title: Integrated miRNA and mRNA expression analysis uncovers drug targets in squamous cell carcinoma patients [miRNA]

city: Botucatu

first: Rainer Marco

middle: Lopez

last: Lapa

state: SP

address: Av. Prof. Mário Rubens Guimarães Montenegro, s/n, s/n

department: Neogene

country: Brazil

institute: UNESP

summary: Expression microarray analyses was used to analyze 35 LSCC  with reference sample of 5 normal tissue. A quality control filter was applied based on Feature Extraction flags (empty spaces replacing values)

overall_design: Experiment condition, 35 LSCC and 5 normal laryngeal tissue samples obtained from total laryngectomies were laleled with Cy3 all samples were mixed and hybridized at slide glasses Agilent 8x60k platform.

first: Rainer

last: Lopez Lapa

first: Mateus

middle: C

last: Barros Filho


title: Integrated miRNA and mRNA expression analysis uncovers drug targets in squamous cell carcinoma patients

status: Public on Jul 31 2019

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

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

overall_design: Refer to individual Series


title: Integrated miRNA and mRNA expression analysis uncovers drug targets in squamous cell carcinoma patients [mRNA]

summary: Expression microarray analyses was used to analyze 35 laryngeal squamous cell carcinoma (LSCC)  with reference sample (pool of 5 normal tissue ). A quality control filter was applied based on Feature Extraction flags (empty spaces replacing values)

overall_design: Experiment condition, 35 LSCC and 5 normal laryngeal tissue samples obtained from total laryngectomies were laleled with Cy3 and a pool of 5 normal larynx tissue was labled with Cy3. Samples Cy3 and Cy5 were mixed and hybridized at slide glasses Agilent 8x60k platform.

middle: M


title: Genome-wide profiles of multiple histone modifications in MDA-MB-231 and LM2-4175 cell lines

city: Shanghai

first: Ji

last: Zhang

state: Select a State or Province

address: 197 Ruijin 2nd Road

country: China

institute: Shanghai Jiao Tong University School of Medicine

type: Genome binding/occupancy profiling by high throughput sequencing

summary: LM2-4175 cell line was originally selected from MDA-MB-231,but has more aggressive characteristics in invasion, migration and metastasis. In addition, LM2 cell line specifically metastasizes to lung. To understand the regulatory mechanisms of lung metastasis in breast cancer, we analyzed the chromatin structure of MDA-MB-231 and LM2-4175 cell lines.

overall_design: ChIP-seq of chromatin modification H3K4me3, H3K27Ac, H3K4me1, H3K27me3, H3K9me3, Pol-II were performed in MDA-MB-231 and LM2-4175 cell lines.

first: Kening

last: Li


title: The APOLO long noncoding RNA directly modulates three-dimensional  conformation of multiple distal loci across the Arabidopsis genome

city: Thuwal

first: Alaguraj

last: Veluchamy

address: Thuwal

department: BESE

country: Saudi Arabia

institute: King Abdullah University of Science and Technology

summary: Proving that a novel mechanism by which the lncRNA APOLO (AUXIN REGULATED PROMOTER LOOP) is able to recognize multiple distant independent loci in the Arabidopsis thaliana genome.

overall_design: Three independent libraries were prepared using the NEBNext Ultra DNA Library Prep Kit for Illumina, for ODD, EVEN and LacZ probes-derived samples

first: Federico

last: Ariel

first: Aurelie

last: Christ

first: Leandro

last: Lucero

first: Maria

middle: F

last: Mammarella

first: Teddy

last: Jegu

first: Kiruthiga

last: Gayathri

first: David

last: Latrasse

first: Thomas

last: Blein

first: Chang

last: Liu

first: Moussa

last: Benhamed

first: Martin

last: Crespi


title: Next generation sequencing analysis of transcriptomes in MDA-MB-231 and LM2-4175 cell lines

type: Expression profiling by high throughput sequencing

summary: LM2-4175 cell line was originally selected from MDA-MB-231,but has more aggressive characteristics in invasion, migration and metastasis. In addition, LM2 cell line specifically metastasizes to lung. To understand the melecular mechanisms of lung metastasis in breast cancer,we analyzed the RNA-seq data of MDA-MB-231 and LM2-4175 cell lines.

overall_design: Total RNA from MDA-MB-231 and LM2-4175 cell lines was sequenced by HiSeq2500. Each cell line has two replicates.


title: Human breast cancer cells MDA-MB-231Br: Control vs. LRRC31 overexpressed

city: New Haven

first: Yong

last: Zhu

state: CT

address: 60 College Street

country: USA

institute: Yal University

summary: Transcriptional profiling of human breast cancer brain metastasis cells (MDA-MB-231Br) comparing control cells with cells with overexpression of LRRC31 gene.

overall_design: Two-condition experiment, Control vs.LRRC31 overexpression. Biological replicates: 3 control, 3 transfected, independently grown and harvested. One replicate per array.

first: Jiangbing

last: Zhou

first: Yanke

last: Chen


title: The androgen receptor regulates a druggable translational regulon in advanced prostate cancer

city: Seattle

first: Sonali

last: Arora

state: WA

address: 1100 Fairview Ave N,

institute: FHCRC


title: The androgen receptor regulates a druggable translational regulon in advanced prostate cancer [ribosome profiling]

summary: The recent advent of highly potent inhibitors of the androgen receptor and androgen biosynthesis has had the unfortunate iatrogenic effect of fueling new lethal prostate cancer phenotypes in patients. In particular, non-neuroendocrine androgen receptor-low castration resistant prostate cancer (AR low CRPC) is increasing in occurrence amongst patients and is uniformly fatal. The mechanisms that promote this phenotype remain poorly understood. Through molecular studies of murine and human models of AR low CRPC, we have identified a new functional interface between the androgen receptor and the translation initiation complex inhibitor 4EBP1. AR directly regulates 4EBP1 expression which translationally represses eIF4F complex formation and a pro-proliferation program. In the context of AR low prostate cancer, de-repression of translation initiation drives the aberrant expression of the pro-proliferation regulon which fuels uncontrolled cell growth. Genetic and pharmacologic inhibition of the downstream eIF4F translation initiation complex reverses the proliferation phenotype in vitro and in vivo. These findings reveal a new previously unrecognized druggable nexus which functionally link the processes of mRNA transcription and translation initiation in a rapidly emerging class of advanced lethal prostate cancer

overall_design:
Androgen receptor low prostate cancer has been on the rise with the advent of potent androgen receptor and androgen biosynthesis inhibitors and is uniformly fatal. The mechanisms underlying disease progression remains unresolved. We have identified a previously unknown direct interaction between the androgen receptor and the translation initiation complex inhibitor 4EBP1 which plays a critical role in protein synthesis rates, mRNA specific translation, and disease progression in vivo. This is mediated through the hyperactivation of the downstream eIF4F translation initiation complex which usurps a network of pro-proliferation mRNAs. Importantly, using both genetic and pharmacologic methods, we demonstrate that dissociation of the eIF4F complex reverses the proliferation program leading to tumor regression. As such, we have identified a new therapeutic paradigm for targeting lethal androgen receptor low prostate cancer.

Ribosome profiling of prostate tissue from castrated or intact PB-Cre4;PTENLoxP/LoxP mice.

first: Yuzhen

first: Jessie

middle: L

last: Horm

first: Kalyan

last: Banda

first: Asha

middle: Z

last: Goodman

first: Yiting

last: Lim

first: Sujata

last: Jana


title: The JA-pathway MYC transcription factors regulate photomorphogenic responses by modulating the expression of HY5 and PIF targets

city: Madrid

first: Jose M.

last: Franco-Zorrilla

state: Madrid

address: Darwin, 3

department: Plant Molecular Genetics

country: Spain

institute: Centro Nacinal de Biotecnologia-CSIC

summary: Jasmonates are key regulators of the balance between defence and growth in plants. However, the molecular mechanisms by which activation of defences reduces growth are not yet understood. Here, we analyze the role of MYC transcription factors (TFs) and JA in photomorphogenic growth. We found that multiple myc mutants share light-related phenotypes with mutants of the phytochrome B photoreceptor, regarding seed germination and hypocotyl growth. Over-expression of MYC2 in a phyB background partially suppressed its long hypocotyl phenotype. We show that the activity of MYC TFs is partially independent of COI1 and that JA inhibition of hypocotyl growth acts through alteration of auxin homeostasis and is partially independent of the classical JA signalling pathway. Transcriptomic analysis of multiple myc mutants confirmed that MYCs are required for full expression of R-light regulated genes, including the master regulator HY5. ChIP-Seq analyses revealed that MYC2 and MYC3 directly bind to the promoter of HY5 and that HY5 gene expression and protein levels are compromised in multiple myc mutants. Moreover, MYC2 and MYC3 share a high amount of direct targets with PIFs, and have an opposite effect on gene expression of these targets. Altogether, our results pinpoint MYCs as photomorphogenic TFs that regulate phytochrome responses by regulating PIFs targets and activating HY5 expression. This has important implication to understand the trade-off between growth and defence, since the same TFs that activate defence responses are photomorphogenic growth regulators.

overall_design: Two experimental conditions: Triple myc2,3,4 mutant vs Col-0 plants grown under white light (WL) conditions; andTriple myc2,3,4 mutant vs Col-0 plants supplemented with monochromatic Far red light.

first: A

last: Ortigosa

first: S

last: Fonseca

first: J

first: P

last: Fernandez-Calvo

first: M

last: Zander

middle: G

last: Lewsey

first: G

last: García-Casado

middle: R

last: Ecker

first: R

last: Solano


title: Activation of PARP-1 by snoRNAs Controls Ribosome Biogenesis and Cell Growth via the RNA Helicase DDX21

city: Dallas

first: W. Lee

last: Kraus

state: TX

address: 5323 Harry Hines Blvd.

institute: UT Southwestern Medical Center

summary:
PARP inhibitors (PARPi) are thought to control cancer cell growth by inducing synthetic
lethality with DNA repair defects (e.g., in BRCA1/2 mutant cells). We have identified an alternate pathway for PARPi-mediated growth control in BRCA1/2-intact breast cancer cells involving rDNA transcription and ribosome biogenesis. PARP-1 binds to snoRNAs, which stimulate PARP-1 catalytic activity in the nucleolus independent of DNA damage. Activated PARP-1 ADPribosylates DDX21, an RNA helicase that localizes to the rDNA locus and promotes rDNA transcription when ADP-ribosylated. Treatment with PARPi or mutation of the ADP-ribosylation sites on DDX21 causes a reduction in rDNA transcription, as well as a reduction in ribosome biogenesis, protein translation, and cell growth. Our studies provide mechanistic insights into PARP-1-dependent ADP-ribosylation of DDX21 and its role in ribosome biogenesis. This pathway can be targeted for disruption in cancer cells that lack defects in DNA repair, but exhibit growth inhibition in response to PARPi.

overall_design: RIP-seq datasets were generated using MCF-7 cells to determine the repertoire of PARP-1-binding RNAs. RNA-seq datasets were generated using MCF-7 cells to normalize the RIP-seq datasets and to generate a genome browser snapshots

first: D

last: Kim

first: C

middle: V

last: Camacho

last: Nagari

first: V

middle: S

last: Malladi

last: Challa

first: W


title: Divergent principles specifying inflammatory versus antiviral transcriptional programs in dendritic cells [ATAC-seq]

city: DEBRECEN

first: LAJOS

last: SZELES

address: NAGYERDEI KRT 98

country: Hungary

institute: UNIVERSITY OF DEBRECEN

summary: Stimulus-specific gene expression programs are enabled by enhancers, on which stimulus-regulated transcription factors (SRTFs) can land in a cell type- and stimulus-dependent manner. In this study, we identified the key features of enhancers that mediate differential responses to Toll-like receptor (TLR)-stimulation. We characterized the TLR3- and TLR9-induced programs and enhancers in CD8+ dendritic cells.The relevance of these features has been confirmed via machine learning application and by mapping SRTF-binding.

overall_design: CD8-positive dendritic cells were left unstimulated or were treated for the indicated periods of time (6h or 90 mins) with 5 mg/ml of high molecular weight Polyinosinic-polycytidylic acid (pIC) or 1 mM class B CpG oligonucleotide 1826 (CpG).

first: Lajos

last: Széles

first: Walter

last: Reith


title: Divergent principles specifying inflammatory versus antiviral transcriptional programs in dendritic cells [RNA-seq]


title: Divergent principles specifying inflammatory versus antiviral transcriptional programs in dendritic cells


title: Gene expression profiles of mice with juvenile HFD exposure for one week

city: Memphis

first: Quynh

last: Tran

state: TN

address: 262 Danny Thomas Place, C4029, Mail Stop 250

department: Pathology

institute: St. Jude Children's Research Hospital

summary: The objective of this study is to determine the gene expression changes in mice after acute exposure to an high fat diet during the developing phase and whether these changes can predispose mice to altered outcomes later in life.

overall_design: Male C57BL/6J mice were fed a chow diet from weaning up until 6 wks of age. Some mice were fasted for 16 h before being sacrificed.  From 6-7wks, the control group (CD) ate a control diet (CD; 10% of total calories  from fat), whereas the juvenile exposure group (HFD) were fed a high fat diet (HFD;  45% total calories from fat). Both groups were maintained on a chow diet during  the wks 7-10, after which all mice were placed on the same HFD until they reached  22 wk of age.

first: Dave

last: Bridges


title: RNAseq analysis of quadriceps muscles from adult mice with constitutively active skeletal and cardiac muscle mTORC1 (through conditional knockout of Tsc1 under the Mck Cre) and their wild type litter mates

summary: The purpose of this study was to determine how constitutively active mTORC1 signalling alters the transcriptome in skeletal muscle and determine how altered mTORC1 signaling influences the metabolic phenotype. We hypothesized that constitutively active skeletal muscle mTORC1 would lead to increased thermogenic capacity of the muscle and that this promotion of energy expenditure would be protective against diet-indued obesity

overall_design: Mice with conditional knockout of the Tsc1 gene were generated. Gastrocnemius muscles were isolated from adult mice n= 28 (7 knockouts and 21 wild types) and total RNA was extracted using TRIzol. Extractions were column purified using a PureLink RNA mini kit and RNA quality was determined using an Agilent bioanalyzer. Sequencing libraries were generated and sent to the UTHSC Molecular Resource Center for RNA sequencing using on AB SOLID 5500 Wildfire.

first: Erin

middle: J

last: Stephenson

first: Innocence

last: Harvey

first: Binbin

last: Lu

first: JeAnna

last: Redd

first: Matthew

last: Peloquin

first: Kaleigh

last: Fisher

first: Jyothi

last: Parvathareddy

middle: T

first: Joan

last: Han

first: Alan

last: Saltiel


title: FACS-sorted ureteric bud-derivative cells at postnatal day one: wildtype (WT) vs. conditional null (MUT) for Bdkrb2

city: New Orleans

first: Samir

last: El-Dahr

state: LA

address: 1430 Tulane Ave

department: Pediatrics

institute: Tulane University School of Medicine

summary: Transcriptional profiling of FACS-sorted ureteric bud-derivative cells from Hoxb7CreGFP mice without floxed Bdkrb2 allele (WT) or with homozygously floxed Bdkrb2 alleles (MUT) at the age of postnatal one. Both WT and MUT mice have R26RTdTomato allele as a recombinase efficiency indicator, which allows the FACS to sort cells according to both GFP and TdTomato. This experiment aimed to uncover the genome-wide alternation in gene expression resulting from the removal of Bdkrb2 in the ureteric buds and their derivative collecting ducts.

overall_design: Two-condition experiment, WT vs. MUT cells. Biological replicates: 3 WTs and 3 MUTs.

first: Lei

last: Yan

first: Sylvia

last: Hilliard


title: mRNA expression profile in WT and ZNF598 knockout HeLa cells stimulated with short poly I:C

status: Public on Jul 30 2019

city: Kamakura

first: Satoshi

last: Kondo

state: Kanagawa

address: 10-1 tebiro 6-chome

country: Japan

institute: Toray Industries,Inc.

summary: mRNA expression profiles were compared between wild-type and ZNF598 knockout cells in the presence or absence of a RIG-I ligand, short poly I:C.

overall_design: WT and ZNF598 knockout HeLa cells were cultured in a 24-well-plate, and were then stimulated with or without 100 ng/ml of short poly I:C for 9 hours. Total RNA was extracted from stimulated and unstimulated HeLa cells, and was subjected to the microarray analysis.

first: Takahisa

last: Kouwaki

first: Hiroyuki

last: Oshiumi


title: Expression data from lymphocytes from skin of pemphigus patients and  healthy control

first: Shengru

last: Zhou

address: No. 197, Rui Jin Er Road

department: Dermatology

institute: Shanghai Jiao Tong University School of Medicine affiliated Rui Jin Hospital

summary:
Total RNA from lymphocytes derived from skin lesions of three pemphigus patients and three healthy control subjects was used for this study.
Elevated mRNA expression levels of the immune cells activation and chemotaxis were observed in pemphigus lesions.

overall_design: 6 samples were analyzed. Lymphocytes derived from skin lesions of three pemphigus patients and three healthy control subjects was used for this study.

first: Huijie

last: Yuan


title: Divergent principles specifying inflammatory versus antiviral transcriptional programs in dendritic cells [ChIP-seq]

first: LAJOS

last: SZELES

first: Lajos

last: Széles

first: Walter

last: Reith


title: Genome-wide screening of VxrB binding sites in Vibrio cholerae

city: Ithaca

first: JUNG HO

middle: Cornell

last: SHIN

state: NY

address: 363 Weill Hall, Cornell University

department: Microbiology

institute: Weill Institute at Cornell University

summary: Bactericidal antibiotics are powerful drugs because they not only inhibit essential bacterial functions, but convert them into toxic processes. Many bacteria are remarkably tolerant against antibiotics, due to inducible damage repair responses. How these responses promote whole population tolerance in important human pathogens is poorly understood. The two-component system VxrAB of the diarrheal pathogen Vibrio cholerae, a model system for tolerance against cell wall damaging (e.g., beta-lactam) antibiotics, is required for high-level beta-lactam tolerance. Here, we report the mechanism of VxrAB-mediated survival. We find that -lactam antibiotics inappropriately induce the Fur-regulated iron starvation response, causing an increase in intracellular free iron and colateral oxidative damage. VxrAB reduces antibiotic-induced toxic influx of Fe by downregulating iron importers and induces cell wall synthesis functions to counteract cell wall damage. Our results highlight the complex responses elicited by antibiotics and suggest that the ability to counteract diverse stresses promotes high-level antibiotic tolerance.

sample_organism: Vibrio cholerae O1 biovar El Tor str. N16961

overall_design: To identify VxrB direct target genes in Vibrio cholerae genome, we sequenced the DNA samples which were pull downed with 6xHis+VxrB (D78E). Especially, VxrB; two component system sense cell wall damage which is triggered by beta-lactam antibioitc such as penicillin (PenG). So we treated PenG 100 ug/ml in Vibrio cells for 3 hour for full induction of VxrB.To characterize highly reproducible and reliable VxrB direct target genes, we sequenced DNA samples which were pooled with biological six replicates. For the exact control experiment, we also sequenced each input samples and penicillin treated or non treated samples as well.

first: Jung-Ho

last: Shin

first: Tobias

last: Doerr


title: Phloem and non-phloem associated translatomes during plum pox virus infection in Prunus domestica L.

city: College Park

first: James

middle: N

last: Culver

state: MD

address: 4291 Fieldhouse Dr.

department: Plant Science and Landscape Architecture

institute: University of Maryland, College Park

summary: In this study we used a translating ribosome affinity purification strategy to identify phloem and non-phloem associated translatomes in Prunus domesitca L during PPV infection. Three different promoter:His6FLAG-RPL18 lines were used. These included two phloem specific promoters (pSUC2 and pSULTR2;2) as well as the more ubiquitously expressed cauliflower mosaic virus 35S promoter (p35S). Immunopurification of ribosome-mRNA complexes was accomplished by the method described in Reynoso et al. (Plant Functional Genomics: Methods and Protocols, 185-207; 2015). The dataset includes samples from plum leaves taken at 2, 4, 6, and 12 weeks post cold induced dormancy.

overall_design: 100 samples, 4 time points (2, 4, 6, and 12 weeks), 3 promoter lines, PPV infected and healthy controls, 2-6 biological replicates

first: J

first: T

middle: D

last: Collum

first: C

last: Dardick


title: Quetiapine induces oligodendrocyte precursor cell differentiation by cholesterol biosynthesis

city: Baltimore

first: Peter

middle: Arthur

last: Calabresi

address: 600 N. Wolfe St

department: Neurology

institute: Johns Hopkins Univbersity

summary: Multiple sclerosis (MS) is characterized by demyelinated lesions in the central nervous system.  Destruction of myelin and secondary damage to axons and neurons leads to significant disability, particularly in people with progressive MS. Accumulating evidence suggests that the potential for myelin repair exists in MS, although for unclear reasons this process fails. The cells responsible for producing myelin, the oligodendrocytes, and their progenitors oligodendrocyte precursor cells (OPCs) have been identified at the site of lesions, even in adults. Their presence suggests the possibility that endogenous remyelination without transplantation of donor stem cells may be a strategy for myelin repair in MS. Strategies to develop novel therapies have focused on induction of signaling pathways that stimulate OPCs to mature into myelin-producing oligodendrocytes that could then possibly remyelinate lesions. We have been investigating pharmacological approaches to enhance OPC differentiation, and have identified that the combination of two agents, triiodothyronine (T3) and quetiapine, leads to an additive effect on OPC differentiation and consequent myelin production via both overlapping and distinct signaling pathways. While the ultimate production of myelin requires cholesterol biosynthesis, we identified that quetiapine enhances gene expression in this pathway more potently than T3. Two blockers of cholesterol production, betulin and simvastatin, reduced OPC differentiation into myelin producing oligodendrocytes. Elucidating the nature of agents that lead to complementary and additive effects, possibly even synergistic effects, on oligodendrocyte differentiation and myelin production may pave the way for more efficient induction of remyelination in people with MS.

overall_design: Purified rat OPCs were treated with T3, quetiapine, a combination of both, or none as control, during 4 days to examine the differentiation effects of quetiapine, a total of 24 samples were included, from 3 biological replicates, with a sample of each condition at 2 days and 4 days.

first: Jaime

last: Gonzalez Cardona

first: Jingya

last: Wang

middle: A


title: IMP dehydrogenase-2 drives aberrant nucleolar activity and structure in glioblastoma

city: Kyoto

first: Risa

last: Kawaguchi

state: Kyoto

address: Shogoin 53

department: Center for iPS Cell Research and Application

institute: Kyoto University

summary: Ribonucleotides serve important cellular functions as energy carriers, signaling molecules and building blocks of RNA. In eukaryotes, rRNA and tRNA synthesis in the nucleolus accounts together for over 90% of all RNA molecules. In many cancers, high proliferation rates correlated with elevation of rRNA and tRNA levels4 and nucleolar hypertrophy. However, the metabolic changes that lead to the increased nucleolar transcription and in turn foster tumorigenesis are incompletely understood. Here we show that in the highly lethal brain cancer glioblastoma (GBM), inosine monophosphate dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for de novo guanine nucleotide biosynthesis, is overexpressed. This leads to increased rRNA and tRNA synthesis and stabilization of the oncogenic GTP-binding protein nucleostemin, and enlarged and malformed nucleoli. Pharmacological or genetic inactivation of IMPDH2 reverses these malignant effects and inhibits GBM cell proliferation, whereas untransformed glia cells are unaffected. Impairment of IMPDH2 activity triggers nucleolar stress and growth arrest of GBM cells even in the absence of functional p53. Our results have uncovered upregulation of IMPDH2 as a prerequisite for aberrant nucleolar function and translational capacity in GBM. This GTP metabolic reprogramming constitutes a primary event in gliomagenesis and has implications for GBM treatment and possible malignant transformation in other cancers.

overall_design: U87MG cells were treated with 10 μM (mycophenolic acid) MPA and/or 100 μM guanosine for 24 hr. DMSO treatment was used as a control. Total RNA was prepared at 24 hr after treatment.

first: Satoshi

last: Kofuji


title: Insulin induced alterations in chromatin acetylation and transcriptome in triple negative breast cancer cells

city: Duarte

first: Parijat

last: Senapati

address: 1500 E. Duarte Rd

institute: Beckman Research Institute, City of Hope

summary: We have performed quantitative H3K9ac ChIP-seq and RNA-seq from untreated and 3h, 6h insulin treated MDA-MB-231 cells.

overall_design: Analysis of H3K9ac enrichment after insulin treatment and gene expression from insulin treated MDA-MB-231 cells.

first: Dustin

middle: E

last: Schones


title: MK2 and MK3 regulate LPS-induced inflammatory response of macrophages [360min]

city: Duesseldorf

first: Christian

last: Ehlting

address: Moorenstrasse 5

department: Clinic for Gastroenterology, Hepatology and Infectiology

country: Germany

institute: University Hospital of the Heinrich-Heine-University Duesseldorf

summary: The p38MAPK downstream targets MK 2 and 3 are critical for the regulation of the macrophage response towards bacterial lipopolysaccharid (LPS). The extent these two kinases act cooperatively in regulating LPS-induced inflammatory cytokine expression and their distinct regulatory effects are still unclear. To address this point, whole transcriptome analyses had been performed using bone marrow derived macrophages (BMDM) generated from MK2-/- or MK2/3-/- animals and from wildtype littermates. The BMDM were treated with 100 ng/ml LPS for 360 minutes or with medium as control. Thereafter, total mRNA was isolated and subjected to array analysis using the SurePrint G3 Mouse 8x60K Microarray Kit from Agilent.

overall_design: In total 23 samples from murine bone marrow derived macrophages (BMDM) were analyzed. These samples include 3 different genotypes (wt, MK2-/-, MK2/3-/-) treated with cell culture medium (control) or with 100 ng/ml LPS for 360 minutes. This study involves 4 replicates for each condition, whereas condition MK2-/- BMDM treated with medium (abbreviation: 4_mk2_med) involves only 3 replicates (4a, 4c, 4e). Values depicted in the columns averaged are the mean values of 3 or 4 replicates, respectively.

first: Julia

last: Rex

first: Ute

last: Albrecht

first: René

last: Deenen

first: Christopher

last: Tiedje

first: Karl

last: Köhrer

first: Oliver

last: Sawodny

first: Matthias

last: Gaestel

first: Dieter

last: Häussinger

first: Johannes

last: Bode


title: RNA-Seq for identification of differntially expressed genes by VxrB(D78E) overexpression

first: JUNG HO

last: SHIN

platform_organism: Vibrio cholerae O1 biovar El Tor str. N16961

overall_design: To identify controlled genes by VxrB, we carried out RNA-Seq analysis with wild type and VxrB(D78E) overexpressed samples.

first: Jung-Ho

last: Shin

first: Tobias

last: Doerr


title: MK2 and MK3 regulate LPS-induced inflammatory response of macrophages

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

overall_design: Refer to individual Series


title: sRNA154 a newly identified regulator of nitrogen fixation in Methanosarcina mazei strain Gö1

city: Cologne

first: Konrad

middle: U.

last: Förstner

state: North Rhine-Westphalia

address: Gleueler Str. 60

department: Information Services

institute: ZB MED - Information Centre for Life Sciences

summary: Trans-encoded sRNA154 is exclusively expressed under nitrogen (N)-deficiency in Methanosarcina mazei strain Gö1. The respective deletion strain showed a significant growth defect under N-limitation, pointing towards a regulatory role of sRNA154 in the N-metabolism. Aiming to elucidate this regulatory function we characterized sRNA154 by biochemical and genetic approaches. 24 homologs of sRNA154 were identified in recently reported draft genomes of Methanosarcina strains, demonstrating high conservation in sequence and predicted secondary structure with two highly conserved single stranded loop regions. In silico target prediction uncovered multiple potential interactions of both conserved loops with mRNA targets 5´untranslated region and coding sequence) encoding key components of the N-metabolism. In line with the computational prediction transcriptome studies of the sRNA154 deletion mutant by an RNA-seq approach uncovered nrpA-mRNA as a potential target, encoding the transcriptional activator of the nitrogen fixation (nif)-operon. Further evidence obtained by electromobility shift-, stability- and complementation assays, strongly argues for a stabilizing effect of sRNA154 on nrpA-mRNA by binding with both loops. Studying the further predicted N-related targets showing lower transcript levels in the absence of sRNA154, demonstrated that nifH transcript levels are most likely indirectly affected by sRNA154 due to enhanced stability of the nrpA transcripts. Besides, translation of glnA2-mRNA, encoding glutamine synthetase, appears to be affected by sRNA154 masking the ribosome binding site (RBS), whereas glnA1-mRNA appears to be stabilized by sRNA154. Overall, we propose that sRNA154 has a crucial role in N-metabolism in M. mazei and allows a feed forward regulation of nif-gene expression by stabilizing nrpA mRNA.

overall_design: Investigation of differential-gene expression profiles of two different M. mazei strains, using duplicates.

first: Daniela

last: Prasse

first: Dominik

last: Jäger

first: Rolf

last: Backofen

middle: U

first: Ruth

last: Schmitz


title: Comprehensive immunophenotypic characterization of Burkitt-like lymphoma with 11q aberration by flow-cytometry

city: Barcelona

first: Itziar

last: Salaverria

address: Rossello 153

institute: Hospital Clínic

summary: Recently, a subset of MYC-translocation negative aggressive B-cell lymphomas resembling Burkitt lymphoma (BL) characterized by proximal gains and distal losses in the long arm of chromosome 11 has been described. In the 2016 revision of the WHO classification these MYC-translocation negative lymphomas have been introduced as new provisional entity designated “Burkitt-like lymphoma with 11q aberration” (MNBLL 11q). Here, we show a comprehensive flow-cytometry analysis of 10 MNBLL 11q cases, well characterized genetically and pathologically. Twenty-three cases of MYC-positive BL, including three cases carrying both MYC rearrangements and 11q aberration, served as controls. All MNBLL 11q were CD20+/CD10+/BCL6+/BCL2- /MUM1- /MYC+/EBV negative , presented a high proliferation rate and showed a three-year overall survival (80%) similar to BL patients, with no recurrence after the end of treatment.  MNBLL 11q  immunophenotype was similar to that of MYC-positive BL without and with 11q, except for less frequent CD38higher expression (10% MNBLL 11q vs 91% MYC-positive BL, p<0.001), less frequent diminished CD45 expression (90% vs 23%, p=0.001), and CD16/CD56 co-expression (60% vs 0%, p<0.001). Our findings suggest subtle but important differences in MNBLL 11q immunophenotypes and MYC-positive BLs, which could not only aid in the differential diagnosis but also in the understanding of the pathogenesis of MNBLL 11q.

overall_design:
CytoSureTM Haematological Cancer and SNP Array (8x60k) (Oxford Gene Technology (OGT).The array has an average resolution of 68 Kb (SNP probe resolution 30Mb), but presents a resolution of 46.6 Kb in the 11q regions linked with hematological neoplasms.
Normal DNA was pooled from normal individuals: 5 random women and 4 random men

first: Grzegorz

last: Rymkiewicz

first: Reiner

last: Siebert


title: Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome

city: Columbia

first: Rocío

middle: Melissa

last: Rivera

state: MO

address: 920 East Campus Drive

department: Division of Animal Sciences

institute: University of Missouri, Columbia

type: Non-coding RNA profiling by high throughput sequencing

summary: The use of assisted reproductive technologies (ART) can induce a congenital overgrowth condition in humans and ruminants, namely Beckwith-Wiedemann syndrome (BWS) and large offspring syndrome (LOS), respectively. Shared phenotypes and epigenotypes have been found between BWS and LOS. We have observed global misregulation of transcripts in bovine foetuses with LOS. microRNAs (miRNAs) are important post-transcriptional gene expression regulators. We hypothesize that there is miRNA misregulation in LOS and that this misregulation is shared with BWS. In this study, small RNA sequencing was conducted to investigate miRNA expression profiles in bovine and human samples. We detected 407 abundant known miRNAs and predicted 196 putative miRNAs from the bovine sequencing results and identified 505 abundant miRNAs in human tongue. Differentially expressed miRNAs (DE-miRNAs) were identified between control and LOS groups in all tissues analysed as well as between BWS and control human samples. DE-miRNAs were detected from several miRNA clusters including DLK1-DIO3 genomic imprinted cluster in LOS and BWS. DNA hypermethylation was associated with downregulation of miRNAs in the DLK1-DIO3. mRNA targets of the DE-miRNAs were predicted and signalling pathways associated with control of organ size (including the Hippo signalling pathway), cell proliferation, apoptosis, cell survival, cell cycle, and cell adhesion were found to be enriched with these genes. Yes associated protein 1 (YAP1) is the core effector of the Hippo signalling pathway, and increased level of active (non-phosphorylated) YAP1 protein was detected in skeletal muscle of LOS foetuses. Overall, our data provide evidence of miRNA misregulation in LOS and BWS.

overall_design: Small RNA-seq of skeletal muscle, tongue, kidney, and liver of artificial insemination-conceived control and assisted reproductive technologies/therapies-conceived normal and LOS bovine ~day 105 fetuses.

first: Yahan

last: Li

first: Darren

last: Hagen

first: Tieming

last: Ji

first: Mohammad Reza

last: Bakhtiarizadeh

first: Whitney

middle: M

last: Frederic

first: Emily

last: Traxler

first: Jennifer

last: Kalish


title: Small RNA-seq from FPLC-fractionated leaf and flower crude extracts

status: Public on Jul 29 2019

city: Godollo

first: Peter

last: Gyula

state: Pest

address: Szent-Gyorgyi Albert u. 4.

department: Department of Plant Biotechnology

institute: Hungarian University of Agricultural and Life Sciences

summary:
Background: RNA interference (RNAi) is an indispensable regulatory mechanism governing developmental processes and stress responses via sequence-specific control of target RNAs mediated by the action of small, 20–24-nt-long, non-coding regulatory (s)RNAs such as micro (mi) and small interfering (si) RNAs. Biogenesis and sorting of miRNAs into ARGONAUTE (AGO) proteins are intensively investigated, however very few information is available about the presence and distribution of distinct sRNA pools in plant cells.
Results: High-throughput sequencing of size-separated sRNA pools of plant crude extracts revealed that the majority of the canonical miRNAs were associated with high molecular weight RNA-induced silencing complexes co-migrating with AGO1 (HMW RISC). In contrast, the majority of 24-nt-long siRNAs were found in association with low molecular weight complexes co-migrating with AGO4 (LMW RISC). Intriguingly, we identified a large set of sRNAs in the cytoplasm, including mature miRNA sequences, in the low molecular size range corresponding to protein-unbound sRNAs. By comparing the RISC-loaded and protein-unbound pools of miRNAs, we identified miRNAs with highly different loading efficiencies. Investigation of some selected miRNAs in a transient expression system validated this finding. We also showed that the availability of RISCs is a limiting factor determining the loading efficiency of miRNAs.
Conclusion: Our data reveal the existence of a regulatory checkpoint,  likely controlled by information carried by the diverse miRNA precursors, determining the RISC-loading efficiencies of various miRNAs by sorting only a subset of the produced miRNAs into the biologically active RISCs.

overall_design: Small RNAs were sequenced from size-fractionated Arabidopsis leaf and flower crude extracts in two biological replicates.

first: Ágnes

last: Dalmadi

first: Péter

first: Jeannette

last: Bálint

first: György

last: Szittya

first: Zoltán

last: Havelda


title: Systematic evaluation of library preparation methods and sequencing platforms for high-throughput whole genome bisulfite sequencing

city: Singapore

first: LI

last: ZHOU

address: 11 Mandalay Road

country: Singapore

institute: Lee Kong Chian School of Medicine, Nanyang Technological University

type: Methylation profiling by high throughput sequencing


title: MK2 and MK3 regulate LPS-induced inflammatory response of macrophages [120min]

first: Christian

last: Ehlting

summary: The p38MAPK downstream targets MK 2 and 3 are critical for the regulation of the macrophage response towards bacterial lipopolysaccharid (LPS). The extent these two kinases act cooperatively in regulating LPS-induced inflammatory cytokine expression and their distinct regulatory effects are still unclear. To address this point, whole transcriptome analyses had been performed using bone marrow derived macrophages (BMDM) generated from MK2-/- or MK2/3-/- animals and from wildtype littermates. The BMDM were treated with 100 ng/ml LPS for 120 minutes or with medium as control. Thereafter, total mRNA was isolated and subjected to array analysis using the SurePrint G3 Mouse 8x60K Microarray Kit from Agilent.

overall_design: In total 23 samples from murine bone marrow derived macrophages (BMDM) were analyzed. These samples include 3 different genotypes (wt, MK2-/-, MK2/3-/-) treated with cell culture medium (control) or with 100 ng/ml LPS for 120 minutes. This study involves 4 replicates for each condition, whereas condition MK2-/- BMDM treated with medium (abbreviation: 5_mk2_med) involves only 3 replicates (5a, 5b, 5e). Values depicted in the columns averaged are the mean values of 3 or 4 replicates, respectively.

first: Julia

last: Rex

first: Ute

last: Albrecht

first: René

last: Deenen

first: Christopher

last: Tiedje

first: Karl

last: Köhrer

first: Oliver

last: Sawodny

first: Matthias

last: Gaestel

first: Dieter

last: Häussinger

first: Johannes

last: Bode


title: Systematic evaluation of library preparation methods and sequencing platforms for high-throughput whole genome bisulfite sequencing [WGBS]

summary: We systematically evaluated alternate strategies for WGBS studies, taking into account opportunites around library preparation methods, sequencing platforms and analysis pipeline optimization. We also assessed the performance and precision of the WGBS method relative to the methylation arrays, in an effort to provide data-driven recommendations for future WGBS studies, in particularly with respect to minimum coverage.

overall_design: Bisulfite-converted DNA for 8 human samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip and Illumina Infinium HumanMethylation850 BeadChip. Whole genome bisulphite sequencing libraries for 8 human samples were prepared by different methods with low DNA input requirement and sequenced by Illumina NovaSeq and HiSeq X10 platforms.

first: Li

last: Zhou

first: Hong

middle: K

last: Ng

first: Daniela

last: Moses

first: Stephan

middle: C

last: Schuster

last: Beck

first: Changhoon

last: Kim

first: John

last: Chambers

first: Marie

last: Loh


title: Transcriptome anaylsis of wild type 2-celled proembryo of Nicotiana tabacum

status: Public on Jul 28 2019

city: Wuhan

first: Ce

last: Shi

address: Bayi Road

institute: Wuhan University

summary: The goal of the present study is to analyze the gene expression during early embryogenesis in N.tabacum

overall_design: 2-celled proembryo were isolated and collected for RNA sequencing (RNA-seq).

first: Meng-xiang

last: Sun

first: An

last: Luo


title: RNA-seq Analysis of Changes in mRNA Expression for the hTERT-HMA/B Human Myometrial Cell Line treated with all Combinations of Progesterone, Forskolin, and Interleukin-1β

status: Public on Jul 26 2019

city: Cleveland

first: Sam

last: Mesiano

state: OH

address: 11100 Euclid Avenue, MacDonald Women's Hospital, Mac 8129

institute: Case Western Reserve University

summary: Parturition involves cellular signaling changes driven by the complex interplay between progesterone (P4), inflammation, and the cyclic adenosine monophosphate (cAMP) pathway.  To characterize this interplay,  comprehensive transcriptomic studies utilizing 8 treatment combinations were performed on the hTERT-HMA/B telomerase immortalized human myometrial cell line and myometrium obtained from term c-section deliveries.  Genome-wide RNA-sequencing was performed on total RNA extracted from hTERT-HMA/B cells treated with all combinations of P4, forskolin (induces cAMP), and interleukin-1β (IL-1β). Gene set enrichment and regulatory network analyses was then used to identify pathways commonly, differentially, or synergistically regulated by each treatment. Tissue similarity index (TSI) was also applied to characterize the correspondence between cell lines and tissue phenotypes.  In addition to their individual anti-inflammatory effects, P4 and cAMP synergistically blocked specific inflammatory pathways/regulators including STAT3/6, CEBPA/B, and OCT1/7, but not NFKB.  TSI analysis indicated that forskolin+P4- and IL-1β-treated cells exhibit transcriptional signatures highly similar to non-laboring and laboring term myometrium, respectively.  The data identify potential therapeutic targets to prevent preterm birth and show that the hTERT-HMA/B cell line provides is an accurate transcriptional model for term ± labor myometrium.

overall_design: Comparisons made between all single stimulus treated cells (P4, FSK, IL-1β) with untreated cells to identify signaling by progesterone, cAMP, and IL-1β and comparisons made between IL-1β conditions to identify anti-inflammatory actions of P4 and/or FSK in the presence of IL-1β.

first: Z

last: Stanfield

first: P

last: Amini

first: J

last: Wang

first: L

last: Yi

first: H

last: Tan

first: S


title: Neural crest-specific deletion of splicing factor Rbfox2 leads to craniofacial abnormalities including cleft palate

first: Manvendra

middle: K.

last: Singh

address: 8 College Road

department: Programme in Cardiovascular & Metabolic Disorders

institute: Duke-NUS MEDICAL SCHOOL

summary: Alternative splicing (AS) creates proteomic diversity from a limited size genome by generating numerous transcripts from a single protein-coding gene. Tissue-specific regulators of AS are essential components of the gene regulatory network, required for normal cellular function, tissue patterning, and embryonic development. However, their cell-autonomous function in neural crest development has not been explored. Here, we demonstrate that splicing factor Rbfox2 is expressed in the neural crest cells (NCCs) and deletion of Rbfox2 in NCCs leads to cleft palate and defects in craniofacial bone development. RNA-Seq analysis revealed that Rbfox2 regulates splicing and expression of numerous genes essential for neural crest/craniofacial development. We demonstrate that Rbfox2-TGF-β-Tak1 signaling axis is deregulated by Rbfox2 deletion. Furthermore, restoration of TGF-β signaling by Tak1 overexpression can rescue the proliferation defect seen in Rbfox2 mutants. We also identified a positive feedback loop in which TGF-β signaling promotes expression of Rbfox2 in NCCs.

overall_design: Examination of differential splicing between craniofacial tissues from control (n = 3) and neural crest-specific Rbfox2 mutant (n = 3) mouse embryos.

first: Dasan

last: Cibi

first: Masum

last: Mia

first: Shamini

middle: G

last: Shekeran

first: Lim

last: Yun

first: Reddemma

last: Sandireddy

first: Priyanka

last: Gupta

first: Monalisa

last: Hota

first: Veerabrahma

middle: P

last: Seshachalam

first: Lei

first: Sujoy

last: Ghosh


title: RNA sequencing of mouse hepatic response to lifespan-extending interventions

status: Public on Jul 25 2019

city: Boston

first: Maxim

last: Gerashchenko

state: Massachusetts

address: 77 Louis Pasteur Ave, NRB 435

department: Medicine

institute: Brigham and Women's Hospital

summary:
This dataset consists of hepatic gene expression profiles of mice subjected to 8 different lifespan-extending interventions, together with the corresponding age-, sex- and strain-matched littermate controls: caloric restriction (CR), methionine restriction (MR), growth hormone receptor knockout (GHRKO), Snell dwarf mice (Pit1 -/-), rapamycin, acarbose, 17-alpha-estradiol (17aE2) and Protandim. Both sexes and different age groups are presented within dataset.
Using this data, we identified general and specific gene expression patterns associated with lifespan extension. We detected a feminization effect associated with growth hormone regulation and diminution of sex-related differences in response to many interventions at transcriptome and metabolome levels. Combining the dataset with publicly available resources, we found that many interventions exhibited similar transcriptome changes, whereas some, including rapamycin, showed distinct patterns. We identified common hepatic signatures of lifespan extension, e.g. upregulation of oxidative phosphorylation and NRF2-regulated enzymes, and found that many perturbed pathways are shared across tissues. Moreover, the response of genes related to glucose metabolism and immune function represented both qualitative and quantitative associations with longevity. Finally, we used the detected longevity signatures to identify new candidates for lifespan extension and built GENtervention, a tool that visualizes associations of gene expression responses with lifespan extension.

overall_design: 6-month-old UM-HET3 male and female mice from University of Michigan Medical School subjected to acarbose (1000 ppm), CR (40%), rapamycin (42 ppm), 17aE2 (14.4 ppm) and Protandim (1200 ppm) for 2 months, together with their littermate controls, were used for the analysis. Acarbose (1000 ppm), CR (40%) and rapamycin (14 ppm) were also analyzed for 12-month-old mice (subjected for 8 months) of the same strain. In case of MR, 2-month-old C57BL/6J male mice were subjected to diet containing 0.12% w/w methionine for 12 months and utilized together with their littermate controls subjected to the same diet but with 0.86% w/w methionine. In case of GHRKO and Snell dwarf mice, 5-month-old male mutants and their age- and sex-matched littermate controls were obtained from (C57BL/6J x BALB/cByJ)/F2 and (PW/J x C3H/HeJ)/F2 strains, respectively. 3 biological replicates were used for each experimental group, including both treated and control mice (78 samples in total). In all cases, interventions continued until the animals were sacrificed. RNA was extracted from liver tissues with PureLink RNA Mini Kit as described in the protocol and passed to paired-end sequencing with 100 bp read length.

first: Alexander

last: Tyshkovskiy

middle: V

first: Vadim

last: Gladyshev


title: Modeling the MYC-driven normal-to-tumour switch in breast cancer.

city: Toronto

first: Corey

last: Lourenco

state: ON

department: Medical Biophysics

country: Canada

institute: University of Toronto

summary: The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated an in vivo model that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the PI3 kinase pathway (PIK3CAH1047R) lead to the development of organized acinar structures in mice. However, expressing both PIK3CAH1047R and deregulated-MYC lead to the development of invasive ductal carcinoma, thus creating a model in which a MYC-dependent normal-to-tumour switch occurs in vivo. These MYC-driven tumours exhibit classic hallmarks of human breast cancer at both the pathological and molecular levels. Moreover, tumour growth is dependent upon sustained deregulated MYC expression, further demonstrating addiction to this potent oncogene and regulator of gene transcription. We therefore provide a MYC-dependent model of breast cancer which can be assayed for in vivo tumour initiation, proliferation, and transformation from normal breast acini into invasive breast carcinoma. Taken together, we anticipate that this novel MYC-driven transformation model will be a useful research tool to both better understand MYC’s oncogenic function and identify therapeutic vulnerabilities.

overall_design: RNA-seq was conducted on 3 biological replicates of each 10A.PE and 10A.PM xenograft tumours.

first: Manpreet

last: Kalkat

first: Kathleen

last: Houlahan

first: Jason

last: De Melo

first: Joseph

last: Longo

first: Susan

middle: J

last: Done

first: Paul

last: Boutros

first: Linda

middle: Z

last: Penn


title: Identification and application of gene expression signatures associated with lifespan extension


title: Study of the role of IL-12p40-related cytokines in colitis of NEMOIEC-KO mice

status: Public on Jul 23 2019

first: Manolis

last: Pasparakis

state: NRW

address: Joseph Stelzmann Strasse, 26

department: Institute for Genetics

institute: University of Cologne

summary: Disruption of the epithelial barrier is considered a potential cause of inflammatory bowel disease (IBD). In this study, we employed the NEMOIEC-KO mouse model to study the immune mechanisms triggering chronic colitis downstream of an epithelial barrier defect. Colitis in NEMOIEC-KO mice is driven by commensal bacteria sensing through MyD88 signaling. The IL-12p40-related cytokines are induced upon microbial sensing and are known to act critically in promoting intestinal inflammation. Yet, the relative contribution of IL-12 versus IL-23 in eliciting intestinal pathology has been controversial. Using IL-12p40, IL-12p35 and IL-23p19 knockout mice we assessed the functional contribution of IL-12 and IL-23 to intestinal inflammation in the NEMOIEC-KO model.

overall_design: To investigate how p40, p35 or p19 deficiencies affect the inflammatory response in the colon of NEMOIEC-KO mice, we conducted RNA-seq-based transcriptome profiling in the colons of 6-week-old NEMOIEC-KO Il12b-/-, NEMOIEC-KO Il12a-/-, NEMOIEC-KO Il23a-/-, NEMOIEC-KO and Nemofl/fl mice. Five mice per genotype were used as biological replicates.

first: Christina

last: Eftychi

first: Prerana

last: Wagle


title: Characterization of the DNA methylome in embryonic retina, retinal progenitors, and RGCs

city: Miami

first: Dmitry

last: Ivanov

state: FL

address: 1638 NW 10th Avenue

department: Ophthalmology

institute: University of Miami Miller School of Medicine

summary: We investigated the dynamics of DNA methylation during differentiation of retinal progenitor cells (RPCs) into retinal neurons using the whole-genome bisulfite sequencing (WGBS) approach

overall_design: To study DNA methylation, the WGBS libraries were prepared using DNA from embryonic-day (E) 11.5 and 12.5 retinas, Notch1+ cells (RPCs) isolated from postnatal-day (P) 0 and 3 retinas, and retinal ganglion cells (RGCs) isolated from P14 retinas. The WGBS libraries were sequenced and bisulfite sequence reads were aligned using the Bismark software package. The global methylation level in studied samples was measured and the percentages of methylation of CpG, CHG, and CHH contexts (where H is A, C or T) were identified.


title: G0/G1 switch gene 2 modulates gliomagenesis and radiation response

city: Shanghai

first: Haizhong

last: Feng

state: Shanghai

address: Pujian Road 160

department: Ren Ji Hospital

institute: Shanghai Jiao Tong University

summary: Glioblastoma multiforme (GBM), a WHO grade IV glioma is the most common and malignant primary cancer of the central nervous system with a grim median survival of 16 to 17 months upon diagnosis. Radiotherapy is the standard first line treatment for newly diagnosed patients with gliomas, but its effectiveness is limited given their intrinsic resistance and propensity for recurrence. Although possible mechanisms have been attributed to GBM resistance to radiation treatments, the molecular mechanisms regulating radiation resistance of GBM are still unclear.

overall_design: Examination of differential gene expression in 2 cells.


title: A kinase inhibitor screen identifies a dual cdc7/CDK9 inhibitor to sensitise triple-negative breast cancer to EGFR-targeted therapy

status: Public on Jul 21 2019

city: Leiden

first: Vera

middle: van der

last: Noord

state: South Holland

address: Einsteinweg 55

department: Drug Discovery and Safety

country: Netherlands

institute: Leiden University

summary:
Purpose: To investigate the impact of combined cdc7, CDK9 and EGFR inhibition on the transcriptomic profile of EGFR-TKI-resistant TNBC cells using high-throughput RNA sequencing.
Methods: EGFR-TKI-resistant TNBC cell lines (Hs578T and SKBR7) were treated with DMSO, lapatinib (3.16 µM), PHA-767491 (1 µM) or co-treated with lapatinib (3.16 µM) & PHA-767491 (1 µM) for 6 hours. RNA was isolated with RNeasy Plus Mini Kit as described by manufacturer (QIAGEN, Cat. 74136). Transcriptome RNA-Sequencing (RNA-Seq) was performed using Illumina high-throughput RNA sequencing.
Results:we mapped about 40 million sequence reads per sample to the human genome (build hg38). RNA-Seq data was normalised by TMM using EdgeR’s normalisation-factor followed by quantile normalisation and presented in Log2 fold change (Log2 FC) scales.Genes with significant down- or up-regulation (Log2 FC ≥ |0.5|) under indicated conditions were analysed by web-based functional analysis tool Ingenuity pathway Analysis (IPA) to visualise and annotate their biological functions and pathways.
Conclusions: 1387 and 2747 genes were down-regulated in co-treated Hs578T and SKBR7 cells, respectively. 2614 genes were up-regulated by co-treatment in Hs578T cells, whilst 243 genes were up-regulated by the same treatment in SKBR7 cells. We identified 845 commonly differentially expressed transcripts in both HS578T and SKBR7 cells after co-treatment of which 141 transcripts were up-regulated and 704 transcripts were down-regulated. 34 of  these commonly differentially expressed transcripts were linked to metastasis-free survival in TNBC patients.

overall_design: Transcriptomic profiles (mRNA) of triple-negative breast cancer cells after treatment with DMSO, PHA-767491 and lapatinib or a combination of both lapatinib and PHA-767491 were generated in triplicate using Illumina RNA sequencing.

first: John

middle: W

last: Martens

first: Marcel

last: Smid


title: RNA-Sequencing of Transplant Stage Idiopathic Pulmonary Fibrosis Lung Reveals Unique Pathway Regulation

status: Public on Jul 24 2019

city: Pennington

first: Ron

last: Ammar

state: New Jersey

address: 311 Pennington Rocky Hill Road

institute: Bristol-Myers Squibb

summary: We report an RNA-seq based transcriptomic fingerprint of severe IPF enriched in pathways of T-cell infiltration/activation, tumor development and cholesterol homeostasis. We highlight novel splice variants, candidate targets and biomarkers in advanced IPF.

overall_design:
All human subject sample acquisitions and experiments were conducted with the appropriate approval from the Institutional Review Board (IRB 806468, IRB 813685). Illumina TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero (cat. No RS-122-2203) was used to generate sequencing libraries per manufacturer’s recommendation. Gene expression was determined via RNA-Seq libraries run on an Illumina HiSeq 2500 platform producing 75bp paired-end reads. We generated on average 40 million PE read for each sample. Reads were aligned to the Human genome (GRCh38) with the Omicsoft Sequence Aligner. Gene and transcript abundance was determined using Ensembl release 90 human gene models using RSEM. All RNA-Seq data were processed in R with Bioconductor packages. RNA-Seq samples were TMM normalized with the edgeR package.
Raw data not provided due to patient privacy concerns

first: Edward

last: Cantu

first: Pitchumani

last: Sivakumar


title: Host susceptibility to recurrent cystitis is shaped by bladder TNF-alpha signaling dynamics

city: St. Louis

first: Lu

last: Yu

state: Missouri

address: 4905 Children’s Place/305 N. Euclid, 10260 McDonnell Pediatric Research Building

department: Molecular Microbiology

institute: Washington University in St Louis

summary: Urinary tract infections (UTI) are common and recurrent. Both host genetics and UTI history impact susceptibility to recurrent UTI (rUTI) in women and in animal models. To identify shared patterns of host response that correlate with susceptibility, we investigated bladder inflammatory and transcriptional kinetics in acute and rUTI models. We found that TNFɑ signaling kinetics differed with mouse strain and infection history. Mice resistant to severe UTI/rUTI displayed a robust TNFɑ-dependent inflammation during the first 6 hours of acute cystitis, which waned by 24 hours; mice that are susceptible varied in their early responses but were prone to severe inflammation at 24 hours post-infection. Depletion of TNFɑ in an rUTI model revealed that early TNFɑ signaling promoted colonization resistance via exfoliation of infected bladder cells, but prolonged TNFɑ signaling exacerbated inflammation, thereby worsening infection. Host genetics and disease history impacts susceptibility by regulating the kinetics of a common TNFɑ pathway.

overall_design: Whole bladder transcritpomes of mice from different genetic background or of different UTI histories were compared upon UPEC infection for different period of time with PBS mock infected counterparts.

first: Valerie

last: O'Brien

first: Denise

last: Dorsey

first: Jonathan

last: Livny

first: Elisha

last: Roberson

first: Marco

last: Colonna

first: Michael

last: Caparon

first: Scott

last: Hultgren

first: Tom

last: Hannan


title: Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators

status: Public on Jul 22 2019

city: Buffalo

first: Soo-Kyung

last: Lee

address: 109 Cooke Hall

department: Department of Biological Sciences

institute: University at Buffalo, The State University of New York

summary: This report contains a scRNA-seq analysis of E15 hypothalamic arcuate nucleus (ARC), which uncovers many cell type-specific markers, including a group of transcription factors. This study newly demonstrate critical roles of two of these transcription factors in specifying the identity of ARC neurons. Many of these transcription factors are enriched in specific single cell transcriptomes while being excluded from other single cell transcriptomes, suggesting their crucial roles in cell fate determination.

overall_design: A single sample was sequenced multiple times to increase coverage. Single cell RNA-seq data were generated on the 10X emulsion platform (10X Genomics, Pleasanton, CA) according to the manufactures instructions. The single-cell RNAseq from the Chromium platform was processed using CellRanger v2.1.1, and subsequent normalization, QC, filtering, differential gene expression analysis, and dimension reduction was performed in R using Seurat v2.0 (http://www.satijalab.org/seurat).

first: Jae

first: Alessio

last: Delogu

first: Christian

last: Huisman

first: Hyeyoung

last: Cho

first: Olivier

last: Brock

first: Su-Jeong

last: Lim

first: Soung-Min

last: Youn

first: Younjung

last: Park

first: Sangsoo

last: Kim


title: Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening

city: Montreal

first: Amandine

last: Bemmo

state: QC

address: 110 Avenue des Pins

institute: IRCM

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

overall_design: Refer to individual Series


title: Transcriptional profiling of CD45RO+CD57+CD4+ T cells

status: Public on Jul 20 2019

city: Oxford

first: Timothy

last: Hinks

state: United Kingdom

address: John Radcliffe Hospital, Headley Way, Oxford

department: NDM Experimental Medicine - New College

country: United Kingdom

institute: University of  Oxford

summary: RNA-seq data to examine transcriptiome of CD57+ versus CD57- memory CD4+ T cells

overall_design: Comparison between CD45RO+CD57+ and CD45RO+CD57- CD4+ T cell subsets

first: Chansavath

last: Phetsouphanh

first: Emanuele

last: Marchi


title: TORC1 and PKA dependent gene regulation

status: Public on Jul 19 2019

city: Tucson

first: Andrew

last: Capaldi

state: AZ

address: 1007 E Lowell St

department: MCB

institute: Univ of Arizona

summary: To determine how TORC1 and PKA cooperate to regulate cell growth, we performed temporal analysis of gene expression in yeast switched from a non-fermentable substrate, to glucose, in the presence and absence of TORC1 and PKA inhibitors.  Quantitative analysis of these data reveals that PKA drives the expression of key cell growth genes during transitions into, and out of, the rapid growth state in glucose, while TORC1 is important for the steady-state expression of the same genes.

overall_design: The study includes 21 experiments that measure the impact that TORC1 and PKA kinases have on gene expression as cells transition from growth in glycerol, to growth in glucose.  All experiments were carried out using the cell line (ACY142), or a derivative of ACY142 (missing Dot6 and Tod6), that is carrying mutations in TPK1, 2 and 3 that render them sensitive to the Shokat inhibitor 1-NM-PP1.

first: Joseph

last: Kunel

first: Xiangxia

last: Luo


title: Anti-inflammatory nutrition with high protein attenuates cardiac and skeletal muscle alterations in a pulmonary arterial hypertension model

city: Wageningen

first: Guido

last: Hooiveld

address: HELIX, Stippeneng 4

department: Div. Human Nutrition & Health

institute: Wageningen University

summary: Pulmonary arterial hypertension (PAH) is characterized by remodelling of the pulmonary arteries and right ventricle (RV), which leads to functional decline of cardiac and skeletal muscle. This study investigated the effects of a multi-targeted nutritional intervention with extra protein, leucine, fish oil and oligosaccharides on cardiac and skeletal muscle in PAH. PAH was induced in female C57BL/6 mice by weekly injections of monocrotaline (MCT) for 8 weeks. Control diet (sham and MCT group) and isocaloric nutritional intervention (MCT + NI) were administered. Compared to sham, MCT mice increased heart weight by 7%, RV thickness by 13% and fibrosis by 60% (all p < 0.05) and these were attenuated in MCT + NI mice. Microarray and qRT-PCR analysis of RV confirmed effects on fibrotic pathways. Skeletal muscle fiber atrophy was induced (P < 0.05) by 22% in MCT compared to sham mice, but prevented in MCT + NI group. Our findings show that a multi-targeted nutritional intervention attenuated detrimental alterations to both cardiac and skeletal muscle in a mouse model of PAH, which provides directions for future therapeutic strategies targeting functional decline of both tissues.

overall_design: Microarray analysis was performed on right ventricle biopsies from mice that received injections with either monocrotaline (MCT) or saline (sham) and were fed a standard semi-synthetic diet or isocaloric nutritional intervention (NI).

first: Paulien

last: Vinke

first: T

middle: S

last: Bowen

first: Mark

last: Boekschoten

first: Renger

middle: F

last: Witkamp

first: Volker

last: Adams

first: Klaske

last: van Norren


title: The magnitude of IFN-g responses is fine-tuned by DNA architecture and the non-coding transcript of Ifng-as1

city: Bethesda

first: Yuka

last: Kanno

state: MD

address: 10 Center Drive, Rm13C120

department: NIAMS

institute: NIH

summary: IFN-g, critical for host defense and tumor surveillance, requires tight control of its expression. Multiple cis-regulatory elements exist around Ifng along with a non-coding transcript, Ifng-as1 (also termed NeST). Here, we describe two genetic models generated to dissect the molecular functions of this locus and its RNA product. DNA Deletion within the Ifng-as1 locus disrupted chromatin organization of the extended Ifng locus, impaired IFN-g response and compromised host defense. Insertion of a polyA signal ablated the Ifng-as1 full-length transcript and impaired host defense, while allowing proper chromatin structure. Transient knockdown of Ifng-as1 also reduced IFN-g production. In humans, discordant expression of IFNG and IFNG-AS1 was evident in memory T cells, with high expression of this lncRNA and low expression of the cytokine. These results establish Ifng-as1 as an important regulator of Ifng expression, as a DNA element and transcribed RNA, involved in dynamic and cell state-specific responses to infection.

overall_design: Integrated analysis of transcriptome and epigenome data from in vitro activated WT or Ifng-as1-deficient Th1 and Th2 cells

first: F

last: Petermann

first: A

last: Pekowska

first: C

middle: A

last: Johnson

first: H

middle: Y

last: Shih

first: K

last: Jiang

last: Sun

first: S

middle: R

last: Brooks

first: Y

first: J

last: O'Shea


title: RNA methylomes reveal the m6A-mediated regulation of DNA demethylase gene SlDML2 that is required for tomato fruit ripening

city: Beijing

first: Leilei

last: Zhou

state: Beijing

address: No. 20 Nanxincun, Xiangshan, Haidian District

department: Institute of botany

institute: Chinese Academy of Sciences

summary: For exploring whether mRNA m6A modification participates in the regulation of tomato fruit ripening, we performed m6A-seq in three tomato fruit samples, including wild-type (WT) at 39 days post-anthesis (DPA) and 42 DPA, and Cnr mutant at 42 DPA, with three biological replicates. mRNA methylome analysis reveals that m6A methylation is a prevalent modification in mRNA of tomato fruit and the m6A sites are predominantly enriched in the stop codon and 3’ untranslated region, where m6A deposition has been proved to negatively correlate with gene expression. Hundreds of ripening-induced and ripening-repressed genes, including the SlDML2,  were found to harbour changed m6A levels during fruit ripening or in the Cnr mutant, implicating the involvement of m6A modification in the regulation of fruit ripening.

overall_design: mRNA m6A methylation profiles in tomato fruits of 39 DPA and 42 DPA wild-type and 42 DPA Cnr mutant were generated by m6A-seq, in triplicate, using Illumina Hiseq X.

first: Guozheng

last: Qin


title: miRNA Expression data from the dentate gyrus of the defeated and control mice

status: Public on Jul 17 2019

city: Hyderabad

first: Arvind

last: Kumar

state: Telangana

address: Uppal Road, Habsiguda

country: India

institute: CSIR-Centre for Cellular and Molecular Biology

summary:
Using various animal models, epigenetic mechanisms have been shown to be mediating the negative effects of chronic stressful events on the progression of depression and other neuropsychiatric disorders. However, non-coding RNAs, another layer of epigenetic regulation is relatively lesser studied in this context.
We used miRNA array to uncover dysregulation in miRNA-mRNA networks in the neurogenic dentate gyrus (DG) region of chronic social defeat stress (CSDS)-induced depressed mice

overall_design: 2 groups of adult male mice were used for the experiments where one group was subjected to 10 days of CSDS while other was used as control. DG was dissected out from these mice followed by RNA isolation. n=4 samples from each group where every sample was prepared by pooling equal amount of RNA from DG of the 3 individual mice

first: Nitin

last: Khandelwal

first: Sandeep

last: Dey


title: Gene Expression data from the differentiating and proliferating neural stem/progenitor cells

summary:
The adverse effect of CSDS on the DG neurogenesis is expected to affect the properties of the resident NSCs/NPCs.We used neurosphere culture system, a well-established ex vivo model to study neurogenesis.
We collected proliferating neurospheres and differentiating NSCs/NPCs from two stages, i.e. early (after 2 days) and late (after 7 days) and isolated RNA for gene arrays.

overall_design: Total RNA obtained from the proliferating neurospheres and differentiating NSCs/NPCs later sunjected to the gene arrays


title: Expression data from human  breast cancer cell line DCIS educated by CAFs

city: Tokyo

first: Yoshihiro

last: Mezawa

address: 2-1-1 Hongo, Bunkyo-ku

institute: Juntendo University

summary: Emerging evidence supports the hypothesis that multicellular tumor clusters invade and seed metastasis. However, whether tumor-associated stroma induces epithelial-mesenchymal plasticity in tumor cell clusters, to promote invasion and metastasis, remains unknown. We demonstrate herein that carcinoma-associated fibroblasts (CAFs) frequently present in tumor stroma drive the formation of tumor cell clusters composed of two distinct cancer cell populations, one in a highly-epithelial (E-cadherin-high ZEB1-low/neg: E-hi) state and another in a hybrid epithelial/mesenchymal (E-cadherin-low ZEB1-high: E/M) state. The E-hi cells highly express oncogenic cell-cell adhesion molecules, such as carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and CEACAM6 that associate with E-cadherin, resulting in increased tumor cell cluster formation and metastatic seeding. The E/M cells also retain associations with E-hi cells, which follow the E/M cells leading to collective invasion. CAF-produced stromal cell-derived factor 1 and transforming growth factor-b confer the E-hi and E/M states as well as invasive and metastatic traits via Src activation in apposed human breast tumor cells. Taken together, these findings indicate that invasive and metastatic tumor cell clusters are induced by CAFs via epithelial-mesenchymal plasticity.

overall_design: The samples included  DCISCAF2cy (n=4), DCIScnt2cy (n=4).

first: Akira

last: Orimo


title: Gene Expression data from the dentate gyrus of the defeated and control mice

summary:
Using various animal models, epigenetic mechanisms have been shown to be mediating the negative effects of chronic stressful events on the progression of depression and other neuropsychiatric disorders. However, non-coding RNAs, another layer of epigenetic regulation is relatively lesser studied in this context.
We used mRNA microarrays to uncover dysregulation in miRNA-mRNA networks in the neurogenic dentate gyrus (DG) region of chronic social defeat stress (CSDS)-induced depressed mice by identifying tagets of the selected miRNAs from this list

overall_design: 2 groups of adult male mice were used for the experiments where one group was subjected to 10 days of CSDS while other was used as control. DG was dissected out from these mice followed by RNA isolation. n=3 samples from each group where every sample was prepared by pooling equal amount of RNA from DG of the 3 individual mice


title: miRNA Expression data from the differentiating and proliferating neural stem/progenitor cells

summary:
The adverse effect of CSDS on the DG neurogenesis is expected to affect the properties of the resident NSCs/NPCs.We used neurosphere culture system, a well-established ex vivo model to study neurogenesis.
We collected proliferating neurospheres and differentiating NSCs/NPCs after 7 days of plating and isolated RNA for microRNA array to identify the altered miRNAs

overall_design: Total RNA obtained from the proliferating neurospheres and differentiating NSCs/NPCs


title: Paradoxical association of TET loss of function with genome-wide hypomethylation

status: Public on Jul 18 2019

city: La Jolla

first: Isaac

middle: F.

last: López-Moyado

state: CA

address: 9420 Athena Cir

department: Division of Signaling and Gene Expression

institute: La Jolla Institute for Immunology

summary: Cancer genomes are characterized by focal increases in DNA methylation, co-occurring with widespread hypomethylation. Here we show that TET loss-of-function results in a similar genomic footprint. Both 5hmC in wildtype genomes, and DNA hypermethylation in TET-deficient genomes, are largely confined to the active euchromatic compartment, consistent with the known functions of TET proteins in DNA demethylation and the known distribution of 5hmC at transcribed genes and active enhancers. In contrast, an unexpected DNA hypomethylation noted in multiple TET-deficient genomes is primarily observed in the heterochromatin compartment. In a mouse model of T cell lymphoma driven by TET deficiency (Tet2/3 DKO T cells), genomic analysis of malignant T cells revealed DNA hypomethylation in the heterochromatic genomic compartment, as well as reactivation of repeat elements and enrichment for single nucleotide alterations, primarily in heterochromatic regions of the genome.

overall_design: WGBS (MethylC-seq), Hi-C, and total (ribodepleted) RNA-seq, in WT and Tet2/3 DKO iNKT cells

first: Ageliki

last: Tsagaratou

first: Hyungseok

last: Seo

first: Benjamin

last: Delatte

first: Sven

last: Heinz

first: Christopher

last: Benner


title: miRNA-mRNA networks in depression associated hippocampal remodeling

platform_organism:
Mus musculus
synthetic construct


title: Differential cellular transcriptional profiles during virus-induced neuroinflammation identified new microglial- and macrophage-specific genes

city: Salt Lake City

first: Chris

last: Stubben

state: Utah

address: 2000 Cir of Hope Dr

department: University of Utah

institute: Huntsman Cancer Institute

summary:
Goal: Determine differences in gene expression profile between microglia and macrophages isoalted from the brains of mice during viral-induced neuroinflammation.
Methods: microglia and macrophages were obtained by FACS cells sorting (based on CD45 and CD11b level of expression) from brains of C57BL/6J mice, 6 days post i.c infection with TMEV or injection with PBS. RNA was extracted with TRYzol and precipitated using glycogen.  polyA mRNA was enriched using oligo d(T)25 magnetic beads Smarter Stranded RNA-Seq Kit was then utilized to prepare cDNA library for RNA-seq.
Results: Using RNA-seq and later RT-qPCR to validate our candidates, we found genes that are speifically expressed by activated microglia or infiltrating macrophages during viral-induced neuroinflamamtion

overall_design: RNA was isolated from macrophages and microglia obtained the brains of 30 TMEV-infected mice and 40 PBS-injected mice

first: Ana

middle: B

last: DePaula-Silva

first: Daniel

last: Doty

first: Carlos

middle: M

last: Gorbea

first: John

last: Sanchez


title: The efficiency of MLL-ENL driven leukemia initiation changes with age and peaks during neonatal development

status: Public on Jul 16 2019

city: St Louis

first: Jeffery

last: Magee

address: 660 S Euclid Ave.

department: Internal Medicine - Cardiovascular Division

institute: Washington University School of Medicine

summary: MLL-ENL target gene expression after fetal or adult induction

overall_design: Hematopoietic progenitors were harvested from neonatal or adult mice after induction of a tetracycline regulated MLL-ENL transgene

first: Jeffrey


title: Chromatin Loops Associated with Active Genes and Heterochromatin Shape Rice Genome Architecture for Transcriptional Regulation

city: Wuhan

first: Shuangqi

last: Wang

state: Hubei

address: No.1,Shizishan Street

institute: Huazhong Agricultural University

summary: We systematically analyze the basic features of chromatin interaction mediated by RNAP2, H3K4me3 and H3K9me2. All interactions further aggregated into higher-order clusters and modular interacting domains with distinct genomic and transcriptional properties. Together, our strategy provides hierarchical and modular 3D genome architecture for transcription regulation in rice.

overall_design: Using the young leaf tissues of rice, through improved ChIA-PET technology

first: Lun

last: Zhao


title: RNA sequencing of CD4+ T cells from mice developmentally exposed to TCDD

status: Public on Jul 15 2019

city: Rochester

first: B. Paige

last: Lawrence

state: NY

address: 601 Elmwood Ave.

institute: University of Rochester

summary: We used next generation RNAsequencing to identify how triggering the aryl hydrocarbon receptor (AHR) during development alters T cell gene expression. Specifically, mice were developmentally exposed to vehicle or the AHR agonist TCDD. At adulthood, mice were infected with influenza A virus. CD44hiCD4+ and CD44loCD4+ T cells were FACs purified from the mediastinal lymph nodes on day 9 post infection. RNA was isolated from these cells, and RNA-seq was performed. Gene expression analysis revealed developmental AHR activation durably changes the expression of genes involved in several important CD4+ T cell functions, including proliferation, differentiation, and metabolism.

overall_design: Comparing gene expression patters of CD44hiCD4+ and CD44loCD4+ T cells from mice developmentally exposed to vehicle or TCDD during influenza a virus infection. 3 biological replicates per sample.

first: Catherine

last: Burke

first: Jason

last: Myers

first: B


title: Durable Response of Enzalutamide-resistant Prostate Cancer to Supraphysiological Testosterone Is Associated with a Multifaceted Growth Suppression and Impaired DNA Damage Response Transcriptomic Program in Patient-derived Xenografts

city: Seattle

first: Ilsa

last: Coleman

state: WA

address: 1100 Fairview Ave N, E2-112

department: Human Biology

institute: Fred Hutchinson Cancer Center

summary: The study aims to determine SPT effect on the CRPC growth and molecular alterations using LuCaP PDX CRPC models.

overall_design: RNA sequencing of castration-resistant PC (CRPC) patient-derived xenograft (PDX) lines using Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500.

first: Hung-Ming

last: Lam

first: Holly

last: Nguyen

first: Lisha

last: Brown

first: Roman

last: Gulati

first: Bryce

last: Lakely

last: Sondheim

first: Mark

last: Labrecque

first: Brett

last: Marck

first: Alvin

last: Matsumoto

first: Elahe

last: Mostaghel

first: Peter

last: Nelson

first: Eva

last: Corey


title: In vivo imaging and deep learning tools expose two distinct E2F cell cycle transcriptional relays (in preparation)

city: Charleston

first: Daokum

last: Sun

state: SC

address: 86 Jonathan Lucas St

institute: Medical University of South Carolina

summary:
Purpose: We used next-generation sequencing (NGS) to identify genes which oscillate during cell cycle in embryos in mRNA level
Methods: Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) bi-transgenic mice (mKO2-hCDT1;mAG-hGEM) mRNA profiles of Embryo day 10.5, 11.5 and 13.5 were generated for deep sequencing. The reads were aligned using STAR program and . qRT–PCR validation was performed using SYBR Green assays
Results: Genes consistently expressed >2 log fold higher (with an adjusted P-value < 0.05) in DR, YE, or GR samples than in BR samples, were denoted ‘proliferation-related’. Of these 258 proliferation-related genes, 86 were previously reported as periodically expressed during the cell cycle. The majority of genes whose expression was enriched in BR samples (267 genes) were related to cell differentiation and non-proliferative processes, and were thus classified as ‘quiescent-related’ . In agreement with measurements made in cell culture systems, E2f1-3a and E2f7-8 mRNA levels increased in cycling cells when compared to cells in G0, with maximum levels observed in S and G2, albeit the increased expression of E2f7-8 was more pronounced. The mRNA levels of E2f3b, E2f4, E2f5 and E2f6 remained relatively unchanged among the various cell cycle fractions
Conclusions: Our research use NGS to deeply study the cell-cyle related gene expression in vivo. The data analysis work flows reported here provides gene expression information regarding to different cell cycle phase and embryo age.

overall_design: Examine the gene expression for different cell cycle phases (BR,DR,YE,GE) using FUCCI wild type 10.5, 11.5 and 13.5 embryos (E10.5,E11.5 and E13.5)

first: Maria

last: Cuitino

first: Leone

last: Gustavo

first: Pecot

last: Thrierry

first: Sun

last: Daokun


title: Search for genes affected by MgtC overexpression in Salmonella enterica serovar Typhimurium 14028s

status: Public on Jul 13 2019

city: Seoul

first: Yong-Joon

last: Cho

address: 1 Gwanak-ro, Gwanak-gu

country: South Korea

institute: Seoul National University

summary: A set of genes are differentially regulated in the presence of extra copy of the mgtC gene. Provide a hint of potental target of the MgtC protein.

sample_organism: Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S

overall_design: RNA expression profile of cells harboring a plasmid with the mgtC gene versus the empty vector, grown in minimal media, using Illumina NextSeq 500.

first: Eun-Jin

last: Lee

first: Daesil

last: Nam


title: Early transcriptional signature in murine cDCs post immunisation with VLPs containing TLR ligands

first: Ariane

middle: Cruz

last: Gomes

address: Roosevelt drive

institute: University of Oxford

summary: We have investigated the in vivo transcriptional signature in dendritic cells (DCs) from mice immunised with VLPs containing distinct classes of nucleic acid and correlated the expression patterns with the efficiency of induced T cell responses.

overall_design: Female C57BL/6 mice were immunised with Qbeta VLPs contaning B type CpG, ssRNA, empty VLP. 24h later splenic cDCs were purified and processed for RNA extraction

middle: C


title: Transcriptome analysis of bone marrow in Phc2 knock out mice

status: Public on Jul 10 2019

first: In byung

last: Park

address: 145, Anam-ro, Seongbuk-gu, Seoul

institute: Korea University

summary: This study investigated the biological function of Phc2 by Phc2 knock out mice. Polycomb group (PcG) proteins function as transcriptional repressors of target genes by mainly modulating histone methylation. The canonical Polycomb repressor complex 1 (PRC1), type of PcG proteins, recognizes and binds to H3K27me3 to sustain the transcriptional repression of a target gene. To investigate the function of canonical PRC1, We identified  potential function of Phc2 that is component of  the canonical PRC1 by Phc2 knock out mice.

overall_design: Phc2+/- (Phc2 heterozygote) mice with a C57BL/6 background were gifted by Dr. Kyoichi Isono (Wakayama Medical University). Wild type and Phc2 knock out mice were bred from Phc2 +/- mice.The bone marrow RNA extracts of Wild type and Phc2 knock out mice were used for transcriptome analysis.

first: Joonbeom

last: Bae

first: Sang-Pil

last: Choi


title: The pause-initiation limit restricts transcription activation in human cells

city: Göttingen

first: Björn

last: Schwalb

address: Fassberg 11

institute: MPI

summary: Eukaryotic gene transcription is often controlled at the level of RNA polymerase II (Pol II) pausing in the promoter-proximal region. Pausing Pol II limits the frequency of transcription initiation (‘pause-initiation limit’), predicting that the pause duration must be decreased for transcriptional activation. To test this prediction, we conducted a genome-wide kinetic analysis of the heat shock response in human cells. We show that the pause-initiation limit restricts transcriptional activation at most genes. Gene activation generally requires the activity of the P-TEFb kinase CDK9, which decreases the duration of Pol II pausing and thereby enables an increase in the productive initiation frequency. The transcription of enhancer elements is generally not pause-limited and can be activated without CDK9 activity. Our results define the kinetics of Pol II transcriptional regulation in human cells at all gene classes during a natural transcription response.

overall_design: Multi-omics in human cells (TT-seq, mNET-seq, RNA-seq)

first: Saskia

last: Gressel

first: Patrick

last: Cramer


title: Transcriptiomic analysis of linker histone H1 mutant

city: Warsaw

first: Maciej

last: Lirski

address: Pawińskiego 5a

department: Department of Protein Biosynthesis

country: Poland

institute: Institute of Biochemistry and Biophysics, Polish Academy of Sciences

summary: mRNA profiles of 21-day old wild type (WT) and 3h1 Arabidopsis plants were generated by deep sequencing, in triplicate.

first: Kinga

last: Rutowicz

first: Magdalena

last: Kroteń


title: RNA-seq of heart left ventricle

status: Public on Jul 08 2019

city: Singapore

first: Aida

last: Moreno-Moral

address: 8 College Road

institute: Duke-NUS Medical School

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

overall_design: Refer to individual Series


title: PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer

status: Public on Jul 09 2019

city: Glasgow

first: Neil

last: Robertson

state: Scotland

address: Switchback Road

department: Beatson Institute for Cancer Research

institute: University of Glasgow

summary: Overcoming cellular growth restriction, including the evasion of cellular senescence, is a hallmark of cancer. We report that PAK4 is overexpressed in all human breast cancer subtypes and associated with poor patient outcome. In mice, MMTV-PAK4 overexpression promotes spontaneous mammary cancer, while PAK4 gene depletion delays MMTV-PyMT driven tumors. Importantly, PAK4 prevents senescence-like growth arrest in breast cancer cells in vitro, in vivo and ex vivo, but is not needed in non-immortalized cells, while PAK4 overexpression in untransformed human mammary epithelial cells abrogates H-Ras-V12-induced senescence. Mechanistically, a PAK4 – RELB - C/EBPa axis controls the senescence-like growth arrest and a PAK4 phosphorylation residue (RELB-Se151) is critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBPa. These findings establish PAK4 as a promoter of breast cancer that can overcome oncogene-induced senescence and reveal a selective vulnerability of cancer to PAK4 inhibition.

overall_design: We quantify transcription via high-throughput RNA sequencing in two human breast cancer cell lines (BT-549 and Hs578T) 72hrs after transient transfection with control (siControl) or PAK4-targetting siRNA.

first: Tania

last: Costa

first: Ting

last: Zhuang

first: Julie

last: Lorent

first: Emilia

last: Turco

first: Helene

last: Olofsson

first: Miriam

last: Masia-Balague

first: Miao

last: Zhao

first: Parisa

last: Rabieifar

first: Raoul

last: Kuiper

first: Jonas

last: Sjolund

first: Matthias

last: Spiess

first: Pablo

last: Hernandez Varas

first: Uta

last: Rabenhorst

first: Pernilla

last: Roswall

first: Ran

last: Ma

first: Xiaowei

last: Gong

first: Johan

last: Hartman

first: Kristian

last: Pietras

first: Peter

middle: D

last: Adams

first: Paola

last: Defilippi

first: Staffan

last: Stromblad


title: Single cell sequencing of Angiotensin II-infused mouse left ventricle

first: Aida

last: Moreno-Moral

summary: Single cell RNA-seq of heart left ventricle a wild type mouse after 28 days of angiotensin II treatment

overall_design: We treated a wild type mouse with angiotensin II infusion for 28 days and harvested left ventricle heart tissue to carry out single RNA-sequencing.

first: Huimei

last: Chen

first: Enrico

last: Petretto


title: Colorectal cancer cells respond differentially to autophagy inhibition in vivo

status: Public on Jul 11 2019

city: Sherbrooke

first: Steve

last: Jean

state: Qc

address: 3201 Rue Jean Mignault

department: Anatomy and Cell Biology

institute: Université de Shebrooke

summary: inhibition of autophagy in vivo had a substantial cell line-dependent impact on tumor growth of different CRC derived cell lines.  RNA sequencing of WT and RAB21 KD tumors in a CAM model was used to determine the gene expression profile associated with these differential responses.

overall_design: 3 tumors per condition were pooled prior to RNA extraction.  2 different CRC cell lines were analysed.  Gene expression profile of WT and RAB21 KD were compared for each cell lines.

first: Annie

last: Lauzier


title: A novel lncRNA lncRNA-AF339830 promotes colorectal carcinogenesis and glucose metabolism by stabilizing and specifying the transcription modification pattern of c-Myc [ChIP-Seq]

city: Shanghai

first: Haoyan

state: Shanghai

address: 145 Shandong Road

institute: Renji Hospital

summary: To elucidate whether  lncRNA-AF339830 plays a role in  colorectal cancer tumorigenesis, a Chip-seq analysis was performed to compare the change of c-myc genome-wide binding  of  lncRNA-AF339830 siRNA and control siRNA transfectants.

overall_design: Chip-seq was performed in DLD1  colorectal cancer cells after lncRNA-AF339830 knock down

first: Yan

last: tingting


title: Mta2, a component of the NuRD complex, regulates B cell development and cooperates with OCA-B in controlling the pre-B to immature B cell transition (RNA-Seq)

city: New York

first: Chi-Shuen

last: Chu

address: 1230 York Ave

institute: The Rockefeller University

summary: The goal of this study is to compare NGS-derived mouse B cell RNA profiling in Mta2 KO, Ocab KO, and double KO mice

overall_design: Pro-B, Pre-B, and small pre-B cell RNA profiles from control, Mta2 KO, OcaB KO, or double KO mice were generated by deep sequencing using Illumina HiSeq 2500. The sequence reads that passed quality filters were analyzed at the transcript isoform level.

first: Xiangdong

last: Lu


title: Conservation, acquisition, and functional impact of sex-biased gene expression in mammalian tissues

city: Cambridge

first: Sahin

last: Naqvi

state: MA

address: 455 Main St

institute: Whitehead Institute

summary: Sex differences are widespread in human health and disease, which are frequently modeled in other mammalian species. However, the extent to which molecular sex differences are conserved across both tissues and species remains unclear. We conducted a 12-tissue, five-species survey of sex differences in gene expression using both publicly available (human) and newly generated (cynomolgus macaque, mouse, rat, and dog) RNA sequencing data. In each of the tissues assessed, we identified between 128 and 805 genes with conserved sex-biased expression.  However, most sex bias in gene expression (~77%) – both female and male – has arisen since the last common ancestor of boroeutherian mammals, likely facilitated by reduced selective constraint. Evolutionary gains and losses of regulation by sex-biased transcription factors drove a significant fraction (~27%) of lineage-specific changes in sex bias. Our study suggests caution in the use of other species as models of human sex differences, and that similar selective pressures have driven sex-biased gene expression both within and outside the reproductive tract.

sample_organism:
Macaca fascicularis
Canis lupus familiaris
Mus musculus
Rattus norvegicus

overall_design: Tissue transcriptomes from 12 tissues and 4 species, 3 males and 3 females per species (before removal of outliers) were sequenced and compared for sex differences

first: David

last: Page


title: Mta2, a component of the NuRD complex, regulates B cell development and cooperates with OCA-B in controlling the pre-B to immature B cell transition

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: MNase analysis of linker histone H1 mutant

first: Maciej

last: Lirski

summary: Nucleosome occupancy profiles of 21-day old wild type (WT) and 3h1 Arabidopsis plants were generated by deep sequencing.

overall_design: Mnase-seq nucleosome occupancy profiles of 21-day old wild type (WT) and 3h1 Arabidopsis plants were generated by deep sequencing.

first: Magdalena

last: Kroteń


title: The Right Ventricular Fibroblast Secretome Drives Cardiomyocyte Dedifferentiation

status: Public on Jul 07 2019

city: Aurora

first: Philip

last: Tatman

state: Colorado

department: Neurosurgery

institute: University of Colorado

summary:
Rationale: In virtually all models of heart failure, prognosis is determined by right ventricular (RV) function; thus, understanding the cellular mechanisms contributing to RV dysfunction is critical.  Whole organ remodeling is associated with cell-specific changes, including cardiomyocyte dedifferentiation and activation of cardiac fibroblasts (Cfib) which in turn is linked to disorganization of cytoskeletal proteins and loss of sarcomeric structures.   However, how these cellular changes contribute to RV function remains unknown.  We’ve previously shown significant organ-level RV dysfunction in a large animal model of pulmonary hypertension (PH) which was not mirrored by reduced function of isolated cardiomyocytes.  We hypothesized that factors produced by the endogenous Cfib contribute to global RV dysfunction by generating a heterogeneous cellular environment populated by dedifferentiated cells.
Objective:  To determine the effect of Cfib conditioned media (CM) from the PH calf (PH-CM) on adult rat ventricular myocytes (ARVM) in culture.
Methods and Results: Brief exposure (<2 days) to PH-CM results in rapid, marked dedifferentiation of ARVM to a neonatal-like phenotype exhibiting spontaneous contractile behavior. Dedifferentiated cells maintain viability for over 30 days with continued expression of cardiomyocyte proteins including TnI and α-actinin yet exhibit myofibroblast characteristics including expression of α-smooth muscle actin. Using a bioinformatics approach to identify factor(s) that contribute to dedifferentiation, we found activation of the PH Cfib results in a unique transcriptome correlating with factors both in the secretome and with activated pathways in the dedifferentiated myocyte.  Further, we identified upregulation of periostin in the Cfib and CM, and demonstrate that periostin is sufficient to drive cardiomyocyte dedifferentiation.
Conclusions: These data suggest that paracrine factor(s) released by Cfib from the PH calf signal a phenotypic transformation in a population of cardiomyocytes that likely contributes to RV dysfunction.  Therapies targeting this process, such as inhibition of periostin, have the potential to prevent RV dysfunction.

sample_organism:
Bos taurus
Rattus norvegicus

platform_organism:
Bos taurus
Rattus norvegicus

overall_design: Two experiments were performed. The first was to identify transcriptome differences between bovine cardiac fibroblasts from high altitude animals to low altitude animals. The second experiment was to determine the effects of the fibroblast conditioned media from the high altitude animals on adult rat ventricular myocytes vs control, untreated cells.

first: Lori

last: Walker


title: MNase-seq and RNA-seq of linker histone H1 mutant


title: A novel lncRNA lncRNA-AF339830 promotes colorectal carcinogenesis and glucose metabolism by stabilizing and specifying the transcription modification pattern of c-Myc


title: Effects of suberanilohydroxamic acid (SAHA) on HeLa cells

city: Memphis

first: Geoffrey

last: Neale

state: TN

address: 262 Danny Thomas Place

department: Hartwell Center

institute: St Jude Childrens Research Hospital

summary: Analysis of HeLa cells treated with histone deacetylase inhibitor SAHA for 24hr. Results provide insight into the effect of SAHA on the activation of lysosomal and autophagy pathways

overall_design: We used microarrays to explore the gene expression profiles differentially expressed in HeLa cells after treatment with DMSO (Control) or after treatment with the histone deactylase inhibitor Suberoylanilide Hydroxamic Acid (SAHA).

first: Ida

last: Annunziata

first: Alessandra

last: D'Azzo


title: Effect of TGFb1 treatment and WISP1 overexpression on 4T1 breast cancer cells

last: Finkelstein

address: 332 N. Lauderdale St.

department: Computational Biology

institute: St Jude Children's Research Hospital

summary: This study set out to identify TGFb1 transcriptional targets in breast cancer cells. 4T1 breast cancer cells were treated with TGFb1 for 24h and transcripts that were significantly regulated were identified. Wisp1 was identified as one of the genes most highly upregulated by TGFb1. To identify the transcriptional targets of Wisp1, 4T1 cells were then virally transduced to increase Wisp1 expression. The gene expression profiles of Wisp1-overexpressing 4T1 cells  were determined and revealed that Wisp1 overexpression does not result in major gene expression changes in 4T1 cells.

overall_design: mRNA profiles from 4T1 breast cancer cells treated with TGFb1 or with Wisp1 overexpression were examined.

first: Myriam

last: Labelle


title: A novel lncRNA lncRNA-AF339830 promotes colorectal carcinogenesis and glucose metabolism by stabilizing and specifying the transcription modification pattern of c-Myc [RNA-Seq]

last: Chen

summary: To elucidate whether  lncRNA-AF339830 plays a role in  colorectal cancer tumorigenesis, a RNA-seq analysis was performed to compare the gene expression profiles of  lncRNA-AF339830 siRNA and control siRNA transfectants.

overall_design: RNA-seq was performed in colorectal cancer cells after lncRNA-AF339830 knock down

first: Jie

last: Hong