title: Changes in the gene expression in the inferior colliculus of the sound stimulated both control Syrian hamsters and the strain GASH:Sal.

status: Public on Dec 31 2015

city: Salamanca

first: Raquel

middle: E.

last: Rodriguez

state: Salamanca

address: C/ Pintor Fernando Gallego, 1

institute: Institute of Neurosciences of Castilla y León

summary:
Using microarray analyses and subsequent verification by RT-PCR, we studied the changes in gene expression in the inferior colliculus after an ictal event in one models of audiogenic epilepsy, genetic audiogenic seizure hamster (GASH:Sal). GASH:Sal, a hamster strain developed at the University of Salamanca, exhibits genetic audiogenic epilepsy similar to human Grand Mal epilepsy. GASH:Sal shows an autosomal recessive inheritance for susceptibility to audiogenic seizures, which manifest more severely in young animals; the seizure severity progressively declines with age.
Genetic animal models of epilepsy are an important tool for further understanding the basic cellular mechanisms underlying epileptogenesis and for developing novel antiepileptic drugs. We conducted a comparative study of gene expression in the inferior colliculus, a nucleus that triggers audiogenic seizures, using two animal models, the Wistar audiogenic rat (WAR) and the genetic audiogenic seizure hamster (GASH:Sal). For this purpose, both models were subjected to auditory stimulation, and 60 minutes after stimulation, the inferior colliculi were collected. As a control, intact Wistar rats and Syrian hamsters were subjected to identical stimulation and tissue preparation protocols to those performed on the experimental animals.

overall_design: A total of 24 animals were used in this study according to the following distribution: 12 control Syrian hamsters (Mesocricetus auratus) and 12 GASH:Sal at 16 weeks of age and a body weight of approximately 60 g. Six animals Syrian and GASH:Sal hamsters, respectively, were exposed to auditory stimulation, and 60 min after the seizures, we harvested the IC for all gene expression analyses (stimulated Syrian hamsters and stimulated GASH:Sal hamsters). As controls,  other six animals Syrian and GASH:Sal hamsters, respectively,  were not exposed to the same stimulation (Syrian hamsters and GASH:Sal hamsters).

last: López-López

last: Herrero-Turrión

first: T

last: López-Alburquerque

first: C

last: Sancho

first: R

last: Gomez-Nieto

first: O

last: Castellano

last: Sanchez-Benito

last: Hernández-Noriega

middle: E

last: López


title: Heterogeneous expression of zinc-finger E-box-binding homeobox 1 plays a pivotal role in metastasis via regulation of miR-200c in epithelial-mesenchymal transition

status: Public on Dec 25 2015

city: Saitama

first: Yuta

last: Muto

address: 1-847 Amanuma-cho, Omiya-ku

department: Department of Surgery

country: Japan

institute: Saitama Medical Center, Jichi Medical University

summary: Although epithelial-mesenchymal transition (EMT) has been implicated as the pivotal event in metastasis, there is insufficient evidence related to EMT in clinical settings. Intratumor heterogeneity may lead to underestimation of gene expression representing EMT. In this study, we investigated the expression of EMT-associated genes and microRNAs in primary colorectal cancer while considering intratumor heterogeneity.

overall_design:
One-hundred and thirty-three multiple spatially separated samples were obtained from 8 patients with metastatic colorectal cancers and 8 with non-metastatic colorectal cancers, from the tumor center (TC), invasive front (IF), and metastasis. Differences in gene and microRNA expression were investigated by microarray and quantitative reverse-transcription PCR.
RNA collection from 38 sites of 8 patients and Universal Human Reference RNA (Agilent Technologies) were used for micro-array analysis.


title: Changes in the gene expression in the inferior colliculus of the sound stimulated rats both Wistar  and the strain susceptible to audiogenic seizures WAR

country: Spain

summary:
Using microarray analyses and subsequent verification by RT-PCR, we studied the changes in gene expression in the inferior colliculus after an ictal event in one models of audiogenic epilepsy, Wistar audigenic rat (WAR). WAR is a genetically selected strain susceptible to audiogenic seizures that was inbred in the School of Medicine of Ribeirão Preto (Brazil) beginning in 1990. This strain is a model of audiogenic idiopathic epilepsy that develops tonic-clonic generalized seizures.
Genetic animal models of epilepsy are an important tool for further understanding the basic cellular mechanisms underlying epileptogenesis and for developing novel antiepileptic drugs. We conducted a comparative study of gene expression in the inferior colliculus, a nucleus that triggers audiogenic seizures, using two animal models, the Wistar audiogenic rat (WAR) and the genetic audiogenic seizure hamster (GASH:Sal). For this purpose, both models were subjected to auditory stimulation, and 60 minutes after stimulation, the inferior colliculi were collected. As a control, intact Wistar rats and Syrian hamsters were subjected to identical stimulation and tissue preparation protocols to those performed on the experimental animals.

overall_design: A total of 15 animals were used in this study according to the following distribution: 9 male WAR and 6 male control rats (Rattus norvegicus, Wistar albino, Charles River Laboratories) at 12 weeks of age and a body weight of approximately 230 g. The animals were exposed to auditory stimulation, and 60 min after the seizures, we harvested the IC for all gene expression analyses. As controls, normal Wistar rats were exposed to the same stimulation according to the identical procedure. For  gene microarray (Rat Gene 1.0 ST), the rats were randomly divided into two groups, and we used both sides of the IC (ipsilateral and contralateral) from each animal: stimulated Wistar rats  and  stimulated WAR rats.

first: D

first: M

middle: J

last: Herrero-Turrion

first: J

middle: A

last: Oliveira

first: N

last: Garcia-Cairasco


title: Expression data from rat orthotopic bladder cancer

status: Public on Jan 12 2016

city: Shanghai

first: Chun-Wu

last: Pan

state: Shanghai

address: 1665 KONG JIANG ROAD

department: Department of Urology

country: China

institute: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

summary:
In the development and progression of bladder cancer, there are many genetic changes. We established a SD rat orthotopic bladder cancer model through intravesical instillation of N-methyl-nitrosourea and pathologic diagnosis is bladder transtional cell carcinomal (BTCC).
We used microarrays to analysis the gene expression changes among these rat bladder carcinoma, adjacent normal tissues and bladder tissues of normal rats.

overall_design: Three paired tumor tissues (Group A) and adjacent normal tissues (Group B) were obtained from 3 SD rats with BTCC, and 3 normal tissues (Group C) obtained from 3 normal SD rats. Affymetrix microarrays analyzed the gene expression changes among above 3 groups of tissues.


title: Acute loss of TET function results in aggressive myeloid cancer in mice [RNA-Seq]

status: Public on Nov 26 2015

city: La Jolla

first: Anjana

last: Rao

state: CA

address: 9420 Athena Circle

department: Signaling and Gene Epression

country: USA

institute: La Jolla institute

type: Expression profiling by high throughput sequencing

summary: TET-family dioxygenases oxidize 5-methylcytosine (5mC) in DNA, and exert tumor suppressor activity in many types of cancers. Even in the absence of TET coding region mutations, TET loss-of-function is strongly associated with cancer. We show that acute elimination of TET function induces the rapid development of an aggressive, fully-penetrant and cell-autonomous myeloid leukemia in mice, pointing to a causative role for TET-loss-of-function in this myeloid malignancy. Phenotypic and transcriptional profiling showed aberrant differentiation of hematopoietic stem/ progenitor cells, impaired erythroid and lymphoid differentiation and strong skewing to the myeloid lineage, with only a mild relation to changes in DNA modification. We also observed progressive accumulation of DNA damage and strong impairment of DNA break repair, suggesting a key role for TET proteins in maintaining genomic integrity.

overall_design: Jungeun, An

first: Edahi

last: Gonzalez Avalos

first: Ashu

last: Chawla

first: Mira

last: Jeong

first: Isaac

last: Fernando López Moyado

first: Wei

last: Li

first: Margaret

last: Goodell

first: Lukas

last: Chavez

first: Myunggon

last: Ko


title: A novel approach to Alzheimer’s Disease treatment: HDACs & PDE5 inhibition

status: Public on Nov 27 2015

city: Pamplona

first: Victor

last: Segura

state: Navarra

address: Avda. Pío XII, 55

department: Unit of Proteomics, Genomics and Bioinformatics

institute: FIMA

summary: Considering the numerous complex and different pathological mechanisms involved in Alzheimer´s disease (AD) progression, treatments targeting a single cause may lead to limited benefits. The goal of this study was the identification of a novel mode of action for this unmet need. Pharmacological tool compounds: suberoylanilide hydroxamic acid (SAHA) and tadalafil, targeting histone deacetylases (HDAC) and phosphodiesterase 5 (PDE5) respectively, were utilized simultaneously for in-vitro and in-vivo Proof-of-Concept (PoC). A synergistic effect was observed in the amelioration of AD signs using the combination therapy in Tg2576 mice. Finally, a therapeutic agent, CM-414, inhibiting simultaneously HDAC2/6 and PDE5 was generated and tested in Tg2576 mice. CM-414 reversed cognitive impairment, reduced amyloid and tau pathology, and rescued dendritic spine density loss in the hippocampus in AD mice. Importantly, the effect obtained was present after a 4-weeks wash-out period.

overall_design: Comparisson of global gene expression profiling in mice hippocampi between diferent treatments

first: Ana

last: García-Osta

first: Mar

last: Cuadrado

first: Julen

last: Oyarzábal


title: IL-27 stimulation in Foxp3+ Tregs improves suppressive function and therapeutic efficacy

status: Public on Nov 01 2015

city: Cleveland

first: Yibayiri

middle: Osee

last: Sanogo

state: OH

address: 9500 S Euclid Ave

department: Genomics Core

institute: Cleveland Clinic Foundation

summary: Foxp3 expressing regulatory T cells (Tregs) are the central regulator of immune homeostasis and tolerance. As it is believed that proper Treg function is compromised under inflammatory conditions, exploring a pathway that enhances Treg function is of great importance. In this study, we report that IL-27, an IL-12 family cytokine known to play both pro- and anti-inflammatory role in T cells, plays a pivotal role in Treg function to control T cell-induced colitis. Unlike WT Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially enhanced suppressive function both in vitro and in vivo. IL-27 stimulation of Tregs induced expression of LAG3, a surface molecule implicated in negatively regulating immune responses. LAG3 expression in IL-27-stimulated Tregs was critical to mediate suppressive Treg function. Finally, human Tregs also displayed enhanced suppressive function and LAG3 expression in response to IL-27 stimulation. Taken together, our results highlight a novel function of the IL-27/LAG3 axis in Treg regulation of inflammatory responses in the intestine.

overall_design: FACS purified Foxp3+ Tregs were stimulated in the presence of media or IL-27 to compare IL-27 induced gene profiles. Four samples (media stimulated or IL-27-stimulated) were collected from four independent experiments. Genes altered by IL-27 treatment were compared to those of media stimulated Tregs.

first: Booki

last: Min

first: Jeongsu

last: Do

middle: O


title: Transcriptome Analysis of Developing Intestine [ChIP-Seq]

status: Public on Nov 13 2015

city: Detroit

first: Katherine

last: Gurdziel

state: MI

address: 275 E. Hancock

institute: Wayne State University

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
Background: The muscularis externa (ME) of the adult intestine consists of two layers of visceral smooth muscle (VISM), the inner circular muscle (ICM) and outer longitudinal muscle (OLM), that form sequentially beginning at embryonic day (E) 13 and E15 in the developing mouse. Coordinated contraction of these two layers facilitates the movement of food down the digestive tract. Though abnormal ME function or development has been linked to pseudoobstruction and irritable bowel syndrome, little is known about the molecular character of the smooth muscle that comprises this tissue. We performed transcriptome analysis to identify genes that are enriched in intestinal mesenchyme tissue at E14.5, when the inner circular muscle (ICM) is well established.
Results: Expression patterns of enriched mesenchyme genes were examined in publically available in situ databases, revealing over one hundred genes that are expressed in the ICM. Examination of the promoter regions for these genes revealed enrichment for cJUN transcription factor binding sites and cJUN itself was also enriched in ICM. A cJUN ChIP-seq at E14.5 showed that cJUN regulatory regions contained characteristics of muscle enhancers.

overall_design: E14.5 mouse intestines were harvested from one litter (8 embryos) and grown for 24 hours in a transwell culture. Intestines were dissociate into single cells, cross-linked and sonicated to an average DNA fragment size of 500 bp prior to incubation with cJUN antibody.  Both cJUN immunoprecipitated and input DNA were submitted for sequencing.


title: Transcriptome Analysis of Developing Intestine

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

overall_design: Refer to individual Series


title: Transcriptome Analysis of Developing Intestine [RNA-Seq]

status: Public on Nov 12 2015

overall_design: E14.5 mouse intestines were harvested and grown for 24 hours in a transwell culture with or without Cyclopamine treatment. Separated epithelial and mesenchyme tissue populations or whole intestines were submitted for sequencing. Three replicates for each condition were collected.


title: Lung miRNA profiling in mouse model of allergic airways disease

city: New Lambton Heights

first: Maximilian

last: Plank

state: Australia

address: Lot 1 Kookaburra Circuit

country: Australia

institute: University of Newcastle

summary: To determine the differential expression of miRNAs in the lungs of mice subjected to a model of allergic airways disease and non-allergic and steroid-treated control animals.

overall_design: Total lung RNA was collected from mice sensitised and challenged with PBS or OVA with or without DEX treatment at day 16 and miRNA microarrays performed.

middle: W

first: Paul

middle: S

last: Foster


title: Transcriptome profile of peripheral blood from pancreatic ductal adenocarcinoma patients

status: Public on Nov 04 2015

city: Jaen

first: Octavio

last: Caba

state: Jaen

address: Paraje de las Lagunillas

department: Health Sciences

institute: University of Jaen

summary:
Analysis of expression profile of peripheral blood from pancreatic ductal adenocarcinoma patients
RNA expression profile of peripheral blood from pancreatic ductal adenocarcinoma patients

overall_design: Total RNA was isolated from peripheral blood. 36 patients with unresectable PDAC were recruited. The diagnosis of PDAC was based on clinical evaluation and imaging studies, which were histologically confirmed by surgery or imaging-guided biopsy. 14 gender, age, and habits matched healthy controls were also included.  A total of 1000 ng of total RNA was processed using Illumina TotalPrep RNA Amplification Kit. Hybridization of human samples was performed on Illumina Human-HT12 Version 4.


title: Gene expression profiling of L-540, SUP-HD1, KM-H2 and L-428 Hodgkin lymphoma cell lines after in vitro and in vivo treatment with the dual PI3K/ERK inhibitor AEZS-136

status: Public on Jan 01 2016

city: Cambridge

first: Giuliano

middle: Giuseppe

last: Stirparo

state: Cambridgeshire

address: 418 Cambridge Science Park Milton Rd

country: United Kingdom

institute: Cerevance ltd

summary: Disease relapse and resistance to chemotherapy represent challenging issues in a subset of Hodgkin Lymphoma (HL) patients. Activity and mechanism(s) of action of a novel PI3K/ERK dual inhibitor AEZS-136 (Æterna Zentaris GmbH, Germany, EU) were examined in L-540, SUP-HD1, KM-H2 and L-428 cell lines. Despite exposure to AEZS-136 induced a significant cell growth inhibition (range, 30-80%), levels of caspase-independent cell death and mitochondrial dysfunction, were only observed in L-540 (62 ±9 vs 14 ±3%, P ≤.0001) and SUP-HD1 (46 ±2% vs 15 ±2%, P ≤.0001) cells. Gene expression profiling indicated that the effects of AEZS-136 treatment are associated with the modulation of cell cycle and cell death pathways. Exposure to AEZS-136 resulted in sustained production of reactive oxygen species (ROS) and activation of necroptotic cell death. The necroptosis inhibitor Necrostatin-1 prevented AEZS-136-induced ROS production, mitochondrial injury, activation of JNK and cell death. Knockdown experiments identified the immediate early response 3 (IER3) as a key signaling molecule that mediates AEZS-136-resistance to oxidative death of HL cells. Furthermore, in vivo xenograft studies demonstrated a 40-70% reduction in tumor burden (P < 0.0001) and a 10-fold increase in tumor necrosis in AEZS-136-treated animals compared to control mice. These data support further clinical evaluation of AEZS-136 in refractory/relapsed HL.

overall_design: The Hodgkin lymphoma cell lines  were obtained from the DSMZ (Braunschweig, Germany, EU). Cells were routinely maintained in RPMI medium 1640 (Lonza, Basel, Switzerland) supplemented with 20% FBS (Lonza) and 2 mM glutamine (Lonza). Cells were maintained at 37°C in a water-saturated atmosphere of 5% CO2 in air. 4x106 HL cells were seeded in 75 cm2 flask and, after 24 hrs, cells were treated with 10 µM AEZS-136 (Aeterna Zentaris, Frankfurt, Germany, EU)  in culture medium for 24 hours. At the end of treatment, cells were collected and RNA extracted.

first: G

middle: G


title: Gene expression profiles of mouse myeloid progenitors stimulated with IL-33

status: Public on Dec 30 2015

city: Fukuoka

first: Hirofumi

last: Tsuzuki

address: 3-1-1 Maidashi, Higashi-Ku

department: Department of Medicine and Biosystemic Science

institute: Kyushu University

summary: Analysis of the effect of IL-33 on mouse myeloid progenitors at gene expression level.  Results provide that myeloid progenitors should act as effector cells in IL-33-related diseases by producing cytokines and chemokines.

overall_design: Total RNA samples were obtained from mouse myeloid progenitors such as eosinophil progenitors (EoPs), basophil progenitors (BaPs), mast cell progenitors (MCPs) and megakaryocyte / erythrocyte progenitors (MEPs) cultured for 48 hours with or without IL-33.


title: Transcriptome Profiles of Gag-Specific CD8+ T Cells Induced by Live Attenuated SIV Vaccine

status: Public on Dec 02 2015

city: Lincoln

first: Wuxun

last: Lu

state: NE

address: 4240 Fair ST

department: School of Biological Sciences

institute: University of Nebraska-Lincoln

summary: SIVmac239Δnef (SIVΔnef) live attenuated vaccine (LAV) induces the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. Time-dependent protection is a unique feature of this vaccine: macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. To elucidate the protection mechanisms induced by SIVΔnef vaccine, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A*01 rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in cell activation, differentiation and maturation toward central memory cells. Our study indicates that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time may contribute to the maturation of time dependent protection.

overall_design: Female Mamu-A*01+ Indian rhesus macaques (Macaca mulatta) were intravenously vaccinated with SIVmac239Δnef. At 3 (n=5) and 20 WPV (n=3), SIV Gag-specific CD8+ T cells were isolated from peripheral blood samples using tetramer staining and flow cytometry. The RNAs were extracted and hybridized on Affymetrix Rhesus Macaque Genome Array.

first: Yanmin

last: Wan

first: Fangrui

last: Ma

middle: R

last: Johnson

first: Ashley

last: Haase

first: Qingsheng

last: Li


title: LR11 knockout in BAT and WAT

city: sakura

first: Hideaki

last: Bujo

address: 564-1 shimoshizu

institute: Toho University Sakura hospital

summary: To study the gene expression profiles of brown (BAT) and white (WAT) adipose tissues in wild type and LR11-deficeint mice.

overall_design: The four RNA sources, WT scWAT, Lr11 -/- scWAT, WT BAT and Lr11 -/- BAT, were prepared from subcutaneous WAT and BAT from wild-type mice and Lr11 -/- mice, respectively (n=3 each).

first: Meizi

last: Jiang


title: mRNA sequence data of individual Drosophila melanogaster male and female flies from 16 Drosophila Genetic Reference Panel lines reared in replicated environments

status: Public on Dec 21 2015

city: Bethesda

first: Brian

last: Oliver

state: MD

address: 50 South Drive

department: LBG

institute: NIDDK, NIH

summary: Our primary objective was to characterize the amount of variation in transcript abundance among individual flies with identical genotypes.  We also wanted to determine which analysis methods would be optimal for RNA-Seq data.  To meet these objectives, we performed transcriptional profiling of whole adult individuals from 16 Drosophila Genetic Reference Panel (DGRP) lines.  We quantified differential expression among genotypes, environments, and sexes.

overall_design: We randomly chose 16 DGRP lines for this experiment: DGRP-93, DGRP-229, DGRP-320, DGRP-352, DGRP-370, DGRP-563, DGRP-630, DGRP-703, DGRP-761, DGRP-787, DGRP-790, DGRP-804, DGRP-812, DGRP-822, DGRP-850, and DGRP-900. We collected 8 virgin male and 8 virgin female flies from the 16 DGRP genotypes in three replicated environments to produce RNA sequence profiles.  We controlled the environmental conditions in the following ways. We seeded the fly cultures with 5 male and 5 female parents.  We reared the progeny in a single incubator on standard Drosophila food (http://flystocks.bio.indiana.edu/Fly_Work/media-recipes/bloomfood.htm) at 25°C, 60% humidity, and a 12:12-hour light:dark  cycle.  We collected and maintained male and female virgins at 20 flies to a same-sex vial for four days prior to RNA extraction to control for social exposure.  Flies were frozen for RNA extraction at the same circadian time (1:00 pm) in 96-well plates.  PolyA RNA stranded libraries were prepared by modifying an existing protocol.  ERCC (External RNA Controls Consortium, SRM2374, beta version, pools 78A/78B) sequences were added during the library preparation as a control. For some samples >1 library was generated to check technical variation. We performed multiplexed single-end 76 bp sequencing on an Illumina HiSeq2000.  Reads were mapped to FlyBase release 5 version 57 and release 6 version 01 of the Drosophila melanogaster genome and the ERCC sequences.  Mapped reads were counted at the gene level.

first: Kseniya

last: Golovnina

first: Zhen-Xia

last: Chen

first: Yanzhu

last: Lin

first: Hina

last: Sultana

first: Susan

last: Harbison


title: Cytogenetic aberrations in Hepatocellular adenoma and carcinoma [III]

city: Boston

first: Lee

middle: Alan

last: Albacker

state: MA

address: 200 Longwood Ave

department: Department of Systems Biology

institute: Harvard Medical School

summary: array CGH (244K) of liver tumors and unaffected liver controls from mice conditionally deficient for Mad2 and p53 in hepatocytes

overall_design: aCGH of sample DNA was hybridized with sex mismatched control DNA from a different mouse. Tumor and unaffected liver tissues were tested for each mouse. 19 tissue samples, 10 tumors, 9 normal samples

first: Ying

last: Yue

first: Darin

last: Takemodo


title: Cytogenetic aberrations in hepatocellular carcinoma [II]

summary: Array CGH (44K) of liver tumors and unaffected liver controls from mice conditionally deficient for Mad2 and p53 in hepatocytes


title: Suppression of virus-induced CCL2, CXCL10 and IL-6:  biomarkers of Lactobacillus-mediated protection at the respiratory tract

status: Public on Nov 02 2015

city: Hamilton

first: Dan

last: Sturdevant

state: MT

address: 903 S 4th street

department: NIAID

institute: NIH

summary: In this manuscript, we present a more extensive analysis of inflammatory suppression mediated by L. plantarum at the respiratory tract.  Via full genome microarray of whole lung tissue, we have generated an extensive list of soluble proinflammatory mediators that are expressed in response to PVM infection and we identify those mediators that are suppressed and also those that are not suppressed in response to L. plantarum priming.  We focused further study on three specific virus-induced soluble mediators that are differentially expressed and that serve as specific biomarkers for Lactobacillus-mediated survival in response to acute respiratory virus infection.  Among several novel directions, we use these biomarker cytokines to explore Lactobacillus-mediated actions at the respiratory tract that are unique and distinct from those taking place at gastrointestinal mucosa.

overall_design: innoculation of mouse using combinations of PBS/BSA, Lactobacillus plantarum and pneumonia virus

first: Caroline

middle: M

last: Percopo

first: Tyler

last: Rice

first: Kimberly

middle: D

last: Dyer

first: Janice

middle: L

last: Luo

first: Daniel

first: Stephen

middle: F

last: Porcella

first: Joseph

middle: B

last: Domachowske

first: Jesse

last: Keicher

first: Helene

last: Rosenberg


title: G9a and ZNF644 physically associate to suppress progenitor gene expression during neurogenesis

first: Yue

last: Li

state: Massachusetts

address: 32 Vassar Street, 32-D528

institute: Massachusetts Institute of Technology

summary: Proliferating progenitor cells undergo unidirectional changes in competence to give rise to post-mitotic progeny of specialized function. These transitions in cell fate typically involve the dynamic regulation of gene expression programs by histone methyltransferase (HMT) complexes. However, the composition, roles and regulation of these HMT complexes in regulating cell fate decisions in vivo are poorly understood. Using affinity purification and mass spectrometry (AP-MS), we identified the uncharacterized C2H2-like zinc finger (ZF) protein ZNF644, which is putatively causally linked to high-grade (degenerative) myopia, as a novel G9a/GLP-interacting protein and co-regulator of histone methylation. Using zebrafish embryos, we characterized the function of two ZNF644 orthologues, znf644a and znf644b, revealing critical neural- specific roles in regulating G9a/H3K9me2-mediated gene silencing in the retina. In addition, by virtue of additional non-overlapping requirements for znf644a and znf644b during retinal differentiation, we gained further insights regarding additional facets of retinal differentiation regulated by the G9a-ZNF644 physical association, such as maintaining retinal cell viability and in transitioning proliferating progenitor cells towards differentiation. Collectively, our data points to the G9a-ZNF644 physical interaction as a critical neural progenitor-specific co-factor of G9a/H3K9me2-mediated gene silencing during neuronal differentiation.

overall_design: Examination of histone modifications in 2 ZNF644a/b mutants versus wildtype.

first: Jonathan

last: Olsen

first: Loksum

last: Wong

first: Hongbo

last: Guo

first: Zhaolei

last: Zhang

first: Jack

last: Greenblatt

first: Vincent

last: Tropepe

first: Andrew

last: Emili


title: Cytogenetic aberrations in Hepatocellular adenoma and carcinoma

first: Lee

last: Albacker


title: Investigation of gene expression responses to acute stress exposure in adults with early childhood adversity experience

status: Public on Nov 30 2015

city: Bochum

first: Robert

last: Kumsta

address: Universitätsstraße 150

department: Department of Genetic Psychology

country: Germany

institute: Ruhr-University Bochum

summary: Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross-talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. Here, we investigated neuroendocrine as well as genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal (HPA) axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed a larger stress-induced increase of cardinal pro-inflammatory transcripts IL6 and FOSB, and an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups. Noteworthy, FKBP5 expression was less responsive to cortisol induction in the early adversity group, with potential effects on the ultra-short feedback loop that balances FKBP5 and glucocorticoid receptor activity. Further exploratory analyses showed differential stress-induced regulation of gene transcription between the groups. Prominent among the differentially regulated transcripts were those coding for genes involved in signal transducer activity, G-protein coupled receptors, and several genes involved in serotonin receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress responsive pathways, which - when chronically or repeatedly activated  - might predispose individuals to stress-related psychopathology.

overall_design: 180 samples were analyzed. 60 healthy adults (30 with history of childhood adversiy, 30 controls without trauma history) were subjected to a standardized laboratory stress protocol. Blood samples for the isolation of CD14+ monocytes were taken at 45 before, and at 45 and 180 minutes post stress.

first: Marion

last: Schwaiger

first: Marianna

last: Grinberg

first: Dirk

last: Moser

first: Markus

last: Heinrichs

first: Jan

last: Hengstler

first: Jörg

last: Rahnenführer

first: Steve

last: Cole


title: Multi-tissue functional genomic study of systemic sclerosis

city: Lebanon

first: Tammara

last: Wood

state: NH

address: WTRB 674

department: Biomedical Data Science

institute: Dartmouth Medical School


title: Cytogenetic aberrations in hepatocellular carcinoma [I]

overall_design: aCGH of sample DNA was hybridized with sex mismatched control DNA from a different mouse. Dye swaps were performed for each sample

first: Ying

last: Yue

first: Darin

last: Takemodo


title: Identification of the BRD1 interactome and its impact on mental disorder risk

status: Public on Oct 29 2015

city: Aarhus

first: Tue

last: Fryland

state: Aarhus

address: Bartholins Allé 6

department: Biomedicine

country: Denmark

institute: Aarhus University

summary: We identified chromatin binding sites for two isforms of BRD1 (BRD1-S and BRD1-L) using ChIP-seq.

overall_design: BRD1 isoforms were cloned, epitope-tagged (pcDNA 6 V5-His6, Lifetechnologies) and stably expressed in HEK293T cells. Chromatin immunoprecipitations were performed using anti V5-antibody conjugated agarose beads (Sigma-Aldrich) and anti HA antibody conjugated agarose beads (Sigma-Aldrich) as controls

first: Anders

last: Borglum

first: Mads

last: Bak

first: Niels

last: Tommerup


title: Ataxia-telangiectasia cerebellar cortex expression

status: Public on Oct 30 2015

city: Piscataway

first: Ronald

middle: P.

last: Hart

state: NJ

address: 604 Allison Rd Rm B430

department: Cell Biology & Neuroscience

institute: Rutgers University

summary:
Cerebellar cortex expression in ataxia-telangiectasia patients and normal controls.

The neurodegenerative disease known as ataxia-telangiectasia (A-T) is caused by the absence of the ATM (A-T mutated) protein. A long-standing mystery surrounding A-T is why cerebellar Purkinje cells (PCs) appear uniquely vulnerable to ATM-deficiency. Here, we present that 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic marker found at high levels in neurons, is substantially reduced in human A-T and Atm-/- mouse cerebellar PCs. TET1, an enzyme that converts 5mC to 5hmC, responds to DNA damage. Manipulation of TET1 activity directly affects neuronal cell cycle reentry and cell death after the induction of DNA damage. Quantitative, genome-wide analysis of 5hmC of samples from human cerebellum showed that in ATM-deficiency there is a remarkable genome-wide reduction of 5hmC enrichment at both proximal and distal regulatory elements. These results reveal a role of TET1-mediated 5hmC in DNA damage response, and provide insights into the basis of a PC-specific DNA demethylation alteration in ATM-deficiency.

overall_design: Human frozen tissue was obtained from the NICHD Brain and Tissue Bank of Developmental Disorders at the University of Maryland, Baltimore, MD. RNA was prepared and run on an Illumina Human HT-12 v4 microarray. 3 ataxia-telangiectasia (A-T) cases and 4 normal controls.

middle: P

first: Jiali

last: Li

first: Karl

last: Herrup


title: Selective loss of 5hmC links to A-T Purkinje cell vulnerability

type: Methylation profiling by high throughput sequencing

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

The neurodegenerative disease known as ataxia-telangiectasia (A-T) is caused by the absence of the ATM (A-T mutated) protein. A long-standing mystery surrounding A-T is why cerebellar Purkinje cells (PCs) appear uniquely vulnerable to ATM-deficiency. Here, we present that 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic marker found at high levels in neurons, is substantially reduced in human A-T and Atm-/- mouse cerebellar PCs. TET1, an enzyme that converts 5mC to 5hmC, responds to DNA damage. Manipulation of TET1 activity directly affects neuronal cell cycle reentry and cell death after the induction of DNA damage. Quantitative, genome-wide analysis of 5hmC of samples from human cerebellum showed that in ATM-deficiency there is a remarkable genome-wide reduction of 5hmC enrichment at both proximal and distal regulatory elements. These results reveal a role of TET1-mediated 5hmC in DNA damage response, and provide insights into the basis of a PC-specific DNA demethylation alteration in ATM-deficiency.


title: Single-cell RNA-Seq resolves cellular complexity in sensory organs from the neonatal inner ear

status: Public on Oct 15 2015

first: Michael

middle: C

last: Kelly

address: 41 Center Drive

department: Center for Cancer Research

institute: NCI

summary: In the inner ear, cochlear and vestibular sensory epithelia utilize grossly similar cell types to transduce different stimuli: sound and acceleration.  Each individual sensory epithelium is composed of highly heterogeneous populations of cells based on physiological and anatomical criteria. However, limited numbers of each cell type have impeded transcriptional characterization. Here we generated transcriptomes for 301 single cells from the utricular and cochlear sensory epithelia of newborn mice to circumvent this challenge. Cluster analysis indicates distinct profiles for each of the major sensory epithelial cell types, as well as less distinct subpopulations. Asynchrony within utricles allows reconstruction of the temporal progression of cell-type specific differentiation and suggests possible plasticity among cells at the sensory-nonsensory boundary. Comparisons of cell types from utricles and cochleae demonstrate divergence between auditory and vestibular cells despite a common origin. These results provide significant insights into the developmental processes that form unique inner ear cell types.

overall_design:
mRNA-seq profiles from 301 single cells and bulk population controls from postnatal day 1 mouse utricle and cochlear epithelia were analyzed

Please note that the *PhenoData.txt files provide additional metadata that are otherwise not easily accessible from the record, including which sample cluster they were identified as belonging to within the associated manuscript.

first: Joseph

last: Burns

last: Hoa

first: Robert

middle: J

last: Morell

first: Matthew

last: Kelley


title: PAD4 Inhibition is Sufficient for the Amelioration of Collagen-Induced Arthritis

status: Public on Oct 08 2015

city: Stanford

first: William

last: Robinson

address: 269 Campus Dr

institute: Stanford University

summary: To examine the effects of GSK199 treatment on antibody responses, a synovial antigen array analysis was performed using day 35 sera derived from mice with CIA treated with 30 mg/kg qd, 30 mg/kg bid GSK199 or saline. The synovial antigen arrays contain nearly 200 peptides and proteins, both citrullinated and uncitrullinated, representing candidate antigens in RA. Significance Analysis of Microarrays identified 7 and 14 autoantibody reactivities that were statistically decreased in CIA mice treated with 30 mg/kg qd or 30 mg/kg bid GSK199 respectively, compared to PBS treatment. By comparison, over 150 native and citrullinated epitopes on the arrays did not exhibit significant differences in reactivity. Sera from mice treated with 30 mg/kg GSK199 qd exhibited decreased IgG reactivity to native epitopes such as peptides from human fibrinogen alpha and beta chains and keratin while sera from mice treated with 30 mg/kg bid GSK199 demonstrated decreased IgG reactivity to native epitopes including collagen IV, heat shock protein 65, peptides from human fibrinogen alpha and beta chains (two of which match those that were decreased in the 30 mg/kg qd group), and vimentin as compared to saline controls (q < 0.1%). Decreased autoantibody reactivity to citrullinated peptides from vimentin and fibromodulin were also observed in sera from mice treated with 30 mg/kg bid GSK199 compared to controls treated with saline (q < 0.1%), but not by GSK199 30 mg/kg qd. There were no differences between treatment with GSK199 or saline alone in the levels of autoantibodies to 38 other citrullinated proteins in the array. These data demonstrated that GSK199 treatment decreases the development of autoantibodies in CIA and impairs epitope spreading to a degree similar to that observed with pan-PAD inhibition.

platform_organism:
Homo sapiens
Mus musculus

overall_design: Custom-spotted protein arrays were probed with day 35 sera samples from individual CIA mice, with seven arrays probed for each of three intervention groups (saline, GSK199 at 30 mg/kg qd, or GSK199 at 30 mg/kg bid).

first: Van

last: Willis

first: Nirmal

middle: K

last: Banda

first: Kristen

last: Cordova

first: Lauren

last: Lahey

middle: H

first: David

last: Cooper

first: Dave

last: Lugo

first: Simon

last: Taylor

first: Rab

last: Prinjha

first: Huw

last: Lewis

first: V

last: Holers


title: Transcriptome analysis of a N. punctiforme sigG mutant

status: Public on Sep 01 2015

city: Northridge

middle: L.

last: Summers

state: California

address: 18111 Nordhoff St

department: Dept. of Biology

institute: California State University Northridge

summary: Nostoc punctiforme is a filamentous cyanobacterium capable if differentiating normal vegetative cells into nitrogen fixing heterocysts and spore-like akinetes.  Here the effects of a sigma factor (sigG) mutation on the transcriptome was analyzed under 1) normal vegetative growth, and 2)  following akinete induction.  A zwf strain grown with fructose differentiates into akinetes following transfer to darkness.  A DNA microarray was used to compare gene expression from the zwf strain to a zwf sigG double mutant two days following akinte induction by darkness.

overall_design: Gene expression in a zwf mutant strain was compared to a zwf sigG double mutant strain under normal vegetative growth and at two days following akinete induction. Each experiment used three array slides with two biological replicates.  A dye swap was used for one biological replicate.


title: Distinct brain transcriptome profiles in c9orf72-associated and sporadic ALS

status: Public on Jul 19 2015

city: Rochester

first: Hu

last: Li

state: MN

address: 200 First Street, Gonda Building G19-408

department: Molecular Pharmacology & Experimental Therapeutics

institute: Mayo Clinic

summary: Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS cases (8,224 AS, 1,437 APA), including changes in ALS-associated genes (e.g. ATXN2 and FUS), and cases of sporadic ALS (sALS; 2,229 AS, 716 APA). Furthermore, hnRNPH and other RNA-binding proteins are predicted as potential regulators of cassette exon AS events for both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS.

overall_design: Examination transcriptiome profiles in c9orf72-associated ALS, sporadic ALS and healthy control

first: Mercedes

last: Prudencio

first: Veronique

middle: V

last: Belzil

first: Leonard

last: Petrucelli


title: miRNA expression profiling of Human Myeloma Cell Lines Pre- and Post- 5'azacytidine Treatment

status: Public on Aug 31 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: We performed genome-wide miRNA expression profiling (MEP) of a panel of four human Myeloma cell lines treated with 5'azacytidine compared to control (DMSO treatment), with the objective of unmasking miRNAs silenced by DNA hypermethylation.

overall_design: Total RNA, including miRNA, were extracted using Qiagen miRNeasy kit and profiled using Agilent Human MiRNA Array (Release 16.0, 8X60k)

first: Wee

last: Chng


title: Transcriptome imposed by Notch ligands (Jag1 or Dll4) on ckit+ and ckit- cells from E11.5 AGM

status: Public on Aug 20 2015

city: Barcelona

first: Anna

last: Bigas

state: Barcelona

address: Dr. Aiguader 88

department: Cancer Research

institute: Institut Hospital del Mar d'Investigacions Mèdiques

summary: Hematopoietic Stem Cells (HSC) are originated during embryonic development from endothelial-like cells located in the ventral side of the dorsal aorta around day E10-12 of murine development. This region is called AGM for Aorta/Gonad/Mesonephros refering to the tissues around the hemogenic aorta. Cells that emerge from the endothelium and show hematopoietic traits can be distinguished by the expression of the c-kit receptor and finally acquire the CD45 marker. The effect of Notch activation by each one of the ligands has been tested on c-kit+ and ckit- cells from the endothelium of the E11.5 AGM . Incubations with stromal cell lines exposed the cells to high levels of ligand and induced changes in the transcriptome of these cells.

overall_design: AGM regions were obtained from E11.5 embryos by dissection and digested with 0.1% collagenase. Cells were stained with anti-CD31, anti-CD45 and anti-Ter119 antibodies. Sorting of the CD31+CD45-Ter119- population was performed and some cells were separated into ckit+ and ckit- (data previously submited GSE35395). The rest of the CD31+CD45- cells were incubated for 2 hours on OP9 stromal cells expressing ectopic Jagged1 or Delta4 (OP9-Jag1 and OP9-Dll4). After culture with each ligand, cells were separated into CD31+CD45-ckit+ and CD31+CD45-ckit-. Cells were harvested for RNA puriication and microarray analysis.

first: Abul

last: Islam

first: Jordi

last: Guiu

first: Leonor

last: Gama-Norton

first: LLuis

last: Espinosa


title: Identification of early targets of SOX2 and PI3K signaling in normal, patient-derived tracheal basal cell lines.

status: Public on Jul 01 2015

city: Toronto

first: carl

last: virtanen

state: Ontario

address: 101 College St

department: Princess Margaret Genomics Centre

country: Canada

institute: University Health Network

summary: Microarrays were used to examine gene expression changes in patient derived tracheal basal cell lines after treatment with Lenti-SOX2. Comparisons were made between baseline, Lenti-SOX2 and Lenti-SOX2 with a PI3K inhibitor (BKM120).

overall_design: Total RNA obtained from celll lnes 36 hours post lentivirus addition.

first: Carl

last: Virtanen

first: Nadeem

last: Moghal

first: Bo

last: Kim


title: Gene expression in rat hippocampal CA1 during the consolidation of contextual fear memory

status: Public on Sep 25 2015

city: Cardiff

first: Kerrie

last: Thomas

state: Wales

address: Maindy Road

department: Neuroscience & Mental Health Research Institute, & Cardiff School of Biosciences

institute: Cardiff University

summary: Adult rats (male Lister hooded) received a single unsignaled scrambled footshock (0.5 mA for 2 s) 2 min into a 3min exposure to a novel context. One half rats received bilateral microinfusions (1 microlitre/hemisphere) of 2 nmol/microlitre BDNF antisense ODN (BDNFASO, 5’-TCTTCCCCTTTTAATGGT-3’ in PBS, pH 7.4) or BDNF missense ODN (BDNFMSO, 5’ -ATACTTTCTGTTCTTGCC-3’ in PBS, pH 7.4) into the dorsal hippocampus (AP -3.50, relative to bregma), 90 min before contextual fear conditioning (CFC). Infusions were made in awake rats via previously surgically implanted indwelling stainless steel cannula.  Rats were housed in the home cages at all times outside the conditioning procedure. Rats were killed by CO2 inhalation 2 hours after CFC. CA1 enriched dorsal hippocampus was immediately dissected on ice before rapid freezing and storage at -80oC. The BDNFASO-infused group represent consolidation-impaired rats.

overall_design: Samples from individual rats were hybridized to separate microarrays. There was no amplification of cDNA before hybridization. There were 16 separate samples. The BDNFMSO-treated rats (n = 8) represent the consolidation group; BDNFASO-treated rats (n = 8) represent the consolidation-impaired group. All tissue was taken 2 hours after contextual fear conditioning.


title: neonatal and adult mice lung

status: Public on Jul 15 2015

city: Fukushima

first: Hayato

last: Go

state: Fukushima

address: Hikarigaoka 1

department: Pediatrics

institute: Fukushima Medical University

summary: We performed miRNA array analysis from 4 groups (neonatal lung control, neonatal lung after hyperoxia, adult lung control, adult lung after hyperoxia).   We used pools of every 100ng of total RNA of three samples for each groups.

overall_design: Examination of miRNA levels during lung development and in hyperoxia

first: Phyllis

last: Dennery


title: Gene expression in rat hippocampal CA1 after the retrieval of contextual fear memory in the absence of extinction.

summary: Adult rats (male Lister hooded) received a single unsignaled scrambled footshock (0.5 mA for 2 s) 2 min into a 3min exposure to a novel context. 48 hours later, rats were reexopsed to the condition context for 2 min (TEST). One half rats received bilateral microinfusions (1 microlitre/hemisphere) of 2 nmol/microlitre Zif268 antisense ODN (ZIFASO, 5’- GGTAGTTGTCCATGGTGG-3’in PBS, pH 7.4) or Zif268 missense ODN (ZIFMSO, 5’ -GTGTTCGGTAGGGTGTCA-3’in PBS, pH 7.4) into the dorsal hippocampus (AP -3.50, relative to bregma), 90 min before TEST. Infusions were made in awake rats via previously surgically implanted indwelling stainless steel cannula.  Rats were housed in the home cages at all times outside the conditioning and TEST procedures. Rats were killed by CO2 inhalation 2 hours after TEST. CA1-enriched dorsal hippocampus was immediately dissected on ice before rapid freezing and storage at -80oC. The ZIFSO-infused group potentially represents reconsolidation-impaired rats.

overall_design: Samples from individual rats were hybridized to separate microarrays. There was no amplification of cDNA before hybridization. There were 16 separate samples. The ZIFMSO-treated rats (n = 8) potentially represent a reconsolidation group; ZIFASO-treated rats (n = 8) represent a reconsolidation-impaired group. All tissue was taken 2 hours after recall of contextual fear memory.


title: Gene expression in rat hippocampal CA1 associated with contextual fear memory formation and recall

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

overall_design: Refer to individual Series


title: Transplantation of gastric organoid-derived spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) cell lineage promotes ulcer repair in the aged stomach

status: Public on Sep 23 2015

city: Cincinnati

first: Mario

last: Medvedovic

state: OH

address: 3223 Eden Av. ML 56

department: Department of Environmental Health

institute: University of Cincinnati

summary:
Background & Aims: Spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) is known to emerge following parietal cell loss and during Helicobacter pylori infection, however its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration.
Methods: Acetic acid ulcers were induced in young (2-3 months) C57BL/6 mice to determine the quality of ulcer repair.  Gastric tissue was collected and analyzed to determine the expression of SPEM within the regenerating epithelium.  As a comparison to native tissue the expression of SPEM was also identified within cultured gastric mouse-derived organoids.
Results:  Wound healing in the mice coincided with the emergence of SPEM expressing CD44v within the ulcerated region.  The emergence of SPEM was also observed in cultured gastric organoids.  Conclusions: These data demonstrate the SPEM may play a role in epithelial regeneration.
Conclusions: These data demonstrate the SPEM may play a role in epithelial regeneration.

overall_design:
4 samples were used for ulcerated and uninjured tissue.  1 sample was used for intact tissue and organoid-derived RNA.
The 'Ulcerated' samples represent C57BL/6 mice with ulcers and the 'Uninjured' samples represent the healthy controls (for "ulcerated" samples). The "Intact stomach tissue" and "Gastric organoids" samples are other types of samples that compared separately. "Gastric organoids" in this comparison are derived from "Intact stomach tissue".

first: Amy

last: Engevik

first: Rui

last: Feng

first: Eunyoung

last: Choi

first: Shana

last: White

first: Jing

last: Li

first: Maxime

last: Mahe

first: Sunghee

last: Oh

first: Eitaro

last: Aihara

first: Kristen

middle: A

first: Marshall

last: H. Montrose

first: Andrew

middle: S

last: Giraud

first: Nina

last: Bertaux-Skeirik

first: Michael

last: Helmrath

first: James

last: Goldenring

first: Yana

last: Zavros


title: mRNA expression changes upon microRNA downmodulation in colorectal cancer cell lines

status: Public on Oct 06 2015

city: Candiolo

first: Enzo

last: Medico

state: TO

address: Strada Prov. 142, km 3,95

department: Oncology

country: Italy

institute: Candiolo Cancer Institute, University of Torino

summary: Colorectal cancer cell lines were transduced with lentiviral antisense miRNA inhibitors (miRZIPs) targeting miR-429, miR-200b, miR-194 and miR-203. Global mRNA expression profiles were generated with Illumina arrays on transduced and control cells to identify mRNAs whose expression is regulated by the above microRNAs.

overall_design: Colorectal cancer cell lines transduced with control vectors or with microRNA targeting vectors were profiled, together with wild-type cells, using two independent RNA extractions.

first: Laura

last: Cantini


title: TALENs-mediated gene disruption of FLT3 in leukemia cells: Using genome-editing approach for exploring the molecular basis of gene abnormality

status: Public on Jun 10 2015

city: Wuhan

first: wang

last: jue

address: Jiefang Avenue 1095

department: Hematology

institute: Huazhong University of Science and Technology, Tongji Hospital

summary: Novel analytic tools are needed to elucidate the molecular basis of leukemia-relevant gene mutations in the post-genome era. We generated isogenic leukemia cell clones in which the FLT3 gene was disrupted in a single allele using TALENs. Isogenic clones with mono-allelic disrupted FLT3 were compared to an isogenic wild-type control clone and parental leukemia cells for transcriptional expression, downstream FLT3 signaling and proliferation capacity. The global gene expression profiles of mutant K562 clones and corresponding wild-type controls were compared using RNA-seq. The transcriptional levels and the ligand-dependent autophosphorylation of FLT3 were decreased in the mutant clones. TALENs-mediated FLT3 haplo-insufficiency impaired cell proliferation and colony formation in vitro. These inhibitory effects were maintained in vivo, improving the survival of NOD/SCID mice transplanted with mutant K562 clones. Cluster analysis revealed that the gene expression pattern of isogenic clones was determined by the FLT3 mutant status rather than the deviation among individual isogenic clones. Differentially expressed genes between the mutant and wild-type clones revealed an activation of nonsense-mediated decay pathway in mutant K562 clones as well as an inhibited FLT3 signaling. Our data support that this genome-editing approach is a robust and generally applicable platform to explore the molecular bases of gene mutations.

overall_design: Global gene expression profiles of three isogenic K562 mutant clones (clones k20, k112, k324) and three randomly selected wild-type clones (clones kw1, kw2, kw3) were generated by RNA-seq, using Illumina Hiseq 2000.

first: Jue

last: Wang

first: Jianfeng

last: Zhou


title: Sox4 links tumor suppression to accelerated aging in mice [Telogen]

status: Public on May 20 2015

city: Madrid

first: Miguel

last: Foronda

state: Select a State or Province

address: Calle Melchor Fernández Almagro

institute: CNIO

summary: Sox4 is a transcription factor expressed during embryonic development and some adult tissues such as lymphoid organs, pancreas, intestine and skin. During embryogenesis, Sox4 regulates the survival of mesenchymal and neural progenitors, lymphocyte and myeloid differentiation, and pancreatic, bone and cardiac development. Aberrantly increased Sox4 expression is linked to malignant transformation and metastasis in several types of human cancer. To study the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display a plethora of age-related degenerative disorders and reduced spontaneous cancer incidence, indicating a role for this protein in maintaining adult tissue homeostasis and in tumor growth. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO) in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and DNA damage accumulation, accompanied by resistance to chemical carcinogenesis. These phenotypes correlate with downregulation of cell cycle, DNA repair and skin stem cell genes in the absence of Sox4. Altogether, these findings highlight the importance of Sox4 in adult tissue homeostasis and cancer.

overall_design: Sox4 WT and cKO (conditional KO in skin) skin  was collected for microarray hybridization, to study the contribution of Sox4 to skin homeostasis in basal conditions (Telogen)

first: Paula

last: Martínez

first: Stefan

last: Schoeftner

first: Gonzalo

last: Gómez-López

first: Ralph

last: Schneider

first: Juana

last: Flores

first: David

middle: G

last: Pisano

first: María

last: Blasco


title: caArray_EXP-608: TCGA (Laml): Analysis of RNA Expression Array Data for Acute Myeloid Leukemia Using Affymetrix HG-U133 Plus 2.0 (WUSTL)

status: Public on May 14 2015

city: Rockville

first: Mervi

last: Heiskanen

address: 9609 Medical Center Drive, 1W378

department: CBIIT

summary: TCGA Analysis of RNA Expression Array Data for Acute Myeloid Leukemia Using Affymetrix HG-U133 Plus 2.0

overall_design:
EXP-608
Assay Type: Gene Expression
Provider: Affymetrix
Array Designs: HG-U133_Plus_2
Organism: Homo sapiens (ncbitax)
Tissue Sites: Blood
Material Types:organism_part, Primary Blood Derived Cancer

first: Shin

last: Leong

first: Timothy

last: Ley


title: Sox4 links tumor suppression to accelerated aging in mice


title: Sox4 links tumor suppression to accelerated aging in mice [Hair regeneration]

overall_design: Sox4 WT and cKO (conditional KO in skin) were plucked and skin  was collected for microarray hibridization, to study the contribution of Sox4 to hair regeneration and hair follicle stem cell activation


title: Gene expression in rat hippocampal CA1 during the extinction of contextual fear memory

first: Kerrie

last: Thomas

summary: Adult rats (male Lister hooded) were pre-exposed for 3 d for 10 min /d (24 hr interval) to two different novel contexts. On day 4 rats received a single unsignaled scrambled footshock (0.5 mA for 2 s) 2 min into a 3min exposure to one of the two contexts. Rats were either returned to the CS conditioned context (CS+, EXT group) or to the other (CS-, NOR group) context for 10 min, 48h after contextual fear conditioning. Rats were housed in the home cages at all times outside the conditioning and re-exposure components. The novel context chosen to be the conditioned context was counterbalanced across the experimental groups. Rats were killed by CO2 inhalation 2 hours after CS- or CS+ exposure. CA1-enriched dorsal hippocampus was immediately dissected on ice before rapid freezing and storage at -80oC. The CS+ group represents rats that underwent extinction of contextual fear memory.

overall_design: Samples from individual rats were hybridized to separate microarrays. There was no amplification of cDNA before hybridization. There were 12 separate samples. The CS+ rats (n = 6) represent the extinction group; CS- rats (n = 6) represent a control group that does not undergo extinction. All tissue was taken 2 hours context re-exposure/extinction training.


title: Nuclear myosin 1 contributes to a chromatin landscape compatible with RNA polymerase II transcription activation

status: Public on May 04 2015

city: Abu Dhabi

first: Piergiorgio

last: Percipalle

state: Abu Dhabi

address: Saadiyat Campus, Abu Dhabi

department: Biology Department, Science Division

country: United Arab Emirates

institute: New York University Abu Dhabi

summary: Nuclear myosin 1c (NM1) is emerging as regulator of transcription and chromatin organization. Using a genome-wide approach we report here that NM1 binds across the mammalian genome with occupancy peaks at class II gene promoters, correlating with distributions of RNA Polymerase II (Pol II) and active epigenetic marks. We show that NM1 synergizes with polymerase-associated actin to maintain active Pol II at gene promoters. NM1 also co-localizes with the nucleosome remodeler SNF2h at class II promoters where they assemble together with WSTF as part of the B-WICH complex to remodel chromatin. Following B-WICH assembly, NM1 mediates physical recruitment of the histone acetyl transferase PCAF and the histone methyl transferase Set1/Ash2 to maintain and preserve H3K9acetylation and H3K4trimethylation for active transcription. We propose a novel genome-wide mechanism where myosin synergizes with Pol II-associated actin to link the polymerase machinery with permissive chromatin for transcription activation.

overall_design: Association of nuclear myosin 1 (NM1) with the genome in mouse embryonic fibroblasts

first: Bader

last: Almuzzaini


title: Gene expression profiles associated with pediatric relapsed AML

status: Public on May 07 2015

city: Amsterdam

first: Costa

last: Bachas

address: CCA 4.28, De Boelelaan 1117

department: Pediatric Oncology/ Hematology

country: Netherlands

institute: VU University Medical Center

summary: In high income countries 90% of the patients achieve complete remission after induction chemotherapy. However, 30-40% of these patients suffer from relapse. These patients face a dismal prognosis, as the majority (>60%) of relapsed patients die within 5 years. As a result, outcome for pediatric acute myeloid leukemia (AML) patients remains poor and has stabilized over the past 15 years. To prevent or better treat relapse of AML is the best option to improve outcome. Despite patient specific differences, most patients do respond to initial therapy. This suggests that at relapse, mechanisms are active that cause the altered response to chemotherapy. Detailed understanding of mechanisms that cause relapse remain largely elusive. To gain insight in the molecular pathways that characterize relapsed AML, we performed genome wide gene expression profiling on paired initial diagnosis and relapsed AML samples of 23 pediatric AML patients. We used pathway analysis to find which molecular pathways are involved in altered gene expression between diagnosis and relapse samples of individual AML patients.

overall_design: 23 paired diagnosis and relapse bone marrow or peripheral blood samples were collected and cryo-preserved. They were later thawed and processed for hybridization to Affymetrix U133 Plus 2.0 arrays.

first: Gerrit

last: Schuurhuis

first: C

last: Zwaan

first: Marry

last: van den Heuvel-Eibrink

first: Monique

last: Den Boer

first: Eveline

last: de Bont

first: Zinia

last: Kwidama

first: Dirk

last: Reinhardt

first: Ursula

last: Creutzig

first: Jacqeline

last: Cloos

first: Gert-Jan

last: Kaspers


title: Statin-induced  transcriptional changes in breast cancer

status: Public on Jun 23 2015

city: Lund

first: Siker

last: Kimbung

address: Scheelevägen 2

department: Department of Oncology and Pathology, Clinical Sciences, Lund

country: Sweden

institute: Lund University

summary: Global gene expression profiling was performed on [1] paired tumor biopsies collected before and after 2 weeks of statin treatment [2] a collection of breast cancer cells lines following 48hrs of atorvastatin treatment with the aim of detecting statin induced transcriptional changes in breast cancer cells in-vitro.

overall_design:
In this phase II clinical study using the “window-of-opportunity” design, in which the treatment-free window between a cancer diagnosis and surgical tumor resection is used to study the biological effects of a certain drug, atorvastatin, a lipophilic statin, was prescribed to patients with primary breast cancer for two weeks pre-operatively. Tumor samples subjected to whole genome transcriptional profiling were collected before patients started treatment and after completing treatment.
In addition, breast cancer cell lines were exposed to atorvastatin treatment for 48 hrs after which total RNA was extracted and subjected to whole genome transcriptional profiling. Vehicle (DMSO) treated samples were included as controls. Three biological replicates were included per sample (condition).

first: Signe

last: Borgquist


status: Public on May 01 2015

city: Winnipeg

first: Parveen

last: Sharma

state: Manitoba

address: 75A Chancellor's Circle

department: Biosystem Engineering

institute: University of Manitoba

summary:
Transcriptomics analysis of biopolymer (medium chain length polyhydroxyalkanoate) producing strain P.putida LS46 cultured with biodiesel derived waste carbon sources: studies of cellular adaptation to the industrial waste streams and metabolic profiling under the polymer producing conditions.
We are reporting RNAseq analysis data here as part of our multi-level Omics study of medium chain length polyhydroxyalkanoate (mcl-PHA) producing strain P.putida LS46 culture with biodiesel derived waste glycerol and waste fatty acids. The data presented here will be used in two separate manuscripts. The objectives of this study are a): to evaluate cellular responses of P.putida LS46 under industrial waste stream. b): to study gene expression profile under two selected mcl-PHA producing conditions of P.putida LS46. Comparative multi-level Omics study: for objective a): Exponential P.putida LS46 cell from waste glycerol culture compared against reagent grade pure glycerol culture. For objective b): Two mcl-PHA producing conditions, namely stationary phase waste glycerol culture and exponential phase waste fatty acid culture of P.putida LS46, were compared against exponential phase waste glycerol culture of P.putida LS46.
Major results from objective a): The waste glycerol substrate induced expression of a large number of genes putatively involved in heavy metal tolerance, including three gene clusters: a putative cusABC transcript unit and two copies of copAB, which are usually involved in copper resistance and tolerance to other monovalent heavy metals. A local gene relocation was observed in cluster 1 consisting cusABC and copAB relative to the KT2440 type strain according to the phylogenetic and gene neighbourhood analyses on various P. putida strains. P. putida LS46 also contains 11 putative MerR family regulators, which sense various environmental stimuli including heavy metals. MerR-1 is an ortholog of the copper response regulator of other gram-negative bacteria, and was highly up-regulated in waste glycerol cultures. Finally, a number of genes involved in cell responses to high extra-cellular Na+ concentrations, and genes of the fatty acid beta-oxidation pathway were up-regulated in waste glycerol cultures
Major results from objective b): Regardless to the type of substrates, up-regulation of two mcl-PHA synthase (PhaC1 and PhaC2), and two phasin proteins (PhaF and PhaI) are the most common genotype under mcl-PHA production conditions. PhaG and possible PhaJ4 connect fatty acid de novo synthesis to mcl-PHA in waste glycerol culture. Interestingly, expression of gene, fabZ, in production of unsaturated fatty acid from fatty acid de novo synthesis was only observed in waste glycerol culture. On the other hand, PhaJ1 and PhaJ4 derived mcl-PHA production via fatty acid beta-oxidation was observed under waste fatty acid culture. These results would help to explain observed different production kinetics and monomer distribution of the polymer. Although under active mcl-PHA production condition, depression on the expression of glpF genes in glycerol transportation system prevent further channelling extra-cellular glycerol into the cell. Waste glycerol culture also triggers trahalose synthesis pathway, a potential competing pathway during mcl-PHA synthesizing. In waste fatty acid culture, the intermediates (acyl-CoA and 3-hydroxyacyl-CoA) of fatty acid beta-oxidation were used for mcl-PHA production and were also likely hydrolysed to their free acid forms via an up-regulated thioesteras coding gene, tesA. Acetyl-CoA cleaved from the pathway was clearly channeled into glyoxylate shut for C2 carbon assimilation over spillage as CO2 through TCA cycle or used in fatty acid biosynthesis pathway.

overall_design: In total 4 sampling points, namely exponential phase of pure glycerol, waste glycerol and waste free fatty acids cultures, and stationary phase of waste glycerol culture. For each sampling point, 2 biological replicates were taken. (Thus 8 samples in total)

first: Jilagamazhi

last: Fu

first: Oleg

last: Krokhin

first: Brian

last: Fristensky

first: John

last: Wilkins

first: Vic

last: Spicer

first: Xiangli

last: Zhang

first: Nazim

last: Cicek

first: Richard

last: Sparling

first: David

last: Levin


title: Genome-wide effect of inhibition of glutamine transporter ASCT2 in PC-3 cells by BenSer or GPNA

status: Public on Apr 10 2015

city: Camperdown

first: Jeff

last: Holst

state: NSW

address: Building 93, Royal Prince Alfred Hospital, Missenden Rd

institute: Centenary Institute

summary: To determine the global effects of ASCT2 inhibition, we used next generation sequencing to determine mRNA expression changes in PC-3 cells treated with BenSer or GPNA for 48 h.

overall_design: Examination of two different ASCT2 inhibitors BenSer and GPNA in prostate cancer cell line PC-3.

first: Qian

last: Wang


title: Gene expression in wild-type vs. G2 -77 enhancer knockout myeloid progenitors

status: Public on Aug 15 2015

city: Madison

first: Kyle

last: Hewitt

state: Wisconsin

address: 1111 Highland Ave.

institute: University of Wisconsin

summary: -77-/- mice exhibited late embryonic lethality, anemia, and a constellation of phenotypes. -77 conferred a unique genetic network in myeloid progenitors, endowing progenitors with potential to produce diverse progeny.

overall_design: E13.5 WT or -77-/- fetal liver cells were isolated and sorted for common myeloid progenitors (CMPs) defined by  Lin-Sca- CD34+FcRlow, and subjected to RNA-sequencing

first: Kirby

middle: d

last: Johnson

first: Colin

middle: n

last: Dewey


title: Global gene expression profiling of human colorectal cancer cell lines

status: Public on Jun 01 2015

first: Enzo

last: Medico

summary: The development of anticancer drugs relies on preclinical models closely recapitulating the molecular profile observed patients. We report here the transcriptional profiles of 155 stable cell lines derived from colorectal cancer and related tissues. For these lines, also mutational and pharmacological profiles are available, which enables their stratification into clinically relevant subgroups.

overall_design: Illumina array-based mRNA expression profiles were generated for 155 established colorectal cancer (CRC) cell lines cultured in vitro under standard conditions. All cell lines have been checked for genetic identity by STR analysis. The identity of one cell line (SNU70) was not confirmed by STR. Two cell lines (FHS and FHC) are of non neoplastic origin, being derived from human fetal intestine.

first: Gabriele

last: Picco

first: Claudio

last: Isella


title: Expression data from human nasopharynx cell line transfected with gene or empty vector.

status: Public on Apr 01 2015

city: Changsha

first: Wei

last: Huang

address: Xiangya road no 110

institute: Central South University

summary: We used microarrays to detail the global gene expression in human nasopharynx cell line transfected with gene or empty vector.

overall_design: human nasopharynx cell line transfected with gene or empty vector were for RNA extraction and hybridization on Affymetrix microarrays.


title: Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington's disease

city: ILLKIRCH

first: Karine

last: Merienne

address: 1 rue Laurent Fries

country: France

institute: IGBMC


title: Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [RNA-seq]

summary: Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease.

overall_design: RNA profiles in Striatum of WT and R6/1 mice by deep sequencing using Illumina HiSeq 2000.


title: Striatal genes regulated by super-enhancers and displaying low paused RNAPII are preferentially down-regulated in Huntington’s disease [ChIP-seq]

overall_design: Examination of H3k27ac and RNA pol II in Striatum by deep sequencing


title: The structure of gene networks that constrain and promote diversification in Heliconius melpomene

status: Public on Mar 31 2015

city: Bogota

first: Carolina

last: Pardo-Diaz

address: Carrera 24 # 63C-69

department: Programa de Biología

country: Colombia

institute: Universidad del Rosario

type: Expression profiling by genome tiling array

summary: Comparison of whole genome and tiled gene expression between different colour pattern races of H. melpomene in developing wings.

sample_organism:
Heliconius melpomene malleti
Heliconius melpomene plesseni

overall_design: A total of 96 ds-cDNA samples labelled with Cy3 were hybridized onto 8 custom-designed Roche NimbleGen 12x135K format microarrays (Roche NimbleGen) for a total of 96 identical subarrays with 135,000 probes of 60 bp each and each hybridising a separate sample. The number of samples corresponded to two races, four stages and four tissue sections (forewing proximal, forewing distal, hindwing and eye), all of them with three independent replicates.


title: MiR-29a regulates liver fibrosis

city: Osaka

first: Yoshinari

last: Matsumoto

institute: Osaka City University

summary: To confirm the mechanism of miR-29a in liver fibrosis healing, we have employed whole genome microarray expression profiling as a discovery platform to identify genes. CCl4 and TAA liver fibrosis model mouse were used for this experiment. After five weeks liver fibrosis induction period, mouse have been observed for one week (1w) or two weeks (2w) and negative control nucleotide (N.C) or miR-29a were injected every 3 days on this period. We used CCl4 1w N.C (n = 1), 1w miR-29a (n = 1), 2w N.C (n = 1), 2w miR-29a (n = 1), and also used TAA model mouse (total n = 8) liver samples for microarray analysis. We can get only one gene (PDGF-c) as a target of miR-29a which relate to liver fibrosis and down-regulated more than 1.5 times in common miR-29a injected group than N.C group.

overall_design: CCl4 and TAA liver fibrosis model mouse were used for this experiment. After five weeks liver fibrosis induction period, mouse have been obserbed for one week (1w) or two weeks (2w) and negative control nucleotide (N.C) or miR-29a were injected every 3 days on this period. We used CCl4 1w N.C (n = 1), 1w miR-29a (n = 1), 2w N.C (n = 1), 2w miR-29a (n = 1), and also used TAA model mouse (total n = 8) liver samples for microarray analysis.

first: Saori

last: Itami

first: Yoshiki

last: Murakami


title: DNA methylation analysis of human skeletal muscle after endurance training

status: Public on Nov 04 2014

city: Stockholm

first: Francesco

last: Marabita

address: Karolinska University Hospital

institute: Karolinska Institutet

type: Methylation profiling by genome tiling array

summary: Regular endurance exercise training induces beneficial functional and health effects in human skeletal muscle. The putative contribution to the training response of the epigenome as a mediator between genes and environment has not been clarified. Here we investigated the contribution of DNA methylation and associated transcriptomic changes in a well-controlled human intervention study. Training effects were mirrored by significant alterations in DNA methylation and gene expression in regions with a homogeneous muscle energetics and remodeling ontology. Differential DNA methylation predominantly occurred in regulatory enhancer regions, where known binding motifs of MRF, MEF2 and ETS proteins were identified. A transcriptional network analysis revealed modules harboring distinct ontologies, and interestingly the overall direction of the changes of methylation within each module was inversely correlated to expression changes. In conclusion, we show that highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus.

overall_design: DNA samples from vastus lateralis muscle bisopsies were included in the study. Specifically, 23 subjects performed three months of supervised endurance training. Biospies were taken at rest, before and after training. DNA methylation levels were profiled using Illumina 450K arrays.

first: Maléne

middle: E

last: Lindholm


title: Global mRNA/LncRNA expression analysis of pancreatic tumors causing type3C Diabetes Mellitus

status: Public on Sep 06 2014

city: Guangzhou

first: Wenchao

last: Gao

state: Guangdong

address: N.O. 107, Yuanjiang Road

department: Department of Hepatobiliary Surgery

institute: Sun Yat-sen Memorial Hospital of Sun Yat-sen University

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

summary: Pancreatic tumors with small size can cause type3C Diabetes Mellitus (PCA-DM) but the mechanism is unknown. In this study we aimed at revealing the mRNA and long noncoding RNA (LncRNA) expression patterns of pancreatic tumors that triggered PCA-DM. Four pancreatic tumors from patients with PCA-DM (A1-A4), four pancreatic tumors from patients without PCA-DM (B1-B4), and four pancreatic tissues from patients with pancreatitis were individually profiled with Agilent microarrays(Arraystar Human LncRNA Array v3.0).

overall_design: Pancreatic tumors with PCA-DM or without PCA-DM, and pancreatic tissues of pancreatitis were individually profiled.

first: Rufu

last: Chen

first: Yu

last: Zhou

first: Quanbo

first: Langping

last: Tan

first: Min

last: Yu

first: Shangyou

last: Zheng


title: Role of NFATc1 in patients with FLT3-ITD AML

status: Public on Sep 27 2014

city: München

first: Torsten

last: Haferlach

address: Max-Lebsche-Platz 31

institute: MLL Munich leukemia laboratory

summary:
Diagnostic samples of peripheral blood form acute myeloid leukemia were analysed for gene expression differences
MLL Munich Leukemia Laboratory

overall_design: FLT3-ITD positive and negative AML were compared

first: Andreas

last: Burchert


title: A platform of patient-derived tumor xenografts (EOC-xenografts) to recapitulate the clinicopathology and genetic alterations of ovarian cancer

status: Public on Jan 07 2015

city: Biella

first: giovanna

last: chiorino

address: via malta 3

department: Cancer Genomics

institute: Fondo Edo Tempia

summary: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. On the basis of its histopathology and molecular-genomic changes ovarian cancer has been divided into subtypes, each with distinct biology and outcome. The aim of this study was to develop a panel of patient-derived EOC-xenografts that recapitulate the molecular and biological heterogeneity of human ovarian cancer. Thirty-four EOC-xenografts were successfully established, either subcutaneously or intraperitoneally, in nude mice. The xenografts were histologically similar to the corresponding patient tumor and comprised all the major ovarian cancer subtypes. After orthotopic transplantation in the bursa of the mouse ovary, they disseminate into the organs of the peritoneal cavity and produce ascites, typical of ovarian cancer. Gene expression analysis and mutation status indicated a high degree of similarity with the original patient and discriminate different subsets of xenografts. They were very responsive, responsive and resistant to cisplatin, resembling the clinical situation in ovarian cancer. This panel of patient-derived EOC-xenografts that recapitulate the recently type I and type II classification serves to study the biology of ovarian cancer, identify tumor-specific molecular markers and develop novel treatment modalities.

overall_design: EOC-xenografts collected from subcutis, abdominal masses and ascitic fluid of mice engrafted with tumors at different passages (from 1 to 6) and from patient specimens, underwent one-color microarray-based gene expression profiling. To assess the amount of human- and mouse-derived cells in the xenograft tumors, total RNA was evaluated by species specific qPCR assays for beta actin. Only samples with a human RNA content > 75% were analyzed. Nine patient specimens and 62 xenograft samples (representing 29 EOC-xenograft models) underwent gene expression analysis with SurePrint G3 Human GE V2 8x60K microarrays.

first: Francesca

last: Ricci

last: Bizzaro

first: Marta

last: Cesca

first: Federica

last: Guffanti

first: Monica

last: Ganzinelli

first: Alessandra

last: Decio

first: Carmen

last: Ghilardi

first: Patrizia

last: Perego

first: Robert

last: Fruscio

first: Alessandro

last: Buda

first: Mauro

last: Signorelli

first: Paola

last: Ostano

first: Giovanna

last: Chiorino

first: Maria

middle: R

last: Bani

last: Damia

first: Raffaella

last: Giavazzi


title: An integrative genomics approach to explore diversity of light harvesting antenna complexes from environmental isolates of the purple non-sulfur bacterium Rhodopseudomonas palustris

status: Public on Mar 01 2015

city: Seattle

first: Caroline

last: Harwood

state: WA

address: 1705 NE Pacific Street

department: Microbiology

institute: University of Washington

summary: Peripheral light harvesting (LH) antenna complexes have been studied extensively in the purple nonsulfur bacterium Rhodopseudomonas palustris because it produces different types of LH complexes under high light intensities (LH2 complex) and low light intensities (LH3 and LH4 complex).  The ability of R. palustris to alter its peripheral LH complexes in response to changes in light intensity is attributed to the multiple operons that encode the a and b peptides that make up these complexes, whose expression is affected by light intensity, light quality, and oxygen tension. However, low resolution structures, amino acid similarities between the complexes, and a lack of transcriptional analysis made it difficult to determine the LH complexes composition and functions under different light intensities. It was also unclear how much diversity of the R. palustris LH complexes exists in nature.Results: To gain insight into the composition of the LH complexes, their function under high light intensities and low light intensities, and their prevalence in the environment we undertook an integrative genomics approach using 15 closely related R. palustris strains isolated from the environment and 5 R. palustris ecotypes whose genomes have been sequenced. We sequenced the genomes for the 15 closely related strains and using RNA-seq carried out transcriptomic analysis on all 20 strains grown under high light intensity and low light intensity. We were able to determine that even closely related R. palustris strains had differences in their pucBA gene content and expression, even under the same growth conditions. We also found that the LH2 complex could compensate for the lack of an LH4 complex under LL intensities but not under extremely LL intensities. Conclusions: This is the first time an integrative genomics approach has been used to study light harvesting in the environment. The variation observed in LH gene composition and expression in environmental isolates of R. palustris likely reflects how these strains have adapted to specific light conditions in the environment. We have also shown that there is redundancy between some of the LH complexes under certain light intensities, which may partially explain why multiple operons encoding LH complexes have evolved and been maintained in R. palustris.

overall_design: Examing the variation observed in LH gene composition and expression in various environmental isolates

first: Kathryn

last: Fixen

first: Yasuhiro

last: Oda

first: Somsak

last: Phattarasukol


title: MicroRNA profile of exosome from serum samples of  Kawasaki disease

status: Public on Sep 03 2014

first: Hong-Ling

last: Jia

address: Huangpu Road

institute: Jinan University

summary: To further development of our miRNA diagnostic approach to Kawasaki disease(KD), we have employed microRNA microarray expression profiling as a discovery platform to identify microRNAs as the potential biomarkers to rapidly diagnose Kawasaki disease. Pooled exosome of serum in equal amount from 5 healthy children, 5 KD patients and 5 KD patients after Intravenous immunoglobulin (IVIG) therapy were used for microRNA microarray analysis.

overall_design: MicroRNA profile of exosome from Kawasaki disease(KD) was analyzed by microRNA microarray analysis in 5 healthy children, 5 KD patients and 5 KD patients after IVIG therapy.

first: Gong

last: Zhang


title: Gene expression profiling in post mortem brain samples of patients with cirrhosis with and without hepatic encephalopathy

status: Public on Oct 23 2014

city: Düsseldorf

first: Boris

last: Goerg

address: Moorenstrasse 5

department: Clinic for Gastroenterology, Hepatology and Infectiology

institute: Heinrich-Heine Universität Düsseldorf

summary: The study aimed at the identification of gene expression changes in brain of cirrhotic patients without or with HE as compared to controls.  Tissue was taken from the fusiform gyrus.

overall_design: The dataset comprises 12 brain tissue samples divided into three sample groups each representing a certain liver disease condition of humans.

last: Görg

first: Dieter

last: Häussinger


title: HITS–CLIP reveals Argonaute 1-associated MicroRNAs and Target Sites in Schistosoma japonicum

status: Public on Nov 11 2014

city: Shanghai

first: Zhao

last: Jing

address: 1239 Siping Road

institute: Tongji university

summary: In this study, we isolated and identified the small RNAs associated with the S. japonicum Argonaute protein, SjAgo1, by HITS-CLIP combined with bioinformatic analysis. These data reveal a genome-wide miRNA-mRNA interaction map in S. japonicum in vivo, which will help us understand the complex gene regulation network in this pathogen and thereby facilitate to develop novel approaches against Schistosomiasis.

first: Jing

last: Zhao

first: Rong

last: Luo

first: Weiqing

last: Pan


title: Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects

status: Public on Jul 09 2014

city: Indianapolis

first: James

last: Marrs

state: IN

address: 723 West Michigan Street

department: Biology

institute: Indiana University-Purdue University Indianapolis

summary:
Gene expression was measured using microarrays in 8 hour postfertilization embryos, comparing control versus ethanol-treated (2 to 8 hours postfertilization) embryos. This experiment was performed to determine the gene expression changes that occur in response to ethanol treatment as a model of fetal alcohol spectrum disorder.
Fetal alcohol spectrum disorder (FASD) occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell), prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented to characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression and distribution, which control epiboly and gastrulation, were not affected. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a), which controls epiboly, was significantly reduced in ethanol-exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol-treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue) microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression.

overall_design: Control vs. ethanol-treated zebrafish embryos that were treated from 2 to 8 hours postfertilization. Total RNA from control and ethanol-treated embryos were harvested at 8 hours postfertilization.

first: Swapnalee

last: Sarmah

first: Pooja

last: Muralidharan

first: Courtney

middle: L

last: Curtis

first: Jeanette

middle: N

last: McClintick

first: Bryce

last: Buente

first: David

last: Holdgrafer

first: Osato

last: Ogbeifun

first: Opeyemi

last: Olorungbounmi

first: Liliana

last: Patino

first: Ryan

last: Lucas

first: Sonya

last: Gilbert

first: Evan

last: Groninger

first: Julia

last: Arciero

first: Howard

last: Edenberg


title: Transcriptional profiling of staurosporine-induced cell death in Vogel's minimal medium with different concentrations of calcium

status: Public on Dec 05 2014

city: Berkeley

first: António Pedro

last: Gonçalves

address: 341A Koshland Hall

department: Plant and Microbial Biology

institute: University of California, Berkeley

summary:
Purpose: Compare the transcriptional profile of staurosporine-treated cells in Neurospora crassa wild type cells grown with different availabilities of calcium.
Methods: Conidial suspensions were obtained and 1 x 106 cells/ml incubated in minimal medium (with the indicated concentrations of calcium) for 6 hours (26ºC, 140 rpm, constant light) followed by the addition of staurosporine (or DMSO) and growth for 1 more hour. For the experiments in 0 Ca2+ or 20 mM CaCl2 media, the concentration of KH2PO4 in the 50x Vogel’s stock solution was limited to 10 mM to avoid precipitation with supplemental calcium. Cells were harvested using 0.45 μm filters and immediately frozen in liquid nitrogen. Total RNA was isolated by the Trizol-Phenol-Chloroform method. After digestion of 25 μg RNA with TURBO DNAse (Life Technologies), mRNA was purified using Dynabeads oligo(dT) magnetic beads (Life Technologies). The mRNA was chemically fragmented using the Ambion RNA fragmentation kit (Life Technologies). First and second strand cDNA synthesis was achieved using appropriate kits (Life Technologies). The illumina TruSeq kit was employed to generate the cDNA libraries with indexing adapters essentially following the manufacturer’s protocol. After purification of the libraries with AMPure XP beads (Roche), the quality of the libraries was analyzed in a Agilent 2100 Bioanalyzer. The cDNA libraries were sequenced in a illumina HiSeq2000 and single reads of 50 bp were obtained. Sequencing data was handled essentially with Tophat, Cufflinks and Cuffdiff. Expression levels are presented as Fragments Per Kilobase of transcript per Million mapped reads (FPKM).
Results: Differences in the concentration of extracellularly available Ca2+ result in distinct transcriptional programs.
Conclusions: Our transcriptomic analysis provides a reference dataset for future investigations on the role of Ca2+ in fungal biology.

overall_design: Transcriptional profile of staurosporine-treated Neurospora crassa wild type cells growing with different concentrations of calcium was compared using illumina HiSeq2000 and single reads of 50 bp.

first: A


title: Transcriptomic analysis of ERR alpha orphan nuclear receptor

status: Public on Sep 17 2014

city: LYON

first: Jean-Marc

last: Vanacker

address: 28 rue A Fleming

institute: IGFL

summary: Determination of the genes regulated by ERRalpha nuclear receptor in MDA-MB231 cells

overall_design: MDA-MB231 cells were inactivated for ERRalpha using siRNA. Three different siRNAs were used (siE1, siE2, siE3). Cells treated with a control siRNA (siC samples) were used for comparison. Duplicate samples were analyzed. Transcriptomic analysis was performed by RNA-Seq

first: Juliette

last: Sailland

first: Violaine

last: Tribollet


title: MicroRNA profiling in Acute Lymphoblastic Leukemia (ALL)

status: Public on Aug 14 2014

city: Hyderabad

first: Lekha

middle: Dinesh

last: Kumar

state: Andhra Pradesh

address: Uppal road, habshiguda

department: Cancer biology

country: India

institute: Centre for cellular and molecular biology

summary: MicroRNA (667) profiling was done using TaqMan MicroRNA Arrays, which contains megaplex primer Pools covering Sanger miRBase version10 of Taqman Low Density Arrays (TLDA)  platform across 50  samples along with the normals consisting of T cell lineage Acute Lymphoblastic Leukemia (T-ALL) and B cell lineage Acute Lymphoblastic Leukemia (B-ALL) subtypes which consists peripheral blood (PB) and bone marrow (BM) samples. The above isolated RNA which displayed good RIN value, linearity (R2>0.96), were used for  reverse transcription (RT) reactions  with the help of TaqMan MicroRNA Reverse Transcription Kit followed by PCR Reaction (ABI 7900 HT) as per illustration provided in kit. Real-time PCR was performed using an Applied Biosystems 7900 HT- TLDA Real-Time PCR System. A pre -amplification step of cDNA with pre-amp megaplex pool primers was done to significantly enhance the ability to detect highly down regulated miRNAs. The TaqMan human microRNA arrays consists of two plates, pool A and pool B. RNU 46 and RNU 48 were used as endogenous controls for data normalization. Another control not related to human is also included as a negative control. Each TaqMan Assay was run in quadruplicate. RNU 46 and RNU 48 expression was consistent in all the samples and displayed good   range of CTs values 22–24 ) where as  in ‘No Template’ Control (NTC) CT value was  above 38. The average CT values of total profiled miRNAs in all samples were normalized with RNU 46 & RNU 48 using spotfire (statminer) software and fold change were represented in terms of log 10, 2 - Δ Δ CT  (RQ ) and log10RQ.  Only valid and significant miRNAs were picked up for further analysis.

overall_design: Taqman Low Density Arrays (TLDA) was performed across 50 samples along with the normal’s consisting of T-ALL and B-ALL subtypes. Another control not related to human is also included as a negative control.

middle: D

first: Rekha

last: Nair


title: The dynamics of DNA methylation fidelity during mouse embryonic stem cell renewal and differentiation

status: Public on May 12 2014

city: Bethesda

first: Mingan

last: Sun

state: Maryland

address: Building 6B, 6 Center Drive

department: Eunice Kennedy Shriver National Institute of Child Health and Human Development

institute: National Institute of Health

summary:
Purpose: we aimed to gain a genome-wide view of the dynamics in DNA methylation inheritance and define the factors associated with methylation fidelity.
Methods: Using mouse embryonic stem cell (ES-E14TG2a) in both undifferentiated and differentiated states as a model system, we exploited the hairpin bisulfite sequencing approach to generate methylation data for DNA double strands simultaneously at single-base resolution. We generated the genome-wide hairpin bisulfite sequencing data to capture the methylation pattern variation during the stem cell transition from self-renewal to commitment, and integrated with various “omics” data to scrutinize the relationships among DNA methylation inheritance, gene expression, histone modification, transcriptional factor binding and distribution of 5-hydroxylmethylation cytosine.
Results and conclusion: Our results indicated that DNA methylation fidelity increases globally during early mouse embryonic stem cell differentiation. Methylation fidelity is remarkably high in promoter regions of actively expressed genes and positively correlated with active histone modification marks and binding of transcriptional factors. Strikingly, methylation fidelity follows a bimodal distribution for the intermediately methylated CpG dyads. In addition, the methylation difference in between two DNA strands rather than different DNA molecules is a major source of the intermediate DNA methylation. Lastly, while 5-hmC and 5-mC tend to coexist, no significant increase in the pairing with unmethylated cytosine was observed.

overall_design: For mouse embryonic stem cell of undifferentiated and spontaneous differentiated states, we determined DNA double strands methylation pattern by hairpin bisulfite sequencing approach and determined gene expression profiles using RNA-seq.

first: Lei

last: Zhao

first: Ming-an

first: Hehuang

last: Xie