title: Whole genome landscapes of major melanoma subtypes

city: North Sydney

first: Graham

middle: J.

last: Mann

address: Poche Centre, 40 Rocklands Road

institute: Melanoma Institute Australia

summary: Cutaneous, acral and mucosal subtypes of melanoma were evaluated by whole-genome sequencing, revealing genes affected by novel recurrent mutations to the promoter (TERT, DPH3, OXNAD1, RPL13A, RALY, RPL18A, AP2A1), 5’-UTR (HNRNPUL1, CCDC77, PES1), and 3’-UTR (DYNAP, CHIT1, FUT9, CCDC141, CDH9, PTPRT) regions. TERT promoter mutations had the highest frequency of any mutation, but neither they nor ATRX mutations, associated with the alternative telomere lengthening mechanism, were correlated with greater telomere length. Genomic landscapes largely reflected ultraviolet radiation mutagenesis in cutaneous melanoma and provided novel insights into melanoma pathogenesis. In contrast, acral and mucosal melanomas exhibited predominantly structural changes, and mutation signatures of unknown aetiology not previously identified in melanoma. The majority of melanomas had potentially actionable mutations, most of which were in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways.

overall_design: Expression arrays from 65 of the 183 tumours analysed were used to determine gene expression levels of genes with recurrent promoter and 3' and 5' UTR mutations. A total of 32 samples is available at GSE54467; the remaining  33 samples are submitted here. The 27 primary melanoma samples (AJCC stage II) were assayed using the HumanHT-12 v4 Expression BeadChip (Illumina® Inc., San Diego, CA, USA; Catalog IDs: BD-103-0204, BD-103-0604). The remaining 6 metastatic (AJCC stage IV) samples were assayed using the HumanWG-6 v3 Expression BeadChip ((Illumina® Inc., San Diego, CA, USA; Catalog IDs: BD-101-0203, BD-101-0603). NEQC normalisation (default parameters) was separately applied to each of the AJCC stage II and IV datasets (http://nar.oxfordjournals.org/content/38/22/e204). Probes for which there were no samples with a detection p-value of less than 0.01 were removed.

first: Nicholas

last: Hayward

first: James

middle: S

last: Wilmott

first: Nicola

last: Waddell

first: Peter

last: Johansson

first: Matthew

last: Field

first: Katia

last: Nones

first: Ann-Marie

last: Patch

first: Hojabr

last: Kakavand

first: Ludmil

middle: B

last: Alexandrov

first: Hazel

last: Burke

first: Valerie

last: Jakrot

first: Stephen

last: Kazakoff

first: Oliver

last: Holmes

first: Conrad

last: Leonard

first: Scott

last: Wood

first: Qinying

first: Nick

first: Varsha

last: Tembe

first: Gulietta

last: Pupo

first: Ricardo

last: De Paoli-Iseppi

last: Vilain

first: Ping

last: Shang

first: Sarah-Jane

last: Schramm

first: Antonia

last: Pritchard

first: Ken

last: Dutton-Regester

first: Anna

last: Fitzgerald

first: Catherine

first: Sean

last: Grimmond

first: Jean

middle: Y

last: Yang

first: Jonathan

last: Stretch

first: Richard

last: Kefford

last: Hersey

first: Georgina

middle: V

last: Long

last: Cebon

first: Mark

last: Shackleton

first: Andrew

last: Spillane

first: Robyn

last: Saw

first: John


title: Expression data from fractionated SH-SY5Y cells

status: Public on Dec 01 2017

city: Callaghan

first: Murray

middle: J

last: Cairns

state: NSW

address: University Drive

country: Australia

institute: University of Newcastle

summary:
miRNA activity is typically associated with the cytoplasm, but a growing body of evidence suggests non-canonical roles for miRNA in the nucleus. We study miRNA dynamics in neurons and wanted to investigate this possibility in a human neuronal model.
We used microarrays to investigate the miRNA and mRNA composition of the nuclear and cytoplasmic compartments of undifferentiated SH-SY5Y cells to identify miRNA-target relationships and networks.

overall_design: SH-SY5Y cultures at 80% confluence were collected by trypsinisation, and the nuclear and cytoplasmic fractions separated by hypotonic lysis.

first: B

last: Goldie

first: C

last: Fitzsimmons

first: J

last: Weidenhofer

middle: R

last: Atkins

first: D

middle: O

last: Wang

first: M


title: Expression data from two neutrophil subsets during murine paramyxovirus type 1 infection

city: Milwaukee

first: Dorothy

last: Cheung

state: WI

address: 8701 Watertown Plank Road

country: USA

institute: Medical College of Wisconsin

summary:
Two subsets of neutrophils, separated by CD49d expression, are present in the airways of mice during an acute respiratory infection from murine paramyxovirus type 1 (SeV).
We used microarrays to compare the transcriptomes of these two subsets to look for up-regulated or down-regulated genes that would account for the seemingly different funtions of the neutrophil subsets.

overall_design: Bronchial alveolar lavage of mice infected with murine paramyxovius type 1 were collected on day 3 post-inoculation.  Cell pellets were stained for Gr-1 (clone RB6-8C5) and CD49d (clone R1-2)and flow-sorted into either Gr-1+/CD49d+ or Gr-1+/CD49d- fractions.  RNA was extracted from each flow-sorted fraction and hybridized on Affymetrix microarrays.  Gene expression was compared between the two fractions.

first: Mitchell

middle: H

last: Grayson


title: Expression data from human airway epithelia exposed to IL13

status: Public on Nov 14 2017

city: Iowa City

first: Alejandro

middle: A

last: Pezzulo

state: IA

address: 169 Newton Rd 6334 PBDB

department: Internal Medicine

institute: University of Iowa

summary:
IL13 exposure results in a distinct gene expression profile in human airway epithelia. We investigated whether this expression profile can be used to identify compounds able to block goblet cell metaplasia
We used microarrays to determine transcriptional changes in cultures of primary human airway epithelia grown at the air-liquid interface after exposure to 20 ng/mL recombinant human IL13

overall_design: Air-liquid interface cultures of primary airway epithelia from 3 de-identified human donors with no known disease were exposed to apical and basolateral IL13 or vehicle at a concentration of 20ng/mL for 21 days. RNA was extracted and processed for Affymetrix Human Gene 1.0 ST arrays.

first: Joseph

last: Zabner


title: Gene expression data from retina of Babl/c mouse under white LED light exposure

status: Public on Nov 28 2017

city: Hangzhou

first: Chen

last: Xie

state: Zhejiang

address: 79 Qingchun Road

department: Department of Ophthalmology

country: China

institute: First Affiliated Hospital, College of Medicine, Zhejiang University

summary:
The widely used white light-emitting diodes (LED) deliver higher levels of blue light than do conventional domestic light sources. The high intensity of blue component is the main source of concern about the health risks of LED with respect to their light-toxicity to the retina. White LED light with higher correlated color temperature (CCT) is more likely to cause retinal injury in mice, significantly reducing the number of ONL nuclei, however apoptosis pathway may not be the only mechanism.
We used the Affymetrix GeneChip (Mouse Genome 430 2.0) to describe the different influence on gene expression of mouse retina under white LED light with different CCT.

overall_design: White LED light with CCT of 2954, 7378K were used for exposure experiments on 10-week-old Babl/c mice for 14 days (light cycle of 12 hours-on / 12 hours-off). Normal control mice were raised in a relatively dark environment. Retinal genome-wide expression patterns of control group, 2954K group and 7378K group were analyzed by Affymetrix GeneChip (Mouse Genome 430 2.0) to describe the overall difference of gene expression in mouse retina. For example, after LED light exposure, we harvested the mouse retina of right eye for RNA extraction and hybridization on Affymetrix microarrays. Each three retinas of the same group are concentrated together and three sample were repeated. The sample ID is as follows: Control Group: NC1, NC2 and NC3; 2954 K Group: 3K1, 3K2 and 3K3; 7378 K Group : 7K1, 7K2 and 7K3.

first: Jianping

last: Tong


title: Transcriptomic changes in the duodenum mucosa after a high-fat (HF) or low-fat (LF) meal ingestion.

status: Public on Nov 26 2017

city: Quebec

first: Ezequiel

middle: L

last: Calvo

state: Quebec

address: 2705 Boul. Laurier

department: Molecular Endocrinilogy

country: Canada

institute: CRCHUL

summary:
Fat intake is an important determinant in the development of obesity. The small intestine is the principal site of digestion and absorption of nutrients, and these short-term circulating nutrients and hormones as well as neural signals derived from the peripheral tissues in responses to a meal act at multiple central nervous system sites where food intake is controlled.
In order to identify the HF-specific peripheral signals that can be therapeutic targets of obesity, we investigated transcriptomic changes in the duodenum mucosa after a HF or LF meal ingestion.

overall_design: One group of mice (n= 20) was sacrificed after fasting, and the others (n = 20 per experimental condition) were fed ad libitum with LF or HF meal, and sacrificed 30 min, 1 h and 3 h after the beginning of the meal. The meal-induced transcriptomic changes in the duodenum mucosa were compared to the fasting condition.

first: Octave

last: Mucunguz

first: Rose-Guerline

last: Cherizo

first: Mayumi

last: Yoshioka

first: André

last: Boivin

first: Ezequiel-Luis

first: Jonny

last: St-Amand


title: Expression data from intestinal epithelial cells (IECs) [Mouse430_2 array]

status: Public on Nov 11 2017

city: Beijing

first: Xicheng

last: Liu

address: 7 Science Park Rd., ZGC life science park

institute: National Institute of Biological Sciences, Beijing

summary:
Polycomb group (PcG) proteins are epigenetic silencers whose dysregulation is frequently linked to cancer via mechanisms that remain unclear. Using conditional knock-out mice in a colitis-associated colorectal cancer (CAC) model, we found that Bmi1 and Mel18 are important initiation and maintenance factors during CAC tumorigenesis. Epithelial depletion of both Bmi1 and Mel18, but not either gene alone, significantly reduces tumor growth and multiplicity.
We used microarrays to detail the global program of gene expression In DKO, Bmi1ΔIEC, Mel18ΔIEC and WT mice and identified distinct classes of up-regulated genes during this process.

overall_design: Mouse IECs were selected at early stages of CAC tumorigenesis for RNA extraction and hybridization on Affymetrix microarrays. To that end, we isolated IECs from the freshly dissected colon of DKO (1), Bmi1ΔIEC (3), Mel18ΔIEC (2) and WT (4) mice for GeneChip Mouse 430 2.0 Array.

first: Rongwen

last: Xi


title: Alteration of Liver Peroxisomal and Mitochondrial Functionality in the NZO Mouse Model of Metabolic Syndrome.

status: Public on Nov 01 2017

city: Duesseldorf

first: Birgit

last: Knebel

address: Auf'm Hennekamp 65

department: Cinical Biochemistry and Pathobiochemistry

country: Germany

institute: German Diabetes Center

summary:
Purpose: MetS consist of five risk factors: elevated blood pressure and fasting glucose, visceral obesity, dyslipidemia and hypercholesterinemia. The physiological impact of lipid metabolism indicated as visceral obesity and hepatic lipid accumulation is still under debate. One major cause of disturbed lipid metabolism might be dysfunction of cellular organelles controlling energy homeostasis, i.e. mitochondria and peroxisomes.
Experimental design: The New Zealand Obese (NZO) mouse model exhibits a polygenic syndrome of obesity, insulin resistance, triglyceridemia and hypercholesterolemia that resembles human metabolic syndrome. We applied a combinatorial approach of lipidomics with liver transcriptomics, 2D-DIGETM and mass spectroscopy based organelle proteomics of highly purified mitochondria and peroxisomes in male mice, to investigate molecular mechanisms related to the impact of lipid metabolism in the pathophysiology of the metabolic syndrome.
Conclusions and clinical relevance: Proteome analyses of liver organelles indicated differences in fatty acid metabolism, oxidative stress and response, mainly influenced by PG-C1α/PPARα mediated pathways. These results were in accordance with serum lipid profiles and elevated organelle functionality. These data emphasize that metabolic syndrome is accompanied with increased mitochondria and peroxisomal activity controlling directly cellular energy homeostasis to cope with dyslipidemia and hypercholesterinemia driven hepatic lipid overflow in developing a fatty liver.

overall_design: C57BL/KS (BKS) and NZO mice (littermates) were kept under standadized conditions with regular chow until NZO mice develop the diabetes, obesity  and metabolic syndrome (18 weeks of age).

first: B

first: J

last: Kotzka


title: DNA methylome analysis identifies transcription factor-based epigenomic signatures of multi-lineage competence in neural stem/progenitor cells

status: Public on Sep 19 2017

city: Shinjuku-ku

first: Tsukasa

last: Sanosaka

state: Tokyo

address: 35 Shinanomachi

department: Department of Physiology

country: Japan

institute: Keio University School of Medicine

summary: We performed a microarray experiment to compare gene expression profiles of neural stem/progenitor cells (NS/PCs) isolated form E11.5, E14.5 and E18.5 mouse brain and differentiated cells such as neurons and glial cells (astrocytes and oligodendrocytes).

overall_design: 18 samples


title: Gene expression of peripheral blood mononuclear cells from adults with sickle cell disease (Howard University cohort)

status: Public on Sep 08 2017

city: Chicago

first: Zhengdeng

last: Lei

state: IL

address: 1853 W Polk St

department: Research Resources Center

institute: University of Illinois at Chicago

summary:
Sickle cell disease is associated with systemic complications, many associated with either severity of disease or increased risk of mortality. We sought to identify a circulating gene expression profile whose predictive capacity spanned the spectrum of these poor outcomes in sickle cell disease.
The Training cohort consisted of patients with SCD who were prospectively recruited from the University of Illinois. The Testing cohort consisted of a combination of patients prospectively seen at two separate institutions including the University of Chicago and Howard University.

overall_design: The gene expression of PBMC from 40 sickle cell disease patients from Howard University were analyzed.

first: Ankit

last: Desai

first: Roberto

last: Machado


title: Gene expression of peripheral blood mononuclear cells from adults with sickle cell disease (University of Chicago cohort)

overall_design: The gene expression of PBMC from 38 sickle cell disease patients from University of Chicago were analyzed.


title: Gene expression profiles of inoculated tumor cells in TNC-KO mice

status: Public on Sep 07 2017

city: Aomori

first: Yuji

last: Nakai

state: Aomori

address: 2-1-1, Yanagawa

department: Institute of Regional Innovation

institute: Hirosaki University

summary: Tenascin-C (TNC), a cancer-associated extracellular matrix glycoprotein, plays a pivotal role in tumor growth. To identify the genes regulated by TNC during tumor growth, we performed a tumor growth assay, DNA microarray analysis, and quantitative real-time PCR (qRT-PCR). Mouse mammary tumor cells were subcutaneously inoculated into GRS/A (WT) and GRS/A-TgH(Tnc) (TNKO) mice. Tumors in WT mice significantly increased in volume with expressing TNC while tumors in TNKO mice showed hardly detectable levels of TNC. Tumor gene expression profiles between TNKO and WT mice were compared using DNA microarray analysis. We found that 447 genes were up-regulated (TNKO>WT) and 667 genes were down-regulated (TNKO<WT) in the TNKO group. We then classified these genes by Gene Ontology (GO) terms in order to elucidate their biological function. There were three GO terms found related to tumor growth, namely, “acute inflammatory response”, “cell adhesion”, and “response to wounding”. Eighty-three of the genes primarily involved in these GO terms were further validated by qRT-PCR. Eight genes: Tnc, Cxcl2, Cxcl1, Hbegf, Chl1, Cd44, Serpina3n, and F3 were significantly down-regulated relative to the WT. Eighteen genes: Saa3, P2rx7, Ptgs1, Ptger2, Comp, Steap4, Il1rn, Il1b, Ncf1, Mst1, Nfκb1, Ctsb, Tnfrsf1a, Tnfrsf1b, Cd24a, Adam17, Mtpn, and Sox4 were significantly up-regulated relative to the WT. These results support our hypothesis that TNC has multi-faceted effects on both the tumor cells and their microenvironment. First, TNC acts on the tumor cells directly by up-regulating genes involved in cancer cell proliferation through the CXCL1/2 and CXCR2 pathway. Second, TNC controls the tumor microenvironment by promoting angiogenesis through the CXCL1/2 and CXCR2 pathway, and by suppressing inflammatory gene expression through a separate pathway.

overall_design: Eight-week-old male GRS/A (WT) and GRS/A-TgH(TnC) (TNKO) mice were used as hosts for tumor growth assays. Three mice were used in each experimental group. GLMT1 (GRS/A Lung Metastasis Tumor 1) cell was washed twice with phosphate buffered saline (PBS(-); Nissui, Tokyo, Japan), and then trypsinized with 0.05% trypsin-EDTA (Gibco BRL) once the cell line reached 90% confluence. The cell suspension was then centrifuged at 1,500 rpm for 5 min at 4°C, after inactivation of tryptic activity by adding 10% FBS-containing medium. Cells were re-suspended in the serum-free medium to adjust the cell density to 1 × 10^7 cells/ml. One hundred microliters of the cell suspension was then inoculated underneath the back skin of both WT and TNKO mice. All animal experiments were carried out in accordance with the University of Tokyo's guideline for animal experimentation, and the University's animal experimentation manual.

first: Kaori

last: Matsumoto

first: Atsushi

last: Hoshino

first: Koki

last: Yamazaki

first: Yoshiaki

last: Takioto

first: Satoru

last: Takadera

first: Takayuki

last: Nakagawa

first: Ryohei

last: Nishimura

first: Moriaki

last: Kusakabe


title: Transcriptomics-based characterization of smoking and cessation effects in mouse lung

status: Public on Oct 20 2017

city: King of Prussia

first: Guanghui

last: Hu

state: PA

address: 709 Swedeland Road

institute: GlaxoSmithKline

summary:
COPD is a disorder characterized by the progressive development of airflow limitation that is not fully reversible. Cigarette smoke has been generally accepted as the most important of many risk factors for the development of COPD.
We used microarray technology to perform comprehensive gene expression profiling of smoke exposure and cessation effects in mouse lung tissue.

overall_design: Mice received nose-only exposure of 4% mainstream cigarette smoke or air (sham exposure) for 2 hours/day, 5 days/week for 2, 12 or 24 weeks.  Mice undergoing smoke cessation received cigarette smoke exposure for 12 weeks, and then sham exposure for 12 weeks.

first: Patricia

last: Podolin


title: Epigenome signatures during gastric carcinogenesis based on next generation sequencing [Affymetrix]

status: Public on Sep 01 2017

city: Daejeon

first: Hee-jin

last: Kim

address: 125 Gwahak-ro, Yuseong-gu

country: South Korea

institute: KRIBB

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

summary: Because gastric cancer cells already had genetic and epigenetic alterations which can affect the gastric carcinogenesis, we tried to characterize genetic and epigenetic changes during gastric carcinogenesis. To do this, we performed SNP array.

overall_design: Copy number alteration profiles of gastric mucosa, intestinal metaplasia, and gastric cancer cells were generated by SNP6.0 Array.

first: Yong

first: Hee-Jin

first: Su-Jin

last: Baek


title: Exon array data for patient-matched primary and metastatic colorectal samples

status: Public on Sep 24 2017

city: Parkville

first: Oliver

last: Sieber

state: VIC

address: 1G Royal Parade

institute: Walter and Eliza Hall Insitute of Medical Reseach

summary: Samples were taken from surgically resected tumor specimens/metastases from patients with colorectal cancer. The expression profiles were determined using the Affymetrix GeneChip Human Exon 1.0 ST Array version 2.

overall_design: The RMA procedure was used for normalization. We then performed further quantile normalization to the sample data from the CMSpredictor R package, and then used this classifyCMS predictor to assign CMS classes for these samples. A class was assigned if both the RF nearest and SSP nearest predictions were the same.

middle: M


title: Comparison of mRNA expression between wildtype and Wnt9bcneo/cneo E15.5 urogenital systems.

status: Public on Oct 26 2017

city: Dallas

first: Thomas

middle: Joseph

last: Carroll

state: Texas

address: 5323 Harry Hines Blvd

department: Internal Medicine and Molecular Biology

institute: UTSW Med Ctr.

summary:
Wnt9b is expressed in the ureteric bud of the kidney at all stages of development. The Wnt9b cneo allele functions as a partial loss of function. Wnt9bcneo/cneo mutant kidneys initially develop normally but exhaust their nephron progenitor cells by E15.5. Here, we have compared expression between Wnt9bcneo/+ and Wnt9bcneo/cneo kidneys. Additional urogenital tissue (adrenal glands, reproductive tracts and bladder) may have been included in some samples.
We used microarrays to compare differences in gene expression between wildtype and Wnt9b mutants. To focus on direct targets, mesenchymes isolated away from the E11.5 ureteric bud were assayed

overall_design: Ell.5 kidneys were manually dissected away from embryos collected from Wnt9b+/- intercrosses. Mesenchymes were isolated away from the ureteric bud after a brief enzymatic digestion (trypsin/pancreatin). Paired mesenchymes were stored int RNA-Later until the genotype was determined. 25-30 Wnt9b-/- or Wnt9b+/- mesenchymes were pooled for each replicate (giving approx. 1ug of total RNA). cRNA was synthesized and hybridized to the Affymetrix  GeneChip Mouse Genome 430.2 Array.

first: Tom


title: Transcriptomics Responses to Hypoxia and Ketamine in Ovine Fetal Hippocampus

status: Public on Aug 31 2017

city: GAINESVILLE

first: Charles

middle: Evans

last: Wood

state: Florida

address: 1345 Center Drive/Room M552

department: Physiology and Functional Genomics

institute: University of Florida

summary: Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain.  The chemoreceptor reflex that is responsible for this physiological response is dependent on glutamatergic neurotransmission which, in times of vigorous activity, could produce cell death secondary to calcium uptake.  We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the hippocampus and that ketamine, an antagonist of NMDA receptors, reduces the damage.  Late-gestation, chronically catheterized fetal sheep were subjected to a 30 min period of ventilatory hypoxia that decreased fetal PaO2 from 17±1 to 10±1 mm Hg, or normoxia (PaO2 17±1 mm Hg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, iv).  One day (24 h) after hypoxia/normoxia, fetal hippocampus was removed and mRNA extracted for transcriptomics and systems biology analysis.  Hypoxia stimulated a transcriptomics response consistent with a an increase in inflammation (e.g., cytokine binding and response to LPS).  Ketamine pretreatment reduced these responses. The inflammation response modeled with transcriptomic system biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the hippocampal tissue that ketamine significantly reduced.  We conclude that transient hypoxia produces inflammation of the fetal hippocampus and that ketamine, in a standard clinical dose, reduces the inflammation response.

overall_design: 4 groups: hypoxia, hypoxia plus ketamine, normoxia, normoxia plus ketamine.   Hypoxia produced by low PO2 in maternal inspired gas for 30 min, followed by normoxia recovery for 23.5 hours. Control fetuses maintained at normoxia for 30 min, followed by another 23.5 h of normoxia.  Fetal hippocampus collected for mRNA at end of 23.5 h recovery period.

first: Eileen

middle: I

last: Chang

first: Miguel

last: Zarate

first: Maria

last: Rabaglino

first: Elaine

last: Richards

last: Arndt

first: Maureen

last: Keller-Wood

middle: E


title: Identification and function of Tbx4 resident fibroblasts as a major source of fibrotic fibroblasts

status: Public on Aug 23 2017

city: Los Angeles

first: ting

last: Xie

state: CA

address: 127 San Vicente Blvd

department: Pulmonary

institute: Cedars-Sinai Medical Center

summary:
Progressive tissue fibrosis is a major cause of morbidity, and idiopathic pulmonary fibrosis (IPF) is a terminal illness characterized by unremitting matrix deposition in the lung with very limited choice of therapies. The imcomplete understanding of the mechanisms of progressive fibrosis curbs the progress in therapeutics development. Of which, the origin of fibrotic fibroblasts has been poorly defined during the pathogenesis of tissue fibrosis. Here, we fate-mapped a early embryonic transcription factor T-box gene 4 (Tbx4)-derived mesenchymal progenitors in injured adult lung and found that Tbx4+ lineage cells are the major source of myofibroblasts. The ablation of Tbx4+ cells or disruption of Tbx4 signaling attenuated lung fibrosis in bleomycin injury model in mice in vivo. Furthermore, Tbx4+ fibroblasts are more invasive and the regulation of fibroblast invasiveness by Tbx4 is through mediating hyaluronan synthase 2 (HAS2). This study identified a major mesenchymal transcription factor driving the development of fibrotic fibroblasts during lung fibrosis. Understanding the origin, signaling, and functions of these fibroblasts would prove pivotal in the development of therapeutics for patients with progressive fibrotic diseases.
We used microarrays to detail the gene expression of Tbx4 and non-Tbx4 cultured fibroblasts.

overall_design: Lung fibroblasts were cultured from Tbx4-Cre;RosaTm mice. Tbx4-Tdtomato positive and Tbx4-Tdtomato negative fibroblasts were sorted by flow cytometry. RNA were extracted and hybridized on Affymetrix microarrays.

first: Ting

first: Dianhua

last: Jiang


title: Transcriptome profiling of antiviral immune and dietary fatty acid dependent responses of Atlantic salmon macrophage-like cells

status: Public on Oct 31 2017

city: St. John's

first: Khalil

last: Eslamloo

state: Newfoundland and Labrador

address: 0 Marine Lab Rd.

department: Ocean Sciences

institute: Memorial University of Newfoundland

summary: A study was conducted to determine if different levels of vegetable and fish oils can alter antiviral responses of salmon macrophage-like cells (MLCs). Atlantic salmon were fed diets containing 7.38% (FO7) or 5.09% (FO5) fish oil. These diets were designed to be relatively low in EPA+DHA (i.e. FO7: 1.41% and FO5: 1%), but near the requirement level, resulting in no significant change in salmon growth. After a 16-week feeding trial, macrophages isolated from fish in these dietary groups were stimulated by a viral mimic (dsRNA: pIC) or PBS (control) for 24 h. A 44K microarray experiment identified the diet-responsive transcripts between dietary treatments and pIC-responsive transcripts within each group.

overall_design: Atlantic salmon were fed for 16 weeks with the FO7 or FO5 diet (4 tanks per diet). Macrophage-like cells were isolated from 2 fish per replicate tank of each dietary group (8 fish from each group in total). The isolated cells from each fish were exposed to PBS (control) or 10 µg ml-1 pIC for 24 h. Samples from 6 individuals (6 PBS and 6 pIC; 12 samples in total per group) in each dietary group were used for microarray experiment. Test samples were labeled with Cy5, whereas the common reference (i.e. a RNA pool of all 24 samples included in microarray experiment) was labeled with Cy3. Each individual test sample was hybridized together with the common reference sample on an array (i.e. 24 arrays in total).

first: Xi

last: Xue

first: Jennifer

last: Hall

first: Nicole

middle: C

last: Smith

first: Albert

last: Caballero-Solares

first: Christopher

last: Parrish

first: Richard

middle: G

last: Taylor

first: Matthew

last: Rise


title: Differential gene expression on islet transplantation with or without the presence of autologous fibroblasts

status: Public on Aug 30 2017

city: Oviedo

first: Alvaro

last: Obaya

state: Asturias

address: Julian Claveria s/n

department: Biología Funcional

country: Spain

institute: Universidad de Oviedo

summary: Pancreatic islet transplantation was performed in the subcutaneous space of diabetic nude mice. In order to promote long survival and function of transplanted islets a plasma-based scaffold was developed in combination with fibroblasts as graft-supporting accesory cells. Gene expression analysis was carried out to evaluate expression differences due to the presence of fibroblast which could explain the long-term glycemic control observed under these circumstances.

overall_design: Pancreatic islet transplantation was performed with or without the presence of autologous fibroblasts and differences on gene expression was followed during 10 days

first: Marco

last: Pérez-Basterrechea


title: Comparison of mRNA expression between wildtype and Wnt9b-/- isolated metanphric mesenchyme from E11.5 kidneys.

first: Thomas

last: Carroll

summary:
Wnt9b is expressed in the ureteric bud of the kidney at all stages of development. In Wnt9b mutants, the ureteric bud forms but the metanephric mesenchyme is never induced to undergo differentiation.
We used microarrays to compare differences in gene expression between wildtype and Wnt9b mutants. To focus on direct targets, mesenchymes isolated away from the E11.5 ureteric bud were assayed

first: Tom


title: Expression profiling of E15.5 pancreases from pancreas-specific Jarid2 knockout (KO) embryos.

status: Public on Sep 26 2017

city: Barcelona

first: Joan Marc

last: Servitja

state: Catalonia

address: Rosselló, 153

institute: IDIBAPS

summary:
Jarid2, a member of the Jumanji family of proteins, is a developmental regulator that is necessary for proper mouse development and stem cell differentiation.  To investigate the specific functions of Jarid2 during pancreas development, we generated pancreas-specific Jarid2 mutants.
We used microarrays to determine gene expression changes resulting from deletion of the Jarid2 gene in the pancreas.

overall_design: Pancreases from pancreas-specific Jarid2 KO and wild-type embryos were harvested at embryonic day 15.5. RNA was extracted and hybridized on Affymetrix microarrays.

first: Sara

last: Cervantes

first: Rosa

last: Gasa

first: Joan-Marc


title: A gene expression database for retinal neuron subtypes

status: Public on Sep 30 2017

first: Yi-Rong

last: Peng

address: 100 Stein Plaza Driveway, B-133

institute: University of California, Los Angeles

summary: The goal of this experiment was to define gene expression patterns of two mouse retinal ganglion cell subsets, labeled by expression of fluorescent proteins in Hb9-GFP and Drd4-GFP mice, all retinal ganglion cells labeled by anti-Thy1 antibody staining.

overall_design: Neurons expressing GFP or labeled by fluorescent protein conjugated anti-Thy1 antibody were purified by flow cytometry. Two biological replicates, origniating from different litters, were collected for each cell type. RNA was extracted from sorted cells and prepared for hybridization to Affrymetrix microarrays.

first: Josh

last: Sanes


title: Gene expression in the embryonic endolymphatic sac of E13.5, E14.5, E16.5 and E17.5 Slc26a4Δ/+ and Slc26a4Δ/Δ mice

status: Public on Sep 22 2017

city: Manhattan

first: Philine

last: Wangemann

state: KS

address: 1600 Dension Avenue

department: Anatomy and Physiology

institute: Kansas State University

summary:
Gene expression was analyzed in endolymphatic sacs of two groups of mice: Slc26a4Δ/Δ and Slc26a4Δ/+ mice.  Slc26a4Δ/Δ mice fail to develop hearing and are a model for Enlarged Vestibular Aqueduct and Pendred Syndrome, two forms of human deafness that are associated with mutations of SLC26A4.  Slc26a4Δ/+ mice develop normal hearing and served a controls. Gene expression was performed at embryonic day (E) 13.5, E14.5, E16.5 and E17.5, which are pathobiologically relevant time points that mark growth and enlargement of the entire inner ear including the cochlea and the vestibular aqueduct.
Affymetrix microarrays were used to analyze gene expression and developmental changes in gene expression in Slc26a4Δ/Δ and Slc26a4Δ/+ mice with the goal to identify genes that are in a functional relationship with Slc26a4, the gene that codes for pendrin.

overall_design: Endolymphatic sacs free of connective tissue and free of endolymphatic ducts were obtained by manual micro-dissection from Slc26a4Δ/+ and Slc26a4Δ/Δ mice at embryonic day (E) 13.5, E14.5, E16.5 and E17.5. Labelled fragments were analyzed following manufacturers procedures (Affymetrix Mouse Genome 430 2.0 GeneChip arrays).    2.0 GeneChip arrays).

first: Xiangming

last: Li

first: Fei

last: Zhou


title: Expression data from rat brain following ischemic stroke or undercut

status: Public on Aug 21 2017

city: Berkeley

first: Soo Young

last: Kim

department: IB

institute: UC Berkeley

summary:
Although it is well known that stroke and head trauma are one of the high risk factors for the development of acquired epilepsy, the cellular mechanisms underlying the epileptogenesis is not well understood. Using rodent models of ischemic stroke and head trauma (partial cortical isolation, undercut), we comparatively analyzed transcription profiles between two different models to explore the commonality.
Despite well-known risk factors such as stroke and head trauma, it has not been clinically effective to prevent acquired epilepsy. To do so, it is crucial to understand what commonly drives neural hyperexcitability. Using comparative transcriptome analyses with different models of acquired epilepsy including stroke and head trauma (the present GEO case), as well as blood-brain barrier (BBB) disruption, albumin, and TGFβ application (GEO accession number: GSE12304), we show that TGFβ signaling activation following BBB disruption commonly occurs regardless of brain region and insult types, accompanied by the strong upregulation of genes relevant to inflammation and extracellular matrix (ECM) modulation.

overall_design:
For undercut: RNAs were extracted from rat cortices 24 hour after either partial cortical isolation (Undercut, UC; n=3) or sham operations (UC_Sham; n=3).
For stroke: The infarction was induced by photothrombisis using Rose Bengal in the somatosensory cortex of rats. RNAs were extracted from ipsilateral hippocampi at three time points (n=1; 12h, 24h, and 7d). RNAs extracted from sham-operated animals served as control at each time point (n=1; 12h, 24h, and 7d).

first: Soo

first: Kristina

last: Lippmann

first: David

last: Prince

first: Uwe

last: Heinemann

first: Alon

last: Friedman

first: Daniela

last: Kaufer


title: Identification of a gene expression signature associated with the metastasis suppressor function of NME1

status: Public on Aug 22 2017

city: Lexington

first: Joseph

middle: Robert

last: McCorkle

state: KY

address: 760 Press Ave.

institute: University of Kentucky

summary:
Transciptome analysis using a panel of WM793 melanoma cell lines following stable overexpression of wild-type or mutant forms of human NME1
NME1 is well known for its ability to suppress melanoma metastasis, however the means by which NME1 accomplishes this remains controversial. Herein, we utilized a bioinformatics approach to systematically identify effector genes of NME1’s metastasis suppressor function by tracking genes regulated by wild-type NME1 but not by metastasis suppressor deficient mutants of NME1. This approach identified a number of novel genes, such as ALDOC, CXCL11, LRP1b and XAGE1 as well as known targets of NME1 such as NETO2. Our NME1-mediated Metastasis Suppressor Signature (MSS) was capable of identifying subpopulations of metastatic melanoma patients with prolonged progression free survival. Interestingly, when patients were clustered by an extension of the MSS, two populations of metastatic melanoma patients were identified with significantly lowered overall and progression free survival times. Together, these data demonstrate that NMEl is a powerful tool for identifying genes that both promote and inhibit melanoma metastasis.

overall_design: Analysis of WM793 (parent) and NME1 (wild-type and 3 mutant (E5A, K12Q, P96S) constructs) overexpressing cell lines using the Affymetrix GeneChip Human Exon 1.0 ST Arrays. 20 arrays were run across the 5 cell lines with 4 technical replicates performed for each cell line. Array data was processed and normalized in R using the RMA method.

first: Mary

middle: K

last: Leonard

first: Marian

last: Novak

first: Qingbei

last: Zhang

first: Eric

middle: X

last: Blalock

first: Amol

last: Shetty

first: Anup

last: Mahurkar

last: Kaetzel


title: Gene expression profiles in E3.0 WT and Klf5 KO embryos

status: Public on Sep 13 2017

city: Edinburgh

first: Takuya

last: Azami

address: Crewe Road

department: Institute of Genetics and Cancer

country: United Kingdom

institute: The University of Edinburgh

summary: Klf5 has essential functions during early embryogenesis and in the derivation of ES cells from inner-cell mass of blastocyst. Among Kruppel-like factor (Klf) family members, only Klf5 shows peri-implantation lethal phenotype, but the precise mechanisms still remain unknown. To understand and identify molecular mechanisms, we performed microarray analysis by using E3.0 WT and Klf5 KO embryos when first phenotype of Klf5 deficiency appears.

overall_design: Wild type (WT) and Klf5 knock-out (KO) embryos were collected from oviduct at E3.0. cDNAs were synthesized from individual embryos in accordance with the protocol described by Kurimoto et al., 2007. Gene expression analysis was performed by GeneSpring GXsoftware

first: Ken

last: Matsumoto

first: Kazuki

last: Kurimoto

first: Mitinori

last: Saitou

first: Masatsugu

last: Ema


title: Intravesical BCG induces CD4+ T Cell Expansion in a Clinically Relevant Immune Competent Model of Bladder Cancer

city: Baltimore

first: Max

last: Kates

state: MD

address: 600 N. Wolfe Street / Marburg 420

institute: Johns Hopkins Medical Institutions

summary: Intravesical BCG Immunotherapy is the standard of care in treating non-muscle invasive bladder cancer, yet its mechanism of action remains elusive.  Both innate and adaptive immune responses have been implicated in BCG activity. While prior research has indirectly demonstrated the importance of T cells and shown a rise in CD4+ T cells in bladder tissue after BCG, T cell subpopulations have not been fully characterized.  We investigated the relationship between effector and regulatory T cells in an immune competent, clinically relevant rodent model of bladder cancer.  Our data demonstrate that cancer progression in the MNU rat model of bladder cancer is characterized by a decline in the CD8/FoxP3 ratio, consistent with decreased adaptive immunity.  By contrast, treatment with intravesical BCG leads to a large, transient rise in the CD4+ T cell population in the urothelium, and is both more effective and immunogenic compared to intravesical chemotherapy.  Interestingly, whole transcriptome expression profiling of post-treatment intravesical CD4+ and CD8+ T cells revealed minimal differences in gene expression after BCG treatment.  Together, our results suggest that while BCG induces T cell recruitment to the bladder, the T cell phenotype does not markedly change, implying that combining T cell activating agents with BCG might improve clinical activity.

overall_design: Digested Rat bladders, sorted for CD8 and CD4 T cells.  Biologic groups are two replicates each of: control bladders, untreated bladders with bladder cancer, and bladders with bladder cancer treated with intravesical BCG

first: Thomas

last: Nirschl

first: Charles

last: Drake

first: Trinity

last: Bivalacqua


title: Expression data in GADD34 knockout cells treated with arsenite

status: Public on Aug 27 2017

city: Singapore

first: Shirish

last: Shenolikar

state: Singapore

address: 8 College Road

department: Neuroscience and Behavioral Disorders

country: Singapore

institute: Duke-NUS Graduate Medical School

summary:
Growth arrest and DNA damage induced protein (GADD34) is a regulator of protein phosphatase 1 and promotes eIF2α dephosphorylation under conditions of various stress. eIF2α phosphorylation at Ser 51 is a key nodule controlling the general rate of protein synthesis and activation of integrated stress response pathways. In GADD34 knockout conditions, dysregulated eIF2α phosphorylation is likely to produce abnormalities in the integrated stres response. GADD34 can be induced by many different stresses but oxidative stress by arsenite produced highest GADD34 levels in various cell lines tested. We aim to evaluate early gene expression changes on arsenite treatment and examine if GADD34 influences the profile of genes induced by oxidative stress.
Using microarrays, we investigated the impact of GADD34 knockout under conditions of oxidative stress induced by arsenite in mouse embryonic fibroblasts.

overall_design: Three replicate experiments were performed. Each experiment included wildtype and knockout GADD34 MEFs untreated or treated with arsenite at 0.1 mM for 2 h. In total there were 12 samples.

first: Catherine

middle: W

last: Goh

first: Irene

last: Lee


title: Dynamic gene expression response to altered gravity in human T cells

status: Public on Aug 11 2017

city: Zurich

first: Cora

middle: S.

last: Thiel

address: Winterthurerstrasse 190

department: Institute of Anatomy

country: Switzerland

institute: University of Zurich

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

overall_design: Refer to individual Series


title: Expression data from an outbred model for type 2 diabetes development

city: Beijing

first: Lei

last: Li

address: No. 55 Zhongguancun East Road, 100190

institute: Academy of Mathematics and Systems Science

summary: To study the development mechanisms of type 2 diabetes, we examined multi-tissues' expression profiles of outbred mice fed with a high-fat diet (HFD) or regular chow at week 1, 9, and 18 and performed a novel dual eigen-analysis.

overall_design: We initiated a project on the development process of T2D using a mouse model. Unlike the knockout approach commonly seen in other literatures, we took an outbred model to mimick the natural human population. The mice of 5-week-old were fed with regular chow (RC) or a high fat diet (HFD). At week 1, week 9 and week 18, we collected tissue samples from both diet groups and measured their mRNA abundances of the adipose, the liver and the pancreas respectively using the Affymetrix Mouse430-2.0 Array.

first: Yong

last: Wang


title: Werner syndrome WRN helicase alters gene expression in a G-quadruplex DNA-dependent manner to antagonize a pro-senescence gene expression program

city: Seattle

first: James

middle: William

last: MacDonald

state: WA

address: 4225 Roosevelt Way NE

department: Environmental and Occupational Health Sciences

institute: University of Washington

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

summary: Werner syndrome (WS) is a human adult progeroid syndrome caused by loss-of-function mutations in the WRN RECQ helicase gene. We analyzed mRNA and miRNA expression in fibroblasts from WS patients and in fibroblasts depleted of WRN protein in order to determine the role of WRN in transcription regulation, and to identify genes and miRNAs that might drive WS disease pathogenesis. Genes altered in WS cells participate in cellular growth, proliferation and survival; in tRNA charging and in oncogenic signaling; and in connective tissue and developmental networks. Genes down-regulated in WS cells were highly enriched in Gquadruplex (G4) DNA motifs, indicating G4 motifs are physiologic substrates for WRN. In contrast, there was a remarkable, coordinate up-regulation of nearly all of the cytoplasmic tRNA synthetases and of genes associated with the senescence-associated secretory phenotype (SASP). These results identify canonical pathways that may drive the pathogenesis of Werner syndrome and associated disease risks.

platform_organism:
Homo sapiens
Mus musculus

overall_design: Primary fibroblasts from 6 patients and 8 matched normal controls, and in 9 primary diploid fibroblasts. The 9  primary diploid fibroblasts included 3 depleted of the WRN protein by WRN-specific shRNA, 3 controls, and 3 scrambled shRNA with no known target sequence in the human genome.

first: Richard

middle: P

last: Beyer

first: Giang

last: Nguyen

first: Ana

last: Robles

first: Weiliang

last: Tang

first: Lucas

last: Gray

first: Nancy

last: Maizels

first: Raymond

middle: J

last: Monnat

first: Curtis

last: Harris


title: A germline mutation in SRRM2, a splicing factor gene, is implicated in papillary thyroid carcinoma predisposition

status: Public on Aug 14 2017

city: Toronto

first: Qun

last: Pan

address: 160 College St.

institute: University of Toronto

type: Expression profiling by high throughput sequencing

summary: Papillary thyroid carcinoma (PTC) displays strong but so far largely uncharacterized heritability. Here we studied genetic predisposition in a family with six affected individuals. We genotyped all available family members and conducted whole exome sequencing of blood DNA from two affected individuals. Haplotype analysis and other genetic criteria narrowed our list of candidates to a germline variant in the serine/arginine repetitive matrix 2 gene (SRRM2). This heterozygous variant, c.1037C>T (Ser346Phe or S346F; rs149019598) cosegregated with PTC in the family. It was not found in 138 other PTC families. It was found in 7/1,170 sporadic PTC cases and in 0/1,404 controls (p=0.004). The encoded protein SRRM2 (also called SRm300) is part of the RNA splicing machinery. To evaluate the possibility that the S346F missense mutation affects alternative splicing, we compared RNA-Seq data in leukocytes from three mutation carriers and three controls. Significant differences in alternative splicing were identified for 1,642 exons, of which a subset of 7 exons was verified experimentally. The results confirmed a higher ratio of inclusion of exons in mutation carriers. These data suggest that the S346F mutation in SRRM2 predisposes to PTC by affecting alternative splicing of unidentified downstream target genes.

overall_design:
We performed high-throughput RNA sequencing (RNA-Seq) of polyadenylated RNA transcripts extracted from blood samples obtained from three PTC patients heterozygous for the SRRM2 mutation and from three wildtype controls.

*The submitters declare they do not have approval to share the raw data.*

first: Jerneja

last: Tomsic

first: Huiling

last: He

first: Keiko

last: Akagi

first: Sandya

last: Liyanarachchi

first: Blake

last: Bertani

first: Rebecca

last: Nagy

first: David

last: Symer

first: Benjamin

last: Blencowe

first: Albert

last: de la Chapelle


title: Gene expression profiles of in vitro induced Foxp3+ regulatory T cells in mice

status: Public on Aug 25 2017

city: Milwaukee

first: Martin

last: Hessner

state: WI

address: 8701 Watertown Plank Road

department: Pediatrics

institute: Medical College of Wisconsin

summary: Platelets are a rich source of many cytokines and chemokines including transforming growth factor β-1 (TGFβ1). TGFβ1 is required to convert conventional CD4+ T (Tconv) cells into induced regulatory T (iTreg) cells that express the transcription factor Foxp3. To explore whether other platelet contents will affect the properties of TGFβ induced Treg cell, we used platelet lysate that contain many other cytokines and chemokines besides TGFβ1 (pltTGFβ) to induce Foxp3 expression (pltTGFb-iTreg) from conventional CD4+ T (Tconv) cells. We used purified TGFβ1 to induce Treg (purTGFβ-iTreg) cells as a control. Gene expression profiles in iTreg cells were analyzed by microarray asay.

overall_design: RNA was purified from pltTGFβ-iTreg, purTGFβ-iTreg, and Tconv cells.  cDNA was labeled and hybridized to the Mouse Genome 430 2.0 GeneChip. Three biological replicates were performed and the results were averaged. Image data were analyzed with Affymetrix Expression Console™ software and normalized with Robust Multichip Analysis (RMA; www.bioconductor.org/) to determine signal log ratios. Probe sets that exhibited a 1.4-fold difference (|log2 ratio| > 0.5) relative to Tconv cells were identified and those that possessed a false discovery rate of <10% were used in subsequent analyses. The statistical significance of differential gene expression was determined through ANalysis Of VAriation (ANOVA) and false discovery rates (FDR) using Partek Genomics Suite 6.6. Hierarchical clustering was conducted with Genesis6.  Pathway analysis was performed with the Database for Annotation, Visualization, and Integrated Discovery.

first: Dipica

last: Haribhai

first: Xiaofeng

last: Luo

first: Juan

last: Chen

first: Shuang

last: Jia

first: Linzheng

last: Shi

first: Jocelyn

middle: A

last: Schroeder

first: Harmut

last: Weilar

first: Richard

middle: H

last: Aster

first: Jianda

last: Hu

first: Calvin

middle: B

last: Wiliams

first: Qizhen


title: Differential expression of Hdc-GFP+/hiCD11b+Gr1+ vs Hdc-GFP-/loCD11b+Gr1+ myeloid cells from mouse bone marrow

city: New York

first: Timothy

middle: Cragin

last: Wang

state: NY

address: 1130 St. Nicholas Ave

department: Medicine- Liver and Digestive Diseases

institute: Columbia University Medical Center

summary: Bone marrow Hdc-GFP+/hi and Hdc-GFP-/loCD11b+Gr1+ cells were isolated from bones from histidine decarboxylase (Hdc) green fluorescent protein (Hdc-GFP) mice Hdc-GFP+/hiCD11b+Gr1+ cells and Hdc-GFP-/loCD11b+Gr1+ cells were sorted by combinations of GFP and myeloid cell surface markers CD11b and Gr1 and their differential mRNA expression compared with Affymetrix microarrays.

overall_design:
a. Hdc-GFP-/loCD11b+Gr1+cells (n=3)
b. Hdc-GFP+/hiCD11b+Gr1+ cells (n=3)

first: Xiaowei

last: Friedman


title: Key transcription factors altered in multiple myeloma patients revealed by logic programming approach combining gene expression pro ling and regulatory networks

status: Public on Sep 20 2017

city: Saint Herblain

first: Wilfried

last: Gouraud

address: bd Jacques Monod

department: Integrated Center of Oncology René Gauducheau

country: France

institute: ICO (Integrated Center of Oncology Nantes)

summary: Innovative approaches combining regulatory networks and genomic data are needed to extract pertinent biological informations to a better understanding of complex disease such as cancer and improve identi cation of entities leading to potential new therapeutic avenues. In this study, we confronted an automatic generated regulatory network with gene expression pro les (GEP) from a large cohort of patients with multiple myeloma (MM) and normal individuals with a causality reasonning method based of graph coloring to identify keynodes. Due to this causality reasoning, it is possible to infer proteins state from these GEP. Also, our method is able to simulate the impact of the perturbation of a node in this regulatory network to identify therapeutic targets. This method allowed us to nd that JUN/FOS and FOXM1, known in MM, and their inhibition as speci c to large group of patients with MM. Moreover, we associated the inhibition of FOXM1 activity with good prognosis, suggesting the inhibition of FOXM1 activity could be a survival marker. Finally, if JUN/FOS activation seems to be a way to strongly perturb the regulatory network in view of GEP, our result suggests the activation of FOXM1 could be interesting way to perturb some sub-group of profiles.

overall_design: 602 myeloma patients examined with regulatory network on gene expression profiling

first: Bertrand

last: Miannay

first: Stéphane

last: Minvielle

first: Olivier

last: Roux

first: Hervé

last: Avet-Loiseau

first: Catherine

last: Guérin-Charbonnel

first: Michel

last: Attal

first: Thierry

last: Facon

first: Nikhil

last: Munshi

first: Philippe

last: Moreau

first: Florence

last: Magrangeas

first: Carito

last: Guziolowski


title: LXR nuclear receptors are transcriptional regulators of dendritic cell chemotaxis

status: Public on Feb 28 2018

city: Madrid

first: ANTONIO

last: CASTRILLO

address: Arturo Duperier 4

department: metabolism and cellular signaling

institute: Instituto Investigaciones Biomedicas Alberto Sols CSIC

summary: The liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DC), are still poorly understood.  Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migration in vitro and in vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished LXR-dependent induction of DC chemotaxis. Using the LDLR-/- mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for efficient emigration of DCs in response to chemotactic signals during inflammation.

overall_design: BM-derived DCs (BMDCs) from LXR WT and LXR double knockout (combined deficiency of LXRalpha and LXRbeta) mice were generated in vitro as described by Inaba et al. (J Exp Med. 1992 Dec 1;176(6):1693-702) with modifications. BM cells were cultured for 6-7 days in RPMI 1640 medium containing 10% fetal bovine serum (FBS) supplemented with mouse GM-CSF (20 ng/mL, Peprotech, UK) every two days. Non-adherent cells were collected and further enriched in CD11c positive DCs by positive selection with CD11c microbeads (MiltenyiBiotec) following the manufacturer instructions. Cells were then further cultured with GMCSF (10ng/ml) as control cells or GMCSF + LPS (100ng/ml) for 24 hours as a model for DC maturation. After treatment, RNA was harvest by column purification with RNAeasy mini-kit (Qiagen). RNA was quantified and submitted for microarray analysis to the Unidad de Genomica, Universidad Complutense de Madrid (UCM)

first: Castrillo

last: Antonio


title: Expression data from Hif-p4h-1 WT vs KO mouse embyonic fibroblasts under normoxic and hypoxic conditions

status: Public on Aug 02 2017

city: Oulu

first: Valerio

last: Izzi

state: Select a State or Province

address: Aapistie 7A

country: Finland

institute: University of Oulu

summary:
The expression of inflammatory genes were downregulated in Hif-p4h-1 KO mouse embryonic fibroblasts both in normoxic and hypoxic condition, whereas the apoptosis regulation genes were upregulated or anti-apoptotic genes were downregulated in Hif-p4h-1 KO mouse embryonic fibroblasts.
We used microarray to study the differential expression of genes in Hif-p4h-1 knockout versus WT mouse embryonic fibroblasts

overall_design: Mouse embryonic fibroblasts were isolated at E14.5 days and total RNA was extracted for microarray analysis.

first: Karim

last: Ullah

first: Johanna

last: Myllyharju


title: Alternative splicing at the last coding exon of Cav2.1 regulates the interaction with Cav4 and plays an essential role in preventing a complex neurological disease in mice

status: Public on Aug 01 2017

city: Bunkyo-ku

first: Kaoru

last: Mogushi

state: Tokyo

address: 2-1-1 Hongo

department: Intractable Disease Research Center

institute: Juntendo University

summary:
Alternative splicing (AS) that occurs at the final coding exon (exon 47) of the Cav2.1 voltage-gated calcium channel (VGCC) gene produces two major isoforms in the brain, MPI and MPc. These isoforms differ in their splice acceptor sites; human MPI is translated into a polyglutamine tract associated with spinocerebellar ataxia type 6 (SCA6), whereas MPc splices to an immediate stop codon, resulting in a shorter cytoplasmic tail.
To gain insight into the functional role of the AS in vivo and its relevance in the pathogenesis of SCA6, here we created knockin mice that exclusively express MPc by inserting the splice-site mutation. The resultant Sca6CtmKO/CtmKO mice developed non-progressive neurological phenotypes resembling those of the Cav4 mutant lethargic (lh/lh), featuring reduced locomotor activity, ataxia and absence seizure without significant alterations in the basic properties of the channel. Interactions of Cav2.1 with Cav4 and Rimbp2 were significantly reduced while those with GABAB2 was enhanced in the cerebellum of Sca6CtmKO/CtmKO mice. Treatment with the GABAB antagonist CGP35348 partially rescued the motor impairments seen in Sca6CtmKO/CtmKO mice. These results suggest that the MPI and MPc-type CaV2.1 channels function in unique Cav2 nano-environments and the carboxyl-terminal domain plays an essential role in the prevention of a complex neurological phenotype.

overall_design: We used MPI 118Q/118Q and CtmKO/CtmKO mice at six weeks old in order to investigate spinocerebellar ataxia type 6 (SCA6). Statistical analysis of differently expressed genes was performed using the Linear Models for Microarray Data (limma) package in R/Bioconductor.

first: Kei

last: Watase

first: Tomonori

last: Aikawa

first: Tateki

last: Watanabe

first: Taisuke

last: Miyazaki

first: Takayasu

last: Mikuni

first: Hiroshi

last: Tanaka

first: Minoru

last: Wakamori

first: Ambika

last: Tewari

first: Kamran

last: Khodakhah

first: Miyano

last: Sakurai

first: Hidenori

last: Aizawa

first: Masahiko

last: Watanebe

first: Masanobu

last: Kano

first: Hidehiro

last: Mizusawa


title: Expression data from the control and Jmjd1c KD ESCs

status: Public on Jul 24 2017

city: Shanghai

first: Ying

last: Jin

state: Shanghai

address: Room 1334 ,Block A, Life Science Research Building, 320 Yueyang Road

institute: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

summary:
The roles of histone demethylases (HDMs) for the establishment and maintenance of the pluripotent state are incompletely defined. Here, we show that JmjC domain-containing protein 1c (Jmjd1c), a putative histone H3 Lys 9 (H3K9) demethylase, is required for mouse embryonic stem cell (ESC) self-renewal. To understand how Jmjd1c knockdown (KD) and resultant changes in the H3K9 methylations would affect ESCs at a global gene expression level, we compared the whole genome transcriptomes between the control and Jmjd1c KD ESCs (6 samples, including 2 shNT control samples and 4 shJmjd1c samples, 2 from #3 and 2 from #4 shRNA, respectively) using affymetrix microarray.
We used microarrays to identify genes affected by Jmjd1c knockdown in mouse ESCs.

overall_design: J1 ESCs were infected with lentiviral supernatants of shNT-pLKO.1, shJmjd1c#3-pLKO.1 or shJmjd1c#4-pLKO.1. One day post-infection, ESCs were selected with puromycin at the final concentration of 1.5ug/ml for 2 days. Subsequently, the puromycin-resistent ESCs were re-plated onto dishes, cultured for 4 days, and collected for RNA isolation. In total, six RNA samples were prepared from the two independent biological duplicates. Microarray analysis was performed with the Affymetrix GeneChip® Mouse Genome 430 2.0 Arrays. The procedures including RNA extraction, cDNA synthesis, labeling, hybridization, washing, and scanning were carried out according to the standard Affymetrix protocol by the Shanghai Biotechnology Corporation.

first: Feng

last: Xiao


title: Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment [microarray]

status: Public on Aug 08 2017

city: Hyderabad

first: Jagan

last: Pongubala

state: Telangana

address: Gachibowli

department: Department of Animal Biology

country: India

institute: University of Hyderabad

summary: Organization of the genome in 3D nuclear-space is known to play a crucial role in regulation of gene expression. However, the chromatin architecture that impinges on the B cell-fate choice of multi-potent progenitors remains unclear. By employing in situ Hi-C, we have identified distinct sets of genomic loci that undergo a developmental switch between permissive and repressive compartments during B-cell fate commitment. Intriguingly, we show that topologically associating domains (TADs) represent co-regulated subunits of chromatin and display considerable structural alterations as a result of changes in the cis-regulatory interaction landscape. The extensive rewiring of cis-regulatory interactions is closely associated with differential gene expression programs. Further, we demonstrate the regulatory role of Ebf1 and its downstream factor, Pax5, in chromatin reorganization and transcription regulation. Together, our studies reveal that alterations in promoter and cis-regulatory interactions underlie changes in higher-order chromatin architecture, which in turn determines cell-identity and cell-type specific gene expression patterns.

overall_design: In situ Hi-C was employed to capture the changes in chromatin organization that underlie the lineage specific gene expression pattern during developmental transition from pre-pro-B to pro-B cell stage.

first: Ravi

last: Boya

first: Anurupa

middle: D

last: Yadavalli

first: Sameena

last: Nikhat

first: Sreenivasulu

last: Kurukuti

first: Dasaradhi

last: Palakodeti

middle: M


title: Expression data from BATF-deficient Treg cells

city: Yokohama

first: Shohei

last: Hori

state: Kanagawa

address: 1-7-22 Suehiro-cho, Tsurumi-ku

institute: RIKEN Center for Integrative Medical Sciences

summary:
FoxP3 is a central regulator of immunological tolerance, controlling the development and function of regulatory T (Treg) cells. To dissect the complex processes orchestrated by FoxP3, we investigated impacts of three autoimmune disease-associated missense FoxP3 mutations in mice. The I363V and R397W mutations were loss-of-function mutations, causing multi-organ inflammation by globally compromising Treg cell physiology. By contrast, the A384T mutation induced a distinctive tissue-restricted inflammation by specifically impairing the ability of Treg cells to compete with pathogenic T cells in certain non-lymphoid tissues.
Because BATF expression was down-regulated in A384T Treg cells, we hypothesized that its down-regulation could account for the A384T Treg cell phenotype and addressed whether BATF-deficient Treg cells are phenotypically similar to A384T Treg cells.

overall_design: CD4(+)hCD2(+) Treg cells from FoxP3hCD2.Batf+/+ or -/- mice were subjected to microarray analysis. All cell populations analyzed were generated in triplicates.

first: Takahisa

last: Miyao


title: Translational profiling of in vivo virus-specific CD8 T cells

status: Public on Jul 10 2017

city: Atlanta

first: Koichi

last: Araki

state: GA

address: 1510 Clifton Rd

department: Department of Microbiology and Immunology

institute: Emory University School of Medicine

summary:
Translation is a critical cellular process to synthesize proteins from their transcripts. However, translational regulation in antigen-specific T cells in vivo has not been well defined.
To address this question, we performed microarray analyses of both total and polysome-associated mRNAs in antigen specific CD8 T cells after acute viral infection.

overall_design: P14 transgenic CD8 T cells specific for GP33 epitope of lymphocytic choriomeningitis virus (LCMV) were adoptively transferred into B6 mice, followed by LCMV Armstrong infection. Day 5 effector and day 8 effector P14 CD8 T cells were purified from the LCMV-infected mice. Naive P14 CD8 T cells were directly purified from P14 transgenic mice. Total and polysome-associated (3 or more ribosomes) mRNAs were isolated from these purified P14 cells, and microarray analyses were performed.

first: Rafi

last: Ahmed


title: Gene expression profiling of 12 month old male C57Bl6 SART+/- liver tumor versus wild-type liver

status: Public on Jul 14 2017

city: La Jolla

first: Mei Yee

last: Koh

state: CA

address: 10901 N Torrey Pines Road

institute: Sanford Burnham Prebys Medical Discovery Institute

summary:
Aim of study was to determine what was causing the liver tumors in the SART1+/- mice
HAF (SART1) is an oxygen-independent ubiquitin ligase for HIF-1α whose physiological role is unknown. Here we show that HAF knockout mice are embryonic lethal suggesting an essential developmental role. Additionally, male SART1+/-  mice spontaneously developed hepatocellular carcinoma (HCC) preceded by steatosis, enhanced liver-neutrophil infiltration and upregulation of HIF-1α in peripheral and liver-infiltrating immune cells. From a cytokine array, we identified a marked (>100-fold) increase in the HIF-1 dependent chemokine, RANTES from SART1+/- -derived Kupffer cells compared to wild-type. Inhibition of RANTES decreased liver neutrophil infiltration, and HCC tumor initiation and growth in SART1+/-  mice. These findings establish new roles for HAF in metabolism and immune cell function, and identify RANTES as a novel target for the treatment of HCC.

overall_design: RNA isolated (using RNAEasy kit) from 3 pieces of a SART+/- liver tumor (histologically verified as hepatocellular carcinoma), 3 pieces from an uninvolved adjacent liver from the same SART+/- mouse, and 3 pieces from a liver from a wild-type mouse. The 3' IVT PLUS Reagent Kit (Affymetrix, P/N 902416) was used to prepare RNA samples for gene expression profiling analysis:

first: Mei


title: Expression data from mutant FoxP3-transduced CD4 T cells

summary:
FoxP3 is a central regulator of immunological tolerance, controlling the development and function of regulatory T (Treg) cells. To dissect the complex processes orchestrated by FoxP3, we investigated impacts of three autoimmune disease-associated missense FoxP3 mutations in mice.
As a initial approach, we retrovirally transduced naïve conventional T (Tconv) cells with WT or mutant (A384T and R397W) FoxP3 and analyzed the gene expression profiles of the transduced T cells.

overall_design: Naïve CD4(+) CD25(-) CD45RB(high) T cells were sorted from BALB/cA mice and retrovirally transduced with either MIGR1, mouse WT FoxP3/MIGR1, A384T FoxP3/MIGR1, or R397W FoxP3/MIGR1 retrovirus. GFP(high) CD4(+) transduced T cells were sorted for RNA extraction and hybridization on Affymetrix microarrays. All cell populations analyzed were genereted in duplicates or triplicates.


title: Effect of TGFb treatment (1 ng/ml) on gene expression in Hepa1-6 cells

status: Public on Jul 01 2017

city: Freiburg

first: Clemens

last: Kreutz

address: Habsburger Str. 46

institute: Freiburg University

summary:
The goal of the study is a high-throughput evaluation of the effect of TGFb treatment on gene expression.
In parallel, complex formation of Smad trimers has been evaluated to link Smad complex formation with regulation of gene expression.

overall_design: 20 samples: treated and untreated for 5 time points (0h, 1h, 3h, 6h, 10h), each of the 2x5 conditions was measured in duplicates.

first: Philippe

last: Lucarelli

first: Marcel

last: Schilling

first: Ursula

last: Klingmüller


title: Alternative processing of GTEx RNA-seq data

status: Public on Jul 12 2017

city: San Francisco

first: Dvir

last: Aran

institute: University of California San Francisco

summary: We reprocessed RNA-Seq data for 1,558 samples across 8 tissue sites from the GTEx project. We follow the exact pipeline performed by Rahman et al. Bioifnormatics 2015 (PMID: 26209429)

overall_design: Using Rsubread version 1.14.2 R package, we aligned the fastq files downloaded from dbGap First, the reads were aligned with align() function to the UCSC hg19 reference genome. Second, featureCounts() function was used to summarize the gene level expression values as integer number. Third, these summarized gene values were normalized to FPKM values.. A supplemental file showing the tissue type of each sample is included for the users.

first: Boris

last: Oskotsky


title: A Systems Biology Understanding of Hypothalamic Inflammation Following Transient Hypoxia in the Late-Gestation Fetal Sheep

status: Public on Jul 31 2017

city: GAINESVILLE

first: Charles

middle: Evans

last: Wood

state: Florida

address: 1345 Center Drive/Room M552

department: Physiology and Functional Genomics

institute: University of Florida

summary: The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. However, little is known about the biochemical and molecular response of the fetal brain to transient hypoxia. The present study was designed to use transcriptomics and systems biology modeling to identify major biological responses of the fetal hypothalamus to transient hypoxia. We also investigated the effect of ketamine, an FDA approved anesthetic that has anti-inflammatory properties in various tissues. Chronically catheterized fetal sheep (122±5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2 ~50 %) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. Messenger RNA was isolated from fetal hypothalamus collected 24 hours after hypoxia, and was analyzed for gene expression using the Agilent 15.5k ovine microarray. Hypoxia increased expression of 280 and decreased expression of 357 genes. Genes increased by hypoxia were associated with immune responses, consistent with stimulation by lipopolysaccharide. Pretreatment of the fetuses with ketamine reduced immune/inflammation responses. Immunohistochemical analysis revealed that the number of microglia/macrophages in the anterior hypothalamus was increased by hypoxia and that the increase was blunted by ketamine. We conclude that transient hypoxia stimulates an inflammatory/immune response in the fetal hypothalamus and that transcriptomics/systems biology modeling is a useful and valid tool for investigation of biological function in the fetal sheep.

overall_design: 4 groups: hypoxia, hypoxia plus ketamine, normoxia, normoxia plus ketamine. Hypoxia produced by low PO2 in maternal inspired gas for 30 min, followed by normoxia recovery for 23.5 hours. Control fetuses maintained at normoxia for 30 min, followed by another 23.5 h of normoxia. Fetal hypothalamus collected for mRNA at end of 23.5 h recovery period.

first: Eileen

middle: I

last: Chang

first: Miguel

last: Zarate

first: Thomas

last: Arndt

first: Elaine

last: Richards

first: Maria

last: Rabaglino

first: Maureen

last: Keller-Wood

middle: E


title: Expression data from Treg cells expressing mutant FoxP3

first: Shohei

last: Hori

summary:
FoxP3 is a central regulator of immunological tolerance, controlling the development and function of regulatory T (Treg) cells. To dissect the complex processes orchestrated by FoxP3, we investigated impacts of three autoimmune disease-associated missense FoxP3 mutations (i.e., I363V, A384T, R397W) through knock-in mutagenesis in mice.
We investigated the impacts of these mutations on Treg cell transcriptome by microarray analysis.

overall_design: CD4(+)hCD2(+) WT or mutant Treg cells were sorted from FoxP3WT or mutant:hCD2/WT:GFP heterozygous mice. CD4(+)GFP(+) WT Treg cells were also sorted from FoxP3WT or A384T:hCD2/WT:GFP mice. CD4(+)hCD2(-)GFP(-) Tconv cells were also obtained from FoxP3WT:hCD2/WT:GFP mice. All cell populations analyzed were generated in duplicates or triplicates.

first: Masashi

last: Tachibana


title: Skin inflammation exacerbates food allergy symptoms in epicutaneously sensitized mice

status: Public on Jun 30 2017

city: Yoshida-gun

first: Yusei

last: Ohshima

state: Fukui

address: 23-3 Shimoaizuki, Matsuoka,

institute: University of Fukui

summary:
Cutaneous exposure to food antigen through impaired skin barrier has been shown to induce epicutaneous sensitization, and thereby cause IgE-mediated food allergy.
We examined whether skin barrier impairment deteriorated food allergy symptoms in epicutaneously sensitized mice. To clarify the association between skin inflammation and food allergy symptoms, we analyzed gene expression at skin lesions using a GeneChip.

overall_design: Epicutaneously ovalbumin (OVA)-sensitized mice were orally challenged with OVA. The mice were treated with epicutaneous application of calcipotriol (MC903) or vehicle ethanol (EtOH). We examined the allergy symptoms, and isolated RNA from the treated skins after the second OVA challenge. The gene expression in the treated skin were analyzed by using Genechip system.

first: A

last: Kawasaki

first: N

last: Ito

first: H

last: Murai

first: M

last: Yasutomi

last: Naiki

first: Y


title: Integrative omics analysis in HCC samples

status: Public on Jun 21 2017

city: Beijing

first: Jin

last: Song

address: No.38 shengmingyuan Road

institute: Beijing Institute of Radiation Medicine

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

overall_design: Refer to individual Series


title: Integrative omics analysis in HCC samples [mRNA expression]

summary:
38 paires of tumor tissues and adjacent non-tumor tissues from HCC patients
The number of known lncRNAs increased sharply upon the tiling microarrays and RNA-sequencing were applied to identify lncRNAs. However, only about a dozen of lncRNAs have been well characterized and demonstrated to be tightly associated with development and progression of HCC. A major challenge remains to identify functional lncRNAs associated with HCC. Previous reports mainly selected differentially expressed lncRNAs in cancer tissue or cell lines as candidates for further validation and characterizing. Here, based on mRNA and lncRNA gene expression profiles data collected from tumor and adjacent normal tissues of thirty-eight HCC patients, we adapted integrative omics strategy to identify HCC-associated lncRNAs.

overall_design: To systematically discover functional lncRNAs in HCC, we recruited tumor tissues and paired adjacent non-tumor tissues from thirty-eight patients of primary HCC undergoing surgery and acquired the protein-coding genes and lncRNAs expression profiles through microarray assay. Particular attention was paid to obtain the “core” part of the tumor mass to avoid the adjacent non-tumor tissues, each specimen was reviewed by a board-certified pathologist to confirm that the frozen sections was histological consistent with tumor or non-tumor tissues, and tumor sections had to contain more than 70% tumor cell nuclei and less than 20% necrosis. Tissues were kept frozen in liquid nitrogen immediately after separation until they were used for molecular studies. This study was performed with the approval of the Medical Ethical Committee of Beijing Institute of Radiation Medicine (Beijing, China). This study represents the mRNA expression component of study.

first: Xinyi

last: Tu

first: Xi

last: Chen

first: Fuchu

last: He

first: Gangqiao

last: Zhou


title: Mouse Wild Type and APP transgenic (Tg2576) hippocampus and response to LXR Agonist

city: Cambridge

first: Andrew

last: Hill

state: MA

address: 300 Technology Square

department: Research Business Technology

institute: Pfizer

summary:
The amyloidogenic processing of APP to A-beta is known to play a central role in Alzheimer’s disease pathogenesis. Despite this, however, the physiological role of APP and its processing still remains elusive.  In the current study we utilzed a transcriptional profiling approach, to determine the pathways that may become dysregulated in the brains of APPswe transgenic mice (Tg2576).  As many pathways linked to Alzheimer’s disease are also linked to cholesterol metabolism, we also treated the Tg2576 mice with LXR agonist TO901317, to determine the effects of LXR agonists on the hippocampal transcriptome of Tg2576 mice.
We used microarrays to identify gene expression modulated in hippocampus of transgenic TG2576 mice that express human APP containing the Swedish mutation and the transcriptional responses to treatment with an LXR agonist.

overall_design: 50 mg/kg of TO901317 was administered once per day for 7 days to 20 weeks old Tg2576 mice or non-transgenic littermates by oral gavage in 2% Tween 80 and 0.5% sodium carboxymethylcellulose. Control animals were dosed with vehicle. One hour after the final dose, the animals were sacrificed, saline perfused and the brains extracted. Each brain was hemisected and the hippocampus dissected. The right hippocampus were processed for RNA extraction and hybridized to the MOE430 2.0 array.

first: Max

last: Follettie

first: Helen

last: Warwick

first: David

last: Riddell


title: Microarray expression analysis of wild type and Erg knockdown bone marrow hematopoietic stem and progenitor cells

status: Public on Jun 20 2017

city: Boston

first: Zhe

last: Li

address: 77 Avenue Louis Pasteur, Room 466

department: Medicine, Genetics Division

institute: Brigham and Women's Hospital

summary:
Erg is an ETS family transcription factor frequently overexpressed in human leukemias and has been implicated as a key regulator of hematopoietic stem cells (HSCs). However how Erg controls normal hematopoiesis, particularly at the stem cell level, remains poorly understood. Using homologous recombination, we generated an Erg knockdown allele (Ergkd) in which Erg expression can be restored upon Cre-mediated excision of a Stopper cassette. In Ergkd/+ mice, ~40% reduction in Erg dosage perturbed both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin-Sca-1+c-Kit+ (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors.
By genetic mosaic analysis, we found Erg-restored HSPCs outcompeted Ergkd/+ HSPCs for contributing to adult hematopoiesis in vivo. Intriguingly, HSC differentiation also appeared attenuated, leading to accumulation of long-term HSCs in the mutant LSK population. Accordingly, microarray analysis of Erg-restored and Ergkd/+ HSPCs from the same animal revealed enrichment of stem cell-related pathways in Ergkd/+ HSPCs. Overall, reduced Erg dosage perturbs hematopoiesis by reducing HSC numbers and impairing HSC differentiation, possibly via two Erg targets, Jun and Myc.

overall_design: Erg-restored (to wild type) YFP+ HSPCs and Erg-knockdown (~40% reduction) YFP- HSPCs were sorted from the same mouse [Mx1Cre;Ergkd/+;Rosa26-Stop-YFP (R26Y)]; RNA was prepared from the sorted HSPCs, amplified by Nugen V2 and applied to Affymetrix mouse genome 430 2.0 arrays.

first: Mia

middle: L

last: Koch


title: Maternal exposure to bisphenol-A during pregnancy increases pancreatic beta-cell growth during early life in male mice offspring

status: Public on Jun 01 2017

city: Barcelona

first: Joan Marc

last: Servitja

state: Catalonia

address: Rosselló, 153

institute: IDIBAPS

summary:
Bisphenol-A is a widespread endocrine disruptor chemical. In utero or perinatal exposure to bisphenol-A (BPA), leads to impaired glucose metabolism during adulthood. To investigate the consequences  of the exposure to bisphenol-A during development  in pancreatic beta-cell growth
We used microarrays to determine gene expression changes resulting from  exposure to bisphenol-A during pregnancy in  pancreatic islets of the male offspring at postnatal day 30.

overall_design: Pregnant mice were treated with vehicle or bisphenol-A (10 or 100 μg/kg/day) from day 9 to 16 of gestation. Pancreatic islets were isolated from male offspring at postnatal day 30 (P30). RNA was extracted and hybridized on Affymetrix microarrays.

first: Marta

last: García-Arévalo

first: Paloma

last: Alonso-Magdalena

first: Joan-Marc

first: Angel

last: Nadal


title: Support for Hemangiosarcoma Mode-of-Action from Studies in Mice with Fenretinide, Troglitazone and Elmiron

city: groton

first: Petra

last: Koza-Taylor

state: CT

address: Eastern Point Road

summary: The goal of this study was to assess key molecular elements with three compounds of varying potency for hemangiosarcoma-induction.

overall_design: Mice were dosed with Fenretinide, Troglitazone or Elmiron for 15 and 29 days and Hemangiosarcoma target tissues were profiled.


title: Identification of HGF/c-MET as a biomarker of resistance to Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors

status: Public on Jul 06 2017

city: Houston

first: Tina

last: Cascone

state: TX

address: 1515 Holcombe Blvd.

department: Cancer Medicine

institute: UT MD Anderson Cancer Center

summary:
Therapeutic resistance to VEGFR signaling inhibitors is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). We investigated the contribution of stromal and tumor cells to resistance of NSCLC to VEGFR tyrosine kinase inhibitors (TKIs).
Gene expression analysis of stromal (mouse) and tumor (human) compartments enabled us to identify the HGF/c-MET pathway as a driver and a potential biomarker of VEGFR TKI resistance.

sample_organism:
Homo sapiens
Mus musculus

overall_design: Murine models of human NSCLC were generated and targeted inhibition studies were performed using AZD2171 (cediranib) and ZD6474 (vandetanib). Species-specific transcriptomic profiling was applied to NSCLC xenografts that were sensitive or resistant to therapy.

first: Humam

middle: N

last: Kadara

first: Wenbin

last: Liu


title: Expression data from influenza A virus (H5N3, H5N2/F118 and H1N1/WSN) infected mouse macrophages at 2 and 24H

status: Public on Jun 23 2017

city: Singapore

first: Richard

last: Sugrue

address: 60 Nanyang Drive

department: School of Biological Sciences

institute: Nanyang Technological University

summary:
We used the microarray data to analyse the host cell responses on mouse macrophages infected with the three Influenza A viruses
The global expression analysis showed increased expression changes in H5N3 infected mouse macrophages compared to H5N2/F118 and H1N1/WSN

overall_design: Influenza A virus infected mouse macrophages were harvested at 4 and 24 hpi and RNA extraction was performed using standard protocol as described by affymetrix. The aim of this study is to investigate mouse macropahge responses to Influenza A virus infections.

first: Biruhalem

middle: T

last: Beyene


title: miR-182 inhibition in AKI

city: Vienna

first: Julia

last: Wilflingseder

address: Währinger Gürtel 18-20

department: Nephrology and Dialysis

country: Austria

institute: Medical University of Vienna

summary: gene expression modification after miR-182 inhibition, day 2 and day 7 after ischemic reperfusion injury

overall_design: comparison between control group and treatment group

first: Wilflingseder

last: Julia

first: Oberbauer

last: Rainer


title: Tfcp2l1 controls cellular patterning of the collecting duct.

status: Public on Jun 19 2017

city: New York

first: Max

last: Werth

address: 1150 St. Nicholas Ave.

department: Medicine

institute: Columbia University

summary: Gene expression analysis of mouse kidney after conditional inactivation of transcription factor Tfcp2l1

overall_design: Differrential gene expression analysis from Tfcp2l1(floxed/floxed);EIIAcre knockouts and Tfcp2l1(floxed/floxed) littermate controls (n=3 each). RNA from P1 kidneys was used. Biotynilated cRNA was prepared and hybridized to Affymetrix Mouse Genome 430.2 Array.

first: Jonathan

last: Barasch


title: Loss of function of Cdh1 causes cell fragility due to aberrant G2/M checkpoint and develops resistant disease in acute lymphoblastic leukemia in mouse and human

status: Public on May 24 2017

city: Bunkyo-ku

first: Kaoru

last: Mogushi

address: 2-1-1 Hongo

institute: Juntendo University

summary: Cdh1 regulates not only mitotic phase and G1 phase, but also G2 checkpoint under irradiation-induced DNA damage. Despite several reports indicating its potential as tumor suppressor, how Cdh1 affects tumorigenesis or tumor progression and its clinical implementation has yet to be evaluated. Considering the pivotal role of Cdh1 on DNA repair, we hypothesized that Cdh1 loss also causes fragility of tumor cells to DNA damage under oncogenic stress or chemotherapy. To test this hypothesis, we established a Cdh1 gene-trapped B cell acute lymphoblastic leukemia (B-ALL) mouse model. Cdh1-deficient B-ALL mice survived longer than Cdh1-intact group, with higher susceptibility to DNA damage. Consistently, reverse phase protein array-based analysis of more than 200 human adult B-ALL samples showed that low Cdh1 was associated with high complete remission rates and long remission durations. Furthermore, the clinical benefit with lower Cdh1 expression diminished after relapse, supported by mouse experiments showing that secondary/tertiary transplants of Cdh1-deficient B-ALL cells developed more progressive/resistant disease than Cdh1-intact group. This indicated that prolonged inactivation of Cdh1 eventually develops resistant clones. Our results collectively demonstrated that Cdh1 is a potential predictive biomarker of B-ALL chemosensitivity, but also alerting that synthetic lethality by targeting DNA repair system may eventually induce resistant disease due to genetic instability.

overall_design: Cdh1GT [f-cDNA]/GT [f-cDNA] mice (Cdh1f/f mice), Mx1-Cre transgenic mice were used. N-myc cDNA was cloned into the retroviral vector pMXs-IG. Mx1-Cre expression was induced by intraperitoneally injecting 7- to 8-week-old conditional gene-trap mice (Mx1-Cre(-)/Cdh1f/f, or Mx1-Cre(+)/Cdh1f/f mice) with pIpC. Both genetic groups of mice were selected from the same littermates in each experiment. At 4 weeks after the final pIpC injection, bone marrow mononuclear cells (BM-MNCs) were collected 2days after intraperitoneal injection of 150 mg/kg 5-fluorouracil (5-FU). To investigate the difference in gene signature between Cdh1-intact and -deficient B-ALL cells, we performed gene expression profiling of GFP+ cells in both groups (n = 3 for each). Statistical analysis of differently expressed genes was performed using the Linear Models for Microarray Data (limma) package in R/Bioconductor.

first: Jo

last: Ishizawa

first: Eiji

last: Sugihara

first: Shinji

last: Kuninaka

first: Norisato

last: Hashimoto

first: Kensuke

last: Kojima

first: Dhruv

last: Chachad

first: Yi

last: Hua Qiu

first: Suk-Young

last: Yoo

first: Shinichiro

last: Okamoto

first: Michael

last: Andreeff

first: Steven

last: Kornblau

first: Hideyuki

last: Saya


title: Pulmonary metastasis in xenograft model after orthotopic implantation

city: Shanghai

first: Meiyi

last: Li

address: No.320 Yueyang Road

institute: Institute of Biochemistry and Cell Biology

summary:
Metastasis is a major factor for mortality in patients with hepatocellular carcinoma (HCC). Thus, there is a need for predictive biomarker(s) for detecting the tipping point before metastasis, so as to prevent further deterioration. To discover early warning signals of pulmonary metastasis in HCC, we analysed time-series gene expression data in the spontaneous pulmonary metastasis mouse HCCLM3-RFP model with our novel dynamic network biomarker (DNB) method.
To simulate tumour growth and metastasis in patient livers, we used the spontaneous pulmonary metastasis mouse model, HCCLM3-RFP, which involves the orthotopic transplanted human HCCLM3 cell line labelled with a stable fluorescent protein.We observed that, hepatic tumours in orthotopic xenograft HCCLM3-RFP mice grew gradually from the second to the fifth week after orthotopic implantation in the primary liver tissue, whereas spontaneous pulmonary metastasis occurredonly at the last time point (the fifth week after orthotopic implantation).Thus, we chose the second, third, fourth, and fifth weeks after orthotopic implantation as observation points to collect liver tumours of five orthotopic xenograft mice at each time point and to assess the whole-genome expression.

overall_design: In total, 20 nude mice that underwent orthotopic tumour implantation, were divided into four groups. After the orthotopic tumour implantation, one group of mice were sacrificed each at the second, third, fourth, and fifth weeks for autopsy.

first: Biwei

last: Yang

first: Wenqing

last: Tang

first: Weixin

last: Liu

first: Si

last: Zhang

first: Luonan

last: Chen

first: Jinglin

last: Xia


title: Deletion of Stk40 impairs definitive erythropoiesis in the mouse fetal liver

status: Public on Jun 12 2017

first: Ying

last: Jin

address: 280 South Chongqing Road, Bldg 5, Rm 206

department: School of Medicine

institute: Shanghai JiaoTong University

summary: The serine threonine kinase Stk40 has been shown to involve in mouse embryonic stem cell differentiation, pulmonary maturation and adipocyte differentiation. Here we report that targeted deletion of Stk40 leads to fetal liver hypoplasia and anemia in the mouse embryos. The reduction of erythrocytes in the fetal liver is accompanied by increased apoptosis and compromised erythroid maturation. Stk40-/- fetal liver cells have significantly reduced colony forming units (CFUs) capable of erythroid differentiation, including burst forming unit-erythroid (BFU-E), colony forming unit-erythroid (CFU-E), and CFU-granulocyte, erythrocyte, megakaryocyte and macrophage (CFU-GEMM), but not CFU-granulocyte/macrophages (CFU-GM). Purified Stk40-/- megakaryocyte-erythrocyte progenitors (MEPs) produced substantially fewer CFU-E colonies compared to control cells. Moreover, Stk40-/- fetal liver erythroblasts failed to form normal erythroblastic islands in association with wild type or Stk40-/- macrophages, indicating an intrinsic defect of Stk40-/- erythroblasts. Furthermore, the hematopoietic stem and progenitor cell pool is reduced in Stk40-/- fetal livers but still retains the multi-lineage reconstitution capacity. Finally, analysis of microarray data of E14.5 fetal liver cells suggests a potential role of aberrantly activated TNF-α signaling in Stk40 depletion induced dyserythropoiesis with a concomitant increase in cleaved Caspase-3 and decrease in Gata1 proteins. Altogether, the identification of Stk40 as a regulator for fetal erythroid differentiation, maturation and survival provides new clues to the molecular regulation of erythropoiesis and related diseases.

overall_design: Six E14.5 mouse fetal liver cells of same genotype were pooled together for each sample. There are two replicates for each genetype. mRNA extraction and hybridization on Affymetrix microarrays were performed by Shanghai Biochip Company.

first: Lina

last: Wang

first: Hongyao

last: Yu


title: Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival outcome to neoadjuvant chemotherapy: results from a multi-institutional validation study

status: Public on May 25 2017

city: Vancouver

first: Elai

last: Davicioni

state: BC

address: 1152 Mainland St #430

institute: GenomeDx

summary: Four different molecular classifications of muscle-invasive bladder cancer (MIBC) based on gene expression have been proposed. With the ultimate goal of utilizing these molecular subtypes for personalized treatment, we investigated their significance in the context of neoadjuvant cisplatin-based chemotherapy (NAC).

overall_design: RNA was isolated from pre-NAC transurethral resection (TUR) specimens from 305 patients with MIBC and whole transcriptome profiling was performed. Samples were classified according to four published molecular subtyping methods.

first: Roland

last: Seiler

first: Hussam

last: Ashab

first: Joost

last: Boormans

first: Christine

last: Buerki

first: Voleak

last: Choeurng

first: Woonyoung

last: Choi

first: Simon

last: Crabb

first: Marc

last: Dall’Era

first: James

last: Douglas

first: Nicholas

last: Erho

first: Elisabeth

last: Fransen van de Putte

first: Ewan

last: Gibb

first: Katherine

last: Hoadley

first: Jordan

last: Kardos

first: William

middle: Y

last: Kim

first: Bernhard

last: Kiss

first: Lucia

last: Lam

first: Seth

last: Lerner

first: David

last: McConkey

first: Scott

last: North

first: Beatrix

last: Palmer-Aronsten

first: Gottfrid

last: Sjödahl

first: Matthew

last: Sommerlad

first: George

last: Thalmann

first: Tilman

last: Todenhöfer

first: Michiel

middle: S

last: van der Heijden

first: Kim

last: Van Kessel

first: Bas

middle: W

last: van Rhijn

first: Qiqi

first: Brian

last: Winters

first: Jonathan

last: Wright

first: Ellen

middle: C

last: Zwarthoff

first: Peter

last: Black


title: Expression analysis of gene expression chang in Homo sapiens Small cell lung carcinoma cells NCIH446  after knock down Follitin1 gene

status: Public on May 27 2017

first: Shi

last: Juan

address: 5 Dong Dan San Tiao

institute: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College

summary: Investigation of whole genome gene expression level changes in a Homo sapiens Small cell lung carcinoma cells NCIH446  after knock down of Follitin1 gene expression

overall_design: A four chip study using total RNA extracted from  NCIH446 cells transfected with siRNA negative control and NCIH446 cells knock down of Follitin1 with siRNA . Each chip measures the expression level of 34.558 genes  collected from the authoritative data source including NCBI

first: Lianmei

last: Zhao


title: Expression data from mouse livers of control mice (RECS1-flox) and hepatocyte specific RECS1 deficiency mice (RECS1-HKO) after fed with HFD for 8 weeks

status: Public on May 08 2017

city: Wuhan

first: Hongliang

last: Li

state: Hubei

address: JieFang Road 238, Wuhan

department: Department of Cardiology

institute: Renmin Hospital of Wuhan University

summary:
To investigate the potential mechanism by which RECS1 regulate metabolic disorder, we treated control mice and RECS1 HKO mice with HFD for 8 weeks, and performed microarray to identify the expression pattern and the potential important molecules regulated by RECS1.
We used microarrays to detect the global gene expression in the livers of control mice and RECS1 HKO mice after treatment with HFD for 8 weeks and identified distinct classes of altered genes in the livers of mice upon HFD compared .

overall_design: Eight weeks old control mice (n=3) and RECS1 HKO (n=3) were treated with HFD, and the livers were dissected after 8 weeks treatment.  Total RNA was extracted and a total of 400ng RNA was used following Affymetrix instruction. 3 biological samples for each genotype

first: Peng

last: Zhang


title: Translational reprogramming of colorectal cancer cells induced by 5-fluorouracil through a miRNA-dependent mechanism

status: Public on May 23 2017

city: Lyon

first: Virginie

last: MARCEL

address: 28 rue Laennec

institute: Cancer Research Center of Lyon

summary: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug in colorectal cancer. Previous studies showed that 5-FU modulates RNA metabolism and mRNA expression. In addition, it has been reported that 5-FU incorporates into the RNAs constituting the translational machinery and that 5-FU affects the amount of some mRNAs associated with ribosomes. However, the impact of 5-FU on translational regulation remains unclear. Using translatome profiling, we report that a clinically relevant dose of 5-FU induces a translational reprogramming in colorectal cancer cell lines. Comparison of mRNA distribution between polysomal and non-polysomal fractions in response to 5-FU treatment using microarray quantification identified 313 genes whose translation was selectively regulated. These regulations were mostly stimulatory (91%). Among these genes, we showed that 5-FU increases the mRNA translation of HIVEP2, which encodes a transcription factor whose translation in normal condition is known to be inhibited by mir-155. In response to 5-FU, the expression of mir-155 decreases thus stimulating the translation of HIVEP2 mRNA. Interestingly, the 5-FU-induced increase in specific mRNA translation was associated with reduction of global protein synthesis. Altogether, these findings indicate that 5-FU promotes a translational reprogramming leading to the increased translation of a subset of mRNAs that involves at least for some of them, miRNA-dependent mechanisms. This study supports a still poorly evaluated role of translational control in drug response.

overall_design: 8 total samples were analyzed. We generated the following pairwise comparisons: -5FU polysome vs -5FU non-polysome +5FU polysome vs +5FU non-polysome +5FU polysome vs -5FU polysome. Genes and exons with an fold change >= 1.5 and a p-value <= 0.05 were selected.

first: Zeina

last: BASH-IMAM

first: Gabriel

last: THERIZOLS

first: Micaela

last: POLAY ESPINOZA

first: Julien

last: TEXTORIS

first: Didier

last: AUBOEUF

first: Martin

last: DUTERTRE

first: Jean-Jacques

last: DIAZ


title: Immune-restricted epigenetic reader SP140 maintains macrophage identity and activation states critical to intestinal homeostasis [array]

status: Public on May 03 2017

first: Kate

last: Jeffrey

state: Massachusetts

address: 50 Blossom St, Thier 340

institute: Massachusetts General Hospital, Harvard Medical School

summary:
Introduction: SP140 is a bromodomain/plant homeo domain (PHD)-containing reader with immune-restricted expression, and single nucleotide polymorphisms (SNPs) within SP140 associate with Crohn’s disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unknown.
Results: Individuals carrying CD-associated SNPs within SP140 had defective SP140 mRNA splicing, diminished SP140 protein, and severely suppressed innate immune signatures that stratified them from other CD patients.
Conclusion: SP140 is a critical orchestrator of macrophage identity, and a loss of SP140 due to genetic variation contributes to a molecularly defined subset of CD characterized by suppressed innate immunity.

overall_design: Microarray expression data of mouse bone marrow derived macrophages containing shRNA derived knockdown of SP140 or not, and stimulated with LPS (100ng/mL, 4h) or not. N=3 for each condition.