title: Growth, blood biochemistry, histology and transcriptomic profile analysis influences liver fat deposition and inflammation process following dietary supplementation of apple peel powder in Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus)

city: Hangzhou

first: li

last: lei

address: xiashas street num 6

summary: GIFT is a type of freshwater farmed fish with high economic value and nutritional value. The liver is an important organ of fish metabolism. Once it is damaged or the disease occurs, it will lead to metabolic disorders and decreased disease resistance, and may cause other secondary diseases. In the high-density intensive culture of tilapia, the feed nutrition is not balanced, especially the addition of high-fat feed. High fat content can accelerate the growth of fish, but long-term feeding of high-fat diet can lead to metabolic disorders of fish, accumulation of fat in the body, easy to cause fatty liver, and ultimately death due to liver necrosis or hemorrhage, seriously affecting the breeding benefits. The main purpose of this study was to investigate the effects of apple peel added to feed on liver fat metabolism and fat deposition in tilapia tilapia; use transcriptomics to analyze related signal regulation pathways, focusing on fat metabolism and inflammatory response; and finally screening differentially expressed genes. The development of this study is helpful to understand the molecular mechanism of apple peel extract powder-mediated liver fat metabolism and inflammatory response in GIFT, and relieve liver stress. It also provides theoretical support for the application of apple peel extract powder as a feed additiion in aquatic products.

overall_design: we selected liver samples of the control group (C), the optimal group of apple peel extracted powders supplementation (0.2%, APE_A) and the high dose group of apple peel extracted powders supplementation (0.8%, APE_H) for transcriptome sequencing.

first: Jun

last: Qiang

first: Omyia

last: Khamis

first: Huo-Jin

last: Jiang

first: Jie

last: He

first: Yi-Fan

last: Tao

first: Pao

last: Xu

first: Jin-Wen

last: Bao


title: Lactate mediated epigenetic reprogramming during cancer associated fibroblast formation

status: Public on Dec 04 2019

city: Bronx

first: Amit

last: Verma

state: NY

address: 1300 Morris Park Ave

department: Medicine

country: USA

institute: Albert Einstein College of Medicine

type: Methylation profiling by high throughput sequencing

summary: We report oxidative bisulfite analysis of whole genome methylation of mesenchymal stem cells (MSCs) and Cancer associated fibroblasts (CAFs)

overall_design: Examination of 5hmC in MSCs and CAFs

first: Kith

last: Pradhan

first: Tushar

last: Bhagat


title: A direct link between Prss53, hair curvature, and skeletal dysplasia

city: Shenzhen

first: CNSA

last: CNGBdb

state: Guangdong

address: Jinsha Road

country: China

institute: CNGB

type: Expression profiling by high throughput sequencing

summary: PRSS53, a member of the membrane-anchored serine proteases, hydrolyzes peptide bonds and is highly expressed in the hair follicle IRS, medulla, precortex and some melanocytes1. Previous studies reported that Prss53 is a psoriasis susceptibility locus and is linked to systemic lupus erythematosus, suggesting its potential roles in skin function2. The Q30R SNP in Prss53 may influence hair shape and is involved in the human variation of head hair shape among different continental groups1. In addition, ENaC activity is regulated by the activity of a channel-activating protease of Prss8 (a homologous gene of Prss53), implying the Prss53 may have an indispensable role in ion channel activity3.The triggering of hair curvature is clearly related to symmetry or asymmetry axis formation in follicles and includes Wnt, TGFβ, BMP, Shh and FGFs, etc. In particular, the Wnt/Ca2+ and Wnt/planar cell polarity (PCP) pathways are additional novel mechanisms that affect hair shape4. Furthermore, disruptions in calcium metabolism may contribute to a wide variety of clinical symptoms, including osteoporosis, osteolysis, nephrocalcinosis and adynamie5.Here, we successfully generated Prss53-deficient rabbits. These rabbits exhibited curved hair, severe skeletal malformation and disrupted calcium metabolism. Altogether, these data suggest that Prss53 play an important role in calcium metabolism and provide the first direct evidence that Prss53 functions in hair curvature shape and skeletal dysplasia.

overall_design: Examination of 3 difference skin in Prss53-/- and wildtype rabbits, respectively

first: Jichao

last: Deng

first: Zhanjun

last: Li


title: Whole transcriptome RNA sequencing of human cells after HCV infection (ML-1 thyroid cell line, primary thyrocytes and Huh7.5 hepatocyte cell line)

city: New York

first: Weijia

last: Zhang

address: 1 Gustave L. Levy Pl

department: Renal

institute: Icahn School of Medicine at Mount Sinai

summary: HCV infection induce thyroid dysfunction by influencing both immune and non immune thyroid-toxic mechanisms.  Similar to hepatocytes, HCV infection of thyrocytes had a significant effect on pathways of lipid and glucose metabolic processes (Figures 6A-C). These findings may suggest that HCV infection has a dual effect, inducing pathways that trigger autoimmunity as well as metabolic pathways.

overall_design: RNA sequencing of HCV infected cells and mock infected cells

first: Sara

middle: S

last: Hammerstad

first: Zhengzi

last: Yi

first: Yaron

last: Tomer


title: Keeping the shoot above water – underwater stem elongation in watercress (Nasturtium officinale)

city: Bayreuth

first: Angelika

last: Mustroph

address: Universitaetsstr. 30, NWI

department: Plant Physiology

country: Germany

institute: University Bayreuth

summary:
Flooding stress is a major environmental threat for many terrestrial plants. The detrimental effects of flooding stress, however, vary between different plant species. Whereas many crops are rather sensitive to flooding, some wild species from flood-prone areas are well adapted to excess water conditions. Morphological adaptations like adventitious roots and aerenchyma formation, or the ability to elongate rapidly the above-ground organs, allow these plants to thrive in water.
The focus of this research is Nasturtium officinale, also known as watercress, which is an auto-tetraploid, dicotyledonous and stem-growing Brassicaceae species. Its natural habitat is near rivers and streams, but absent from stagnant water. Submergence induces underwater elongation of stems and growth suppression of petioles in Nasturtium officinale. By using the RNA sequencing technique, we aimed to uncover the underlying mechanisms for these contrasting responses. Combining submergence experiments with hormone manipulations revealed that ABA degradation is required for stem elongation.

overall_design: One species (Nasturtium officinale) x two tissues (stem, petiole) x two treatments (air, submergence) x two timepoints (1 day, 2 days)

first: Jana

middle: T

last: Mueller

first: Melis

last: Akman

first: Hans

last: van Veen

first: Rashmi

last: Sasidharan


title: Expanding the editable genome and CRISPR-Cas9 versatility using DNA cutting-free gene targeting based on in trans paired nicking

city: Stanford

first: Richard

middle: L

last: Frock

state: California

address: 269 Campus Drive

department: Radiation Oncology

institute: Stanford University

summary: Genome editing typically involves recombination between donor nucleic acids and genomic sequences subjected to double-stranded DNA breaks (DSBs) made by programmable nucleases (e.g. CRISPR-Cas9). Yet, amongst other deleterious by-products, DSBs yield translocations, off-target mutations and, most pervasively, unpredictable on-target allelic disruptions. Remarkably, hitherto, the untoward phenotypic consequences of on-target disruptions at allelic and non-allelic (e.g. pseudogene) sequences have received scant scrutiny and, crucially, remain to be addressed. Here, we demonstrate that gene-edited cells can lose fitness due to on-target DSBs and report that simultaneous single-stranded DNA break formation at donor and target DNA by CRISPR-Cas9 “nickases” overcomes, to a great extent, such genotype-phenotype disrupting events. Moreover, in trans paired nicking gene editing can efficiently and precisely add large DNA segments (i.e. live-cell reporter tags) into essential and multiple-copy genomic sequences while circumventing most of the allelic and non-allelic collateral mutations and chromosomal rearrangements characteristic of nuclease-dependent gene editing procedures.

overall_design: We employed an saCas9:RAG1.1 gRNA bait DNA double strand break to map genome-wide repair outcomes in the presence or absence of the spCas9:AAVS1 gRNA nuclease or the D10A nickase variant using LAM-HTGTS

first: Xiaoyu

last: Chen

first: Francesca

last: Tasca

first: Manuel

middle: A

last: Goncalves


title: Overexpression of GATA2 enhances development and maintenance of human embryonic stem cell-derived hematopoietic stem cell-like progenitors

city: Chengdu

first: Zhou

last: Ya

address: No.26,Huacai Road,Longtan Economic City Headquarter,Second Session of East Third Ring Road

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

summary: GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HSC-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34+CD45+CD90+CD38- HSC-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HSC-like cells in a quiescent state by arresting the cell cycle at G0/G1 phase. RNA-sequencing showed that hPSC-derived-HSC-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to generate hPSC-derived HSCs.

overall_design: Transcriptome analysis of CD38+, CD90+, and GATA2 overexpression CD90+ HSC-like cells derived from hESCs.

first: Ya

last: Zhou

first: Feng

last: Ma


title: DNA methylation profiling in recurrent miscarriage

status: Public on Dec 03 2019

city: Shanghai

first: Li

last: Pi

address: Xietu Road

institute: Shanghai Institute of Planned Parenthood Research

summary: We used the Illumina Infinium HumanMethylation450 array platform to conduct a genome-wide screening of DNA methylation in decidua samples from the products of conception of women with recurrent miscarriage and to identify novel methylation variable positions (MVPs) and differentially methylated regions (DMRs).

overall_design: Bisulphite converted DNA from the 6 samples were hybridised to the Illumina Infinium HumanMethylation450K Beadchip v1.0

first: Jing

last: Du


title: Comparitive transcriptome study of resistant  NILs PB1+Pi1 and PB1+Pi54 and susceptible rice line (PB1) after M oryzae inoculation

city: New Delhi

first: T

middle: R

last: Sharma

state: Delhi

address: Pusa Campus New

country: India

institute: NRCPB

summary:
Purpose: This study gives insight into transcriptomic dynamics and the set of important candidate acting as modules to regulate the changes in resistant NIL upon M.oryzae infection.
Methods: Rice leaves were collected after M. Oryza (Mo-nwi-53) infection from resistant NILs and suceptible line were frozen in liquid nitrogen. RNA was extracted using Spectrum™ Plant Total RNA Kit (Sigma). Standard Illumina protocols was used for preparing RNA sequencing libraries.
Results: Around 30 million pairs of filtered 101 base paired reads were obtained for each biological replicate.
Conclusions: Pathway, gene set enrichment and co-expression analysis of SDEL unique to each resistant NIL respectively  decipher the common broad spectrum resistance mechanism found in resistant NIL and provide important candidate genes.

overall_design: Deciphering Magnaporthae induced signalling network in broad spectrum resistant NIL compared to susceptible control PB1 using RNAseq

first: Priyanka

last: Jain

first: Himanshu

last: Dubey

first: Pankaj

middle: K

last: Singh

first: Amolkumar

middle: U

last: Solanke

first: Ashok


title: Small RNA sequencing in patients with Tetralogy of Fallot and healthy unaffected individuals

city: Berlin

first: Silke

last: Sperling

state: Berlin

address: Lindenberger Weg 80

department: Cardiovascular Genetics

institute: Experimental and Clinical Research Center (ECRC), Charité / MDC for Molecular Medicine

type: Non-coding RNA profiling by high throughput sequencing

summary: Right ventricular small RNA profiles from 22 patients with Tetralogy of Fallot (TOF) and small RNA-seq profiles from the left and right ventricle (LV and RV, respectively) of 4 healthy unaffected individuals (NH) were generated. The total RNA was isolated from the 30 human heart samples using TRIzol. Small RNAs were isolated from total RNA and prepared for microRNA sequencing using Illumina Kit FG-102-1009 according to the manufacturer's protocol (Preparing Samples for Analysis of Small RNA Illumina 2007). The sequencing libraries were generated using a non-strand-specific library construction method. The purified DNA fragments were used directly for cluster generation, and 36 cycles of single-end read sequencing were performed using the Illumina Genome Analyzer. Sequencing reads were extracted from the image files using the open source Firecrest and Bustard applications (Illumina Genome Analyzer pipeline 1.3.2).

overall_design:
Right ventricular small RNA-seq profiles from 22 patients with Tetralogy of Fallot and small RNA-seq profiles from the left and right ventricle of 4 healthy unaffected individuals.

Supplementary processed data files:
GSE36759_mature_miRNA_expression_levels.txt: Mature miRNA expression profiling data for all samples.
GSE36759_mature_miRNA_expression_levels_normalized.txt: Normalized mature miRNA expression profiling data for all samples.
Genome build: hg18


title: Hypoxia effects on the transcriptome of HeLa cells

city: Frankfurt am Main

first: Kathi

last: Zarnack

address: Max-von-Laue-Str. 15

institute: BMLS - Buchmann Institute for Molecular Life Sciences

summary: Hypoxia is associated with several diseases, including cancer. Circular RNAs (circRNAs) are a novel class of non-coding RNAs that have been implicated in multiple cancers and attract increasing attention as potential biomarkers. In this study, the transcriptome-wide response of human HeLa cervical cancer cells to hypoxia was investigated. The circRNA signatures as well as differential gene expression and alternative splicing were analyzed by integrating available tools with custom approaches for quantification and statistical analysis.

overall_design: 5 samples; 2 conditions: normoxia vs. hypoxia (24 h, 0.2% oxygen); 2-3 replicates per condition

first: Michaela

last: Müller-McNicoll

first: Camila

last: Oliveira Freitas Machado

first: Antonella

last: Di Liddo


title: Distinct Expression Profiles of long non-coding RNAs and messenger RNAs in circulating leukocytes of Parkinson’s disease

city: Wuhan

first: yun

last: fan

address: 1095 Jie Fang Avenue

department: Tongji Hospital，Tongji Medical College

institute: Huazhong University of Science and Technology

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

summary: The molecular mechanism underlying Parkinson's disease (PD), an increasingly common neurodegenerative disease, remains unclear. Long non-coding RNA (lncRNA) plays essential roles in gene expression and human disease. We hypothesize that lncRNAs are involved in the pathogenesis of PD. We profiled the expression of lncRNA in circulating leukocytes of 5 PD patients and 5 healthy controls using microarray.

overall_design: LncRNA and mRNA expression profiles of circulating leukocytes from age and sex-matched PD patients and healthy controls were measured by microarray. Each group includes five subjects.

first: Zheng

last: Xue

first: Yun

last: Fan


title: IL-33 signaling alters regulatory T cell diversity in support of tumor development [2014]

city: Cambridge

first: Rebecca

middle: H

last: Herbst

state: MA

address: 415 Main Street

department: Klarman Cell Observatory

institute: Broad Institute of MIT and Harvard

summary: Regulatory T cells (Tregs) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. Tregs in human tumors span diverse transcriptional states distinct from those of peripheral Tregs, but their contribution to tumor development remains unknown. Here, we use single cell RNA-Seq to longitudinally profile dynamic shifts in the distribution of Tregs in a genetically-engineered mouse model of lung adenocarcinoma. In this model, interferon-responsive Tregs are more prevalent early in tumor development, while a specialized effector phenotype characterized by enhanced expression of the interleukin 33 receptor ST2 is predominant in advanced disease. Treg-specific deletion of ST2 alters the evolution of effector Treg diversity, increases infiltration of CD8+ T cells into tumors, and decreases tumor burden. Our study shows that ST2 plays a critical role in Treg-mediated immunosuppression in cancer, highlighting potential paths for therapeutic intervention.

overall_design: Regulatory T cells were isolated from KP, Foxp3RFP mice. Their transcriptional profiles are analyzed with RNA-seq.

first: Amy

last: Li

first: David

last: Canner

first: Jason

middle: M

last: Schenkel

first: Olivia

middle: C

last: Smith

first: Jonathan

middle: Y

last: Kim

first: Michelle

last: Hillman

first: Arjun

last: Bhutkar

first: Michael

last: Cuoco

first: C

middle: G

last: Rappazzo

first: Patricia

last: Rogers

first: Celeste

last: Dang

first: Livnat

last: Jerby-Arnon

first: Orit

last: Rozenblatt-Rosen

first: Le

last: Cong

last: Birnbaum

first: Aviv

last: Regev

first: Tyler

last: Jacks


title: IL-33 signaling alters regulatory T cell diversity in support of tumor development [2018]

first: Rebecca

last: Herbst

overall_design: Regulatory T cells were isolated from KPfrt, Foxp3-Cre or KPfrt, Foxp3Cre, Il1rl1fl/fl mice. Their transcriptional profiles are analyzed with RNA-seq.

last: Li


title: IL-33 signaling alters regulatory T cell diversity in support of tumor development

overall_design:
Tumors were microdissected and dissociated into single cell suspensions. CD45+ and CD45- cells were then magnetically separated using MACS CD45 MicroBeads (Miltenyi Biotec) as per manufacturer’s instructions. CD45+ and CD45- single cells were processed through the 10X Genomics Single Cell 3' platform using the Chromium Single Cell 3′ Library & Gel Bead Kit V2 kit (10X Genomics), per manufacturer’s protocol. Briefly, 6,000 cells were loaded onto each channel. Cell lysis and barcoding occur, followed by amplification, fragmentation, adaptor ligation and index library PCR. Libraries were sequenced on an Illumina HiSeqX at a read length of 98 base pairs. De-multiplexing, alignment to the mm10 transcriptome and unique molecular identifier (UMI)-collapsing were performed using the Cellranger toolkit from 10X Genomics version 1.1.0.
Please note that the counts data is from both samples together, and the cell name entails both the cell barcode and also which sample this cell came from.

first: Amy

last: Canner

last: Schenkel


title: IL-8 released from human pancreatic cancer and tumor associated stromal cells signals through a CXCR2-ERK1/2 axis to induce muscle atrophy

city: Boston

first: Boston University

last: Microarray and Sequencing Resource

address: 72 East Concord Street, E631

department: Microarray and Sequencing Resource

institute: Boston University

summary:
Serum levels of interleukin-8 (IL-8) are increased in the serum of people with pancreatic cancer and associated with the loss of body weight and low muscle mass.  We have identified that systemic (intraperitoneal) injection of IL-8 into mice induces significant skeletal muscle atrophy.  Transcriptional profiling of muscle harvested from these same mice identified the genes and biological processes associated with this IL-8 induced atrophy including gene clusters related to chromatin modification, muscle cell differentiation, and ubiquitin ligase complex.
In this dataset, we include the expression data obtained from the tibialis anterior muscle from vehicle-injected mice, KC-injected mice, and IL-8 injected mice. The purpose of this study was to identify the broader transcriptional networks changed in skeletal muscle in response to a systemic increase in IL-8 or KC.

overall_design: For microarray analysis, a total of 12 RNA samples across three groups are included. The groups are as follows: Vehicle-injected control mice (n = 3);  KC-injected mice (n = 4); IL-8 injected mice (n = 5). To identify broader gene networks changed in skeletal muscle in response to systemic delivery of KC or IL-8, we performed differential expression analysis between vehicle injected controls and KC-injected mice, and between vehicle-injected controls and IL-8-injected mice.

first: Chandler

last: Callaway

first: Andrea

last: Delitto

first: Rohan

last: Patel

first: Rachel

last: Nosacka

first: Andrew

last: D'Lugos

first: Daniel

last: Deyhle

first: Jose

last: Trevino

first: Sarah

last: Judge


title: HSV-1 infection of neural system-derived cells, including SH-SY5Y and U87MG cells at 0, 4 and 10 hour post infection with an MOI of 0.01,to identify the differentially expressed miRNAs and perform pathway enrichment analysis using KEGG.

city: kunming

first: yongzhong

last: duan

state: Yunnan

address: chongrong west road, chenggong new district

institute: kunming medical university

summary: we employed human miRNA Microarray assay to identify differentially expressed (DE) miRNAs in response to HSV-1 infection of SH-SY5Y and U87MG cells. The significantly DE miRNAs existed in U87MG but not SH-SY5Y cells at 4 hours post-infection (hpi), HSV-1 latency-associated transcripts (LAT)-derived miRNAs were not abundantly expressed in both SH-SY5Y and U87MG cells, meanwhile, HSV-1 replication was significantly inhibited in U87MG but not SH-SY5Y. Pathway enrichment analysis results showed that target genes of 10 down-regulated DE miRNAs were significantly enriched in Janus kinase-signal transducers and activator of transcription (JAK-STAT) signaling and Herpes simplex virus infection in U87MG cells at 4 hpi. These results indicated that DE of miRNAs may contribute to the HSV-1 replication inhibition in U87MG cells and also may be linked to HSV-1 latency in neurons.

overall_design: The celluar miRNAs expression profile respond to HSV-1 infection in SH-SY5Y and U87MG cells at 0, 4 and 10 hours post infection with an MOI of 0.01. 1 independent experiment was performed at the each time point (total 6 experiments)


title: Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons

city: Freiburg im Breisgau

first: Galina

last: Erikson

address: Stübeweg 51

institute: Max Planck Institute of Immunobiology and Epigenetics

summary: The goals of this study are to generate and study neurons from MDD patients and examine specific aspects of serotonergic neurotransmission in selective serotonin reuptake inhibitor (SSRI) remitters ® and SSRI-nonremitters (NR)

overall_design: From patients (NR, R) and healthy controls (H),  forebrain neurons were derived from iPSCs for further study (Vadodaria et al, 2019)

first: Krishna

last: Vadodaria

first: Fred

last: Gage


title: Transcriptome-wide Profile of Cerebral Cavernous Malformations Patients Reveal Important Long noncoding RNA molecular signatures

city: Jammu

first: Santhilal

last: Subhash

state: Jammu and Kashmir

address: Jagti, NH-44, PO Nagrota

department: Biosciences and Bioengineering

institute: Indian Institite of Technology Jammu

summary: In this study, by transcriptome-wide approach we demonstrate that lncRNAs are prevalent in CCMs disease and are likely to play critical roles in regulating important signaling pathways involved in the disease progression. We believe, that detailed future investigations on these set of identified lncRNAs can provide useful insights into the biology and, ultimately, in preventing this debilitating disease.

overall_design: Next Generation Sequencing analyses of transcriptome profiles from CCM patients

first: Souvik

last: Kar

first: Chandrasekhar

last: Kanduri


title: Suppression of ribosomal pausing by eIF5A is necessary to maintain the fidelity of start codon selection

city: Dallas

first: Joshua

last: Mendell

state: TX

address: 6000 Harry Hines Blvd., NA6.200A

department: Molecular Biology

institute: UT Southwestern Medical Center

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

overall_design: Refer to individual Series


title: Characterization of Dendritic Cell Subtypes in Human Cord Blood by Single-Cell Sequencing

city: Beijing

first: Xiaoyang

last: Jin

state: -- Please, Select --

address: 15 Datun Road, Chaoyang District

institute: Institute of Biophysics, CAS

summary: Dendritic cells (DCs) are professional antigen-presenting cells (APCs). The key functions of DCs include engulfing, processing and presenting antigens to T cells and regulating the activation of T cells. There are two major DC subtypes in human blood: plasmacytoid DCs (pDCs) and conventional DCs (cDCs). To define the differences between the adult and infant immune systems, especially in terms of DC constitution, we enriched dendritic cells from human cord blood and generated single-cell RNA sequencing data from ~7,000 cells using the 10X Genomics Single Cell 3’ Solution. After incorporating the differential expression analysis method in our clustering process, we identified all known dendritic cell subsets. Interestingly, we also found a group of DCs with gene expression that was a mix of megakaryocytes and pDCs. Further, we verified the expression of selected genes at both the RNA level by PCR and the protein level by flow cytometry. This study further demonstrates the power of single-cell RNA sequencing in dendritic cell research.

overall_design: To acquire enriched DCs from cord blood mononuclear cells (CBMCs), we labeled T cells, B cells, NK cells and monocytes with the lineages-specific markers CD3, CD19, CD16 and CD14, respectively, followed by magnetic bead depletion. Then, we applied single-cell RNA sequencing on all lineage-negative cells.

first: Liguo

last: Zhang


title: Massively Parallel Genetic Disruption of Enhancers Active During Human Corticogenesis

city: New Haven

first: James

last: Noonan

state: CT

address: 333 Cedar St

institute: Yale University

summary: Changes in gene regulation have been linked to the expansion of the human cerebral cortex and to neurodevelopmental disorders. However, the biological effects of genetic variation within developmental regulatory elements on human corticogenesis are not well understood. We used sgRNA-Cas9 genetic screens in human neural stem cells (hNSCs) to disrupt 10,674 expressed genes and 2,227 enhancers active in the developing human cortex and determine the resulting effects on cellular proliferation. Gene disruptions affecting proliferation were enriched for genes associated with risk for human neurodevelopmental phenotypes including primary microcephaly and autism spectrum disorder. Although disruptions in enhancers had overall weaker effects on proliferation than gene disruptions, we identified enhancer disruptions that severely perturbed hNSC self-renewal.  Disruptions in Human Accelerated Regions and Human Gain Enhancers, regulatory elements implicated in the evolution of the human brain, also perturbed hNSC proliferation, establishing a role for these elements in human neurodevelopment. Integrating proliferation phenotypes with chromatin interaction maps revealed regulatory relationships between enhancers and target genes that contribute to neurogenesis and potentially to human cortical evolution.

overall_design: A multiplex genome-wide CRISPR-Cas9 proliferation screen targeting expressed genes and cortical enhancers active in human neural stem cells.

first: Evan

last: Geller

middle: P


title: Characterization of Genomic Heterogeneity and Evolution in Pancreatic Ductal Adenocarcinoma of KPC and KPTC

city: Baltimore

first: Noushin

last: Niknafs

state: MD

address: 3400 N Charles St, Hackerman 220

institute: Johns Hopkins University

summary: Identification of somatic sequence and structural alterations and their intra-tumor heterogeneity in PDAC tumors from GEMMs

overall_design: Genomic profiling is performed on 35 distinct mouse tumor regions. Matched normal kidney tissue from each mouse is used to determine somatic copy number aberrations in each tumor region.


title: Suppression of ribosomal pausing by eIF5A is necessary to maintain the fidelity of start codon selection (RNA-sequencing)

summary: Sequences within 5' untranslated regions (UTRs) dictate the site and efficiency of translation initiation. In this study, an unbiased screen designed to interrogate the 5' UTR-mediated regulation of the growth-promoting gene MYC unexpectedly revealed the ribosomal pause-relief factor eIF5A as a regulator of translation initiation codon selection. Depletion of eIF5A enhanced upstream translation within 5' UTRs across yeast and human transcriptomes, including on the MYC transcript where this resulted in increased production of an N-terminally extended protein. Furthermore, ribosome profiling experiments established that the function of eIF5A as a suppressor of ribosomal pausing at sites of suboptimal peptide bond formation is conserved in human cells. We present evidence that proximal ribosomal pausing on a transcript triggers enhanced usage of upstream suboptimal or non-canonical initiation codons. Thus, we propose that eIF5A functions not only to maintain efficient translation elongation in eukaryotic cells, but also to maintain the fidelity of translation initiation.

overall_design: Ribosome profiling (and complementary RNA-sequencing) was performed in HCT116 cells that received, via lentivirus, Cas9 and sgRNAs targeting either EIF5A, DOHH or non-targeting control sgRNAs. Two sgRNAs were used for each condition, and thus 6 biological samples were used for these experiments.

first: Hema

last: Manjunath

first: He


title: Suppression of ribosomal pausing by eIF5A is necessary to maintain the fidelity of start codon selection (Ribosome profiling)


title: DNA methylation analysis validates organoids as a viable model for studying human intestinal aging (expression)

city: Los Angeles

first: Daniel

last: Nachun

state: CA

address: 695 Charles E Young Dr S

institute: UCLA

summary: The epithelia of the intestine and colon turn over rapidly and are maintained by adult stem cells at the base of crypts. While the small intestine and colon have distinct, well-characterized physiological functions, it remains unclear if there are fundamental regional differences in stem cell behavior or region-dependent degenerative changes during aging. Mesenchyme-free organoids provide useful tools for investigating intestinal stem cell biology in vitro and have started to be utilized for investigating age-related changes in stem cell function. However, it is unknown whether organoids maintain hallmarks of age in the absence of an aging niche. Here we test whether stem cell enriched organoids preserve the DNA methylation-based aging profiles associated with the tissues and crypts from which they were derived. To address this, we use standard human methylation arrays and the human 'epigenetic clock' as a biomarker of age to analyze in vitro derived three-dimensional stem cell-enriched intestinal organoids.  We find that human stem cell-enriched spheroids maintain segmental differences in methylation patterns and that age, as measured by the epigenetic clock, is largely maintained in spheroids. Surprisingly, we find that small intestine spheroids exhibit striking epigenetic age reduction relative to colon spheroids.

overall_design: Total RNA obtained from colon and duodenum crypts.

first: Sophie

last: Lewis

first: Leanne

last: Jones


title: The role of archaeal histones in gene expression - a synthetic biology perspective [Escherichia coli RNA-seq]

city: London

first: Tobias

last: Warnecke

address: Du Cane Road

country: United Kingdom

institute: Imperial College

summary: Since their discovery, archaea have not only proven a fascinating domain in their own right, but also helped us understand the evolution and function of molecular components they share with bacteria or eukaryotes. Archaeal histones are homologous to their eukaryotic counterparts, but operate in a less constrained bacterial-like cellular environment and their role in transcription and genome function remains obscure. In order to understand how archaeal histones affect transcriptional processes, we induced expression of the two histones from the archaeon Methanothermus fervidus in a naive bacterial system (E. coli) that has not evolved to integrate this kind of proteins. We show, using a series of MNase digestion experiments, that these histones bind the bacterial genome and wrap DNA in vivo in a pattern consistent with a previously proposed multimerisation model, in a similar pattern observed natively. We correlate genome-wide occupancy maps and gene expression profiles in different phases of growth to show that – although expression of archaeal histones triggers morphological changes in E. coli – there appears to only be an indirect effect on transcription.  Since their discovery, archaea have not only proven a fascinating domain in their own right, but also helped us understand the evolution and function of molecular components they share with bacteria or eukaryotes. Archaeal histones are homologous to their eukaryotic counterparts, but operate in a less constrained bacterial-like cellular environment and their role in transcription and genome function remains obscure. In order to understand how archaeal histones affect transcriptional processes, we induced expression of the two histones from the archaeon Methanothermus fervidus in a naive bacterial system (E. coli) that has not evolved to integrate this kind of proteins. We show, using a series of MNase digestion experiments, that these histones bind the bacterial genome and wrap DNA in vivo in a pattern consistent with a previously proposed multimerisation model, in a similar pattern observed natively. We correlate genome-wide occupancy maps and gene expression profiles in different phases of growth to show that – although expression of archaeal histones triggers morphological changes in E. coli – there appears to only be an indirect effect on transcription.

overall_design: Correlation between genome-wide occupancy of the archaeal histones HMfA and HMfB in E.coli and transcriptional changed triggered by their expression, coupled with comparison between the histones' binding patterns in Methanothermus fervidus and E. coli.

first: Maria

last: Rojec


title: Expression data from Drosophila heads at difeerent temperatues, after AGO1 immnuprecipitation or input [microarray]

city: Waltham

first: Sebastian

last: Kadener

address: 415 South Street

institute: Brandeis University

summary: We used microarrays to detail the global programme of gene expression changing with temperature

overall_design: Flies were grown at either 18, 25 or 19 degrees. Heads were collected and AGO1-IP was eprformed as in Kadener et al. 2009


title: Total RNA from different species fly heads

summary: Total RNA seq from different species fly heads at different temperatures

sample_organism:
Drosophila simulans
Drosophila virilis
Drosophila yakuba

overall_design: Flies were grown at 3 temperatures, heads from them were collected at 2 circadian tiempoints.


title: Kinetics of cytokine receptor trafficking determine signaling and functional selectivity

city: WEST LAFAYETTE

first: Majid

last: Kazemian

state: IN

address: 201 S. University Street

department: Biochemistry and Computer Science

institute: Purdue University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Cytokines activate signaling via assembly of cell surface receptors, but it is unclear whether modulation of cytokine-receptor binding parameters can modify biological outcomes. We have engineered IL-6 variants with different affinities to gp130 to investigate how cytokine receptor binding dwell-times influence functional selectivity. Engineered IL-6 variants showed a range of signaling amplitudes and induced biased signaling, with changes in receptor binding dwell-times affecting more profoundly STAT1 than STAT3 phosphorylation. We show that this differential signaling arises from defective translocation of ligand-gp130 complexes to the endosomal compartment and competitive STAT1/STAT3 binding to phospho-tyrosines in gp130, and results in unique patterns of STAT3 binding to chromatin. This leads to a graded gene expression response and differences in ex vivo differentiation of Th17, Th1 and Treg cells. These results provide a molecular understanding of signaling biased by cytokine receptors, and demonstrate that manipulation of signaling thresholds is a useful strategy to decouple cytokine functional pleiotropy.

overall_design: Examination of IL6 variants in human Th1 cells. The mutated regions in A1, C7 and Mut3 are included in the file "IL6_mutated_regions.txt", available at the foot of this record.

first: Jonathan

last: Martinez-Fabregas

first: Stephan

last: Wilmes

first: Luopin

last: Wang

first: Maximillian

last: Hafer

first: Elizabeth

last: Pohler

first: Juliane

last: Lokau

first: Christoph

last: Garbers

first: Adeline

last: Cozzani

first: Jacob

last: Piehler

first: Suman

last: Mitra

first: Ignacio

last: Moraga


title: RNA seq from fly heads at different temperatures and circadian timepoints [independent replicate 2]

summary: The goal of this set of experiments is to determine the differences in circadian rhythms in fly at different temperatures.

overall_design: RNA seq from fly heads at 3 temperatures (18, 25, 29C) and circadian timepoints (zt3, zt7, zt11, zt15, zt18,  zt23)


title: IL-33 signaling alters regulatory T cell diversity in support of tumor development

first: Rebecca

last: Herbst


title: RNA seq from fly heads at different temperatures and circadian timepoints [independent replicate 1]

summary: The goal of this set of experiments is to determine the differences in circadian rhythms in fly at different temperatures

overall_design: Flies were grown at 3 temperatures, heads from them were collected at 3  circadian timepoints for 18 and 29c and at 2 circadian timepoints for 25C


title: The role of archaeal histones in gene expression - a synthetic biology perspective [Escherichia coli]


title: Differential Metabolic and Multi-tissue Transcriptomic Responses to Fructose Consumption among Genetically Diverse Mice [Liver]

first: Xia

last: Yang

address: 2000A, 610 Charles E Young Dr S

summary: The escalating prevalence of metabolic syndrome (MetS) poses significant risks to type 2 diabetes mellitus, cardiovascular diseases, and non-alcoholic fatty liver disease. High fructose intake has emerged as an environmental risk for MetS and the associated metabolic diseases. To examine inter-individual variability in MetS susceptibility in response to fructose consumption, here we fed three inbred mouse strains, namely C57BL/6J (B6), DBA (DBA) and FVB/NJ (FVB) with 8% fructose in drinking water for 12 weeks. We found that fructose-fed DBA mice had significantly higher amount of body weight, adiposity, and glucose intolerance starting from the 4th week of fructose feeding compared to the control group, while B6 and FVB showed no differences in these phenotypes over the course of fructose feeding. In addition, elevated insulin levels were found in fructose-fed DBA and FVB mice, and cholesterol levels were uniquely elevated in B6 mice. To explore the molecular underpinnings of the observed distinct phenotypic responses among strains, we applied RNA sequencing to investigate the effect of fructose on the transcriptional profiles of liver and hypothalamus tissues, revealing strain- and tissue-specific patterns of transcriptional and pathway perturbations. Strain-specific liver pathways altered by fructose include fatty acid and cholesterol metabolic pathways for B6 and PPAR signaling for DBA. In hypothalamus tissue, only B6 showed significantly enriched pathways such as protein folding, pancreatic secretion, and fatty acid beta-oxidation. Using network modeling, we predicted potential strain-specific key regulators of fructose response such as Fgf21 (DBA) and Lss (B6) in liver, and Fmod (B6) in hypothalamus. We validated strain-biased responses of Fgf21 and Lss to fructose in primary hepatocytes. Our findings support that fructose perturbs different tissue networks and pathways in genetically diverse mice and associates with distinct features of metabolic dysfunctions. These results highlight individualized molecular and metabolic responses to fructose consumption and may help guide the development of personalized strategies against fructose-induced MetS.

overall_design: Male DBA, B6 and FVB mice (Jackson Laboratory) of 7 weeks old weighing 20-25 g were randomly assigned to 8% fructose treatment (n=8-12, 8% w/v fructose in the drinking water) and control group (n=8-10, drinking water) for 14 weeks. We chose 8% fructose to mimic the average fructose consumption found in sugar-sweetened beverages (~10% w/v) consumed in humans. Mice had free access to water and diets and were maintained under standard housing condition (room temperature 22-24 ??C) with 12 h light/dark cycle. Daily food and drink intake were monitored on per-cage basis. The mice were examined for changes in metabolic phenotypes including body weight, body fat, lean mass, intraperitoneal glucose tolerance test (IPGTT), and serum levels of insulin, glucose, total cholesterol (TC), high density lipoprotein cholesterol (HDL), un-esterified cholesterol, free fatty acids (FFA), and triglycerides (TG), as detailed in the following sections. Mice were sacrificed at the end of the 14-week fructose treatment experiment, and hypothalamus and liver tissues were dissected out, flash frozen and stored at ?70??C until use.


title: Rescue of T cell exhaustion by ingenol mebutate

city: San Diego

first: Jaroslav

last: Zak

address: 10550 North Torrey Rd

department: Immunology and Microbial Sciences

institute: The Scripps Research Institute

summary: Inhibitory receptors (IR) and inhibitory ligands function as critical regulators of immune responses by tempering T cell activity to microbial infections and cancers. In humans, several types of persisting viruses such as HIV, HBV and HCV, as well as cancers exploit IR signaling by upregulating IR ligands, resulting in suppression of T cell function (i.e., exhaustion). This allows escape from immune surveillance and continuation of disease. By screening a collection of bioactive small molecules, we identified and validated compounds that restore cytokine production and enhance proliferation of exhausted T cells. Analysis of our top hit ingenol mebutate, a protein kinase C inducing diterpene ester, revealed a role for this molecule in overriding the suppressive signaling cascade mediated by IR signaling on T cells.

overall_design: exhausted virus-specific CD8+ T cells cultured with ingenol mebutate or vehicle

first: Brett

last: Marro

first: Michael

middle: B

last: Oldstone


title: Differential Metabolic and Multi-tissue Transcriptomic Responses to Fructose Consumption among Genetically Diverse Mice


title: Transcriptional shifts during juvenile Coho salmon (Oncorhynchus kisutch) life stage changes in freshwater and early marine environments [liver]

city: Nanaimo

first: Shaorong

last: Li

state: British Columbia

address: 3190 Hammond Bay Road

department: Salmon and Freshwater Ecosystems Division

country: Canada

institute: Fisheries and Oceans Canada

summary: There is a paucity of information on the physiological changes that occur over the course of salmon early marine migration. Here we aim to provide insight on juvenile Coho salmon (Oncorhynchus kisutch) physiology using the changes in gene expression (cGRASP 44K microarray) of four tissues (brain, gill, muscle, and liver) across the parr to smolt transition in freshwater and through the first eight months of ocean residence. We also examined transcriptome changes with body size as a covariate. The strongest shift in the transcriptome for brain, gill, and muscle occurred between summer and fall in the ocean, representing physiological changes that we speculate may be associated with migration preparation to feeding areas. Metabolic processes in the liver were positively associated with body length, generally consistent with enhanced feeding opportunities. However, a notable exception to this metabolic pattern was for spring post-smolts sampled soon after entry into the ocean, which showed a pattern of gene expression more likely associated with depressed feeding or recent fasting. Overall, this study has revealed life stages that may be the most critical developmentally (fall post-smolt) and for survival (spring post-smolt) in the early marine environment. These life stages may warrant further investigation.

overall_design: A total of 735 microarrays were run over 284 Coho salmon.  1 experimental sample and 1 pooled reference sample per microarray.   These samples were comprised of four salmon tissues (brain, gill, liver and muscle) and represented six life stages, two of which occurred in freshwater (parr, smolt) and four postsmolt which occurred in saltwater (spring, summer, fall, winter).   All four tissues were run for 48 samples (17%) and brain, liver and muscle were examined for 148 (52%) of the samples.  The lack of gill tissue for some samples was due to the fact that the gill slides were split between Coho salmon (Oncorhynchus kisutch) and Sockeye salmon (Oncorhynchus nerka).

first: Aimee

last: Houde

first: Angela

middle: D

last: Schulze

first: Karia

last: Kaukinen

first: Jeffrey

last: Strohm

first: David

last: Patterson

first: Terry

last: Beacham

first: Anthony

last: Farrell

first: Scott

last: Hinch

first: Kristina

last: Miller


title: Transcriptional shifts during juvenile Coho salmon (Oncorhynchus kisutch) life stage changes in freshwater and early marine environments [gill]


title: Transcriptional shifts during juvenile Coho salmon (Oncorhynchus kisutch) life stage changes in freshwater and early marine environments [muscle]


title: Differential Metabolic and Multi-tissue Transcriptomic Responses to Fructose Consumption among Genetically Diverse Mice [Adipose]


title: Cellular and viral transcription profiles in Equine Papillomavirus Type 2 positive squamous cell carcinomas

city: Zurich

first: Kurt

last: Tobler

address: Winterthurerstrasse 266a

department: Veterinary Virology

country: Switzerland

institute: University of Zurich

summary: Equine Papillomavirus Type 2 (EcPV2) appears to be a causal factor for the development of genital especially penile squamous cell carcinomas (SCC) and as such have an important clinical impact on horses. However, the pathomechanisms associated with this cancer transformation are not known, yet. To analyze the host’s and viral transcriptome in EcPV2 affected horses, tissue samples were collected from horses with EcPV2-positive genital lesions as well as from healthy EcPV2-negative horses. Expression levels of host and viral genes were evaluated by RNA-Seq.

first: Sophie

last: Ramsauer

first: Claude

last: Favrot

first: Mathias

last: Ackermann

first: Cornel

last: Fraefel


title: Transcriptional shifts during juvenile Coho salmon (Oncorhynchus kisutch) life stage changes in freshwater and early marine environments [brain]


title: Transcriptional shifts during juvenile Coho salmon (Oncorhynchus kisutch) life stage changes in freshwater and early marine environments


title: Suppression of ribosomal pausing by eIF5A is necessary to maintain the fidelity of start codon selection (CRISPR screen)

first: Joshua

last: Mendell

overall_design: A genome-scale CRISPR/Cas9-mediated loss of function screen was performed in HCT116 cells expressing either a MYC 5' UTR EGFP reporter or a control EGFP reporter.

first: Hema

last: Manjunath

first: He

last: Zhang


title: Gene expression profile of bone marrow and circulating miRNA profile from MMTV-NeuT mouse model of spontaneous mammary carcinogenesis.

city: Milan

first: Matteo

last: Milani

state: Milan

address: Via Amadeo, 42

country: Italy

institute: IRCCS Istituto Nazionale dei Tumori


title: Gene expression profile of bone marrow from MMTV-NeuT mouse model of spontaneous mammary carcinogenesis.

summary: We investigated, in a spontaneous mouse model of breast carcinogenesis (MMTV/NeuT), the modifications in the hematopoietic and stromal bone marrow (BM) compartments and their correlation with the pathological stage of the primary mammary lesions, following the idea that signs of the cross-talk between the BM and elements located in the tumor microenvironment, either neoplastic or stroma/immune cells, can be identified in the very early phases of cancer development, and lead to the instruction of a tumor-promoting hematopoiesis.

overall_design: Total RNA was extracted from BM cells of MMTV-NeuT transgenic females, and age-matched non transgenic siblings, at 6, 12 and 24 weeks of age, using Trizol reagent (Life Technologies) following the manufacturer’s instruction. RNA integrity was verified using the RNA 6000 Nano Kit (Agilent Technologies, Palo Alto, USA). All samples had an RNA integrity number (RIN) > 7, indicating good quality.  For gene expression profile (GEP), RNA was reverse transcribed, labeled with biotin and amplified overnight using the Illumina TotalPrep RNA Amplification Kit (Life Technologies). Biotinylated complementary RNA was hybridized to mouseWG-6 v2.0 Expression BeadChips (Illumina, San Diego, USA). Illumina mouseWG-6 v2.0 Expression BeadChips microarrays were scanned with Illumina BeadArray Reader, and raw data obtained using Illumina BeadStudio v3.3.8 were processed using the lumi package from R/Bioconductor. Raw data were log2-transformed, normalized using robust spline normalization and filtered; only the probes with a detection p-value <0.01 in at least one sample were further analysed.

first: Mario

last: Colombo

first: Claudia

last: Chiodoni

first: Loris

last: De Cecco

last: Dugo


title: RNA seq from fly heads at different temperatures and circadian timepoints [independent replicate 3]

first: Sebastian

last: Kadener

overall_design: RNA seq from fly heads at 3 temperatures (18, 25, 29C) and circadian timepoints (zt3, zt7, zt11, zt15, zt18,  zt23); independent replicate of the same experiment


title: Circulating miRNA profile of MMTV-NeuT mouse model of spontaneous mammary carcinogenesis.

summary: We investigated, in a spontaneous mouse model of breast carcinogenesis (MMTV/NeuT), the modifications in the level of circulating miRNAs during different stages of disease, from early dysplastic stage to overt carcinoma, and their correlation with the pathological stage of the primary mammary lesions.

overall_design: MMTV-NeuT transgenic females, and age-matched non transgenic siblings, were sacrified at 6,12 and 24 weeks of age. 500 ul of blood was collected by intracardiac puncture with 20 ul of EDTA 0.5 M pH 8.0 and processed for the plasma separation within 2 hours.


title: Activation of HOTTIP lncRNA perturbs HSC function leading to AML like disease

city: Hangzhou

first: Huacheng

last: Luo

state: Zhejiang

address: No. 150, Fucheng Road, Qiantang District

institute: Hangzhou Institute of Medicine (HIM), The Chinese Academy of Sciences

summary: We found that posterior HOXA-associated HOTTIP lncRNA is aberrantly activated in MLL-rearranged AMLs and required for the posterior HOXA chromatin structure and gene expression. Knock-out of HOTTIP attenuates leukemic progressions of the transplanted humanized AML mice by blocking posterior HOXA-associated AML gene expression programs while the dCas-VP160 mediated reactivation of HOTTIP restores HOXA locus chromatin structure and HOXA9-A13 gene expression in the CBS7/9 boundary depleted AML cells. Finally, transgenic expression of HOTTIP lncRNA in mouse bone marrow hematopoietic cells resulted in perturbation of the balance of HSC self-renewal and differentiation and development of AML like disease by aberrant altering HOXA associated chromatin structure and transcription program. Thus, HOTTIP lncRNA acts as oncogene to reprogram leukemic associated chromatin and gene transcription.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: We have finished the RNA-SEQ, ATAC-seq, ChIP-seq, CHIRP-seq, HiC-seq and whole exome-seq to investigate the role of lncRNA HOTTIP and CTCF boundaries in hematopoiesis and leukemogenesis. LSK cells (Lin- Sca1+ Kit+) were sorted by FACS from the bone marrow of  WT and Hottip transgenic mice for RNA-seq, ATAC-seq assay. MOLM13 leukemia cells were used to perform the CHIRP-seq, RNA-seq, CHIP-seq and HiC-seq analysis.

first: Suming

last: Huang


title: TRAIL expressing monocyte/macrophages reduce inflammation and attenuate atherosclerosis

city: Sydney

first: Ruby

middle: CY

last: Lin

state: NSW

address: 176 Hawkesbury Road, Westmead

country: Australia

institute: The Westmead Institute for Medical Research

summary: Circulating TRAIL is reduced in cardiovascular disease patients and TRAIL deletion in mice exacerbates disease. The source of TRAIL and protective mechanism(s) are unclear. Monocyte TRAIL mRNA was reduced from coronary artery disease patients, strikingly associating with reduced plasma TRAIL. A strong inverse correlation between plasma TRAIL and IL-18 was observed, with IL-18 repressing monocyte TRAIL mRNA. In mice, two sources were investigated using bone-marrow (BM) transplants; TRAIL expressed only in BM (BM-TRAIL) or everywhere except BM (parenchymal-TRAIL), vs. whole-body TRAIL ablation (null-TRAIL). BM-TRAIL attenuated macrophage content and atherosclerosis. BM-derived macrophages with TRAIL deletion were more inflammatory, with impaired migration and reduced expression of cholesterol efflux, efferocytosis and nitric oxide-controlling genes. TRAIL expression also reduced islet macrophage content, but only parenchymal-TRAIL islets had improved function. Recombinant TRAIL administration stimulated insulin expression and islet mass. We propose TRAIL maintains monocyte/macrophage homeostasis and limits the progression of atherosclerosis and islet dysfunction.

overall_design: Gene expression of aortic tissue from wildtype C57Bl6/J mice (n=3) were compared to Trail-/- knockout mice (n=3) to identify overall effect of TRAIL knockout. Trail knockout mice were sourced from Amgen.

first: Sian

last: Cartland

first: Mary

last: Kavurma


title: The Global Landscape of Multiscale Transcriptomic Networks and Key Regulators in Parkinson’s Disease

city: New York

first: Bin

state: NY

address: 1470 Madison Ave

institute: Icahn School of Medicine At Mount Sinai

summary: Despite the advance of genetic and genomic analysis of Parkinson’s disease (PD), our understanding of PD pathophysiology remains limited due to unclear etiology of idiopathic PD and unavailable integrated approach for large-scale multi-dimensional data. Herein we report a novel multiscale network approach to establish transcriptomic network from postmortem PD brain data. The analysis delineates structures of gene-gene regulatory networks in PD and identifies novel network regulators that are functionally connected to previously identified PD risk genes. We identify STMN2, encoding a neuron-specific stathmin family protein and down-regulated in PD brains, as the top regulator of the transcriptomic network underlying PD. Knock-down of Stmn2 in mice validates its regulatory role, and Stmn2 deficient mice show dopaminergic neuron vulnerability, phosphorylated a-synuclein elevation, and locomotor function deficits. As predicted from the network analysis, reduced STMN2 expression impairs synaptic vesicle trafficking in midbrain neurons. Our approach sheds light on the complexity of PD pathogenic network and thus facilitates identification of novel PD therapeutic targets.

overall_design: AAV that carries Stmn2 shRNA or scrambled control shRNA was injected into the midbrain in 2 month old male C57BL/6J mice unilaterally. After 30 days, mice were sacrificed and the infected midbrain tissue were isolated and total RNA was extracted using Qiagen RNeasy mini kit. 3 controls and 4 knockdown samples were sequenced and analyzed

first: Qian

last: Wang

first: Zhenyu

last: Yue


title: Differential Metabolic and Multi-tissue Transcriptomic Responses to Fructose Consumption among Genetically Diverse Mice [Hypothalamus]

first: Xia

last: Yang


city: Delhi

first: Arnab

last: Mukhopadhyay

address: Aruna asaf ali marg

institute: National Institute of Immunology

overall_design: RNA-seq profile of two daf-2 (e1370);daf-12(m20) samples.

first: Neeraj

last: Kumar


title: The impact of p53 on aristolochic acid I-induced gene expression in vivo

status: Public on Dec 02 2019

first: Mateja

last: Sborchia

state: Greater London

address: 150 Stamford Street

department: Analytical, Environmental and Forensic Sciences

institute: King's College London

summary: Exposure to aristolochic acid (AA) is linked to kidney disease and urothelial cancer in humans. The major carcinogenic component of the AA plant extract is aristolochic acid I (AAI). The transcription factor p53 acts as a tumour suppressor and is frequently mutated in AA-induced tumours. Using a mouse model, we previously showed that Trp53 genotype impacts on AAI-induced nephrotoxicity in vivo (i.e. p53 protects from AAI-induced renal proximal tubular injury), but the underlying mechanism(s) involved remain to be further explored. In the present study, we investigated the impact of p53 on AAI-induced gene expression in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with 3.5 mg/kg body weight (bw) AAI daily for 6 days. The Clariom™ S Assay microarray was used to elucidate gene expression profiles in mouse kidneys after AAI treatment in order to identify potential mechanisms by which AAI drives renal injury in Trp53(-/-) kidneys. Principle component analysis and hierarchical clustering in Qlucore Omics Explorer showed that gene expression in AAI-exposed Trp53(+/+), Trp53(+/-) and Trp53(-/-) kidneys is treatment-dependent. However, gene expression profiles did not segregate in a clear-cut manner according to Trp53 genotype, hence further investigations were performed by pathway analysis with MetaCore™. Several pathways, such as those related to epithelial-to-mesenchymal transition, transcription of hypoxia-inducible factor 1 targets, renal injury and secretion of xenobiotics were significantly altered to varying degrees for AAI-exposed kidneys. The top ten up-regulated genes included cyclin-dependent kinase inhibitor 1a (Cdkn1a), a mediator of cell cycle arrest; and neutrophil gelatinase-associated lipocalin (Ngal), which has been shown to play a role in nephritis by promoting inflammation and apoptosis. Members of the solute carrier (Slc) family (i.e. Slc22a2, Slc22a6, Slc22a7, Slc22a8) were amongst the top ten down-regulated genes. Pathway analysis also identified genes that are uniquely affected by AAI treatment in Trp53(+/+), Trp53(+/-) and Trp53(-/-) kidneys. Apoptotic pathways were modulated in Trp53(+/+) kidneys; whereas oncogenic and pro-survival pathways were significantly altered for Trp53(+/-) and Trp53(-/-) kidneys, respectively. Microarray gene expression analysis identified significant toxicogenomic responses to AAI that give novel insights into its mechanism of nephrotoxicity. Alterations of biological processes by AAI in Trp53(+/+), Trp53(+/-) and Trp53(-/-) kidneys could explain the mechanisms by which p53 protects from or p53 loss drives AAI-induced renal injury in vivo.

overall_design:
Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice were treated daily with 3.5 mg/kg body weight aristolochic acid I for 6 days (n = 5/group). Controls were treated with water only (n = 5/group). Total RNA was extracted from kidney tissues and the mouse Clariom™ S Assay was performed according to the manufacturer's instructions. Microarray data was analysed with TAC, QLUCORE and MetaCore softwares.

Microarray performed by Genomics Centre at King's College London.

first: Hector

last: Keun

first: David

last: Phillips

first: Volker

last: Arlt


title: ESRRG gene expression profile in gastric cancer cells

city: Seoul

first: YUNYONG

last: PARK

address: 84 Heukseok-ro

country: South Korea

institute: ChuangAng University

summary: ESRRG is one of nuclear receptor super family. ESRRG contributes to many physiological pathway. Especially, ESRRG is clearly involved in various cancers. To identify the downstream target of ESRRG in gastric cancer, we carried out microarray.

overall_design:
ESRRG was over expressed in AGS and MKN45 cell. Each group is trplicate sample (Control=3, ESRRG over-expression=3)

GSE78050 was erroneously cited in PubMed ID 29228735.

first: Myoung-Hee

last: Kang

first: Yun-Yong

last: Park


title: The identification of genes altered by RORα in progression of non-alcoholic steatohepatitis (NASH)

first: Hyeon-Ji

last: Kim

address: 1 Gwanak-ro, Gwanak-gu

institute: Seoul National University

summary:
Purpose: To identify the target genes of RORα associated with development of NASH
Methods: RNA isolation for sequencing analysis from liver tissues of High fat diet (HFD)-fed RORα-LKO and RORα f/f mice and mRNA-sequencing
Conclusion: When calcuated by dividing the normalized read count of HFD-fed RORα-LKO by that of RORαf/f,.there are 8505 genes altered by RORα deletion (cut-off, 0.8-fold, 1.5-fold).

overall_design: mRNA profiles of HFD-fed control (RORα f/f) and RORα liver-specific KO (LKO) mice

first: Mi-ock

last: Lee


title: Transcriptional profiling of astrocytes in the prefrontal cortex, hippocampus, accumbens nucleus and caudate putamen of a Aldh1l1-TRAP (JD130) mouse line after chronic social defeat stress

first: Laura

last: Kus

address: 1230 York Avenue # 260

department: Heintz Laboratory

institute: The Rockefeller University

summary: Psychiatric disorders, especially major depressive disorder, are prominent cause of disability worldwide, and in dire need of better diagnostic and therapeutic tools. In order to identify the cellular mechanisms underlying major depressive disorder we sought to understand the role of astrocytes, the most numerous subtype of glia, in this disease utilizing the TRAP gene expression analysis and chronic social defeat mouse model of depression. TRAP translational profiling is a method that allows investigators to genetically characterize specific cell types in complex tissues such as mouse brain. Using this technique we obtained RNA-Seq data from actively translating transcripts present in astrocytes. We generated the molecular profile of astrocytes from multiple brain regions affected by stress-induced depression, the prefrontal cortex, hippocampus, accumbens nucleus and caudate putamen of adult Aldh1l1-EGFP/Rpl10a (JD130) mice after chronic social defeat stress paradigm. The results of this study will further our understanding of depression pathophysiology and will provide possible targets for novel or supplementary therapies.

overall_design: Adult Aldh1l1-EGFP/Rpl10a (JD130) mice were subjected to 10 days of social defeat and screened for social interaction (SI). They were divided in three groups based on their SI index: control-CTRL (no stress exposure, but present in the same environment-room, SI>1), resilient-RS (exposed to stress but showing no depressive-like symptoms, SI >1) and stress susceptible-SS (showing low social interaction index as a measure of depressive-like symptoms, SI<1). Two days after the last day of social defeat TRAP-Seq of astrocytes isolated from the prefrontal cortex (PFC), hippocampus (HIP), accumbens nucleus (NAC) and caudate putamen (CPU) was performed. Each biological replicate sample contained pooled regions isolated from 2 (for PFC, HIP and CPU) or 4-6 (for NAC) mice. The bioinformatics analysis was done comparing gene expression datasets from CTRL, RS, and SS mice. Genes showing significant change in expression in SS compared to RS and CTRL were further analyzed.

first: Ana

last: Milosevic

first: Scott

middle: J

last: Russo


title: Molecular determinants of response to high dose androgen therapy in prostate cancer

city: Seattle

first: Ilsa

last: Coleman

state: WA

address: 1100 Fairview Ave N, E2-112

department: Human Biology

institute: Fred Hutchinson Cancer Center

summary: Clinical trials of high-dose androgen therapy for prostate cancer have shown promising efficacy but are limited by lack of criteria to identify likely responders. To elucidate factors that govern the growth-repressive effects of high-dose androgens we applied an unbiased integrative approach utilizing genetic screens and transcriptional profiling of prostate cancer cells with or without demonstrated phenotypic sensitivity to androgen-mediated growth repression. Through this comprehensive analysis, we identified genetic events and related signaling networks that determine the response to both high-dose androgen and androgen withdrawal. We applied these findings to develop a gene signature that may serve as an early indicator of treatment response and identify men with tumors amenable to high dose androgen therapy.

overall_design: RNA sequencing of human prostate tumor cell lines using Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500.

first: Michael

last: Nyquist

first: Alexandra

last: Corella

first: Osama

last: Mohamad

first: Arja

last: Kaipainen

first: Daniel

last: Kuppers

first: Jared

last: Lucas

first: Patrick

last: Paddison

first: Stephen

last: Plymate

first: Peter

middle: S

last: Nelson

first: Elahe

last: Mostaghel


title: Wnt inhibition facilitates RNA-mediated reprogramming of human somatic cells to naïve pluripotency

city: Cambridge

first: Giuliano

middle: Giuseppe

last: Stirparo

state: Cambridgeshire

address: 418 Cambridge Science Park Milton Rd

institute: Cerevance ltd

summary: We report conditions for transgene-free reprogramming of human somatic cells to naïve pluripotency. We find that Wnt inhibition promotes RNA-mediated induction of naïve pluripotency.

overall_design: The deposited data are RNAseq data for whole genome transcriptome analysis comparing naïve, primed iPSCs and embryo derived HNES1 cells.

first: Ge

last: Guo


title: Transcriptome of ESCs upon VD3 treatment (+/-) MLL1 inhibition

city: Ann Arbor

first: Fengbiao

last: Mao

state: Michigan

address: 1301 Catherine St

department: Department of Pathology

institute: University of Michigan

summary: This study describes the transcriptome profiling of: 1) Mll1fl/fl mESCs in LIF/Serum medium as control; 2) VD3 and MM-401 (Mll1i) treated mESCs  in LIF/serum medium ; 2) VD3 treated mESCs  in LIF/serum medium.

overall_design: RNA-Seq profiling on mouse pluripotent cells. Biological duplicates of each sample are labled as rep1/2.

first: Yali

last: Dou


title: Genome-wide DNA methylation in post-mortem hippocampus of patients with bipolar disorder and controls

city: Houston

first: Gabriel

middle: Rodrigo

last: Fries

address: 1941 East Rd, Suite 5102A

department: Psychiatry

institute: University of Texas Health Science Center

summary: Evidence suggests accelerated aging mechanisms in bipolar disorder (BD), including DNA methylation (DNAm) aging in blood. However, it is unknown whether such mechanisms are also evident in the brain. To investigate this, we interrogated genome-wide DNA methylation in postmortem hippocampus from 32 BD-I patients and 32 age-, sex-, and race-matched non-psychiatric controls from the NIMH Human Brain Collection Core.

overall_design: Infinium MethylationEPIC BeadChip (Illumina) was used to interrogate genome-wide DNA methylation levels in the post-mortem hippocampal tissue of 32 patients with bipolar disorder type I and 32 age-, sex- and race-matched non-psychiatric controls.

first: Isabelle

last: Bauer

first: Giselli

last: Scaini

first: Samira

last: Valvassori

first: Consuelo

last: Walss-Bass

first: Jair

last: Soares

first: Joao

last: Quevedo


title: Single cell transcriptome of ESCs upon MLL1 inhibition/deletion

city: beijing

first: Xu

last: hanshi

address: 167 Beilishi Road

institute: State Key Laboratory of Cardiovascular Disease

summary: This study describes the single-cell transcriptome profiling of: 1) Mll1fl/fl mESCs as control; 2) Mll1fl/fl mESCs with  4-OHT (Mll1-/-) or with MM-401 (Mll1i)  in LIF/15KSR/5% serum KO DMEM medium on Matrigel.

overall_design: Single cell RNA-Seq profiling on mouse pluripotent cells.


title: Native Chromatin Proteomics Reveals a Role for Specific Nucleoporins in Heterochromatin Organization and Maintenance.

city: Durham

first: Nahid

last: Iglesias

state: NC

address: 101 Science Drive, CIEMAS Rm. 2323

department: Biomedical Engineering

institute: Duke University

summary: Spatially and functionally distinct domains of heterochromatin and euchromatin play important roles in the maintenance of chromosome stability and regulation of gene expression, but a comprehensive knowledge of their composition is lacking. Here, we develop a strategy for the isolation of native Schizosaccharomyces pombe heterochromatin and euchromatin fragments and analyze their composition by using quantitative mass spectrometry. The shared and euchromatin-specific proteomes contain proteins involved in DNA and chromatin metabolism and in transcription, respectively. The heterochromatin-specific proteome includes all proteins with known roles in heterochromatin formation and, in addition, is enriched for subsets of nucleoporins and inner nuclear membrane (INM) proteins, which associate with different chromatin domains. While the INM proteins are required for the integrity of the nucleolus, containing ribosomal DNA repeats, the nucleoporins are required for aggregation of heterochromatic foci and epigenetic inheritance. The results provide a comprehensive picture of heterochromatin-associated proteins and suggest a role for specific nucleoporins in heterochromatin function.

overall_design: ChIP-seq analysis of histone modifications and chromatin associated proteins

first: Danesh

last: Moazed


title: Tankyrase inhibition facilitates RNA-mediated reprogramming of human somatic cells to naïve pluripotency

first: Felix

last: Krueger

address: Granta Park

department: Bioinformatics

institute: Altos Labs

summary: In contrast to conventional human pluripotent stem cells (hPSC) that are related to post-implantation embryo stages, naïve hPSC exhibit features of pre-implantation epiblast. Naïve hPSC are established by resetting conventional hPSC, or are derived from dissociated embryo inner cell masses. Here we investigate conditions for transgene-free reprogramming of human somatic cells to naïve pluripotency. We find that RNA-mediated induction of naïve pluripotency is enhanced by Wnt inhibition. We demonstrate application to independent human fibroblast cultures and endothelial progenitor cells and show that induced naïve hPSC can be clonally expanded with a diploid karyotype. They exhibit distinctive surface marker, transcriptome, and methylome properties of naïve epiblast identity. Induced naïve hPSC lines undergo somatic lineage differentiation following formative transition. Efficient, facile, and reliable induction of transgene free naïve hPSC offers a robust platform for delineation of human reprogramming trajectories and for evaluating the attributes of isogenic naïve versus conventional hPSC.

overall_design: WGBS-seq of newly generated human iPSCs lines

first: Ferdinand

last: von Meyenn

first: Austin

last: Smith


title: Brain Gene Expression Pattern of Individuals with Dual Diagnosis who died by suicide

city: Mexico City

first: Brenda

last: Cabrera

address: Periférico Sur

country: Mexico

institute: National Institute of Genomic Medicine

summary: We compared the gene expression profile in the dorsolateral prefrontal area of subjects with dual diagnosis who died by suicide to the transcriptome of subjects with mood disorders and subjects with substance use disorder who died by suicide.

overall_design: 38 samples were collected.

first: Nancy

last: Monroy-Jaramillo

first: Humberto

last: Nicolini


title: Respones to treatment of H209 and H838 cell lines to treatment with the non-covalent inhibitor of TRXR1, DKFZ-608

city: Heidelberg

first: Nikolas

last: Gunkel

institute: DKFZ

summary: DKFZ-608 induces oxidative stress in the cytoplasm of treated cancer cell lines. The molecular reason for this is the inhibition of the cytoplamic thioredoxin reductase TRXR1. The EC50 of cytotoxicity differes substantialy in SCLC (hypersensitive) and NSCLC (resistant). The experiment aims to identify stress response pathways induced by the compound which could explain the cytotoxic activity of the compound and its differential effect.

overall_design: Total RNA obtained from duplicates or triplicates of H209 and H838 cells which were treated for  4h, 8h and 24h with  either 100nM DKFZ-608 formulated in cycodextrin (16 treatment samples) or with cyclodextrin alone (18 control samples). Timepoint 0h was treated only with cyclodextrin (6 samples).


title: Whole genome analysis of skin from three immunologically diverse mouse models

city: Oklahoma City

first: Lerin

last: Luckett-Chastain

state: OK

address: 1110 N. Stonewall

department: Pharmaceutical Science

institute: OUHSC

summary: In the present study, the basal expression of the whole transcriptome of Th1 (C57BL/6) versus Th2 (BALB/c) predominant mice as well as a strain on the C57 background lacking a single cytokine, IL-6, was characterized.

overall_design:
Total RNA sequencing was performed on untreated C57BL/6 (control), BALB/c, and IL-6 deficient skin samples and found over 3400 genes differentially modulated between strains. It was found each strain modulated it’s own transcriptional “profile” associated with skin homeostasis
Together, this data not only provides a comprehensive view of the transcriptional changes in homeostatic skin of different mouse strains; but also highlights the possible influence of the Th1/Th2 balance as well as a role for IL-6 in overall skin immunity

first: Randle

last: Gallucci


title: Transcriptome of ESCs upon MLL1 inhibition/deletion

first: Fengbiao

last: Mao

summary: This study describes the transcriptome profiling of: 1) Mll1fl/fl mESCs in LIF/Serum medium as control; 2)  Mll1fl/fl mESCs with  4-OHT (Mll1-/-), MM-401 (Mll1i)  in LIF/serum medium ; 2) Mll1fl/fl mESCs with 2i  in LIF/serum-free (KSR) medium.

first: Yali

last: Dou


title: BNC1 is a master regulator of human epicardial cell heterogeneity and function

city: Great Chesterford

first: Nicolas

last: Gambardella

state: Essex

address: Lewis House, Great Chesterford Court

institute: aSciStance Ltd

summary: Single cell RNAseq of a model of epicardium derived from human pluripotent stem cell (hPSC-epi) reveals that distinct epicardial sub-populations are defined by high levels of expression for the transcription factors BNC1 and TCF21. Cells positive for the transcription factor WT1 are included in the BNC1 population, which confirms the heterogeneity observed in the mouse with TCF21 and WT1. Analysis of genes differentially expressed between the two populations suggests differences in their biological activities. We identified THY1 as a membrane marker of the TCF21 population and we show that THY1+ cells can differentiate into cardiac fibroblast and smooth muscle cells while THY1- cells mostly produce the latter. Knocking-down BNC1 during the establishment of the populations led to an homogeneous epicardium containing mostly the TCF21high populations and differentiating mainly into cardiac fibroblasts. Using network inference methods and transcriptomic data from the different epicardial lineages derived from the hPSC-epi, we identified a core transcriptional network organized around WT1, TCF21 and BNC1 and orchestrated by BNC1.

overall_design: Enginnered lateral mesoderm and epicardium cells were sorted in 96 wells plates, their RNA extracted, libraries prepared using a SmartSeq approach and single-end sequencing at 100bp performed on an Illumina HiSeq 2500.

first: Laure

first: Victoria

last: Moignard

last: Le Novère

first: Bertie

last: Gottgens

first: Sanjay

last: Sinha


title: Embryoid Body-based RNA-seq Analyses Reveal a Potential TBPPA Multifaceted Developmental Toxicity

city: Beijing

first: Shaojun

last: Liang

address: 18 Shuangqing Road

institute: Chinese academy of sciences

summary: In this study, we differentiated mouse ESCs via 3D aggregates called embryoid bodies in presence of environmental and human relevant TBPPA concentrations for 28 days. We collected samples at different time points and analyzed TBBPA-dependent global gene expression changes by RNA-seq. Our analyses revealed a potential TBBPA multifaceted developmental toxicity with effects on the nervous and cardiac/skeletal muscle systems. Mechanistically, our findings suggest TBBPA endocrine disrupting activities in part via prolactin signaling.

overall_design: we exposed mouse EB developmental process to TBBPA and analyzed TBBPA-dependent global gene expression at different time point.

first: Hui

last: Zhou

first: Nuoya

last: Yin

first: Francesco

last: Faiola


title: Differences in circadian rhythms in fly at different temperatures

city: Waltham

first: Sebastian

last: Kadener

state: MA

address: 415 South Street

institute: Brandeis University

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

sample_organism:
Drosophila melanogaster
Drosophila simulans
Drosophila virilis
Drosophila yakuba

overall_design: Refer to individual Series


title: Transcriptome and epigenome of ESCs upon MLL1 inhibition/deletion


title: Hepatocyte-intrinsic Ifnar1 signaling modulates hepatic metabolism and adaptive immunity

city: Vienna

first: Andreas

last: Bergthaler

address: Lazarettgasse 14 AKH BT25.3

country: Austria

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


title: Netrin-1 signalling function in mouse pluripotent stem cells [RNA-seq]

city: Lyon

first: Fabrice

last: Lavial

address: 28 rue Laennec

country: France

institute: CRCL

summary: We describe here the consequences of the activation of the netrin-1 signalling pathway in mouse embryonic stem cells (mESC).

overall_design: Comparison of transcriptomes of WT mESC and mESC exogenously expressing the WT form of netrin-1 or point mutants of interaction with its receptors.


title: Netrin-1 signalling function in mouse pluripotent stem cells [ChIP-Seq]

overall_design: Comparison of H3K4me3 and H3K27me3 ChIP-seq profiles of WT mESC and mESC exogenously expressing netrin-1.


title: Next-gen sequencing for transcriptomic differences in HuH-7 human hepatocellular carcinoma cell line models of hepatotoxicity

city: Bronx

first: Sanjeev

last: Gupta

address: 1300 Morris Park Ave.

department: Medicine

institute: Albert Einstein College of Medicine

summary: The gene expression profiles were analyzed of HuH-7 cells treated with cytotoxic agents, such as acetaminophen, arsenic or copper, along with cells that were treated for potential benefits with either caffeine or exosomes isolated from pooled human sera

overall_design: Ribosomal RNA depleted total RNAs for 9 different conditions were used to perfom high throughput sequensing by Ion Torrent Proton instrument

first: Yogeshwar

last: Sharma

first: Tatyana

last: Tchaikovskaya

first: Preeti

last: Viswanathan

first: Charles

last: Rogler

first: David

last: Rhee

first: Pilib

middle: O

last: Broin

first: Wilber

last: Quispe

first: Alexander

last: Maslov

first: Thirunavukkarasu

last: Chinnasamy

first: Aaron

last: Golden


title: Next-gen sequencing for miRNA content of exosomes and hepatocytes in mice with acetaminophen toxicity

summary:
Micro RNA content of extracellular vesicles/exosomes may serve as a marker of certain pathophysiological conditions.
We report differential expression of micro RNA in exosomes isolated from mouse blood or medium of cultured primary mouse hepatocytes versus parental hepatocytes or whole liver.
Studies included exosomes from blood of mice or medium of cultured primary hepatocytes with acetaminophen toxicity as well as a potentially therapeutic cytokine with acetaminophen.

overall_design: Exosomal, cellular and tissue small RNAs from healthy and injuried states were used to perfom high throughput sequensing by Ion Torrent PGM and Proton instrument

first: Tatiana

last: Gorbachova


title: Obesity Alters the Composition and the Activity of the Hematopoietic Stem Cell Compartment Through Dysregulation of Gfi1 Expression (single-cell RNA-Seq)

city: Cincinnati

first: Nathan

last: Salomonis

state: OH

address: 3333 Burnet Avenue

department: Biomedical Informatics

institute: Cincinnati Children's Hospital

summary: Obesity is a chronic organismal stress that disrupts multiple systemic and tissue-specific functions. Here, we describe the effects of established obesity on the activity of the hematopoietic stem cell (HSC) compartment. We show that obesity promotes the selection of a quiescent HSC subset primed for activation, leading to aberrant hematopoietic stress responses. We establish that the transcription factor Gfi1 is a key regulator of the HSC fate in obesity as its increased expression in obesity induces their abnormal activity. We demonstrate that these dysregulations are initially triggered by the chronic oxidative stress associated with obesity. Once acquired, we show that the impact of obesity on HSCs is long lasting and cannot be reversed by weight loss or transplantation. These results demonstrated that obesity promotes irreversible changes on the long-term fitness of the HSC compartment, a phenomenon that is likely to contribute to the hematopoietic dysregulations observed in obese patients.

overall_design: Single cell RNA seq to identify the gene expression changes associated with obesity in murine CD150+CD48-LSK HSCs.  HSCs were isolated from WT and leptin-receptor mutant mice (db/db) at 4 and 14 months of age.

first: Jung-Mi

last: Lee

first: Bryan

last: Goddard

first: Vinothini

last: Janakiram

first: Ashwini

last: Hinge

first: Marie-Dominique

last: Filippi

first: Kakajan

last: Komurov

first: Bruce

last: Aronow

first: Jose

middle: A

last: Cancelas

first: H

middle: L

last: Grimes

first: Damien

last: Reynaud


title: Expression data of Frankia CcI3 in plant root nodules under salt stress

first: Louis

last: Tisa

state: NH

address: 46 College Rd

department: MCBS

institute: University of New Hampshire

summary: Purpose: To compare RNASeq data of  Frankia CcI3 in plants under salt stress.  Casuarina glauca root nodules infected with Frankia CcI3 were exposed to either no salt or 100 mM NaCl for 21 days.  RNA-seq analysis provided insight into how the sybiont responds to salt stress.

overall_design: mRNA profiles of bacteria from plant root nodules under salt stress and control were generated by deep sequencing and mapped to Frankia CcI3 genome by CLC Genomic Workstation.  The transcriptome profiles of the salt stress cells were compared to the control condition.

first: Sheldon

last: Hurst IV

first: Rediet

last: Oshone

first: Mariama

last: Ngom

first: Valerie

last: Hocher


title: Rat liver tissue: IR vs. iPoC

city: Taipei

first: Han Chen

last: Lin

state: 中正區

address: R642, 6F, No.1, Ren Ai Road Section 1

department: Institute of Anatomy and Cell Biology

country: Taiwan

institute: National Taiwan University

summary: microRNAs expression of rat liver tissue comparing ischemia-reperfusion (IR) group with ischemic postconditioning(iPoC) group

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus

overall_design: Two-condition experiment, IR vs. iPoC.Biological replicates: 3 IR, 3 iPoC

first: Han-Chen

first: I-Rue

last: Lai


title: Genome profiling of Mll1 binding and H3K4me distribution in mouse embryo stem cells

first: Fengbiao

last: Mao

institute: University of Michigan

summary: This study describes the epigenetic profiling of Mll1 and H3K4me1/2/3 in mouse ES cells with or without MLL1 inhibition/deletion

overall_design: ChIP-Seq profile of Mll1 was generated in Mll1fl/fl mESCsmESCs.  ChIP-Seq profiles of H3K4me1/2/3 were generated in Mll1fl/fl mESCs with 4-OHT (Mll1-/-), MM-401 (Mll1i)  in LIF/15KSR/5% serum KO DMEM medium on Matrigel.  Corresponding sequence profiles of genomic DNA (Input) for each data set are also included.

first: Yali

last: Dou


title: Eomes and Brachyury control pluripotency exit and germ-layer segregation by changing the chromatin state

city: Freiburg

first: Sebastian

middle: J.

last: Arnold

address: Albertstrasse 25

department: Pharmacology

institute: University of Freiburg

summary: We aimed to elucidate molecular mechanisms of first lineage decision in the mouse pluripotent epiblast that segregates mesoderm and endoderm (ME) from neuroectoderm (NE). By analyzing mouse embryonic stem cells (ESCs) and embryos deficient for two T-box (Tbx) transcription factors Eomes and Brachyury we demonstrate that this process is controlled by the changes in the chromatin accessibility of ME gene enhancers and activation of the target genes, but also direct repression the opposing pluripotency and NE gene programs.

overall_design:
We differentiated WT ESCs, cells deficient for Eomes and Brachyury individually (EoKO and BraKO cells) as well as in combination (dKO cells) for 4-5 days using embryoid bodies treated with Activin A. We tested different doxycycline inducible constructs for the ability to rescue the observed dKO phenotype, with GFP, VP16 and EnR fusions, as well as with cDNAs encoding Mesp1, Msgn1, Mixl1 and Foxa2. Generated cells were characterized by RNA-seq, ChIP-seq and ATAC-seq. We show that cells recapitulate the phenotype of mutant embryos by analyzing RNA-seq from embryonic day E7.5 EomesDEpi , T2J/2J and double mutant T2J/2J;EomesDEpi mouse epiblasts. For RNA-seq experiments, biological triplicates were always used, and ChiP-seq and ATAC-seq experiments were done in biological duplicates.

As most of the processed data files were generated from multiple samples, they were linked as Series supplementary files and indicated both in the corresponding sample description field and processed_data_file_list.txt

first: Jelena

last: Tosic

first: Gwang-Jin

last: Kim


title: Gene expression analysis in immortalized brown adipocyte cell line treated 18h with Z16078526

status: Public on Dec 01 2019

city: Los Angeles

first: laurent

last: vergnes

state: CA

address: 695 Charles E Young Dr south

department: Human Genetics

institute: University of california, Los Angeles

summary: Strategies to increase energy expenditure are an attractive approach to reduce excess fat storage and body weight to improve metabolic health. In mammals, uncoupling protein-1 (UCP1) in brown and beige adipocytes uncouples fatty acid oxidation from ATP generation in mitochondria and promotes energy dissipation as heat. We set out to identify small molecules that enhance UCP1 levels and activity using a high-throughput screen of nearly 12,000 compounds in mouse brown adipocytes. We identified Z16078526 that increases Ucp1 and mitochondrial-related gene expression in mouse brown adipocytes.

overall_design:
The aim was to characterize the effect of Z16078526 on brown adipocyte.
Brown adipocytes were differentiated for 8 days before treatment with 10 µM Z16078526.  Total RNA from immortalized brown adipocyte cell line treated 18h with Z16078526.

first: Laurent

last: Vergnes

first: Karen

last: Reue


title: NK cells expressing CD27 and CD11b are mature NK intermediates with organ specific distribution in cynomolgus macaque.

city: Singapore

first: Sarah

last: Daud

address: 1E Kent Ridge Road,NUHS Tower Blk,Lvl 12,

country: Singapore

institute: National University of Singapore

summary: In this study, we aim to establish the means to characterize cynomolgus macaque natural killer (NK) cells, and to investigate the CD27/CD11b NK maturation model in Macaca fascicularis NK cell subpopulations. The NK development studies performed mainly in mice models have demonstrated four functionally distinct subsets as defined by CD27 and CD11b, however this has not yet been established in nonhuman primates. The expression data of these macaque NK subsets will be associated with the antibody-dependent cellular cytotoxicity and missing-self responses produce by each subset.

overall_design: Unstimulated NK cell subsets were profiled for gene expression after 10-colour flow cytometry cell sorting based on CD27 and CD11b surface expression.

first: S

first: M

last: Yawata


title: Deep small RNA profiling of anthers of Brassica rapa R-o-18 and rdr2 mutant

city: St. Louis

first: Blake

middle: C.

last: Meyers

state: MO

address: 975 N Warson Road

institute: Donald Danforth Plant Science Center

summary: Identifications of small RNAs in anther tissues and compare them with rdr2 mutant of Brassica rapa.

overall_design: anther tissues with two genotypes

first: Rebecca

last: Mosher


title: Persistent epigenetic memory impedes rescue of the telomeric phenotype in human ICF iPSCs following DNMT3B correction

city: Napoli

first: Maria

middle: Rosaria

last: Matarazzo

address: Via Pietro Castellino 111

institute: Institute of Genetics and Biophysics "ABT"

summary: DNA methyltransferase 3B (DNMT3B) is the major DNMT that methylates mammalian genomes during early development. Mutations in human DNMT3B disrupt genome-wide DNA methylation patterns and result in ICF syndrome type 1 (ICF1). To study whether normal DNA methylation patterns may be restored in ICF1 cells, we corrected DNMT3B mutations in induced pluripotent stem cells from ICF1 patients. Focusing on repetitive regions, we show that in contrast to pericentromeric repeats, which reacquire normal methylation, the majority of subtelomeres acquire only partial DNA methylation and, accordingly, the telomeric ICF1 phenotype persists. Subtelomeres resistant to de novo methylation were characterized by abnormally high H3K4 trimethylation (H3K4me3), and short-term reduction of H3K4me3 by pharmacological intervention partially restored subtelomeric DNA methylation. These findings demonstrate that the abnormal epigenetic landscape established in ICF1 cells restricts the recruitment of DNMT3B, and suggest that rescue of epigenetic diseases with genome-wide disruptions will demand further manipulation beyond mutation correction.

overall_design: In this study we examined the DNA methylation patterns of human subtelomeric regions by performing whole genome bisulfite sequencing in iPSCs derived from fibroblasts of healthy individuals, individuals affected by ICF syndrome type1 (ICF1-iPSCs) and ICF1-iPSCs corrected in the DNMT3B mutations following CRISPR/Cas9 editing.

first: Miriam

last: Gagliardi

first: Shir

last: Toubiana

middle: R

first: Sara

last: Selig


title: single-cell RNA-seq profile of adult microglia under acute Csf1r inhibition and early repopulation

city: New York

first: Li

last: Gan

address: 413 East 69th Street, 9th Floor BB904

institute: Helen and Robert Appel Alzheimer’s Disease Research Institute

summary: Microglia are the resident myeloid cell in the central nervous system (CNS). Like other terminally differentiated myeloid cells, microglia rely on Csf1r signaling for survival and maintenance. Surprisingly, a small subset of microglia in the murine brain can survive without Csf1r signaling, as shown in Csf1r KO mice as well as in mice that have been treated with Csf1r inhibitor PLX5622. The nature of such Csf1r independent microglial population has not been fully characterized. Here we applied single-cell RNA-seq to examine the remaining microglia in C57/BL6J mice that were treated with PLX5622 diet (1200 mg/kg, 14 days), which results >90% microglial removal.

overall_design:
Mice were placed on PLX diet (1200 mg/kg) for 14 days to deplete microglia (D0). The early stage microglia repopulation (D2) group was switched to control diet (CD) for 2 days.
Adult microgia from ctrl (untreated) and the treated mice were isolated by FACS using Cd11b antibody.

first: Lihong

last: Zhan


title: Establishment and characterization of NF2/CDKN2A-double knockout gene in human mesothelial cell line generated by using CRISPR/Cas9 technology

city: Nagakute

first: Karnan

last: Sivasundaram

state: Aichi

address: Yazakokarimata

department: Biochemisy

country: Japan

institute: Aichi Medical University

summary: To investigate the effect of NF2/p16 on gene expression, we have emoloyed whole genomic microarray expression profiling using MeT-5Acells

overall_design: The MeT-5A cells were plated at 80% confluence and cultured for 24 hours in vitro.

first: Akinobu

last: Ota

first: Sivasundaram

last: Karnan


title: Targeting of the dosage-compensated male X-chromosome during early Drosophila development

city: Providence

first: Erica

last: Larschan

address: 185 Meeting St.

institute: Brown University

summary: The essential process of dosage compensation, which corrects for the imbalance in X-linked gene expression between XX females and XY males, represents a key model for how genes are targeted for coordinated regulation. However, the mechanism by which dosage compensation complexes identify the X-chromosome during early development remained unknown because of the difficulty of sexing embryos prior to zygotic transcription. We used meiotic drive to sex Drosophila embryos prior to zygotic transcription and ChIP-seq to measure dynamics of dosage compensation factor targeting. The Drosophila Male-Specific Lethal dosage compensation complex (MSLc) requires the ubiquitous zinc-finger protein Chromatin-Linked Adaptor for MSL Proteins (CLAMP) to identify the X-chromosome. We observe a multi-stage process in which MSLc first identifies CLAMP binding sites throughout the genome followed by concentration at the strongest X-linked MSLc sites. We provide insight into the dynamic mechanism by which a large transcription complex identifies its binding sites during early development.

overall_design: We performed 0- to 4-h timed lays and collected and fixed embryos according to Blythe and Wieschaus (2015). We then hand-sorted embryos using a Zeiss Discovery.V8 microscope under GFP excitation using an X-CITE 120Q stereo light source. We pooled 200 (NC 11–14) to 400 (NC < 11) embryos and performed ChIP as in Blythe and Wieschaus (2015) using 3 μL of rabbit anti-CLAMP antibody per sample.

first: Leila

last: Rieder

first: William

last: Jordan


title: Persistent epigenetic memory impedes rescue of the telomeric phenotype in human ICF iPSCs following DNMT3B correction.

city: Haifa

address: 1 Efron st.

country: Israel

institute: Technion

overall_design: We examined the DNA methylation patterns of selected subtelomeric regions by performing targeted bisulfite sequencing. Samples used in this study correspond to iPSCs derived from fibroblasts of healthy individuals, individuals affected by ICF syndrome type1 (ICF1-iPSCs), ICF1-iPSCs corrected in the DNMT3B mutations following CRISPR/Cas9 editing, parental fibroblasts and fibroblast-like cells (FLs) differentiated from iPSCs. The study includes iPSCs treated with the small molecule OICR-9429 to pharmacologically reduce the H3K4me3 level.


title: The histone modification landscape of neonatal CD4+ T cells contributes to decreased T cell receptor signaling

city: Iowa City

first: Jennifer

middle: Rachelle

last: Bermick

state: IA

address: 431 Newton Road, 505 EMRB

department: Pediatrics

country: USA

institute: University of Iowa

summary: Chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) was performed to establish the H3K4me3 landscape in neonatal and adult naive CD4+ T cells. As development progressed from neonate to adult, naive CD4+ T cells gained the activating mark H3K4me3 at immunologically important promoter sites. Adult naive CD4+ T cells had enrichment of H3K4me3 at genes important in T cell receptor signaling, which was associated with improved markers of activation and cytokine expression in adult naive CD4+ T cells after engagement of the T cell receptor.

overall_design: Examination of H3K4me3 in naïve CD4+ T cells in 7 experimental groups, each in triplicate: under 30 weeks gestation preterm healthy neonate, under 30 weeks gestation preterm chorioamnionitis-exposed neonate, 30-36 weeks gestation preterm healthy neonate, 30-36 weeks gestation preterm chorioamnionitis-exposed neonate, over 37 weeks gestation term healthy neonate, over 37 weeks gestation term chorioamnionitis-exposed neonate, healthy adult