title: Blast preconditioning protects retinal ganglion cells and reveals targets for prevention of neurodegeneration following blast-mediated TBI

city: Iowa City

first: Matthew

last: Harper

state: IA

address: Bldg 42 VAMC

institute: University of Iowa

summary:
Purpose: The purpose of this study was to examine the effect blast preconditioning on the structure and function of retinal ganglion cells (RGC), and to identify molecular pathways that contribute to RGC loss.
Methods: To examine the effect of blast-preconditioning three groups of mice were analyzed, including those 1) subjected to sham injury followed by one single 20 PSI injury one week later, 2) mice exposed to two low intensity preconditioning blast exposures separated by one week (5 PSI, 5 PSI) and 3) mice exposed to a preconditioning injury (5 PSI) followed by a single 20 PSI blast exposure one week later. RNAseq analysis was used to identify transcriptional changes between groups.
Conclusions: Preconditioning protects RGC from blast injury. Protective effects appear to involve changes in kynurenine-3-monooxygenase activity, whose inhibition is also protective.

overall_design: Retinal mRNA profiles were generated in triplicate for each of the 24 total samples (split into 3 groups), resulting in biological n=8. Mice were subjected to various blast wave pressures. Group 1: preconditioned (5 PSI then 20 PSI). Group 2: blast (0 PSI then 20 PSI). Group 3: sham (5 PSI then 5 PSI).

first: Lucy

last: Evans


title: Selective eradication of leukemia cells with reprogramming factors (ATAC-Seq)

status: Public on Sep 23 2019

city: Tianjin

first: Kuangyu

last: Yen

address: Nanjing Road

department: State Key Laboratory of Experimental Hematology

country: China

institute: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We used ATAC-seq to evaluate the global programme of chromtain accessibility after Dox inducible Yamanaka factors ectopic expression during this biological process.

overall_design: To investigate the chromatin accessibility changes for the elimination of leukemia cells after Dox inducible Yamanaka factors (Oct4,Sox2,Klf4,c-Myc) expression, we sorted GFP+ MLL-AF9 acute myeloid leukemia cells (MLL-AF9) from leukemic mice and normal c-kit+ cells (WT) from 4F transgenic mice. Leukemia cells and ckit+ cells were sorted from distinct groups at different time points

first: Ting

last: Lu

first: Hui

last: Cheng


title: Selective eradication of leukemia cells with reprogramming factors (RNA-Seq)

type: Expression profiling by high throughput sequencing

summary: We used RNA-seq to evaluate the global programme of gene expression after Dox inducible Yamanaka factors ectopic expression during this biological process.

overall_design: To investigate the gene exoression changes for the elimination of leukemia cells after Dox inducible Yamanaka factors (Oct4,Sox2,Klf4,c-Myc) expression, we sorted GFP+ MLL-AF9 acute myeloid leukemia cells (MLL-AF9) from leukemic mice and normal c-kit+ cells (WT) from 4F transgenic mice. Leukemia cells and ckit+ cells were sorted from distinct groups at different time points


title: Selective elimination of leukemia cells by reprogramming factors

address: 288 Nanjing road

institute: Institute of Hematology

summary: To investigate the molecular mechanism for the elimination of leukemia cells after Dox induced OSKM expression, we sorted  MLL-AF9 leukemia cells from Dox untreated and treated groups (48h and 72h) leukemic mice for gene expression profiling analysis.

overall_design: leukemia cells were sorted from distinct groups at different time points. Microarray was performed at GMINIX in Shanghai. Total RNA was isolated with TRIzol reagent (Invitrogen, Canada) and purified using RNeasy Mini Kit (Qiagen, German), including a DNase digestion treatment. RNA concentrations were determined by NanoDrop 2000 (Thermo, America). RNA was labeled using the GeneChip® WT Terminal Labeling and Controls Kit combined with the Ambion® WT Expression Kit. Labeled cRNA was hybridized to Mouse Gene 2.0 ST GeneChip® arrays (Affymetrix, America).

first: Tao

first: Yajie

last: Wang


title: Multileveled reduction of p21 expression by Linc-ASEN represses cellular senescence [RNA-seq]

status: Public on Sep 24 2019

city: Incheon

first: Donghee

last: Kang

address: 100 Inha-ro, Michuhol-gu

department: Medicine

country: South Korea

institute: Inha University

summary: Long noncoding RNAs regulating diverse cellular processes implicate in many diseases. Here, we report the identification of a novel long intergenic noncoding RNA, Linc-ASEN, expressed in prematurely senescent cells, that associates with UPF1 and represses cellular senescence by reducing p21 production transcriptionally and post-transcriptionally. The Linc-ASEN-UPF1 complex suppressed p21 transcription by recruiting Polycomb Repressive Complex 1 (PRC1) and PRC2 to the p21 locus, and thereby preventing binding of the transcriptional activator p53 on the p21 promoter.  Moreover, the Linc-ASEN-UPF1 complex repressed p21 expression post-transcriptionally by lowering p21 mRNA stability in association with DCP1A.  Accordingly, Linc-ASEN levels were found inversely correlated with p21 mRNA levels in tumor tissues from patient-derived xenograft mice, in various human cancer tissues, and in aged mice tissues. Our studies reveal that Linc-ASEN prevents cellular senescence by reducing the transcription and stability of p21 mRNA in concert with UPF1, and suggest that Linc-ASEN might be a potential therapeutic target in processes influenced by senescence, including cancer.

overall_design: To identify the molecular mechanisms that Linc-ASEN prevents senescence, we performed RNA-Seq analysis after transfection of Linc-ASEN siRNA.


title: Chromatin Assembly Factor 1 (CAF-1) facilitates the establishment of facultative heterochromatin during pluripotency exit

city: New York

first: zhiguo

last: zhang

state: NY

address: 1130 St. Nicholas Avenue

department: Pediatric and Genetics and Development

country: USA

institute: Columbia University

summary: Establishment and subsequent maintenance of distinct chromatin domains during embryonic stem cell (ESC) differentiation are crucial for lineage specification and cell fate determination. Here we show that the histone chaperone Chromatin Assembly Factor 1 (CAF-1), which is recruited to DNA replication forks through its interaction with proliferating cell nuclear antigen (PCNA) for nucleosome assembly, participates in the establishment of H3K27me3-mediated silencing during differentiation. Deletion of CAF-1 p150 subunit impairs the silencing of many genes including Oct4, Sox2 and Nanog as well as the establishment of H3K27me3 at these gene promoters during ESC differentiation. Mutations of PCNA residues involved in recruiting CAF-1 to the chromatin also result in defects in differentiation in vitro and impair early embryonic development as p150 deletion. Together, these results reveal that the CAF-1-PCNA nucleosome assembly pathway plays an important role in the establishment of H3K27me3-mediated silencing during cell fate determination.

overall_design: To assess how CAF-1 affect mouse ESC differentiation, we depleted p150 in mESC through CRISPR/Cas9 system,  performed RNA-seq, H3K4me3 and H3K27me3 ChIP-seq in  both WT and p150-depleted ESC and differentied EBs.

first: Liang

first: Haiyun

last: Gan

first: Xu

last: Hua

first: Tamas

last: Ordog

first: Zhiguo

last: Zhang


title: Gene expression pattern comparison depend on morphological change in rat pXEN cells

city: Ansan

first: Yixiang

last: Zhong

state: Gyeonggi-do

address: 55 Hanyangdeahak-ro, Sangnok-gu

institute: Hanyang University

summary: pXEN cells have intrinsic property for vacuolation generally and in proper condition, vacuolated cells contribute to cavitation, so call vesiculation, via merge together. So, we want to find meaning of morphogenesis and connection with in vivo gastrulation stage.

overall_design: Samples were cultured in each different condition and prepared each 3 per sample independently. Vacuolated cells were collected from three differnet way, in BCS and Chir99021 with and without sorting, and vesicles were prepared from two condition, with and without serum.

first: Minjae

last: Kim

first: Kyoung

middle: H

last: Jung

first: Young

middle: G

last: Chai


title: Gene expression in skeletal muscle in older individuals subject to ten days of complete bed rest.

city: Orlando

first: Rick

last: Vega

state: FL

address: 303 E. Princeton

institute: AdventHealth

summary: Older individuals were subjected to complete bed rest for 10 days. Muscle biopsies from the vastus lateralis were obtained immediately prior and at the conclusion of the bed rest. RNA-sequencing was performed to determine the gene expression changes associated with bed rest. Marked decrease in the expression of genes associated with mitochondrial energy metabolism including fatty acid oxidation, TCA cycle and the electron transport chain was observed. Upstream regulator analysis revealed that many of these genes are downstream targets of the transcription factors PPAR, ERR and PGC-1alpha.

overall_design: RNA-sequencing was performed on 3 individual subjects before and after 10 days of complete bed rest.

middle: B

first: Michelle

last: Trevino

first: Xiaolei

first: Robert

middle: A

last: Standley

first: Bret

last: Goodpaster

first: Daniel

middle: P

last: Kelly

first: Paul

middle: M

last: Coen


title: RNA-seq Analysis of mRNA profiles in Purβ-overexpressing and Purβ-knocking down hepatocytes

city: Harbin

first: Zheng

last: Chen

state: Heilongjiang

address: 92 Xidazhijie  Harbin Institute of Technology

institute: Harbin Institute of Technology

summary:
Purpose: The goal of this study is to investigate how Purβ regulates hepatic glucose production in primary hepatocytes.
Methods: mRNA profiles of Purβ-overexpressing, and Purβ-knocking down hepatocytes were generated by deep sequencing using an Illumina NovaSeq 6000 platform. Paired-end clean reads were aligned to the mouse reference genome(Ensemble_GRCm38.96) with TopHat (version 2.0.12), and the aligned reads were used to quantify mRNA expression by using HTSeq-count (version 0.6.1).
Conclusion: Our study represents the first detailed analysis of mRNA profiles in Purβ-overexpressing, and Purβ-knocking down hepatocytes, generated by RNA-seq technology. Our results identified Adcy6 was a target of Purβ. RNA-seq analysis showed that Purβ overexpression increased Adcy6 expression, whereas Purβ knockdown decreased Adcy6 expression.

first: Linna

last: Jia


title: Overloading MuSCs

city: Fukuoka

first: Yasuyuki

last: Ohkawa

address: 3-1-1 Maidashi

country: Japan

institute: Medical Institute of Bioregulation

summary: Skeletal muscle possesses the ability to adapt its size in response to milieus, which is called plasticity. Overload like resistance training induces the increment of muscle mass called muscle hypertrophy. Muscle stem cells (also known as muscle stem cells) function to supply new nuclei for myofiber during the overload in muscle. Using compensatory hypertrophy in plantaris muscles, we isolated MuSCs from plantaris muscles 4 days after surgery. Control MuSCs were also prepared from sham plantaris muscles.

overall_design: Control and overloaded satellite cells from Pax7-CreERT2:Rosa-YFP were used for RNA-seq analysis.

first: Akihito

last: Harada

first: Sumiaki

last: Fukuda

first: So-ichiro

last: Fukada


status: Public on Sep 22 2019

city: Daejeon

first: Jimyung

last: Seo

address: 291 Daehak-ro

institute: Korea Advanced Institute of Science and Technology (KAIST)

summary: Transcriptional regulator YAP is activated in multiple human cancers and plays critical roles in tumor initiation, progression, metastasis, and drug resistance. However, therapeutic targeting of the Hippo-YAP pathway has been challenging due to its low druggability and limited knowledge of YAP regulation in cancer. Kinome siRNA library screening using an oncogenic YAP activation model identified the serine/threonine kinase MK5 as a positive regulator of YAP. To explore transcriptome signatures of MK5 activity, we performed RNA sequencing analysis after MK5 knockdown in LATS1/2-null RPE1 cells.

overall_design: We performed RNA sequencing analysis from three biologic replicates of LATS1/2-null RPE1 cells transfected with either control or MK5 siRNAs for 48 hr.

first: MinHwan

first: Hyowon

last: Hong

first: Hyunsoo

last: Cho

first: Seongyeol

last: Park

first: Sang-Kyum

first: Joon


title: Codon and amino acid identity are major determinants of mRNA stability in humans

city: Aurora

first: Olivia

middle: S

last: Rissland

state: CO

address: 12801 E 17th Avenue

department: Department of Biochemistry and Molecular Genetics

institute: RNA Bioscience Initiative, University of Colorado Denver School of Medicine

summary: To investigate the effects of the coding sequence on mRNA decay, we globally analyzed the stability of endogenous mRNAs as well as those derived from the human ORFeome collection, which contains full-length coding sequences in the context of invariant UTRs.

overall_design: HEK293T cell lines expressing subsets of the human ORFeome collection were generated. Cell lines were either left untreated, treated with DMSO, or treated with translation inhibitor 4EGI-1, and then subjected to 4SU based metabolic labeling. RNA sequencing libraries were prepared using TruSeq Stranded mRNA Sample Preparation Kit (Illumina). Sequenced reads that passed quality filters were mapped to the reference genome using STAR aligner, and quantified at the gene level using HT-seq.

first: Ashrut

last: Narula

first: James

last: Ellis


title: Transcriptome analysis of Caspase-3 deficient and proficient MCF-7 cells after docetaxel exposure

city: Dijon

first: Romain

last: Boidot

address: 1, rue Pr Marion

country: France

institute: CGFL

summary: We report that the presence of Caspase-3 induced expression of specific genes

overall_design: Examination of the expression profile of Caspase-3 deficient and proficient MCF-7 cells after 24 hours of docetaxel exposure

first: Frédérique

last: Végran

first: Sandy

last: Chevrier


title: Histone modifications (H3K4me1, H3K4me3, and H3K27ac) in IGF-2-preprogrammed macrophages and control macrophages

city: Shanghai

first: Lin

last: Liangyu

state: Shanghai

address: 320 Yueyang Road

institute: Shanghai Institutes for Biological Sciences, Chinese Academy of Science

summary: Macrophages with innate immune memory are in a modified steady-status with altered responsiveness to stimulation featured by rewired epigenetic program. To better convey the concept of IGF-2-mediated innate immune memory and help understanding the anti-inflammatory responsiveness of macrophages, we analyzed histone modifications (H3K4me1, H3K4me3, and H3K27ac) by whole genome chip-sequencing analysis in control macrophages and IGF-2-preprogrammed macrophages. In the whole genome chip-sequencing analysis, we found that IGF-2 has limited effects on H3K4me1and H3K4me3, but mainly modulates H3K27ac status during macrophages maturation.

overall_design: Examination of 3 different histone modifications in cotrol macrophages and IGF-2-preprogrammed macrophages

first: Liangyu

last: Lin

first: Liming

last: Du


title: Transcriptome analysis of Caspase-3 inhibited or not MDA-MB-231 tumors after docetaxel treatment

summary: We report that the inhibition of Caspase-3 reduced angiogenesis in vivo after docetaxel treatment

overall_design: Examination of the expression profile of Caspase-3 inhibited or not MDA-MB-231 tumors after docetaxel treatment in vivo


title: Multileveled reduction of p21 expression by Linc-ASEN represses cellular senescence [ChIP-seq]

first: Donghee

last: Kang

overall_design: Analysis of genome wide binding sites of UPF1 via ChIP-seq in MCF7 breast cancer cells.


title: Chromatin interaction analysis of Caspase_3_after_docetaxel_treatment

summary: We report that Caspase-3 interactes with DNA, especially with promoters of pro-angiogenic genes

overall_design: Examination of the interaction of active Caspase-3 after its activation by docetaxel treatment


title: Napabucasin-mediated transcriptomic changes in human pancreatic cancer cell lines

city: Cold Spring Harbor

first: David

middle: A.

last: Tuveson

address: 1 Bungtown Rd.

department: Cancer Center

institute: Cold Spring Harbor Laboratory

summary: This study aimed to determine what genes are differentially expressed following 2 hours' treatment with napabucasin (BBI-608) alone or in combination with NQO1 depletion.

overall_design: RNA-sequencing of MiaPaCa2 cells ("MiaPaca2 Parental," cells purchased from ATCC), MiaPaCa2 cells stably expressing either the Rosa26 control vector ("MiaPaCa2 Rosa26") or MiaPaCa2 cells stably expressing different CRISPR guide-RNAs to mutate the NQO1 gene, resulting NQO1 loss ("MiaPaCa2 NQO1-71" and "MiaPaCa2 NQO1-163)", treated for 2 hours with 500 nM napabucasin or with DMSO as vehicle control. For each cell line and treatment condition, 3 biological replicates were performed, except for MiaPaCa2 Rosa26 which has 2 biological replicates for the vehicle-treated control.

first: Lindsey

last: Baker


title: Multileveled reduction of p21 expression by Linc-ASEN represses cellular senescence [ChIRP-seq]

overall_design: Analysis of genome wide binding sites of Linc-ASEN via ChIRP-seq in MCF7 breast cancer cells.


title: Selective eradication of leukemia cells with reprogramming factors

status: Public on Sep 21 2019

first: Kuangyu

last: Yen

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

overall_design: Refer to individual Series


title: Overlapping roles and requirement of histone deacetylase 1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development

city: Hangzhou

first: Yanna

last: Dang

email: yannadang@126.com, yannadang@zju.edu.cn

state: Zhejiang

address: 866 Yuhangtang Rd

department: College of Animal Sciences

institute: Zhejiang University

summary: Epigenetic modifications, including DNA methylation and histone modifications, are reprogrammed considerably following fertilization during mammalian early embryonic development. Incomplete epigenetic reprogramming is a major factor leading to poor developmental outcome in embryos generated by assisted reproductive technologies, such as somatic cell nuclear transfer. However, the role of histone modifications in preimplantation development is poorly understood. Here, we show that co-knockdown (cKD) of Hdac1 and 2 (but not individually) resulted in developmental failure during the morula to blastocyst transition. This outcome was also confirmed with the use of small-molecule Hdac1/2-specific inhibitor FK228. We observed reduced cell proliferation and increased incidence of apoptosis in cKD embryos, which were likely caused by increased acetylation of Trp53. Importantly, both RNA-seq and immunostaining analysis revealed a failure of lineage specification to generate trophectoderm and pluripotent cells. Among many gene expression changes, a substantial decrease of Cdx2 may be partly accounted for by the aberrant Hippo pathway occurring in cKD embryos. In addition, we observed an increase in global DNA methylation, consistent with increased DNA methyltransferases and Uhrf1. Interestingly, deficiency of Rbbp4 and 7 (both are core components of several Hdac1/2-containing epigenetic complexes) results in similar phenotypes as those of cKD embryos. Overall, Hdac1 and 2 play redundant functions required for lineage specification, cell viability and accurate global DNA methylation, each contributing to critical developmental programs safeguarding a successful preimplantation development.

overall_design: Mouse zygotes were injected with nonspecific control siRNA (NC), Sin3a siRNA (Sin3a KD) or Hdac1/2 siRNA (Hdac1/2 cKD). At E2.75, embryos were collected  (60 embryos per sample, n=3). Total RNA was isolated from embryos using Picopure RNA isolation kit (Life Technologies, Grand Island, NY, USA) according to the manufacturer's instruction. Before RNA extraction, 2 × 106 copies of RFP and GFP mRNA was added. mRNAs were separated with oligo(dT)25 beads, and was used to prepare sequencing libraries with NEB Next Ultra RNA Library Prep Kit for Illumina (New England Biolabs). Briefly, mRNA was fragmented and reverse transcribed. The cDNA library was subject to end repair, poly(A)-tailing, adaptor ligation, and PCR amplification of 12–15 cycles for sequencing library construction. The library was sequenced by Illumina Hiseq X Ten and RNA-seq reads were assigned directly to transcripts and counted with Salmon (https://combine-lab.github.io/salmon/).

first: Kun

last: Zhang


title: Profiling the lncRNA interqaction network in the Oct4 promoter of fibroblasts in reprogramming by chromatin in situ reverse transcription trap sequencing

city: Palo Alto

first: Jifan

last: Hu

state: CA

address: 3801 Miranda Ave, Bldg 100, Room E4-200

department: Palo Alto Veterans Institute for Research

institute: Stanford University Medical School

summary: “chromatin-lncRNA in situ reverse transcription trap sequencing” (CRIST-Seq) approach was used to profile the lncRNA interactome in the promoter of stem cell core factors  Oct4

overall_design: Fibroblasts (FIB) were transfected with CRISPR Cas9 and two gRNAs derived from the gene promoter. Cells were crosslinked with formaldehyde to fix the chromatin structure. Long noncoding RNAs (lncRNAs) in the chromatin complex of the OCT4 promoter was in situ reverse transcribed with biotin-dCTP. After immunoprecipitation with Cas9 antibody and streptavidin bead purification, lncRNA derived cDNAs were used for Illumina library sequencing.

first: Yichen

last: Wang


title: H2A.Z Facilitates Licensing and Activation of Early Replication Origins

city: Beijing

first: Liwei

address: 15 Datun Road, Chaoyang District, Beijing, 100101, China

department: National Laboratory of Biomacromoluclues

institute: Institute of Biophysics

summary: DNA replication is a tightly regulated process that ensures the precise duplication of the genome during cell cycle. Licensing and activation of eukaryotic replication origins are controlled primarily by chromatin. However, the chromatin features involved and the regulatory mechanism remain largely unknown. In this study, we found that H2A.Z binds Suv420H1 directly to promote H4K20me2 deposition on nucleosome both in vitro and in vivo. ORC1 is subsequently recruited to chromatin for licensing and activation of early replication origins. Depletion of H2A.Z results in defects of DNA replication and cell proliferation in both HeLa cells and T cells. Thus, our results provide novel mechanistic insights that the histone variant H2A.Z epigenetically regulates licensing and activation of the early DNA replication origins through the Suv420H1-H4K20me2-ORC1 pathway.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: We first analyzed the interaction among H2A.Z, H4K20me2, ORC1, then investigated the role of H2A.Z on DNA replication through this pathway.

first: Haizhen

last: Long


title: Translational profiling of proximal tubule in fibrotic kidney

city: St. Louis

first: Haojia

last: Wu

state: Missouri

address: 600 S Euclid Ave

department: Renal Division/Internal Medicine

institute: Washington University in St. Louis

summary: Injury to the proximal tubule plays a central role in the initiation and progression of kidney fibrosis, and rates of chronic kidney disease progresses approximately 50% faster in males compared to females. We applied Translating Ribosome Affinity Purification (TRAP) followed by RNA-sequencing to characterize the cell-specific proximal tubule transcriptional landscape during fibrosis in male vs. female mice.

overall_design: Promixal tubule was profiled by Translating Ribosome Affinity Purification (TRAP)

first: Benjamin

middle: D

last: Humphreys


title: A375 melanoma parental and persister cells

status: Public on Sep 20 2019

city: Villejuif

first: Shensi

last: SHEN

address: 114 Rue Edouard Vaillant

institute: Gustave Roussy Institute

type: Methylation profiling by high throughput sequencing


title: m6A-seq of melanoma parental and persister cells

summary: We study the m6A distribution on mRNAs from melanoma drug-naïve parental and persister cells treated with BRAF and MEK inhibitors.

overall_design: We examine m6A modification location on mRNAs from both total lysates and polysome fractions to compare the difference between drug-naïve parental cells and BRAF/MEK inhibitor treated persister cells.

last: Shen

first: Stéphan

last: Vagner

first: Caroline

last: Robert


title: Molecular determinants of nephron vascular specialization in the kidney

city: New York City

first: Balvir

last: Kunar

state: New York

address: 1300 York Ave

department: Regenerative Medicine; Physiology, Biophysics, & Systems Biology

institute: Weill Cornell Medical College

summary: The kidney vasculature is specialized to filter waste products from the blood, regulate blood pressure, and balance electrolytes. Although recent advances in stem cell studies have enabled the partial generation of kidney tissues in vitro, recapitulating the complex vascular structures of the kidney remains a daunting task. The molecular pathways that specify and sustain kidney vascular heterogeneity to perform these diverse tasks are not well characterized. Here, we have employed high throughput bulk and single-cell RNA sequencing of the non-lymphatic vasculature of the kidney to uncover the progression of pathways that dictate the developmental transition of nephrogenesis and vascular zonation from embryos to adulthood. We show that glomeruli and its associated vessels, manifest vascular-specific signatures expressing defined transcription factors, ion channels, solute transporters, and paracrine factors choreographing kidney functions. Notably, the ontology of the glomerulus coincides with induction of several unique transcription factors, including Tbx3, Gata5, Prdm1, and Pbx1. Selective deletion of Tbx3 in endothelial cells result in glomerular hypoplasia, microaneurysms and regressed fenestrations leading to fibrosis. Unraveling the molecular determinants of kidney vascular signatures will lay the foundation for rebuilding nephrons and understanding the pathogenesis of kidney diseases.

overall_design: Expression profiling by high throughput sequencing data of transgenic Tbx3 mutant mice, transduced HUVEC cell lines, and human kidney ECs; GPL21103 Illumina HiSeq 4000 (Mus musculus); GPL20301 Illumina HiSeq 4000 (Homo sapiens).

last: Barry

first: Shahin

last: Rafii


title: Chromatin environment and cellular context specify compensatory activity of paralogous MEF2 transcription factors

status: Public on Sep 26 2019

city: st. louis

first: Naveen

last: Reddy

state: MO

address: 660 S Euclid Ave

institute: Washington University In St. Louis

summary: Compensation among paralogous transcription factors (TFs) confers genetic robustness of cellular processes. Despite the prevalence of this phenomenon, an in vivo genome-scale understanding of how TFs dynamically respond to paralog depletion is still needed. We explore this question in the mammalian brain by studying the highly conserved MEF2 family of TFs, which confer phenotypic robustness in multiple brain regions. Employing single and double conditional knockout of MEF2A and MEF2D in granule neurons of the mouse cerebellum, we find MEF2A and MEF2D play functionally redundant roles in cerebellar-dependent motor learning. To explore the molecular basis underlying this phenomenon, we systematically characterize in vivo genome-wide occupancy of MEF2A and MEF2D in the presence or absence of one another. Although highly co-expressed in granule neurons, MEF2D is the predominant genomic regulator of gene expression. Strikingly, upon depletion of MEF2D, the occupancy of MEF2A robustly increases at a subset of sites normally bound to MEF2D. Epigenome and transcriptome analyses reveal that sites experiencing compensatory MEF2A occupancy undergo functional compensation for genomic activation and gene expression. In contrast, a distinct population of sites without compensatory MEF2A activity undergo significant dysregulation upon loss of MEF2D. The two populations of MEF2 target sites are further stratified by relative chromatin accessibility, with compensatory MEF2A activity concentrated within more open chromatin. Finally, we reveal that motor activity-induced changes in neuronal state induce a dynamic switch from non-compensatory to compensatory MEF2-dependent gene regulation, demonstrating the context-dependent nature of paralogous TF interdependency. Collectively, these studies define the first in vivo genome-wide characterization of functional interdependency between paralogous TFs.

overall_design: Examination of interdependency of MEF2A and MEF2D via transcriptomic and epigenomic characterization in control and conditional knockout mammalian cells.

first: Shahriyar

last: Majidi

middle: C

first: Michael

middle: J

last: Moore

first: Hao

last: Chen

first: Tomoko

last: Yamada

first: Milena

last: Andzelm

first: Timothy

last: Cherry

first: Linda

middle: E

last: Greenberg

first: Azad

last: Bonni


title: Lin28 expression affect embryonic lung development

city: Ramat Gan

first: Achia

last: Urbach

address: Ramat Gan

department: Faculty of Life Sciences

country: Israel

institute: Bar Ilan University

summary: Lin28A and its paralog Lin28B are RNA binding proteins that regulate gene expression by inhibition of the maturation of the Per/Pri Let-7 miRNAs family and also via Let-7 independent mechanism. To study the effect of Lin28A ectopic-expression on mouse embryonic development we used a transgenic mice strain that combine a Cre-Lox system and a Tet-On system (herein Lox-stop-Lox-TetOn-Lin28A mice) and enable spatial and temporal control of transgenic Lin28A over-expression. Here we show that global Lin28A over-expression (by crossing Lox-stop-Lox-TetOn-Lin28A males with VasaCre females) in the mouse embryo prevents embryonic lung development. To study the precise developmental stage affected by Lin28A expression we preformed RNA sequencing analysis for transgenic and control lungs from E12.5, E14.5, E16.5 and E18.5 embryos. This analysis revealed that the development of the lung was delayed but not completely abrogated by Lin28A expression. We further showed that the effect of Lin28A expression in the mesenchymal cells (by crossing Lox-stop-Lox-TetOn-Lin28A males with Wt1Cre females)  of the lung leads to the same phenotype as global Lin28A expression while expression in the lung epithelial cells (by crossing the Lox-stop-Lox-TetOn-Lin28A males with Nkx2.1Cre females) result in a milder developmental phenotype.

overall_design: RNA seq analysis was preformed for the following samples in triplicate (unless otherwise indicated): E12.5, E14.5, E16.5, E18.5 (5 repeats) control lungs. E12.5, E14.5 (4 repeats), E16.5, E18.5 (5 repeats) transgenic lungs derived from embryos with global Lin28A overexpression. E18.5 transgenic lungs derived from embryos with specific Lin28A expression in the lung epithelial cells. E18.5 transgenic lungs derived from embryos with Lin28A expression in the lung mesenchymal cells (duplicate).

first: Gross-Carmel

last: Ilana

first: Armon

last: Leah

first: Urbach

last: Achia


title: Prostaglandin D2 Signaling in Tendon Healing

city: New York

first: Christopher

middle: L

last: Mendias

address: 535 E 70th St

institute: Hospital for Special Surgery

summary: We report RNA sequencing data from the plantaris tendons of 3-month old Sprague Dawley rats that were treated with vehicle or GSK2894631A to inhibit the HPGDS enzyme. Rats underwent a bilateral plantaris tendon tear followed by immediate repair, and samples were obtained either 7 or 21 days after surgical intervention.

overall_design: Differential expression of mRNAs were evaluated between the plantaris tendons of control rats or rats that were subjected to a plantaris tendon tear and repair and received 0mg/kg, 2mg/kg, or 6mg/kg of GSK2894631A twice daily for 7 or 21 days.


title: Regulation of fetal liver transcription by maternal nutritional stress

city: Baltimore

middle: J.

last: Wolfgang

state: MD

address: 855 N Wolfe Street

department: Institute for Basic Biomedical Sciences

institute: The Johns Hopkins University School of Medicine

summary: Pregnancy is a time of extreme metabolic demand that requires coordinated adaptations between mother and fetus. To determine the contributions of maternal and fetal metabolism to metabolic plasticity during gestation, mice with a liver-specific Carnitine Palmitoyltransferase-2 knockout mice (Cpt2-/-), or Pparα KO mice were subjected to late-gestation nutrient stress, a 24hr fast from E16.5 to E17.5. The fetal response to maternal fasting was dominated by maternal lipid metabolism as the loss of maternal hepatic fatty acid oxidation or Pparα signaling accelerated fetal liver transcriptional programing. These data show that maternal nutritional environment is a major driver of perinatal metabolic programing and plasticity.

overall_design: Examination of wild-type and Ppara KO E17.5 fetal liver following a 24hr fast in WT, Cpt2-/-, and Ppara KO dams, with 4 biological replicates each.


title: ATAC-seq profiling assessing the impact of IFNg and Pictilisib on human SqCC/Y1 cells

city: Atlanta

first: Chris

last: Scharer

state: GA

address: 1510 Clifton Rd, Suite 3086A

department: Microbiology and Immunology

institute: Emory University

summary: To examine differences in chromatin accessibility SqCC/Y1 cells were treated with Pictilisib to inhibit PI3K signaling in combination with DMSO or IFNg for 48 hours and ATAC-seq performed.

overall_design: Triplicate samples of SqCC/Y1 cells were treated with combinations of DMSO, Pictilisib, and IFNg.

first: C


title: Enhancer activation by FGF signalling during otic induction

status: Public on Sep 19 2019

city: London

first: Andrea

last: Streit

address: Centre for Craniofacial & Regenerative Biology, King's College London

country: United Kingdom

institute: Kings College London

summary: We report that FGF exposure of sensory progenitors (pPPR) leads to rapid deposition of active chromatin marks H3K27ac near hundreds of FGF-responsive, otic-epibranchial progenitor (OEP) genes, while   H3K27ac is depleted in the vicinity of non-otic genes. Genomic regions that gain H3K27ac act as cis-regulatory elements controlling OEP gene expression in time and space and define a unique transcription factor signature likely to control their activity. Thus, during ear induction FGF signalling modifies the chromatin landscape to promote enhancer activation and chromatin accessibility.

overall_design: Examination of 2 different histone modifications in Cnt and FGF2 treated posterior pre-placodal (pPPR) explants.

first: Monica

last: Tambalo

first: Maryam

last: Anwar

first: Mohi

last: Ahmed


title: Characterization of organ-level specification of murine vascular endothelial cells from embryonic-stage to post-puberty adulthood.

first: Balvir

last: Kunar

summary: Vascular endothelial cells (ECs) establish via paracrine signaling tissue-specific niches that promote organ revascularization and regeneration. Given these executive functions, transplantation of ECs into the vasculature has been used to stimulate organ repair. However, challenges in faithfully deriving tissue-specific endothelium within in vitro culture conditions limit large-scale expansion potential, long-term functional stability, and the cell homing and engraftment potential towards the target organ. Identification of the transcriptional regulators that modulate the specification of generic or unspecified endothelial cell populations into tissue-specific vascular ECs may provide novel factors to be incorporated into standard stem-cell differentiation protocols. Such controlled expression of the appropriate angiocrine factors—in combination with the niche microenvironment—could support the necessary crosstalk and cell-to-cell membrane interactions necessary for positioning and anastomosis when transplanted. Previously, investigation of the transcriptome profiles of ECs originating from diverse vascular beds has helped identify potential transcriptional regulators and gene markers of EC tissue specification. We aim to expand on these studies by elaborating on the progression of EC tissue specification as it occurs from embryonic development to adulthood. A better understanding of how ECs acquire their tissue specificity and deconvolution of the transient expression patterns of key molecular regulators could provide crucial information on the establishment of EC tissue-specific function which can then be recapitulated in vitro. Our long-term goal is to generate transcriptionally stable and functional tissue-specific ECs from stem-cell derived EC banks suitable for transplantation for the purpose of promoting non-fibrotic tissue regeneration after organ injury.

overall_design: Expression profiling by high throughput sequencing data; GPL21103 Illumina HiSeq 4000 (Mus musculus).

first: David

last: Barry

first: Shahin

last: Rafii


title: A novel genetic circuitry governing hypoxic metabolic flexibility, commensalism and virulence in the fungal pathogen Candida albicans

city: Montreal

first: Adnane

last: Sellam

address: 5000, rue Bélanger

country: Canada

institute: Universite de Montreal

summary: Inside the human host, the pathogenic yeast Candida albicans colonizes predominantly oxygen-poor niches such as the gastrointestinal and vaginal tracts, but also oxygen-rich environments such as cutaneous epithelial cells and oral mucosa. This suppleness requires an effective mechanism to reprogram reversibly the primary metabolism in response to oxygen variation. Here, we have uncovered that Snf5, a subunit of SWI/SNF chromatin remodeling complex, is a major transcriptional regulator that links oxygen status to the metabolic capacity of C. albicans. Snf5 and other subunits of SWI/SNF complex were required to activate genes of carbon utilization and other carbohydrates related process specifically under hypoxia. snf5 mutant exhibited an altered metabolome reflecting that SWI/SNF plays an essential role in maintaining metabolic homeostasis and carbon flux in C. albicans under hypoxia. Snf5 was necessary to activate the transcriptional program linked to both commensal and invasive growth. Accordingly, snf5 was unable to maintain its growth in the stomach, the cecum and the colon of mice. snf5 was also avirulent as it was unable to invade Galleria larvae or to cause damage to human enterocytes and murine macrophages. Among candidates of signaling pathways in which Snf5 might operate, phenotypic analysis revealed that mutants of Ras1-cAMP-PKA pathway, as well as mutants of Yak1 and Yck2 kinases exhibited a similar carbon flexibility phenotype as did snf5 under hypoxia. Genetic interaction analysis indicated that the adenylate cyclase Cyr1, a key component of the Ras1-cAMP pathway genetically with Snf5. Our study yielded new insight into the oxygen-sensitive regulatory circuit that control metabolic flexibility, stress, commensalism and virulence in C. albicans.

overall_design: To investigate the role of the SWI/SNF subunit, Snf5, in metabolic flexibility under hypoxia in C. albicans, we performed genome-wide transcriptional profiling by microarray. Both WT (SN250) and snf5 mutant cells were grown on YP-Sucrose under both hypoxia and normoxia and their transcriptomes were characterized.

first: Anaïs

last: Burgain

first: Émilie

last: Pic

first: Laura

last: Markey

first: Faiza

last: Tebbji

first: Carol

last: Kumamoto


title: Next Generation Sequencing to compare gene expression of PC-3M-Pro4 in cell culture and in zebrafish metastasis

city: Leiden

first: Lanpeng

last: Chen

state: South Holland

address: Einsteinweg 55, GW3.19

department: Institute of Biology

country: Netherlands

institute: Leiden University

summary: We report how engrafted human prostate cancer cells respond to zebrafish microenvironment during metasatic colonization.

sample_organism:
Danio rerio
Homo sapiens

platform_organism:
Danio rerio
Homo sapiens

overall_design: RNA was isolated from metastasese in zebrafish (70 fish/group), from  uninjected fish (70fish/group), and from cells in culture, in triplicate. Transcriptomics of human cancer cells were compared between in culture and in metastases. PBS-injected fish was set as  control to analyze how engrafted cancer cells modulate gene expression of the host stromal cells

first: Ron

last: Dirks


title: Mycobacterium abscessus virulence traits unraveled by transcriptomic profiling in amoebae and macrophages

city: Paris

first: Rachel

last: Legendre

address: 28, rue du docteur Roux

department: Research and Resource Center for Scientific Informatics

institute: Institut Pasteur

summary: We report the transcriptome of M. abscessus in amoebae and macrophages. M. abscessus intra-amoebal and intra-macrophagic transcriptomes demonstrate of the potential of M. abscessus to adapt to an intracellular lifestyle, though amoebae largely contribute to the enhancement of M. abscessus survival macrophages.

sample_organism:
Mycobacteroides chelonae
Mycobacteroides abscessus

overall_design: RNA sequencing of M. abscessus RNA in amoebae 4/16 hours post-infection (hpi) and macrophages 16 hpi and Mycobacterium chelonae RNA in amoebae 16 hpi.  Amoeba Acanthamoeba castellanii and J774.2 murine macrophages cell lines were used for the purpose of this study.

first: Violaine

last: Dubois

first: Alexandre

last: Pawlik

first: Anouchka

last: Bories

first: Vincent

last: Le Moigne

first: Odile

last: Sismeiro

first: Rodriguez

last: Pilar

first: Jean-Louis

last: Gaillard

first: Jean-Yves

last: Coppée

first: Roland

last: Brosch

last: Herrmann

first: Fabienne

last: Girard-Misguich


title: JASPer controls interphase H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila (Sonication ChIP-seq experiments)

city: Planegg-Martinsried

first: Christian

last: Albig

address: Großhaderner Strasse 9

department: Biomedical Center

country: Germany

institute: Ludwig-Maximilians-University Munich

summary: In flies, the chromosomal kinase JIL-1 is responsible for most interphase H3S10 phosphorylation and has been proposed to protect active chromatin from acquiring heterochromatic marks like H3K9me2 and HP1. Here, we show that JIL-1’s targeting to chromatin depends on a new PWWP domain containing protein JASPer (JIL-1 Anchoring and Stabilizing Protein). The JASPer/JIL-1 (JJ)-complex is the major form of the kinase in vivo and is targeted to active genes and telomeric transposons via binding of the PWWP domain of JASPer to H3K36me3 nucleosomes. Put in place, the complex modulates the transcriptional output. JIL-1 and JJ-complex depletion in cycling cells induce small changes in H3K9me2 distribution at active genes and telomeric transposons. Finally, we identified many new interactors of the endogenous JJ-complex and propose that JIL-1 not only prevents heterochromatinisation, but also coordinates chromatin based regulation in the transcribed part of the genome.

overall_design: Sonication ChIP-Seq of JASPer in S2 cells

first: Tamas

last: Schauer

first: Silke

last: Krause

first: Peter

last: Becker

first: Catherine

last: Regnard


title: JASPer controls interphase H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila (RNA-seq experiments)

overall_design: RNA-Seq in S2 cells and Kc cells treated with control, jil-1 or jasper RNAi


title: JASPer controls interphase H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila (MNase ChIP-seq experiments)

overall_design: MNase ChIP-Seq of JASPer, JIL-1, H3K36me3 and MSL3 in S2 cells and Kc cells


title: JASPer controls interphase H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila (Spike-in ChIP-seq experiments)

overall_design: Spike-in ChIP-Seq of JASPer, MSL3, H3K9me2 and H4K16ac in S2 cells after control and jil-1 RNAi treatment.


title: Translational control of mTOR/4E-BP1 axis in MiaPaca-2 cells

status: Public on Sep 18 2019

city: Toulouse

first: Yvan

last: Martineau

address: 2 Avenue Hubert Curien, CS 53717,

department: UMR1037 Inserm CRCT

institute: Inserm

summary: Pancreatic ductal adenocarcinoma (PDAC) relies on hyper-activated protein synthesis. Consistently, human and mouse PDAC lose expression of the translational repressor and mTOR target 4E-BP1. Using genome-wide polysome-profiling, we here explore mRNAs whose translational efficiencies depend on the mTOR/4E-BP1 axis in Miapaca-2 cells.  This was performed by isolating cytoplasmic and efficiently translated (heavy polysome-associated) mRNAs from MiaPaca-2 cells upon PP242-mediated mTOR inhibition

overall_design: Miapaca-2 cells were treated with 2.5μM PP242 for 12 hours. Both cytoplasmic and polysome-associated mRNA was extracted from treatments and a vehicle treated control and probed with microarrays. Experiments were done in 4 replicates for a total of 16 samples.

first: David

last: Muller


title: The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells [dataset 8, BIBO]

city: Vancouver

first: Michael

middle: S.

last: Kobor

state: BC

address: 950 West 28th Avenue

department: Medical Genetics

institute: Centre for Molecular Medicine and Therapeutics / University of British Columbia

type: Methylation profiling by genome tiling array

summary:
The development of current biological markers of aging has primarily focused on adult samples. The epigenetic clock is one promising tool for measuring biological age that shows impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several agerelated phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this crucial gap, we aimed to develop a highly accurate, noninvasive biological measure age specific to pediatric samples by using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032) and the performance was assessed in a separate dataset (n = 689). The DNAm at 94 CpG sites was highly predictive of age in the test cohorts (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.
The BIBO (Dutch abbreviation for Basale Invloeden op Baby Ontwikkleing) is one of the cohorts to develop the PedBE clock.

overall_design: In the BIBO cohort (dataset 8), 193 mothers and their children have been followed since week 37 of pregnancy. At age 6 DNA was collected with buccal swabs in 148 of the children, which was used to measure DNA methylation with the Illumina EPIC array by the Kobor Lab at UBC in collaboration with Kieran O'Donnell and Michael Meaney at McGill.

first: Lisa

last: McEwen

first: Kieran

last: O’Donnell

first: Megan

last: McGill

first: Rachel

last: Edgar

first: Meaghan

last: Jones

first: Julia

last: MacIsaac

middle: T

last: Lin

first: Katia

last: Ramadori

first: Alexander

last: Morin

first: Nicole

last: Gladish

first: Elika

last: Garg

first: Eva

last: Unternaehrer

first: Irina

last: Pokhvisneva

first: Neerja

last: Karnani

first: Michelle

middle: Z

last: Kee

first: Torsten

last: Klengel

first: Nancy

last: Adler

first: Ronald

last: Barr

last: Letourneau

first: Gerald

middle: F

last: Giesbrecht

first: James

middle: N

last: Reynolds

first: Darina

last: Czamara

first: Jeffrey

last: Armstrong

first: Marilyn

last: Essex

first: Carolina

last: de Weerth

first: Roseriet

last: Beijers

first: Marieke

last: Tollenaar

first: Bekh

last: Bradley

first: Tanja

last: Jovanovic

first: Kerry

last: Ressler

first: Meir

last: Steiner

first: Sonja

last: Entringer

first: Pathik

last: Wadhwa

first: Claudia

last: Buss

middle: R

last: Bush

first: Elisabeth

last: Binder


title: Single cell RNA sequencing revealed a chemokine self-feeding of myeloma cells for extramedullary metastasis

first: Xiannian

last: Zhang

address: Yiheyuan Road No.5

institute: Peking University

summary: To determine the mechanisms of the initial extramedullary translocation of myeloma cells from bone marrow into peripheral blood.  We found that the clonal cPCs were more frequently detected by flowcytometry in extramedullary plasmacytoma patients and worsened their prognosis.  It is technically much easier to collect single cPCs using FACS than it is to perform EMP biopsy.  Combining imaging extramedullary plasmacytoma diagnosis and cPCs detection may be a promising strategy for prognostic stratification.  Using single-cell transcriptome analysis, we found that CXCL12, a key molecule for the CXCR4-dependent cell retention mechanism in bone marrow, was abnormally up-regulated in cPCs and might initially enable cPCs evasion and translocation into blood.

overall_design: We perform single cell RNA-seq using Smart-Seq2 for single myeloma cells derived from bone marrow of a patient with multiple myeloma.

first: Shuang

last: Geng

first: Jing

last: Wang

first: Jia-jia

first: Fan

last: Wu

first: Yuhong

last: Pang

first: Yuping

last: Zhong

first: Jianbin

first: Wenming

first: Xiaoqing

last: Lyu

first: Yanyi

last: Huang

first: Hongmei

last: Jing


title: Physical and functional compartmentalization of archaeal chromosomes

city: Kyoto

first: Naomichi

last: Takemata

address: Kyoto University, Katsura, Nishikyo-ku

department: Synthetic Chemistry and Biological Chemistry

institute: Kyoto University

summary: The three-dimensional organization of chromosomes can have a profound impact on their replication and expression. The chromosomes of higher eukaryotes possess discrete compartments that are characterized by differing transcriptional activities. Contrastingly, most bacterial chromosomes have simpler organization with local domains, the boundaries of which are influenced by gene expression. Numerous studies have revealed that the higher-order architectures of bacterial and eukaryotic chromosomes are dependent on the actions of Structural Maintenance of Chromosomes (SMC) superfamily protein complexes, in particular the near-universal condensin complex. Intriguingly, however, many archaea, including members of the genus Sulfolobus do not encode canonical condensin. We describe chromosome conformation capture experiments on Sulfolobus species. These reveal the presence of distinct domains along Sulfolobus chromosomes that undergo discrete and specific higher-order interactions, thus defining two compartment types. We observe causal linkages between compartment identity, gene expression and binding of a hitherto uncharacterized SMC superfamily protein that we term “coalescin”.

sample_organism:
Sulfolobus acidocaldarius
Saccharolobus islandicus

overall_design: Hi-C, ChIP-seq, and RNA-seq experiments were performed on Sulfolobus acidocaldarius DSM639 and Sulfolobus islandicus REY15A strains. Genome DNA of a S. islandicus REY15A strain lacking oriC1 was sequenced for marker frequency analysis.

first: Rachel

middle: Y

last: Samson

first: Stephen

last: Bell


title: Transcriptomic signatures indicative of a non-genotoxic adverse outcome pathway for small intestine cancer in the duodenum of mice exposed to hexavalent chromium, captan, or folpet

city: Austin

first: Grace

last: Chappell

state: TX

address: 9390 Research Blvd, Bldg 2, Ste. #100

department: Health Sciences

institute: ToxStrategies, Inc.

summary: We evaluated duodenal tissues of B6C3F1 mice exposed to either Cr(VI) (180ppm in drinking water), captan (≤12000ppm in diet), or folpet (≤16000ppm in diet) for 28 days. TempO-Seq technology was used to measure the sentinel geneset, S1500+, representing ~3000 toxicology-relevant genes. Global exposure-induced transcriptional responses were similar between agents (all Pearson correlation coefficients ≥0.61). Focusing on responses at doses of captan and folpet that correlate most closely with effects of Cr(VI), a gene-level comparison identified that 126/546 (23%) differentially expressed genes were altered in the same direction across all three agents. Pathway-level comparisons identified 25 up-regulated pathways commonly modulated between Cr(VI), captan, and folpet. Commonly altered genes and pathways were related to cellular metabolism, stress, immune response, and cell proliferation. No up-regulated pathways relevant to genotoxicity were associated with responses to any agent.

overall_design: Examination of ~3000 genes by targeted sequencing in duodenal tissue from mice from 6 treatment groups.

middle: A

first: Julia

last: Rager

first: Chad

last: Thompson


title: Fate specific mRNA storage in seeds

city: Wageningen

first: Leónie

last: Bentsink

address: Droevendaalsesteeg 1

institute: Wageningen University

summary:
We analyzed the monsome and polysome associated transcripts of seeds and seedlings and identify transcripts specifically associated with monosome and polysome in both tissues
The aim was to generate a global view about the state of mRNA storage in the seeds and the their fate during seed germination.

overall_design: Transcript level on both total mRNA and polysomal RNA of seeds and seedlings of Col-0 were evaluated. For each RNA fraction, three replicates were used.

first: Bing

last: Bai

first: Sjors

last: van der Horst

first: Jan

last: Cordewener

first: Twan

last: America

first: Johannes

last: Hanson


title: Expression data from A375 melanoma parental and persister cells

city: Villejuif

first: Shensi

last: SHEN

address: 114 Rue Edouard Vaillant

institute: Gustave Roussy Institute

summary:
Identify transcriptionnally and translationally regulated mRNA in melanoma parental and persister cells
In this dataset, we include expression data of A375 melanoma drug-naïve parental cells and A375 melanoma persister cells that survived from BRAF and MEK inhibition. The expression data are studied in both total RNA and polysome-bounded RNA.

overall_design: We have perform microarray analysis from total RNA and Polysomal associated RNA.

last: Shen

first: Stéphan

last: Vagner

first: Caroline

last: Robert


title: The PedBE clock estimates DNA methylation age in pediatric buccal cells [dataset 7, WSFW]

status: Public on Sep 17 2019

first: Michael

last: Kobor

summary: The development of current biological markers of aging has primarily  focused on adult samples. The epigenetic clock is one promising tool  for measuring biological age that shows impressive accuracy across  most tissues and age ranges. In adults, deviations from the DNA  methylation (DNAm) age prediction are correlated with several agerelated phenotypes, such as mortality and frailty. In children,  however, fewer such associations have been made, possibly because  DNAm changes are more dynamic in pediatric populations as  compared to adults. To address this crucial gap, we aimed to  develop a highly accurate, noninvasive biological measure age  specific to pediatric samples by using buccal epithelial cell  DNAm. We gathered 1,721 genome-wide DNAm profiles from  11 different cohorts of typically developing individuals aged 0 to  20 y old. Elastic net penalized regression was used to select 94  CpG sites from a training dataset (n = 1,032) and the performance was assessed in a separate dataset (n = 689). The DNAm  at 94 CpG sites was highly predictive of age in the test cohorts  (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE)  clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and  adult age ranges, and the association with obstetric outcomes. The  PedBE tool for measuring biological age in children might help in  understanding the environmental and contextual factors that shape  the DNA methylome during child development, and how it, in  turn, might relate to child health and disease.

overall_design: The Illumina Infinium HumanMethylation450 Beadchip was used to obtain genome-wide DNA methylation measures in human buccal epithelial swabs (n = 179) from   WSFW (Wisconsin Study of Families and Work, Dataset 7) is a longitudinal cohort focused on family health during second trimester and post-partum. For the current study, only samples at age 18 years old were included.

first: Lisa

middle: M

last: McEwen

first: Kieran

last: ODonnell

first: Megan

middle: G

last: McGill

last: Edgar

first: Meaghan

last: Jones

last: MacIsaac

first: David

last: Lin

first: Katia

last: Ramadori

first: Alexander

last: Morin

first: Nicole

last: Gladish

first: Elika

last: Garg

first: Eva

last: Unternaehrer

first: Irina

last: Pokhvisneva

first: Neerja

last: Karnani

first: Michelle

last: Kee

first: Torsten

last: Klengel

first: Nancy

last: Adler

first: Ronald

last: Barr

last: Letourneau

first: Gerald

last: Giesbrecht

first: James

last: Reynolds

first: Darina

last: Czamara

first: Jeffrey

last: Armstrong

first: Marilyn

last: Essex

first: Carolina

last: de Weerth

first: Roseriet

last: Beijers

first: Marieke

last: Tollenaar

first: Bekh

last: Bradley

first: Tanja

last: Jovanovic

first: Kerry

last: Ressler

first: Meir

last: Steiner

first: Sonja

last: Entringer

first: Pathik

last: Wadhwa

first: Claudia

last: Buss

last: Bush

first: Elisabeth

middle: B

last: Binder


title: The PedBE clock estimates DNA methylation age in pediatric buccal cells [APrON]

first: Michael

last: Kobor

summary: The development of current biological markers of aging has primarily focused on adult samples. The epigenetic clock is one promising tool for measuring biological age that shows impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several agerelated phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as  compared to adults. To address this crucial gap, we aimed to develop a highly accurate, noninvasive biological measure age specific to pediatric samples by using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032) and the performance was assessed in a separate dataset (n = 689). The DNAm at 94 CpG sites was highly predictive of age in the test cohorts (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.

overall_design: The Illumina Infinium HumanMethylation450 Beadchip was used to obtain genome-wide DNA methylation measures in human buccal epithelial swabs (n = 145) from   APrON (Albert Pregnancy Outcomes and Nutrition, Dataset 1) which is a Canadian cohort of pregnant women with 3-year child follow-up. DNA methylation was collected at birth (cord blood) and at age 3 months (buccal epithelial), however, we only included the buccal epithelial data in the current study. Tissue extraction/genomic DNA isolation: Genomic DNA was extracted using the Gentra Puregene Buccal Cell Kit (Qiagen #158845). Bisulfite conversion: genomic DNA was bisulfite converted using the EZ DNA Methylation Kit (Zymo Research).

first: Lisa

last: McEwen

first: Kieran

last: ODonnell

first: Megan

last: McGill

first: Rachel

middle: D

last: Edgar

first: Meaghan

last: Jones

first: Julia

last: MacIsaac

first: David

last: Lin

first: Katia

last: Ramadori

first: Alexander

last: Morin

first: Nicole

last: Gladish

first: Elika

last: Garg

first: Eva

last: Unternaehrer

first: Irina

last: Pokhvisneva

first: Neerja

last: Karnani

first: Michelle

last: Kee

first: Torsten

last: Klengel

first: Nancy

last: Adler

first: Ronald

last: Barr

last: Letourneau

last: Giesbrecht

middle: S


title: JASPer controls interphase H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila

first: Christian

last: Albig

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

overall_design: Refer to individual Series


title: Loss of the FOXP1 transcription factor leads to deregulation of B lymphocyte development and function at multiple stages

first: Joseph

last: Dekker

address: 2506 Speedway Blvd, NMS 1.264

department: Molecular Biosciences

institute: University of Texas at Austin

summary:
This study examined the loss of Foxp1 in B cells at different stages. RNA-seq was performed to examine gene expression differences fromB cells from wildtype and Foxp1 cKO spleens.
We found strong enrichment for signatures related to down-regulation of immune responses, apoptosis and germinal center biology, including direct activation of Bcl6 and downregulation of Aicda/AID, the primary effector of SHM and CSR.
These observations support a role for FOXP1 as a direct transcriptional regulator at key steps underlying B cell development in the mouse.

overall_design: Splenic B cell mRNA profiles were compared among WT and CD19creFoxp1 cKO C57Bl/6 mice

first: Haley

middle: O

last: Tucker


title: Identification of a unique subtype of lung squamous cell carcinoma defined by SOX2 and a neural differentiation factor BRN2 [RNA-seq]

first: Hideo

last: Watanabe

address: One Gustave L. Levy Place

department: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine

institute: Icahn School of Medicine at Mount Sinai

summary: Lineage-specific transcriptional regulators control differentiation states not only during normal development but also during cancer evolution. By investigating super-enhancer landscape of lung squamous cell carcinoma (LUSC), we identified a unique ‘neural’ subtype defined by Sox2 and a neural lineage factor Brn2. Robust protein-protein interaction and genomic co-occupancy of these factors indicated their transcriptional cooperation in this ‘neural’ LUSC in contrast to the cooperation of Sox2 and p63 in the classical LUSC. Introduction of p63 expression in the “neural’ LUSC invoked the classical LUSC lineage accompanied by Brn2 downregulation and increased activities of ErbB/Akt and MAPK-ERK pathways. Collectively, our data demonstrate a unique LUSC lineage featured by Sox2 cooperation with Brn2 instead of p63, for which distinct therapeutic approaches may be warranted.

overall_design: Transcriptomic profiles in control and DNp63-overexpressed LK2 cells

first: Takashi

last: Sato

first: Seungyeul

last: Yoo


title: A cell fitness selection model for neuronal survival during development

status: Public on Sep 16 2019

city: Stockholm

first: Francois

last: Lallemend

state: Stockholm

address: Tomtebodavägen 16

department: Neuroscience

country: Sweden

institute: Karolinska Institutet

summary: Developmental cell death plays an important role in the construction of functional neural circuits. In vertebrate, the canonical view proposes a selection of the surviving neurons through stochastic competition for target-derived neurotrophic signals, implying an equal potential for neurons to compete. Here we show an alternative cell fitness selection of neurons that is defined by a specific neuronal heterogeneity code. Proprioceptive sensory neurons that will undergo cell death and those that will survive exhibit different molecular signatures that are regulated by the retinoic acid and transcription factors, and are independent of neurotrophins and of the target. These molecular features are genetically encoded, representing two distinct subgroups of neurons with contrasted survival outcome and functional maturation states. Thus, in our model, a heterogeneous code of intrinsic cell fitness in neighboring neurons provides differential competitive advantage resulting in the selection of cells with higher intrinsic capacity to survive and to functionally integrate into neural networks.

overall_design: In total 2 samples (dorsal root ganglia dissociated single neurons at E11.5 and E12.5) were collected.

first: Yiqiao

last: Wang

first: Haohao

last: Wu

first: Paula

last: Fontanet

first: Simone

last: Codeluppi

first: Natalia

last: Akkuratova

first: Charles

last: Petitpré

first: Yongtao

last: Xue-Franzén

first: Karen

last: Niederreither

first: Anil

last: Sharma

first: Fabio

last: Da Silva

first: Glenda

last: Comai

first: Gulistan

last: Agirman

first: Domenico

last: Palumberi

first: Sten

last: Linnarsson

first: Igor

last: Adameyko

first: Aziz

last: Moqrich

first: Andreas

last: Schedl

first: Gioele

last: La Manno

first: Saida

last: Hadjab

first: François


title: Repertoires of CD4Foxp- cells from SfTCRmini and TCRmini mice.

first: Leszek

last: Ignatowicz

address: 100 Piedmont Ave SE

department: Institute for Biomedical Sciences

institute: Georgia State University

summary: We examined the transcriptional signatures and CDR3 TCRa chain repertoire of hundreds of individual Scurfy CD4Foxp3GFP- cells and from control TCRmini mice.

overall_design: Sorted CD4Foxp3GFP-CD44+CD62L- subsets from SfTCRmini and TCRmini mice were encapsulated using a 10X Chromium Controller for scRNAseq analysis and TCR sequencing.

first: Anna

last: Cebula


title: Transcriptional profiling of Setd5 mutant cortical tissue

city: Milano

first: Luca

last: Massimino

state: MI

address: Via Olgettina, 58

department: Gastroenterology

country: Italy

institute: Ospedale San Raffaele

summary: Setd5 inactivation in neural stem cells, zebrafish and mouse leads to a significant H3K36 hypo-methylation mostly detectable along the gene bodies. Consequently, this chromatin alteration perturbs RNA processing during elongation, compromising the transcriptional output. This gene dysregulation affects proliferative dynamics of NSCs and synaptic wiring in the neuronal derivatives, ultimately resulting in behavioral deficits in adult mice.

overall_design: 3 wt and 3 Setd5 heterozygous adult cortex

first: Alessandro

last: Sessa

first: Vania

last: Broccoli


title: Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG

city: Philadelphia

first: Alison

middle: J

last: Carey

state: PA

address: 245 N 15th Street Room 18119

department: Pediatrics

institute: Drexel Univeristy

summary: Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old mice are exceptionally sensitive to influenza virus infection and exhibit high mortality and viral load. Intranasal pre- and post-treatment of neonatal mice with Lactobacillus rhamnosus GG (LGG), an immune modulator in respiratory viral infection of adult mice and human preterm neonates, considerably improves neonatal mice survival after influenza virus infection. We determine that both live and heat-killed intranasal LGG are equally efficacious in protection of neonates. Early in influenza infection, neonatal transcriptional responses in the lung are delayed compared to adults. These responses increase by 24 hours post-infection, demonstrating a delay in the kinetics of the neonatal anti-viral response. LGG pretreatment improves immune gene transcriptional responses during early infection and specifically upregulates type I IFN pathways.

overall_design: Neonates were treated on day of life 1 and 2 intranasally  with 1e6 CFU of Lactobacillus rhamnosus GG and Instranasally Infected with TCID50 0.04 PR8 Influenza A virus.

first: Ogan

middle: K

last: Kumova

first: Joshua

middle: C

last: Mell


title: Integrative genomic analysis identifies key pathogenic mechanisms in primary mediastinal large B-cell lymphoma

first: Christian

last: Steidl

state: British Columbia

address: 675 10th Avenue West

department: Lymphoid Cancer Research

institute: BC Cancer

summary: Primary mediastinal large B-cell lymphoma (PMBL) represents a clinically and pathologically distinct subtype of large B-cell lymphomas. Furthermore, molecular studies, including global gene expression profiling, have provided evidence that PMBL is more closely related to classical Hodgkin lymphoma (cHL). Although targeted sequencing studies have revealed a number of mutations involved in PMBL pathogenesis, a comprehensive description of disease-associated genetic alterations and perturbed pathways is still lacking.  Here, we performed whole-exome sequencing of 95 PMBL tumors to inform on oncogenic driver genes and recurrent copy number alterations. The integration of somatic gene mutations with gene expression signatures provides further insights into genotype-phenotype interrelation in PMBL.  We identified highly recurrent oncogenic mutations in the JAK-STAT and NF-kB pathways, and provide additional evidence of the importance of immune evasion in PMBL (CIITA, CD58, B2M, CD274, PDCD1LG2). Our analyses highlight the IRF-pathway as a putative novel hallmark with frequent alterations in multiple pathway members (IRF2BP2, IRF4, IRF8). In addition, our integrative analysis illustrates the importance of JAK1, RELB and EP300 mutations driving oncogenic signaling.  The identified driver genes were significantly more frequently mutated in PMBL as compared to diffuse large B-cell lymphoma, whereas only a limited number of genes were significantly different between PMBL and cHL, emphasizing the close relationship between these entities. Our study, performed on a large cohort of PMBL, highlights the importance of distinctive genetic alterations for disease taxonomy with relevance for diagnostic work-up and therapeutic decision-making.

overall_design: RNA was extracted from PMBL tumors and analyzed in the context of mutational data to ascertain the impact of recurrent mutations on transcriptional profiles

first: Stacy

last: Hung

first: Lauren

last: Chong

first: Anja

last: Mottok


title: Translation complex profiling for bacteria [Ribo-seq]

city: Guwahati

first: B

last: Anand

state: Assam

address: North guwahati

department: Biosciences and Bioengineering

country: India

institute: Indian institute of technology guwahati

summary: Ribosomes were arrested during initiation, elongation and termination complex formation using formaldehyde crosslinking. The complex protected footprints were isolated after MNase treatment and sequenced.

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: Studying translation initiation in Wt and assembly defecient strains

first: Himanshu

last: Sharma


title: Analysis of gene expression in hTERT/cdk4 immortalized human myoblasts from multiple muscle pathologies compared to their primary populations

city: Londonderry

first: William

middle: John

last: Duddy

address: C-TRIC building, Altnagelvin Hospital Campus

department: Northern Ireland Centre for Stratified Medicine

institute: Ulster University

summary: hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically-pertinent models of various neuromuscular disorders and in numerous fundamental studies of muscle cell function. However, the cell cycle is linked to other cellular processes such as integrin regulation, the PI3K/Akt pathway, and microtubule stability, raising the question as to whether transgenic modification of the cell cycle results in secondary effects that could undermine the validity of these cell models. Here we subjected healthy and disease myoblasts to intensive transcriptomic analysis, comparing immortalized cell populations, and clonal lines derived from them, with their parent primary populations. We found that immortalization has no measurable effect on the myogenic cascade or on any other cellular processes, and that it was protective against the systems level effects of senescence that are observed at higher division counts of primary cells.

overall_design: This dataset includes gene expression data of myoblasts derived from 4 human subjects: 1 healthy, 1 limb girdle muscular dystrophy type 2b (LGMD-2B), 1 facioscapulohumeral muscular dystrophy (FSHD), and 1 oculopharyngeal muscular dystrophy (OPMD). It consists of 36 samples, including primary myoblasts, their immortalized populations, and a clone from each immortalized population (3 cell culture replicates each).


title: Glutarylation of Histone H4 Lysine 91 Regulates Chromatin Dynamics

city: Hong Kong

first: Jason

last: Wong

address: L1-51, Laboratory Block, 21 Sassoon Road

country: Hong Kong

institute: The University of Hong Kong (HKU)

summary: Chromatin is decorated with diverse histone posttranslational modifications (PTMs) that are involved in regulating chromatin structure and dynamics during various DNA-associated processes such as gene transcription, DNA replication and DNA damage repair. Here, we combine a chemical reporter with mass spectrometry to identify a new class of histone PTM, lysine glutarylation (Kglu), occurring at 27 lysine residues on human core histones. The characterization of an evolutionarily conserved Kglu mark at histone H4 lysine 91 (H4K91glu) using a semisynthetic glutarylated protein reveals that this negatively charged modification greatly destabilizes nucleosome by weakening the interactions between histone H2A/H2B dimers and H3/H4 tetramer in vitro. The replacement of H4K91 by glutamic acid in S. cerevisiae to mimic glutarylation influences chromatin structure and thereby results in a global up-regulation of transcription and defects in cell cycle progression, DNA damage repair and telomere silencing in vivo. In mammalian cells, H4K91glu is mainly enriched at promoter regions of highly expressed genes. A down-regulation of H4K91glu is tightly associated with chromatin condensation during mitosis and in response to DNA damage. The cellular dynamics of H4K91glu is controlled by Sirt7 as a deglutarylase and KAT2A as a glutaryltransferase. This study designates a new histone mark (Kglu) as a new regulatory mechanism for chromatin dynamics.

sample_organism:
Saccharomyces cerevisiae
Homo sapiens

platform_organism:
Saccharomyces cerevisiae
Homo sapiens

overall_design: ChIP-seq and RNA-seq

first: Xiang

last: Li

middle: W

first: Xiucong

last: Bao


title: The N6-methylation of adenosine (m6A) in FZD10 mRNA contributes to PARP inhibitor resistance

status: Public on Sep 14 2019

first: Priyankara

last: Wickramasinghe

address: 3601 Spruce Street

department: Bioinformatics

institute: The Wistar Institute

summary: Chemical modifications of RNAs have emerged as a new layer of epigenetic gene regulation. N6-methyladenosine (m6A) is the most abundant chemical modification of messenger RNA (mRNA). The m6A modification affects RNA fate and functions such as RNA stability.  Despite the high initial response rates to PARP inhibitors in BRCA1/2-mutated epithelial ovarian cancers (EOC), PARP inhibitor (PARPi) resistance remains a major challenge.  The role of m6A modification in PARPi resistance has not previously been explored.  Here we show that m6A modification of FZD10 mRNA contributes to PARPi resistance by upregulating the Wnt/-catenin pathway in BRCA-mutated EOC cells.  Global m6A profile reveals a significant increase in m6A modification in FZD10 mRNA.  This correlates with an increase in FZD10 mRNA stability and an upregulation of the Wnt/-catenin pathway in PARPi resistant cells.  FZD10 knockdown or inhibition of the Wnt/-catenin sensitizes the resistant cells to PARPi.  Mechanistically, downregulation of m6A demethylases FTO and ALKBH5 is sufficient to increase FZD10 mRNA m6A modification and reduce PARPi sensitivity, which correlates with an increase in homologous recombination activity.  Moreover, PAPRi and Wnt/-catenin inhibitor showed synergistic suppression of growth of PAPRi resistant cells both in vitro and in vivo in a xenograft ovarian cancer mouse model. Our results show that m6A contributes to PAPRi resistance in BRCA-deficient EOC cells by upregulating the Wnt/-catenin pathway through stabilizing FZD10.  They also suggest that inhibition of Wnt/-catenin pathway represents a potential strategy to overcome PARPi resistance.

overall_design: MeRIP-Seq in Parental and PARPi resistant PEO1 cells

first: Rugang

last: Zhang

first: Takeshi

last: Fukumoto


title: Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

status: Public on Sep 15 2019

city: Rochester

first: Surendra

last: Dasari

state: MN

address: 200 First Street SW

department: Quantitative Health Sciences Research

institute: Mayo Clinic

summary: Background: Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in animal models of diabetes. Human studies have also revealed loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages in full thickness gastric biopsies from gastroparesis patients.  Aim: We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in full thickness gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying and symptoms.   Methods: Full-thickness gastric antrum biopsies were obtained from nine DG, seven IG patients and five non-diabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1300 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity Pathway Analysis and correlations were carried out. Multiple-testing corrected p-values <0.05 were considered statistically significant.    Results: 73 proteins were differentially expressed in DG, 132 proteins in IG and 40 proteins were common to DG and IG. In both DG and IG, “Role of Macrophages, Fibroblasts and Endothelial Cells” was the most statistically significant altered pathway (DG FDR: 7.9x10-9; IG FDR: 6.3x10-12). In DG, properdin expression correlated with GCSI-bloating (r: -0.99, FDR: 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C zeta type and complement C2 correlated with 4 hr gastric retention (r: -0.97, FDR: 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG.   Conclusions: Protein expression changes suggest a central role of macrophage-driven immune dysregulation and complement activation in gastroparesis.

overall_design: Full thickness gastric biopsies were collected from IG, DG and control subjects. Proteins were extracted and assayed using SomaLogic 1.3k array technology.

first: Madhusudan

last: Grover


title: Evaluation of the physiological property of D-allulose on obesity and its comorbidities in diet-induced obese mice based on mRNA-seq analysis

status: Public on Sep 13 2019

city: Daegu

first: Youngji

last: Han

address: Daehakro 80

institute: Kyungpook National University

summary: ackground/Objectives: The aim of the current study was to elucidate the effects of long-term supplementation with D-allulose on obesity and associated comorbidities by analyzing transcriptional and metabolic responses. Subjects/Methods: C57BL/6J mice were divided into three groups and fed a normal diet, high-fat diet (HFD), or high-fat + 5% (w/w) D-allulose diet for 16 weeks. Results: Body weight and body fat mass were significantly decreased in HFD-fed with D-allulose supplemented mice and their levels were similar to that of the normal diet. Also, major symptoms of obesity, such as high plasma lipid profiles and cytokine levels, were attenuated by D-allulose supplementation.   D-allulose supplement induced the alteration of mRNA expression in epididymal white adipose tissue (eWAT) and hepatic tissue. D-allulose normalized mRNA expression related lipid metabolism in eWAT and hepatic tissue. In Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapper analyses, D-allulose supplementation were down regulated the “cytokine-cytokinereceptor interaction”, “chemokinesignaling pathway”, “MAPK signaling pathway”and“toll-like receptor signaling pathway” in eWAT and hepatic tissue.

overall_design: Total RNA of liver and adipose tissues was obtained from normal diet, high-fat diet and D-allulose added high-fat diet-fed mice and mRNA expression-associated with lipid metabolism and inflammation was measured.

first: Joon

last: Yoon

first: Heebal

last: Kim

first: Myungsook

last: Choi


title: c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program [RNA-seq]

city: Durham

first: Maria

last: Ciofani

state: NC

address: 207 Research Drive, 128 Jones Building

department: Integrative Immunobiology

institute: Duke University School of Medicine

summary: The transcription factor c-Maf is an essential regulator of group 3 ILC homeostasis and effector plasticity. c-Maf limits acquisition of the type 1 program and conversion to the ILC1 fate through restraint of T-bet expression and function.

overall_design: Evaluation of differential expression in Maf--deficient ILC subsets from the small intestine lamina propria. RNA was extracted from three replicate samples of NKp46+ ILC3, CCR6+ ILC3, and ILC2s from cohoused Maf+/+ Il7r-Cre and Maf fl/fl Il7r-Cre mice.

first: Morgan

middle: E

last: Parker

first: Alejandro

last: Barrera


title: Validation of the DNA Damage Immune Response (DDIR) Signature in Triple-Negative Breast Cancer (TNBC) Patients from the SWOG 9313c Trial

city: Kansas City

first: Priyanka

last: Sharma

address: 3901 Rainbow Boulevard

institute: University of Kansas Medical Center

summary: Purpose: The purpose of this study was to independently validate two biomarkers, a 44-gene DNA Damage Immune Response (DDIR) signature and stromal tumor-infiltrating lymphocytes (sTILs), as prognostic markers in TNBC patients treated with adjuvant doxorubicin (A) and cyclophosphamide (C) in SWOG 9313.  Materials & Methods: 425 centrally determined TNBC cases from S9313 were identified. DDIR signature was performed on RNA isolated from FFPE tumor tissue (n=381), and samples were classified as DDIR-negative or positive using predefined cutoffs. Evaluation of sTILs was performed as previously described. Markers were tested for prognostic value for disease-free and overall survival (DFS, OS) using Cox regression models adjusted for treatment assignment nodal status and tumor size.  Results: Among 425 TNBC patients, median age was 45 years, and 33% were node-positive. DDIR was successfully tested in 90% (381/425) of cases, of which 62% were DDIR signature-positive. DDIR signature positivity was associated with improved DFS (HR=0.67; 95% CI 0.48–0.92, P=0.014) and OS (HR=0.61; 95% CI 0.43–0.89, P=0.009). sTILs density assessment was available in 99% of patients and was associated with improved DFS (HR=0.70; 95% CI 0.51–0.96, P=0.028 for sTILs density ≥20% vs. <20%) and OS (HR=0.59; 95% CI 0.41–0.85, P=0.004 for sTILs density ≥20% vs. <20%). The DDIR signature score and sTILs density were moderately correlated (r=0.62) which precluded statistical significance for DFS in a joint model (P=0.08 for DDIR and P=0.25 for sTILs).   Conclusion: The prognostic role of sTILs and DDIR in early-stage TNBC was confirmed. DDIR signature conferred improved prognosis in two-thirds of TNBC patients treated with adjuvant AC. DDIR signature has potential to stratify outcome and identify patients with less projected benefit following AC chemotherapy. Clinical trial number: Int0137 (The trial pre-dates Clinicaltrial.Gov website establishment)

overall_design: For this validation cohort, 381 triple negative breast cancer patients were profiled on cDNA microarray, originally collected prospectively as part of the S9313 study.  In S9313, patients with either high-risk node-negative or node-positive breast cancer were randomly assigned to one of two equivalent dose schedules of AC chemotherapy, given either sequentially or concurrently. A total of 13 process controls (ES-2 cell lines) were also included throughout microarray profiling for quality control and surveillance.

first: P

first: W

last: Barlow

first: A

last: Godwin

first: E

last: Parkes

first: L

last: Knight

first: S

last: Walker

first: R

last: Kennedy

first: D

middle: P

last: Harkin

first: G

last: Logan

first: C

last: Steele

last: Lambe

last: Badve

first: Y

last: Gokmen-Polar

first: H

last: Pathak

first: K

last: Isakova

last: Linden

last: Porter

last: Pusztai

last: Thompson

last: Tripathy

last: Hortobagyi

middle: F

last: Hayes


title: MCPyV targets NDRG1 to promote cellular proliferation

city: LYON

first: Alexis

last: Robitaille

state: Rhône-Alpes

address: 150 Cours Albert Thomas

department: Section of Infections

institute: International Agency for Research on Cancer (IARC)

summary: Merkel cell polyomavirus (MCPyV) is the first human polyomavirus etiologically associated with Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. Similar to other polyomaviruses, MCPyV encodes early T antigen genes, a viral oncogene required for MCC tumor growth. To identify the unique oncogenic properties of MCPyV, we analysed the gene expression profiles in human spontaneously immortalized keratinocytes (NIKs) expressing the early genes from five distinct human polyomaviruses (PyVs), including MCPyV. A comparison of the gene expression profiles revealed 28 genes specifically deregulated by MCPyV.

overall_design: Comparative analyses of deregulated cellular gene expression mediated by the 6 PyVs

first: Purnima

last: Gupta

first: Naveed

last: Shahzad

first: Hector

last: Hernandez-Vargas

first: Geoffroy

last: Durand

first: Florence

last: Le Calvez-Kelm

first: Tarik

last: Gheit

first: Rosita

last: Accardi

first: Massimo

last: Tommasino


title: c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program [ATAC-seq]

first: Maria

last: Ciofani

overall_design: Evaluation of differential ATAC-seq accessibilty in cohoused Maf-deficient NKp46+ ILC3 and CCR6+ ILC3. The Omni ATAC protocol was performed on replicate samples of both NKp46+ ILC3 and CCR6+ ILC3s  isolated from the small intestine lamina propria of Maf+/+ Il7r-Cre and Maf fl/fl Il7r-Cre mice. Evaluation of  ATAC-seq accessibilty during transition of DN ILC3 to NKp46+ ILC3 to ILC1 using both C57Bl/6 and Rorc(t) GFP/+ mice. The Omni ATAC protocol was performed on replicate samples for each population  isolated from the small intestine lamina propria of C57Bl/6 and Rorc(t) GFP/+ mice.

first: Morgan

last: Parker

first: Alejandro

last: Barrera


title: Metformin-induced alterations in peripheral blood cell trancriptome of healthy individuals

city: Riga

first: Monta

last: Brīvība

address: Ratsupites 1

country: Latvia

institute: Latvian Biomedical Research and Study Centre

summary: Metformin is a commonly used antihyperglycaemic agent for the treatment of type 2 diabetes. Nevertheless, the exact mechanisms of action, underlying the various therapeutic effects of metformin, remain elusive. The goal of this study was to evaluate the alterations in longitudinal whole-blood transcriptome profiles of healthy individuals after a one-week metformin intervention in order to identify the novel molecular targets and further prompt the discovery of predictive biomarkers of metformin response.  Next generation sequencing-based transcriptome analysis revealed four clusters of functionally related genes with a subject-specific differential expression even after a single dose of metformin: ribosomal genes and their pseudogenes (e.g., RNA5-8SN1, RNA5-8SN5, RNY4P10), small nuclear RNAs (e.g., SNORA20, SCARNA5, SNORA80E), genes relevant to insulin production (HNF1B, HNF1A, HNF4A, GCK, INS, NEUROD1, PAX4, PDX1, ABCC8, KCNJ11) and cholesterol homeostasis (APOB, LDLR, PCSK9). After accounting for subject-specific expression, the enrichment of pathways associated with immune responses, such as intestinal immune network for IgA production and cytokine-cytokine receptor interaction were observed for the majority of the cohort.  The results of the study reveal for the first time a strong inter-individual variation of the metformin effect on the transcriptional regulation, that goes in line with well-known variability of the therapeutic response to the drug.

overall_design: RNA-Seq data of venous blood samples collected from 25 healthy volunteers at three consecutive time points:before administration of metformin, 10 hours after the first does, after 7 days long metformin course.

last: Ustinova

first: Ivars

last: Silamikelis

first: Ineta

last: Kalnina

first: Laura

last: Ansone

first: Vita

last: Rovite

first: Ilze

last: Elbere

last: Radovica-Spalvina

first: Davids

last: Fridmanis

first: Jekaterina

last: Aladyeva

last: Konrade

first: Valdis

last: Pirags

first: Janis

last: Klovins


title: Effect on tomato plants of asymptomatic infection with southern tomato virus

city: Kusatsu, Shiga

first: Midori

last: Tabara

address: 1-1-1, Noji-Higashi

institute: Ritsumeikan University

summary: Southern tomato virus (STV) often infects healthy tomato plants (Solanum lycopersicum). In this study, we compared STV-free and STV-infected cultivar M82 plants to determine the effect of STV infection on the host plant. STV-free plants exhibited a short and bushy phenotype, whereas STV-infected plants exhibited increased height. STV-infected plants produced more fruit than STV-free plants, and the germination rate of seeds from STV-infected plants was higher than that of seeds from STV-free plants. This phenotypic difference was also observed in progeny plants (siblings) derived from a single STV-infected plant in which the transmission rate of STV to progeny plants via the seeds was approximately 86%. These results suggest that the interaction between STV and host plants is mutualistic. Transcriptome analyses revealed that STV infection affected gene expressions in host plants, notably evidenced by down-regulation of genes involved in ethylene biosynthesis and signaling. STV-infected tomato plants thus might be artificially selected due to their superior traits as a crop.

overall_design: RNA-seq analyses using three 1-month-old STV-infected and three 1-month-old STV-free tomato plants of cv. M82

first: Toshiyuki

last: Fukuhara

first: Hisashi

last: Koiwa

first: Hideki

last: Takahashi


title: c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program

first: Maria

last: Ciofani

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

overall_design: Refer to individual Series


title: SIGNAL INTEGRATION AND TRANSCRIPTIONAL REGULATION OF THE INFLAMMATORY PROGRAM ASSOCIATED WITH THE GM-/M-CSF SIGNALING AXIS IN HUMAN MONOCYTES [METHYLATION DATA SET]

city: Derio

first: Ana

middle: Maria

last: Aransay

state: BIZKAIA

address: Parque tecnologico de Bizkaia, Building 801-A

department: Genome Analysis Platform

country: Spain

institute: CIC bioGUNE

summary: In recent years, the M-CSF and GM-CSF cytokines have been identified as opposing regulators of the inflammatory program. However, the two cytokines are simultaneously present in the inflammatory milieu, and it is not clear how cells integrate these signals. In order to understand the regulatory networks associated with the GM/M-CSF signaling axis we analyzed DNA methylation in human monocytes. Our results indicate that GM-CSF induces activation of the inflammatory program and extensive DNA methylation changes, while M-CSF-polarized cells are in a less differentiated state. This inflammatory program is mediated via JAK2 associated with the GM-CSF receptor and the downstream ERK signaling. However, PI3K signaling is associated with a negative regulatory loop of the inflammatory program and M-CSF autocrine signaling in GM-CSF-polarized monocytes. Our findings describe the regulatory networks associated with the GM/M-CSF signaling axis and how they contribute to the establishment of the inflammatory program associated with monocyte activation.

overall_design: Two replicates were used per cell type. Each sample of Monocytes, M1 and M2 were obtained from a pool of three individuals. Hematopoietic progenitors CD34+ were used as reference samples.

first: Ramon

last: Rodriguez

first: Beatriz

last: Suarez-Alvarez

first: Jose

middle: L

last: Lavín

first: Alex

last: Ascensión

first: Monika

last: González

first: Juan

last: Lozano

first: Aroa

last: Raneros

first: Paula

last: Bulnes

first: Covadonga

last: Huidobro

first: Cristina

last: Martin-Martin

first: Amaya

last: Puig-Kröger

first: Angel

last: Corbí

first: Marcos

last: Araúzo-Bravo

first: Carlos

last: Lopez-Larrea

middle: R

last: Vidal-Castiñeira

last: Sanz

first: Marta

last: Ruiz-Ortega


title: Epigenome analysis of endometrial endometrioid adenocarcinoma tissues

city: Koto-ku

first: Osamu

last: Gotoh

state: Tokyo

address: Ariake 3-8-31

institute: Japanese Foundation For Cancer Research

summary: We performed genome-wide DNA methylation profiling of endometrial endometrioid adenocarcinoma tissues derived from patients in the Cancer Institute Hospital of Japanese Foundation for Cancer Research.

overall_design: DNA methylation status was analyzed using genomic DNA from each tumor on the Illumina Infinium MethylationEPIC BeadChip Arrays (n=103), according to the manufacturer’s instructions.

first: Yuko

last: Sugiyama


title: Clonal copy-number mosaicism in T-lymphocytes in NOD mice

city: Montréal

first: Constantin

last: Polychronakos

state: Québec

address: 1001 Décarie

institute: MUHC-RI

type: Genome variation profiling by genome tiling array

summary: In Type 1 Diabetes (T1D), imperfect concordance in monozygotic twins and in males of the inbred NOD mouse model, despite genetic identity and shared environment during the years of peak incidence, points to stochastic determinants. One plausible such stochastic event, never explored, is post-zygotic genetic changes in the expanding antigen-specific autoreactive T-cell lineages. The contribution of such mutations in tumorigenesis is well established but little is known about potential role in autoimmunity. Here, with high-resolution comparative genomic hybridization (CGH) of DNA from memory CD4 T-cells from pancreatic lymph nodes of NOD mice, we found mosaic somatic copy-number aberrations (CNAs) with highly non-random independent involvement of the same gene(s) across different mice. A few CNAs were also found in lymphocytes expanded during normal host defense but were significantly smaller. Our data strongly support a causal role for post-zygotic mutations in autoreactive T-cells in T1D. They challenge the classical notions of autoimmune disease and open conceptual avenues towards individualized prevention and therapeutics.

overall_design: Comparing genome from PLN of diabtic NOD mice against germline DNA from each mouse. Test samples: 25 diabetic NOD mice, Control: mice infected with L major, (10 NOD and 7 BALB/c)

first: Maha

last: AL-Riyami

first: Quan

last: Li

first: Luc

last: Marchand

first: Xiaoyu

last: Du

first: Martin

last: Olivier