title: Advanced biofilm analysis in streams receiving organic deicer runoff

status: Public on May 13 2019

city: Northfield

first: Heather

middle: Elizabeth

last: Driscoll

state: VT

address: 158 Harmon Drive

department: Biology

institute: Norwich University

summary: Prolific heterotrophic biofilm growth is a common occurrence in airport receiving streams containing deicer and anti-icer runoff.  This study investigated relations of heterotrophic biofilm prevalence and community composition to environmental conditions at stream sites upstream and downstream of Milwaukee Mitchell International Airport in Milwaukee, WI, during two deicing seasons (2009–2010 and 2010–2011).  Modern genetic tools (such as microarray) have not previously been applied to biofilm communities in this type of setting.  We used microarray results to characterize biofilm community composition as well as the response of the biofilm community to environmental factors (i.e., organic content (using chemical oxygen demand concentration) and temperature).

platform_organism: Bacteria Archaea

overall_design: An eleven array study using metagenomic DNA recovered from four primary sites and several subsites at six time points. Samples were run on a second-generation (G2) PhyloChip (Affymetrix; Thermo Fisher Scientific) microarray platform.

first: Michelle

last: Nott


title: Characterisation of DNA methylation during mesenchymal stem cell chondrogenesis

status: Public on May 24 2019

city: Newcastle upon Tyne

first: David

last: Young

address: Institute of Genetic Medicine

country: United Kingdom

institute: Newcastle University

type: Methylation profiling by genome tiling array

summary: Regulation of transcription occurs in a cell type specific manner orchestrated by epigenetic mechanisms including DNA methylation. Methylation changes may also play a key role in lineage specification during stem cell differentiation. To further our understanding of epigenetic regulation in chondrocytes we characterised DNA methylation changes during chondrogenesis of mesenchymal stem cells (MSCs) by Infinium 450K methylation array. Significant DNA hypomethylation was identified during chondrogenesic differentiation including changes at many key cartilage gene loci. Integration with chondrogenesis gene expression data revealed an enrichment of significant CpGs in upregulated genes, while characterisation of significant CpG loci indicated their predominant localisation to enhancer regions. Comparison with methylation profiles of other tissues, including healthy and diseased adult cartilage, identified chondrocyte-specific regions of hypomethylation and the overlap with differentially methylated CpGs in osteoarthritis. Taken together we have associated DNA methylation levels with the chondrocyte phenotype. The consequences of which has potential to improve cartilage generation for tissue engineering purposes and also to provide context for observed methylation changes in cartilage diseases such as osteoarthritis

overall_design: Bisulphite converted DNA from the 12 samples were hybridised to the Illumina Infinium HumanMethylation450 BeadChip array.

first: Kathleen

last: Cheung

first: Matt

last: Barter


title: HDAC10 deletion in Treg

status: Public on May 28 2019

city: Philadelphia

first: Wayne

middle: W

last: Hancock

state: PA

address: 916B ARC, 3615 Civic Ctr Blvd

country: USA

institute: CHOP/UPenn

summary: HDAC10–/– (B6N(Cg)-Hdac10tm1.1(KOMP)Mbp/J) and wild type (WT) CD4+CD25+ Treg were isolated and RNA procured. Single strand cDNA was generated, fragmented and labeled, and hybridized to Affymetrix GeneChip Mouse Gene 2.0 ST Arrays for microarray analysis.

overall_design: WT or HDAC10–/– Treg cell RNA was isolated using RNeasy kits (QIAGEN). Total RNA was assessed by UV absorbance and all had 260/280 nm ratios above 1.7.  Additionally, samples were run on the Agilent RNA 6000 Nano chip and all had RINs in the 8.0 range. Microarray experiments were performed using whole-mouse-genome oligoarrays (GeneChip™ Mouse Gene 2.0 ST Array), and array data were analyzed using Transcriptome Analysis Console 4.0 software (ThermoFisher Scientific). Array data were subjected to robust multiarray average normalization. To assess differential gene expression, fold changes of up- and downregulated genes were calculated, and significance assessed via one-way ANOVA. Data with a false discovery rate <0.1 and >1.5-fold differential expression were included in the analysis.

first: Ulf

middle: H

last: Beier


title: Colonic epithelium of WKY and SHR

status: Public on May 04 2019

city: Gainesville

first: tao

last: yang

state: Florida

address: McKnight Brain Institute, 1149 Newell Drive

institute: University of Florida

type: Expression profiling by high throughput sequencing

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Protein-coding changes preceded cis-regulatory gains in newly evolved transcription circuit

status: Public on Jun 25 2019

city: San Franisco

first: Candace

middle: Sarah

last: Britton

state: CA

address: N372 Genentech Hall, 600 16th Street, Box 2200

department: Microbiology and Immunology

institute: University of California, San Francisco

summary: While changes in both the coding-sequence of transcriptional regulators and in the cis-regulatory sequences recognized by them have been implicated in the evolution of transcriptional circuits, little is known of how they evolve in concert. We describe an evolutionary pathway in fungi where a new transcriptional circuit (a-specific gene repression by Matα2) evolved by coding changes in an ancient master regulator followed millions of years later by cis-regulatory sequence changes in the genes of its future regulon. We discerned this order of events by analyzing a group of species in which the coding changes in the regulator are present, but the cis-regulatory changes in the target genes have not yet occurred. In this group we show that the coding changes became necessary for the regulator’s deeply conserved function and were therefore preserved. We propose that the changes first arose without altering the overall function of the regulator (although changing the details of its mechanism) and were later co-opted to “jump start” the formation of the new circuit.

overall_design: Gene expression was measured in wildtype a/α and α cell of the yeast W. anomalus, and compared to a/α and α cells with deletions of single genes encoding mating type transcriptional regulators.

middle: S

first: Alexander

middle: D

last: Johnson


title: Transcriptome profiling of abiotic responses to heat, cold, salt, and osmotic stress of Capsicum annuum L.

status: Public on Jun 18 2019

city: Jinju

first: Seon-In

last: Yeom

address: 501, Jinjou-daero

country: South Korea

institute: Gyeongsang National University

summary: We sought to investigate the scope of transcriptome analyses of peppers subjected to four major environment stresses (heat, cold, drought, and salinity). For this, at the six-true-leaf stage, plants were subjected to a temperature of 10°C or 40°C to mimic cold or heat stress, respectively. For salinity stress, plants were treated with 50 mL of a 400 mM NaCl solution; for osmotic stress, the peppers were treated with 50 mL of 400 mM mannitol. For RNA-seq library construction, the third or fourth leaves from four plants were harvested per replicate at 0, 3, 6, 12, 24, and 72 h after treatment. A total of 204.68 Gb of transcriptome data were generated using transcriptome analysis pipelines consisting of quality control, quantification, and differential gene expression analyses. A hierarchical clustering of gene expression data were used to infer the quality of the RNA-seq data and the characteristics of samples in each treatment. The extensive transcriptome data obtained will provide valuable information for future studies of crops exposed to abiotic stresses.

overall_design: RNA-Seq profiling of abiotic responses to heat, cold, salt, and osmotic stress in Capsicum annuum L. leaves

first: Won-Hee

last: Kang

first: Young-Mi

last: Sim

first: Namjin

last: Koo

first: Jae-Young

last: Nam

first: Junesung

last: Lee

first: Nayoung

last: Kim

first: Yong-Min


title: Systematic functional characterization of BAF mutations yields novel intra-complex synthetic lethalities [RNA-Seq]

status: Public on Apr 30 2019

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: Aberrations in genes coding for subunits of the BAF chromatin remodeling complex are highly abundant in human cancers. Currently, it is not understood how these loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer type specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knock-out cell lines deficient for 22 targetable BAF subunits. We observe strong, specific and often discordant alterations dependent on the targeted subunit and show that these explain intra-complex co-dependencies, including the novel synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest novel approaches to therapeutically target BAF mutant cancers.

overall_design: RNA-seq samples for knockouts of BAF complex in the HAP1 cell line.

first: Sandra

last: Schick

first: André

middle: F

last: Rendeiro

first: Kathrin

last: Runggatscher

first: Anna

last: Ringler

first: Bernd

last: Boidol

first: Melanie

last: Hinkel

first: Peter

last: Májek

first: Loan

last: Vulliard

first: Thomas

last: Penz

first: Katja

last: Parapatics

first: Christian

last: Schmidl

first: Jörg

last: Mensche

first: Guido

last: Boehmelt

first: Mark

last: Petronczki

last: Mueller

first: Stefan

last: Kubicek


title: Genome wide CRISPR screen for Venetoclax resisatnce in MOLM13 cells using Y. Kosuke library

city: Portland

first: Olga

last: Nikolova

state: OR

address: 2720 SW Moody Ave

department: Computational Biology

institute: OHSU

summary: MOLM13 cells were infected with CRISPR/Cas9 library, selected for puromycn resistance for integration events and exposed to Venetoclax or vehicle, DMSO, at 1microMolar concentrations.  Cells were collected at time 0 (post puromycin selection), day 7 and 14 , DNA was extracted and sgRNA barcodes were amplified. PCR library was deep sequenced using highthroughput Illumina platform Hiseq using 6 samples per lane.

overall_design: perform pairwise comparisons between sgRNA distributions at initial time point (DMSO day 0) and plasmid, between DMSO and Venetoclax treated cells at corresponding time points.

first: Tamilla

last: Nechiporuk

first: Steve

last: Kurtz

first: Shannon

last: McWeeney


title: Topoisomerase II-induced Chromosome Breakage and Translocation Is Determined by Chromosome Architecture and Transcriptional Activity [Nascent RNA]

status: Public on Apr 26 2019

city: Safed

first: Yaakov

last: Maman

address: Henrietta Szold 8

department: Azrieli Faculty of Medicine

country: Israel

institute: Bar-Ilan University

summary: Topoisomerase II (TOP2) relieves torsional stress during transcription, DNA replication and chromosome segregation, by forming transient cleavage complex intermediates (TOP2ccs) that contain TOP2-linked DNA breaks. While TOP2ccs are normally reversible they can be ‘trapped’ by chemotherapeutic drugs such as etoposide, and subsequently converted into irreversible TOP2-linked  DSBs that threaten genome stability. Here, using genomics approaches, we have quantified the etoposide-induced trapping of TOP2ccs, their conversion into irreversible TOP2-linked DSBs,  and their processing during DNA repair genome-wide, as a function of time. We find that while TOP2 trapping is independent of transcription it requires pre-existing binding of cohesin to DNA.  In contrast, the conversion of trapped TOP2ccs to irreversible DSBs during DNA repair is accelerated two-fold at transcribed loci, relative to non-transcribed loci. This conversion is dependent on proteasomal degradation and TDP2 phosphodiesterase activity. Quantitative modeling shows that only two critical features of pre-existing chromatin structure- namely, cohesin binding and transcriptional activity- can be used to accurately predict the kinetics of TOP2-induced DSBs.  Thus, our study permits a mechanistic understanding of TOP2 induced genome instability.

overall_design: Nascent RNA-seq profile in Abelson-transformed pre-B cell, upon treatment with DRB, IFNb, or not treated

first: Andres

last: Canela

first: Shar-yin

middle: N

last: Huang

first: Gordana

last: Wutz

first: Weng

last: Tang

last: Zagnoli-Vieira

first: Elsa

last: Callen

first: Nancy

last: Wong

first: Amanda

last: Day

first: Jan-Michael

last: Peters

first: Keith

last: Caldecott

first: Yves

last: Pommier

first: André

last: Nussenzweig


title: Unlocking the transcriptomic potential of formalin-fixed paraffin embedded clinical tissues: Comparison of gene expression profiling approaches

status: Public on May 03 2019

city: Edinburgh

first: Carlos

last: Martinez-Perez

address: Western General Hospital, Crewe Road South

department: Institute of Genetics and Molecular Medicine

institute: The University of Edinburgh


title: Topoisomerase II-induced Chromosome Breakage and Translocation Is Determined by Chromosome Architecture and Transcriptional Activity [ChIP-seq]

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: ChIP-seq profile in B, MEFs, pre-B, T, and Neurons

first: Guido


title: Transcriptomic analysis of liver mRNA from TSP-1 KO and WT mice fed with normal diet or choline deficient amino acid defined diet (CDAHFD, human NASH model)

status: Public on May 31 2019

city: Cambridge

first: Ju

last: Wang

state: MA

address: 610 Main Street

department: Inflammation & Immunology

institute: Pfizer Inc

summary: Transcriptomic profiles of wild type and TSP1 knockout mice that were fed control (normal) diet or CDAHFD (choline deficient amino acid defiend high fat diet) chow for 12 weeks to model Non-alcoholic Steatohepatitis (NASH) disease in humans.

overall_design: Liver mRNA profiles of TSP-1 KO and WT mice that were fed control or CDAHFD (choline deficient amino acid defined high fat diet) chow for 12 weeks. (n=5 for each group). On day 0, C57/BL6 mice or TSP1 Knockout mice (JAX stock #006141) were provided with either Control chow (Research Diets A08051501) or CDAHFD chow (Choline deficient L-amino acid-defined high fat diet; Research Diets A06071309). After 12 weeks all groups were terminated with liver tissues were collected. One section of right medial lobe of liver was taken and snap-frozen in liquid nitrogen for RNA extraction. RNA was extracted with Trizol (Thermo Fisher Scientific # 15596026)  after homogenization by Omni TH tissue homogenizer.

first: Jessica

last: Min-DeBartolo

first: Franklin

last: Schlerman

first: He

last: Wen

first: Zhang

last: Baohong

first: Robert

middle: V

last: Martinez


title: RRBS of colonic epithelium of WKY and SHR

first: tao

last: yang

summary: Alterations in DNA methylation between WKY and SHR epithelium

overall_design: examine DNA methylation profiles

first: Yang

last: Tao

first: Raizada

last: Mohan


title: RNA-seq of colonic epithelium of WKY and SHR

summary: Alterations in genes between WKY and SHR epithelium

overall_design: examine gene expression profiles


title: The TP53 Apoptotic Network is a Primary Mediator of Resistance to BCL2 inhibition in AML Cells

first: Olga

last: Nikolova


title: Topoisomerase II-induced Chromosome Breakage and Translocation Is Determined by Chromosome Architecture and Transcriptional Activity

status: Public on Apr 24 2019

first: Yaakov

last: Maman

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells [ChIP-seq]

status: Public on Apr 23 2019

city: Salt Lake City

first: Jason

last: Gertz

state: UT

address: 2000 Circle of Hope

department: Oncological Sciences

institute: University of Utah

summary: Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression; however, the molecular mechanisms underlying ER’s regulatory role in endometrial cancer are poorly understood. In breast cancer cells, ER genomic binding is enabled by FOXA1 and GATA3, but the transcription factors that control ER genomic binding in endometrial cancer cells remain unknown. We previously identified ETV4 as a candidate factor controlling ER genomic binding in endometrial cancer cells and here we explore the functional importance of ETV4. Homozygous deletion of ETV4, using CRISPR/Cas9, led to greatly reduced ER binding at the majority of loci normally bound by ER. Consistent with the dramatic loss of ER binding, the gene expression response to estradiol was dampened for most genes. ETV4 contributes to estrogen signaling in two distinct ways; ETV4 loss impacts chromatin accessibility at some ER bound loci and impairs ER nuclear translocation. The diminished estrogen signaling upon ETV4 deletion led to decreased growth, particularly in 3D culture where hollow organoids were formed. Our results show that ETV4 plays a necessary role in estrogen signaling in endometrial cancer cells.

overall_design: ChIP-seq was used to study genome binding of ER and ETV4 after ETV4 KO or ectopic expression

first: Adriana

middle: C

last: Rodriguez


title: RNA-seq of human aneuploid cell lines with Trisomy 21

status: Public on May 16 2019

city: Marseille

first: Bianca

middle: Habermann

last: Hermine

address: 163 Avenue de Luminy

country: France

institute: Aix-Marseille University, CNRS, IBDM UMR 7288, 13009 Marseille, France

summary: Trisomy 21, a form of aneuploidy, is one of the few viable forms of trisomy. The goal of this study was to assess the effect of an additional chromosome 21 on gene expression in two different human aneuploid model cell lines.

overall_design: HiSeq Illumina sequencing of total RNA for two whole-chromosome aneuploid cell lines with an extra copy of chromosome 21 and their corresponding parental cell line.

first: Milena

last: Dürrbaum

first: Annie

last: Yim

first: Prasanna

last: Koti

last: Habermann

first: Zuzana

last: Storchova


title: ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells


title: Genome-wide gene expression of HML58-3 (a derivative cell line of HCT116) after treatment of DAC (decitabine), OR-2003, and OR-2100

status: Public on Aug 01 2019

city: Tokyo

first: Naoko

last: Hattori

address: 5-1-1 Tsukiji, Chuo-ku

department: Research Institute

country: Japan

institute: National Cancer Center

summary: A derivative cell line of HCT116, HML58-3, was established to detect DNA demethylating agents [Okochi-Takada E, Epigenetics. 2018;13:147-55.]. HML58-3 cells were treated with DNA demethylating agents (decitabine, OR-2003, and OR-2100) or mock. A genome-wide gene expression analysis was performed using SurePrint G3 Human Gene Expression 8 x 60K v2 Microarray.

overall_design: Cy3-labeled cRNA was synthesized from 100 ng of total RNA using a Low Input Quick Amp Labeling Kit, and 600 ng of labeled cRNA was fragmented and hybridized to SurePrint G3 Human GE 8x60K Microarray Ver3.0 Microarray.

first: Toshikazu

last: Ushijima


title: Topoisomerase II-induced Chromosome Breakage and Translocation Is Determined by Chromosome Architecture and Transcriptional Activity [HTGTS]

overall_design: High-throughput genome wide translocation sequencing (HTGTS) profiles performed in Abelson-transformed pre-B cell

first: Canela

last: Andres

first: Maman

last: Yaakov

first: Huang

last: Shar-yin N.

first: Wutz

last: Gordana

first: Tang

last: Weng

first: Zagnoli-Vieira

last: Guido

first: Callen

last: Elsa

first: Wong

last: Nancy

first: Day

last: Amanda

first: Peters

last: Jan-Michael

first: Caldecott

last: Keith W.

first: Pommier

last: Yves

first: Nussenzweig

last: André


title: Transcript degradation and codon usage as gene regulation in a lytic phage

status: Public on May 01 2019

city: Austin

first: Claus

last: Wilke

state: Texas

address: 2500 Speedway, A4800

department: Integrative Biology

institute: University of Texas at Austin

summary: We analyze transcript abundances of T7 over the course of an infection and find evidence for differential transcript degradation.

sample_organism:
Escherichia coli
Escherichia phage T7

platform_organism:
Escherichia coli
Escherichia phage T7

overall_design: E. coli were infected with wildtype T7 at 25C and sampled for RNA-sequencing at 5, 10, 15, and 25 minutes. There are three biological replicates, and two technical replicates for each biological replicate.

first: Benjamin

middle: R

last: Jack

first: Daniel

last: Boutz

first: Matthew

middle: L

last: Paff

first: Bartram

last: Smith

first: James

middle: J

last: Bull

middle: O


title: Genome wide CRISPR screen for Venetoclax resisatnce in MOLM13 cells using Brunello library

first: Olga

last: Nikolova

first: Tamilla

last: Nechiporuk

first: Steve

last: Kurtz

first: Shannon

last: McWeeney


title: Transcriptome sequencing wide functional analysis of human mesenchymal stem cells with PolyIC treatment

status: Public on Apr 03 2019

city: Ansan

first: Young Gyu

last: Chai

state: Gyeonggi-do

address: 55 Hanyangdaehak-ro

department: Molecualr & Life Science

institute: Hanyang Univ.

summary: Using RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs polyIC (10 ug/ml).

overall_design: Examination of effects of PolyIC-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2500 (101 cycles PE lane).

first: Young

middle: G

first: Jin


title: Systematic functional characterization of BAF mutations yields novel intra-complex synthetic lethalities [ChIP-Seq]

first: Christoph

last: Bock

overall_design: ChIP-seq or ChIPmentation libraries for histone modifications or BAF complex members in the HAP1 cell line.

first: Sandra

last: Schick

first: André

last: Rendeiro

first: Kathrin

last: Runggatscher

first: Anna

last: Ringler

first: Bernd

last: Boidol

first: Melanie

last: Hinkel

first: Peter

last: Májek

first: Loan

last: Vulliard

first: Thomas

last: Penz

first: Katja

last: Parapatics

first: Christian

last: Schmidl

first: Jörg

last: Mensche

first: Guido

last: Boehmelt

first: Mark

last: Petronczki

last: Mueller

first: Stefan

last: Kubicek


title: Systematic functional characterization of BAF mutations yields novel intra-complex synthetic lethalities

last: Bock

overall_design: Refer to individual Series


title: Transcriptome sequencing wide functional analysis of human mesenchymal stem cells (Poly(I:C) and LPS)

first: Young Gyu

last: Chai


title: Systematic functional characterization of BAF mutations yields novel intra-complex synthetic lethalities [ATAC-Seq]

first: Christoph

overall_design: ATAC-seq samples for knockouts of BAF complex in the HAP1 cell line.

last: Schick

last: Rendeiro


title: Topoisomerase II-induced Chromosome Breakage and Translocation Is Determined by Chromosome Architecture and Transcriptional Activity [END-seq]

first: Yaakov

last: Maman

overall_design: END-seq profile in B, MEFs, pre-B, T, and Neurons untreated and upon etoposide treatment, and upon treatment with transcription inhibition drugs

first: Andres

last: Canela

first: Shar-yin

last: Huang

first: Gordana

last: Wutz

first: Weng

last: Tang

last: Zagnoli-Vieira

first: Elsa

last: Callen

first: Nancy

last: Wong

first: Amanda

last: Day

first: Jan-Michael

last: Peters

first: Keith

last: Caldecott

first: Yves

last: Pommier

last: Nussenzweig


title: Transcriptome sequencing wide functional analysis of human mesenchymal stem cells (Poly(I:C))

summary: Using RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs Poly(I:C) (10ug/ml)

overall_design: Examination of effects of LPS-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2500(101 cycles PE lane).

first: Y

first: J


title: Oxaliplatin resistance is enhanced by saracatinib via upregulation of ABCG1 and Wnt/β-catenin signaling in hepatocellular carcinoma

status: Public on Mar 30 2019

city: Xi 'an

first: Xia

last: Liao

state: Shaanxi

address: 277# West Yanta Road

country: China

institute: Department of nutrition

summary:
Background:Oxaliplatin-resistant hepatocellular carcinoma (HCC) is associated with increased insulin-like growth factor 1 (IGF1) paracrine signaling, and the IGF1 receptor can be downregulated by inhibition of Src kinases. Therefore, we sought to determine whether Src inhibition and oxaliplatin treatment exerted synergistic effects on HCC cell lines.
Methods: The antitumor effects of combined treatment with saracatinib and oxaliplatin on proliferation were evaluated in HCC cells as well as in saracatinib- and oxaliplatin-resistant HCC cell lines using cell viability assays, plate colony formation assays, and cell cycle distribution detection. RNA sequencing was used to explore the resistance mechanism, and the effects on ABCG1 and Wnt signaling in oxaliplatin resistance were confirmed.
Results: Chemotherapy with oxaliplatin and saracatinib individually induced strong anti-HCC effects, while combined or sequential treatment of HCC cells with these two drugs exhibited reduced efficacy compared to treatment with the single drugs. Furthermore, treatment with saracatinib caused oxaliplatin resistance. RNA sequencing revealed 458 genes that were altered by treatment with saracatinib and oxaliplatin. Of these, the gene encoding the ATP-binding cassette transporter G1 ABCG1 and Wnt-associated genes were significantly upregulated. Upregulation of ABCG1 and oxaliplatin resistance were associated with activation of Wnt signaling. Interference with ABCG1 expression or inhibition of Wnt signaling resulted in reversal of the saracatinib-induced oxaliplatin resistance in the HCC cell lines.
Conclusions: These studies demonstrated that combined or sequential chemotherapy with oxaliplatin and saracatinib reduced antitumor efficacy, and this antagonism was attributed to the upregulation of ABCG1 and activation of Wnt signaling pathway by saracatinib.

overall_design: RNA sequencing was used to compared MHCC97L with MHCC97L-SRC and MHCC97L with MHCC97L-OXA.

first: Ge

last: Song

first: Yang

last: Bu

first: Fan

last: Chang

first: Fengan

last: Jia

first: Xuelian

last: Xiao

first: Mei

last: Zhang

first: Pengbo

last: Ning

first: Qingan


title: The role of beta-catenin signaling in regulating barrier vs. non-barrier gene expression programs in circumventricular organ and ocular vasculatures

status: Public on Mar 26 2019

city: Baltimore

first: Mark

last: Sabbagh

state: MD

address: 725 North Wolfe Street

department: Molecular Biology and Genetics

institute: Johns Hopkins University School of Medicine

summary: The mammalian brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum and parenchyma, a property that defines the blood-brain and blood-retina barriers. Exceptions to this pattern are found in the circumventricular organs (CVOs), a set of small midline brain structures that are supplied by high permeability capillaries. In the eye and brain, high permeability capillaries are also present in the choriocapillaris, which supplies the retinal pigment epithelium and photoreceptors, and the ciliary body and choroid plexus, the sources of aqueous humor and cerebrospinal fluid, respectively. We show here that endothelial cells in these vascular systems exhibit a low level of beta-catenin signaling. By elevating beta-catenin signaling in endothelial cells, these vasculatures can be partially converted to a barrier state. In one CVO, the area postrema, high permeability is maintained, in part, by local production of Wnt inhibitory factor-1.

overall_design: RNA-seq and ATAC-seq of adult vascular endothelial cells (ECs) from the cerebellum, anterior pituitary, and posterior pituitary of Tie2-GFP mice, with and without beta-catenin stabilization; RiboTag RNA-seq of adult vascular ECs from the cortex and choroid plexus, with and without beta-catenin stabilization. Information about the RiboTag mouse is available at: https://depts.washington.edu/mcklab/RiboTag.html

first: Yanshu

last: Wang

first: Xiaowu

last: Gu

first: Amir

last: Rattner

first: John

last: Williams

first: Jeremy

last: Nathans


title: Whole transcriptome profiling of static and suspension-cultured schizonts of the P. falciparum strains W2mef and Dd2.

status: Public on Apr 18 2019

city: Accra

first: Prince

middle: Berko

last: Nyarko

state: Greater Accra

address: WACCBIP, Volta Road, University Of Ghana

department: Department of Biochemistry, Cell and Molecular Biology

country: Ghana

institute: West African Centre for Cell Biology of Infectious Diseases, University of Ghana

summary:
Overview: RNA-seq was used to profile the whole-transcriptome gene expression of highly replicated schizont-stage cultures of W2mef and Dd2 grown under static and suspended conditions.
Methods: Transcript profiles of schizont stages of static and suspended W2mef and Dd2 were generated by RNA sequencing. Two to eight replicates were sequenced per sample. Illumina stranded TruSeq libraries were sequenced using an Illumina MiSeq. Hisat2 was used to align paired-end fastQ files and indexed bam files generated with samtools. Bam files were filtered to exclude reads with MAPQ scores below 60, reads counted using the SummarizeOverlaps feature of the GenomicAlignments package in R and differential expression analysis conducted using DESeq2 in R.
Results: We show that in addition to invasion-related genes, parasites that have been induced to switch invasion phenotype upon culturing in suspension increase the expression of a number of genes most of which belong to gene families that code for exported proteins.
Conclusions: Our data suggest that in addition to invasion phenotype switch, suspension cultures may select for other parasite properties that may be essential for parasite survival in vivo.

overall_design: TruSeq stranded mRNA libraries of two to eight schizont-stage replicates of static and suspended W2mef and Dd2 were sequenced using an Illumina MiSeq.

middle: B

first: Gordon

middle: A

last: Awandare


title: TCR and inflammatory signals tune human MAIT cells to exert specific tissue repair and effector functions

status: Public on Apr 17 2019

city: Oxford

first: Timothy

last: Hinks

state: United Kingdom

address: John Radcliffe Hospital, Headley Way, Oxford

department: NDM Experimental Medicine - New College

institute: University of  Oxford

summary: We sought to describe in detail human MAIT cell activation using a transcriptomic approach to define the basic transcriptome of MAIT cells in  humans and to determine how this is modulated by activation. Fresh human peripheral blood cells were obtained from three donors, and were magnetically enriched on CD8+ cells, and flow-sorted for live CD161++TCR Va7.2+ MAIT cells. These were cultured in media for 20 hours (“unstimulated”) or in the presence of anti-CD3/CD28 TCR beads (T), cytokines (IL-12, 2ng/ml, IL-18, 50ng/ml, IL-15, 25ng/ml, and TL1A, 100ng/ml), or TCR beads and cytokines combined (TC).

overall_design: Illumina sequencing of human MAIT cells. 3 biological replicates of each of the following conditions: Human peripheral blood MAIT cell unstimulated. Human peripheral blood MAIT cells stimulated for 20 h with anti-CD3/CD28 beads. Human peripheral blood MAIT cells stimulated for 20 h with cytokines (IL-12, 2ng/ml, IL-18, 50ng/ml, IL-15, 25ng/ml, and TL1A, 100ng/ml). Human peripheral blood MAIT cells stimulated for 20 h with anti-CD3/CD28 beads and cytokines (IL-12, 2ng/ml, IL-18, 50ng/ml, IL-15, 25ng/ml, and TL1A, 100ng/ml). Full details of the study can be downloaded at https://www.biorxiv.org/content/early/2018/11/26/475913

first: Emanuele

last: Marchi

first: Tianqi

last: Leng


title: Modeling protein destiny in developing tomato fruit

status: Public on Mar 23 2019

city: Villenave-d'Ornon

first: Isma

last: Belouah

address: 71 Avenue Edouard Bourlaux

department: Gironde

institute: Institut National de la Recherche Agronomique (INRA)

summary: Proteomics and transcriptomics data of tomato fruits (Solanum lycopersicum L. var. Moneymaker) at 9 developmental stages were used to calculate with a mathematical model the rate constants of synthesis and degradation for over 1,000 proteins. Proteome and transcriptome were extracted  from the pericarp tissue and analyzed using label-free LC-MS/MS (Orbitrap Q-Exactive) and RNA Sequencing (Illumina), respectively. Absolute quantification of transcriptome has been obtained by spiking-in internal standard before total-RNA extraction. Absolute quantification of the proteome has been approximated using the "Total Protein" approach. An OD equation defining the changes of protein content has been used to determine the synthesis and degradation rate constants (day -1). Almost 2,400 transcript-protein pairs were identified and the translation and degradation rate constants were determined for more than a thousand proteins. The model predicted median values of about 2 min for the translation and a lifetime of approximately 11 days. Proteins involved in protein synthesis had higher ks and kd values, indicating that the protein machinery is particularly flexible. None sequenced-based features were found that could be used to predict these rate constants.

overall_design: Absolute concentration mRNA from tomato fruit (Solanum lycopersicum L. var. Moneymaker, pericarp tissue) were quantified at nine developmental stages using Illumina sequencer. Each stage analysis was perfomed in triplicates.

first: Christine

last: Nazaret

first: Pierre

last: Pétriacq

first: Sylvain

last: Prigent

first: Camille

last: Bénard

first: Virginie

last: Mengin

first: Mélisande

last: Blein-Nicolas

first: Alisandra

middle: K

last: Denton

first: Thierry

last: Balliau

first: Ségolène

last: Augé

first: Olivier

last: Bouchez

first: Jean-Pierre

last: Mazat

last: Stitt

first: Bjorn

last: Usadel

first: Michel

last: Zivy

first: Bertrand

last: Beauvoit

first: Yves

last: Gibon

first: Sophie

last: Colombié


title: Transcriptomic profiling of cleavage-resistant RIPK1 induced autoinflammation syndrome patients

status: Public on Mar 01 2019

city: Bethesda

first: Daniel

last: Kastner

address: 9000 Rockville Pike

department: NHGRI

institute: NIH

summary: RIPK1 is known to play an important role  in TNF induced immune signaling. We have identified three pedigrees with heterozygos mutations in RIPK1 that disrupts its cleavage. We studied the transcriptional profiles of whole blood from one patient.

overall_design: RNAseq using the whole blood of a patient having heterozygous mutation in RIPK1 cleavage site (p.D324Y)

first: Hirotsugu

last: Oda


title: Differential DNA methylation profile in hepatocellular carcinoma

status: Public on Mar 04 2019

city: Taipei

first: Ming-Whei

last: Yu

address: Room 522 No.17, Xuzhou Road Zhongzheng District, Taipei City 10055, Taiwan

department: Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health

country: Taiwan

institute: National Taiwan University

summary: Genome-wide DNA methylation profiling was performed in peripheral leukocytes to identify biomarkers that could track hepatitis B progression to hepatocellular carcinoma (HCC). Samples included 48 HBsAg carriers who developed HCC and 48 HBsAg carriers who did not during follow-up.

overall_design: Bisulphite converted DNA from 96 samples were hybridized to the Illumina HumanMethylation450 BeadChip arrays.


title: Differential gene expressions for androgen-induced benign prostatic hyperplysia rat underwent oral treatment of metabolic peptide ghrelin

status: Public on Apr 11 2019

city: Munich

first: Yiming

last: Wang

state: Bavaria

department: Department of Urology

country: Germany

institute: Ludwig-Maximilans University

summary: To preliminary distinguish differential gene expressions in BPH-rat prostate after oral treatment of ghrelin.

overall_design: BPH rats were distributed into sham/control/ghrelin treatment groups. Benign prostatic hyperplaysia was induced by dihydrotestosterone for 4 weeks, and ghrelin were orally administrated for 2 weeks.

first: Wang

last: Yiming

first: Martin

last: Hennenberg


title: Bulk RNA sequencing of CD44Neg, CD44LoKitNeg, CD44LoKitPos and CD44High populations from mouse Aorta-Gonad-Mesonephros (AGM) region

status: Public on Mar 29 2019

city: Monterotondo

first: Christophe

last: Lancrin

state: RM

address: Via Ramarini 32

department: EMBL Rome

country: Italy

institute: EMBL

summary: The aim of the experiment was to compare newly defined CD44Neg, CD44LoKitNeg, CD44LoKitPos and CD44High populations from mouse Aorta-Gonad-Mesonephros (AGM) region

overall_design: AGM from E9.5, E10 and E11 C57Bl/6 mouse embryos were isolated and single cell suspensions were generated. Cells were stained with the anti-VE-Cadherin, anti-CD44 and anti-Kit antibodies and 25 Vecadpos_CD44neg cells (n=10), 25 Vecadpos_CD44LoKitNeg cells (n=6), 25 Vecadpos_CD44LoKitPos (n=3) and 25 Vecadpos_CD44High cells (n=3) were sorted by flow cytometry. The SMART-Seq 2 method was then used to produce cDNA from these 22 samples. Sequencing libraries were generated and were later sequenced together on the Illumina Next Seq 500 sequencer.

first: Kerstin

last: Ganter


title: PRC2 inactivation cooperates with JAK3 mutant signaling in the development of T-cell acute lymphoblastic leukemia

city: Leuven

first: Sofie

last: Demeyer

address: Herestraat 49 / bus 912

department: Center for Cancer Biology

country: Belgium

institute: KULeuven / VIB

summary: T-ALL is characterized by deregulation of transcriptional control and impairment of epigenetic homeostasis. We observed that T-ALL cases with mutations in the IL7R-JAK-STAT pathway frequently harbor inactivating mutations in the PRC2 complex, in particular SUZ12 mutations. PRC2 is an epigenetic complex responsible for writing the H3K27me3 mark associated with gene repression. To assess whether loss of SUZ12 cooperates with mutant JAK3 signaling during T-ALL development, we expressed the JAK3(M511I) mutant in mouse bone marrow cells in vivo and tested the effect of Cas9-mediated inactivation of Suz12 on leukemia development. The mice developed a T-cell leukemia that infiltrated most hematological organs (bone marrow, thymus, spleen, lymph nodes, blood). At time of sacrifice the majority of cells in the blood and hematopoietic organs was JAK3(M511I) positive and Suz12 negative. Reduced Suz12 protein and H3K27me3 levels were confirmed with flow cytometry. Moreover, JAK3(M511I) also cooperates with Suz12 gRNA-mediated inactivation in vitro. Pro-T cells carrying both JAK3(M511I) and Suz12 gRNA were able to transform to IL7 independent growth, whereas single mutant (JAK3(M511I) only or Suz12 gRNA only) pro-T cells could not. In order to get insight in the mechanism of cooperation between JAK3 mutant signaling and Suz12 inactivation, we performed and integrated RNA- and ChIP-sequencing (Suz12, H3K27me3, H3K27Ac, H3K4me1, H3K4me3) on leukemic cells from the mice. This showed a global upregulation of many genes, including known PRC2 target genes upon loss of Suz12. Moreover, Suz12 was bound to promoters of Wnt signaling genes (Fzd7, Lrp4) and Wnt target genes (Axin2, Jag2, Mmp9), concomitant with high H3K27me3 levels. Loss of Suz12 led to drastic reduction of H3K27me3 at these loci and upregulation of these Wnt genes. As Wnt signaling is ectopically activated, we wanted to test whether JAK3(M511I) + Suz12 gRNA cells are more sensitive to Wnt inhibitor. JAK3(M511I) + Suz12 pro-T cells and leukemic spleen cells exhibited increased sensitivity to Wnt inhibitor compared to JAK3 mutant control cells, indicating that Wnt signaling contributes to the cooperation between Suz12 loss and JAK3 mutant signaling. In conclusion, our data show that Suz12 inactivation cooperates with mutant JAK3 signaling to drive leukemia development in vivo and demonstrates the use of Cas9 transgenic mice to study the role of tumor suppressor genes in T-ALL mouse models. Moreover, Suz12 loss leads to ectopic activation of Wnt signaling, a pathway contributing to the cooperation of Suz12 loss and JAK3 mutant signaling that can also be targeted with inhibitors.

overall_design:
RNA-sequencing of transgenic mouse samples with different conditions: wildtype, JAK3 mutant, SUZ12 inactivation, JAK3 mutant+SUZ12 inactivation
ChIPmentation sequencing in transgenic mouse samples with different conditions (see RNA-sequencing) with multiple antibodies: Suz12, H3K27ac, H3K27me3, H3K4me3, H3K4me1

first: Michael

last: Broux

first: Charles

last: De Bock

first: Jan

last: Cools


title: miRNA and mRNA expression data from CD133+CD15+ chordoma cells (Chordoma Cance Stem Cells) and CD133-CD15- chordoma cells

status: Public on Apr 15 2019

city: Istanbul

first: Emre Can

last: Tüysüz

address: Ibrahimaga Mah.

country: Turkey

institute: Yeditepe University

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

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

platform_organism:
Homo sapiens
synthetic construct


title: Regulatory T cell depletion causes compensatory immune suppression and accelerated pancreatic carcinogenesis.

city: Ann Arbor

first: Bioinformatics

last: Core

state: MI

address: 2800 Plymouth Road

department: BRCF Bioinformatics Core

institute: University of Michigan

summary: Regulatory T cells (Treg) are common in the tumor microenvironment in both human pancreatic cancer and in genetically engineered mouse models of the disease. Previous studies in orthotopic syngeneic models of pancreatic cancer -recapitulated in our own data- indicated that Treg depletion results CD8+ T cell-mediated tumor regression. In human patients and in mouse models, regulatory T cells accumulate during the onset of Pancreatic Intraepithelial Neoplasia (PanIN), the earliest steps of carcinogenesis. We thus generated a genetic model to investigate the role of regulatory T cells during the onset of pancreatic carcinogenesis. Unexpectedly,  depletion of Tregs during early stages of carcinogenesis led to accelerated tumor progression.

overall_design: We are using KC;Foxp3DTR mice generated by crossing KC (Ptf1a-Cre;LSL-KrasG12D) with Foxp3DTR (B6.129(Cg)-Foxp3tm3(DTR/GFP)Ayr/J, Jackson Laboratory). We depleted Foxp3-expressing Tregs by Diphtheria Toxin (DT) injection to determine the requirement of Tregs during oncogenic Kras induced Pancreatic Intraepithelial Neoplasia (PanIN) formation and maintenance. To investigate the mechanisms underlying the tumor-promoting effect of Treg depletion in KC; Foxp3DTR mice we performed RNA sequencing (RNAseq) for myeloid cells (DAPI-EpCAM-CD45+CD11b+) flow-sorted from KC and KC; Foxp3DTR pancreata.

first: Marina

middle: P

last: Di Magliano

first: Yaqing

last: Zhang

first: Chris

last: Gates

first: Rebecca

last: Tagett


title: Catalytic subunits switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells [ChIP-seq]

status: Public on Feb 10 2019

city: Philadelphia

first: Priyankara

last: Wickramasinghe

address: 3601 Spruce Street

department: Bioinformatics

institute: The Wistar Institute

summary: The SWI/SNF chromatin remodeling complex is altered in ~20% of human cancers.  ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is the most frequently mutated epigenetic regulator in human cancers. Inactivation of the SWI/SNF complex is synthetically lethal with inhibition of EZH2 activity.  EZH2 inhibitors are entering clinical trials for specific tumor types with SWI/SNF mutations.  However, mechanisms of de novo or acquired resistance to EZH2 inhibitors in cancers with inactivating SWI/SNF mutations are unknown.  Here we show that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2 drives resistance to EZH2 inhibitors in ARID1A-mutated ovarian cancer cells.

overall_design: Parental TOV21G cell line and and resistant to EZH2 inhibitor GSK126 treatment clones were assayed by RNA-seq and BRG1 CHIP-seq

first: Rugang

first: Shuai

last: Wu


title: Catalytic subunits switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells [RNA-seq]


title: Distinct gene expression changes in human peripheral blood mononuclear cells treated with different tobacco product preparations

status: Public on Feb 25 2019

city: Winston-salem

first: Prasad

last: GL

state: NC

address: 401 N Main St

institute: RAISC

summary:
Cigarette smoking exerts diverse physiological effects including immune suppression. Existing US epidemiological data show that consumption of smokeless tobacco products, such as moist snuff, is less harmful relative to cigarette smoking. In efforts to understand the molecular changes due to consumption of different tobacco product classes, we have shown recently that smokers exhibit distinct peripheral blood mononuclear cells (PBMCs) gene expression patterns relative to moist snuff users and non-tobacco consumers (NTCs). To better characterize the biological effects exerted from the use of different tobacco products, a genome-wide gene expression study, using a cultured PBMC model, was performed.
Global gene expression profiling results showed that 5,421 genes (2,809 upregulated and 2,612 downregulated) were dose-dependently changed by WSCM (pFDR < 0.01). Some gene expression changes detected in the cultured system were also observed in clinical studies. For example, FEZ1 and SLAMF7 were suppressed by WSCM while CCR2 and HHEX genes were upregulated by WSCM commonly in the cultured experiment and clinical studies. WSCM exposures, but not STE, uniquely affected genes involved in immune cell development and inflammatory response. Ingenuity Pathway Analysis identified upstream regulators, such as TNF, IL1β, and NFκB to be likely responsible for the observed gene expression changes and that these cascading signals were generally suppressed by WSCM, but not STE. Collectively, these findings sµggested that combustible and non-combustible tobacco products produce distinct biological effects which could explain the observed chronic immune suppression in smokers.

overall_design: We investigated global gene expression changes in PBMCs exposed to aqueous extracts of cigarette smoke (whole smoke conditioned media [WSCM]) and moist snuff extract (smokeless tobacco extract [STE]). PBMCs were isolated from whole blood of four healthy NTC donors and exposed under different doses of WSCM or one dose of STE.

first: Quynh

middle: T

last: Tran

first: G

last: Prasad


title: Global gene expression profiles of cardiomyocytes differentiated from human pluripotent stem cells (hiPSC-CMs) in 3D culture exposed to ethanol

status: Public on Jan 31 2019

city: Atlanta

first: Antonio

last: Rampoldi

state: Georgia

address: 2015 Uppergate Dr

department: Pediatrics

institute: Emory University Hospital

summary:
Methods: RNA-seq libraries were prepared using the Illumina TruSeq RNA kit and the TrueSeq method was employed for mRNA enrichment. The libraries were quantified and samples were multiplexed in each lane of the flowcell. Cluster generation was performed and then sequenced on the Illumina HiSeq2500 system. Reads were mapped on the Human Genome Reference and normalized expression table was generated.
Results: RNA-seq results reveal gene expression of cardiac toxicity in hiPSC-CMs that are consistent with alcohol-induced pathophysiology observed in animal models.  For example MMP9 is among the top 5 upregulated genes in ethanol-treated hiPSC-CMs,  MMP9 concentrations are significantly higher in human sera of chronic alcohol abusers and MMP9 mRNA and protein levels are increased in the myocardium of rats following acute ethanol exposure.
Conclusions: Data demonstrate significant alteration in gene expression, among the top 60 genes significantly altered by ethanol exposure, 8 genes are involved in ion channels, which may be in part contributing to the abnormal intracellular Ca2+ transients. Ethanol up-regulated the expression of genes associated with collagen metabolism and extracellular matrix (MMP9, EMID1, COL14A1), most of the downregulated genes are involved in cardiovascular system development (NPPB, DNAAF3), actin filament-based process (LMOD2, MYH4) and muscle contraction (MYL2).  These findings are consistent with previous studies showing a correlation between alcohol exposure and defects in heart and circulatory system development.

overall_design: RNA-sequencing analysis was performed to compare global gene expression profiles of cardiomyocytes under ethanol treatment vs. control.

first: Meixue

last: Duan

first: Greg

last: Gibson

first: Chunhui

last: Xu


title: Catalytic subunits switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells

state: PA

overall_design: Refer to individual Series


title: Gene expression profiles of primary human NK cells before and after expansion on CSTX002 feeder cells, with and without IL-21 stimulation

city: Columbus

first: Dean

last: Lee

state: Ohio

address: 700 Children’s Drive

department: Hematology & Oncology

institute: Nationwide Children’s Hospital

summary: NK cell development, maturation, and activation by cytokines is driven by alterations in gene expression mediated by activation and repression or transcriptional programs. In particular, we have extensively studied the role of STAT3 in human NK cells. This was based in part on a method we developed for in vitro expansion of large numbers of highly active NK cells using a genetically-modified feeder cell expressing 4-1BBL and membrane-bound IL-21. To dissect the various gene expression profiles induced by IL-21 from the various other signals received from the feeder cell, we purified peripheral NK cells from 4 healthy subjects (naïve, N), expanded NK cells for 14 days using CSTX002 feeder cells (expanded, E), and extracted RNA from the cells without (Neg) or after (Pos) the cells were activated with IL-21. We then performed RNA sequencing on each sample.

overall_design: NK cells were purified from buffy coats obtained from 4 normal healthy blood-bank donors using RosetteSep NK for negative depletion of other cell subsets. NK cells were expanded by weekly stimulation with irradiated CSTX002 feeder cells. Naïve or expanded NK cells were stimulated for 30 minutes with 20 ng/ml recombinant human IL-21. Total RNA was prepared using the Total RNA Purification Plus Kit (Norgen Biotek, Ontario, ON, Canada). Libraries were prepared using the TruSeq RNA Sample Preparation Kit (Illumina Inc., San Diego, CA). 60–80 million paired-end 150 bp sequence reads per library were generated using the Illumina HiSeq4000 platform.

first: Nitin

last: Chakravarti


title: mRNA regions where 80S ribosomes pause during translation elongation in vivo interact with protein uS19, a component of the decoding site

status: Public on Mar 14 2019

city: Novosibirsk

first: Marsel

last: Kabilov

address: Lavrentyev av. 8

country: Russia

institute: ICBFM SB RAS

summary: 80S-ribosome bound uS19 translatome-wide crosslinking sites in human mRNAs revealed by PAR-CLIP

overall_design: We focused on determining the uS19 contacts with mRNAs in vivo by applying the photoactivatable-ribonucleoside enhancing cross-linking and immunoprecipitation method to a stable HEK293 cell line inducibly producing FLAG-tagged uS19 and grown on a medium containing 4-thiouridine.

first: Elena

middle: S

last: Babaylova

first: Alexander

last: Gopanenko

first: Konstantin

last: Bulygin

first: Alexey

middle: E

last: Tupikin

last: Malygin

first: Galina

last: Karpova


title: Gene expression in eggs is influenced by the domestication process in Eurasian Perch (Perca fluviatilis)

status: Public on Apr 01 2019

city: Rennes

first: Aurelie

last: LE CAM

address: Campus de Beaulieu

department: PHASE

institute: INRA

summary: The domestication is an evolutionary process during which individuals will progressively adapt to an environment controlled by humans. It is accompanied by epigenetic and genetic modifications potentially leading to modifications in the transcriptomic profile in various tissues. The reproduction process is among the biological functions highly affected whatever the species and/or the way of domestication. Indeed, the reproduction success often decreases in domesticated populations. For fish, the molecular content of the eggs is crucial for the proper embryogenesis. Among these molecules the mRNA content depends directly from the gene expression and thus may reflect the genetic modifications occurring during this process. Here, we investigated the transcriptomic profile of eggs coming from females of two populations (F1 and Fx) that were reared in the same conditions and were genetically close. Our main goal was thus to determine how the domestication process may affect the reproduction success in the Eurasian perch and if it was mediated by the regulation of the transcription in the eggs. A regular follow up of the oogenesis progression showed few differences of the hormonal production between the two populations. Nevertheless, the histological study showed that the F1 females were more developed by the end of the oogenesis induction than the domesticated ones and as a result, they spawned earlier than the domesticated ones. The study of the early developmental success revealed significant differences between the populations. The microarray analysis of unfertilized eggs presented more than 350 transcripts differently expressed between the two populations. Among them, some specific genes were drastically more expressed in the domesticated (mex3B, hace1 and an uncharacterized protein) or F1 (per) populations. Our data show that the F1 population is more sensitive to the environmental conditions to advance oogenesis and reach the spawning season earlier. The transcriptomic profiles in eggs coming from the two populations were different and may lead to developmental impairments having a potential link with the domestication process. Further analyses are needed to explain these differences.

overall_design: 31 samples were analyzed. The F1 population was represented by 18 samples and the Fx one had 13 samples.

first: Tainá

last: Rocha de Almeida

first: Maud

last: Alix

first: Aurélie

last: Le Cam

first: Jérôme

last: Montfort

first: Lola

last: Toomey

first: Yannick

last: Ledore

first: Julien

last: Bobe

first: Dominique

last: Chardard

first: Bérénice

last: Schaerlinger

first: Pascal

last: Fontaine


title: Transcriptome Sequencing of Penicillium digitatum

city: Zhenjiang

first: Qian

last: xin

state: Jiangsu

address: 301 Xuefu Road

institute: Jiangsu University

summary: Penicillium digitatum is the pathogen of Green mold in Postharvest citrus. After inoculating Penicillium digitatum into the wound of citrus to infect it, transcriptome sequencing was carried out and compared with the results of transcriptome sequencing of Penicillium digitatum before inoculation in order to screen the differentially expressed genes and reveal its infection mechanism.

overall_design: Penicillium digitatum before and after infected Citrus (Tangerine).

last: Xin


title: Epigenome regulation during epidermal lineage commitment

status: Public on Jan 28 2019

city: Stanford

first: Anthony

last: Oro

state: CA

address: 269 Campus Drive, CCSR 2145c

department: Dermatology

institute: Stanford University

overall_design: Refer to individual Series this includes RNA-Seq, ChIP-Seq and ATAC-Seq


title: RNAseq of MAIT cells in human peripheral blood from acutely infected, HIV+ donors

status: Public on Feb 20 2019

city: Silver Spring

first: Dohoon

last: Kim

address: 503 Robert Grant Avenue

department: MHRP

institute: Henry M Jackson

summary: Mucosa-associated invariant T (MAIT) cells recognize microbial-derived riboflavin metabolites presented by the evolutionarily conserved MR1 molecule. Their persistent loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we explore MAIT cell dynamics in the critical acute stages of HIV-1 infection for the first time

overall_design: We FACS sorted MAIT cells identified as Va7.2+ CD161++ of CD3+ T cells from cryopreserved human peripheral blood and performed bulk RNAseq on these cells.

first: Michael

last: Eller

first: Johan

last: Sandberg

first: Kerri

last: Lal


title: Transcriptomics of mild drought response in barley

status: Public on Mar 09 2019

city: Katowice

first: Agnieszka

last: Janiak

address: Jagiellonska 28

department: Department of Genetics

country: Poland

institute: University of Silesia in Katowice

summary: The data present global gene expression profiling of roots of two barley genotypes with contrasting ability to cope with drought stress. We used the whole root system and the second leaf of CamB and Maresi genotypes subjected to 10-days of mild drought at seedling stage. The transcriptomes of leaves served in the presented study as a background to depict, which genes may respond with the expression changes in an organ-specific manner. Our data indicate that the mild drought resulted in more changes in the transcriptomes of roots than in the leaves and more differentially expressed genes (DEGs) were root-specific. We also found that similar number of DEGs were induced or repressed by the stress in roots of CamB genotype, whereas in roots of more drought susceptible Maresi a down-regulation of gene expression prevailed. We identified 88 genes encoding transcription factors and gene expression regulators that were differentially expressed in roots and the majority of them were root-specific. We discuss their probable function in drought response and tolerance and predicted a possible regulatory network downstream of selected transcription factors.

overall_design: Two barley genotypes were used for the study: a German semidwarf cultivar Maresi and a Syrian breeding line Cam/B1/CI08887//CI05761 (CamB), adapted to dry environments. Two water regimes were used: control conditions and a mild drought, which was applied at the 3-leaf seedling stage and lasted for 10 days. The experiment was carried out in three replicates and tissue for RNA extraction was collected from five plants per replicate.

first: Miroslaw

last: Kwasniewski


title: Epigenome regulation during epidermal lineage commitment [RNA-seq]

summary: Recent advances in human pluripotent stem cell (hPSC) technology provide a unique resource for skin tissue replacement, but the detailed understanding of regulatory  mechanisms limits standardization and broad clinical application. Here, we interrogate chromatin accessibility and transcriptome dynamics during hPSC-derived epidermal  differentiation, and discover two critical transition periods: surface ectoderm initiation and keratinocyte maturation. Using inference network modeling, we develop a computational  framework for each transition, and identify TFAP2 and TP63 and their cofactors as key regulators. Surprisingly, functional studies demonstrate the sufficiency of TFAP2C to  initiate surface ectoderm differentiation by activating the early TF network and its chromatin landscape changes, while loss of TFAP2C inhibits early commitment. TFAP2Cinitiated  cells are competent to further differentiate into functional keratinocytes in selective media, accompanied by activation of the keratinocyte maturation network and  decline of the early network. Mechanistically, TFAP2C activates the expression and increases binding site accessibility and positive autoregulation of the master regulator  P63, while loss of P63 results in failure to close TFAP2-initiated early program and leads to maturation and survival defects, revealing a positive-negative feedback loop that  ensures complete transition from progenitor to maturation tissue. Our work reveals the logic underlying dynamic epigenome-transcription factor interactions during human  epidermal lineage commitment that will facilitate improved tissue engineering and regenerative medicine.

overall_design: chromatin accessibility and gene expression profile in epidermal differention from normal hESC, and hESCs containing inducible expression of TFAP2C or p63 KO  were generated by ATAC-seq and RNA-seq, in two replicates at each stage, using illunia Hiseq 2000 and Nextseq 500.

first: Lingjie

last: Li

first: Gautam

last: Shankar


title: Epigenome regulation during epidermal lineage commitment [ATAC-seq, RNA-seq]

overall_design: Chromatin accessibility and gene expression profile in epidermal differentiation from normal hESC, iPSC , and hESCs containing inducible expression of TFAP2C or p63 KO  were generated by ATAC-seq and RNA-seq, in two replicates at each stage, using illunia Hiseq 2000 and Nextseq 500. Chromatin accessibility (NextSeq 500) and gene expression profile (HiSeq 2000) in normal human keratinocye (NHK).


title: Characterization of microRNA-493-5p targets in liver cell lines (2nd set of data)

status: Public on Jan 22 2019

city: Wako

first: Luc

last: Gailhouste

state: Saitama

address: 408 Main Research Building, 2-1 Hirosawa

department: Cluster for Pioneering Research

institute: RIKEN

summary: Primary hepatic tumors mainly include hepatocellular carcinoma (HCC), which is one of the most frequent causes of cancer-related deaths worldwide. Thus far, HCC prognosis has remained extremely poor given the lack of effective treatments. Numerous studies have described the roles played by microRNAs (miRNAs) in cancer progression and the potential of these small noncoding RNAs for diagnostic or therapeutic applications. The current consensus supports the idea that direct repression of a wide range of oncogenes by a single key miRNA may critically affect the malignant properties of cancer cells in a synergistic manner. In this study, we aimed to investigate the oncogenes controlled by miR-493-5p, a major tumor suppressor miRNA that inactivates miR-483-3p oncomir in hepatic cancer cells. Using global gene expression analysis, we highlighted a set of candidate genes potentially regulated by miR-493-5p. In particular, the canonical MYCN proto-oncogene (MYCN) appeared to be an attractive target of miR-493-5p given its significant inhibition via 3’-UTR targeting in miR-493-5p-rescued HCC cells. We showed that MYCN was overexpressed in liver cancer cell lines and clinical samples from HCC patients. Notably, MYCN expression levels were inversely correlated with miR-493-5p in tumor tissues. We confirmed that MYCN knockdown mimicked the anti-cancer effect of miR-493-5p by inhibiting HCC cell growth and invasion, whereas MYCN rescue hindered miR-493-5p activity. In summary, miR-493-5p is a pivotal miRNA that modulates various oncogenes after its re-expression in liver cancer cells, suggesting that tumor suppressor miRNAs with a large spectrum of action may provide valuable tools for miRNA replacement therapies.

overall_design: To identify miR-493-5p targets, Hep3B and HepG2 cells were transfected using miR-493-5p mimics and negative control miRNA mimics.

first: L

first: T

last: Ochiya


title: Gene expression changes in A375 melanoma cells in response to ERK3 knockdown.

city: Dayton

last: Markey

state: OH

address: 3640 Colonel Glenn Hwy.

department: Biochemistry and Molecular Biology

institute: Wright State Unviersity

summary: Gene expression microarrays were used to compare A375 cells treated with a control siRNA or an siRNA targeting ERK3 (MAPK6).

overall_design: Three replicates are included for each condition (siCon and siERK3). Total RNA was extracted using Trizol® reagent (Ambion) three days post-siRNA-transfection. RNA quality was assessed on an Agilent 2100 Bioanalyzer following the manufacturer’s protocol.  Samples with RNA integrity numbers (RIN) >6 were used for further analysis. RNA concentration was measured by NanoDrop™ One Spectrophotometer (Thermo Fisher Scientific). Affymetrix microarray system was used for gene expression analysis using Clariom™ S Pico Assay (human) platform with WT PLUS Kit and GeneChip® Hybridization, Wash, and Stain Kit following the manufacturer’s protocols.


title: Next Generation Sequencing of Wildtype and Thioredoxin-A knockout of a clinical isolate of Acinetobacter baumannii

status: Public on Jan 14 2019

city: San Antonio

first: Bernard

last: Arulanandam

state: Texas

address: 1 UTSA Cir

department: Biology

institute: University of Texas at San Antonio

summary: RNA sequencing was used to analyze the transcriptome of a thioredoxin-A knockout of  a clinical isolate of Acinetobacter baumannii

overall_design: Bacteria was grown to mid-log phase and RNA-extraction and mRNA enrichment was complete on full cell

first: Holly

last: May

first: Jieh-Juen

last: Yu

first: Hao

last: Zhang

first: Yufeng

last: Wang


title: Transcriptomic analysis of microglia 4 month old ML4 Fabry and control mice

status: Public on Jan 01 2019

city: bethesda

first: antony

middle: cyril

last: cougnoux

state: md

address: BG 10-CRC RM 1-3288 10 CENTER DR

department: nichd

institute: nih

summary: the study aims to describe the modifications occurring the microglia isolated from mouse models of 2 lysosomal storage diseases: Mucolipidosis type 4 and fabry disease.

overall_design: FACS isolated microglia (Cx3cr1+cd45+cd11b+) in PBS+BSA were wash twice in PBS and RNA was extracted using trizol. Microglia were isolated from Fabry (Fab), Mucolipidosis type 4 (ML4) and littermate control (B6_plus)


title: Sex-specific gene expression differences are evident in human embryonic stem cells and during in vitro differentiation of human placental progenitor cells

status: Public on Dec 31 2018

first: Montserrat

last: Anguera

address: 3800 Spruce Street, Rosenthal Room 390EB

department: Biomedical Sciences

institute: University of Pennsylvania School of Veterinary Medicine

summary: Here, we examine sex-specific gene expression differences during in vitro differentiation of male and female human embryonic stem cells (hESCs) into trophoblastic progenitors, as our current understanding of the early events of human trophoblast formation is limited. We perform RNA-Sequencing in 3 female and 3 male hESC lines at days 0 and 5 of BMP4/A/P trophoblastic progenitor cell differentiation. Differential gene expression was performed with DESeq2, and reveals significant sex differences with transcriptomic profiles in hESCs and trophoblastic progenitors, and also with the differentiation process itself.

overall_design: Comparison of male and female hESC transcriptome during trophectoderm differentiation.

first: Camille

middle: M

last: Syrett


title: Keeping Siblings Together: Enterovirus Collective Dispersal through Extracellular Vesicles Involves Genetically Related Viral Particles

status: Public on Dec 29 2018

city: Paterna

first: Juan

middle: Vicente

last: Bou

state: Valencia

address: Carrer del Catedratic Agustin Escardino Benlloch, 9

department: Genetics

country: Spain

institute: University of Valencia

type: Genome variation profiling by high throughput sequencing

summary: Viruses can disperse collectively using extracellular vesicles and other types of multi-virion structures. It has been hypothesized that, by increasing the cellular multiplicity of infection, this dispersal mode may favor cooperation among viral genomes. However, the spread of defective variants that function as social cheaters could also be promoted. To better understand the nature of virions present in vesicles, here we examine the genetic diversity harboured by vesicles of coxsackievirus B3 (CVB3), a model enterovirus. Our results confirm that CVB3 vesicles contain multiple infectious particles. However, we also find that virus variants coinfecting a cell typically allocate their progenies into different vesicles, precluding long-term interactions among them. Furthermore, Illumina sequencing indicates that dispersal through vesicles does not increase viral population genetic diversity appreciably. We conclude that vesicles enable the co-dispersal of groups of virions, but that these groups are highly related since they share the same parental genome. This should restrict the evolution of defective viruses, but also makes cooperation among different viral genetic variants unlikely. Our results are in line with a fundamental tenet of social evolution theory, according to which the evolution of cooperation typically requires that the interacting partners are genetically related.

overall_design: Examination of genetic diversity accumulated after 20 serial transfers of coxsackievirus b3 at low multiplicity of infection selecting, in duplicate, vesicles (V), broken-vesicles (bV) and free viral particles (S) using Illumina Miseq sequencing. Genetic diversity of the founder was evaluated sequencing the viral population that was used to initiate the evolution.

middle: V

first: Ron

last: Geller

first: Rafael

last: Sanjuán


title: Gold Compound Induces Immune Suppression via AHR-TGF-β1 Signaling

status: Public on Jan 16 2019

city: Frankfurt am Main

first: Xinlai

last: Cheng

state: Hessen

address: Max-von-Laue-Strasse 15. R. 3.652

department: Chemical Biology

institute: Goethe Frankfurt University. BMLS

summary: Gold compounds containing planar N-heterocyclic (NHC) carbene ligands are potent aryl hydrocarbon receptor (AHR) ligands. Further studies with the lead compound (called MC3), show that MC3 activates TGFβ signaling while repressing CD4+ T-cell activation in vitro, in human and mouse T-cells, and in scurfy mouse, while repression of AHR activity or TGFβ-SMAD cascades compensated its immune suppressive function. The in-vivo induction of Tgfb1 expression was associated with reduced severity of the autoimmune markers.

overall_design: Total RNA was extracted from MC3-treated and non-treated HepG2 cells for 1 and 24 hours. The cell culture was carried out in standard well-plate culture.

first: Rodrigo

last: Gama-Brambila


title: Transcriptional Sequencing Uncovers Survival Mechanisms of Salmonella enterica serovar Enteritidis in Antibacterial Egg White

city: Shanghai

first: Xiaozhen

last: Huang

address: 800 Dongchuan RD. Minhang District.

department: School of Agriculture & Biology

institute: Shanghai Jiao Tong University

summary:
Purpose: To elucidated key metabolic pathways important for S. Enteritidis survival in egg white.
Methods: RNA sample of Mid-log phase bacteria cultures that grown in M9FeS medium were taken as 0h sample, and bacteria incubated with egg white for 6h 12h and 24h were taken as 6,12,24h RNA sample respectively. Three biological replicates were carried out per sample. RNA sample was sequenced with Illumina HiSeq 2000 System. DESeq2 method was used to calculate the differentially expressed genes. qRT–PCR and gene mutation were used to validate RNA-seq result.
Results: A total of 12 samples were sequenced. The average output of each sample was 1.33 Gb, and the average comparison rate with the reference genome was 97.51%. M9FeS and egg whites cultivation resulted in 2400 to 2700 expressed genes accounting for 53 to 58% of the whole genome. In this group, 1240 to 1470 genes had significant levels of log2 fold changes ≥1, (Padj <0.05) compared with control. These accounted for 27.3 to 32.2% of the whole genome indicating a large shift in the transcriptional response to egg whites. qRT–PCR result of 21 selected genes highly consistent with the RNAseq results at all three timepoints. 8 out of 12 DEGs mutants showed decreased survival ability in egg white, suggested that the DEGs from the RNAseq results correlated significantly with the egg white resistance phenotype.
Conclusions: Using strand-specific RNA sequencing, we found pathways significantly changed in egg white. Genes involved in SOS-dependent and independent DNA damage repair, alkaline pH adaption, osmotic stress adaption, envelope damage repair including maintaining periplasm homeostasis and reinforcing peptidoglycan layer, nitrogen assimilation, Salmonella pathogenicity island 2, iron absorption and biotin synthesis, were significantly up regulated in bacteria surviving in egg whites. Differentially expressed genes involved in energy metabolism, translation, and cell motility, Salmonella pathogenicity island 1 were significantly down-regulated in egg whites.

sample_organism: Salmonella enterica subsp. enterica serovar Enteritidis

overall_design: Three biological repetitions of 0h samles and 3 egg whte incubation samples, totally for 12 samples were conducted RNA sequncing. 0h sample was used as control.

first: Ben

last: Jia

first: Xianming

last: Shi


title: AhR mediated changes in the murine lung dendritic cell transcriptome

status: Public on Dec 18 2018

city: Rochester

first: Paige

last: Lawrence

state: NY

address: 601 Elmwood Ave

institute: University of Rochester

summary: Analysis of gene expression in isolated mouse lung dendritic cells isolated during influenza A virus infection, with and without activaiton of the aryl hydrocarbon receptor (AHR).

overall_design: To determine genome wide changes in dendritic cells mediated by aryl hydrocarbon receptor activation

first: Anthony

last: Franchini

first: Jason

middle: R

last: Myers

first: Guang-bi

last: Jin

first: B


title: Characterization of epigenetically silenced microRNAs in liver cancer cells

status: Public on Dec 05 2018

first: Luc

last: Gailhouste

summary: Numerous studies have described the critical role played by microRNAs (miRNAs) in cancer progression and the potential of these small non-coding RNAs for diagnostic or therapeutic applications. However, the mechanisms responsible for the altered expression of miRNAs in malignant cells remain poorly understood. Herein, via epigenetic unmasking, we identified a group of miRNAs located in the imprinted delta like non-canonical Notch ligand 1 (DLK1)-maternally expressed 3 (MEG3) locus that were repressed in hepatic tumor cells. Notably, miR-493-5p epigenetic silencing was correlated with hypermethylation of the MEG3-differentially regulated region (DMR) in liver cancer cell lines and tumor tissues from patients. Experimental rescue of miR-493-5p promoted an anti-cancer response by hindering hepatocellular carcinoma (HCC) cell growth in vitro and tumor progression in vivo. We found that miR-493-5p mediated part of its tumor-suppressor activity by abrogating overexpression of insulin-like growth factor 2 (IGF2) and the IGF2-derived intronic oncomir miR-483-3p in HCC cells characterized by IGF2 loss of imprinting (LOI). In summary, this study describes an unknown miRNA-dependent regulatory mechanism between two distinct imprinted loci and a possible therapeutic window for liver cancer patients exhibiting IGF2-miR-483 LOI and amplification.

overall_design: To identify miRNAs epigenetically silenced in liver cancer, the human HCC cell line HepG2 was treated with the demethylating agent 5-azacytidine (5-AZA) for 12 days (epigenetic unmasking).

first: L

first: T

last: Ochiya


title: Epigenome regulation during epidermal lineage commitment [ChIP-seq]

status: Public on Jan 29 2019

last: Oro

overall_design:
Chromatin accessibility, gene expression profile and TF binding sites in epidermal differention from normal hESC, and hESCs containing inducible expression of TFAP2C or p63 KO were generated by ATAC-seq, RNA-seq and ChIP-seq, in two replicates at each stage, using illunia Hiseq 2000 and Nextseq 500.
This series includes the ChIP-seq data sets.

first: Lingjie

last: Li

first: Gautam

last: Shankar


title: Gene expression profiles of KK.Cg-Ay/J (KKAy) mice and KK-a/a (KKa) mice

status: Public on Dec 13 2018

city: Taichung

first: Fuu-Jen

last: Tsai

address: No.2, Yude Rd., North Dist.

department: Department of Medical Research

institute: China Medical University Hospital

summary:
The differential gene expression in hepatocytes was compared between the KK.Cg-Ay/J mice and the KK-a/a mice, corresponding to the Diabetic strain and the control. The microarrays were used to screen the candidates supporting to the essential pathogenesis of Type-2 Diabetes in the pre-developing, early and developing stages, corresponding to the 6 weeks, 16 weeks and 42 weeks.
To determine the significant biological processes and pathways contributing to development of Diabetic phenotypes in the KKAy mouse, we identified the candidates with the differential gene expression of the livers by comparison of the KKAy and KKa mice. These genes have relationship linkage to construct the networks for mechanistic explanation of the disease.

overall_design: The comparison of gene expression profiles between the KKa mice and the KKAy mice, which are described as the Diabetic model with obesity. There were four KKAy mice and four KKa mice in each investigating stage and we totally had three stages for 6, 16 and 42 weeks old for the experiment. Samples from the liver tissues of the four grouped mice were mixed together with equal weight, with two replicates for microarray analysis.

first: Tran

last: Thai

first: Shih

middle: Y

last: Chen

first: Fuu


title: DNA methylation profiles of KK.Cg-Ay/J (KKAy) mice and KK-a/a (KKa) mice

summary:
The differential DNA methylation in hepatocytes was compared between the KK.Cg-Ay/J mice and the KK-a/a mice, corresponding to the Diabetic strain and the wild-type known as control. The methylation microarrays were used to support gene expression for screening the candidates susceptibility to the pathogenesis of Type-2 Diabetes in the pre-development, early and development stages, corresponding to the 6, 16 and 42 weeks old.
To determine the methylation-dependent biological processes and pathways contributing to development of Diabetic phenotypes in the KKAy mouse, we identified the candidates with the differential DNA methylation levels between the KKAy and KKa mice. The expression of methylation-dependent genes have relationship linkage to construct the networks for mechanistic explanation of the disease.

overall_design: The comparison of DNA methylation profiles between the KKa mice and the KKAy mice, which are described as the Diabetic model with obesity. There were four KKAy mice and four KKa mice in each investigating stage and we totally had three stages for 6, 16 and 42 weeks old for the experiment. Samples from the liver tissues of the four grouped mice were mixed together with equal weight, with two replicates for microarray analysis.

middle: J


title: Genome-wide DNA methylation profiling in progressive supranuclear palsy (PSP)

status: Public on Dec 01 2018

city: Evry

first: Jorg

last: Tost

address: 2 rue Gaston Cremieux

institute: CEA-Institut de Genomique, Centre National de Genotypage

summary: Genome wide Methylation profiling of DNA extracted from post-mortem forebrains of PSP patients (n=94) and of controls (n=72). The Illumina Infinium HumanMethylation450 BeadChip was used representing 485,000 potentially methylated CpG sites throughout the genome.

overall_design: Bisulphite converted DNA from 166 samples (n=94 PSP and n=72 controls) were hybridised to the  Illumina Infinium HumanMethylation450 BeadChip

first: Axel

last: Weber

first: Sigrid

last: Schwarz

first: Pawel

last: Tacik

first: Jörg

first: Florence

last: Busato

first: Dietrich

last: Trümbach

first: Pia

last: Winter

first: Anita

middle: C

last: Windhorst

first: Thomas

last: Arzberger

first: Elen

last: Gelpi

first: Catriona

last: McLean

first: Daniela

last: Vogt-Weisendorn

first: Wolfgang

last: Wurst

first: Dennis

middle: W

last: Dickson

first: Günter

middle: U

last: Höglinger

first: Ulrich

last: Müller


title: Gene expression and DNA methylation profiles of KK.Cg-Ay/J (KKAy) mice and KK-a/a (KKa) mice

first: Fuu-Jen

last: Tsai

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

overall_design: Refer to individual Series

first: Tran

last: Thai

first: Shih

last: Chen

first: Fuu


title: In search for materials able to be colonized by a normal endothelium: сharacterization and NGS gene expression profiling of human primary endotheliocytes cultivated on electrospun 3D matrices

status: Public on Nov 29 2018

first: Petr

last: Laktionov

address: Lavrenitev ave 8/2

institute: Institute of molecular and cellular biology SD RAS

summary: Endothelization of the luminal surface of vascular grafts is required for their long-term functioning. In order to select the best surface we have cultivated HUVEC on different 3D matrices and assessed the efficacy of cell proliferation and the changes in the gene expression profiles. 3D matrices were produced by electrospinning from solutions of poly(D,L-lactide-co-glycolide) (PLGA), polycaprolactone (PCL) and blends of PCL with gelatin (PCL-Gl) and glutaraldehyde-treated PCL-GL (PCL-Gl-glu)  in hexafluoroisopropanol. Gene expression profiling was executed using Illumina HiSeq2500 platform.

overall_design: RNA-Seq gene expression profiling of HUVEC cells grown on different 3D matrices. We used HUVEC cells obtained from two donors, thus we obtained two biological replicates for each matrix tested (namely, control/tissue culture polystyrene (TCPS), PCL, PLGA, PCL-Gl, PCL-Gl-glu)  and generated 10 RNA-Seq gene expression profiles in total.

first: Alena

last: Stepanova

first: Anna

last: Cherepanova

first: Vera

last: Chernonosova

first: Georgiy

last: Shevelev

first: Ivan

last: Zaporozhchenko

first: Alexander

last: Karaskov

first: Pavel


title: Obesity Remodels Activity and Transcriptional State of a Lateral Hypothalamic Brake on Feeding

status: Public on May 02 2019

city: Chapel Hill

first: Marcus

middle: Luis

last: Basiri

address: 115 Mason Farm Road

institute: UNC Chapel Hill

summary: We demonstrate that high fat diet (HFD)-induced obesity alters the transcriptional state of lateral hypothalamic glutamate neurons in mice.

overall_design: High-throughput single-cell RNA sequencing of lateral hypothalamic area (LHA) tissue in mice given ad libitum access to HFD or taste-matched control chow.

middle: L

first: Mark

last: Rossi

first: Garret

middle: D

last: Stuber


title: Transcriptome sequencing wide functional analysis of human mesenchymal stem cells (LPS)

status: Public on Apr 03 2019

city: Ansan

first: Young Gyu

last: Chai

state: Gyeonggi-do

address: 55 Hanyangdaehak-ro

department: Molecualr & Life Science

institute: Hanyang Univ.

summary: Using RNA-seq, we report here that BM-MSC cells have a distinct transcriptomic signature and express a unique cluster of transcripts in response to 4 hrs LPS (1ug/ml).

overall_design: Examination of effects of LPS-stimulated BM-MSCs, were generated by deep sequencing on an Illumina HiSeq 2500(101 cycles PE lane).

first: Y

middle: G

first: J


title: Hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells

status: Public on Nov 19 2018

city: Cleveland

first: Peter

middle: A

last: Wilkinson

address: 2103 Cornell Road

department: Pathology / Systems Biology & Bioinformatics

institute: Case Western Reserve University

summary: Innate lymphoid cells (ILCs) play critical roles in mucosal barrier defense and tissue homeostasis. While ILCs are depleted in HIV-1 infection, this phenomenon is not a generalized feature of all viral infections.  Here we show in untreated SIV-infected rhesus macaques (RMs) that ILC3s are lost rapidly in mesenteric lymph nodes (MLN) yet preserved in SIV+ RMs with pharmacologic or natural control of viremia.  In healthy uninfected RMs, experimental depletion of CD4+ T cells in combination with DSS is sufficient to reduce ILC frequencies in the MLN.  In this setting and in chronic SIV+ RMs, IL-7R alpha chain expression diminishes on ILC3s in contrast to the IL-18R alpha chain expression which remains stable. In HIV-uninfected patients with durable CD4+ T cell deficiency, deemed idiopathic CD4+ lymphopenia, similar ILC deficiencies in blood were observed, collectively identifying determinants of ILC homeostasis in primates and potential mechanisms underlying their depletion in HIV/SIV infection.

overall_design: There are 12 samples, 3 healthy, 8 SIV infected of which there are 4 acute and 4 chronic SIV infected.

last: Mudd

first: K

last: Busman-Sahay

first: S

last: DiNapoli

last: Lai

first: V

last: Sheik

first: A

last: Lisco

first: C

last: Deleage

first: B

last: Richardson

first: David

last: Palesch

first: M

last: Paiardini

last: Cameron

first: I

last: Sereti

last: Reeves

last: Estes

last: Brenchley

first: P


title: A bipartite boundary element restricts UBE3A imprinting to mature neurons

status: Public on Jan 07 2019

city: Farmington

first: Justin

last: Cotney

state: CT

address: 400 Farmington Avenue

department: Genetics and Genome Sciences

institute: UConn Health

summary: CTCF binding and three-dimensional chromatin interactions (4C-seq) in the region of human chromosome 15 associated with imprinting of UBE3A

overall_design:
IPW, PWAR1 and a 24kb region spanning these genes on Chromosome 15 were deleted or inverted in an iPSC cell line derived from a patient with Angelman Syndrome and CTCF binding and three-dimensional chromatin interactions were assessed to study the structural requirements of this region in restricting imprinted UBE3A expression to neurons.
Please note that the *dumbell_interactions.bigBed procesed data was generated from both replicates and is linked to the corresponding *_1_4C-seq sample records.

first: Stormy

last: Chamberlain

first: Andrea

last: Wilderman


title: miR-762 overexpression effect on tongue cancer cells

status: Public on Nov 09 2018

city: 北京

first: shuai

last: chen

state: State...

address: 北京市海淀区中关村南大街22号

institute: THE PEKING UNIVERSITY

summary:
Analysis of SCC-15 tongue cancer cells overexpressing miR-762. miR-762 is frequently upregulated in primary tongue cancer. Results provide insight into the role of miR-762 in the pathogenesis of tongue cancer.
We used micorarrays to detailed the genes regulated by miR-762 in SCC-15 cells.

overall_design: We trasfected SCC-15 cells with miR-NC (control) or miR-762 mimics (30nM). 36 hours later,  RNA was extracted by Qiangen RNA Isolation Kit.

first: Shuai

last: Chen

first: Heyu

last: Zhang

first: Tiejun

last: Li


title: Specific targeting of the common gamma chain blocks cooperative reprogramming of human tissue-resident cytotoxic T lymphocytes by IL-15 and IL-21

status: Public on Oct 06 2018

city: Montreal

first: Alain

last: Pacis

state: QC

address: 740 Dr Penfield Ave

country: Canada

institute: Canadian Centre for Computational Genomics (C3G)

summary: The common gamma chain (γc) is required for productive signaling by interleukin (IL)-15, IL-21 and IL-2, which are critically involved in immune activation and regulation. IL-21 and IL-15 are implicated in the pathogenesis of type-1 diabetes, graft-versus-host disease, and celiac disease (CeD), a gluten-mediated autoimmune-like enteropathy. Attempts to treat type-1 diabetes and graft-versus-host disease with biologics targeting one particular cytokine have failed. Both IL-15 and IL-21 have been suggested to drive activation of cytotoxic T cells (CTL) that are the effectors mediating tissue destruction in CeD and organ-specific autoimmune disorders. We show that the concomitant upregulation of IL-15 and IL-21 occurs only in full-blown CeD with villous atrophy. BNZ-2, a peptide that targets the γc, was able to block the cooperative IL-15/IL-21 mediated transcriptional activation of human tissue-resident intraepithelial CTL. Importantly, this inhibition was specific and did not interfere with IL-2 signaling, a cytokine with known immunoregulatory functions. Moreover, BNZ-2 blocked gluten-induced IFN-γ production in small intestinal organ cultures from CeD patients. These observations identify BNZ-2 as a therapeutic candidate for immune disorders in which IL-15 and IL-21 cooperate to induce CTL-mediated tissue damage.

overall_design: Gene expression profiles of human tissue-resident IE-CTLs (both in vitro and ex vivo), before and after simulation with IL-15 and IL-21 (individually and in combination).

first: Ciszewski

last: Cezary

first: Discepolo

last: Valentina

first: Pacis

last: Alain

first: Doerr

last: Nick

first: Maglio

last: Mariantonia

first: Basheer

last: Asjad

first: Al-Mawsawi

last: Laith

first: Troncone

last: Riccardo

first: Azimi

last: Nazli

first: Tagaya

last: Yutaka

first: Barreiro

last: Luis

first: Jabri

last: Bana


title: RNA-seq of synchronized S phase or G2 phase cells treated with an ATR inhibitor

status: Public on Nov 15 2018

city: Stanford

first: Karlene

middle: Anne

last: Cimprich

address: 318 Campus Drive

country: USA

institute: Stanford University

summary: We performed RNA-seq in cells synchronized to S or G2 phase to identify genes that were transcriptionally regulated by ATR activity.

overall_design: RPE-1 cells were synchronized to late S (4 hours post-release from thymidine block), or to G2 phase (6 hours post-released from thymidine block) and either mock-treated or ATR-inhibited to identify genes that were transcriptionally controlled by ATR. An asynchronous control and an un-released from the thymidine block control were included. These 6 conditions were repeated in 3 independent experiments (total of 18 samples) and analyzed by RNA-seq.

first: Michael

last: Bocek

first: Joshua

last: Saldivar

first: Stephan

last: Hamperl


title: Extrinsic C5a Activation Regulates Squamous Carcinogenesis and Limits Clonal T Cell Responses to Chemotherapy (Blood)

status: Public on Nov 28 2018

city: Portland

first: Lisa

last: Coussens

state: Oregon

address: SW Sam Jackson Park Rd

institute: OHSU

summary: In the K14-HPV16 transgenic mouse model of squamous carcinogenesis, activation of C5a receptor (C5aR1) in early neoplastic tissues fosters protumorigenic properties of C5aR1+ mast cells and macrophages, and in turn, suppression of CD8+ T cell cytotoxicity. Therapeutic inhibition of C5a receptor (C5aR1) with a peptide antagonist improved efficacy to paclitaxel chemotherapy associated with CXCR3-dependent CD8+ T cell activation. To investigate the effects of combination therapy on the T cell repertoire, we performed deep sequencing of the complementarity-determining region (CDR) 3 of the T cell receptor (TCR)b chain in matched tumor lysates and peripheral blood mononuclear cells (PBMCs). Intratumoral TCRβ clonotypes were hyperexpanded and increasingly detected in matched peripherally-expanded T cell populations, thereby implicating antigen-dependent peripheral priming in response to systemic C5aR1 inhibition.

overall_design: Deep sequencing of the complementarity-determining region (CDR) 3 of the T cell receptor (TCR)b chain in matched tumor lysates and peripheral blood mononuclear cells (PBMCs)

first: Terry

last: Medler

first: Dhaarini

last: Murugan

first: Wesley

last: Horton

first: Sushil

last: Kumar

first: Tiziana

last: Cotechini

first: Alexandra

last: Forsyth

first: Patrick

last: Leyshock

first: Justin

last: Leitenberger

first: Molly

last: Kulesz-Martin

first: Adam

last: Margolin

first: Zena

last: Werb


title: Extrinsic C5a Activation Regulates Squamous Carcinogenesis and Limits Clonal T Cell Responses to Chemotherapy (Skin)


title: The Regulation of IFN Type I Pathway Related Genes RSAD2 and ETV7 Specifically Indicate Antibody-Mediated Rejection After Kidney Transplantation

status: Public on Oct 04 2018

city: Berlin

first: Pawel

last: Durek

address: Charitéplatz 1

institute: Deutsches Rheuma-Forschungszentrum

summary: We performed  total RNA-Seq and compared expression levels of genes of whole blood cells isolated from patients after kidney transplantation with stable graft function, antibody mediated- and t cell mediated graft rejection.

overall_design: Whole blood cells were isolated from 6 patients with stable graft function, 6 patients with histologically verified antibody mediated graft rejection episode and 4 patients with histologically verified T cell mediated graft rejection after kidney transplantation. Total RNA was extracted and cDNA libraries for total RNA sequencing were generated using “TruSeq® Stranded Total RNA Library” kit (Illumina, San Diego, CA, USA).

first: Mareen

last: Matz

first: FrederiK

last: Heinrich

first: Qiang

last: Zhang

first: Christine

last: Lorkowski

first: Kaiyin

last: Wu

first: Nils

last: Lachmann

first: Richard

middle: K

last: Addo

first: Mir-Farzin

last: Mashreghi

first: Klemens

last: Budde


title: Extrinsic C5a Activation Regulates Squamous Carcinogenesis and Limits Clonal T Cell Responses to Chemotherapy

first: Lisa

last: Coussens


title: Histone deacetylase 1 (HDAC1) complexes regulate both histone acetylation and crotonylation in vivo

status: Public on Oct 02 2018

city: LEICESTER

first: RICHARD

middle: DAVID WILLIAM

last: KELLY

address: LANCASTER ROAD

department: BIOCHEMISTRY

country: United Kingdom

institute: UNIVERSITY OF LEICESTER

summary: Genome binding/occupancy profiling of H3K18ac and H3K18cr by high throughput sequencing.

overall_design: We performed chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq) for H3K18ac and H3K18cr in control and HDAC1/HDAC2 DKO ES cells.

first: R

last: Kelly

first: A

last: Chandru

first: P

last: Watson

first: Y

last: Song

first: M

last: Blades

first: N

last: Roberts

last: Jamieson

first: J

last: Schwabe

first: S

last: Cowley


title: Integrated epigenome, exome and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids [DNA methylation]

status: Public on Oct 05 2018

city: Houston

first: Katayoun

last: Rezvani

address: 1515 Holcombe Blvd

department: Department of Stem Cell Transplantation and Cellular Therapy

institute: The University of Texas MD Anderson Cancer Center

summary: Uterine fibroids are benign myometrial smooth muscle tumors of unknown etiology that when symptomatic are the most common indication for hysterectomy in the USA.  We conducted an integrated analysis of fibroids and adjacent normal myometria by whole exome sequencing, DNA methylation (Human Methylation EPIC) array, and RNA-sequencing.  Unsupervised clustering by DNA methylation segregated normal myometria and fibroids, and further separated the fibroids into subtypes marked by MED12 mutation, HMGA2 activation (HMGA2hi) and HMGA1 activation (HMGA1hi). Upregulation of HMGA2 expression in HMGA2hi fibroids did not always appear to be dependent on translocation, as has been historically described, and was associated with hypomethylation in the HMGA2 gene body.  Furthermore, we found that expression of HOXA13 was highly upregulated in fibroids and that overexpression of HOXA13 in a myometrial cell line induced expression of genes classically associated with uterine fibroids. Transcriptome analyses of the most differentially expressed genes between cervix and myometrium also showed that uterine fibroids and normal cervix clustered together and apart from normal myometria. Together, our integrated analysis shows a role for epigenetic modification in fibroid biology and strongly suggests that homeotic transformation of myometrium cells to a more cervical phenotype is important for the etiology of the disease.

overall_design: Uterine samples including 24 fibroids and 10 normal myometria are analyzed.

first: Jose

middle: M

last: Teixeira


title: Rescue of premature aging defects in Cockayne Syndrome Derived Stem Cells by Targeted Gene Correction

status: Public on Dec 21 2018

city: Beijing

first: Zunpeng

last: Liu

address: Beichen West Road

department: Institute of Zoology, Chinese Academy of Sciences

institute: State Key Laboratory of Stem Cell and Reproductive Biology

summary: Cockayne Syndrome (CS) is a rare autosomal recessive inherited disorder characterized by a variety of clinical features including sensitivity to sunlight, progressive neurological abnormalities and appearance of premature aging. However, the pathogenesis of CS yet remains unclear due to the limitations of current disease models. Here we generate integration free-induced pluripotent stem cells (iPSCs) from CS patient fibroblast bearing mutations in CSB/ERCC6 and further derive isogenic gene corrected (GC)-iPSCs using CRISPR/Cas9 system. CS cellular phenotypes are recapitulated in CS mesenchymal stem cells (MSCs) and neural stem cells (NSCs), both of which display compromised susceptibility to DNA damage stress. We next map the transcriptome landscapes of CS- and GC-iPSCs and their adult stem/progenitor cell derivatives under ultraviolet (UV) and replicative stress, indicating the defects in DNA repair in confronting the acute and chronic stress contribute to CS-disease pathology. Through RNA sequencing analysis, we also identify a panel of potential targets for treating CS. Moreover, we generate clinical GC-MSCs displaying safer and superior stem cell activity in vitro and in vivo, which may provide better cell materials for future stem cell replacement therapy in CS-disease. Our models serve to facilitate the discovery of novel disease features and molecular mechanism, as well as lay a foundation for development of novel therapeutic strategies to treat CS.

overall_design: Transcriptome analysis of human CS- and gene corrected (GC)-iPSCs, and CS-,GC-MSCs upon UV treatment or under replicative senescence stress, as well as CS-, GC-NSCs upon UV treatment.

first: Guanghui

first: Yang

last: Yu