title: Identification of nucleolin-targeted RNA transcripts

status: Public on Feb 28 2021

city: Seoul

first: Boyoun

last: Park

address: 50 Yonsei-ro, Seodaemun-gu

country: South Korea

institute: Yonsei University

summary: Although Rrp6 contains a helicase and RNase D domain at the C-terminus, it is not involved in stable RNA interactions. We thus hypothesized that mRrp6-mediated nucleolar inflammatory RNA degradation may depend on the pre-mRNA substrate that is delivered to the mRrp6-exosome complex by nucleolin as a guide factor. To demonstrate this possibility, we examined nucleoplasmic RNAs which were bound to nucleolin through RNA-IP-sequencing at the late time points of LPS stimulation.

overall_design: Nucleoplasimc RNAs were immunoprecipiated with anti-nucleolin antibodies during LPS stimulation and then analyzed by Illumina Hiseq 2000

first: Taeyun

middle: A

last: Lee


title: CRISPR/Cas9 Genome Editing of the Human Topoisomerase IIα Intron-19 5′ Splice Site Circumvents Etoposide Resistance in Human Leukemia K562 Cells

city: Columbus

first: Hatice Gulcin

last: Ozer

state: OH

address: 1800 Cannon Dr

department: Biomedical Informatics

country: USA

institute: The Ohio State University

type: Expression profiling by high throughput sequencing

summary: Results indicate that CRISPR/Cas9 gene editing of a suboptimal E19/I19 5′ splice site in the TOP2α gene results in circumvention of acquired drug resistance to etoposide and other TOP2-targeted drugs in a clonal K562 cell line by enhancing removal of intron 19 thereby decreasing formation of a truncated TOP2α/90 isoform and increasing expression of full-length TOP2α/170 in these resistant cells.

overall_design: An etoposide-resistant K562 clonal subline, K/VP.5, with reduced levels of TOP2α/170, expresses high levels of a novel C-terminal truncated TOP2α isoform (90 kDa, TOP2α/90). TOP2α/90, the translation product of a TOP2α mRNA that retains a processed intron 19 (I19), heterodimerizes with TOP2α/170 and is a resistance determinant through a dominant negative effect on drug activity. We hypothesized that genome editing to enhance I19 removal would provide a tractable strategy to circumvent acquired TOP2α-mediated drug resistance. To enhance I19 removal in K/VP.5 cells, CRISPR/Cas9 was utilized to make changes (GAG//GTAAAC→GAG//GTAAGT) in the TOP2α gene’s suboptimal exon 19/intron 19 5′ splice site (E19/I19 5′ SS).

first: Terry

middle: S

last: Elton

first: Jack

middle: C

last: Yalowich

first: Hatice

middle: G

first: Victor

last: Hernadez


title: RNAseq for MCL cells with ibrutinib treatment

status: Public on Feb 26 2021

city: Philadelphia

first: Wasik

last: Mariusz

state: Pennsylvania

address: 422 Curie Blvd

institute: University of Pennsylvania

summary: In this study we compared the effects of BTK inhibitor on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from a patient with Anaplastic Mantle Cell Lymphoma. we used RNAseq to map the genome-wide gene expression patterns in MCL cells in response to BTK inhibition

overall_design: 7 samples of two or one contol and two treatment for two cell lines' cells

first: Qian

last: Zhang

first: Mariusz

last: Wasik

first: Hong

middle: Y

last: Wang

first: Xiaobin

last: Liu


title: Gene expression data of livers from C57BL/6J mice treated with vehicle control or dexamethasone

city: Shanghai

first: Yan

last: Lu

address: 180 Fenglin Road

department: Department of Endocrinology and Metabolism

country: China

institute: Zhongshan Hospital, Fudan University

summary: We report the RNA-Sequencing data for the livers of C57BL/6J mice treated with vehicle control (CON) or dexamethasone (DEX)

overall_design: 10-week-old male C57BL/6J mice were purchased from the Shanghai Laboratory Animal Company (SLAC, Shanghai, China).Dexamethasone (Sigma-Aldrich, St. Louis, MO, USA) or vehicle control (Saline) was administered daily at a dose of 1.0 mg/kg body weight by intraperitoneal injection for 14 days. Then, mice were sacrificed and livers were harvested for RNA extraction.


title: The role of TMEM43 in cardiac fibrosis and dysfunction

city: Houaton

first: Ali

middle: J

last: Marian

state: Texas

address: 6770 Bertner Ave DAC C900a

department: Centre for Cardiovascular Genetics

institute: UTHSC, Houston

summary: Deletion of Tmem43 encoding nuclear membrane protein TMEM43, specifically in mouse cardiac myocytes leads to cardiac fibrosis and dysfunction. Temporal RNA-seq identified early and late trascriptomic changes and implicates TGFb1 in the pathogenesis of ACM caused by Tmem43 haploinsufficiency.

overall_design: RNA-seq from Cardiac myocytes was performed at two time point to analysis early (4 month) and late transcriptomic changes (9 Month)  upon  myocyte specific deletion of Tmem43.

first: Coarfa

last: Cristian


title: Small RNA Sequencing Reveals a Potential miRNA-Mediated Interaction Network in Sugar Beet Response to Alkaline Stress

city: Taigu

first: Chunlei

last: Zou

address: No.1 Mingxian Road

institute: Shanxi Agricultural University

type: Non-coding RNA profiling by high throughput sequencing

summary: To identify known and novel miRNAs involved in the response and adaptation of sugar beet to short-term and long-term alkaline stress, miRNAs were identified by analysis of the deep sequencing of sRNA

overall_design: Five-week-old sugar beet (Beta vulgaris L.) seedlings were treated with Hoagland solution, containing 75 mM mixed alkaline solution (Na2CO3:NaHCO3, 1:2) for 0 day (control, designated as C), 3 days (short-term treatment, designated as ST) and 7 days (long-term treatment, designated as LT). Fresh leaves from the same position of seedlings at different treatments were collected. Sample from each treatment represented a pool of more than 10 independent individuals. All the harvested leaves were immediately frozen in liquid nitrogen after collection and stored at −80 °C for RNA-seq.

first: Caifeng

last: Li


title: Infection with Toxoplasma gondii induces inheritable epigenetic changes in mouse sperm

status: Public on Feb 25 2021

city: Melbourne

first: Shiraz

last: Tyebji

state: Victoria

address: 1G Royal Parade

department: Infectious diseases and immune defence division

country: Australia

institute: The Walter and Eliza Hall Institute of Medical Research

summary: In this study we sought to analyse if infection with the common human parasite Toxoplasma gondii aftered sperm epigenetics by sequecing small RNA from parasite infected and mock infected mice. Epigenetic changes in sperm is a well described process of inheritanece of paternal environmental experiences to their progeny. Using high throughput Illumina sequencing, we revealed differences between the sperm small RNA profiles of Toxoplasma-infected and control animals . We found 25.88% of small RNAs were differentially expressed after correcting for false discovery rate, of which 9.21% and 16.67% were up- and down-regulated, respectively. Further quantitative analysis revealed enriched small RNA load in our samples and biotypes composition analysis showed a majority tRNA population followed by miRNA and piRNA populations, while the rest contained various other small RNA transcripts.When we looked at miRNA changes between Toxoplasma-infected and control samples, we found that of the total miRNA mapped (585), 174 were differentially expressed in the Toxoplasma-infected group (FDR < 0.05) of which 35 were down- and 75 were up-regulated with a Log2FC < -2 and > 2, respectively. Lastly, using gene enrichment analysis, we identified pathways regulated by small RNA’s that are differentially expressed and found that small RNA’s targeted distinct biological pathways.

overall_design: Sequencing of sperm small RNA from mice injected with PBS control or Toxoplasma. 5 biological replicates in each group,  each consisting of samples pooled from 2 mice.

first: Tyebji

last: Shiraz

first: Tonkin

last: Christopher


title: In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions

city: Memphis

first: Hongbo

last: Chi

state: TN

address: 262 Danny Thomas Place

department: Immunology

institute: St Jude Children's Research Hospital

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Effects of fluoxetine and venlafaxine in the mouse neural embryonic stem cell test

status: Public on Feb 27 2021

city: Bilthoven

first: Jeroen

last: Pennings

address: A. van Leeuwenhoeklaan 9

country: Netherlands

institute: Natl. Inst. Public Health & Environment

summary: The neural embryonic stem cell test (ESTn) is in vitro test that mimics early neural differentiation. The aim of this study was to define the biological domain of ESTn based on gene expression of selective markers for certain cell types, and to investigate the effects of two antidepressants, fluoxetine (FLX) and venlafaxine (VNX), on neural differentiation.

overall_design: 49 samples, covering seven time+treatment groups

first: Victoria

last: de Leeuw


title: Gene expression data of livers from C57BL/6J mice fed ad libitum or were fasted for 16 hour.

first: Ling

last: Wu

address: 639 Zhizaoju Road, Huangpu District, Shanghai.

department: Department of Assisted Reproduction

institute: Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine

summary: We report the RNA-Sequencing data for the livers of C57BL/6J mice fed ad libitum or were fasted for 16 hour.

overall_design: 10-week-old male C57BL/6J mice were purchased from the Shanghai Laboratory Animal Company (SLAC, Shanghai, China). Mice were fed ad libitum or fasted for 16 hour. Then, mice were sacrificed and livers were harvested for RNA extraction.


title: RNA-seq data for EphA2 knockdown in Huh7 cells

city: Maywood

first: Wei

last: Qiu

state: IL

address: 2160 S 1st Ave

department: Surgery

institute: Loyola University Chicago

summary: RNA-seq data for EphA2 knockdown (KD) in Huh7 cells

overall_design: We knocked down EphA2 using shRNA in Huh7 cells and compared scrambled and EphA2 KD cells by RNA-seq. 3 replicates for each group.

first: Hao


title: Role of ZBP1 in myeloma cell biology

city: London

first: Kanagaraju

last: Ponnusamy

address: 4th Floor common wealth building, Du Cane Road

department: Hematology

country: United Kingdom

institute: Imperial College London

summary: Whole transcriptome of ZBP1-depleted myeloma cells was analysed using a high-throughput RNA-seq approach. ZBP1 was depleted by 2 different shRNAs in MM1.S and H929 cells, and total RNA was isolated on day 4 post-lentiviral transduction. Poly A-tail enriched RNA was sequenced and the analysis of commonly regulated genes by both shRNAs from 2 independent experiments revealed that ZBP1 regulates genes that are involved in cell cycle regulation.

overall_design: Analysis of ZBP1-depleted transcriptome in MM1.S and H929 myeloma cells

first: Anastasios

last: Karadimitris


title: In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions [microarray_dataset1]

summary: The role of nutrient signaling processes in the fate decision of CD8 is incompletely understood. By performing in vivo pooled CRISPR-Cas9 screening, we uncovered nutrient signaling processes underpinning the dynamics and heterogeneity of CD8 T cell fate decisions.

overall_design: We used microarray to compare gene expression of sgNTC (‘spike for sgPofut1’)- and sgPofut1-transduced P14 cells from the dual-color transfer system at day 5 and day 7.5 post-infection from spleen; We used microarray to compare the global transcription profiles of terminal effector cells (TE′, KLRG1hiCXCR3loCD127lo), memory precursor effector cells (MP, KLRG1loCXCR3hiCD127hi) and intermediate cells (TINT, CXCR3hiCD127lo) from sgNTC-transduced P14 cells at day 7.5 post-infection from spleen.

first: Hongling

last: Huang

first: Yogesh

last: Dhungana

last: Shi


title: Neural tube closure defect

city: Houston

first: Rachel

last: Keuls

state: TX

address: One Baylor Plaza, Alkek N1020

institute: Baylor College of Medicine


title: Transcriptional profiling of strains with different levels of Mrr1 activity in Candida lusitaniae (RNA-Seq)

city: Riverside

first: Jason

last: Stajich

state: CA

address: 900 University Ave

department: Microbiology and Plant Pathology

institute: University of California-Riverside

summary: We sequenced mRNA from U04, U04 mrr1Δ and four strains complemented with different MRR1 alleles in the U04 mrr1Δ strain background to define the Mrr1 regulon in C. lusitaniae and assess how Mrr1 activity effects expression in three conditions: control, diamide and hydrogen peroxide.

overall_design: Overnight cultures grown in YPD at 30 C were back diluted into 5 ml YPD and grown at 37 C to mid-exponential phase on a roller drum, diluted into pre-warmed medium then grown, at 37 C, to mid-exponential phase again before 30 minutes treatment with vehicle, 0.5 mM diamide or 0.5 mM hydrogen peroxide.

first: Elora

last: Demers

middle: E

first: Deborah

last: Hogan


title: Genome-wide analysis of the CARD9/Dectin-1 transcriptional program in neutrophils and macrophages by RNA-seq

city: Durham

first: Mari

middle: L

last: Shinohara

state: NC

institute: Duke University School of Medicine

summary:
Purpose: To characterize Card9-dependent and Card9-independent Dectin-1 mediated gene expression changes in neutrophils and to compare response to Dectin-1 stimulation in neutrophils and macrophages.
Method: BM neutrophils from WT and Card9-/- mice were isolated by MACS column purification and treated with or without the Dectin-1 agonist, curdlan for 3 hrs. WT BM-derived macrophages were also treated with or without curdlan for 3hrs before sample collection.
Results: We identified both Card9-dependent and Card9-independent gene expression changes with Dectin-1 stimulation in neutrophils. We also identified cell-type specific differences in the response to Dectin-1 stimulation in neutrophils and macrophages.
Conclusions: Dectin-1 stimulation induces significant gene expression changes regulated by either canonical Card9-dependent or non-canonical Card9-independent mechanisms.

overall_design: WT and Card9-deficient neutrophils +/- curdlan  (n=3/group); WT macrophages +/- curdlan  (n=2/group)

first: M

last: Deerhake


title: Illumina miRNA sequencing revealed Citrus adaptation to long-term B-toxicity through modulation of lateral root development by miR319

city: Fuzhou

first: Jing-Hao

state: Fujian

address: Wusi Road

department: Pomological Institute

institute: Fujian Academy of Agricultural Sciences

summary: We report the application of Illumina sequencing for high-throughput profiling of miRNA in citrus root responded to long-term boron toxicity. We find miR319 is involved in citrus adapation to long-term boron toxicity via targeting a MYB gene, Ciclev10000756m.g.v1.0, which is homologus with several MYBs that modulate lateral root development in Arabidopsis.

sample_organism:
Citrus sinensis
Citrus maxima

platform_organism:
Citrus sinensis
Citrus maxima

overall_design: Citrus sinensis and C. grandis seedlings were sand cultured and treated  with different levels of H3BO3 for 15 weeks. At the end of B treatments, root tips were used for total RNA extraction. small RNA libraries were then constructed and sequenced with an Illumina HiSeq 2500.

first: Li-Song

last: Chen


title: Respiratory syncytial virus induces alternative mRNA processing

city: Middleton

first: Allan

last: Brasier

state: WI

address: 715 Highland

institute: university of Wissconsin

summary: we examine the effect of RSV infection in human small airway epithelial cells (hSAECs)

overall_design: wild type small airway epithelial cells were infected 0, 24 h prior to single molecule RNA sequencing (PacBio sequencing).

first: Xiaofang

last: Xu


title: Developmental Genetics of Color Pattern Establishment in Cats

city: Huntsville

first: Christopher

middle: Bryan

last: Kaelin

state: AL

address: 601 Genome Way

institute: HudsonAlpha Institute for Biotechnology

summary: We apply developmental and single cell gene expression analysis to fetal skin of domestic cats, together with genetic characterization of Mendelian color variation, to identify when, where, and how, during fetal development, felid color patterns are established. Prior to the appearance of hair follicle placodes, we identify changes in epidermal thickness that represent a signature of color pattern establishment, and that are preceded by a pre-pattern of gene expression in which the secreted Wnt inhibitor encoded by Dickkopf 4 (Dkk4) plays a central role. We also demonstrate that mutations in Dkk4 underlie the Ticked pattern mutation in cats. Our results bring molecular understanding to how the leopard got its spots, suggest that similar mechanisms underlie periodic color pattern and periodic hair follicle spacing, and provide a genomic framework to explore natural selection for diverse pattern types in wild felids.

overall_design: 3 single-cell RNAseq data sets generated from fetal cat skin at different fetal timepoints

middle: B

first: Kelly

last: McGowan

first: Gregory

last: Barsh


title: Transcriptomic analysis of GLUD1-knockdown 786-0 cells under amino acid deprivation

first: Jialiang

last: Shao

address: No. 100 Haining Road, Hongkou District, Shanghai

institute: Department of Urology, Shanghai General Hospital, Jiaotong University

summary: shGLUD1 and shNT 786-0 cells were pretreated by amino acid starvation for 12 hours, then total mRNA were extracted for sequencing.

overall_design: mRNA profiles of shGLUD1 and shNT 786-0 cells, in duplicate.

first: Xiongjun

last: Wang


title: sRNA sequence of Seminal plasma from male infertility patients

city: Suzhou

first: Qiu

address: 199 Renai Road

institute: Soochow University

summary: we reported the seminal plasma piRNA change of infertility patients

overall_design: compare seminal plasma piRNA of male infertility patients with that of fertility male

first: Ying

last: Zhao

first: Fengmei

last: Cui


title: RNA-seq of in Kruppel-like factor 6 Knockout Bovine Mammary Epithelial Cells

city: Changchun

first: Lixin

last: Xia

state: Jilin

address: No.5333 Xi'an Road,Luyuan District

department: College of Animal Science

institute: Jilin University

summary: In our exprement, the kruppel-like factors 6 (KLF6) gene was completely knocked out in BMECs using CRISPR/Cas9.Total RNA was extracted using the TRIzol reagent from KLF6-KO and wild type BMECs. The quality of RNA was assessed by the Agilent 2100 (Agilent, USA). The samples with a minimum RIN value of 7.0 were used for RNA-seq.RNA-seq helps to analyze the changes of functional gene expression levels and metabolic pathway in BMECs after KLF6 gene knockout.

overall_design: KLF6 knockout BMECs and wild type BMECs

first: Zhihui

first: Xibi

last: Fang


title: The NK cell stress response status modulates anti-tumor immunity [RNA-seq]

city: New York

first: Kathryn

middle: Grace

last: Hockemeyer

state: New York

address: 550 1st Avenue

department: Pathology

institute: NYU Langone Health

summary: The tumor microenvironment (TME) comprises numerous forms of cellular stress, which can activate Heat Shock Factor 1 (HSF1), the master transcription factor of the proteotoxic stress response. We profiled HSF1 activity across tumor-infiltrating immune populations, revealing the highest activity in CD8+ T cells and the lowest in natural killer (NK) cells. To elucidate the mechanisms through which HSF1 regulates immune surveillance, we generated an in vivo model of augmented HSF1 activity. Tumor challenge revealed that accumulation of HSF1 dampens NK-mediated tumor immunity and impairs both cytotoxicity and production of interferon gamma (IFN-γ) in NK cells. Single-cell transcriptional profiling identified a loss of anti-tumor signaling pathways, including interferon signaling, within the HSF1-enhanced TME. In NK cells, integration of chromatin accessibility with transcriptomics revealed that HSF1 deregulates accessibility and expression of genes encoding for NK receptors, leading to an inhibitory bias.

overall_design: Single-cell RNA-sequencing was performed in tumors engrafted in wild-type (WT) controls and mice bearing serine to alanine mutations in amino acids 303 and 307 (S303/7A). Tumors from 4 mice were pooled for  Transcriptomic and epigenetic profiling of NK cells was performed by mRNA sequencing and assay for transposase-accessible chromatin (ATAC) sequencing in splenic NK cells isolated from wild-type and HSF1-enhanced mice under steady state conditions. For RNA-seq, 3 biological replicates of NK cells from WT and S303/7A were used. For ATAC-seq, 4 biological replicates of NK cells from WT and S303/7A mice were used.

first: Iannis

last: Aifantis


title: Dynamic and systemic regulation occurs in the liver of rainbow trout (Oncorhynchus mykiss) in response to environmental hypoxia

city: Xining

first: Delin

last: Qi

address: No. 251, Ningda Road

institute: Qinghai university

summary: The hypoxia frequently occurs in natural aquatic systems and aquaculture environment due to the natural reasons and human factors such as extreme climate, high density farming, environmental pollution and global warming, which have gradually become a huge threat to aquatic ecosystem functions and aquatic organism survival, causing serious ecological damage and enormous economic losses. Rainbow trout (Oncorhynchus mykiss), as a hypoxia-sensitive fish species, is a good model to study hypoxia stress. The molecular regulation and oxidative stress of rainbow trout still remains unknown in response to environmental hypoxia and reoxygenation stress. In this study, the transcriptome and biochemical indexes of rainbow trout liver in response to hypoxia for different durations were analyzed to highlight the changes in the molecular regulation and oxidative stress.

overall_design: Rainbow trout liver in response to hypoxia for different durations to highlight the changes in the molecular regulation

first: Jinqiang

last: Huang

first: Yongjuan

last: Li


title: Nucleo-cytoplasmic RNA distribution responsible for maintaining neuroinflammatory microenvironment.

city: Luzhou

first: Zheng

last: Bao

state: Sichuan

address: No. 25, Taiping Street

institute: The Affiliated Hospital of Southwest Medical University

summary: Characteristics of subcellular localization of RNAs are closely associated with their transcriptional outputs and, therefore, involved in the physiological process of many cases of central nervous system diseases, such as hemorrhagic stroke, which threatens millions of people and causes of death and long-term disability world-wide.  Using whole-transcriptome sequencing (RNA-seq), here we report a subcellular gene profiling during hemorrhagic damage. Differentially expressed genes owing to spatial distribution of oxyhemoglobin (oxy-hb) treated-microglial nuclear and cytoplasmic fractions were enriched in biological processes in RNA metabolism and RNA splicing regardless of the duration of stimulation; while hemorrhage-induced differentially expressed genes played roles in inflammation regardless of the duration of stimulation. Interestingly, nuclear-retained intron of microglial nucleocytoplasmic transport genes may result in their down-regulation in 24 hours of oxy-Hb stimulation. This transcriptome study advances our understanding of the contributor of subcellular components, revealing new insights into cytoplasmic non-coding RNAs in response to hemorrhage and provide a resource for investigating comparable diseases.

overall_design: BV2 mouse microgial cells were treated with 10μM oxyhemoglobin for 0, 12 or 24 hours and harvested to produce nuclear and cytoplasmic RNA samples

first: Yuyan

last: Liao

first: Chenghao

last: Kuang


title: Transcriptome analysis of myeloma cells after IRF3 depletion by shRNAs

first: Kanagaraju

last: Ponnusamy

summary: Whole transcriptome of IRF3-depleted myeloma cells was analysed using a high-throughput RNA-seq approach. IRF3 was depleted by 2 different shRNAs in MM1.S cells, and total RNA was isolated on day 4 post-lentiviral transduction. Poly A-tail enriched RNA was sequenced and the analysis of commonly regulated genes by both shRNAs from 2 independent experiments revealed that IRF3 regulates genes that are involved in cell cycle regulation.

overall_design: Analysis of IRF3-depleted transcriptome in MM1.S myeloma cells

first: Anastasios

last: Karadimitris


title: Bulk RNA-seq analysis of Exhausted CD8 T cell subsets

city: St. Louis

first: Saravanan

last: Raju

email: sraju89@gmail.com, rajus@wustl.edu

state: MO

address: 660 S Euclid Avenue

institute: Washington University in St. Louis

summary: CD8+PD-1+ cells were sorted from Prdm1-EYFP mice 16 days following LCMV-c13 infection.

overall_design: 3 Prdm1-EFYP mice were infected with LCMV-13. Splenocytes were harvested on Day 16, enriched for CD8 T cells using Dynabeads FlowComp Kit and subject to FACS. 4 populations were isolated including YFP–Tim3–CX3CR1–, YFP+CX3CR1+Tim3–, YFP+CX3CR1+Tim-3+, YFP+CX3CR1–Tim3+

first: Takeshi

last: Egawa


title: RNA-seq of Pseudarthrobacter psychrotolerans YJ56: on temperature

city: Seoul

first: SON

last: YONGJUN

address: 145, Anam-ro, Seongbuk-gu

institute: Korea University

summary: Comparison for gene expression of Pseudarthrobacter psychrotolerans YJ56: grown on 13℃ or 25℃

overall_design: 1 control (R2A, 13℃) and 1 sample (R2A, 25℃)

first: Yongjun

last: Son


title: A host-dependent transcriptional response correlates with Dengue virus infection rate in healthy humans.

city: Singapore

first: Aida

last: Moreno-Moral

address: 8 College Road

country: Singapore

institute: Duke-NUS Medical School

summary: Dengue virus (DENV) infection is a major emerging disease in tropical and subtropical countries and the influence of host genetics during early phases of infection remains to be fully elucidated. Here we use dendritic cells (DCs) and macrophages from healthy individuals to establish inter-individual variability in DENV infection and antibody-mediated enhancement (ADE). We show that host-related factors determine the severity of the infection rate both in DENV-infected DCs and macrophages following ADE. We then correlate the inter-individual variability in infection rates with genome-wide transcript abundance measured by RNA sequencing in DCs following DENV infection. We report 190 host-related transcripts in DCs that correlate markedly with infection rates that form an ubiquitin-mediated antiviral network. Furthermore, these transcripts are enriched for glycolysis, which we show is critical for the early phases of infection. Among virus induced transcripts (i.e. significant correlation only after DENV), we identify DUSP10 as the best indicator of the severity of infection. These results indicate the importance of host genetics in shaping the severity of DENV infection rates in DCs and identify novel potential DENV-susceptibility targets.

overall_design: Primary human DCs and macrophages were infected with dengue virus or dengue+antibody against dengue for 6 hours. As a control, cells were treated with medium only (DCs) or anti-prM dengue protein only (macrophages). After incubation time, cells were washed with warm PBS before adding 500 µl TRIzol reagent (Invitrogen) and RNA was isolated.

first: Iris

last: Scherwitzl

first: Enrico

last: Petretto

first: Wanwisa

last: Dejnirattisai

first: Imprialou

last: Marta

first: Marta

last: Bagnati

first: Gavin

middle: R

last: Screaton

first: Juthathip

last: Mongkolsapaya

first: Behmoaras

last: Jacques


title: Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma

city: Shanghai

first: Chunlai

last: Lu

address: 180 Fenglin Road

institute: Fudan University

summary: Esophageal squamous cell carcinoma (ESCC) remains one of the most deadly cancer types worldwide. Comprehensively dissecting the molecular characterization of ESCC paves the way for developing more promising therapeutics. Here, we performed RNA-seq and ATAC-seq on three pairs of ESCC tumor tissues and patient-matched adjacent normal tissues.

overall_design: RNA-seq and ATAC-seq analyses of ESCC tumor tissues and patient-matched adjacent normal tissues.

first: Lu

last: Chunlai


title: Neural tube closure defect: Single Cell ATAC and single cell mRNA seq

status: Public on Feb 24 2021

first: Rachel

last: Keuls

summary: Single-cell mRNA sequencing was overlaid with single-cell ATAC sequencing of the mouse E9.5 cranial region for both wildtype and miR-302 knockout embryos, an established example of a neural tube closure defect. The goals of this study were to compare changes in gene expression and chromatin accessibility upon loss of a stem cell miRNA and neural tube closure defect.

overall_design:
The cranial region of E9.5 wildtype and miR-302 knockout embryos were dissociated and single cell/ single nuclei suspension was partitioned on a 10x chromium platform. One set of embryos was used for single cell mRNA and one set of embryos was used for single-cell ATAC sequencing
This Series represents scATAC-seq data.


title: Transcriptomic profilling of Arabidopsis thaliana roots infected by Fusarium oxysporum

city: Xi'an

first: Li

last: Guo

state: Shaanxi

address: 28 Xianning West Road

institute: Xi'an Jiao Tong University

summary: Using next-generation sequencing, we sequenced transcriptomes of A. thaliana plants infected by the pathogenic and the symbiotic fungus and analyzed plant and fungal gene expression changes between pathogenic and symbiotic interactions. Infected plants were sampled at early infection stages, 12, 24, 48 and 96 HPI (hours post inoculation)

sample_organism:
Arabidopsis thaliana
Fusarium oxysporum

platform_organism:
Arabidopsis thaliana
Fusarium oxysporum

overall_design: Infected plants were sampled at early infection stages, 12, 24, 48 and 96 HPI (hours post inoculation), and root tissues here fungal penetration and subsequent colonization take place were isolated for whole transcriptome sequencing (RNA-seq). Water-treated plants and auxenic fungal mycelia were used as control.

first: Li-Jun

last: Ma


title: Gene expression-based, chronic active T cell-mediated rejection (CA TCMR)

city: Portland

first: Vanderlene

last: Kung

state: OR

address: 3181 SW Sam Jackson Park Rd

institute: OHSU

summary: Expression profiling of a total of 1305 genes in 25 CA TCMR cases

overall_design: A total of 1305 unique transcripts previously shown to be related to allograft rejection and/or fibrosis were quantified on formalin fixed parrafin embeded tissue from 25 cases of CA TCMR, of which 6 were treatment responsive.


title: Modulating Bone Marrow Hematopoietic Lineage Potential to Prevent Breast Cancer Bone Metastasis

city: Boston

first: Jessalyn

last: Ubellacker

state: MA

address: 4 Blackfan Circle

institute: Harvard University

summary: The presence of disseminated tumor cells in patient bone marrow (BM) aspirates predicts decreased recurrence-free survival, yet little is known about whether hematopoietic BM cells impact bone metastases. Here, we report that the BM can be rendered metastasis-suppressive by the bone-targeting bisphosphonate, zoledronic acid (ZA). In particular, ZA modulates hematopoietic myeloid/osteoclast progenitor cell (M/OCP) lineage potential to render them metastasis-suppressive. Granulocyte-colony stimulating factor (G-CSF) promotes resistance to ZA by re-directing M/OCP differentiation. We identified BM transcriptional programs that associate with metastasis suppression and resistance to ZA. Analysis of patient blood samples taken at randomization revealed that women with plasma G-CSF levels >23 pg/mL experienced significantly worse outcome with adjuvant ZA than those on ZA who had lower plasma G-CSF levels. Our findings establish that hematopoietic cells and M/OCP lineage potential profoundly impact bone metastasis and support the discovery of biomarkers that stratify therapeutic responses in patients at risk of recurrence.

overall_design: To test in murine bone marrow and osteoclast precursor cells the effects on gene expression of treatment with ZA and G-CSF. At least two replicates from each treatment were used (including no treatment and combination treatment) and analyzed in a pairwise fashion.

first: John

last: Hutchinson

first: Sandra

last: McAllister


title: Gene expression profile of wild-type MCF10-A or rho0 MCF10-A cells after cellular irradiation

city: New York City

first: Marco

last: Tigano

address: 540 First Avenue

institute: NYU Grossman School of Medicine

summary: Goal is to uncover genes that fail to be activated by cellular irradiation when mitochondrial DNA is depleted in MCF10-A. To this end we delivered 20gy of ionizing radiation at 0.8gy/minute and waited 6 days. Total RNA was collected and DE genes were compared between wild-type irradiated cells and rho0 irradiated cells.

overall_design: 4 total samples; 2 biological replicas, 1 wild-type + IR and 1 rho0 +IR each

first: Agnel

last: Sfeir


title: Gene expression profile of human ARPE-19 cells subjected to mitochondrial DNA double stranded breaks through expression of mitochondrial TALENs

summary: Goal is to analyze the expression profile of cells shortly after induction of mitochondrial double stranded breaks. ARPE-19 cells are transfected with constructs coding for mitochondrial TALENs, either active or dead. These constructs target two different locations of mtDNA (ATP8 and Dloop). Gene expression is then compared between untransfected and transfected cells (either active or dead TALENs), or between active TALEN (cells with mitochondrial double stranded breaks) and dead TALEN (expressing the same protein without cutting the mitochondrial genome)

overall_design: 11 total samples: 2 replicates for non transfected cells, 3 replicates for TALEN ATP8, 3 replicates for TALEN ATP8 dead, 3 replicates for TALEN Dloop.


title: Allergen-specific immunotherapy induces the suppressive secretoglobin 1A1 in cells of the lower airways

city: Munich

first: Ulrich

middle: M

last: Zissler

address: Biedersteiner Str. 29

department: Center of Allergy & Environment (ZAUM)

country: Germany

institute: Technical University of Munich & Helmholtz Center Munich

summary:
While several systemic immunomodulatory effects of allergen-specific immunotherapy (AIT) have been discovered, local anti-inflammatory mechanisms in the respiratory tract are largely unknown. We sought to elucidate local and epithelial mechanisms underlying allergen-specific immunotherapy in a genome-wide approach. We induced sputum in hay fever patients and healthy controls during the pollen peak season and stratified patients by effective allergen-immunotherapy or as untreated.  Sputum was directly processed after induction and subjected to whole transcriptome RNA microarray analysis. Nasal secretions were analyzed for Secretoglobin1A1 (SCGB1A1) and IL-24 protein levels in an additional validation cohort at three defined time points during the three-year course of AIT. Subsequently, RNA was extracted and subjected to an array-based whole transcriptome analysis.
AIT inhibited pro-inflammatory CXCL8, IL24 and CCL26 mRNA expression, while SCGB1A1, IL7, CCL5, CCL23 and WNT5B mRNAs were induced independently of the asthma status and allergen season. In our validation cohort, local increase of SCGB1A1 occurred concomitantly with the reduction of local IL-24 in upper airways during the course of AIT. Additionally, SCGB1A1 was identified as a suppressor of epithelial gene expression.AIT induces a yet unknown local gene expression footprint in the lower airways that on one hand appears to be a result of multiple regulatory pathways and on the other hand reveals SCGB1A1 as novel anti-inflammatory mediator of long-term allergen specific therapeutic intervention in the local environment.

overall_design: Induced sputa were performed in healthy controls, allergic rhinitis with and without concomittant asthma in and out of grass pollen season. Some of the patients received allergen-specific immunotherapy (AIT).

first: U

first: C

last: Jakwerth

first: F

last: Guerth

first: L

last: Lewitan

first: S

last: Rothkirch

first: M

last: Davidovic

last: Ulrich

last: Oelsner

first: H

last: Garn

last: Schmidt-Weber

first: A

last: Chaker


title: Convergent organization of aberrant MYB complexes controls oncogenic gene expression in acute myeloid leukemia [RNAseq_MV411]

first: Richard

last: Koche

institute: Memorial Sloan Kettering Cancer Center

summary: Dysregulated gene expression is one of the most prevalent features in human cancers. Here, we show that most subtypes of acute myeloid leukemia (AML) depend on the aberrant assembly of the MYB transcriptional co-activator complex. By rapid and selective peptidomimetic interference with the binding of CBP/P300 to MYB, but not CREB or MLL1, we find that the leukemic functions of MYB are mediated by CBP/P300-mediated co-activation of a distinct set of transcriptional factor complexes that are aberrantly assembled with MYB in AML cells. This therapeutic remodeling is accompanied by dynamic redistribution of CBP/P300 complexes to genes that control cellular differentiation and growth. Thus, aberrantly organized transcription factor complexes control convergent gene expression programs in AML cells. These findings establish a compelling strategy for pharmacologic reprogramming of oncogenic gene expression that supports its targeting for leukemias and other human cancers caused by dysregulated gene control.

overall_design: RNA-sequencing of a human leukemia cell line (MV411) treated with control PBS and peptidomimetic inhibitors over time

first: Lauren

last: Forbes

first: Sumiko

last: Takao

middle: P

first: Jose

last: Pineda

first: Robert

middle: K

last: Bradley

first: Alex

last: Kentsis


title: Convergent organization of aberrant MYB complexes controls oncogenic gene expression in acute myeloid leukemia [RNAseq_4cellLines]

overall_design: RNA-sequencing of human leukemia cell lines (HL-60, Kasumi-1, OCI-AML3, and U937) treated with control PBS and peptidomimetic inhibitors over time


title: Expression data from the cardiac tissue of Wild Type (WT) and ACKR4-knockout (ACKR4-KO) mice

city: Wuhan

first: Min

last: Zhang

state: Hubei

address: 1277 Jiefang Avenue, Wuhan 430022, China

department: Department of Cardiology

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

summary:
Purpose:Atypical classical chemokine receptor 4 (ACKR4) is a newly reported atypical classical chemokine receptor. However, its expression and role in MI are still unknown. This  study aims to determine whether ACKR4 modulates cardiac remodeling following MI and to explore the specific molecular mechanism.
Methods: RNA sequencing of infarcted hearts from WT and ACKR4-KO mice was performed at day 14 post-MI.
Results: We generated a library of distinct transcriptome expression patterns.The consistency in the clustering suggested a homogeneous genomic activity with limited background signal and high levels of reproducibility across the three biological replicates in each group.Utilizing a P value < 0.05 and fold changes of 1.5 or greater,  we identified 774 genes that are differentially expressed in ACKR4-KO mice compared to WT mice.The downregulated-genes belonged to the GO classes taxis, chemotaxis, extracellular matrix, and cytokine activity.
Conclusions: These data provide the first insight into the role and mechanism of ACKR4 in MI.

overall_design: Cardiac mRNA profiles of WT and ACKR4-KO mice at day 14 post-MI.

first: Muyang

last: Gu

first: Xiang

last: Cheng


title: Differential gene expression analysis for BAL cells isolated from LysM Cre and Netrin1loxp/loxp LysM Cre mice after intratracheal LPS challenge

city: Houston

first: Nathaniel

middle: Karl

last: Berg

state: Texas

address: 6431 Fannin Street, MSB 5.026

institute: University of Texas Health Science Center at Houston

summary:
Purpose: The goal of this study is to compare NGS-derived transcriptome profiling (mRNA-seq) of expressed genes between LysM Cre and Netrin1loxp/loxp LysM Cre mice 3 days after intratracheal LPS challenge in order to explain the worsened outcomes and increased levels of inflammation we measure in the Netrin1loxp/loxp LysM Cre mice
Methods: Three days after mice were treated with intratracheal injections of LPS, BAL cells were collected and then depleted for neutrophils using antibody-mediated depletion. The remaining cells were used for RNA isolation. mRNA profiles were generated by deep sequencing, in quadruplicate (one sample in the Netrin1loxp/loxp LysM Cre group was excluded as the sequence depth was only half compare to other 3 replicates), using paired-end 75-cycle sequencing on an Illumina NextSeq 550 System. Bases with quality scores < 20 and adapter sequences were removed from raw data with Cutadapt (v1.15), followed by alignment of clean RNA-seq reads to GRCm38 with STAR(v2.5.3a). Gene abundance was counted by HTseq-count uniquely-mapped reads number with default parameter using GencodeM15. Genes with > 5 reads in at least one sample were included for differential expression analysis by DESeq2 software.

overall_design: DEG analysis from LysM Cre and Netrin1loxp/loxp LysM Cre mice after intratracheal LPS challenge

first: Guangsheng

last: Pei

first: Zhongming

last: Zhao


title: RIPK3 is a tumor suppressor in mesothelioma

city: Philadelphia

first: yinfei

last: tan

state: PA

address: 333 cottman ave

department: Genomic Core

institute: Fox Chase Cancer Center

summary: RIPK3 locus is methylated in mesothelioma cell lines

overall_design: Promoter methylation analysis

first: Yinfei

last: Tan


title: Skin multi-omics-based interactome analysis: Integrating the tissue and mucus exuded layer for a comprehensive understanding of the teleost mucosa functionality as model of study

city: Santiago

first: Felipe

middle: E.

last: Reyes-López

state: Santiago

address: Av. Libertador Bernado O'Higgins 3363

country: Chile

institute: Universidad de Santiago de Chile

summary: In this study, we analyzed both together the epithelial tissue and the secreted mucus response using a holistic interactome-based multi-omics approach. The effect of the gilthead sea bream (Sparus aurata) skin mucosa to a dietary inclusion of spray-dried porcine plasma (SDPP) was evaluated.

overall_design: Fish (BWi = 10.6 ± 0.1 g, n = 400, mean ± standard deviation, SD) were fed for 95 days with a control diet (Diet C; equivalent to commercial diet containing 51% crude protein, 17% crude fat and 20.6 MJ/kg gross energy that fulfil the nutritional requirements of juvenile sea bream) or spray-dried porcine plasma (SDPP) diet (same control diet formulation but the Fishmeal LT70  was substituted by 3% SDPP). For each experimental group (control; SDPP group) Total RNA samples were pooled (n= 3 pools each group; n= 4 fish each pool, n= 1 fish taken at random from each tank for each pool) using the same final concentration (133 ng/µl each pool). One-color microarray was carried out according to the manufacturer’s protocols (Agilent Technologies).

first: Eva

last: Vallejos-Vidal

first: Enric

last: Gisbert


title: Characterization of a KDM5 Small Molecule Inhibitor with Antiviral Activity against Hepatitis B Virus

city: Foster City

first: Ricardo

last: Ramirez

address: 333 Lakeside Drive

institute: Gilead Sciences, Inc.

summary: Chronic hepatitis B (CHB) is a global health care challenge and a major cause of liver disease. Existing therapies do not result in a functional cure in most individuals, necessitating new antiviral strategies against Hepatitis B virus (HBV). To identify additional therapeutic avenues, we performed a focused screen of epigenetic modifiers to identify inhibitors of HBV replication. From this work we identified small molecule inhibitors of the histone lysine demethylase 5 (KDM5) with antiviral activity against HBV. To enhance the cellular permeability and liver accumulation of the most potent KDM5 inhibitor identified (GS-080) a prodrug was developed (GS-5801) that resulted in improved bioavailability and liver exposure as well as increased accumulation of the H3K4me3:H3 ratio on chromatin. GS-5801 treatment of HBV-infected primary human hepatocytes inhibited HBV replication and antigen levels. Evaluation of GS 5801 antiviral activity in a humanized mouse model of HBV infection, however, did not result in antiviral efficacy, despite achieving pharmacodynamic levels of H3K4me3:H3 predicted to be efficacious. Together these data highlight discordance between the antiviral effects of GS 5801 observed in HBV-infected primary human hepatocytes.

overall_design: HBV-infected primary human hepatocytes from three donors were treated with GS-5801 every three to four days for 13 days and total cellular mRNA was isolated and sequenced on days 1, 3, 10, and 13 after initiation of dosing

first: Sarah

last: Gilmore

first: Madeleine

last: Willkom

first: Gabriel

last: Birkus

first: Li

last: Li


title: Convergent organization of aberrant MYB complexes controls oncogenic gene expression in acute myeloid leukemia

city: New York

first: Richard

last: Koche

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

overall_design: Refer to individual Series


title: Convergent organization of aberrant MYB complexes controls oncogenic gene expression in acute myeloid leukemia [ChIPseq]

overall_design: ChIP-sequencing of a human leukemia cell line (MV411) treated with control PBS and peptidomimetic inhibitors over time

first: Lauren

last: Forbes

first: Sumiko

last: Takao

first: Jose

last: Pineda

first: Robert

last: Bradley

first: Alex

last: Kentsis


title: Generation and characterization of human iPSC-derived microglia-like cells for the use in drug discovery

city: Basel

first: Roland

last: Schmucki

address: Grenzacherstrase

country: Switzerland

institute: F. Hoffmann - La Roche AG

summary: For the development of human cellular models of microglial that allow for exploring disease underlying mechanisms and testing potential therapeutic compounds on a larger scale we generated microglia-like cells from human induced pluripotent stem cells (iPSC) and performed subsequent phenotypic and functional testing and validation by using bulk RNASeq.

overall_design: We compared the differentiation of myeloid progenitors for additional 14 days to microglia like-cells and compared these monocultures to already published co-cultures.

first: Fabian

last: Koechl

first: Marvin

last: Reich

first: Ignacio

last: Paris

first: Simon

last: Gutbier

first: Nadine

last: Dahm

first: Christophe

last: Schweitzer

first: Dieter

last: Reinhardt

first: Sally

middle: A

last: Cowley

first: Martin

last: Ebeling

first: David

last: Zhang

first: Christoph

last: Patsch

first: Markus

last: Britschgi


title: Gene expression analysis using RNA-seq of control and Elavl1 knockdown W20 cells during osteogenic differentiation

first: Satya

last: Kota

address: 188 Longwood Ave

institute: Harvard School of Dental Medicine

summary: RNA sequencing of Elavl1 knockdown in W20 cells.

overall_design: RNA sequencing was performed on total RNA isolated from W-20 control shRNA or Elavl1 knockdown cells cultured in the presence of osteogenic differentiation medium for 10 days.


title: Gene expression profiling of the 414C2 iPSC line during hypertrophic chondrocyte induction

city: Kyoto

first: Junya

last: Toguchida

address: 53 Kawahara-cho, Shogoin, Sakyo-ku

country: Japan

institute: Center for iPS Cell Research and Application

summary:
In order to better understand the mechanisms of chondrocyte hypertrophy, we induced hypertrophic chondrocytes from 414C2 iPSCs and analyzed their gene expression profile.
This dataset includes the expression data obtained from iPSC-derived sclerotome and cartilage on days -1, 28, and 56 of induction. Day 56 samples were compared to day 28 samples to analyze pathways involved in chondrocyte hypertrophy.

overall_design: A total of 9 samples were analyzed (3 biological replicates from each timepoint of induction).

first: Yann

last: Pretemer


title: Genome wide RNA-Seq of LOG OX1 and wildtype Chlorella variabilis cultures

city: Thiruvananthapuram

first: Saraswati

last: Nayar

state: Kerala

address: Thycaud Post, Poojappura

country: India

institute: Rajiv Gandhi Centre for Biotechnology

summary: To assess the significant downstream pathways affected by the overexpression of LONELY GUY in Chlorella, transcriptome analysis was carried out using RNA sequencing of three biological replicates each from WT and LOG OX1 at 14 dpi (1h before dark phase). The 14 dpi was chosen for the analysis because it was in the middle of the growth phase, where the slower growth of LOG OX1 was evident.

overall_design: mRNA profiles of 14 dpi (days post inoculation) cultures of LOG OX1 and wild type Chlorella variabilis


title: Whole hepatic transcriptomic analysis of C26 cachectic mice treated or not with cholestyramine

city: Brussels

first: Laure

last: Bindels

address: Avenue E. Mounier, 73 bte B1.73.11

department: Metabolism and Nutrition Research Group

country: Belgium

institute: Louvain Drug Research Institut

summary: We found out that bile acid pathways were deeply altered in cachectic mice bearing ectopic tumor, leading to an increase in portal and liver conjugated bile acid levels. Counteracting this increased level in conjugated bile acids using cholestyramine, a bile acid sequestrant, reduced hepatic inflammation in cachectic mice with no impact on steatosis and minor effects on thermogenesis. Hepatic whole transcriptome analysis identified 16 pathways altered in cachectic mice which were counteracted by cholestyramine, pointing out the large contribution of bile acids to hepatic disturbances occurring in cancer cachexia.

overall_design: Hepatic mRNA profiles of sham-injected mice (CT), untreated C26-transplanted mice (C26) and C26-injected mice receiving cholestyramine in their diet (C26-CHO) (2% w/w in their diet, from day 1 to 10 after cell injection) (N=8).

first: Morgane

last: Thibaut


title: DC-SCRIPT (Zpf366) binding in cDC1 and cDC2 cells from wildtype and DC-SCRIPT knockout mice

city: Parkville

first: Gordon

last: Smyth

state: Vic

address: 1G Royal Pde

department: Bioinformatics

institute: Walter and Eliza Hall Institute of Medical Research

summary: The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of this lineage diversity, its genetic basis is not fully understood. DC-SCRIPT (Zfp366) is a poorly known transcription factor expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8-dependent conventional DC1 (cDC1), while cDC2 differentiated normally. The residual DC-SCRIPT-deficient cDC1s had impaired CD8+ T-cell cross-priming, which could be in part explained by the direct control of DC-SCRIPT on IL-12p40 production. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8. Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.

overall_design: cDC1s and cDC2s were sorted from the spleens of WT and Zfp366-/- mice. CUT&Tag was used for genome-wide profiling of DC-SCRIPT binding. One to three biolological replicates were prepared (n=3 for WT cDC1, n=1 for WT cDC2, n=2 for cDC1 KO and n=2 for cDC2 KO).

first: Hannah

middle: D

last: Coughlan


title: Supplementation with Probiotic Lactobacillus plantarum 299v  in Men With Stable Coronary Artery Disease Suppresses Systemic Inflammation

city: Milwaukee

last: Hessner

address: 8701 Watertown Plank Road

department: Pediatrics

institute: Medical College of Wisconsin

summary: Recent clinical trials demonstrate the efficacy of treatment strategies to reduce cardiovascular events in patients with coronary artery disease (CAD) that focus in reducing inflammatory signaling. Emerging data implicate the gut microbiota as a critical regulator of systemic inflammation. We recently demonstrated that supplementation with Lactobacillus plantarum 299v (Lp299v) improved vascular endothelial function in men with stable CAD. In this study we investigated whether the favorable effects of Lp299v on vascular health are due in part to coordinated suppression of systemic inflammation. We applied pre- and post-Lp299v supplementation plasma from these patients to peripheral blood mononuclear cells of a healthy donor to determine the transcriptional response to this intervention.

overall_design: UPN119 cells were stimulated with plasma samples obtained prior to and immediately following 6 weeks of Lp299v supplementation from 19 men with stable CAD (n=19 PRE, n=19 POST). Gene expression analysis was perfromed in order to evaluate induced overal transcriptome changes as well as inflammatory signature changes associated with post-Lp299v supplementation plasma.

first: Benjamin

middle: C

last: Hofeld

first: Venkata

last: Puppala

first: Sudhi

last: Tyagi

first: Kwang

middle: W

last: Ahn

first: Shuang

last: Jia

first: Amberly

last: Anger

first: Nita

middle: H

last: Salzman

first: Michael

last: Widlansky


title: Characterization of a KDM5 Small Molecule Inhibitor with Antiviral Activity in Rodent Livers

first: Ricardo

last: Ramirez

state: CA

summary: Chronic hepatitis B (CHB) is a global health care challenge and a major cause of liver disease. Existing therapies do not result in a functional cure in most individuals, necessitating new antiviral strategies against Hepatitis B virus (HBV). To identify additional therapeutic avenues, we performed a focused screen of epigenetic modifiers to identify inhibitors of HBV replication. From this work we identified small molecule inhibitors of the histone lysine demethylase 5 (KDM5) with antiviral activity against HBV. To enhance the cellular permeability and liver accumulation of the most potent KDM5 inhibitor identified (GS-080) a prodrug was developed (GS-5801) that resulted in improved bioavailability and liver exposure as well as increased accumulation of the H3K4me3:H3 ratio on chromatin. GS-5801 treatment of HBV-infected primary human hepatocytes inhibited HBV replication and antigen levels. Evaluation of GS 5801 antiviral activity in a humanized mouse model of HBV infection, however, did not result in antiviral efficacy, despite achieving pharmacodynamic levels of H3K4me3:H3 predicted to be efficacious. Together these data highlight discordance between the antiviral effects of GS 5801 observed in rodent livers.

overall_design: Male Wistar Han rats were dosed p.o. once daily for seven days with 10, 30, or 100 mg/kg of GS-5801 or water (vehicle control). 100 mg samples of liver tissue (left lateral lobe) were collected, snap frozen using liquid nitrogen, and stored at -80 °C for subsequent transcriptome analysis by RNAseq.

first: Sarah

last: Gilmore

first: Chelsea

last: Snyder

first: Li

last: Li


title: Best practices for the visualization, mapping, and manipulation of R-loops

city: Davis

first: Frederic

last: Chedin

address: 1 Shields Avenue

department: MCB

institute: UC Davis

summary: R-loops represent an abundant class of large non-B DNA structures in genomes. Even though they form transiently and at modest frequencies, interfering with R-loop formation or dissolution significantly impacts genome stability. Addressing the mechanism(s) of R-loop-mediated genome destabilization requires a precise characterization of their distribution in genomes. A number of independent methods have been developed to visualize and map R-loops, but their results are at times discordant, leading to confusion. Here we review the main existing methodologies underlying R-loop mapping and assess their limitations and the robustness of existing datasets. We offer a set of best practices to improve the reproducibility of maps, hoping that such guidelines could be useful for authors and referees alike. Finally, we offer a possible resolution to the apparent contradictions in R-loop mapping outcomes between antibody-based and RNase H1-based mapping approaches.

overall_design: DRIPc-seq was performed on human HeLa and K562 cells with and without RNase H treatment. DRIP-seq was performed on human HeLa cells.

first: Stella

last: Hartono

first: Lionel

last: Sanz

first: Vincent

last: Vanoosthuyse


title: Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS

city: Ann Arbor

first: Mats

last: Ljungman

state: Michigan

address: NCRC, B520 Room 1346 2800 Plymouth Rd.

institute: University of Michigan

summary: We hereby provide the initial portrait of lincNORS, a spliced lincRNA generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen signals. Biochemically, this lincRNA fine-tunes cellular sterol/steroid biosynthesis by repressing the expression of multiple pathway components. Mechanistically, the function of lincNORS requires the presence of RALY, an RNA-binding protein recently implicated in cholesterol homeostasis. We also noticed the proximity between this locus and naturally-occurring genetic variations highly significant for sterol/steroid -related phenotypes, in particular the age of sexual maturation. An integrative analysis of these variants provided a more formal link between these phenotypes and lincNORS, further strengthening the case for its biological relevance.

overall_design: Examination of primary transcript level using the nascent RNA Bru-seq method, in MCF-7 cells cultured under normoxia (21% O2) or hypoxia (1% O2).

first: Xue

last: Wu

first: Cristina

last: Niculite

first: Mihai

last: Preda

first: Annalisa

last: Rossi

first: Toma

last: Tebaldi

first: Elena

last: Butoi

first: Mattie

last: White

first: Oana

last: Tudoran

first: Daniela

middle: N

last: Petrusca

first: Amber

middle: S

last: Jannasch

first: William

last: Bone

first: Xingyue

last: Zong

first: Fang

last: Fang

first: Alexandrina

last: Burlacu

first: Michelle

middle: T

last: Paulsen

first: Brad

last: Hancock

first: George

last: Sandusky

first: Sumegha

last: Mitra

first: Melissa

last: Fishel

first: Aaron

last: Buechlein

last: Ivan

first: Spyros

last: Oikonomopoulos

first: Myriam

last: Mosley

first: Milan

last: Radovich

first: Utpal

last: Davé

first: Jiannis

last: Ragoussis

first: Kenneth

last: Nephew

first: Bernard

last: Mari

first: Alan

last: McIntyre

first: Heiko

last: Konig

first: Diana

last: Cousminer

first: Paolo

last: Macchi

first: Mircea


title: Differential expression genes analysis of knocking down Prmt1 and Ripk1 in MC38/gp100 cell line

first: Weiyi

last: Peng

address: 3517 Cullen Blvd, Room 3025

institute: University of Houston

summary: Despite approval of immunotherapy for a wide range of cancers, the majority of patients fail to respond to immunotherapy or relapse following initial response. These failures may be attributed to immunosuppressive mechanisms co-opted by tumor cells. However, it is challenging to utilize conventional methods to systematically evaluate the potential of tumor intrinsic factors to act as immune regulators in cancer patients. To identify immunosuppressive mechanisms in non-responders to cancer immunotherapy in an unbiased manner, we performed genome-wide CRISPR immune screens and integrated our results with multi-omics clinical data to evaluate the role of tumor intrinsic factors in regulating two rate-limiting steps of cancer immunotherapy, namely T cell tumor infiltration and T cell-mediated tumor killing.Our studies revealed two distinct types of immune resistance regulators and demonstrated their potential as therapeutic targets to improve the efficacy of immunotherapy. Among them, PRMT1 and RIPK1 were identified as a dual immune resistance regulator and a cytotoxicity resistance regulator, respectively. Although the magnitude varied between different types of immunotherapy, genetically targeting PRMT1 and RIPK1 sensitized tumors to T-cell killing and anti-PD-1/OX40 treatment. Interestingly, a RIPK1-specific inhibitor enhanced the antitumor activity of T cell-based and anti-OX40 therapy, despite limited impact on T cell tumor infiltration. Collectively, the data provides a rich resource of novel targets for rational immuno-oncology combinations.

overall_design: mRNA profiles of MC38/gp100 stable cell lines transduced with non-targeting gRNA, gRNA targeting Prmt1 and Ripk1

first: Jiakai

last: Hou

first: Yunfei

last: Wang


title: Transcriptome of cytoplasmic and nuclear small RNAs in innate immune cells

city: shang hai

first: Qian

last: Zhang

address: xiangyin road 800

institute: Second military medical university

summary: We isolated RNAs from cytoplasmic or nuclear fraction of dendritic cells, and subject these RNAs for high throughput sequencing. After mapped to mouse genome, sequencing reads (18-30nt) were calculated as the log2 ratio using the normalized TPM (transcripts per million reads) value to determine the expression difference of each sRNA from nuclear and cytoplasmic fractions. We then picked up the superior nucleus-localized sRNAs according to the criteria that abundance of each sRNA was over 20 and x>10y (x: abundance of sRNA from nuclear fraction; y: abundance of sRNAs from cytoplasm fraction).

overall_design: Identifying nuclear-enriched small RNAs in innate immune cells.

first: Xuetao

last: Cao

first: Yang

last: Shi


title: A multiOMICs approach shed light on the higher yield phenotype and abiotic stress tolerance in tobacco lines expressing the carrot lycopene β-cyclase1

city: Potsdam

first: Juan Camilo

last: Moreno Beltran

state: Brandenburg

address: Am Muehlenberg 1

department: Molecular Physiology

institute: MPI for Molecular Plant Physiology

summary: Recently we published a set of tobacco lines, expressing the Dacucus carota (carrot) DcLCYB1 gene, with accelerated development, increased carotenoid content, and plant yield. Due to this, expression of DcLCYB1 might be of general interest in crop species as a strategy to accelerate plant development and increase biomass production under adverse field conditions. However, to follow this path, a better understanding of the molecular basis of this phenotype is essential. Here, we combine OMICs (RNAseq, proteomics, metabolomics, and lipidomics) and stress experiments to advance our understanding on the broader effect of the LCYB expression on the tobacco genome and metabolism.

overall_design: Overall 12 samples were analyzed including 3 transgenic lines and 1 wild type (control) and each sample consist of 3 biological replicates.

first: Juan

last: Moreno

first: Silvia

last: Martinez-Jaime

first: Monika

last: Kosmacz

first: Philipp

last: Schulz

first: Axel

last: Fischer

first: Urszula

last: Luzarowska

first: Michel

last: Havaux

first: Aleksandra

last: Skirycz


title: SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice

city: London

first: Karine

last: Rizzoti

address: 1 Midland Road

institute: Francis Crick Institute


title: SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice III

summary: Exploration of the molecular mechanisms underlying melanotroph tumourigenesis and the role of SOX2 in both SCs and melanotrophs

overall_design: Single cell RNA sequencing analysis on pituitary intermediate lobe dissected from three-month old tamoxifen treated Sox9iresCreERT2/+;p27-/- , Sox9iresCreERT2/+;Sox2fl/+;p27-/- animals and control Sox9iresCreERT2/+ animals.

first: Veronica

last: Moncho-Amor

first: Robin

last: Lovell-Badge


title: SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice II

summary: Characterization of the effects of Sox2 heterozygosity on tumorigenesis in p27-/- pituitary tumors.

overall_design: Transcriptomic analyses from two to three-months old dissected pituitary intermediate lobe obtained from wt, p27-/-, p27-/-;Sox2+/- mice.


title: SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice I

summary: Characterization of the initiation and development of pituitary intermediate lobe tumors in p27-/- mice.

overall_design: Transcriptomic analyses from two- and seven-months old dissected pituitary intermediate lobe obtained from wt and p27-/- mice.


title: Expression changes in immune and epigenetic gene pathways associated with nutritional metabolites in maternal blood from pregnancies resulting in autism and atypical neurodevelopment

first: Janine

last: LaSalle

address: Medical Microbiology and Immunology

summary: The prenatal period is a critical window to study factors involved in the development of autism spectrum disorder (ASD). Environmental factors, especially in utero nutrition, can interact with genetic risk for ASD, but how specific prenatal nutrients in mothers of children later diagnosed with ASD or non-typical development (Non-TD) associate with gestational gene expression events is poorly understood. Maternal blood collected prospectively during pregnancy provides a new opportunity to gain insights into nutritional effects on gene pathways and neurodevelopment. Using differential gene expression analysis, six transcripts associated with four genes (TGR-AS1, SQSTM1, HLA-C and RFESD) showed genome-wide significance (FDR q < 0.05) with child outcomes. Genes nominally differentially expressed compared to TD (p < 0.05) specifically in ASD, but not Non-TD, significantly overlapped with seven high confidence ASD genes. 218 transcripts in common to ASD and Non-TD differential expression compared to TD were significantly enriched for functions in immune response to interferon-gamma, apoptosis, and metal ion transport. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG and betaine. A module enriched in DNA methylation functions showed a protective association with folic acid/5-MeTHF concentrations and ASD risk. Independent of child outcome, maternal plasma betaine and DMG concentrations associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results support the premise that the prenatal maternal blood transcriptome is a sensitive indicator of gestational nutrition and children’s later neurodevelopmental outcomes.

overall_design: Genome-wide transcriptome levels were measured using microarrays in 300 maternal blood samples (including 214 mother given consent forms) from all three trimesters in the Markers of Autism Risk in Babies -Learning Early Signs (MARBLES) study. Sixteen different nutrient metabolites, including folic acid, betaine, 5’-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured in the same samples. Differential expression analysis and weighted gene correlation network analysis (WGCNA) compared gene expression between children later diagnosed as ASD and typical development (TD), Non-TD and TD, and to nutrient metabolites.

first: Yihui

last: Zhu

first: Rebecca

middle: J

last: Schmidt


title: MAP3K7 and CHD1 are novel mediators of resistance to oncolytic vesicular stomatitis virus in PC3 prostate cancer cells

city: Winston-Salem

first: Douglas

middle: Scott

last: Lyles

state: NC

address: Medical Center Blvd.

department: Biochemistry

institute: Wake Forest School of Medicine

summary: A key principle of oncolytic viral therapy is that many cancers develop defects in their antiviral responses, making them more susceptible to virus infection. However, some cancers display resistance to viral infection. Many of these resistant cancers constitutively express interferon-stimulated genes (ISGs). The goal of these experiments was to determine the role of two tumor suppressor genes, MAP3K7 and CHD1, in viral resistance and ISG expression in PC3 prostate cancer cells resistant to oncolytic vesicular stomatitis virus (VSV). MAP3K7 and CHD1 are often co-deleted in aggressive prostate cancers. Silencing expression of MAP3K7 and CHD1 in PC3 cells increased susceptibility to M protein mutant M51R-VSV as shown by increased expression of viral genes, increased yield of progeny virus, and reduction of tumor growth in nude mice. Silencing MAP3K7 alone had a greater effect on virus susceptibility than silencing CHD1. Silencing MAP3K7 and CHD1 decreased constitutive expression of ISG mRNAs and proteins, whereas silencing MAP3K7 alone decreased expression of ISG proteins, but actually increased expression of ISG mRNAs. These results suggest a role for the protein product of MAP3K7, transforming growth factor β-activated kinase 1 (TAK1), in regulating translation of ISG mRNAs and a role of CHD1 in maintaining the transcription of ISGs.

overall_design: mRNAs were analyzed from uninfected or M51R-VSV-infected PC3 cells expressing nontargeting shRNA or shRNA against MAP3K7, CHD1, or both. Three independent replicates of each condition were sequenced to a target read depth of 30M reads per library on the Illumina NextSeq 500.


title: Gene expression profiling of immune cells from patients with acute on chronic liver failure (ACLF)

city: Paris

first: Pierre

last: de la Grange

address: 29, rue du Faubourg Saint-Jacques

department: Paris Biotech Santé

country: France

institute: GenoSplice technology

summary:
Whole blood from 7 patients with stable cirrhosis, 7 patients with acutely decompensated cirrhosis without ACLF and 17 patients with ACLF (8 related to sepsis and 9 unrelated to sepsis) was sampled into tempus tubes (Applied biosystems, Ambion). The same method was used to sample whole blood from 7 healthy subjects and from 8 patients with septic shock without cirrhosis that were used as comparators.RNA was then extracted using the PerfectPure RNA blood kit (3 PRIME) according to manufactuter instructions.
100 ng of RNA per sample were then hybridized on Human Transcriptome Array 2.0

overall_design: Prospective trial comparing whole blood transcriptome of different group of patients according to the existance of chronic liver disease and to its severity

first: Richard

last: Moreau

first: Emmanuel

last: Weiss


title: Adaptive laboratory evolution restores solvent tolerance in the plasmid-cured Pseudomonas putida S12; a global transcriptional analysis

city: Leiden

first: Johannes

middle: Han

last: de Winde

address: Sylviusweg 72

department: Faculty of Science

institute: Leiden University

summary: Pseudomonas putida S12 is an inherently solvent-tolerant strain and constitutes a promising platform for biotechnology applications in whole-cell biocatalysis of aromatic compounds. The genome of P. putida S12 consists of a 5.8 Mbp chromosome and a 580 kbp megaplasmid pTTS12. pTTS12 encodes several genes which enable the tolerance to various stress conditions, including the main solvent efflux pump SrpABC. Removal (curing) of megaplasmid pTTS12 and subsequent loss of solvent efflux pump SrpABC caused a significant reduction in solvent tolerance of the resulting strain. In this study, we succeeded in restoring solvent tolerance in the megaplasmid-cured P. putida S12 using adaptive laboratory evolution (ALE) and molecular analysis to investigate the intrinsic solvent tolerance of P. putida S12. RNA-seq was performed to study the global transcriptomic response of the solvent-adapted plasmid-cured P. putida S12 in the presence of toluene. This analysis revealed the downregulation of ATP synthase, flagella and other RND efflux pumps, which indicates the importance of maintaining proton motive force during solvent stress.

overall_design: RNA-seq analysis and comparison of the wildtype, plasmid-cured, and ALE derived plasmid-cured Pseudomonas putida S12 grown in liquid Lysogeny broth in the absence and presence of toluene (0.1 %)

first: Hadiastri

last: Kusumawardhani

first: J


title: Cancer associated HIF-2a governs trunk neural crest stemness

city: Lund

first: Sofie

last: Mohlin

address: TCR, MV404:C3, Scheelevagen 8

department: Clinical Sciences

country: Sweden

institute: Lund University

summary: We report that cancer associated protein HIF-2a is expressed in trunk neural crest neuroblastoma precursor cells in the developing embryo in three different species; human, mouse and avian. Dysregulation of HIF-2a leads to alterations in embryonic development, and neural crest cell migration, proliferation and self-renewal capacity. With RNAsequencing we report that alterations of HIF-2a expression affects the global transcriptome and that gene ontology enrich for the same processes observed in vivo.

overall_design: Examination of differences in gene expression in avian trunk neural crest cells with knockdown of HIF-2a vs control.


title: Clinical drug resistance linked to reversible phenotypic transition and epigenetic alteration in multiple myeloma

city: Charlestown

first: Maolin

last: Ge

state: Massachusetts

address: 149 13th Street

department: MGH Cancer Center

institute: Harvard Medical School

summary: The development of proteasome inhibitors (PIs) for the treatment of multiple myeloma (MM) has dramatically increased treatment responses and improved survival. The first-in-class PI, bortezomib, was used in a twice-weekly intravenous as a sustained single or combinational regimen for relapsed and subsequently for newly diagnosed MM. The relatively rapid acquisition of drug resistance to PI treatment remains a crucial obstacle. Gradual familiarity with toxicity and optimizing dose schedules have formed the current use of PIs as key components in promoting response and eliminating resistance. Combination therapies and schedule adaptation to once-weekly use of PIs have meanwhile been shown to be both more tolerable and highly efficacious. Interestingly, patients may remain sensitive to PIs after relapse of initial therapy, implying that PI resistance is reversible and suggest a previously unrecognized drug resistance mechanism via epigenetic changes that may be intrinsic to PI treatment.

overall_design: Examination of differential expressive genes in (i) relapsed and reversed (rev) B cell maturation antigen (BCMA) positive cells of MM patients; (ii) MM cell line MM1.S and the corresponding tolerant and reversed cells, and (iii) xenograft MM mouse models treated with vehicle (ctrl), sustained low concentration of bortezomib (bort_low), intermittent high concentration of bortezomib (bort_high), combined bortezomib and SAHA (bort_SAHA), or mice in which bortezomib was withdraw after treatment (rev).

first: Han

last: Liu


title: Gene expression profiling patients with cirrhosis and acute on chronic liver failure (ACLF)

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

overall_design: Refer to individual Series


title: Gene expression profiling of neutrophils from patients with cirrhosis and acute on chronic liver failure (ACLF)

summary:
Neutrophils were isolated (using Ficoll, Dextran and water to lyse the red cells) from whole blood of 5 healthy subjects, 5 patients with stable cirrhosis and 5 patients with ACLF.  RNA was then extracted and amplified
100 ng of RNA per sample were then hybridized on ClarionS array (Affymetrix, Thermofischer scientific)

overall_design: Prospective trial comparing transcriptome of neutrophils from different group of patients according to the existence of chronic liver disease and to its severity


title: Treatment of MCF-7 cells with TRAIL and Smac mimetic (LCL-161) [seq]

first: Christer

last: Larsson

address: Medicon Village, Bldg 404:C3

department: Laboratory Medicine

institute: Lund university

summary: The aim was to identify the effect of caspase inhibition on changes in gene expression in MCF-7 cells induced by a combination of TRAIL and LCL-161. Treated samples and control samples were collected after 24 h of treatment.

overall_design: Four treatments with four biological replicates. The groups were Control, LCL-161+TRAIL, zVZD, and LCL-161+TRAIL+zVAD

first: Christian

last: Holmgren

first: Victoria

last: Granqvist


title: Gibberellins synthesis is involved in the reduction of cell flux and elemental growth rate in maize leaf under low nitrogen supply

city: zheng zhou

first: xiaohuan

last: mu

address: zhengzhou long zi hu

institute: Henan Agricultural University

summary: One strategy for plants to adapt to low nitrogen (LN) stress is to reduce shoot growth and allocate more N and carbon for root growth. The physiological mechanism underlying the response of leaf growth to LN stress remains largely unknown. In this study, we investigated cell division and elongation in maize leaf growth in response to LN stress using an integrated approach including kinematic growth analysis, tissue-specific RNA-seq dissection and hormone determination.

overall_design: Using an integrated approach including kinematic growth analysis, tissue-specific RNA-seq dissection and hormone determination to investigated cell division and elongation in maize leaf growth in response to LN stress . Two biological replicates were generated for each tissue.

first: Xiaohuan

last: Mu

first: Qinwu

last: Chen

first: Xiangyu

last: Wu

first: Fanjun

first: Lixing

last: Yuan

first: Guohua

last: Mi


title: XerD is required to unload bacterial SMC complexes at the replication terminus

city: Bloomington

first: Xindan

last: Wang

state: IN

address: 1001 E 3rd St

department: Biology

institute: Indiana University at Bloomington

summary: Bacillus subtilis SMC complexes are topologically loaded at centromeric sites adjacent to the replication origin by the partitioning protein ParB. These ring-shaped ATPases then translocate down the left and right chromosome arms while tethering them together. Here we show that the site-specific recombinase XerD that resolves chromosome dimers is required to unload SMC tethers when they reach the terminus. We identify XerD-specific binding sites in the terminus region and show that they dictate the site of unloading in a manner that depends on XerD but not its catalytic residue, its partner protein XerC, or the recombination site dif. Finally, we provide evidence that ParB and XerD homologs perform similar functions in Staphylococcus aureus. Thus, loading and unloading of SMC complexes are mediated by two broadly conserved factors: one involved in origin segregation, the other in terminus resolution. Similar site-specific unloading activities could modulate eukaryotic SMC complexes during interphase and mitosis.

sample_organism:
Staphylococcus aureus
Bacillus subtilis PY79

overall_design: Hi-C and ChIP-seq experiments were performed on wild type and mutant cells of Bacillus subtilis PY79 and Staphylococcus aureus HG003 growing in rich media.

first: X


title: RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk [ChIP-seq]

city: Stuttgart

first: Cristiana

last: Lungu

state: BW

address: Allmandring 31

department: Institute of Cell Biology and Immunology

institute: University of Stuttgart

summary:
In this study, we focused on elucidating the role of Ring Finger Protein 40 (RNF40) in bone development by using a conditional knockout mouse approach during different stages of osteoblast (OB) differentiation and maturation. RNF40 forms an obligate E3 ubiquitin ligase complex together with RNF20 and mediates the monoubiquitination of lysine 120 of histone H2B (H2BK120ub1). We provide evidence that RNF40 regulates OB differentiation in a stage-dependent manner. Additionally, we show that RNF40 is required for bone cell crosstalk whereby loss of RNF40 leads to a reduction in osteoclast numbers and function through modulation of vitamin D receptor (VDR)-induced Rankl expression in OBs. Taken together, these data imply an important role of RNF40-mediated H2Bub1 in bone formation and remodeling and provide a basis for further investigation of its  anti-resorptive  potential for the treatment of conditions such as osteoporosis or cancer-associated osteolysis.
In this study we show that RNF40 is required in earlier stages of osteoblast differentiation and is involved in bone cell crosstalk by regulating vitamin D induced Rankl expression

overall_design:
We generated ChIP-Sequencing data from calvarial osteoblasts isolated from RNF40RosaCreERT2 mutant mice: H2Bub1 and RNAPII in differentiated CalOBs ± 4-hydroxytamoxifen treatment (TAM); H2Bub1 in DMSO and VitD treated CalOBs; and H3K4me3 in DMSO or VitD treated CalOBs ± TAM

Please note that each processed data was generated from both replicates and is linked to the corresponding *_A sample records

first: Steven

last: Johnsen

first: Zeynab

last: Najafova


title: RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk


title: RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk [RNA-seq]

overall_design: We generated RNA-Sequencing data from calvarial osteoblasts isolated from RNF40RosaCreERT2 mutant mice.


title: Combination Anti-PD-1 and Anti-retroviral Therapy Provides Therapeutic Benefit Against SIV

city: Atlanta

first: Gregory

last: Tharp

state: GA

address: 954 Gatewood Dr

department: Developmental and Cognitive Neuroscience

institute: Yerkes National Primate Research Center

summary: Therapeutic strategies that enhance anti-viral immunity and reduce the viral reservoir are critical to achieving durable remission of HIV. The co-inhibitory receptor programmed death-1 (PD-1) regulates CD8+ T cell dysfunction during chronic HIV and SIV infections 1-4. In addition, PD-1+ CD4+ T cells constitute a significant fraction of the HIV/SIV viral reservoir5-7. We previously demonstrated that in vivo blockade of PD-1 during chronic SIV infection improves the function of anti-viral CD8+ T cells and B cells 4,8. However, the immunological effects of PD-1 blockade during anti-retroviral therapy (ART) and the potential to destabilize the persistent HIV/SIV reservoir have not been studied. Here, we show that administration of anti-PD-1 antibody (PD-1 Ab) 10 days prior to initiation of ART rapidly enhanced anti-viral CD8+ T cell function and diminished interferon stimulated genes (ISGs) that resulted in markedly improved viral suppression in plasma and better Th17 cell reconstitution in the rectal mucosa following ART initiation. In addition, PD-1 blockade during suppressive ART resulted in transient increases in plasma viremia, induction of gene signatures associated with effector CD8+ T cell function and ISGs, and lower levels of cell associated replication-competent virus suggesting destabilization of the viral reservoir. Following ART interruption, PD-1 Ab treated animals showed markedly higher expansion of proliferating CXCR5+ Perforin+ Granzyme B+ effector CD8+ T cells and lower regulatory T cells that resulted in delayed viral rebound and better control of viremia. PD-1 blockade administered only during suppressive ART however was only partially effective. Our results indicate an optimal regimen of PD-1 blockade administered in combination with ART, that augments anti-viral CD8+ T cell function and reduces the viral reservoir leading to improved control of viral rebound after ART interruption. These results have important implications for developing novel therapeutic interventions to achieve durable remission of HIV.

overall_design: To determine the effects of PD-1 blockade in combination with ART and its potential to enhance anti-viral immunity and reduce the viral reservoirs, we performed PD-1 blockade in two phases: I) prior to initiation of ART and II) during suppressive ART. In phase I of the study, we administered 5 doses of PD-1 Ab (3 mg/kg/dose) intravenously on days 0, 3, 7, 10, and 14 to 10 SIVmac251-infected rhesus macaques (RMs) between 24-30 weeks after infection (Fig. 1A). As a control, we treated 10 SIVmac251-infected RMs with saline. We initiated ART in all animals at day 10 after the initiation of PD-1 blockade. To determine the effects of PD-1 blockade on a global scale, we performed RNASeq to compare gene signatures in the blood of 10 PD-1 Ab treated and 5 saline treated animals at day 0 and day 10 of PD-1 blockade. To determine the additive biological effects of PD-1 blockade on anti-viral immunity and the persistent viral reservoirs when administered during suppressive ART (phase II), the 10 RMs given PD-1 Ab during phase I were again treated with PD-1 Ab (double treated) at 26-30 weeks following ART initiation. Three monthly infusions of PD-1 Ab were administered at 10mg/kg/dose (Fig. 3A). To test the influence of PD-1 blockade administered only during suppressive ART, we split the 10 RMs from the saline group into two groups and gave either PD-1 Ab (single treated group; n=5) or saline (saline control group; n=5). RNASeq was only performed on the double treated and single treated groups, not the saline control group. We again looked to compare gene signatures in the blood of PD-1 Ab treated RMs from day 0 of first PD-1 Ab infusion under ART and 7 days after.

first: Geetha

last: Mylvaganam

first: Lynette

last: Chea

first: Sakeenah

last: Hicks

first: Vijayakumar

last: Velu

first: Smita

last: Iyer

first: Jacob

last: Estes

middle: E

last: Bosinger

first: Gordon

last: Freeman

first: Rafi

last: Ahmed

first: Rama

middle: R

last: Amara


title: Agaricus bisporus respiratory bursts

city: Utrecht

first: Robert-Jan

last: Bleichrodt

address: Padualaan 8

institute: Utrecht University

summary: Respiratory bursts were observed in A. bisporus. CO2 production and O2 consumption increased up to 3.5 fold during these 3 h bursts while compost temperature increased up to 3 °C. We set out to find which pathways were characteristic for these bursts and the interval between these bursts.

overall_design: Total RNA expression by Agaricus bisporus production strain A15, was analyzed during respiratory bursts, after a burst and in the interval between two bursts (i.e. ~0.5 h, 4.5 h, and 8.5 h after a burst started, respectively), by Illumina sequencing. In total 9 samples were sequenced, each sample point of a burst having each 3 replicates.

first: Aurin

middle: M

last: Vos

first: Koen

last: Herman

first: Robin

last: Ohm

first: Heike

last: Schmitt

first: Luis

middle: G

last: Lugones

first: Han

last: Wösten


title: ATAC-seq in HUDEP-2 cells

status: Public on Feb 23 2021

city: Boston

first: Divya

last: Vinjamur

address: 1 Blackfan Circle

institute: Boston Children's Hospital

summary: ATAC-seq was performed in HUDEP-2 cells grown in expansion phase medium following the OMNI-ATAC protocol (Corces MR, et al. Nat. Methods, 2017).

overall_design: 3 ATAC-seq replicates were performed in HUDEP-2 cells grown in expansion medium.

first: Mir

last: Hossain

first: Daniel

last: Bauer


title: Expression data from human hamstring tendon

city: Auckland

first: Dorit

last: Naot

address: Private Bag 92019

department: Medicine

country: New Zealand

institute: University of Auckland

summary:
The hamstring tendon is used as autograft in surgical reconstruction of tears of the anterior cruciate ligament. The rate of re-rupture after surgery is higher in younger patients.
The aim of the study was to identify molecular mechanisms that underlie the greater susceptibility of tendon from younger people to tear.

overall_design: We used superfluous tissue of hamstring tendon from reconstructive surgeries to compare gene expression between two groups of patients: 9 patients under the age of 20 years and 10 patients over the age of 20 years at time of surgery.

first: David

last: Musson


title: The Tec kinase ITK optimizes differential NFAT, NF-κB, and Erk1/2 signaling to regulate graded gene induction in mouse CD8+ T cells [RNA-seq]

city: Aurora

first: Leslie

last: Berg

state: Colorado

address: 12800 East 19th Avenue MS 8333, RC1 North room P18-8101

department: Immunology and Microbiology Department

institute: University of Colorado School of Medicine

summary: In this study we generated SMART-seq cDNA libraries from mouse CD8+ OT-I T cells that were stimulated with WT splenocytes loaded with OVA peptide or OVA peptide variants, with or without presence of ITK inhibitor PRN-694 at early time points (0, 30min, 60min, or 120min).

overall_design: RNA-seq data of peptide-stimulated OT-I T cells at early time points.

first: Michael

middle: P

last: Gallagher

first: James

last: Conley

first: Pranitha

last: Vangala

first: Manuel

last: Garber

first: Andrea

last: Reboldi


title: The Tec kinase ITK optimizes differential NFAT, NF-κB, and Erk1/2 signaling to regulate graded gene induction in mouse CD8+ T cells [ATAC-seq]

summary: In this study we generated ATAC-seq libraries from mouse CD8+ OT-I T cells that were stimulated with WT splenocytes loaded with OVA peptide or OVA peptide variants, with or without presence of ITK inhibitor PRN-694 at early time points (0, 30min, 60min, or 120min).

overall_design: ATAC-seq data of peptide-stimulated OT-I T cells at early time points.


title: Acute myeloid leukemia-induced functional inhibition of healthy CD34+ hematopoietic stem and progenitor cells

city: Duesseldorf

first: Thomas

last: Schroeder

address: Moorenstr. 5

department: Department of Hematology, Oncology and Clinical Immunology

institute: University of Duesseldorf, Medical Faculty

summary: Exposure to AML-derived supernatants significantly inhibited proliferation, cell cycling, colony formation and differentiation of healthy CD34+ HSPC. RNA sequencing of healthy CD34+ HSPC after exposure to leukemic conditions revealed a specific signature of genes related to proliferation, cell cycle regulation and differentiation thereby reflecting their functional inhibition on a molecular level.

overall_design: Healthy CD34+ HSPC are exposed to AML-derived supernatants

first: Felix

last: Bormann

first: Stefanie

last: Geyh

first: Karl

last: Köhrer

first: Patrick

last: Petzsch

first: Rainer

last: Haas


title: TBX5 ChIP from the Fetal Lung

city: CHICAGO

first: Jeffrey D.

last: Steimle

state: IL

address: 900 E. 57th Street, KCBD 5240

institute: University of Chicago

summary: T-box transcription factors have been shown to play critical roles in the development and identity of the lungs. Tbx5 has been implicated as an initiator of pulmonary development through direct regulation of signaling molecules of the posterior second heart field (pSHF) and cardiopulmonary progenitors (CPs) (Arora et al. 2012 PLOS Genetics; Steimle et al 2018 PNAS). We hypothesize TBX5 regulates additional targets required for lung development. To this end, we performed ChIP-sequencing to identify localization of TBX5 during fetal lung development.

overall_design: Lungs were dissected from E14.5 CD-1 mouse embryos. Two biological replicates were generated. For immunoprecipitation, the chromatin extract was incubated with 5ug of the anti-TBX5 antibody (Santa Cruz Biotechnology sc-17866; Lot #G1516) at 4°C for >12 hours in a total volume of 200 _L. Libraries from ChIP and input DNA were prepared using NEBNext Ultra DNA Library Prep Kit (E7370S). During library preparation, adaptor-ligated DNA fragments of 200-650 bp in size were selected before PCR amplification using Sera-Mag magnetic beads (GE, 6515-2105-050-250). DNA libraries were sequenced using Illumina Hi-seq instruments (single-end 50 base) by the Genomics Core Facility at the University of Chicago.

first: Jeffrey

first: Kohta

last: Ikegami

first: Ozanna

last: Burnicka-Turek

first: Ivan

last: Moskowitz


title: The Tec kinase ITK optimizes differential NFAT, NF-κB, and Erk1/2 signaling to regulate graded gene induction in mouse CD8+ T cells

first: Leslie


title: Microglia contributes to remyelination in cerebral but not spinal cord ischemia

city: Düsseldorf

first: Goran

last: Pavic

state: NRW

address: Moorenstrasse 5

department: Neurologische Klinik

institute: Universitätsklinikum Düsseldorf

summary:
Inflammation after injury of the central nervous system (CNS) is increasingly viewed as a therapeutic target. However, comparative studies in different CNS compartments are sparse. To date only few studies based on immunohistochemical data and all referring to mechanical injury have directly compared inflammation in different CNS compartments. These studies revealed that inflammation is more pronounced in spinal cord than in brain. Therefore, it is unclear whether concepts and treatments established in the cerebral cortex can be transferred to spinal cord lesions and vice versa or whether immunological treatments must be adapted to different CNS compartments. By use of transcriptomic and flow cytometry analysis of equally sized photothrombotically induced lesions in the cerebral cortex and the spinal cord, we could document an overall comparable inflammatory reaction and repair activity in brain and spinal cord between day 1 and day 7 after ischemia. However, remyelination was increased after cerebral versus spinal cord ischemia which is in line with increased remyelination in grey matter in previous analyses and was accompanied by microglia dominated inflammation opposed to monocytes/macrophages dominated inflammation after spinal cord ischemia. Interestingly remyelination could be reduced by microglia and not hematogenous macrophage depletion.
Our results show that despite different cellular composition of the postischemic infiltrate the inflammatory response in cerebral cortex and spinal cord are comparable between day 1 and day 7. A striking difference was higher remyelination capacity in the cerebral cortex, which seems to be supported by microglia dominance.

overall_design: 32 total samples were analyzed

first: Robin

last: Jansen

first: Katharina

last: Raba

first: Nicole

last: Rychlik

first: Ioannis

last: Simiantonakis

last: Küry

first: Peter

last: Göttle

first: Hans-Peter

last: Hartung

first: Sven

last: Meuth

first: Sebastian

last: Jander

first: Michael

last: Gliem


title: T cell-intrinsic prostaglandin E2-EP2/EP4 signaling is critical in pathogenic Th17 cell-driven inflammation

city: Seoul

first: Jinju

last: Lee

address: 88, Olympic-ro 43-gil, Songpa-gu

institute: University of Ulsan

summary: IL-23 induces ptgs2 encoding cyclooxygenase 2 in Th17 cells and produces PGE2, which acts back on PGE2 receptors EP2 and EP4 in these cells and enhances IL-23-induced expression of an IL-23 receptor subunit gene, Il23r, by activating STAT3, CREB1 and NF-κB through cAMP-protein kinase A signaling. This PGE2 signaling also induces expression of various inflammation-related genes, which possibly function in Th17 cell-mediated pathology. Combined deletion of EP2 and EP4 selectively in T cells suppressed accumulation of IL-17A+ and IL-17A+IFN-γ+ pathogenic Th17 cells and abolished skin inflammation in IL-23-induced psoriasis mouse model. Analysis of human psoriatic skin biopsies shows positive correlation between PGE2 signaling and the IL-23/Th17 pathway.

overall_design: IL-23 mobilizes T cell-intrinsic PGE2-EP2/EP4 signaling, which is critical in IL-23-induced pathogenic Th17 cell generation. Combined blockade of EP2 and EP4 suppressed IL-23-induced skin inflammation, suggesting this pathway as potential therapeutic target of Th17-mediated diseases.

first: Tomohiro

last: Aoki


title: WDR5 promotes histone deacetylation via direct interaction with HDAC2 in human CCA cells.

city: Jinan

first: Tianli

last: Chen

state: Shandong

address: 107 West Wenhua Road

department: Department of General Surgery

institute: Qilu Hospital of Shandong University

summary: As an essential component of histone methyltransferase complex SET1/MLL, WDR5 participates in histone 3 lysine 4 methylation (H3K4me) and promotes transcription by generating an open chromatin structure and enabling better access to the transcriptional machinery. Moreover, WDR5 interacts with histone deacetylases (HDACs) to promotes histone deacetylation, which induces the compact state of nucleosome, thus represses DNA transcription. However, the modulation of WDR5 on histone methylation and acetylation is tissue- and context-specific, and this function has not been elucidated in cholangiocarcinoma yet.

overall_design: Examination of H3K4 acetylation in scramble and shWDR5 QBC-939 cells.

first: Yunfei

last: Xu


title: Sox2-Evf2 lncRNA mechanisms of chromosome topological control in developing forebrain

city: Chicago

first: Jhumku

last: Kohtz

state: Illinois

address: 303 E Chicago

department: Neurology

institute: Northwestern University

summary: Evf2 lncRNA controls Sox2, BRG1 (Smarca4) and Dlx binding in E13.5 mouse brain ganglionic eminences.  Sox2 controls Dlx5/6ultraconserved enhancer  (Dlx5/6UCE) interactions across chromosome 6.  A subset overlap with Evf2 regulated Dlx5/6UCE interaction sites.

overall_design: We used CUT&RUN to analyze Sox2, Smarca4 and Dlx binding profiles in three mouse models  Evf2+/+ [WT], Evf2TS/TS (loss of Evf2) and Evf1TS/TS (loss of Evf1, truncation of Evf2).  We use 4Cseq and Dlx5/6UCE as bait to determine Dlx5/6UCE interactions in the presence of Sox2 (Sox2fl/fl cre negative) and absence of Sox2 in GABAergic progenitors (Sox2fl/fl Dlx5/6cre positive) in mouse E13.5 GEs

first: Abhijit

last: Chakraborty

first: Ivelisse

last: Cajigas

first: Ferhat

last: Ay