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

status: Public on Jul 31 2019

city: Dallas

first: W. Lee

last: Kraus

state: TX

address: 5323 Harry Hines Blvd.

country: USA

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

first: Dae-Seok

last: Kim

first: Venkat

middle: S

last: Malladi

first: W

middle: L


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

type: Expression profiling by high throughput sequencing

summary: PARP inhibitors (PARPi) prevent 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 ADP-ribosylates DDX21, an RNA helicase that localizes to nucleoli and promotes rDNA transcription when ADP-ribosylated. Treatment with PARPi or mutation of the ADP-ribosylation sites reduce DDX21 nucleolar localization, rDNA transcription, ribosome biogenesis, protein translation, and cell growth. The salient features of this pathway are evident in xenografts in mice and human breast cancer patient samples. Elevated levels of PARP-1 and nucleolar DDX21 are associated with cancer-related outcomes. Our studies provide a mechanistic rationale for efficacy of PARPi in cancer cells lacking defects in DNA repair whose growth is inhibited by PARPi.

overall_design: We performed Total RNA-seq for RIP-seq input. polyA-enriched, polyA-depleted RNA-seq to check the expression of snoRNA and their host genes and LucKD, DDX21 KD polyA enriched RNAseq to check host gene expression upon DDX21 KD.


title: Master transcription factors form interconnected circuitry and orchestrate transcriptional networks in esophageal adenocarcinoma [4C-Seq]

status: Public on Jul 30 2019

city: Los Angeles

first: Li

last: Chen

state: CA

address: 8700 Beverly Blvd

department: Medicine

institute: Cedars-Sinai Medical Center

summary: We report the application of circular chromatin conformation capture (4C) sequencing technology for master transcription factor (KLF5 and ELF3) in human esophageal adenocarcinoma cancer cell lines (ESO26) . By baiting  the promoters of KLF5 and ELF3, we esatblished the interaction with unknown enhnacer marks.

overall_design: 4C sequencing analysis of espohageal adenocarcinoma cell line

first: Moli

last: Huang

first: Jasmine

last: Plummer

first: Jian

last: Pan

first: Yan-Yi

last: Jiang

first: Qian

last: Yang

first: Tiago

middle: C

last: Silva

first: Nicole

last: Gull

first: Stephanie

first: Ling-Wen

last: Ding

first: Omer

last: An

first: Henry

first: Yulan

last: Cheng

first: Jonathan

middle: W

last: Said

first: Ngan

last: Doan

first: Winand

middle: N

last: Dinjens

first: Kevin

middle: M

last: Waters

first: Richard

last: Tuli

first: Simon

middle: A

last: Gayther

first: Samuel

middle: J

last: Klempner

first: Stephen

last: Meltzer

first: Benjamin

middle: P

last: Berman

first: De-Chen

last: Lin

first: H

last: Koeffler


title: Changes in total RNA in BK deficient mice after 4h sleep deprivation [individuals]

city: Zurich

first: Steven

last: Brown

address: Winterthurerstrasse 190

department: Institute of Pharmacology and Toxicology

country: Switzerland

institute: University of Zurich

summary: Animals deficient for the alpha subunit of the large conductance calcium dependent potassium channel (BK) were sleep deprived for 4 hours and compared to wildtype littermates as well as animals (wildtype littermate and BK deficient) left undisturbed for the same time.

overall_design: 4 hours sleep deprivation compared to undisturbed baseline for BK deficient and wildtype littermate control animals, all brains harvested at TZ4. Sequenced as individual animals.

first: Christine

last: Muheim


title: Wine strains of S. cerevisiae fermenting with/without lipid supplementation

city: Sassari

first: Giacomo

last: Zara

address: v.le Italia, 39

department: Department of Agraria

country: Italy

institute: University of Sassari

summary: Goal was to identify yeast genes whose expression changed as a function of the presence/absence of lipid nutrients during fermentation of two S. cerevisiae wine strains characterized by a different fermentative behaviour.

overall_design: Cells of Saccharomyces cerevisiae strains EC1118 (commercial strain, Lallemand) and M25 (wild-type strain, University of Sassari culture collection) were precultured at 28°C in orbital shaker in synthetic juice (SJ): glucose 200 g/l; tartaric acid 2 g/l; malic acid 2 g/l; citric acid 0.2 g/l; YNB w/o amino acids and ammonium sulphate 1.7 g/l; ammonium sulphate 2 g/l; pH 3.3. After 24h, cells from precultures were washed twice in sterile water and inoculated in SJ and FSJ (SJ + ergosterol 15 mg/l + oleic acid 15mg/l) to the final concentration of 1,000,000 cells/ml. After 60h, cell samples were harvested, washed in sterile water at 4°C, pelleted and immediately stored in liquid nitrogen for subsequent RNA isolation. Four different conditions, each represented by three biological replicates, were assessed: i) EC1118 in SJ; ii) EC1118 in FSJ; iii) M25 in SJ; iv) M25 in FSJ. This experimental design allowed to discard the influences of strain-specific genetic backgrounds and to consider the differences metabolic responses due to the adaptation to the stress condition tested.

first: Marilena

last: Budroni

first: Hennie

last: van Vuuren


title: Age effects on CL-induced beige fat remodeling

city: Cincinnati

first: Hee-Woong

last: Lim

state: Ohio

address: 3333 Burnet Ave. MLC 7024

department: Division of Biomedical Informatics

institute: Cincinnati Children's Hospital Medical Center

summary: Analysis of iWAT tissues from young (2 month) and aged (12 month) C57bl/6 male mice with vehicle or CL treatments. CL-induced tissue remodeling is severely impaired in aged mice. Results provide insight into molecular mechanisms underlying age-related changes in iWAT.

overall_design: Young and aged mice were acclimated to thermoneutrality for 2 weeks, and then administrated with vehicle or CL for 5 days.

first: Wenshan

last: Wang

first: Hee

first: Patrick

last: Seale


title: Changes in total RNA in BK deficient mice after 4h sleep deprivation

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

overall_design: Refer to individual Series


title: Master transcription factors form interconnected circuitry and orchestrate transcriptional networks in esophageal adenocarcinoma

first: Li

last: Chen

type: Genome binding/occupancy profiling by high throughput sequencing


title: Couple transcriptome and genomic data obtained from the PDXs to identify pathways linking oncogenic alterations

city: Milano

first: Marine

last: Melixetian

address: via Adamello 16

institute: European Institute of Oncology

summary:
Purpose: Study  the changes in cell transcriptome in breast cancer with respect to normal breast tissue in association with somatic mutations
Methods: RNA was extracted from frozen normal breast tissues and PDXs cells
Results: We found over-expression of oncogenic pathways associated with oncogenic mutations in PDXs

overall_design: Analysis of differential gene expression in metastatic breast cancer PDXs

first: Simona

last: Punzi

last: Meliksetyan

first: Laura

last: Riva

first: Federica

last: Marocchi

first: Giancarlo

last: Pruneri

first: Carmen

last: Criscitiello

first: Franco

last: Orsi

first: Lorenzo

last: Spaggiari

first: Giuseppe

last: Curigliano

first: Pier

middle: G

last: Pelicci

first: Luisa

last: Lanfrancone


title: Next Generation Sequencing Analysis of Wild Type and SRSF2-/- 5 month mice liver Transcriptomes

city: Shanghai

first: cheng

middle: yuan

last: ming

address: NO.320 Yueyang Road

country: China

institute: Shanghai Institutes for Biological Science CAS

summary: We generated the liver specific SRSF2 -/- mice, and collected their liver at 5 month after born and controls. Then, we extracted RNAs and performed next generation sequencing. By comparing sequcing data from WT and SRSF2 -/- samples, we profiled the alternative splicing events and gene expression regulated by SRSF2 during mouse liver development process.

overall_design: 5 month liver mRNA profiles of wild type (WT) and  liver specific SRSF2-/- mice were generated by deep sequencing, using Illumina HiSeq2000.

first: Yuanming

last: Cheng


title: Gene expression analysis of wild type and YAP-activated embryonic mouse stomach

city: Worcester

first: Julie

last: Zhu

state: MA

address: 364 Plantation Street

department: Molecular Cellular and Cancer Biology

institute: UMass Medical School

summary: Hippo-YAP signaling plays important roles in gut development and homeostasis. In this study, we use RNAseq to analyze the gene expression profiles of wild type stomach and YAP5SA-expressing stomach at E13.5. The goal of this study is to understand the transcription program regulated by YAP in the developing gut.

overall_design: Total RNA obtained from freshly isolated E13.5 stomach tissue from wild type and NKX3.2Cre;R26-YAP5SA animals

first: Jennifer

last: Cotton

first: Junhao

last: Mao


title: Single cell RNA-seq analysis of medulloblastoma

city: Boston

first: Volker

last: Hovestadt

address: 360 Longwood Avenue

department: Pediatric Oncology

institute: Dana-Farber Cancer Institute

summary: Medulloblastoma is a malignant childhood cerebellar tumour comprised of distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. We used single-cell transcriptomics to investigate intra- and inter-tumoural heterogeneity in twenty-five medulloblastomas spanning all molecular subgroups. WNT, SHH, and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours were exclusively comprised of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, whose relative proportions distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide novel insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.

overall_design: We prospectively obtained fresh surgical resections from a series of twenty-five MB patients, including 23 diagnostic samples and two recurrences, and eleven patient-derived xenograft (PDX) models. Samples were obtained as fresh tumour biopsies from three different treating centers, including LeBonheur Children?s Hospital (n=12), Boston Children?s Hospital (n=4), and Vienna General Hospital (n=9). Patients were predominantly male (19 males vs. 6 females) and ages ranged from 3-17 years (median=9 years). Classic (n=16), large-cell/anaplastic (n=6), and desmoplastic/nodular (n=3) histologies were included in our series and there was an abundance of patients with metastatic disease (16/25, 64%).

first: Kyle

last: Smith

first: Laure

last: Bihannic

first: Mariella

last: Filbin

first: Bradley

middle: E

last: Bernstein

first: Mario

last: Suva

first: Paul

last: Northcott


title: Master transcription factors form interconnected circuitry and orchestrate transcriptional networks in esophageal adenocarcinoma [ChIP-Seq]

first: Li

last: Chen

summary: We profiled fresh-frozen esophageal tumor and normal samples and cell lines with chromatin immunoprecipitation sequencing (ChIP-Seq). Mathematically modeling was performed to establish (super)-enhancers landscapes and inter-connected transcriptional circuitry formed by master TFs. Coregulation and cooperation between master TFs was investigated by ChIP-Seq, RNASeq, 4C-Seq and luciferase assay. Biological functions of candidate factors were evaluated by measuring cell proliferation, colony formation, cell apoptosis and xenograft growth.

overall_design: Esophageal Cancer and normal cell lines and fresh-frozen tissues were harvested, and ChIPseq was performed using H3K27Ac and transcription factor antibodies.

first: Moli

last: Huang

first: Jasmine

last: Plummer

first: Jian

last: Pan

first: Yan-Yi

last: Jiang

first: Qian

last: Yang

first: Tiago

last: Silva

first: Nicole

last: Gull

first: Stephanie

first: Ling-Wen

last: Ding

first: Omer

last: An

first: Henry

first: Yulan

first: Jonathan

last: Said

first: Ngan

last: Doan

first: Winand

last: Dinjens

first: Kevin

last: Waters

first: Richard

last: Tuli

first: Simon

last: Gayther

first: Samuel

last: Klempner

first: Stephen

last: Meltzer

first: Benjamin

last: Berman

first: De-Chen

last: Lin

first: H

last: Koeffler


title: Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis [scRNA-seq]

city: Vienna

first: Christoph

last: Bock

address: Lazarettgasse 14

country: Austria

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

summary: Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a characteristic hybrid position between cancers and inflammatory diseases, which makes it an attractive model for studying cancer development. To explore the molecular mechanisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity, we investigated the transcriptomic and epigenomic diversity in primary LCH lesions. Using single-cell RNA sequencing, we identified multiple recurrent types of LCH cells within these biopsies, including putative LCH progenitor cells and several subsets of differentiated LCH cells. We confirmed the presence of proliferative LCH cells in all analysed biopsies using immunohistochemistry, and we defined the epigenomic and gene-regulatory basis of the different LCH cell subsets using chromatin profiling. In summary, our single-cell analysis of LCH uncovered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, reflecting complex developmental hierarchies in LCH lesions.

overall_design:
Single-cell RNA-sequencing (10x Genomics): 7 LCH biopsies from different tissues.

**The submitter declares that the raw sequence data have been deposited at the European Genome-Phenome Archive (EGA) to protect patient privacy.**

first: Florian

last: Halbritter

first: Matthias

last: Farlik

first: Raphaela

last: Schwentner

first: Gunhild

last: Jug

first: Nikolaus

last: Fortelny

first: Thomas

last: Schnöller

first: Hanja

last: Pisa

first: Linda

last: Schuster

first: Andrea

last: Reinprecht

last: Czech

first: Johannes

last: Gojo

first: Wolfgang

last: Holter

first: Milen

last: Minkov

last: Bauer

first: Ingrid

last: Simonitsch-Klupp

first: Caroline

last: Hutter


title: Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis

last: Bock


title: Prdm16 overexpression effect on inguinal white adipose tissue:stromal-vascular cells

first: Hee-Woong

last: Lim

summary: Analysis of SV cells transducted with control or Prdm16 retrovirus. Results provide insight into molecular mechanism underlying Prdm16 function in iWAT white adipose tissues.

overall_design: SV cells were isolated from iWAT, and then transducted with control (puro) or Prdm16 retrovirus.

first: Wenshan

last: Wang

first: Megan

last: Kissig

first: Hee

first: Patrick

last: Seale


title: Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis [ATAC-seq]

first: Christoph

summary: Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a characteristic hybrid position between cancers and inflammatory diseases, which makes it an attractive model for studying cancer development. To explore the molecular mecha-nisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity, we investi-gated the transcriptomic and epigenomic diversity in primary LCH lesions. Using single-cell RNA se-quencing, we identified multiple recurrent types of LCH cells within these biopsies, including putative LCH progenitor cells and several subsets of differentiated LCH cells. We confirmed the presence of pro-liferative LCH cells in all analysed biopsies using immunohistochemistry, and we defined the epigenomic and gene-regulatory basis of the different LCH cell subsets using chromatin profiling. In summary, our single-cell analysis of LCH uncovered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, reflecting complex developmental hierarchies in LCH lesions.

overall_design:
ATAC-seq analysis of three FACS-enriched LCH cell subsets (in duplicate) from a biopsy = 6 datasets total.
**The submitter declares that the raw sequence data have been deposited at the European Genome-Phenome Archive (EGA) to protect patient privacy.**

first: Florian

last: Halbritter

first: Matthias

last: Farlik

first: Raphaela

last: Schwentner

last: Jug

last: Fortelny


title: Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming

first: Antonio

last: Fernandez-Perez

address: 5323 Harry Hines Blvd

department: Internal Medicine-Cardiology


title: Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (ATAC-seq)

summary: Gata4, Mef2c, Hand2, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure.  Here we explored the role of Hand2 in iPM formation by using a combination of transcriptome, genome, and biochemical assays.  We found many shared transcriptional signatures between iPMs and endogenous sinoatrial node (SAN), yet key regulatory networks remain missing.  We demonstrate that Hand2 augments chromatin accessibility at loci involved in sarcomere organization, electrical coupling, and membrane depolarization.  Focusing on an established cardiac Hand2 cistrome, we observe selective reorganization of chromatin accessibility to promote pacemaker-specific gene expression.  Moreover, we identify a novel Hand2 cardiac subtype diversity (CSD) domain through biochemical analysis of the N-terminus.  By integrating our RNA-seq and ATAC-seq datasets, we highlight desmosome organization as a hallmark feature of iPM formation.  Collectively, our results illuminate Hand2-dependent mechanisms that may guide future efforts to rationally improve iPM formation.

overall_design: GHMT driven Hcn4-GFP pacemaker cells, GMT-iCMs, and control samples  were harvested after 14 days of induction for ATAC and RNAseq library preparation.

first: Nikhil

middle: V

last: Munshi


title: Locust bean gum derived galacto-manno-oligosaccharides utilization by Lactobacillus plantarum WCFS1

city: Mysuru

first: Mukesh

last: Kapoor

state: Karnataka

address: CFTRI

department: Protein Chemistry and Technology

country: India

institute: CSIR-Central Food Technological Research Institute

summary: In order to understand  LBG derived galacto-manno-oligosaccharides utilization by a probiotic bacterium, Lactobacillus plantarum WCFS1, we have grown Lactobacillus plantarum WCFS1 (in duplicates) till mid log phase (OD600nm ~0.5, 10 h) in carbon free MRS (de Man, Rogosa Sharpe ) media containing either galacto-manno-oligosaccharides, mannose, glucose or galactose (1% w/v) as the sole carbon source.

overall_design: Organism : Lactobacillus plantarum, Agilent's lactobacillus Gene Expression  8x15k Array (AMADID: 067475)  designed by Genotypic Technology private Limited

first: Deepesh

last: Panwar

first: Bipin

last: Chand


title: B cell single cell seq in allergen-specfic immunotherapy

city: La Jolla

first: Veronique

last: Shulten

address: 9420 Athena Circle

institute: LJI

summary: IgE-producing memory cells are hard to detect in the periphery. Here, we sorted IgE+ memory B cells from allergic patients who had received allergen-immunotherapy for grass pollen. Cells were FACS-sorted and subseuqenlty sequenced by single cell RNAseq to determine isotype and phenotype. Two out of 90 cells were determiend to be true IgE producing memory B cells.

overall_design: 95 single B cells were sorted, no replicates were perfromed. One control sample was included.

first: Bjoern

last: Peters

first: Véronique

last: Schulten

first: Ilka

last: Hoof

first: Peter

last: Anderson

first: Claus

last: Lundegaard

first: Ashu

last: Chawla

first: Jason

last: Greenbaum


title: Gene expression data of  iPS clones before bladder urothelium differentiation

city: Kobe City

first: Michiyo

last: Koyanagi-Aoi

address: Chuo-ku, Kusunoki-cho 7-5-1

country: Japan

institute: Kobe University

summary: We developed a method for the directed differentiation of hiPSCs into mature stratified bladder urothelium.

overall_design: We extracted total RNAs from iPS line 3AB4 and performed microarray for pluritest.

first: Kotaro

last: Suzuki

first: Mariko

last: Taniguchi-Ikeda

first: Takashi

last: Aoi


title: Genome-Wide Transcriptome Analysis Reveals Intermittent Fasting-Induced Metabolic Rewiring in the Liver

city: Singapore

first: Gavin

last: Ng

address: Block MD9, Level 4  2 Medical Drive  117597

department: Physiology

country: Singapore

institute: National University of Singapore

summary: Intermittent fasting (IF) has been extensively reported to participate in improved energy homeostasis and metabolic switching, which in turn promotes protection against numerous age-associated metabolic diseases that have plagued the global population in recent years. Despite the observation that IF may be a plausible strategy to ameliorate these epidemiological burdens in many societies, investigation into the underlying molecular mechanisms behind these purported effects are still in their infancy. Particularly, the relationship between IF and genetic changes are poorly understood, which forms the basis of this research.

overall_design: Mice were randomly assigned, and subjected to ad libitum (AL), IF for 16-hour (IF16) and 24-hour (hereby termed as every-other-day (EOD)) for a period of three months. After which, genome-wide transcriptome analysis was performed using RNA sequencing in the liver.

middle: Y

first: Sung-Wook

last: Kang

first: Joonki

last: Kim

first: Asfa

last: Alli-Shaik

first: Sang-Ha

last: Baik

first: Dong-Gyu

last: Jo

first: M

last: Hande

first: Christopher

last: Sobey

first: Jayantha

last: Gunaratne

first: David

last: Fann

first: Thiruma

last: Arumugam


title: Impact of EPA 50uM on gene exprezsion in MC38 mouse colorectal cancer cells

city: LEEDS

first: Milene

last: Volpato

address: St James University Hospital

department: LIRM

country: United Kingdom

institute: University of Leeds

summary:
Genone wide differential gene expression analysis
Identification of gene linked to mouse colorectal cancer cell response to EPA treatment through differential gene expression analysis in an EPA-sensitive cell line.

overall_design: MC38 cells treated for 24h with 50uM EPA in its free fatty acid form, total RNA isolated from control and treated cells

last: Hull


title: Progression of progenitor B cell leukemia is associated with alterations of the bone marrow micro-environment

city: Linköping

first: Mikael

last: Sigvardsson

address: Campus US

country: Sweden

institute: Linköping University

summary: Many of the clinical manifestations of B-lymphoid leukemia is a consequence of disrupted formation of normal blood cells. Upon diagnosis. the disease has often progressed into a state with a dramatic dominance of leukemic cells in the BM making it difficult to understand the environmental changes underlying the disruption in blood cell formation. To investigate this process in more detail we have explored pre-clinical stages of leukemia in a mouse model based on transplantation of B-ALL cells from  mice trans-heterozygote for mutations in the Ebf1 and Pax5 genes to non-conditioned hosts. This revealed that while the recipient HSC compartment was relatively intact, the presence of erythroid progenitors and in more advanced disease, lymphoid progenitors was reduced. Progression of disease was also reflected in changes of the cellular composition of non hematopoietic compartments as well as changes in gene expression patterns in specific cellular subpopulations. This included increased expression of the cytokine Il7 in the mature stroma cell compartments. The relevance for Il7 in tumor progression was evident from the finding that leukemia development was delayed when tumor cells were transplanted to Il7 deficient mice. Our data suggest that progressive development of B-ALL primarily target the production of normal progenitor cells and that the micro-environment undergo changes that can be predicted to result in a more permissive environment for tumor growth.

overall_design: For short term transplantations ProB cells were sorted from lymph nodes of sick mice as Lin-CD19+IgM+igD-CD43+Kit+. 100.000 cells were iv-injected to each recipient. Mice were euthanized at indicated time points and organs harvested. As controls, for each experiment setup, four animals were injected with PBS/iFCS. RNA-seq was performed on primary bone marrow and lymph node derived ProB cells from leukemic Pax5+/-Ebf1+/- mice and Wt mice, as well as on non hematopoietic bone marrow stroma cells. Data analysis was performed by alignment to mouse reference genome (mm10 /GRCm38) and mapped with STAR  (Dobin et al, Bioinformatics, 2013)  followed by analysis by DESeq2 in R.

first: Josefine

last: Åhsberg

first: Pingnan

last: Xiao

first: Kazuki

last: Okuyama

first: Rajesh

last: Somasundaram

first: Tobias

last: Strid

first: Hong

last: Qian


title: Enhancement of Human B Cell Differentiation and Function in Lymph Nodes by the TLR9 Agonist MGN1703

city: Philadelphia

first: Priyankara

last: Wickramasinghe

state: PA

address: 3601 Spruce Street

department: Bioinformatics

institute: The Wistar Institute

summary: TLR9 agonists are being developed as immunotherapies to increase immune effector cell activity against malignancies and pathogens. However, the in vivo impacts of TLR9 agonism on human B cells are incompletely known and the impacts of such treatments on human lymph node B cells are unknown. These are major knowledge gaps given the high TLR9 expression levels in B cells and the importance of lymph nodes for B cell activity. Therefore, we assessed TLR9 agonist-mediated effects on lymph node B cells as planned secondary endpoints within our clinical trial dosing the TLR9 agonist MGN1703 (Lefitolimod) in the context of developing an HIV cure strategy (NCT02443935).

overall_design: RNA-seq for lymph nodes from patients at baseline and after 24 weeks of TLR9 agonist MGN1703 immunotherapy

first: Mariane

middle: H

last: Schleimann

first: Paul

last: Denton


title: Transcriptomic profiling of triple-negative breast cancer (TNBC) patient-derived xenografts (PDX) sensitive and resistant to docetaxel.

city: Hospitalet de Llobregat

first: Eva

last: González-Suárez

state: Barcelona

address: Hospital Duran i Reynals - 3a planta -Gran Via de l'Hospitalet, 199

department: Epigenetics and Cancer Biology

country: Spain

institute: Institut d'Investigació Biomèdica de Bellvitge

summary: SurePrint G3 Human Gene Expression Microarray v2 was used to obtain gene expression profiles of two different TNBC PDX models sensitive to docetaxel and in the docetaxel resistant TNBC PDX models derived from both initially sensitive.

overall_design: RNA was isolated from frozen tumors of two different TNBC PDXs models sensitive to docetaxel and from the docetaxel resistant-derived TNBC PDX models. DNAse treated RNA from each sample (n=22) was hybridized to the SurePrint G3 Human Gene Expression Microarray v2 (ID 039494). The Two-Color Microarray-Based Gene Expression Analysis v. 6.5 (Agilent) was used for the labeling.

first: Jorge

last: Gómez-Miragaya


title: Comparison of gene expression in EPA sensitive and EPA resistant mouse colorectal cancer cells

summary:
Genone wide differential gene expression analysis
Identification of gene linked to mouse colorectal cancer cell resistance to EPA treatment through differential gene expression analysis in an isogenic cell line pair

overall_design: Basal gene expression comparison between the EPA- sensitive MC38 cells and the EPA-resistant MC38r cells (6-fold increase in IC50 value after EPA continuous exposure), total RNA isolated from each cell line

first: M


title: RNA-seq analysis of A498 cell line treated with siSETD2 or si-NC

city: Wuhan

first: Libin

last: Yan

state: Hubei

address: No.1095, Jiefang Avenue

department: Urology

institute: Tongji Hospital,Tongji Medical College, Huazhong University of Science Technology

summary: the coordinated expression of SETD2-miRNAs-MAPK/JNK may be predictive of poor prognostic in patients with RCC. Our findings also emphasize the therapeutic potential of MAP4K4 in RCC therapy and support the development of an effective therapeutic strategy to target MAP4K4 by molecularly targeted approaches.

overall_design: six samples. Including three siSETD2 samples and three control samples

first: Haoran

last: Liu


title: Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming (RNA-seq)

city: Dallas

first: Antonio

last: Fernandez-Perez

institute: UT Southwestern Medical Center

first: Nikhil

last: Munshi


title: HMGA1 and FOXM1 synergistically regulate a common gene network modulating angiogenesis in breast cancer

status: Public on Jul 29 2019

city: Trieste

first: Silvano

last: Piazza

address: localita' Padriciano 99

institute: ICGEB

summary: One of the factors involved in TNBC aggressiveness is HMGA1, a member of non-histone chromatin proteins. The High mobility group A1 is an architectural transcription factor which, by altering chromatin structure and interacting with transcription factors, can regulate the transcription of several genes. HMGA1 protein is defined as an oncofetal protein as it is highly expressed during the embryogenesis while its expression decreases or is absent in adults, and it is re-expressed in a variety of tumors, including breast cancer. Several works established that, in breast cancer, HMGA1 expression is correlated with high tumor grade and tumor metastasis, resistance to therapies and poor prognosis. The goal of this project is to find out in details, which are the genes that are modulated by HMGA1 in MDA-MB-231 triple negative breast cancer cell line model.

overall_design: In order to identify the HMGA1-molecular partners involved in developing TNBC aggressiveness, we performed RNA sequencing analysis (RNA-Seq), on the MDA-MB-231 triple-negative cell line at 24 and 72 hours after HMGA1 silencing, looking for transcription factors as putative upstream regulators of HMGA1-gene networks.

first: Silvia

last: Pegoraro

first: Rossella

last: Zanin

first: Yari

last: Ciani

first: Guidalberto

last: Manfioletti


title: REV-ERBa and REV-ERBb function as key factors regulating Mammalian Circadian Output

city: Kyoto

first: Kazuhiro

last: Yagita

address: Kawaramachi-Hirokoji, Kamigyo-ku

institute: Kyoto Prefectural University of Medicine

summary: The circadian clock regulates behavioural and physiological processes in a 24-h cycle. The nuclear receptors REV-ERBa and REV-ERBb are involved in the cell-autonomous circadian transcriptional/translational feedback loops as transcriptional repressors. A number of studies have also demonstrated a pivotal role of REV-ERBs in regulation of metabolic, neuronal, and inflammatory functions including bile acid metabolism, lipid metabolism, and production of inflammatory cytokines. Given the multifunctional role of REV-ERBs, it is important to elucidate the mechanism through which REV-ERBs exert their functions. To this end, we established a Rev-erba/Rev-erbb double-knockout mouse embryonic stem (ES) cell model and analyzed the circadian clock and clock-controlled output gene expressions. A comprehensive mRNA-seq analysis revealed that the complete knockout of both Rev-erba and Rev-erbb does not abrogate expression rhythms of E-box-regulated core clock genes but drastically changes a diverse set of other rhythmically-expressed output genes. Of note, REV-ERBa/b deficiency does not compromise circadian expression rhythms of PER2, while REV-ERB target genes, Bmal1 and Npas2, are significantly upregulated. This study emphasizes REV-ERBs function to form an essential link between the circadian clock and a wide variety of cellular physiological functions.

overall_design: Control (WT) and Rev-erba/Rev-erbb deficient (KO) mouse ES cells on Per2::Luciferase knock-in background were differentiated for 28 days upon embryoid body formation, treated with 100 nM dexamethasone, and subjected to RNA extraction at 4-h intervals from 12 h to 56 h after dexamethasone stimulation.

first: Yoshiki

last: Tsuchiya

first: Nobuya

last: Koike


title: Transcriptomics of mouse ileal stem cell-derived epithelium grown on transwells

city: St Louis

first: Lisa

middle: Jean

last: Funkhouser-Jones

state: MO

address: 660 S. Euclid Avenue

department: Molecular Microbiology

institute: Washington University School of Medicine

summary: Purpose: The goal of this study was to identify transcriptional changes that occur in mouse ileal stem cell-derived epithelium plated on transwells after the establishment of an air-liquid interface (ALI). Methods: Mouse ileal stem cell spheroids were plated on transwells and grown in L-WRN conditioned medium (top and bottom compartment) for 7 days, at which point the top medium was removed to establish ALI. Samples were collected for sequencing on the day of ALI initiation (non-ALI Day 0) and three days post top medium removal (ALI Day 3). Control samples were also collected from transwells submerged for all 10 days of the experiment (non-ALI Day 3) and from the initial stem cell spheroid cultures. Results: Non-ALI Day 0 and non-ALI Day 3 samples had similar transcriptional profiles, whereas ALI transwells showed upregulation of transcriptional factors that induce secretory cell lineages, as well as a general upregulation of metabolic genes involved in oxidative phosphorylation and downregulation of those involved in glycolysis. Conclusions: Removal of L-WRN conditioned medium from the top compartment of transwells plated with stem cell-derived intestinal epithelial cells establishes an air-liquid interface that changes the metabolic profile of the cultures and initiates a differentiation cascade for intestinal secretory cells such as goblet cells and paneth cells.

overall_design: mRNA profiles of ileal stem cell-derived epithelium on transwells in an undifferentiated or differentiated state (4 replicates each) or undifferentiated ileal stem cell spheroids as a control (3 replicates)

first: Georgia

last: Wilke

first: L

middle: D

last: Sibley


title: Amino acids availability and subsequent metabolic reprogramming sustain endocrine resistance in breast cancer (mRNA)

status: Public on Jul 28 2019

city: Firenze

first: Matteo

last: Ramazzotti

address: viale Morgagni 50

department: Experimental and Clinical Biomedical Sciences

institute: University of Florence

summary: The majority of breast tumours express oestrogen receptor (ER) and receive endocrine therapy (ET) as standard care. Despite its efficacy, ~40% of women relapse with endocrine therapy-resistant (ETR) disease. A global transcription analysis and subsequent integrative approaches of ETR cells showed a deregulated node between miR-23b-3p and the amino acids transporter SLC6A14. Mechanistic analysis supports a model in which such deregulation impairs amino acids metabolism in the ETR cells with subsequent activation of autophagy and enhanced aspartate and glutamate import mediated by the SLC1A2 transporter. The clinical significance of these findings was validated by multiple orthogonal approaches in a large cohort of ET-treated patients, in patient-derived xenografts and in in vivo experiments. Targeting such reprogramming impairs the aggressive features of ETR cells and offers predictive biomarkers and potential targetable pathways to be exploited to combat or delay ETR in ER positive breast cancers.

overall_design: This dataset consist in 9 samples obtained from 3 independent RNA extactions of parental cell line MCF7 (model of breast adenocarcinoma), in presence (MCF7+E2) or absence (MCF7-E2) of oestrogen (E2), and their derivative LTED (Long Term Estrogen Deprived)

first: Manuela

last: Ferracin

first: Andrea

last: Morandi


title: Amino acids availability and subsequent metabolic reprogramming sustain endocrine resistance in breast cancer

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: Amino acids availability and subsequent metabolic reprogramming sustain endocrine resistance in breast cancer (microRNA)


title: Mesenchymal stem/stromal cell engulfment reveals metastatic advantage in breast cancer

city: Ann Arbor

first: Yu-Chih

last: Chen

state: MI

address: 1301 Beal Ave.

institute: University of Michigan

summary: We isolated the engulfing MDA-MB-231 breast cancer cells and would like to see the differences as compared to WT

overall_design: We compared the wild-type (WT) and engulfing (ENG) MDA-MB-231 breast cancer cell line


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

first: LI

last: ZHOU

address: 11 Mandalay Road

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

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

last: Schuster

last: Beck

first: Changhoon

last: Kim

first: John

last: Chambers

first: Marie

last: Loh


title: RNA-Seq study of Hypothalamus from intact and castrated Spring and Autumn migratory Buntings

city: DELHI

first: AAKANSHA

last: SHARMA

state: DELHI

address: CHATTRA MARG

department: ZOOLOGY

institute: UNIVERSITY OF DELHI

summary: We report the mRNA found in hypothalamus tissue of Spring and Autumn migratory Buntings. The aim of this study was to investigate how the castrations affects mRNA makeup of hypothalamus tissue varies under different seasonal migratory states.

overall_design: Study of total mRNA from hypothalamus in intact and castrated seasonal migrants, using Illumina sequencing.

first: Aakansha

last: Sharma

first: Subhajit

last: Das


title: poly-A RNA profiling of Drosophila intermediate neural porgenitors (INPs) of three different temporal states reveal genes involved in temporal patterning

city: Vienna

first: Thomas

middle: Rainer

last: Burkard

address: Dr. Bohrgasse 7

institute: IMBA

summary: Neural stem cells (NSCs) generate highly diverse neurons over time by acquiring new features, a phenomenon called as temporal patterning. However the mechanisms underlying temporal patterning still remains poorly understood. Here, we describe a method that allows to isolate different temporal stages of Drosophila transit amplifying cells called intermediate neural porgenitors (INPs). We identified odd-paired (opa) as the regulator of the transition from first to second temporal stages, which are defined by D and Grh expression. We demonstrated that opa is required for correct neural output and brain morphology.  We showed that opa achieves this transition via repressing D. Together with upstream SWI/SNF complex, D and opa forms an incoheren feed forward loop, which results in successive expression of temporal identities.

overall_design: Comparison of transcriptomes of wild-type INPs of different temporal stages (D+, Grh+ or Ey+) isolated by FACS from Drosophila melanogaster larval brains

first: Merve

last: Abdusselamoglu

first: Elif

last: Eroglu

middle: R

first: Juergen

last: Knoblich


title: Overexpression of UGT2B17 in MEC1 and JVM2 leukemia cell lines

city: Québec

first: Chantal

last: Guillemette

state: Québec

address: 2705 blvd Laurier

department: Faculty of Pharmacy

country: Canada

institute: Laval University

summary: UGT2B17 is a recently identified molecular marker for poor prognosis in Chronic Lymphocytic Leukemia (CLL), which is the most prevalent adult leukemia subtype in the western world. The goal of this study was to determine the effects of UGT2B17 expression in leukemia cells and to find molecular pathways associated with high UGT2B17 expression. We characterized the effects of UGT2B17 in two leukemia cell lines (MEC1 and JVM2) overexpressing a functional UGT2B17 enzyme. A first line of inquiries based on RNA sequencing analysis revealed a series of genes differentially expressed in UGT2B17 overexpressing cells compared to controls, with several genes related to arachidonic acid metabolism and signaling.

overall_design: The MEC-1 and JVM-2 cell lines were transfected with an expression vector containing the coding sequence of human UGT2B17. MEC1 control cells have a stable repression of UGT2B17 by shRNA knock-down, while JVM2 controls are transfected with an empty pcDNA6 vector. Each condition was analyzed in triplicate.

first: Eric

last: Allain

first: Michèle

last: Rouleau


title: Next Generation Sequencing Quantitative Analysis of Small RNA in Livers of Adult Male Offspring of Obese Female Mice

status: Public on Jul 27 2019

city: Cambridge

first: Lucas

last: Pantaleao

address: 11A Glisson Road

institute: University of Cambridge

summary: Obesity during pregnancy is associated with increased risk of non-alcoholic fatty liver disease in the offspring. We used RNA next generation sequencing analysis (HiSeq2000) to have a glance at the miRNome in twelve week-old male offspring exposed to maternal obesity and weaned onto an obesogenic diet.

overall_design: Thirty-five female C57BL/6J mice were fed either a standard control diet, RM1 [7% simple carbohydrates/3% lipids (w/w)] or an energy-rich obesogenic diet [10% simple carbohydrates/20% lipids (w/w)] plus sweetened condensed milk [55% simple carbohydrates, 8% lipids, 8% protein (w/w), supplemented with mineral and vitamin mix AIN93G]. Female mice were mated, and maintained on their diets until weaning. On post-natal day 21, male offspring were weaned onto either standard chow (RM1) or the obesogenic diet, generating 4 experimental groups: maternal and offspring control diet (CC), maternal control diet and offspring obesogenic diet (CO), maternal obesogenic diet and offspring control diet (OC), maternal and offspring obesogenic diet (OO). At 12 weeks of age, mice were killed by raising on a fasted state. Liver were dissected, and snap frozen. Three high quality RNA samples from each group were randomly selected and subjected to a cDNA library preparation for further sRNA sequencing using TruSeq RNA Library Preparation kit

middle: C

first: Susan

last: Ozanne


title: Small RNA Expression in the Chorioallantois, Endometrium and Serum of Mares Following Experimental Induction of Placentitis

city: Lexington

first: Shavahn

last: Loux

state: KY

address: 1400 Nicholasville

department: Veterinary Science

institute: University of Kentucky

type: Non-coding RNA profiling by high throughput sequencing

summary: To better characterize placentitis, we examined the sRNA expression patterns occurring in the endometrium, chorioallantois and serum of mares.   Disease was induced in 10 mares via intracervical inoculation of Streptococcus equi ssp. zooepidemicus, either with moderate or high levels of inoculum; three un-inoculated gestationally-matched mares were used as controls.  Matched chorioallantois and endometrium were sampled in two locations: region 1 - main lesion by cervical star with placental separation; and region 2 - gross inflammation without placental separation.

overall_design: Next-generation sequencing of two regions of the chorioallantois and endometrium in mares with and without experimentally-induced placentitis

first: Claudia

middle: B

last: Fernandes

first: Pouya

last: Dini

first: Kai

last: Wang

first: Xiaogang

last: Wu

first: David

last: Baxter

first: Mats

last: Troedsson

first: Edward

middle: L

last: Squires

first: Barry

last: Ball


title: QuantSeq analysis in the hippocampus of WT and PHF2 t/g mice

city: Seoul

first: Hyejin

last: Kim

address: 103 Daehakro

country: South Korea

institute: Seoul National University College of Medicine

summary: Long-term memory formation is attributed to experience-dependent gene expression. Dynamic changes in histone methylation status are essential for epigenetic regulation of memory consolidation-related genes. Here, we demonstrated that plant homeodomain finger protein 2 (PHF2) histone demethylase is upregulated in the mouse hippocampus during experience and plays an essential role in memory formation. QuantSeq analysis was performed to examine differential gene expression in the hippocampus of WT and PHF2 t/g mice. Transgenic mice were created by injecting the CMV-Flag-PHF2 vector into fertilized eggs from C57BL6 mice. Transgenic lines were established from 9 founders that were identified via PCR-based genotyping. Among the transgenic lines, mice with high PHF2 expressed brains were singled out for breeding. First, selected heterozygote males were bred with heterozygote females which produced homozygote, heterozygote and wild littermates. Since it is difficult to differentiate between hetero and homo mice with genotyping, we separated homo mice from hetero mice by breeding each of hetero and homo mice with wild type mice and confirming the genotypes of their offspring. In other words, hetero mice bred with wild type mice would have both wild type and hetero genotype of offspring, while homo mice bred with wild type mice would only have hetero genotype of offspring. Through this process, we particularly selected the homo mice and this transgenic line was used and maintained for this experiment.

overall_design:
In order to examine the change in hippocampus mRNA between WT and PHF2 t/g mice, we performed QuantSeq analysis. In result, compared to the WT group, PHF2 t/g group contained 119 up-regulated genes and 56 down regulated genes.
Hippocampus mRNA profiles of 16-weeks old wild type (WT) and PHF2 t/g mice were generated by sequencing, in triplicate, using Illumina NextSeq 500.

first: Hye-Jin

first: Sung-Won

last: Hur

first: Jun-Bum

last: Park

first: Jieun

last: Seo

first: Jae-Jin

last: Shin

first: Seon-Young

first: Myoung-Hwan

first: Do-Hyun

last: Han

first: Jong-Wan

first: Joo-Min

first: Sang-Jeong

first: Yang-Sook

last: Chun


title: Next Generation Sequencing Transcriptome Quantitative Analysis of Livers of Adult Male Offspring of Obese Female Mice

first: Lucas

last: Pantaleao

summary: Obesity during pregnancy is associated with increased risk of non-alcoholic fatty liver disease in the offspring. We used RNA next generation sequencing analysis (HiSeq2000) to have a snapshot of the liver transcriptome in twelve week-old male offspring exposed to maternal obesity and weaned onto an obesogenic diet.

overall_design: Thirty-five female C57BL/6J mice were fed either a standard control diet, RM1 [7% simple carbohydrates/3% lipids (w/w)] or an energy-rich obesogenic diet [10% simple carbohydrates/20% lipids (w/w)] plus sweetened condensed milk [55% simple carbohydrates, 8% lipids, 8% protein (w/w), supplemented with mineral and vitamin mix AIN93G]. Female mice were mated, and maintained on their diets until weaning. On post-natal day 21, male offspring were weaned onto either standard chow (RM1) or the obesogenic diet, generating 4 experimental groups: maternal and offspring control diet (CC), maternal control diet and offspring obesogenic diet (CO), maternal obesogenic diet and offspring control diet (OC), maternal and offspring obesogenic diet (OO). At 12 weeks of age, mice were killed by raising on a fasted state. Liver were dissected, and snap frozen. Three high quality RNA samples from each group were randomly selected and subjected to a cDNA library preparation for further mRNA sequencing using TruSeq RNA Library Preparation kit

first: Susan

last: Ozanne

first: Ania

last: Wilczynska


title: NHLRC1 re-expression in cancer cells

status: Public on Jul 26 2019

city: lexington

first: ramon

middle: chang

last: sun

address: 741 S. Limestone, BBSRB, B177

institute: University of kentucky

summary: Flag-tagged NHLRC1 expression in three different cancer cell lines

overall_design: RNAseq

first: Matthew

last: Gentry

first: Ramon

last: Sun


title: Identification of microRNA-668 and microRNA-489 targets by RISC immunoprecipitation

city: Milwaukee

first: Pengyuan

last: Liu

state: Wisconsin

address: 8701 Watertown Plank Road

institute: Medical College of Wisconsin

summary: MicroRNAs inhibits their target mRNA translation by forming RISC complex. Immunoprecipitation of RISC will pull down both microRNA and their target mRNAs. To systemetically examine the potential targets of microRNA-668 and microRNA-489, HEK293 cells were overexpressed with negative control, microRNA-668, or microRNA-489 mimics. Both total RNA samples and RNA samples from RISC complex pulled down by Ago-2 immunoprecipitation were examined by RNA-seq.

overall_design: RNAs from 6 groups of samples were analyzed (NC total, mir-668 total, mir-489 total, NC IP, mir-668 IP, mir-489 IP). Each groups has three repeats (n=3).

first: Qingqing

last: Wei

first: Zheng

last: Dong

first: Yong

first: Mingyu

last: Liang


title: mRNA and miRNA expression changes at the neurovascular unit reveal a role for autophagy and DNA binding in the cerebral microvasculature of the ageing brain  (human)

city: Sheffield

first: Paul

middle: Roy

last: Heath

state: S. Yorks

address: SITraN, 385a Glossop Road

department: Academic Neurology Unit

institute: University of Sheffield

summary: Objective: To examine changes in the transcriptome of the neurovascular unit in ageing individuals

overall_design: Gene expression profiling utilised total RNA extracted from LCM derived neurovascular unit derived from human prefrontal cortex sections of individuals of different ages.

first: Emily

middle: F

last: Goodall

first: Vicki

last: Leach

first: Chunfang

last: Wang

first: Johnathan

last: Cooper-Knock

first: David

last: Baker

last: Drew

first: M

middle: J

last: Saffrey

first: Julie

last: Simpson

first: Ignacio

middle: A

last: Romero

first: Stephen

last: Wharton


city: Amherst

first: Derek

last: Lovley

address: University of Massachusetts at Amherst, Dept. of Microbiology, Morrill IV north room 202

department: Microbiology

institute: University of Massachusetts Amherst

summary: Gene expression in a Geobacter sulfurreducens strain overexpressing the two-component system GsuTCS1

overall_design: Three biological replicates were hybridized in duplicate. Experimental (GsuTCS1 overexpression) was labeled with cy5, control (vector) was labeled with cy3.

first: Toshiyuki

last: Ueki


title: RNA seq analysis of SHP099 treated Leukemic Cells Expressing Genetic and Epigenetic Mutations

city: Indianapolis

first: Chi

last: Zhang

state: IN

institute: INDIANA UNIVERSITY

summary: 10 to 30% normal karyotype acute myeloid leukemia (AML) patients express mutations in regulators of DNA methylation such as TET2 or DNMT3A in conjunction with activating mutation in receptor tyrosine kinase, FLT3, which can be present in up to 50% of normal karyotype AML patients. These patients have poor prognosis since they do not respond well to established therapies. Here, utilizing mouse models of AML that recapitulate cardinal features of the human disease and bear a combination of loss of function mutations in either Tet2 or Dnmt3a along with expression of Flt3ITD, we show that inhibition of SHP2, a protein tyrosine phosphatase, essential for cytokine receptor signaling, including FLT3, by a small molecule allosteric inhibitor, SHP099, impairs growth and induces differentiation of leukemic cells without impacting normal hematopoietic cells. We further show that SHP099 normalizes gene expression program associated with increased cell proliferation and self-renewal in leukemic cells by down regulating the Myc signature. Our results provide a new and more effective target for treating a subset of AML patients bearing a combination of genetic and epigenetic mutations.

overall_design: To elucidate the mechanism of action of SHP099 on leukemic myeloid cells, lineage depleted cells were isolated from bone marrow of Tet2-/-Flt3ITD mice and cultured in presence of cytokines (SCF, IL-6, IL-3) to expand primitive myeloid committed cells. The cells from Tet2-/-Flt3ITD mice were treated with SHP099 or vehicle for 24 hr and RNA-seq was performed on samples from 3 independent cultures established from individual mice. For comparison of gene expression profile, lineage depleted wild type (WT) cells were similarly isolated and cultured.

first: Ruchi

last: Pandey

first: Reuben

last: Kapur


title: Comparative gene expression profiling of human primary endotheliocytes cultivated on polyurethane-based electrospun 3D matrices and natural decellularized vein

city: Novosibirsk

first: Petr

last: Laktionov

address: Lavrenitev ave 8/2

country: Russia

institute: Institute of molecular and cellular biology SD RAS

summary: We have evaluated the functional state of HUVEC cultivated on the surface of autologous decellularized human umbilical vein and electrospun polyurethane-based matrices by NGS gene expression profiling

overall_design: In this study gene expression profiling of HUVEC (human endothelial cells from the umbilical vein) cultivated on the basal layer of decellularized human umbilical vein (dUV), tissue culture polystyrene (TCPS) and electrospun 3D matrices produced from TECOFLEX™ EG-80A polyurethane (Tec), TECOFLEX™ EG-80A polyurethane with gelatin (Tec-Gl) and TECOFLEX™ EG-80A polyurethane with gelatin and bivalirudin (Tec-Gl-Bv). Cells were obtained from three biological donors.

first: Vera

last: Chernonosova

first: Ivan

last: Murashov

first: Alexander

last: Karaskov

first: Pavel


title: CD93 negatively regulates astrogenesis in response to MMRN2 through transcription repressor ZFP503 in the developing brain

city: Beijing

first: Jianwei

last: Jiao

state: Beijing

address: 1 Beichen West Road

department: State Key Laboratory of Reproductive Biology

institute: Institute of Zoology, Chinese Academy of Sciences

summary: Astrogenesis is repressed in the early embryonic period, and occurs in the late embryonic period. A variety of external and internal signals contribute to the sequential differentiation of neural stem cell. Here, we discover that the immune-related CD93 plays a critical role in the onset of astrogenesis in mouse. CD93 expression is detected in neural stem cell and neuron but bot in astrocyte, and declines as differentiation proceeds. CD93 knockout increases astrogenesis at the expense of neuron production during the late embryonic period. CD93 responds to the ECM protein MMRN2 to trigger the repression of astrogenesis. In mechanism, CD93 delivers the signal through a series of phosphorylation cascade to β-Catenin, then β-Catenin transfers to nucleus to activate Zfp503 transcription. The transcription repressor ZFP503 inhibits Gfap transcription by binding to the Gfap promoter with the help of Grg5. Furthermore, the abnormal differentiation in astrogenesis and neurogenesis caused by CD93 knockout results in autism-like behaviors. Taken together, our study reveals that CD93 is a negative regulator in controlling the proper time of astrogenesis, and provides a new sight in therapy for psychiatric disorders.

overall_design: mRNA profiles from E16 cerebral cortex of wild type and CD93 KO mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.

first: Qingli

last: Liang

first: Libo

last: Su


title: Microarray analysis of skeletal muscle in aged mice

city: Kyoto

first: Yasutomi

last: Kamei

address: 1-5 Shimogamo-Hangicho, Sakyo-ku

institute: Kyoto Prefectural University

summary: Sarcopenia is the age-induced, progressive loss of skeletal muscle mass and function, which is accompanied by reduced muscle performance. Individuals with sarcopenia often become bedridden or dependent on a wheelchair, leading to decreased quality of life. In this study, to better understand changes in skeletal muscle during sarcopenia, we performed a microarray analysis of skeletal muscle in young (13-week-old) and aged (26-month-old) mice. The microarray data shows that expression of the enzymes related to glucose and polyamine metabolism were decreased in aged mice compared with young mice.

overall_design: For microarray analysis, RNA was isolated from the gastrocnemius skeletal muscle of young mice (13 weeks of age) and aged mice (26 months of age). Samples from young and aged mice (N = 3 for each group) were used.


title: miRNA profiling of MWCNT exposed mice

city: Morgatown

first: Nancy

middle: Lan

last: Guo

state: WV

address: 2816 Health Sciences Center

department: Occupational and Environmental Health Sciences

institute: West Virginia University

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Macaca mulatta
Homo sapiens
Mus musculus
Rattus norvegicus

overall_design: Refer to individual Series


title: miRNAs expression in murine liver during Schistosoma japonicum infection

city: Nanjing

first: Yangyue

last: Ni

state: Jangsu

address: 101 Longmian Avenue

department: Department of Pathogen Biology

institute: Nanjing Medical University

summary: It is well recognized that parasitic helminth infections, which afflict more than one billion people globally, correlate with a decreased prevalence of metabolic diseases, including obesity and type 2 diabetes, but the molecular mechanisms involved remain to be determined. Using microarrays, we quantified the temporal gene expression profiles in the liver of Schistosoma japonicum-infected C57BL/6 mice at 9 weeks post infection with that from uninfected mice as controls.  More than 150 miRNAs were differentially expressed in the liver during S. japonicum infection, and miRNA-mRNA network would provide new evidence for the negtive correlation between S. japonicum infection and metabolism.

overall_design: miRNAs expression in the livers of C57BL/6 mice was measured at 9 weeks after S. japonicum infection.  5 liver samples combined from uninfected mice or S. japonicum-infected mice.

first: Zhipeng

last: Xu

first: Yuxiao

last: Zhu

first: Ran

last: Liu

first: Fan

first: Min

last: Hou

first: Minjun

last: Ji


title: miRNA profiling of lung tissues exposed to MWCNT

summary:
MicroRNA array data for 144 Mouse lung tissue RNA samples were processed, out of which, 139 passed the visual Quality Control (QC) and  data QC.
To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, we determined up- and down-regulated miRNA expression in lung tissue at 1 year post-exposure.

overall_design: Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration and lactate dehydrogenase (LDH) activity and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 month, 6 months, and 1 year post-exposure. As MWCNT are often structurally compared to asbestos, a 120 μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all 3 post-exposure times. Asbestos exposure elevated LDH activity at all 3 post-exposure times and PMN infiltration at 1- and 6 months post-exposure.


title: The effect of ATR inhibition on the replication timing program

city: Pittsburgh

first: Hatice

middle: Ulku

last: Osmanbeyoglu

address: 5117 Centre Ave

institute: University of Pittsburgh

summary: As a part of the project looking into the role of ATR in regulating replication initiation, we report the replication timing analysis of the U2OS cells treated with ATR kinase inhibitor AZD6738

overall_design: U2OS cells were treated with DMSO or 5uM AZD6738 for 30 minutes before labelling of the ongoing replication with 10uM BrdU.

first: Tatiana

middle: N

last: Moiseeva

first: Norie

last: Sugitani

first: Christopher

last: Bakkenist

first: Chenao

last: Qian

middle: U


title: Transcriptome analysis of CD4+ T cells differentiated from wild-type and tumor bearing C57BL/6J mice

city: Dijon

first: Romain

last: Boidot

address: 1, rue Pr Marion

country: France

institute: CGFL

summary: We report a crosstalk between T follicular helper (Tfh) and Th2 cells mediated by the Prostaglandin D2 (PGD2) and it's deletrious impact in cancer.

overall_design: Examination of the expression profile of CD4+ T cells after 48h of in vitro differentiation and cell sorting from tumor bearing C57BL/6J mice.

first: MARY

last: Romain

first: BOIDOT

first: VEGRAN

last: Frédérique

first: GHIRINGHELLI

last: François


title: The ribosomal prolyl-hydroxylase OGFOD1 decreases during cardiac differentiation, modulates translation and spliceosomal processes

city: Bethesda

first: Yanqin

last: Yang

state: Maryland

address: 10 Center Dr.

institute: NIH

summary: In this study we provide the gene expression profiles and MISO analyses for alternative splicing events such as exon skipping in wildtype versus OGFOD1 (oxoglutarate, glucose and iron dependent protein 1)-knock-out iPSC-derived cardiomyocytes, we further compare the profiles to wildtype which were treated with a drug  inhibiting α-ketoglutarate-dependent hydroxylases (dimethyloxalylglycine) versus vehicle control. Altered translation and splicing processes play a role in differentiation processes and have been shown to be involved in disease progression in e.g. heart failure. OGFOD1 is a ribosomal prolyl-hydroxylase and which influences translation, here we show its further importance in cardiac differentiation and alternative splicing.

overall_design: Biological replicates of RNA-seq data from wildtype versus OGFOD1 (oxoglutarate, glucose and iron dependent protein 1)-knock-out iPSC-derived cardiomyocytes; wildtype treated with dimethyloxalylglycine or vehicle control

first: Andrea

last: Stoehr

first: Elizabeth

last: Murphy


title: Genome-wide analysis of coding and long non-coding RNAs involved in cabbage cuticular wax biosynthesis

city: Shanghai

first: Xiaowei

address: Jinqi Road No.1000

institute: Shanghai Academy of Agricultural Sciences

summary: We report the application of high-throughput RNA sequencing for comparing the expression levels of the coding and long noncoding RNAs (lncRNAs) in leaf samples from a glossy mutant nwgl and its wild-type (WT) in cabbage. By obtaining over 163.35 Gb cleaned data generated from six libraries (on average, more than 26.48 Gb clean data for each sample replicate), we identified 1247 differential expressed genes (DEGs) and 148 differential expressed lncRNAs in nwgl leaves relative to WT. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEGs and cis-regulated target genes for differential expressed lncRNAs were significantly enriched in wax and lipid biosynthetic and/or metabolic processes. Our results provide the novel foundation to explore the complex molecular basis of cuticular wax biosynthesis.

overall_design: Identification of differential expressed coding and long noncoding RNAs between a glossy mutant nwgl and its wild-tye (WT).

first: Xiang

last: Tai


title: Retention of paternal epigenetic memory in the developing teleost germline [alt-splicing]

city: Sydney

first: Ksenia

last: Skvortsova

state: NSW

address: 384 Victoria St, Darlinghurst

department: Genomics and Epigenetics

country: Australia

institute: Garvan Institute

summary: Two waves of DNA methylation reprogramming occur during mammalian embryogenesis; during preimplantation development and during primordial germ cell (PGC) formation. However, it is currently unclear how evolutionarily conserved these processes are. Here we characterize the DNA methylomes of zebrafish PGCs at four developmental stages and unravel retention of paternal epigenetic memory, in stark contrast with the findings in mammals. Gene expression profiling of zebrafish PGCs at same developmental stages revealed that the embryonic germline is defined by a small number of markers that display strong developmental stage-specificity and that are uncoupled from DNA methylation-mediated regulation.

overall_design: In order to perform alternative splicing analysis, PGC 7 hpf, PGC 24 hpf, Soma 7 hpf and Soma 24 hpf low-input RNA-seq samples have been sequenced on an additional lane of Nova-seq 6000 and analyzed together with the previous RNA-seq run (GSE122480).

first: Ozren

last: Bogdanovic


title: Retention of paternal epigenetic memory in the developing teleost germline [BiSulfite-seq]

type: Methylation profiling by high throughput sequencing

overall_design: Using WGBS we have profiled adult zebrafish liver methylome


title: mRNA and miRNA expression changes at the neurovascular unit reveal a role for autophagy and DNA binding in the cerebral microvasculature of the ageing brain (mouse)

first: Paul

last: Heath

summary: Objective: To examine changes in the transcriptome of the neurovascular unit in ageing individual mice

overall_design: Gene expression profiling utilised total RNA extracted from LCM derived neurovascular unit derived from murine cortex sections of individuals of different ages.

first: Emily

last: Goodall

first: Vicki

last: Leach

first: Chunfang

last: Wang

first: Johnathan

last: Cooper-Knock

first: David

last: Baker

last: Drew

first: M

last: Saffrey

first: Julie

middle: E

last: Simpson

first: Ignacio

last: Romero

first: Stephen

last: Wharton


title: TRIM33 deficiency in mature myeloid cells impairs resolution of colonic inflammation

city: Paris

first: Franck

last: Letourneur

address: 22 rue mechain

institute: INSERM

summary: Mature myeloid cells play a crucial role in the pathogenesis of Crohn disease (CD) but the molecular players that regulate their functions in CD are not fully characterized. Here we show that Trim33 mRNA level is decreased in CD patient’s blood monocytes and characterize TRIM33 functions in monocytes during dextran sulfate sodium (DSS) induced colitis. Mice deleted for trim33 only in mature myeloid cells (Trim33-/- mice) display an impaired resolution of colonic inflammation. This deficiency is associated with an increased number of blood and colon neutrophils and monocytes and a decreased number of colonic macrophages. In accordance, Trim33-/- monocytes are less competent that wild type monocytes for recruitment and differentiation into macrophages at the inflammatory site. Furthermore, during resolution of DSS-induced colitis, Trim33-/- colonic macrophages display an impaired M1/M2 switch and express a low level of membrane bound TNFα known to regulate resolution of inflammation. Altogether, these results show an important role of TRIM33 in monocytes/macrophages during the resolution of DSS-induced colonic inflammation and pinpoint TRIM33 as a novel Crohn disease biomarker and as a potential therapeutic target.

overall_design: monocytes cells cells from blood of C57BL/6 LyzCre TRIM33  mice vs WT mice sorted as CD11b+ CD115+ Ly6C high for Tmem using a FACS-ARIA3 flow cytometer.

first: Aude

last: PARCELIER

first: Cecile

last: MATHE

first: Vilma

last: BARROCA

first: Claire

last: TORRES

first: FEDERICA

last: FERRI

first: DANIEL

last: LAWANDOWSKI

first: Oceane

last: DINET

first: Gilles

last: BOSCHETTI

first: Vanessa

last: PETIT

first: Paul-Henri

last: ROMEO


title: Gcn5 Controls Virulence of the Human Fungal Pathogen Candida albicans through Multiple Regulatory Networks

city: NEWARK

first: Neeraj

last: Chauhan

state: New Jersey

address: 225 Warren Street

department: Department of Microbiology, Biochemistry & Molecular Genetics

institute: NJMS-PHRI

summary: Transcriptomic analysis of wild type and GCN5-deficient Candida albicans cells prior to and after treatment with Caspofungin 15 min and 45 min was done to determine the transcriptional changes in these strains

overall_design: RNA Sequencing was performed of wild type and Gcn5-deficient Candida albicans strains prior to and after treatment with Caspofungin 15 min and 45 min. Cells were grown to the exponential phase in YPD at 30oC. Aliquots were harvested for RNA isolation and to the remaining culturecaspofungin was added to a final concentration of 10 ng/ml. After 15 min and 45 min incubation at 30°C cells were harvested for RNA isolation. Three biological replicates for each time-points of wild-type (wt) treated with caspofungin (CSP, 0, 15 and 45 min), as well as homozygous deletion (gcn5∆/∆) and two biological replicates for the remaining two time-points of gcn5∆/∆ (CSP, 15 min and 45 min) were sequenced

first: Raju

last: Shivarathri


title: Genome wide screen of CREB and CRTC2 occupancy in LKB1 mutant NSCLC cell line A549

city: San Diego

first: Ezra

last: Wiater

state: CA

address: 10010 N Torrey Pines Rd

department: PBL

institute: Salk Institute For Biological Studies

summary: CREB and CRTC2 ChIPseq analysis in LKB1-deficient and LKB1-reconstituted A549 NSCLC cells

overall_design: A549 cells expressing the pBabe vector or full length LKB1 were cultured and ChIPseq for CRTC2 and CREB was performed.

first: Laura

last: Rodón

first: Robert

last: Svensson

first: Matthew

middle: H

last: Chun

first: Wen-Wei

last: Tsai

first: Lillian

last: Eichner

first: Reuben

last: Shaw

first: Marc

last: Montminy


title: miRNA profiling of blood samples from MWCNT exposed mice

first: Nancy

last: Guo

summary:
Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 yr postexposure.
To identify non-invasive miRNA biomarkers, miRNA profiling was performed in blood samples collected from MWCNT exposed mice.

overall_design: MWCNT used in this study were obtained from Hodogaya Chemical Company (MWNT-7, lot #05072001K28) and manufactured using a floating reactant catalytic chemical vapor deposition method followed by high temperature thermal treatment in argon at 2500°C using a continuous furnace (Kim et al. 2005). Extensive characterization of the MWCNT was previously published (Porter et al., 2010). In summary, the number of walls ranged from 20 to 50, median length was 3.86 ± 1.9 μm, and count mean width was 49 ± 13.4 nm. Trace metal contamination was 0.78%, with sodium (Na, 0.41%) and iron (Fe, 0.32%) being the two major metal contaminants. The crocidolite asbestos [(Na2(FeIII)2(FeII)3Si8O22(OH2)] used is this study was originally obtained from a mine in the Kalahari Desert, South Africa (Cheng et al., 1999) and previously characterized. Briefly, asbestos had a median fiber length of 11.5 μm (range: 2 – 30 μm), diameter of 160 – 800 nm, surface area of 17.1 m2/g, and Fe content (% weight) of 18% (Cheng et al., 1999, Shvedova et al., 2014). Endotoxin levels in the MWCNT and asbestos samples were below the levels of detection (Cheng et al., 1999; Porter et al., 2010). Male C57BL/J6 mice (7 weeks old, average weight 21.19 g ± 0.06 g) were obtained from Jackson Laboratories (Bar Harbor, ME). This study consisted of 3 components: bronchoalveolar lavage (BAL), pulmonary histopathology, and lung tissue mRNA microarray analysis. Each component consisted of 8 mice per exposure group (dispersion media [DM, negative control]; 1, 10, 40, or 80 μg MWCNT; 120 μg crocidolite asbestos [positive control]) to be sacrificed at 1, 6 or 12 months post-exposure, for a total of 144 mice per each arm of BAL, pulmonary histopathology, and lung tissue/blood miRNA microarray analysis and 432 mice for the total study.


title: Retention of paternal epigenetic memory in the developing teleost germline [WGBS]

first: Ksenia

last: Skvortsova

overall_design: Using WGBS we have profiled transcriptomes of zebrafish primordial germ cells (PGCs) and age-matched somatic cells at 4 (blastula), 7 (gastrula), 24 (pharyngula prim-5) and 36 (pharyngula prim-25) hours post-fertilization

first: Ozren

last: Bogdanovic


title: Multiwalled carbon nanotube-induced blood genomic changes following aspiration exposure in mice: A 1-year postexposure study.

summary:
Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to perform genome-wide mRNA profiling in mice blood to identify non-invasive blood based biomarkers for medical and occupational surveillance.
The pathological results in this 1-year MWCNT post-exposure study was previously published in Snyder-Talkington et al. J Toxicol Environ Health A. 2016;79(8):352-66. doi: 10.1080/15287394.2016.1159635. Epub 2016 Apr 19. PMID: 27092743

overall_design: We evaluated bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration and lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs after 1 year post-exposure to a dispersion media (DM) control (Porter et al., 2008); 1, 10, 40, or 80 ug MWCNT; or 120 g crocidolite asbestos by pharyngeal aspiration. Additionally, we determined gene expression changes in mouse lung tissue with increasing doses of MWCNT at 1 year post-exposure to determine potential underlying mechanisms of fibrotic signaling after exposure to MWCNT.


title: Neonatal mice adopt to pressure overload by inducing cardiomyocyte proliferation and angiogenesis

city: Mannheim

first: Joerg

last: Heineke

state: Baden Wuttemberg

address: Ludolf-Krehl-Str. 7-11

department: – Department of Cardiovascular Research (HKF)

country: Germany

institute: Medizinische Fakultät Mannheim

summary: Backgound: Cardiac pressure overload, for example in patients with aortic stenosis, induces irreversible damage in the myocardium leading to cardiac dysfunction, cardiomyocyte hypertrophy and interstitial fibrosis. We therefore hypothesized that insufficient cardiac regeneration might contribute to the progression of pressure overload dependent disease. Here, we aimed to elucidate whether pressure overload in the regenerative stage shortly after birth could lead to a more adaptive cardiac response than in the non-regenerative stage in mice.nTAC in the non-regenerative stage induced cardiac dysfunction, myocardial fibrosis and cardiomyocyte hypertrophy. In contrast, during induction of nTAC in the regenerative stage, cardiac function remained intact and this was associated with enhanced myocardial angiogenesis and innervation as well as increased cardiomyocyte proliferation, but neither hypertrophy nor fibrosis. Mechanistically, inhibition of cardiomyocyte proliferation and angiogenesis in nTAC in the regenerative phase by rapamycin triggered mortality and myocardial fibrosis, which both also similarly occurred upon inhibition of angiogenesis by PTK787, suggesting that both processes are essential for the adaptive cardiac response to nTAC. A comparative genome-wide transcriptomic analysis between hearts after nTAC in the regenerative versus the non-regenerative stage defined differentially expressed functional gene classes, and a related bioinformatics analysis suggested the transcription factor GATA4 as master regulator of the regenerative gene-program. Indeed, cardiomyocyte specific deletion of GATA4 converted the regenerative nTAC into a non-regenerative, maladaptive response.tablished a new model of neonatal pressure-overload in mice, which when applied in the regenerative postnatal stage, triggers a purely adaptive myocardial response. Employing this model to identify new regulators might lead to novel therapeutic strategies to combat pressure overload induced myocardial disease.

overall_design: We established a transverse aortic constriction protocol in neonatal mice (nTAC) that could be induced either in the regenerative (at postnatal day P1) or in the non-regenerative stage (at P7) after birth. Echocardiography was used to assess cardiac dimensions and function in neonatal mice. Myocardial histological examinations were conducted to assess interstitial fibrosis, angiogenesis, innervation and cardiomyocyte proliferation. RNA deep sequencing was employed to compare the cardiac gene-expression pattern between nTAC in the regenerative versus the non-regenerative stage.

first: Mona

middle: M

last: Mohammadi

first: Julio

last: Cordero


title: The effect of engineered del(7q) on induced pluripotent stem cells (iPSCs) derived from patients with Shwachman Diamond Syndrome (SDS).

city: Cambridge

first: Gabriela

last: Alexe

state: MA

address: 415 Main St.

department: Computational Biology and Bioinformatics

country: USA

institute: Broad Institute

summary: Monosomy 7 or deletion of 7q (del(7q)) frequently arise in inherited and acquired bone marrow failure, and are associated with progression to high grade Myelodysplastic Syndrome (MDS) and acute leukemia.  Current non-transplant approaches to treat marrow failure may be complicated by potential stimulation of clonal outgrowth.  To study the biological consequences of del(7q) within the context of a failing marrow, we utilized induced pluripotent stem cells (iPSCs) derived from patients with Shwachman Diamond Syndrome (SDS) and genomically engineered a deletion of (7q). Deletion of 7q failed to confer a relative fitness advantage in either pluripotent SDS iPSC or in iPSC-derived SDS CD34+ cells.  The TGF-beta pathway was the top differentially regulated pathway in transcriptome analysis with the TGF pathway found activated in SDS-iPSCs, compared to SDS-del(7q) iPSCs.  Increased phosphorylation of SMAD2 in SDS-iPSCs was reduced following del(7q) and increased upon restoration of 7q diploidy, in support of an effect of 7q dosage on the activation status of the TGF-beta pathway in SDS.  Inhibition of the TGF-beta pathway rescued hematopoiesis in SDS-iPSCs and in primary bone marrow cells from SDS patients without improving hematopoiesis of the SDS-del(7q) cells.  Together, these results utilizing an iPSC model of MDS in BMF identified a targetable vulnerability for potential therapeutic strategies to ameliorate bone marrow failure without promoting outgrowth of the del7q clone.

overall_design: RNA-seq transcriptome profiling of triplicate iPSCs with and without deletion of chr7q.  iPSCs were  generated from bone marrow mononuclear cells of two patients with SDS that carried homozygous c.258+2T>C SBDS mutations. The long arm of chromosome 7 was deleted by targeted insertion of two inverted loxP sites into the long arm of chromosome 7 followed by transient expression of Cre-recombinase. iPSCs samples without chromosome 7q deletion were labeled SDS. iPSCs samples with chromosome 7q deletion were labeled SDS del(7q).

first: Akiko

last: Shimamura

first: Melisa

last: Ruiz-Gutierrez


title: Induced pluripotent stem cell modeling of bone marrow failure and MDS identifies therapeutic targets

overall_design: Refer to individual Series


title: ChIP-seq analysis reveals alteration of H3K4 trimethylation occupancy in cancer-related genes by cold atmospheric plasma

city: Goyang-si

first: sung bin

last: park

state: Gyeonggi-do

address: 32, Dongguk-ro, Ilsandong-gu

department: Department of Life Science

institute: Dongguk University-Seoul


title: Transcriptomes of  C. albicans aox2 deletion mutant or wild-type C. albicans SC5314 treated with pyocyanin

city: Canterbury

first: Lucian

last: Duvenage

address: Giles Lane

department: School of Biosciences

institute: University of Kent

summary: We compared the early gene expression profiles (30 min) of log-phase wild type C. albicans SC5314  growing in YPD at 30 °C to an aox2 deletion mutant or to wild-type SC5314 in response to 80 micromolar pyocyanin or 0.5 mM SHAM

overall_design: C. albicans aox2 deletion mutant  or wild type treated with respiration inhibitors in duplicate and high-throughput sequencing using Illumina NextSeq500


title: Expression profile of lncRNAs and mRNAs in 4 brain regions of adult mouse

city: Hefei

first: xiaoyuan

last: song

address: Huangshan Road

institute: University of Science & Technology of China

summary: We aimed to decipher the spatial expression landscape of well-annotated lncRNAs in brain regions. To this end, we dissected adult male mice brain tissues from olfactory bulb (OB), hypothalamus (Hypo), hippocampus (Hippo) and cerebellum (Cereb) and subjected to Arraystar Mouse LncRNA Microarray V3.0. We found a new type of genome organization formed by highly conserved lncRNA cluster and nearby TF in the non-imprinting regions that is associated with human CNS disorders.

overall_design: 10-week-old male BALB/c mice (Vital River Laboratories, Beijing, China) were used in this study and the mice were housed in a temperature-controlled room under a 12 hours light/12 hours dark cycle, with free access to food and water ad libitum. Three mice were used for microarray analysis, and three to ten mice were used for validation. The mice were euthanized by cervical dislocation and brains were carefully dissected using stereomicroscope to separate the four experimental brain regions (olfactory bulb, hypothalamus, hippocampus as well as cerebellum) according to mouse brain atlas (26).

first: Fei

last: Wang

first: Dalong

last: Ren

first: Xiaolin

last: Liang

first: Shengwei

last: Ke

first: Bowen

last: Zhang

first: Bin

last: Hu

first: Xiaoyuan

last: Song

first: Xiangting


title: Effect of cold atmospheric plasma (CAP) on MCF-7 breast cancer cell (Agilent Human GE v3 8x60K Microarray)

summary: Genom-wide expression profiling of MCF-7, MCF-7 and CAP-treated MCF-7 cell. In result, cold atmospheric plasma different effect the CAP-treated MCF-7 breast cancer cell.

overall_design: Total RNA is obtained from MCF-7 and CAP-treated MCF-7.

first: Sungbin

last: Park

first: Sunjung

last: Kim


title: Whole-transcriptome analysis of grapevine-Botrytis cinerea interaction during latent infection of berries

city: Rome

first: Teresa

last: Colombo

address: p.le A. Moro 7

department: Institute of Molecular Biology and Pathology (IBPM)

institute: Consiglio Nazionale delle Ricerche (CNR)

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

sample_organism:
Vitis vinifera
Botrytis cinerea

platform_organism:
Vitis vinifera
Botrytis cinerea


title: Whole-transcriptome microarray analysis of grapevine-Botrytis cinerea interaction during latent infection of berries (“noble rot”)

summary: Purpose: Microarray technologies provide a unique opportunity to deeply investigate the molecular mechanisms involved in plant-pathogen interaction. Botrytis cinerea, is the agent of grapevine grey mould, but in yet uncharacterized environmental conditions, a latent infection can occur determining favourable metabolic and physico-chemical berry modifications which possibly contribute to the typical aromas of “passito” wines (“noble rot”). The present project aims at the identification of the grapevine responses to B. cinerea during fungal colonization in the latent form, in comparison with control berries.   Methods: A total of 150 untreated berries were sampled as time 0 of the experiment. Moreover, 300 healthy berries have been artificially inoculated one by one with B. cinerea by injecting conidia under berry skin, in controlled conditions, reproducing an early stage (T1) and  a late stage (T2) of noble rot pourri plein. Control samples (300 berries) have been inoculated with water and sampled at the same time of infected berries. The microarray experiments on T0 and healthy or infected samples in biological triplicate resulted in 15 samples to be analyzed (Agilent-048771 4x44K Grape all custom microarray chip; Agilent Technologies, Santa Clara, CA, USA).  Conclusions: This work identified important molecular mechanisms involved in Botrytis cinerea colonization of grapevine berries during the noble rot infection.

overall_design: mRNA profiles of Muller-Thurgau berries infected with Botrytis cinerea (noble rot) at T1 and T2 stage of pourri plein were either compared to mRNA profiles of uninfected Garganega berries (control berries) or  to those T0 samples. All mRNA profiles were generated from three biological replicates.

first: Arianna

last: Lovato

first: Giovanni

last: Tornielli

first: Annalisa

last: Polverari

first: Elodie

last: Vandelle

first: Sara

last: Zenoni


title: ChIP-seq analysis reveals alteration of H3K4 trimethylation occupancy of cancer-related genes by cold atmospheric plasma

first: sung bin

last: park

summary: Cold atmospheric plasma (CAP) has obtained credits for cancer treatment by its ability to preferentially induce cancer cell death, while its molecular mechanism is under elucidation. Here, an epigenetic effect of CAP on cancer cell was examined by performing a genome-wide ChIP-seq for H3K4me3 in the MCF-7 breast cancer cell.

first: Seungyeon

last: Lee


title: Whole-genome expression profiling of metastatic versus non-metastatic mammary tumors in MMTV-Wnt1 transgenic mice

city: Atlanta

first: Carlos

middle: S.

last: Moreno

state: GA

address: Michael Street

department: Pathology & Laboratory Medicine

institute: Emory University

summary: To identify genes that mediate lung metastasis in breast cancer, we compared expression profiles of metastatic versus non-metastatic mammary tumors in MMTV-Wnt1 transgenic mice. A subset of biologically relevant genes with statistically significant changes was selected for validation. These genes include Alox15, Ptn, Ror2, Sox9, Jag2 and Runx2. These genes encode proteins that play important roles in the immune and inflammatory responses as well as osteogenesis and skeletal morphogenesis.

overall_design: We performed whole-transcript array analysis of three normal mammary glands, three non-metastatic mammary tumors and three metastatic mammary tumors from  MMTV-Wnt1 transgenic mice using Affymetrix GeneChip® Mouse Gene 2.0 ST Array.

middle: S


title: Gene expression profiling induced by high dose ionizing radiation on MDA-MB-231 cells

city: Cefalù

first: Valentina

last: Bravatà

address: Contrada Pietrapollastra Pisciotto

institute: IBSBC CNR

summary: Radiation therapy (RT) remains a vital component of the curative multimodality therapy for many types of cancer including breast cancer (BC). Even if great number of BC patients receive RT, not all of them report benefits, due to radioresistance activation depending also by  hormone receptor status. We analyze and compare molecular responses, in term of gene expression profile (GEP) changes, induced by high dose of Ionizing Radiation (IR), in MDA-MB-231 with ER-/PR-HER2- receptor status. Moreover, we selected a MDA-MB-231 Radioresistent Cell Fraction (RCF), in which we highlighted specific molecules able to drive radioresistance.   We trust that this study could have a role in the evaluating of RT response in term of radioresistance process activation to define a personalized biological-driven treatment plan in  triple negative BC.

overall_design: Changes in gene expression in tumorigenic MDA-MB-231 breast cancer cell lines, exposed to 9 and 23Gy of electron irradiation, were analyzed as two-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays. In addition, we have used the our existing samples following listed:  GSM2916578-83; GSM3032684-89. Moreover, new samples were named as follow: MDA-MB-231_RCF rep1-rep6.


title: Transcriptome analysis of embryonic axes of soybean seeds germinating in the presence of the gibberellin (GA) biosynthesis inhibitor paclobutrazol (PBZ)

city: Campos Dos Goytacazes

first: Rajesh

middle: Kumar

last: Gazara

address: Avenida Alberto Lamego, 2000

department: CBB

country: Brazil

institute: Universidade Estadual do Norte Fluminense Darcy Ribeiro

summary: Purpose: A time-course transcriptome study to identify probable GA-responsive genes in soybean embryonic axes during seed germination. Methods: Seeds were germinated in the presence or absence of 200 µM PBZ. Seeds were germinated in 28°C temperature and 12/12h photoperiod (dark/light) and harvested at 12, 24 and 36 hours after imbibition (HAI). Three biological replicates were performed. Results: Identification of GA-responsive genes during germination in Glycine max.

overall_design: RNA-Seq analysis of embryonic axes of soybean seeds at 12, 24 and 36 hours after imbibition in the presence of paclobutrazol, a gibberellin biosynthesis inhibitor.

first: T

last: Venancio

first: R

middle: K


title: Pan-ampk activation improves renal function in a rat model of progressive diabetic nephropathy

status: Public on Jul 25 2019

city: Boston

first: eric

last: muise

address: 33 Ave Louis Pasteur

department: Genetics and Pharmacogenomics

institute: Merck

summary: Chronic kidney disease (CKD) remains a tremendous and growing burden on the healthcare system and new therapies are needed to prevent or slow disease progression. Metabolic dysregulation and mitochondrial dysfunction are important features of acute and chronic tissue injury across species, and human genetics and preclinical data suggest that the master metabolic regulator 5'-adenosine monophosphate activated protein kinase (AMPK) may be an effective therapeutic target for CKD. Merck has recently disclosed a pan-AMPK activator MK-8722 which was shown to have beneficial effects on metabolic parameters in preclinical models. In this study we investigate the effects of MK-8722 in a progressive model of diabetic nephropathy to determine whether activation of AMPK would be of therapeutic benefit. We find that MK-8722 administration in a therapeutic paradigm is profoundly reno-protective. We provide evidence that the therapeutic effects may be mediated by modulation of renal mitochondrial quality control as well as by attenuating fibrotic and lipotoxic mechanisms in kidney cells. These data further validate the concept that targeting metabolic dysregulation in CKD could be a potential therapeutic approach.

overall_design: Total RNA from kidney cortex and kidney medulla from rats treated with either vehicle, Enalapril, or MK-8722 (2 doses), for 28 weeks was sequenced (5 replicates per group).

first: Eric

last: Muise

first: Xiaoyan

last: Zhou


title: Effect of cold atmospheric plasma (CAP) on MCF-7 breast cancer cell (Illumina HumanHT-12 V4.0 beadchip)

summary: genom-wide expression profiling of MCF-7, MCF-7 and CAP-treated MCF-7 cell. In result, cold atmospheric plasma different effect the CAP-treated MCF-7 breast cancer cell.

overall_design: Total RNA is obtained from MCF-7 and CAP treated MCF-7.

first: Sunjung


title: The effect of spontaneous acquisition of an extra chromosome 7 for engineered del(7q) on induced pluripotent stem cells (iPSCs) derived from patients with Shwachman Diamond Syndrome (SDS).

first: Gabriela

last: Alexe

overall_design: RNA-seq transcriptome profiling of triplicate iPSCs with and without spontaneous acquisition of an extra chromosome 7 after deletion of chr7q.  iPSCs were  generated from bone marrow mononuclear cells of two patients with SDS that carried homozygous c.258+2T>C SBDS mutations. The long arm of chromosome 7 was deleted by targeted insertion of two inverted loxP sites into the long arm of chromosome 7 followed by transient expression of Cre-recombinase. iPSCs samples without chromosome 7q deletion were labeled SDS. iPSCs samples with spontaneous acquisition of an extra chromosome 7 following 7q deletion were labeled SDS del(7q)+7.

first: Akiko

last: Shimamura

first: Melisa

last: Ruiz-Gutierrez


title: Whole-transcriptome RNA-seq analysis of grapevine-Botrytis cinerea interaction during latent infection of berries (“noble rot”)

first: Teresa

last: Colombo

country: Italy

summary:
Purpose: High throughput sequencing technologies provide a unique opportunity to deeply investigate the molecular mechanisms involved in plant-pathogen interaction. Botrytis cinerea, is the agent of grapevine grey mould, but in yet uncharacterized environmental conditions, a latent infection can occur determining favourable metabolic and physico-chemical berry modifications which possibly contribute to the typical aromas of “passito” wines (“noble rot”). The present project aims at the identification of the genes deployed by B. cinerea during grape berries colonization in the latent form, in comparison with the saprophytic growth in vitro.
Methods: A total of 300 healthy berries have been artificially inoculated one by one with B. cinerea by injecting conidia under berry skin, in controlled conditions, reproducing the pourri plein stage of noble rot. Control samples (300 berries) have been inoculated with water. The saprophytic growth was obtained in liquid nutrient medium in laboratory flasks, and the mycelium collected by filtration. The RNA-sequencing experiments on healthy or infected samples in biological triplicate resulted in 27 data sets to be analyzed (Illumina NextSeq500 paired-end sequencing; 533.779.730 total reads, 150 Gb of data).
Conclusions: This work identified important molecular mechanisms involved in Botrytis cinerea colonization of grapevine berries during the noble rot infection.

overall_design: mRNA profiles of Garganega berries infected with Botrytis cinerea (noble rot) were either compared to mRNA profiles of uninfected Garganega berries (control berries) or  to those of Botrytis cinerea grown in vitro (saprophytic growth). All mRNA profiles were generated by deep sequencing, in triplicate, using Illumina NextSeq500.

first: Arianna

last: Lovato

first: Giovanni

middle: B

first: Annalisa