains in the brain after tumor removal. We found that PT-GICs are less proliferative but more invasive compared to TM-GICs.

overall_design: Gene expression arrays of cells derived from the tumor mass and the peritumoral tissue of three glioblastoma cases

first: Patricia

last: Ruiz

first: Jose

last: Orgaz

first: Miguel

last: Lafarga

middle: A

last: Martinez-Climent

first: Victoria

last: Sanz-Moreno

last: Fernandez-Luna


title: Differential regulation of gene expression by two isoforms of the human transcriptional coactivator MKL1

status: Public on May 14 2015

city: Basel

first: Tim

last: Roloff

address: Maulbeerstrasse 66

department: Functional Genomics

country: Switzerland

institute: FMI

summary: We identified two isoforms of human MKL1 that differ in their N-terminal domains. Since MKL1 is a transcriptional coactivator of SRF and regulates many SRF target genes, we wanted to analyze if transcription is differentially regulated by the two isoforms upon stimulation of the Rho-actin-MKL1-SRF pathway.

overall_design: Activity of the Rho-actin-MKL1 pathway was induced in EcR293 cell lines stably over-expressing the empty vector control, a 5’UTR-full length MKL1_S construct, or a 5’UTR-full length MKL1_L construct by LPA treatment.

first: Matthias

last: Scharenberg

first: Stéphane

last: Thiry


title: Cancer stem cells subpopulations within the CD44high human breast cancer stem cell compartment [HMT clones]

status: Public on Apr 30 2015

city: Odense

first: Rikke

last: Leth-Larsen

address: JB Winsloewsvej 25

department: Institute of Molecular Medicine

country: Denmark

institute: University of Southern Denmark

summary: The CD44hi compartment in human breast cancer is enriched in tumor-initiating cells, however the functional heterogeneity within this subpopulation remains poorly defined. From a human breast cancer cell line with a known bi-lineage phenotype we have isolated and cloned CD44hi populations that exhibited mesenchymal/Basal B and luminal/Basal A features, respectively:CD44+/CD24-,Basal B (G4, H6) cells and CD44hi/CD24lo epithelioid Basal A (A4, AB) cells.

overall_design: Seven replicates of A4, seven replicates of G4, three replicates of AB, three replicates of H6

first: Henrik

last: Ditzel


title: Infection of Myeloid Angiogenic Cells (MACs) with Bartonella henselae (B.h.) induces a chord formation phenotype in vitro.

status: Public on Apr 23 2015

city: Frankfurt

first: Fiona

last: O'Rourke

state: Hessen

address: Theodor Stern Kai 7

institute: University Hospital Frankfurt

summary: Myeloid Angiogenic Cells (MACs) were infected with the intracellular, bacterial pathogen Bartonella henselae (B.h.). Infected cells were seeded onto Matrigel coated plates. While uninfected cells showed no phenotypic changes and died over time, infected cells showed strong phenotypic changes and developed into complex 2D chord networks over the course of long term culture (eg 49d). To examine the changes in gene expression associated with the development of the B.h.dependent chord formation phenotype, RNA was isolated from MACs shortly after isolation (d4) and from cells of the chord structures (+B.h. Matrigel). As primary endothelial cells are also know to form chord networks when cultured on Matrigel, a sample of human umbilical vein endothelial cells (HUVECs) cultured on Matrigel for 12hr was also included in the analysis as a control.

overall_design: myeloid angiogenic cells (MACs) from three donors were compared d4 after isolation with MACs infected with Bartonella henselae and cultured on Matrigel coated plates for up to 49 days, 1 sample from human umbilical cord vein endothelial cells (HUVECs) cultured for 12hr on Matrigel coated plates were also included as a control.

first: Claudia

last: Döring


title: Gene expression data of diagnostic childhood T-ALL samples

city: Paris

first: Andre

last: Bortolini Silveira

address: 26 rue d'Ulm

institute: Institut Curie

summary:
The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
Global gene expression data of diagnostic T-ALL samples were used to analyse whether a gene expression signature of higher PI3K pathway activity is associated with worse prognosis. Patients entered treatment from 2000 to 2007 at Centro Infantil Boldrini. Risk classification and treatment was performed according to the Brazilian Childhood Cooperative Group-Protocol ALL-99.

overall_design: Guanidine thiocyanate solution-preserved post-ficoll bone marrow mononuclear cells obtained from consecutive patients with newly diagnosed childhood T-ALL were analysed.

first: André

middle: B

last: Silveira

first: Ângelo

last: Laranjeira

first: Paulo

last: Leal

last: Cardoso

first: João

last: Barata

first: Rosendo

last: Yunes

first: Nilson

middle: I

last: Zanchin

first: Sílvia

last: Brandalise

first: José


title: Effects of CBD on the glioma stem cell molecular signature

status: Public on Apr 17 2015

city: Newark

first: Saleena

last: Ghanny

address: 185 South Orange Ave

institute: Rutgers University

summary:
Primary glioma stem cells cultured as neurospheres in NBL media with growth factors were subjected to treatment with the non-toxic, non-psychoactive cannabis compound
cannabidiol (CBD). Control and CBD- treated cultures were used to generate RNA used to hybridize on Affymetrix DNA arrays

overall_design: Fluorescence intensities data were RMA-normalized using Partek software.

first: Liliana

last: Soroceanu


title: Gene expression in obese humans before and during treatment with rimonabant

status: Public on Apr 21 2015

city: Stockholm

first: Birgitta

last: Sander

country: Sweden

institute: Karolinska Institutet

summary: Rimonabant was prescribed to eight patients, admitted to the Overweight Study Unit at the Department of Medicine, Karolinska University Hospital. All patients had a BMI > 35 kg/m2, were treated on clinical indications (metabolic and mechanical disability) and without mental disturbances. Blood samples were collected before treatment and at the first clinical control, when the patients had received rimonabant, 20 mg daily, for 4 weeks.

overall_design: Blood mononuclear cells were isolated by Ficoll separation (Ficoll-Paque PLUS, GE Healthcare). From the cell-pellet total RNA was prepared using Qiagen midi plus kit (Qiagen GmbH, Hilden Germany) as recommended by the manufacturer and was quality controlled on an Agilent Bioanalyzer (Agilent Technologies, Inc. Palo Alto, CA). Six pretreatment samples and seven samples obtained after rimonabant treatment passed the quality control. The cRNA synthesis for microarray experiments and the hybridizations were carried out using Affymetrix Human Gene 1.0 ST Array (Affymetrix, Inc., Santa Clara, CA) according to standard Affymetrix protocols at the core facility for Bioinformatics and Expression Analysis, Department of Biosciences and Nutrition, Karolinska Institutet.


title: Profiling ethanol-targeted transcription factors in human carcinoma cell-derived embryoid bodies.

status: Public on Apr 15 2015

city: Ansan

first: Young Gyu

last: Chai

state: Gyeonggi-do

address: 55 Hanyangdaehak-ro

department: Molecualr & Life Science

country: South Korea

institute: Hanyang Univ.

summary:
A total of 493 differentially expressed genes were identified in response to 50 mM ethanol exposure, in which 111 of them were up-regulated and 382 were down-regulated. Gene ontology term enrichment analysis revealed that the genes are involved in the important biological processes like neurological system process, cognition, behavior, sensory perception of smell, taste and chemical stimuli and synaptic transmission. In consistent, disease enrichment chart showed relevant categories like neurological diseases, developmental disorders, skeletal and muscular disorders, connective tissue disorders.
Furthermore, we have shorted out a group of 26 genes that encode transcription factors. We validated relative gene expression of several transcription factors from the list by quantitative real time PCR. We hope that our study substantially contributes to the understanding of the molecular mechanism underlying the pathology of alcohol mediated anomalies and ease further research.

overall_design: Our aim was to provide a profile of important regulator that exerts ethanol related genomic alteration. For this, we have analyzed gene expression pattern of human carcinoma cell derived embryoid bodies in absence or presence of ethanol. A cDNA microarray analysis was used to profile mRNA expression in embryoid bodies at day 7 with or without ethanol treatment.

first: Kyoung

middle: H

last: Jung

first: Young

middle: G


title: UGT2B17 knock down in chronic lymphocytic leukemia cell line MEC-1

city: Vienna

first: Robin

last: Ristl

address: Spitalgasse 23

country: Austria

institute: Medical University Vienna

summary:
Comparison of gene expression after stable shRNA induced knock down of UGT2B17 and scrambled shRNA in the cell line model MEC-1. Transfection was performed using lentiviral particles, RNA was harvested after culture for 2 weeks.
Results provide insight into functional UGT2B17 involvement in CLL cells.

overall_design: Knock down of UGT2B17 in comparison to scrambled shRNA in three independent replicates each.

first: Michaela

last: Gruber

first: Ulrich

last: Jäger


title: Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development

city: Mannheim

first: Harsh

last: Dweep

state: baden wurttemberg

address: Theodor-Kutzer-Ufer 1-3

department: Medical Research Center, Medical Faculty of Mannheim of the University of Heidelberg

institute: University of Heidelberg

platform_organism:
Rattus norvegicus
synthetic construct


title: Analysis of compartment-specific gene expression in breast cancer tumors

city: Lund

first: Christer

last: Larsson

address: Medicon Village, Bldg 404:C3

department: Laboratory Medicine

institute: Lund university

summary: Triple-negative primary breast cancer tumors, rich in inflammatory stroma, were laser microdissected and global mRNA expression was analyzed in stroma compartment, cancer cell compartment, and in total tumor tissue.

overall_design: Three FFPE breast cancer tumors wer laser microdissected and the cancer cell and stroma compartments were collected. A piece of t

first: Sofia

last: Winslow

first: Karin

last: Leandersson

first: Anders

last: Edsjö


title: Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells [HuGene-1_0-st]

city: Boston

first: Adam

middle: C

last: Gower

state: MA

address: 72 East Concord Street, E632

department: Department of Medicine

institute: Boston University School of Medicine

summary: We monitored 9 pluripotent stem cell lines across three time points of hepatic directed differentiation, representing 3 developmental stages: undifferentiated (T0), definitive endoderm (T5), and early hepatocyte (T24). ESCs (n=3) and patient-derived normal (n=3) or PiZZ (n=3) iPSCs were analyzed in the undifferentiated state (T0), after differentiation to definitive endoderm (T5), and upon reaching hepatic stage (T24) for a total of 27 samples.  We sought to test the hypothesis that a single transgene-free iPSC clone from each donor could be used to detect disease-specific differences between the normal cohort and the PiZZ cohort, anticipating that this difference would emerge only at a developmental stage in which the mutant AAT gene is expressed. Cells were sorted before analysis at T0 and T5 after antibody staining for TRA1-80+/SSEA3+ (T0) or C-kit+/CXCR4+ (T5) cells.

overall_design: ESCs (n=3) and patient-derived normal (n=3) or PiZZ (n=3) iPSCs were analyzed in the undifferentiated state (T0), after differentiation to definitive endoderm (T5), and upon reaching hepatic stage (T24) for a total of 27 samples.  Cells were sorted before analysis at T0 and T5 after antibody staining for TRA1-80+/SSEA3+ (T0) or C-kit+/CXCR4+ (T5) cells. RNA was extracted at each stage, biotin labeled, and hybridized to either Affymetrix GeneChip Human Gene 1.0 ST or miRNA 2.0 arrays. For methylation analysis, gDNA was sorted from the same 27 samples before undergoing bisulfite conversion. Bisulfite converted DNA was then amplified and purified prior to overnight hybridization to Illumina’s Infinium HumanMethylation 450 BeadChips.  Next day staining of hybridized arrays produced methylation-dependent differential fluorescence that was detected via an Illumina iScan array scanner.

first: Andrew

last: Wilson

first: Darrell

middle: N

last: Kotton


title: Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development [miRNA]

summary: This study tested the hypothesis that miRNA expression profiles change in the muscular type rat saphenous artery during early postnatal development. To explore this, we performed miRNA microarray analysis on muscular type saphenous arteries of young (10-12 days) and adult (2-3 months) rats.

overall_design: For one sample four saphenous arteries from 2 young animals (n = 4 samples per group) or two saphenous arteries from one adult animal (n = 4 samples per group) were used to profile miRNA (n = 8; GeneChip® miRNA 3.0) expression changes during the muscular type rat saphenous artery during early postnatal development. In this study, 10-12 days old (“young”) and 2 - 3 months old (“adult”) male Wistar rats were used.

first: Dina

last: Gaynullina

first: Torsten

last: Gloe

first: Olga

middle: S

last: Tarasova

first: Carsten

last: Sticht

first: Norbert

last: Gretz

first: Rudolf

last: Schubert


title: Suppression of SOX7 by DNA methylation and its tumor suppressor function in acute myeloid leukemia

status: Public on Apr 14 2015

city: Hong Kong

first: Cheuk Him

last: Man

address: L816, LAB BLK, FMB, HKU

country: Hong Kong

institute: HKU

summary:
SOX7 was commonly downregulated in AML by hypermethylation.
Re-expression of SOX7 in AML reduced the survival of AML

overall_design: Overexpression of GFP-SOX7 by lenti-viral transduction in 3 AML cell lines and compared the expression level of genes normalized to GFP control

first: Cheuk-Him

first: Haixia

last: Wan

first: Tsz-Kan

last: Fung


title: Gene expression comparison between fibroblasts samples of control and SPOAN affected patients

status: Public on Apr 03 2015

city: SAO PAULO

first: JOAO PAULO

last: KITAJIMA

state: SP

address: RUA CUBATAO 86 CJ 1602

country: Brazil

institute: MENDELICS

summary: Objective: Analyze expression patterns of genes located at linkage region of SPOAN syndrome (11q12-13), in order to identify genes differentially expressed in samples of SPOAN individuals compared to healthy controls.

overall_design: Fibroblast samples of 8 samples where analyzed: 4 SPOAN affected patients and 4 healthy controls. There are no replicates and there are not affected and control from the same patient.

first: Uira

last: Souto Melo

first: Fernando

last: Kok

first: Joao

last: Kitajima

first: Thalita

last: Figueiredo

first: Lucia

last: Macedo-Souza


title: Gene array comparison of highly and poorly chondrogenic clones of adult human mesenchymal stem cells (MSCs)

city: Bristol

first: Anthony

last: Hollander

address: University Walk

department: School of Cellular and Molecular Medicine

institute: University of Bristol

summary:
MSCs are a heterogeneous population of cells with different capacities for lineage differentiation. MSC clones were prepared from a single adult human bone marrow sample and screened for their chondrogenic capacity using cartilage tissue engineering (measured by type II collagen content).
The aim was to compare genes expressed by highly and poorly chondrogenic clones to identify genes associated with those MSCs with an enhanced capacity for cartilage formation.

overall_design: The 4 most highly chondrogenic and the 4 least chondrogenic MSC clones identified following screening by cartilage tissue engineering were selected for gene array comparison using Affymetrix microarrays.

first: Sally

last: Dickinson

first: Catherine

last: Sutton

first: Wael

last: Kafienah


title: Expression data from MS individuals homozygous for IL7R haplotypes

city: Hamburg

first: Christian

last: Schulze

address: Falkenried 94

institute: ZMNH

summary: Genome-wide association studies in multiple sclerosis (MS) identified a polymorphism (rs6897932) located in the coding region of the alpha chain of the cytokine receptor interleukin 7 receptor (IL7R) as a component that increases susceptibility to develop the disease. This single nucleotide polymorphism (SNP) affects the splicing of the primary transcript leading to genotype-defined transcript ratios encoding either a full length membrane spanning form or a soluble receptor chain. Genotyping at the IL7R locus reveals that the region can be described by four haplotypes. Interestingly, only one out of three haplotypes harbouring the associated SNP is positively associated with MS whereas the other two do not show association. The minor allele containing haplotype shows a reduced susceptibility to develop MS. We hypothesized that additional functional or phenotypic differences exist between individuals homozygous for haplotypes shown to have either positive, negative, or neutral effect, on susceptibility to develop MS. Gene expression profiles of CD4+ T cells from MS individuals before and after stimulation with IL7 were recorded. Haplotype-specific gene signatures were found indicating small alterations in IL7/IL7R signal processing/sensitivity through JAK/STAT and p38/MAPK14. We can not exclude that the obtained signatures result from differences within the CD4+ T cell compartment that, in fact, should be seen as a consequence of systemic haplotype-specific processing of homeostatic and proliferation signals transmitted through IL7/IL7R.

overall_design:
Samples of CD4+ cells were obtained from 7 MS patients (homozygous for Hap1 (3), Hap2 (2), Hap3 (2)). CD4+ cells were collected from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and CD4+ cells were purified by magnetic bead separation. Purity and viability of cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human Gene 1.0 ST Array (affymetrix).

IL7R haplotypes and susceptibility to develop MS:
Hap1 homozygous <-> Risk <-> positive effect on MS susceptibility
Hap2 homozygous <-> Hap2 <-> neutral effect on MS susceptibility
Hap3 homozygous <-> Prot <-> neutral effect on MS susceptibility
[Note: Haplotype nomenclature subject to revision.]

first: Jan

last: Jäger

first: Sabine

last: Rösner

first: Roland

last: Martin


title: Expression data from prostate cancer cell lines LNCap (androgen dependent) and DU145 (androgen independent), transfected with Pin1 or control siRNA

status: Public on Apr 01 2015

city: Tokyo

first: Akifumi

last: Kushiyama

address: 2-2-6, Nihonbashi Bakurocho, Chuo-ku

country: Japan

institute: The Institute for Adult Diseases, Asahi Life Foundation

summary:
Pin1 inhibiton exerts anti-oncogenic effects on LNCaP and DU145 cells despite the gene regulation patterns by Pin1 were different in both cells.
We investigated how Pin1 modulates the gene expressions in the androgen-dependent as well as the androgen-independent prostate cancer cell lines

overall_design: For the knockdown of human Pin1, the siRNAs against Pin1 (Pin1 shRNA-1: 5’-CGGCAACAGCAGCAGUGGUGGCAAA-3’ and Pin1 shRNA-2: 5’-GCCCUGGAGCUGAUCAACGGCUACA-3’) and control siRNA were purchased from Invitrogen (Stealth/siRNA duplex oligoribonucleotides)

first: Ryuhei

last: Kanaoka

first: Tomoichiro

last: Asano


title: Gene expression signature of primary T-ALL cells treated with the PI3K inhibitor AS605240

first: Andre

last: Bortolini Silveira

summary: The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.

overall_design: Cryopreserved post-ficoll bone marrow mononuclear cells obtained from consecutive patients with newly diagnosed T-ALL were cultured for 6h with 20 μM of AS605240 or vehicle.

first: André

last: Silveira

first: Angelo

last: Laranjeira

first: Paulo

last: Leal

first: Bruno

last: Cardoso

first: João

last: Barata

first: Rosendo

last: Yunes

first: Nilson

last: Zanchin

first: Sílvia

last: Brandalise

first: José

first: Gisele

middle: O

last: Rodrigues


title: Expression data from human heart right ventricular wall

status: Public on Apr 02 2015

city: Nashville

first: James

last: West

state: TN

address: 4200 E 9TH Ave, Box B133

institute: Vanderbilt University

summary: Gene expression in the right ventricle is different in control patients as compared to either idiopathic dilated cardiomyopathy or pulmonary arterial hypertension

overall_design: Two human hearts obtained at autopsy from each of control, pulmonary hypertension, and dilated cardiomyopathy

first: Anna

last: Hemnes


title: Expression of Neutrophil-related genes in patients with early sepsis-induced ARDS

city: San Francisco

first: Alisha

last: Holloway

state: CA

address: 1650 Owens Street

institute: Gladstone Institutes

summary:
Clinical study of critically ill patients with sepsis and sepsis-related ARDS with whole blood RNA collected within the first 24 hours of admission
Goal of the study was to determine whether biologically relevant genes were identified  to be differentially expressed genes in patients with sepsis alone and sepsis with ARDS

overall_design: Prospective observational study, case cohort design

first: Kirsten

last: Kangelaris

first: Carolyn

last: Calfee


title: The epithelial cell transcriptome after alpha-toxin treatment

status: Public on Mar 31 2015

city: Greifswald

first: Joerg

last: Mostertz

address: F.-L.-Jahnstr 15

department: Competence Center Functional Genomics

institute: Greifswald University

summary: Responsiveness of cells to alpha-toxin (Hla) from Staphylococcus aureus appears to occur in a cell-type dependent manner. Here, we compare two human bronchial epithelial cell lines, i.e. Hla-susceptible 16HBE14o- and Hla-resistant S9 cells, by a quantitative multi-omics strategy for a better understanding of Hla-induced cellular programs. Phosphoproteomics revealed a substantial impact on phosphorylation-dependent signaling in both cell models and highlights alterations in signaling pathways associated with cell-cell and cell-matrix contacts as well as the actin cytoskeleton as key features of early rHla-induced effects. Along comparable changes in down-stream activity of major protein kinases significant differences between both models were found upon rHla-treatment including activation of EGFR and MAPK1/3 signaling in S9 and repression in 16HBE14o- cells. System-wide transcript and protein expression profiling indicate induction of an immediate early response in either model. In addition, EGFR and MAPK1/3-mediated changes in gene expression suggest cellular recovery and survival in S9 cells but cell death in 16HBE14o- cells. Strikingly, inhibition of the EGFR sensitized S9 cells to Hla indicating that the cellular capacity of activation of the EGFR is a major protective determinant against Hla-mediated cytotoxic effects.

overall_design: Design includes two different human bronchial epithelial cell lines, one control treatment (mock treatment for 2 hours) and one condition (2 alpha toxin treatment for 2 hours). Experiments for both cell line were replicated twice (biological replication).

first: Ravi

middle: K

last: Chilukoti