title: APOE Expression and Secretion are Modulated by Copper-Dependent and -Independent Mitochondrial Dysfunction

city: Middlebury College

first: Amanda

last: Crocker

state: Vermont

address: 276 Bicentennial Way

department: Neuroscience

institute: Middlebury College

summary:
Mitochondria are dynamic organelles that influence cellular function through both cell-autonomous and non-cell autonomous mechanisms, such as production of paracrine and endocrine factors. Here, we demonstrate that mitochondrial regulation of the secretome is more extensive than previously appreciated, as both genetic and pharmacological disruption of the inner mitochondrial membrane caused upregulation of the Alzheimer’s disease risk factor apolipoprotein E (APOE) and other secretome components. This upregulation of secretory proteins was of a similar extent as modifications to the mitochondrial annotated proteome. Gene editing of SLC25A family inner mitochondrial membrane transporters, as well as genetic and pharmacological disruption of copper-dependent and independent steps of electron transport chain assembly and function, caused upregulation of APOE transcript, protein, and secretion, up to 16-fold. These APOE phenotypes were robustly expressed in diverse cell types and iPSC-derived human astrocytes as part of an inflammatory gene expression program. We propose that mitochondria act as novel upstream regulators of APOE-dependent cellular processes in health and disease.
We report RNAseq profiles of human cell lines with CRISPR mediated mutagenesis of SLC25A1 and SLC5A4.

overall_design: Comparative gene expression profiling of  Wild type or gene-edited HAP1 cells (SLC25A1 and SLC25A4).

first: Victor

last: Faundez


title: Effect of adipose tissue insulin resistance on gene expression of liver in diet-induced NASH model.

status: Public on Nov 09 2022

city: Kobe

first: Yusei

last: Hosokawa

address: 7-5-2 Kusunoki-cho, Chuo-ku

department: Division of Diabetes and Endocrinology, Department of internal medicine

country: Japan

institute: Kobe University graduate school of medicine

type: Expression profiling by high throughput sequencing

summary:
To investigate the alterlation of liver gene expression in diet-induced NASH model with adipose tissue insulin resistance, we evaluated liver of control mice
and adipocyte-specific PDK1 knockout (PDK1KO) mice  fed either normal chow(NC) or  Gubra amylin NASH (GAN) diet for 16weeks after weaning
at 4 weeks old. We then performed gene expression profiling analysis using data obtained from RNA-seq of these 4 groups.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for liver of 4 groups[Control(NC), Contro(GAN), PDK1KO(NC),PDK1KO(GAN)].

first: Tetsuya

last: Hosooka

first: Wataru

last: Ogawa


title: Spatial profiling of tumour microenvironment (TME) in head and neck squamous cell carcinoma for biomarkers of response to immunotherapy

status: Public on Nov 14 2022

city: brisbane

first: Arutha

last: Kulasinghe

address: 37 kent st

country: Australia

institute: University of Queensland

summary:
Nanostring DSP was performed on 187 ROIS from 17 HNSCC patients and differential analysis was performed by patient response groups to immunotherapy.
DE proteins were identified in both tumour and stromal tissue compartments

overall_design: Comparitive groups were best response to immunotherapy, Progression, Stable disease, partial response, complete response. 71 protein markers were tested

first: Habib

last: Sadeghirad

first: Ning

last: Liu

first: James

last: Monkman

first: Chin

middle: W

last: Tan


title: RNA interactome capture in E. coli to identify RNA-binding proteins

status: Public on Nov 13 2022

city: Uppsala

first: Erik

last: Holmqvist

state: Uppland

address: Husargatan 3, Box 596, Uppsala University, Dept. of Cell and Molecular Biology

country: Sweden

institute: Uppsala University

summary: RNA-binding proteins (RPBs) are deeply involved in fundamental cellular processes in bacteria and are vital for their survival. Despite this, few studies have so far been dedicated to globally identifying bacterial RBPs. We have adapted the RNA interactome capture (RIC) technique, originally developed for eukaryotic systems, to globally identify RBPs in bacteria. RIC takes advantage of the base pairing potential of poly(A) tails to pull-down mRNA-protein complexes. By overexpressing poly(A) polymerase I, we drastically increase the fraction of polyadenylated RNA in Escherichia coli, allowing us to pull-down RNA-protein complexes using immobilized oligo-d(T) as bait. With this approach, we identified 169 putative RBPs, roughly half of which are already annotated as RNA-binding

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

overall_design: Addition of poly(A) tails to E. coli RNA by overexpression of PAPI combined with UV-light crosslinking to allow for purification of polyadenylated RNA along with co.purification of interacting proteins using oligo d(T) beads

first: Thomas

middle: S

last: Stenum

first: Jonas

last: Kjellin


title: HDAC9-mediated Epithelial Cell Cycle Arrest in G2/M Contributes to Kidney Fibrosis

status: Public on Nov 10 2022

city: Jinan

first: Zhang

last: Yang

address: 44 Wenhua West Road

department: Department of  Pharmacology

country: China

institute: Shandong University

summary: Renal tubulointerstitial fibrosis is the pathological feature of AAN. Aristolochic acid nephropathy (AAN)was induced by a one-time intraperitoneal injection of aristolochic   acid in PBS. By RNA sequencing analysis in AAN mice, we observed the significant changes of genes important in regulating cell cycle.

overall_design:
We established the mouse model of AAN to explore the precise mechanism.
The gene expression of 6 samples from the AAN mice was compared to 4 sham samples by RNA sequencing.

first: Yang

last: Zhang

first: Min


title: CD146+ mural cells from infantile hemangioma

status: Public on Nov 04 2022

city: Shanghai

first: Jialin

last: Chen

address: 639 Zhizaoju Road, Huangpu District

institute: Shanghai Ninth People's Hospital

summary:
To investigate celltype and function of hemangioma mural cells
We then performed gene expression profiling analysis using data obtained from RNA-seq of hemangioma mural cells and hemangioma stem cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for hemangioma mural cells and hemangioma stem cells.

first: Lei

last: Chang

first: Yajing

last: Qiu

last: Yu

first: Qianyi

first: Yuanbo

last: Li

first: Shih-jen

first: Zongan

first: Xiaoxi

last: Lin


title: Gene expression profile at single cell level of CD8+ tumor infiltrating lymphocytes from the CT26 murine colon carcinoma model subdivided by antigen binding capacity

city: Denver

first: Jennifer

middle: R.

last: Knapp

state: Colorado

address: 1400 Jackson St

department: Center for Genes Envionment and Health

country: USA

institute: National Jewish Health

summary: CD8+ tumor infiltrating lymphocytes can have a range of binding strengths for a single tumor associated antigen. The impact this has on the transcriptional profile of the diverse CD8+ tumor infiltrating lymphocyte population was investigated by single cell RNA sequencing.

overall_design: Cells were isolated from the CT26 colon carcinoma tumor, CD8 T cells were enriched for by magnetic isolation, and stained in preparation for flow cytometry with the gp70423-431 loaded H-2Ld MHC tetramer (tetramer). CD8 T cells were isolated by fluorescence-activated cell sorting based on their capacity to bind tetramer, into high tetramer binders, low tetramer binders, and non-tetramer binders. These populations were then analyzed using scRNAseq.

first: Zachary

middle: L

last: Hay

middle: R

first: Roman

middle: E

last: Magallon

first: Brian

middle: P

last: O'Conner

first: Jill

last: Slansky


title: Differential protease content of mast cells in C57BL/6 and BALB/c mice and the   processing of IL-33 in Alternaria alternata induced allergic asthma in mice

status: Public on Oct 31 2022

city: Ghent

first: Olga

last: Krysko

address: C. Heymanslaan 10

department: Department of Head and Skin

country: Belgium

institute: Ghent University

summary: Background: Recent in vitro studies strongly implicated mast cell-derived proteases as   regulators of IL-33 activity by enzymatic cleavage in its central domain. A better   understanding of the role of mast cell proteases on IL-33 activity in vivo is needed. We aimed   to compare the expression of mast cell proteases in C57BL/6 and BALB/c mice, their role in   the cleavage of IL-33 cytokine, and their contribution to allergic asthma.  Results: In vitro, full-length IL-33 protein was efficiently degraded by mast cell supernatants   of BALB/c mice in contrast to the mast cell supernatants from C57BL/6 mice. RNAseq   analysis indicated major differences in the gene expression profiles of bone marrow-derived   mast cells from C57BL/6 and BALB/c mice, showing two major gene clusters. In Alt-treated   C57BL/6 mice the full-length form of IL-33 was mainly present, while in BALB/c mice, the   processed shorter form of IL-33 was more prominent. The observed cleavage pattern of IL-33   was associated with a nearly complete lack of mast cells and their proteases in the lungs of   C57BL/6 mice. While most inflammatory cells were similarly increased in Alt-treated   C57BL/6 and BALB/c mice, C57BL/6 mice had significantly more eosinophils in the   bronchoalveolar lavage fluid and IL-5 protein levels in their lungs than BALB/c mice.   Conclusion: Our study demonstrates that lung mast cells differ in number and protease   content between the two tested mouse strains, affecting IL-33 processing and inflammatory   outcome of Alt -induced asthma. We suggest that mast cells and their proteases play a   protective role in IL-33-induced lung inflammation by limiting its proinflammatory effect via   the IL-33/ST2 signaling pathway.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for BMMCs of BALB/c and C57BL/6 mice on day 20.

first: Korsakova

last: Darya

first: Andrea

last: Teufelberger

first: Amse

last: De Meyer

last: Steels

first: Natalie

last: De Ruyck

first: Judith

last: van Ovost

first: Sharon

last: Van Nevel

first: Gabriele

last: Holtappels

first: Frauke

last: Coppiters

first: Mikhail

last: Ivanchenko

first: Harald

last: Braun

first: Maria

last: Vedunova

first: Dmitri

middle: V

first: Claus

last: Bachert


title: Plasma Small Extracellular RNA as a Biomarker of Autoimmune Flairs and Beta Cell Death in Type 1 Diabetes Using Frequent Prospective Peri-Onset Sampling

status: Public on Oct 30 2022

city: Houston

first: exRNA

last: BRL

state: TX

address: One Baylor Plaza

department: Molecular & Human Genetics - Milosavljevic

institute: Baylor College of Medicine

type: Non-coding RNA profiling by high throughput sequencing

summary: We seek to discover small RNA biomarkers of autoimmune activity andor beta cell damage in type 1 diabetes. Pilot studies showed that heparinized plasma failed analyses, but that EDTA and citrated plasma did well, so 353 appropriate plasma samples average 11 per subject prospectively collected every 1 to 3 months from 32 high risk MAB or newly diabetic children and adolescents were collected, and the first 94 analyzed, for circulating small regulatory RNAs. 92 of 94 resulting cDNA libraries gave adequate numbers of miRNA mapped reads, but QC using spiked RNA internal standards showed abnormally high small RNA levels in 8 mildly hemolyzed plasma samples, leaving 84 of 94 with analyzable data. Equal numbers of EDTA and citrated plasma were analyzed successfully. Over the next period we will complete series on another 6 subjects, sequence the remaining 26070340 samples, and analyze the data for patterns of disease association with small RNA molecules in the prediabetic, perionset, and immediate post onset period. These patterns may identify biomarker small RNA predictive of autoimmune flares or beta cell loss, including predicting impending clinical onset.

overall_design: smRNA-seq of longitudinal plasma samples from 36 individuals, no replicates

first: David

last: Galas

first: William

last: Hagopian

first: Andrew

last: Banman

first: Alton

last: Etheridge

first: Nikita

last: Sakhanenko


title: Estrogen Receptor Beta 1: A Potential Therapeutic Target for Triple Negative Breast Cancer

status: Public on Oct 28 2022

city: Urbana

first: Yvonne

last: Ziegler

state: IL

address: 407 S Goodwin Ave.

department: MIP

institute: University of Illinois

summary: Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). These receptors are well characterized and often serve as targets in breast cancer treatment. As a result, TNBCs are difficult to treat and have a high propensity to metastasize to distant organs. For these reasons, TNBCs are responsible for over 50% of all breast cancer mortalities while only accounting for 15% - 20% of breast cancer cases. However, estrogen receptor beta 1 (ERβ1) has emerged as a potential therapeutic target in the treatment of TNBCs. Using an in vivo xenograft preclinical mouse model with human TNBC, we found that expression of ERβ1 significantly reduced both primary tumor growth and metastasis in the animals. Moreover, TNBCs with elevated levels of ERβ1 showed reduction in epithelial-to-mesenchymal transition (EMT) markers and breast cancer stem cell (BCSC) markers, and increases in the expression of genes associated with inhibition of cancer cell invasiveness and metastasis, suggesting possible mechanisms underlying the antitumor activity of ERβ1. Treatment with ERβ1 agonist ligand often enhanced the suppressive activity of ERβ1, suggesting their potential utility in improving TNBC treatment. The findings enable understanding of the mechanisms by which ERβ impedes TNBC growth, invasiveness and metastasis and consideration of ways by which treatments involving ERβ might improve TNBC patient outcome.

overall_design: Examine how the presence of liganded and unliganded estrogen receptor beta isoform 1 influences gene expression, growth and metastasis of triple negative breast cancer cells.

first: Parama

last: Dey

first: Alexander

last: Wang

first: Sandeep

last: Kumar

first: Shunchao

last: Yan

first: Sung

middle: H

last: Kim

first: John

middle: A

last: Katzenellenbogen

first: Benita


title: Dendrimer-targeted immunosuppression of microglia reactivity further enhances promotes photoreceptor regeneration kinetics in the zebrafish retina

status: Public on Oct 25 2022

city: Baltimore

first: Kevin

last: Emmerich

state: MD

address: 400 N Broadway

department: Human Genetics

institute: Johns Hopkins University

summary: We used a zebrafish model of inducible rod photoreceptor death and investsgate the effect of Dexamethasone and nanoparticle-conjugated Dex on regeneration kinetics

overall_design: We used bulk-RNA seq to analyze expression of zebrafish eyes at 7 days old that were untreated, treated with Mtz (to kill rods), treated with Mtz + D-Dex (induce immunosupression) or treated with D-Dex alone

first: Jeff

last: Mumm


title: Next Generation Sequencing Facilitates Quantitative Analysis of control of Pseudomonas aeruginosa PAO1 and geraniol-treated P. aeruginosa PAO1 Transcriptomes

status: Public on Dec 08 2022

city: Guangzhou

first: Wenru

last: Li

address: No.100, Xianliezhong Road

institute: Institute of Microbiology, Guangdong Academy of Sciences

summary:
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare transcriptome profiling of control of P. aeruginosa PAO1 (RNA-seq) to transcriptome profiling of geraniol-treated P. aeruginosa PAO1 and to evaluate protocols for optimal high-throughput data analysis.
Methods:LB medium (50 mL) was inoculated with exponential growth phase P. aeruginosa PAO1 at a concentration of 1.0E8 CFU/mL. Diallyl trisulfide  was then added at a concentration of either 0 (control) or 0.63 μl/mL, respectively, in triplicate. All nine experiment groups were incubated in a water bath shaker at 37 ºC with a shaking rate of 180 rpm for 5 h. Cells were then sampled and centrifuged from the three control groups and three farnesol treatment groups, respectively. The cell precipitates were separately snap-frozen at -80ºC.  Total RNA was isolated from cells using Trizol (Life Technologies, USA) according to the manufacturer’s protocol.
Results: The transcriptome sequencing data of control and geraniol-treated groups were compared and analyzed in the form of the following: control vs geraniol. The details of the differentially expressed genes among the two groups showed that the amount of differential expressed genes between control group and geraniol-treated group was high (total 5788, up-regulated 1169, down-regulated 852).

overall_design: The mRNA profiles of P. aeruginosa PAO1 (control) and geraniol-treated P. aeruginosa PAO1  were generated by deep sequencing, in triplicate, using Illumina Higseq 2000.

first: Wen-Ru

first: Zhi-Qing

last: Zhang


title: Telomere-to-mitochondria signaling by ZBP1 mediates replicative crisis (RNA-Seq)

status: Public on Dec 12 2022

city: La Jolla

first: Jingting

last: Yu

state: CA

address: 10010 N Torrey Pines Rd

institute: Salk Institute for Biological Studies

summary: Transcriptional response to telomere shortening or dysfunction

overall_design: Comparative gene expression profiling analysis of RNA-seq data for growing and crisis IMR90E6E7 (3 replicates each); growing and crisis WI38SV40LT (3 replicates each), pre-crisis IMR90E6E7 transfected with non-targeting siRNA (control) or two individual siRNAs against ZBP1 (3 replicates each), growing IMR90E6E7 expressing either a dox-inducible TRF1(DN) or dox-inducible VP16-TRF1(DN) and constitutive expression of either ZBP1(S)WT-Flag or ZBP1(S)DZa2-Flag (3 replicates each), and pre-crisis IMR90E6E7 expressing GFP-targeting gRNA (control), MAVS-targeting gRNA, or STING-targeting gRNA (2 replicates each).

first: Joe

last: Nassour

first: Jan

last: Karlseder


title: Aging-associated changes in gene expression of the lung tissue of the National Center for Geriatrics and Gerontology (NCGG) C57Bl/6J mice

status: Public on Oct 20 2022

city: Obu

first: Masataka

last: Sugimoto

state: Aichi

address: 7-430 Morioka-cho

department: Cellular Pathology

summary: To investigate the aging-associated gene expression in lung tissue of the National Center for Geriatrics and Gerontology (NCGG) Aging Farm mice, RNA was prepared from lung of the male 3-, 6-, 12- and 24-month-old C57Bl/6J  mice. RNA was subjected to RNA-seq and the gene expression profiling analysis.

overall_design: Three mice were independently analyzed for each age.

first: Koichiro

last: Kawaguchi

first: Mitsuo

last: Maruyama

first: Noboru

last: Ogiso


title: Mapping of matrsisome production by alveolar epithelial cells cultured in decellularized human lung scaffolds

city: Lund

first: Oskar

last: Rosmark

address: Sölvegatan 19

department: Experimental medical science

institute: Lund university

summary: The alveolar epithelial cells are known producers of basement membrane components of the ECM, we hypothesize that they may also contribute substantially to remodeling of interstitial ECM in the alveolar compartment in chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Primary human alveolar type II epithelial cells (AECII) were isolated from human lungs without lung disease or with end stage COPD, using the surface marker HT2-280. Isolated cells were cryopreserved without prior expansion and then directly seeded into decellularized distal lung parenchyma from healthy human lungs. Cells were cultured for 13 days with addition of a profibrotic stimuli in the form of 2 ng/ml of TGF-ß1 at day 7, to a subgroup samples with cells derived from healthy lungs. AECII cells comes from 5 healthy cell donors and 3 with COPD, decellularized scaffolds were prepared from 5 different healthy lungs. The data set contains a total of 71 samples each representing a unique cell/scaffold/treatment combination at either day7 or day 13 of culture. For each sample there exists a matched proteomics sample from mass spectrometry analysis deposited to the ProteomeXchange Consortium via the PRIDE partner repository. The data indicate a substantial potential of alveolar epithelial cells to directly contribute to matrisome turnover and ECM remodeling in the lung.

overall_design: AECII cells comes from 5 healthy cell donors and 3 donors with end stage COPD. Decellularized scaffolds were prepared from 5 different healthy lungs. The data set contains a total of 71 samples each representing a unique cell/scaffold/treatment combination at either day 7 or day 13 of culture.

first: Måns

last: Kadefors


title: Transcriptome analysis of microglia at day 3 and 20 following sepsis induction

status: Public on Oct 17 2022

city: Jena

first: Philipp

last: Koch

address: Beutenbergstraße 11

department: Core Facility Life Science Computing

country: Germany

institute: Leibniz Institute on Aging - Fritz Lipmann Institute

summary: Sepsis-associated encephalopathy is a common complication during systemic inflammation. Microglia are key player in this process. For a better understanding we compared isolated microglia from mice at day 3 and day 20 following induction of polymicrobial sepsis. We found a long-lasting inflammatory response of microglia following sepsis.

overall_design: 14 samples in 4 groups: 1) 4 replicates: No PCI treatment (sham), extraction after 3 days. 2) 4 replicates: PCI treatment, extraction after 3 days. 3) 3 replicates: No PCI treatment (sham), extraction after 20 days. 4) 3 replicates: PCI treatment, extraction after 20 days.

first: Marco

last: Groth

first: Ha-Yeun

last: Chung

first: Christian

last: Geis


title: Swc4 protects nucleosome free chromatin of telomeres, tRNA genes and rDNA loci to inhibit genome instability

status: Public on Oct 14 2022

first: Yue

last: Pan

address: 320 Yue Yang Road

department: Center for Excellence in Molecular Cell Science, CAS

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

type: Genome binding/occupancy profiling by high throughput sequencing

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

relation:
SuperSeries of: GSE202946
SuperSeries of: GSE215374
SuperSeries of: GSE233269

overall_design: Refer to individual Series


title: Replication transcriptome of Pseudomonas aeruginosa

status: Public on Nov 07 2022

city: Třeboň

first: Jürgen

last: Tomasch

address: Novohradská 237

country: Czech Republic

institute: Center Algatech, Institute of Microbiology of the Czech Academy of Science

summary: Transcriptiomes of non-replicating, replicating and pre-divisonal P. aeruginosa PA14 FACS subpopulations during replication-coupled growth in  LB medium.

overall_design: Three biological replicates for sorted subpopulations and RNAprotect- or formaldehyde-fixed and unsorted cells as controls.

first: Kathrin

last: Alpers

first: Susanne

last: Häussler


title: Explore plasma exosomal derived lncRNA and mRNA expression in adolescent with major depressive disorder

status: Public on Nov 17 2022

city: Taiyuan

first: Yifan

last: Xu

address: 85# of Jie Fang Road

institute: First Hospital of Shanxi Medical University

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

summary: Major Depressive Disorder (MDD) during adolescence significantly jeopardizes both mental and physical well-being. However, the etiology underlying MDD in adolescents remains unclear. Extracellular vesicles (EVs), long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) played significant roles in regulating various biological processes. 10 drug-naïve adolescents with MDD patients and 10 age, sex matched healthy control were enrolled. Draw whole blood from the cubital vein from participants, plasma was centrifuged at 3500rpm 10min. An exoRNeasy Midi and Maxi Kits were used to isolate the plasma exosome and extract exosomal RNA per the manufacturer’s instruction. Microarray technology was used to detect lncRNAs and mRNAs. Bioinformatics analysis was applied to explore function of differential expression genes and screen candidate genes.

overall_design: 10 drug-naïve adolescent with MDD patients and 10 age, sex matched healthy control were enrolled to isolate plasma from whole blood. Plasma exosomal derived RNA was extracted and microarray technology was used to detect lncRNAs and mRNAs, bioinformatics analysis was applied to explore function of differential expression genes and screen candidate genes.

first: Zhifen

last: Liu


title: Transcriptomic study (RNAseq) of diurnal expression of Brachypodium distachyon ecotypes Bd21 and Bd21-3 under submergence stress

status: Public on Oct 15 2022

city: Tuxtepec, OAX

first: Julian

middle: M

last: Pena-Castro

state: South America

address: Circuito Central 200

department: Biotechnology

country: Mexico

institute: Universidad del Papaloapan

summary: To study the diurnal transcriptome (RNA-seq) expressed by the monocot model plant B. distachyon under submergence stress, we analyzed two different ecotypes (Bd21, submergence sensitive; Bd21-3, submergence tolerant) at 5 different time points (dawn, ZT0; midday, ZT8; dusk, ZT16; middnight ZT20, end of night, ZT24).

overall_design: We studied mRNA expression in aerial plant tissue of submerged plants (S) and two types of controls: low light controls (LL) and normal growth controls (NG). All samples had 3 biological replicates. Each replicate consisted of a pool of 5 plants.

first: Julián

last: Peña-Castro

first: Piyada

last: Juntawong

first: Lucisabel

last: Medina-Chávez


title: Enterococcus Grad-seq and KhpB RIP-seq

status: Public on Nov 03 2022

city: Würzburg

first: Jörg

last: Vogel

address: Josef-Schneider-Straße 2

department: Institute for Molecular Infection Biology

institute: Würzburg University

summary: We investigated the RNA-protein interactome of Enterococcus faecalis V583 and Enterococcus faecium Aus0004 by native gradient fractionation of complexes coupled to RNA-sequencing. Whole bacterial cell lysates were analysed by size and density in a glycerol gradient. At native conditions, RNA-protein complexes stay intact and sediment as a whole. Sedimentation profiles of individual RNAs appear correlated in case of interaction in a complex. The profile of KhpB caught our attention and we determined its RNA interactome by immunoprecipitation that suggests a role at the post-transcriptional level, binding notably several tRNAs, sRNAs, and 3’UTRs.

sample_organism:
Enterococcus faecalis V583
Enterococcus faecium Aus0004

overall_design: Cellular lysate was analysed by gradient fractionation into 20 fractions plus the Pellet (P) for E. faecalis and faecium. Subsequently, RNA samples were prepared and sequenced to obtain sedimentation profiles of RNAs. For the RNA-immunoprecipitation of KhpB, we raised two antibodies (Ab1, Ab2) against E. faecalis KhpB, precipitated KhpB from E. faecalis lysate, and sequenced RNA interaction partners, the pre-immune-serum (ctrl1,ctrl2) was used as a negative control.

first: Milan

last: Gerovac

first: Charlotte

last: Michaux


title: RNA-seq data of "Tfap2b acts in GABAergic neurons to control sleep in mice"

city: Goettingen

first: Yang

last: Hu

institute: MPIBPC

summary: We investigated how Tfap2b regulates gene expression during embryonic development. Tfap2b +/+ as controls  and Tfap2b-/- as mutant embryos at stage E14.5 were collected for RNA-sequencing.

overall_design: Brains from E14.5 embryos were extracted and dissected into prosencephalon (SP) and diencephalon/midbrain/hindbrain (DMH) areas from three female and three male individuals per sex and genotype. Thus, we used 12 embryos x 2 brain ares, which made into 24 samples in total. Four comparisons were made between genotypes in the same brain areas: male SP control v.s. male SP mutant; male MDH control v.s. male MDH mutant; female SP control v.s. female SP mutant;female MDH control v.s. female MDH mutant.

first: Henrik

last: Bringmann


title: NURD dependent Reprogramming by Sall4-Jdp2-Esrrb-Glis1 (ChIP-seq)

status: Public on Oct 12 2022

first: Li

last: Chen

state: Guangdong province

address: 190 Kai Yuan Avenue, Science Park

institute: Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences

summary: Cell fate decision involves rewiring of the genome, but remains poorly understood at the chromatin level. We report a system to reprogramming somatic cells to pluripotency by four factor combination (Sall4, Esrrb, Jdp2, Glis1). Mechanism study demonstrate that the Sall4-NuRD axis plays a critical role in the early phase of reprogramming. These results identify a previously unrecognized role of NuRD in reprogramming, may help establish early chromatin closing as a pre-requisite step in cell fate control.

overall_design: Based on a reprogramming system of 4 factor (WT/N12 Jdp2, Esrrb, Glis1, WT/K5A Sall4), knocking down Gatad2b, Chd4 or dropout single factor.

first: Wang

last: Bo

first: Ming

last: Jin


title: Estrogen receptor alpha mutations regulate gene expression and cell growth in breast cancer through microRNAs

status: Public on Oct 05 2022

city: Salt Lake City

first: Jason

last: Gertz

state: UT

address: 1950 Cir of Hope Dr

institute: University of Utah


title: Tissue fluidification promotes a cGAS/STING-mediated cytosolic DNA response in invasive breast cancer [RNA-seq of Organoids]

status: Public on Sep 28 2022

city: Milan

first: Giorgio

last: Scita

state: Mi

address: via Adamello, 16

country: Italy

institute: IFOM, The AIRC Institute of Molecular Oncology

summary: The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state that occurs in various tissues. Whether this tissue-level mechanical transition impact phenotypes during carcinoma progression remains unclear. We show, here that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. Cells react to these protracted mechanical stresses by mounting a mechano-protective response that includes enlarged nuclear size and rigidity, altered heterochromatin distribution, and the remodeling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS/STING-dependent cytosolic DNA response gene program. This mechanically-driven transcriptional rewiring ultimately results in a change in cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemo-resistance in invasive breast carcinoma.

overall_design: RNA-seq,  2 conditions (rotating and non-rotating), 5 organoids (3 rotating and 2 non-rotating) derived from 5 patients

first: Emanuela

last: Frittoli

first: Andrea

last: Palamidessi

first: Fabio

last: Iannelli

first: Federica

last: Zanardi

first: Giulia

last: Della Chiara

first: Massimiliano

last: Pagani


title: Gene expression analysis of  bleomycin-challenged mouse lung tissues with/without repetitive hyperbaric oxygen treatment

status: Public on Sep 29 2022

city: Southampton

first: Yihua

last: Wang

address: University Road

country: United Kingdom

institute: University of Southampton

summary: Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive disease leading to death with few effective treatments. Our previous study suggested that repetitive hyperbaric oxygen (HBO) treatment alleviates bleomycin-induced pulmonary fibrosis in mice, but the underlying mechanism is not clear. In this study, we compared the RNA-seq data from bleomycin challenged mouse lung tissues with or without repetitive HBO treatment, to figure out the affected biological processes and pathways. Combined with integrative analysis of public data from GEO, our study support HBO treatment as a viable strategy against pulmonary fibrosis.

overall_design: Six to eight weeks old male C57BL/6 mice (20-25 g) after bleomycin instillation were randomly divided into bleomycin (BLM) group and BLM+HBO group in day 7 post bleomycin instillation. Then mice in BLM+HBO group were exposed to repetitive HBO treatment (2.5 ATA, 90 min/time/day) for 14 consecutive days, while the mice in the BLM group were placed in the chamber for the same duration without pure oxygen pressurization. The lung tissues were collected at day 21. RNA-seq based on next generation sequencing was applied with 4 samples in bleomycin group and 3 samples in bleomycin + HBO group.

first: Yuan

last: Yuan

first: Guoqiang

last: Qiao

first: Jiajiao

last: Zhou

first: Yilu

first: Xia

last: Li

first: Zhenglin

last: Jiang


title: Structural variants drive context dependent oncogene activation in cancer

status: Public on Oct 04 2022

first: Jesse

last: Dixon

address: 10010 N. Torrey Pines Rd.

summary: Higher order chromatin structure is important for regulation of genes by distal regulatory sequences. Structural variants that alter 3D genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer. However, only a small minority of structural variants are associated with altered gene expression and it remains unclear why certain structural variants lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation. By analyzing Hi-C data from 92 cancer cell lines and patient samples, we identified loci affected by recurrent alterations to 3D genome structure, including oncogenes such as MYC, TERT, and CCND1. Using CRISPR/Cas9 genome engineering to generate de novo structural variants, we show that oncogene activity can be predicted using “Activity-by-Contact” models that consider partner region chromatin contacts and enhancer activity. However, Activity-by-Contact models are only predictive of specific subsets of genes in the genome, suggesting that different classes of genes engage in distinct modes of regulation by distal regulatory elements. These results indicate that structural variants that alter 3D genome organization are widespread in cancer genomes and begin to illustrate predictive rules for the consequences of structural variants on oncogene activation.

overall_design: Analysis of Hi-C data and structural variant in 92 cancer samples and cell lines. Analysis of Hi-C and RNA-seq data in 37 engineered cell lines. Of note, 10 of the samples from the Xu et al. study were from primary human patient tumor samples and are available through dbGap accession phs003227.


title: Microglia mediate neurocognitive deficits by eliminating C1q tagged synapses in sepsis-associated encephalopathy

first: Philipp

last: Koch


title: Transcriptome analysis of microglia depleted and non-depleted hippocampus tissue

summary: Sepsis-associated encephalopathy is a common complication during systemic inflammation. Microglia are key player in this process. For a better understanding we compared hippocampal tissue following sepsis induction of microglia depleted and non-depleted mice. We show an overall reduction of inflammatory response in the hippocampus of microglia depleted animals.

overall_design: 24 samples, 4 replicates in each group. 6 groups: 1) No PCI treatment (sham), normal diet (AIN), extraction after 3 days. 2) PCI treatment, normal diet (AIN), extraction after 3 days. 3) No PCI treatment (sham), normal diet (AIN), extraction after 10 days. 4) PCI treatment, normal diet (AIN), extraction after 10 days.  5) No PCI treatment (sham), PLX5622 diet (PLX), extraction after 10 days. 6) PCI treatment, PLX5622 diet (PLX), extraction after 10 days.

first: Marco

last: Groth

first: Ha-Yeun

last: Chung

first: Christian

last: Geis


title: Transcriptome changes with GSK-J4 treatment in an ex vivo post-cataract surgery model

status: Public on Sep 20 2022

city: Philadelphia

first: Morgan

last: Basta

state: Pennsylvania

address: 1020 Locust Street

institute: Thomas Jefferson University

summary: Cell reprogramming to a myofibroblast responsible for the pathological accumulation of extracellular matrix is fundamental to the onset of fibrosis. Here, we explored how condensed chromatin structure marked by H3K72me3 becomes modified to allow for activation of repressed genes to drive emergence of myofibroblasts. In the early stages of myofibroblast precursor cell differentiation, we discovered that H3K27me3 demethylase enzyme UTX creates a delay in the accumulation of H3K27me3 on nascent DNA revealing a period of decondensed chromatin structure. This period of decondensed nascent chromatin structure allows for binding of pro-fibrotic transcription factor, MRTF-A to nascent DNA. Inhibition of UTX enzymatic activity condenses chromatin structure, prevents MRTF-A binding, blocks activation of the pro-fibrotic transcriptome, and results in an inhibition of fibrosis in lens and lung fibrosis models. Our work reveals UTX as a central coordinator of fibrosis, highlighting the potential to target its demethylase activity to prevent organ fibrosis.

overall_design: Comparative gene expression profiling analysis using data obtained from mRNA-seq of chicken lenses treated with vehicle control (DMSO) or GSK-J4

first: Janice

last: Walker


title: Application of annotation-agnostic RNA sequencing data analysis tools for biomarker discovery in liquid biopsy.

status: Public on Sep 22 2022

city: Moncton

first: Rodney

last: Ouellette

address: 35 Providence St.

country: Canada

institute: ATLANTIC CANCER RESEARCH INSTITUTE

summary: We demonstrate an agnostic method to identify transcribed fragments from small Rna-Seq data using ALS patients and healthy donorâ€™s plasma.

overall_design: Plasma Extracellular Vesicles were isolated using Vn96 from Control donor plasma and ALS patients.

first: Gabriel

last: Wajnberg

first: Eric

last: Allain

first: Annie-Pier

last: Beauregard

first: Jeremy

last: Roy

first: Shruti

last: Srivastava

first: Daniel

last: Saucier

first: Pier

middle: J

last: Morin

first: Andrew

last: Joy

first: Alier

last: Marrero

first: Colleen

last: O'Connell

first: Anirban

last: Ghosh

first: Stephen

last: Lewis

first: Nicolas

last: Crapoulet


title: NURD dependent Reprogramming by Sall4-Jdp2-Esrrb-Glis1

first: Li

last: Chen


title: NURD dependent Reprogramming by Sall4-Jdp2-Esrrb-Glis1 (RNA-seq)

first: Wang

last: Bo

first: Ming

last: Jin


title: Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling (Mouse II).

status: Public on Sep 16 2022

city: Cincinnati

first: Yan

last: Xu

state: OH

address: 3333 Burnet Ave

institute: Cincinnati Children's Hospital Medical Center

summary: Pulmonary fibrosis results from dysregulated repair of damaged tissue caused by persistent injury of lung epithelium. Multiple cell types in the lung are involved in the process of repair.  During lung fibrogenesis, normal endothelial cells (EC) are re-programmed into fibrosis-associated EC. Transcriptional factors that control re-programming are poorly understood. Using single cell RNA-sequencing of EC from donor and idiopathic pulmonary fibrosis (IPF) lungs, and lungs from bleomycin-treated mice, we identified endothelial transcription factors (TF) that were differentially expressed during fibrosis.  Focusing on one of endothelial TF, FOXF1, we demonstrated that FOXF1 is decreased in EC within human IPF and mouse bleomycin-injured fibrotic lungs.

overall_design: Dissociated single-cell preparations from bleomycin treated both tamoxifen- induced deletion in endFoxf1+/- mice (n = 3; PdGFb-creER; foxf1fl/+ ) and control mice (n=3; foxf1fl/+) were enriched for endothelial cells by FACS for CD45 (hematopoietic) negative, CD31 (endothelial) positive cells after dissociation by proteases. RNA from endothelial cells were extracted.

first: Fenghua

last: Bian

first: Tien

last: Le

first: Shuyang

last: Zhao

first: Matthew

last: Bacchetta

first: Ahmed

last: Hozain

first: Yuliya

last: Tipograf

first: Tanya

last: Kalin


title: NURD dependent Reprogramming by Sall4-Jdp2-Esrrb-Glis1 (ATAC-seq)


title: A previously uncharacterized Kidney-Associated Membrane Protein (KAMP) is associated with evolutionary adaptation, energy balance and kidney physiology

status: Public on Oct 01 2022

city: Vienna

first: Irina

last: Poverennaya

state: Österreich

address: Spitalgasse 4 / Medizinishe Universitat Wien, Zentrum fur Hirnforschung

department: Neuroimmunology

country: Austria

institute: Medical University of Vienna

summary: During the evolution of vertebrates, specific molecular innovations ensured adaptations which resulted in the split of different animal groups. Here comparative genomic analysis became a valued instrument to identify genes associated with the divergence of taxa and speciation events. Using this approach, we identified the association of the previously uncharacterized gene (mouse (1700011H14RIK, human C14ORF105/CCDC198), hereby named Kamp (Kidney-associated membrane protein) with the evolutionary split leading to birds and mammals. Furthermore, by comparing single nuclear polymorphisms of modern humans with Neandertals at the locus of Kamp, we identified gene-flow of Kamp from Neandertals into modern humans.  Analyzing the expression of Kamp in humans revealed a restriction to the kidney, pancreas, and few other organs. A knockout of this gene in mice resulted in a structurally normal kidney as validated with micro-computed microtomography scans and single-cell transcriptomics, but with higher Albumin levels in the urine lower serum ferritin levels. Further, interactomics screening revealed an interaction between KAMP and ferritin (heavy chain), which was cross-validated by the analysis of co-localization of both proteins in vesicular and plasma membranes. The membranal localization of KAMP appeared regulated by its N-terminal myristoylation site, as KAMP became cytoplasmic in the absence of this specific sequence. Kamp knockout animals demonstrated increased body weight and decreased energy expenditure. This corresponded to Genome-Wide Association Studies of Kamp linked with higher BMI, diabetes-related pathologies, and macular degeneration in humans. Subsequent gain-of-function experiments showed altered proliferative dynamics and accumulation of KAMP during mitosis. Bioinformatics analysis indicated a protective role of KAMP in renal and liver cancer progression, as suggested by an association of KAMP with epithelial-to-mesenchymal transition and altered localization in tumors versus healthy tissue. Altogether, our results revealed several important roles played by KAMP in a vertebrate body, with specific emphasis on metabolite excretion and energy expenditure.

overall_design: The kidneys of widltype and KAMP knock-out mutant littermate mice (both male and female) were dissected out, dissociated and then subjected to single cell transcriptomics sequencing using 10x Chromium approach.

first: Julian

last: Petersen

first: Artem

last: Artemov

first: Maria

last: Kastriti

first: Thibault

middle: G

last: Bouderlique

first: Igor

last: Adameyko


title: Transcriptomic analysis on effects of 1-methylcyclopropene (1-MCP) and ethylene treatment of kiwifruit (Actinidia chinensis) ripening

status: Public on Oct 07 2022

city: Anseong-si

first: Dasom

last: Choi

state: Gyeonggi-do

address: 4726, Seodong-daero

country: South Korea

institute: Chung-Ang University

summary: We identified oppositely responsive TFs during ripening which are potentially key signaling factors of ET- or 1-MCP-mediated physiological changes.

overall_design: Control (untreated) and ET or 1-MCP treated fruits of the green kiwifruit “Hayward” for RNA-seq analysis were harvested at 0, 3, 5, and 7 days after treatment.

first: Jeonghee

first: Jungho

last: Lim

first: Dong-Hwan

last: Kim


title: Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [RNA-seq]

city: Shanghai

first: Ting

last: Guo

state: Shanghai

address: Shanghai Putuo District,Luding road No.355

department: Department of General surgery

institute: Shanghai Children's Hospital

summary:
To determine which signaling pathway may have been affected by HDAC8, we designed NEC mice model with PCI34051 supplementation.
We then performed gene expression profiling analysis using data obtained from RNA-seq of intestinal tissues (control group, NEC group, PCI34051+NEC group)  treated with PCI34051 (10 mg/kg/d).

overall_design: Comparative gene expression profiling analysis of RNA-seq data for intestinal tissues from control or NEC mice under the condition of  PCI34051 (10 mg/kg/d,once a day for 5 days) treatment.

first: Shaohua

last: Hu

first: Weijue

last: Xu

first: Jin

last: Zhou

first: Feng

last: Chen

first: Tingting

last: Gao

first: Wenqian

last: Qu

first: Faling

first: Zhibao

last: Lv

first: Li

last: Lu


title: Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling (Human).

first: Yan

overall_design:
Using the 10x Chromium platform sequencing, transcriptomes of single cells from donor human lung and IPF patient lung were analyzed.
----------------------------------
Authors state "raw data will be submitted to dbGap".

first: Fenghua

last: Bian

first: Tien

last: Le

first: Shuyang

last: Zhao

first: Matthew

last: Bacchetta

first: Ahmed

last: Hozain

first: Yuliya

last: Tipograf

first: Tanya

last: Kalin


title: Tissue fluidification promotes a cGAS/STING-mediated cytosolic DNA response in invasive breast cancer [SAMMY-seq]

status: Public on Sep 27 2022

first: Giorgio

last: Scita

overall_design: SAMMY-seq analysis was performed in three biological replicates for of control and RAB5 overexpression samples in MCF10DCIS.com cells.

first: Chiara

last: Lanzuolo

first: Cristiano

last: Petrini

first: Francesco

last: Ferrari

first: Andrea

last: Palamedessi

first: Emanuela

last: Frittoli


title: Estrogen receptor alpha mutations regulate gene expression and cell growth in breast cancer through microRNAs (NanoString)

first: Jason

last: Gertz

summary: Estrogen receptor α (ER) mutations occur in up to 30% of metastatic ER-positive breast cancers. Recent data has shown that ER mutations impact the expression of thousands of genes not typically regulated by wildtype ER. While the majority of these altered genes can be explained by constant activity of mutant ER or genomic changes such as altered ER binding and chromatin accessibility, as much as 33% remain unexplained, indicating the potential for post-transcriptional effects. Here we explored the role of microRNAs in mutant ER-driven gene regulation and identified several microRNAs that are dysregulated in ER mutant cells. These differentially regulated microRNAs target a significant portion of mutant-specific genes involved in key cellular processes. When the activity of microRNAs is altered using mimics or inhibitors, significant changes are observed in gene expression and cellular proliferation related to mutant ER. An in-depth evaluation of miR-301b led us to discover an important role for PRKD3 in the proliferation of ER mutant cells. Our findings show that microRNAs contribute to mutant ER gene regulation and cellular effects in breast cancer cells.

overall_design: microRNA profiles from T-47D breast cancer ESR1 mutant or WT cell lines and from ESR1 mutant or WT breast cancer patient derived xenograft (PDX) models

first: Spencer

last: Arnesen


title: Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer

city: Singapore

first: Khine

last: Myint

address: 14 Medical Drive

department: Medicine

country: Singapore

institute: Cancer Science Institute/NUS

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

overall_design: Refer to individual Series


title: Histone methylation regulates reproductive diapause in Drosophila melanogaster

first: Abigail

last: DiVito Evans

address: 433 S University Ave, 205 Carolyn Lynch Lab

department: Biology

institute: University of Pennsylvania

summary: RNA-seq on Drosophila melanogaster ovary (stages 1-7) in: diapause at 12ºC (after 28 days), reproductive at 12ºC (after 28 days), and age-matched control at 25ºC in two inbred genotypes. Each biological replicate is a pool of 25 ovary pairs, and each treatment has three biological replicates.

overall_design: Comparative gene expression analysis of RNA-seq comparing diapause, reproductive, and age-matched control ovaries of two inbred genotypes ("High Plasticity", or HP, and "Low Plasticity", or LP)

first: Regina

last: Fairbanks

first: Paul

last: Schmidt

first: Mia

middle: T

last: Levine


title: Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer [RNA-Seq]

summary: We reported earlier that IQGAP3 is an important stem cell factor in rapidly proliferating  isthmus stem cells in the stomach. Furthermore, we observed robust induction of  IQGAP3 expression in terminally differentiated chief cells and de-differentiated cells  following tissue damage. The elevated expression of IQGAP3 in cancer and its  association with metastasis suggest a fundamental role for IQGAP3 in proliferating  cancer stem cells. What causes the upregulation of IQGAP3 in cancer is unclear. Here,  we show that IGF2BP1 and IQGAP3 expression levels are highest in the blastocyst,  with both showing decreases during adulthood. This suggests that IQGAP3, like  IGF2BP1, is an early developmental gene that is aberrantly upregulated upon reexpression  of IGF2BP1 during carcinogenesis. We found that IGF2BP1 binds and  stabilizes m 6 A-modified IQGAP3 transcripts. Furthermore, downstream targets of  IGF2BP1, namely SRF and FOXM1, also upregulate IQGAP3 expression. These  multiple layers of IQGAP3 regulation, which may safeguard against inappropriate stem  cell proliferation, present additional drug targets to inhibit IQGAP3-driven malignant growth.

overall_design: RNA expression profile of NTERA2 cells treated with sicontrol, siSRF, siIGF2BP1, siFOXM1 and siIQGAP3 for 7 days. Total RNA from the cell pellets was extracted using RNeasy Kit (Qiagen) with the removal of genomic DNA using the RNase-free DNase Set (Qiagen) according to the manufacturer’s instructions. RNA samples were sent to Beijing Genomics Institute (BGI) for cDNA synthesis, PCR amplification, transcriptome library preparation and sequencing.Triplicate samples are shown.

first: Linda

last: Chuang

first: Yu

middle: X

last: Teh

first: Nur

last: Mawan

first: Edward

last: Shi

first: Michelle

last: Mok

first: Napat

last: Nuttonmanit

first: Junichi

last: Matsuo

first: Ying

last: Li

first: Henry

last: Yang

first: Atsushi

last: Okabe

last: Kaneda

first: Motomi

last: Osato

first: Jimmy

middle: B

last: So

first: Wei

last: Yong

first: Patrick

last: Tan

first: Khay

last: Yeoh

first: Yoshiaki

last: Ito


title: Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling

first: Yan

last: Xu

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: NTF3 as a biomarker for prediction allergic diseases in children postnatal or adolescence

city: Chiayi County

first: Mita

last: Tran

address: 168 University Road

department: Biomedical Sciences

country: Taiwan

institute: National Chung Cheng University

type: Methylation profiling by genome tiling array

summary: DNA methylation alteration marks phthlate mediated transgenerational inheritance in murine allergic diseases.

overall_design:
Pregnant women attending E-Da Hospital for routine prenatal examinations in their first trimesters were consecutively recruited. We excluded pregnant women: 1) who had history of systematic diseases such as cancer, hypertension and diabetes, chronic use of corticosteroids or immunosuppressant drugs; 2) whose age was older than 45 years; and 3) whose pregnancy was multiparous. Then, the eligible study women were interviewed by a standardized questionnaire and blood and one-spot urine specimens were collected. The same study protocol was also applied to their second and third trimesters, during delivery, and 2-3 weeks after delivery, except the questionnaire was changed to one short diet questionnaire. During delivery, additional specimens of maternal stool, amniotic fluid, placenta, cord blood, and baby meconium were also collected and, 2-3 weeks after delivery, another additional specimen of breast milk was collected. All these different biospecimens have been aliquoted and stored frozen at -70oC for different studies of gene-environmental effect on pregnant women and their offspring.
Human placenta samples were collected and clasified in two groups including low and high DEHP exposure. Each group contains 6 samples. All chosen samples were done Bisulfite Epic Illumina microarray.

first: Michael

last: Chan

first: Jau-Ling

last: Suen

first: Ming-Tsang

last: Wu


title: Tissue fluidification promotes a cGAS/STING-mediated cytosolic DNA response in invasive breast cancer [ChIP-seq]

first: Giorgio

last: Scita

overall_design: ChIP-seq for H3K9me3 histone mark in control and RAB5 overexpression samples. Two replicates obtained with different antibodies are reported.

first: Giulia

last: Della Chiara

first: Massimiliano

last: Pagani

first: Andrea

last: Palamidessi

first: Emanuela

last: Frittoli


title: Tissue fluidification promotes a cGAS/STING-mediated cytosolic DNA response in invasive breast cancer [RNA-seq]

overall_design: RNA-seq, 3 replicates per condition, 2 conditions (CTR, RAB5A), 2 cell lines

first: Fabio

last: Iannelli

first: Federica

last: Zanardi

first: Stefano

last: Villa

first: Leonardo

last: Barzaghi

first: Hind

last: Abdo

first: Valeria

last: Cancila

first: Galina

last: Beznuskenko

middle: d

last: Chiara

first: Chiara

last: Malinverno

first: Dipanjan

last: Bhattacharya

last: Pisati

first: Weimiao

last: Yu

first: Viviana

last: Galimberti

first: Giuseppina

last: Bonizzi

first: Emanuele

last: Martini

first: Alexandre

last: Mironov

first: Ubaldo

last: Gioia

first: Fabrizio

last: d’Adda di Fagagna

last: Rossi

first: Marco

last: Lucioni

first: Richard

last: Tancredi

first: Paolo

last: Pedrazzoli

last: Vecchione

first: Cristiano

last: Petrini

first: Francesco

last: Ferrari

last: Lanzuolo

first: Guilherme

last: Nader

last: Foiani

first: Matthieu

last: Piel

first: Roberto

last: Cerbino

last: Giavazzi

first: Claudio

last: Tripodo


title: Differences in the phenotypes and transcriptomic signatures of chimeric antigen receptor T lymphocytes manufactured via electroporation or lentiviral transfection

status: Public on Sep 01 2022

city: Chongqing

first: Jintao

last: Zou

state: China

address: Gaotanyanstreet

institute: Army Medical University

summary: Chimeric antigen receptor (CAR)-T cell therapy is an innovative treatment for CD19-expressing lymphomas. CAR-T cells are primarily manufactured via lentivirus transfection or transposon electroporation. While anti-tumor efficacy comparisons between the two methods have been conducted, there is a current dearth of studies investigating the phenotype and transcriptome alterations induced in T cells by the two distinct manufacturing methods. Here, we established CAR-T signatures using fluorescent imaging, flow cytometry, and RNA-sequencing. A small fraction of CAR-T cells that were produced using the PiggyBac transposon (PB CAR-T cells) exhibited much higher expression of CAR than those produced using a lentivirus (Lenti CAR-T cells). PB and Lenti CAR-T cells contained a more cytotoxic T cell subsets than control T cells, and Lenti CAR-T cells presented a more pronounced memory phenotype. RNA-sequencing further revealed vast disparities between the two CAR-T cell groups, with PB CAR-T cells exhibiting greater upregulation of cytokines, chemokines, and their receptors. Intriguingly, PB CAR-T cells singularly expressed IL-9 and fewer cytokine release syndrome-associated cytokines when activated by target cells. In addition, PB CAR-T cells exerted faster in vitro cytotoxicity against CD19-expressing K562 cells but similar in vivo anti-tumor efficacy with Lenti CAR-T. Taken together, these data provide insights into the phenotypic alterations induced by lentiviral transfection or transposon electroporation and will attract more attention to the clinical influence of different manufacturing procedures.

overall_design: T cell were transduced with/without CAR gene by lentivirus(Lenti) or electroporation with PiggyBac Transposon Vector System(PB). Comparative gene expression profiling analysis of RNA-seq data for control T cells, Lenti CAR-T cells, and PB CAR-T cells.

first: Anna

last: Niu

first: Xiaopeng

last: Zhang


title: A genomic enhancer signature associates with Hepatocellular Carcinoma prognosis

status: Public on Sep 02 2022

first: Pierce

middle: Kah Hoe

last: Chow

address: 11 Hospital Cres

institute: National Cancer Center Singapore

summary: We investigated the genomic enhancer landscape of Hepatocellular Carcinoma (HCC) using H3K27ac ChIP-seq and HiC/HiChIP data from resected tumour samples of 30 patients, whose genome, transcriptome, and clinical trajectory data were available. Differential enhancer analysis revealed dysregulated enhancer loci, but without strong enrichment of underlying DNA mutation hotspots. As many of the gain-in-tumour enhancer associated genes were fetal liver hepatoblast genes, we investigated the stochastic expression pattern of the overlapping genes (epigenetic oncofetal genes) using previously published single cell RNA-seq data, in which the patients partially overlapped. The proportion of cells expressing epigenetic oncofetal genes clustered liver tissue samples into two groups - adjacent normal liver-like, or oncofetal-like. Notably, gain-in-tumour enhancer associated genes showed prognostic value, with patient clusters revealed by co-clustering the differential gene expression pattern. Altogether, we report the genomic enhancer signature that associates with differential prognosis in HCC. Findings that cohere with oncofetal reprogramming in HCC is underpinned by genome-wide enhancer rewiring. Our results present the epigenetic changes in HCC that offer the rational selection of epigenetic-driven gene targets for therapeutic intervention or disease prognostication in HCC.

overall_design: H3K27ac ChIP-seq data of adjacent normal and tumour samples obtained from resected HCC tissues of 30 patients

first: Ah-Jung

last: Jeon

first: Chukwuemeka

last: Anene-Nzelu


title: RNA profiling of IL-34 overexpressing acute myeloid leukemia (AML) cells

city: Tianjin

first: Dongyue

address: 288 nanjing Road

institute: institute of blood

summary: Acute myeloid leukemia (AML) is a highly heterogeneous disease. In our study, we found that overexpressing IL-34 in AML cells accelerates the  AML progression and shorten the mice survival, which is medicated by LSC level. We used one of the LSC markers, c-Kit, to divide AML cells. The goals of this study aim to reveal the mechanism mediated by IL-34 overexpression, we performed the RNAseq profiling of MA9-c-kit-, MA9-c-kit+ and MA9-IL-34 AML cells.

overall_design: c-kit+ cells were isolated from MA9 and MA9-IL-34 mice. c-kit- cells were isolated from MA9 mice. mRNA profiles of these cells were generated by RNA sequencing.

first: GuoGuang

last: Zheng

first: Rong

last: Wang

first: Xiaoxi

last: Cui


title: Human primed and naïve PSCs are equally potent in differentiating into bona fide trophoblast stem cells

status: Public on Sep 21 2022

city: Rehovot

first: Noa

last: Novershtern

address: Weizmann Institute

department: Molecular Genetics

country: Israel

institute: Weizmann Institute of Science


title: Gene expression related to tumor infiltrating lymphocytes status and BRAFV600E status in naive melanoma cancer patients

status: Public on Aug 31 2022

city: roskilde

first: Soraya

last: Naimy

state: Sjaelland

address: sygehusvej 9

department: department of pathology

country: Denmark

institute: zealand universityhospital

summary: Gene expression profiling of a total of 770 genes included in the PanCancer IO 360™  panel+ 20 genes of interest  were studied in 198 melanomas cases and correlated to TILS and BRAF600E mutation status

overall_design: In the study presented here, a traetment naive, well-defined cohort of 198 melanoma cases, followed up more than five years, was used to acquire expression profiles of a total of 770+20 genes, leading to identifying genes involved in immune response

first: Jens

last: Ole Eriksen


title: Genome-wide chromatin loop landscape in HCC

overall_design: HiC and H3K27ac HiChIP data of 2 adjacent normal and 8 tumour samples obtained from resected HCC tissues. 7 HiC libraries and 3 H3K27ac HiChIP libraries are included


title: Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [CUT&Tag]

first: Ting

last: Guo

summary:
To verify that arginine metabolic enzymes are directly regulated by H3K9ac, we established FHs74Int cells and HDAC8-overexpressing FHs74Int cells
We then performed gene expression profiling analysis using data obtained from CUT&Tag of 4 different treatment conditions in control or HDAC8 stably overexpressed FHs74Int cells ,which treated with PCI34051 (10 µmol/L for 24 h) or LPS (10 µg/ml for 48 h).

overall_design:
Con group, LPS group and PCI34051 + LPS group were peformed with FHs74Int cells. LPS group was treated with LPS (10 µg/ml for 48 h). PCI34051 + LPS group  was treated with PCI34051 (10 µmol/L for 24 h) and then LPS (10 µg/ml for 48 h). HDAC8 + PCI34051 + LPS group was treated with PCI34051 (10 µmol/L for 24 h) and then LPS (10 µg/ml for 48 h) in HDAC8 stably overexpressed FHs74Int cells.
CUT&Tag data for FHs74Int cells and its HDAC8-overexpressing cells under the condition of PCI34051 (10 µmol/L for 24 h) or LPS (10 µg/ml for 48 h).

first: Shaohua

last: Hu

first: Weijue

last: Xu

first: Jin

last: Zhou

first: Feng

last: Chen

first: Tingting

last: Gao

first: Wenqian

last: Qu

first: Faling

first: Zhibao

last: Lv

first: Li

last: Lu


title: RNA editing modulates pathways critical to B cell lymphomagenesis

city: Heidelberg

first: F. Nina

last: Papavasiliou

address: Im Neuenheimer Feld 280

department: Tumor Immunology Unit

institute: German Cancer Research Center (DKFZ)

summary: Diffuse large B cell lymphoma (DLBCL) is one of the most common and aggressive types of B cell lymphoma. Subtype heterogeneity cannot be completely explained by genomic alterations and/or gene expression differences, suggesting that additional mechanisms are involved. Here, we explore the contribution of an epitranscriptomic modification to B cell lymphomagenesis. Our data demonstrate that ADAR1-mediated RNA editing (deamination of adenosine to inosine) targets novel candidate driver genes within well-known disease-associated pathways in DLBCL. Within these pathways, DNA mutations and RNA editing events are often mutually exclusive at the gene level, suggesting that tumours can modulate pathway outcomes by altering sequence at either the genomic or the transcriptomic level. In contrast to what has been found in solid tumours, in DLBCL low ADAR1 expression correlates with low interferon-stimulated gene (ISG) scores and with a microenvironment that is not inflamed. To investigate the molecular mechanism behind the inability of DLBCL to mount an ISG response upon loss of ADAR1, we focused on one candidate MAVS, a central regulator of ISG (as well as NFkB) signaling. MAVS is never mutated but robustly edited by ADAR1 at its 3’UTR, and editing correlates with increased MAVS protein levels and increased downstream activation of the ISG as well as NFkB pathways. Using targeted base editing tools to specifically restore MAVS editing in ADAR1-deficient cells, we demonstrate that MAVS editing is directly causal to an increase in expression of genes downstream this signaling pathway. Our data imply that DLBCL tumours edit MAVS to strengthen NFkB signaling, to which they are dependent on survival; thus, targeted loss of MAVS editing might sensitize tumours to cell death. Overall, ADAR1-mediated RNA editing represents a new tumour evasion mechanism underlying DLBCL lymphomagenesis, with features distinct from those derived from solid tumours to date.

overall_design: ADAR1 KO 3 replicates were generated for RC-K8 and A549 cell lines. 3 WT replicates from A549 cell line, and 3 ctrl clones from RC-K8 cell line (here called WT), were employed as controls. Total RNA was extracted from ADAR1 KO and WT replicates with the RNAeasy Plus mini kit from Qiagen (Cat No./ID: 74134). The total RNA extracted was treated with DNase (TURBO, Thermofisher, Cat No. AM1907). Libraries for total RNA-seq were generated according to Illumina instructions for 125bp paired-end sequencing with universal adapters.

first: Riccardo

last: Pecori

first: Weicheng

last: Ren

first: Mohammad

last: Pirmoradian

first: Dongbing

last: Liu

first: Xiaofei

last: Ye

first: Wei

last: Li

first: Rafail

middle: N

last: Tasakis

first: Annette

last: Arnold

first: Sandra

last: Wüst

first: Shida

last: Zhu

first: Yong

last: Hou

first: Kui

last: Wu

first: Huilai

last: Zhang

first: Marco

last: Binder

first: Karthika-Devi

last: Selvasaravanan

first: Yvonne

last: Fuell

first: Thorsten

last: Stafforst

first: F

first: Qiang

last: Pan-Hammarström


title: Elevated expression of histone deacetylase HDAC8 suppresses arginine-proline metabolism in necrotizing enterocolitis [PCI34051 study]

first: Ting

last: Guo


title: H3K4 Methylation in β-cells prevents transcriptional downregulation and variance associated with type 2 diabetes.

status: Public on Aug 11 2022

city: Vancouver

first: Brad

last: Hoffman

state: BC

institute: University of British Columbia

sample_organism:
Drosophila melanogaster
Mus musculus

platform_organism:
Drosophila melanogaster
Mus musculus


title: Sitravatinib Plus Nivolumab in Patients Undergoing Nephrectomy for Locally Advanced Clear Cell Renal Cell Carcinoma

status: Public on Sep 06 2022

city: San Diego

first: Peter

last: Olson

state: California

address: 3545 Cray Court

institute: Mirati Therapeutics

summary: Sitravatinib is an immunomodulatory tyrosine kinase inhibitor that can augment responses when combined with programmed death-1 (PD-1) inhibitors such as nivolumab. We report a phase 2 study of neoadjuvant sitravatinib in combination with nivolumab in patients with locally advanced clear cell renal cell carcinoma (ccRCC) prior to curative nephrectomy (NCT03680521). The primary endpoint was objective response rate (ORR) prior to surgery with a null hypothesis ORR = 5% and the alternative hypothesis set at ORR = 30%. Secondary endpoints included correlative immune effects and disease-free survival (DFS). Twenty patients were evaluable for safety and 17 for efficacy. The ORR was 11.8%, and 24-month DFS probability was 88·0% (95% CI 61.0 to 97.0). There were no grade 4/5 treatment-related adverse events. Correlative blood and tissue analyses showed changes in the tumour microenvironment resulting in an immunologically active tumour by the time of surgery. These data suggest that short-term neoadjuvant sitravatinib and nivolumab does not substantially increase ORR but can modulate the immune microenvironment and yield high DFS probabilities in patients with locally advanced ccRCC.

overall_design: Expression profiling of patient data before treatment and after treatment with single drug and drug combination

first: Jose

last: Karam

first: Pavlos

last: Msaouel


title: Transcriptional profile of human epithelial cells in response to H. pylori infection

status: Public on Aug 01 2022

city: Erlangen

first: Bodo

last: Linz

address: Staudtstrasse 5

institute: Friedrich Alexander University Erlangen

summary: Purpose: To identify genes that are differently expressed during infection with wild-type (wt) H. pylori or an isogenic DhtrA mutant.

overall_design: Comparing the gene expression of uninfected cells versus cell infected with the wt or mutant H. pylori for 2 hours or 6 hours.

first: Irshad

last: Sharafutdinov


title: NAT10 depletion suppresses fatty acid metabolism in MCF7 breast cancer cells

status: Public on Aug 03 2022

city: Jeddah

first: Mohammad

middle: Imran

last: Khan

state: Makkah

address: King Abdullah Road

department: Biochemistry

country: Saudi Arabia

institute: King Abdulaziz University

summary:
NAT10 is an RNA cytidine transferase known to add acetyl group on RNA transcripts thereby promoting translational efficiency. It was reported that NAT10 regulates epithelial to mesenchymal transition (EMT), DNA damage, and cell proliferation in cancers. However, weather NAT10  regulates other crucial pathways is unknown.
In our study we conducted gene expression profiling analysis using data obtained from RNA-seq of MCF7 NAT10 KO and scramble control. High throughput sequencing revealed fatty acid metabolism as the top enriched pathway with fatty acid metabolic genes such ELOVL6, ACSL1, ACSL3, ACSL4, ACADSB, and ACAT1 were found to be differentially down-regulated.
Overall our results revealed NAT10 depletion suppresses fatty acid metabolism in MCF7.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MCF7 cells and its KD derivatives (siNAT10).

first: Dalhat

last: Hassan

first: Khan

last: Imran


title: H3K4 Methylation in β-cells prevents transcriptional downregulation and variance associated with type 2 diabetes [ChIP-seq]

summary: Insufficient insulin release by β-cells is the primary etiology in type 2 diabetes (T2D) and coincides with impaired expression of genes essential to β-cell function, but drivers of gene expression dysregulation are not well resolved. We find that H3K4me3 peak breadth correlates with gene expression dysregulation in T2D. Using an adult β-cell Dpy30-KO mouse model, we show that global reduction of H3K4 methylation causes downregulation of genes also downregulated in T2D. Reduction of H3K4 methylation increases transcriptional entropy and reduces insulin production and glucose-responsiveness. Depletion of H3K4 methylation causes global dilution of epigenetic complexity but does not generally reduce gene expression – instead, genes related to β-cell function and/or in particular chromatin environments are specifically affected. Our data further suggests that promoter-associated H3K4me1 is sufficient to maintain expression in the absence of H3K4me3. These data implicate dysregulation of H3K4 methylation in destabilizing gene expression and contributing to β-cell dysfunction in T2D.

overall_design: ChIP-seq for 4 histone modifications in 2 replicates from Dpy30-KO or CTRL mouse beta cells with 50% Drosophila S2 cell spike-in

first: Ben

last: Vanderkruk

first: Nina

last: Maeshima

first: Daniel

last: Pasula

first: Meilin

last: An

first: Priya

last: Suresh

first: Aline

last: Daniel

first: Cassandra

middle: L

last: McDonald

first: Dan

middle: S

last: Luciani


title: Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling (Mouse I).

first: Yan

last: Xu

institute: Cincinnati Children's Hospital Medical Center

summary: Pulmonary fibrosis results from dysregulated repair of damaged tissue caused by persistent injury of lung epithelium. Multiple cell types in the lung are involved in the process of repair.  During lung fibrogenesis, normal endothelial cells (EC) are re-programmed into fibrosis-associated EC. Transcriptional factors that control re-programming are poorly understood. Using single cell RNA-sequencing of EC from donor and idiopathic pulmonary fibrosis (IPF) lungs, and lungs from bleomycin-treated mice, we identified endothelial transcription factors (TF) that were differentially expressed during fibrosis.  Focusing on one of endothelial TF, FOXF1, we demonstrated that FOXF1 is decreased in EC within human IPF and mouse bleomycin-injured fibrotic lungs.

overall_design: Using the 10x Chromium platform sequencing, transcriptomes of single cells from normal mouse lung and bleomycin treated mouse lung were analyzed.

first: Fenghua

last: Bian

first: Tien

last: Le

first: Shuyang

last: Zhao

first: Matthew

last: Bacchetta

first: Ahmed

middle: E

last: Hozain

first: Yuliya

last: Tipograf

first: Tanya

last: Kalin


title: Dynamics of RNA-m5C Modification during Brain Development

city: Blacksburg

first: Zachary

last: Johnson

state: VA

address: 1015 Life Science Cir

department: FLSI

institute: Virginia Tech

summary: In this study we evaluate the changes in m5C methylation at critical post-natal stages of brain development and links to methylation levels of neuronal stem cells and cortical neurons. We identify transcript-specific changes in methylation level associated with gene expression.

overall_design: Analysis of RNA BS-seq and RNAseq data in P0, P17, and 6W whole brain and NSC and E16.5 cortical neuron culture

first: Xiguang

first: Hehuang

last: Xie


title: IFT20 is important for effector function of CD4+ T cell

status: Public on Jul 31 2022

city: Daejeon

first: Jiung

last: Jeong

address: 291, Daehak-ro, Yuseong-gu

institute: KAIST

summary: Recent studies have suggested that formation of supramolecular activation cluster (SMAC), a large ‘immunological synapse’ composed of various signaling complexes, enhances CD4+ T cell activation. Critically, although the composition of SMAC is known, the proteins involved in SMAC formation have not been fully investigated. We identified that intraflagellar transport 20 (IFT20) play central roles in the effector functino of CD4+ T cells.

overall_design: We analyzed in vitro activated CD4 T cell by single cell RNA sequencing (scRNAseq) with 10X genomics. CD4+ T cells for T cell activation were extracted from spleens of Ift20f/f or Ift20f/f CD4cre mice. Following single cell isolation, the MagnisortTM Mouse CD4 naïve T cell Enrichment Kit (Invitrogen) was used to obtain purified naïve T cells. Naïve CD4 + T cells were activated with 1-μg/mL anti-CD3 (Invitrogen) and 1-μg/mL anti-CD28 antibodies (BioLegend) for 24 hours.

first: Chae

middle: W

last: Kim

first: Hyeon

middle: C

first: Young

last: Choi

first: Jaeho

first: Heung

middle: K

last: Lee


title: Drosophila immune priming to Enterococcus faecalis relies on immune tolerance rather than resistance

city: Boston

first: Kevin

last: Cabrera

state: Massachusetts

address: 610 Commonwealth Avenue

institute: Boston University

summary: Innate immune priming increases an organism’s survival of a second infection after an initial, non-lethal infection. We used Drosophila melanogaster and an insect-derived strain of Enterococcus faecalis to study transcriptional control of priming. In contrast to other pathogens, the enhanced survival in primed animals does not correlate with decreased E. faecalis load. Further analysis shows that primed organisms tolerate, rather than resist infection. Using RNA-seq of immune tissues, we found many genes were upregulated in only primed flies, suggesting a distinct transcriptional program in response to  initial and secondary infections. In contrast, few genes continuously express throughout the experiment or more efficiently re-activate upon reinfection. Priming experiments in immune deficient mutants revealed Imd is largely dispensable for responding to a single infection but needed to fully prime. Together, this indicates the fly’s innate immune response is plastic — differing in immune strategy, transcriptional program, and pathway use depending on infection history.

overall_design: Comparative RNA-seq of dissected Drosophila melanogaster Oregon-R fat bodies and hemocytes infected with E. faecalis, and/or re-infected in immune priming studies

first: Duncan

last: Hoard

first: Olivia

last: Gibson

first: Daniel

middle: I

last: Martinez

first: Zeba

last: Wunderlich


title: H3K4 Methylation in β-cells prevents transcriptional downregulation and variance associated with type 2 diabetes [RNA-seq]

first: Brad

last: Hoffman

overall_design:
RNA-seq of 3 replicates at 2 time points, scRNA-seq of 1 replicate at 1 time point, from Dpy30-KO or CTRL mouse beta cells
Please note that the "scRNAseq_commands.txt" contains the processing pipeline details to regenerate the processed data from raw data for scRNA-seq. The file "mtmg_long.fa" containing egfp and tdtomato sequences is necessary to regenerate the processed data.

first: Ben

last: Vanderkruk

first: Nina

last: Maeshima

last: Pasula

first: Meilin

last: An

first: Priya

last: Suresh

first: Aline

last: Daniel

first: Cassandra

last: McDonald

first: Dan

last: Luciani


title: Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus

status: Public on Jul 29 2022

city: Chicago

first: Aly

middle: Azeem

last: Khan

state: IL

address: 6045 S. Kenwood Ave.

institute: University of Chicago

summary: The influence of the microbiota on viral transmission and replication is well appreciated. However, its impact on retroviral pathogenesis outside of transmission/replication control remained unknown. Using Murine Leukemia Virus (MuLV), we found that some commensal bacteria promoted the development of leukemia induced by this retrovirus. The promotion of leukemia development by commensals was due to suppression of the adaptive immune response through upregulation of several negative regulators of immunity. These negative regulators included Serpinb9b and Rnf128, which are associated with a poor prognosis of some spontaneous human cancers. Upregulation of Serpinb9b was mediated by sensing of bacteria by NOD1/NOD2/RIPK2 pathway. This work describes a novel mechanism by which the microbiota enhances tumorigenesis within gut-distant organs and points at potential new targets for cancer therapy.

overall_design: RNAseq was performed on splenic RNA from infected and uninfected GF and SPF BALB/cJ mice

first: Jessica

last: Spring

middle: A

first: Tatyana

last: Golovkina


title: PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing

status: Public on Jul 28 2022

city: Melbourne

first: David

last: Goode

state: Victoria

address: 305 Grattan Street

department: Research Division

country: Australia

institute: Peter MacCallum Cancer Centre

summary: To investigate the full effects of inhibition of CDK4/6 on splicing events in melanoma and the extent to which they are dependent on PRMT5 . We performed full-length mRNA sequencing on CHL1 and A375 melanoma cell lines treated with the CDK4/6 inhibitor palbociclib and the PRMT5 inhibitor GSK3326595 and CTX085 and analysed data for differential gene expression and differential pre-mRNA splicing induced by these agents.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for CDK4/6 and PRMT5 inhibited CHL1 and A375 melanoma  cells.

first: Lok

middle: H

last: Chan

first: Peihan

last: Wang

first: Shatha

last: Abuhammad

first: Joseph

last: Cursons

first: Karen

last: Sheppard


title: Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer [RIP-Seq]

first: Khine

last: Myint

address: 14 Medical Drive

institute: Cancer Science Institute/NUS

summary: We reported earlier that IQGAP3 is an important stem cell factor in rapidly proliferating  isthmus stem cells in the stomach. Furthermore, we observed robust induction of  IQGAP3 expression in terminally differentiated chief cells and de-differentiated cells  following tissue damage. The elevated expression of IQGAP3 in cancer and its  association with metastasis suggest a fundamental role for IQGAP3 in proliferating  cancer stem cells. What causes the upregulation of IQGAP3 in cancer is unclear. Here,  we show that IGF2BP1 and IQGAP3 expression levels are highest in the blastocyst,  with both showing decreases during adulthood. This suggests that IQGAP3, like  IGF2BP1, is an early developmental gene that is aberrantly upregulated upon reexpression  of IGF2BP1 during carcinogenesis. We found that IGF2BP1 binds and  stabilizes m 6 A-modified IQGAP3 transcripts. Furthermore, downstream targets of  IGF2BP1, namely SRF and FOXM1, also upregulate IQGAP3 expression. These  multiple layers of IQGAP3 regulation, which may safeguard against inappropriate stem  cell proliferation, present additional drug targets to inhibit IQGAP3-driven malignant growth.

overall_design: RIP-seq in NTERA2 cells with Flag-tagged IGF2BP1 overexpression.

first: Linda

last: Chuang

first: Yu

last: Teh

first: Nur

last: Mawan

first: Edward

middle: J

last: Shi

first: Michelle

middle: M

last: Mok

first: Napat

last: Nuttonmanit

first: Junichi

last: Matsuo

first: Ying

last: Li

first: Henry

last: Yang

first: Atsushi

last: Okabe

last: Kaneda

first: Motomi

last: Osato

first: Jimmy

last: So

first: Wei

middle: P

last: Yong

first: Patrick

last: Tan

first: Khay

middle: G

last: Yeoh

first: Yoshiaki

last: Ito


title: Hepatitis C virus RNA is 5’ flavin adenine dinucleotide (FAD) capped

city: Copenhagen N

first: Jeppe

last: Vinther

address: Ole Maaloes Vej 5

institute: University of Copenhagen

summary: RNA viruses have developed elaborate strategies for 5’ capping and protection of their genomes. However, so far no 5’ RNA cap has been identified for Hepatitis C virus (HCV), which cause chronic infection, liver cirrhosis and cancer in humans4. Here, we demonstrate that the cellular metabolite flavin adenine dinucleotide (FAD) is used as noncanonical initiating nucleotide by the viral RNA-dependent RNA polymerase resulting in a 5’ FAD cap on the HCV RNA. FAD capping is completely conserved for the HCV replication intermediate negative RNA strand and partially for the positive RNA strand. The prototype strain J6/JFH1 RNA is FAD capped when isolated from the liver and serum of a human liver chimeric mouse model and in vitro the FAD capping frequency is ~75 %, which is the highest metabolite RNA capping frequency observed. Furthermore, we show that 5’ FAD capping protects RNA from cell-intrinsic innate immune recognition but has limited effect on HCV RNA stability. These results establish capping with cellular metabolites, such as FAD, as a novel viral RNA capping and immune evasion strategy, which potentially could be used by many viruses for protection of their intermediate RNA strands and thereby affect viral treatment outcomes and persistency.

sample_organism:
Homo sapiens
Bos taurus
Tick-borne encephalitis virus
Bovine viral diarrhea virus 1-NADL
Chikungunya virus
Hepacivirus hominis

overall_design: Total RNA was isolated from cells infected with different viruses. CapZyme-seq protocol was applied to total RNA or RNA treated with TEX enzyme. RNA was enzymatically treated with de-capping enzymes that specifically convert different 5’ cap structures to 5’ monophosphates. 5’-phosphate dependent adapter ligation was performed followed by reverse transcription. Libraries were generated using PCR with custom Illumina compatible primers. For experiments with HCV genotype 2a J6/JFH1-clone2, 5 biological replicates with 2 technical replicates per each biological replicate were analyzed for each enzymatic treatment condition (NUDX23, Rpp and no enzyme control). For the experiments with other HCV strains, 1 biological replicate was analyzed for each enzymatic condition. For the experiments with BVDV, 3 biological replicates were analyzed for each enzymatic conditions. For the experiments with CHKV, 2 biological replicates were analyzed for each enzymatic conditions. For the experiments with TBEV, 3 biological replicates were analyzed for each NUDX23, Rpp and no enzyme control enzymatic conditions and 3 biological replicates were analyzed for each NudC, Rpp and no enzyme control enzymatic conditions.

first: Anna

middle: V

last: Sherwood


title: Ex Utero Development of Post-Gastrulation Synthetic Embryos Generated Solely from Naïve Pluripotent Stem Cells

first: Noa

last: Novershtern

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

overall_design: Refer to individual Series


title: The key factors of drug resistance with cell-cell interactions

status: Public on Jul 12 2022

city: Bunkyo-ku

first: Morito

last: Kurata

state: Tokyo

address: １－５－４５ Yushima Bunkyo-ku

department: Comprehensive Pathology

country: Japan

institute: Tokyo Medical and Dental University

summary: The inductional abilities of drug resistance by the knockout of C9orf89, MAGI2, MLPH, or RHBDD2 in supporting cells were solidly confirmed by the reduction of apoptosis by cell-cell interactions.

overall_design: HEK293T clones of C9orf89-CRISPR-KO, C19orf70-CRISPR-KO, C21orf33-CRISPR-KO, MAGI2-CRISPR-KO, MLPH-CRISPR-KO, and RHBDD2-CRISPR-KO were established with the limiting dilution methods and conducted in the following co-culture experiment.

first: Keisuke

last: Sugita


title: The impact and outcomes of cancer-macrophage fusion

city: Los Angeles

first: Yi-Ling

last: Lin

address: 10833 Le Conte Ave, CHS 53-058

department: School of Dentistry

country: USA

institute: University of California, Los Angeles

summary:
Background: Cancer's hallmark feature is its ability to evolve, leading to metastasis and recurrence. Although genetic mutations and epigenetic changes have been implicated, they don't fully explain the leukocytic traits that many cancers develop. Cell fusion between cancer and somatic cells, particularly macrophages, has been suggested as an alternative pathway for cancer cells to obtain new traits by acquiring exogenous genetic material.

Methods: This study aims to investigate the potential biological outcomes of tumor-myeloid cell fusion by generating tumor-macrophage hybrid cells. Two clones with markedly different tumorigenicity were selected, and RNA-seq was used to compare their RNA expressions with that of the control cells. Based on the results that the hybrid cells showed differential activation in several upstream regulator pathways that impact their biological behaviors, the hybrid cells' abilities to recruit stromal cells and establish angiogenesis as well as their cell cycle distributions were investigated through in vitro and in vivo studies.

Results: Although both hybrid clones demonstrated p53 activation and reduced growth rates, they exhibited distinct cell cycle distributions and ability to grow in vivo. Notably, while one clone was highly tumorigenic, the other showed little tumorigenicity. Despite these differences, both hybrid clones were potent environmental modifiers, exhibiting significant abilities to recruit stromal and immune cells and establish angiogenesis.

Conclusions: The study revealed that tumor-somatic cell fusion is a potent environmental modifier that can modulate tumor survival and evolution, despite its relatively low occurrence. These findings suggest that tumor-somatic cell fusion could be a promising target for developing new cancer therapies. Furthermore, this study provides an experimental animal platform to investigate cancer-myeloid fusion and highlights the potential role of tumor-somatic cell fusion in modulating the tumor environment.

overall_design:
Comparative gene expression profiling analysis of RNA-seq data of SCCVII/SF cells, SCCVII/SF-macrophage hybrid D2 and SCCVII/SF-macrophage hybrid D3.

**Please note that processed data files contain additional data columns (i.e. D3-1B, D2-4A), which are not discussed in the publication associated with the current study.

first: Mengtao


title: Immunosuppression induced by brain specific HDAC6 deletion improves motor performance and extends lifespan in Drosophila melanogaster

city: Beijing

first: Jing-Dong

middle: Jackie

last: Han

address: 5 Yiheyuan Rd, Haidian District

country: China

institute: Peking University

summary: RNA-seq data of adult day 2 and adult day 12 Drosophila head with or without HDAC6 knockdown were generated.

overall_design: Examination of HDAC6 KD influence on AD2 and AD12 Drosophila

last: Yu


title: Molecular and radiopathologic spectrum between HCC and intrahepatic cholangiocarcinoma

city: Suwon

first: Hyun Goo

last: Woo

address: 164 Worldcup-ro Yeongtong-gu

institute: Ajou University School of Medicine

summary:
Background and aims: Primary liver cancers (LCs), including HCC and intrahepatic cholangiocarcinoma (iCCA), are derived from a common developmental lineage, conferring a molecular spectrum between them. To elucidate the molecular spectrum, we performed an integrative analysis of transcriptome profiles associated with patients' radiopathologic features.

Approach and results: We identified four LC subtypes (LC1-LC4) from RNA-sequencing profiles, revealing intermediate subtypes between HCC and iCCA. LC1 is a typical HCC characterized by active bile acid metabolism, telomerase reverse transcriptase promoter mutations, and high uptake of gadoxetic acid in MRI. LC2 is an iCCA-like HCC characterized by expression of the progenitor cell-like trait, tumor protein p53 mutations, and rim arterial-phase hyperenhancement in MRI. LC3 is an HCC-like iCCA, mainly small duct (SD) type, associated with HCC-related etiologic factors. LC4 is further subclassified into LC4-SD and LC4-large duct iCCAs according to the pathological features, which exhibited distinct genetic variations (e.g., KRAS , isocitrate dehydrogenase 1/2 mutation, and FGF receptor 2 fusion), stromal type, and prognostic outcomes.

Conclusions: Our integrated view of the molecular spectrum of LCs can identify subtypes associated with transcriptomic, genomic, and radiopathologic features, providing mechanistic insights into heterogeneous LC progression.

overall_design: Transcriptome profiling from 78 cases of HCC and 59 cases of iCCA tissue were performed. Four subtypes: LC1, LC2, LC3, LC4

first: H


title: Gene expression of HUVECS treated with either siRNA to CTRL, PDHA1, or SREBF2 and treated with TNF 16 hours

status: Public on Jul 11 2022

city: New Haven

first: Joseph Wayne

middle: Montano

last: Fowler

state: CT

address: 10 Amistad St.

department: Pharmacology

institute: Yale University

summary: The endothelium is a major target of the proinflammatory cytokine, tumor necrosis factor alpha (TNFα). Exposure of endothelial cells (EC) to proinflammatory stimuli leads to an increase in mitochondrial metabolism, however, the function and regulation of elevated mitochondrial metabolism in EC in response to pro-inflammatory cytokines remains unclear. Using high-resolution metabolomics and 13C-glucose labeled flux techniques, we demonstrate that pyruvate dehydrogenase activity (PDH) and tricarboxylic acid cycle flux is elevated in human umbilical vein ECs (HUVECs) in response to overnight (16 hrs) treatment with TNFα (10 ng/mL). Mechanistic studies indicate that TNFα mediates these metabolic changes via mitochondrial specific protein degradation of pyruvate dehydrogenase kinase 4 (PDK4, inhibitor of PDH) by the Lon protease via an NF-κB dependent mechanism. Using RNA sequencing following siRNA mediated knockdown of the catalytically active subunit of PDH, PDHE1a (PDHA1 gene), we show that PDH flux controls the transcription of approximately one-third of the genes that are upregulated by TNFa stimulation. Notably, TNFa induced PDH flux regulates a unique signature of proinflammatory mediators (cytokines and chemokines) but not inducible adhesion molecules. Using metabolomics and ChIP sequencing (H3AcK27), we demonstrate that TNFα induced PDH flux promotes histone acetylation of specific gene sets via citrate accumulation and ATP-citrate lyase activity. Together, these results indicate that targeting endothelial glucose oxidation and/or acetyl CoA generation may offer a novel therapeutic strategy in the treatment of vascular inflammation.

overall_design: Comparative gene expression of early passage HUVECs treated with either siRNA to CTRL, PDHA1, or SREBF2 and treated with TNF 16 hours.

first: Nabil

last: Boutagy

first: Joseph

first: Kariona

last: Grabinska

first: Rebecca

last: Cardone

first: Quishi

last: Sun

first: Raja

last: Chakraborty

first: Kathleen

last: Martin

first: Richard

last: Kibbey

first: Casey

last: Romanoski

first: William

last: Sessa


title: Deficiency of IFT20 in CD4+ T cell alleviates protease-induced neutrophilic asthma-like inflammation

first: Jiung

last: Jeong

summary: Many neutrophilic asthma patients do not respond to current medications, highlighting the need for novel therapeutic targets. Here, we investigated the role of intraflagellar transport (IFT) complex protein IFT20 in neutrophilic asthma. Mice lacking CD4+ T cell-specific IFT20 displayed reduced protease-induced neutrophilic asthma inflammation. Thus, IFT20 may represent a promising therapeutic target for treatment of patients with neutrophilic asthma.

overall_design: We analyzed infiltrated immune cells in lung by single cell RNA sequencing (scRNAseq) with 10X genomics. C57BL/6 background Ift20f/f or Ift20f/f CD4 cre mice were administered 25-μg of papain intranasally for three consecutive days to sensitize them to the allergen. On day 14 after first administration of papain, mice were challenged with the same concentration of papain administered via intranasal injection. Immune cells were harvested from lung tissue on day 15.

first: Chae

last: Kim

first: Hyeon

first: Young

last: Choi

first: Jaeho

first: Heung

last: Lee


title: Bulk RNAseq of C1Q knockout TauP301S hippocampi

status: Public on Jul 16 2022

city: South San Francisco

first: Brad

last: Friedman

state: CA

address: 1 DNA Way

department: Neuroinformatics

institute: Genentech, Inc.

summary: The effect of C1q knockout on brain gene expression was examined in non-transgenic and TauP301S mice. Complement pathway has been shown to play an important role in neurodegenerative diseases, and in-house data show that C1QC KO protects against neurodegeneration in Alzheimer's disease (AD) model. TauP301S mice have neuroinflammation and neurodegeneration in the brain and is AD model. The most severe pathology of this disease model is in hippocampus.

overall_design: This experiment examines RNA expression profiles in mouse hippocampi bulk tissue from WT or C1QC KO mice crossed with TauP301S or non-transgenic mice.

first: Jesse

last: Hanson

first: Mitchell

last: Rezzonico

first: Yuanyuan

last: Wang

first: Alyaa

last: Mohamed

first: Dwight

last: Newton


title: SREBP2 regulates several genes in the endothelial response to inflammation via direct transcriptional activation of KLF6

status: Public on Jul 14 2022

first: Joseph Wayne

last: Fowler

summary: Immunometabolism is a growing field that centers on a core paradigm: perturbations in metabolism alter a cell’s biological response in immunity and, likewise, inflammatory signals, such as cytokines and pathogens, can directly influence cellular metabolism. Although the carbons within cholesterol cannot be used for catabolic energy production, there is a growing appreciation that a similar relationship exists between cholesterol homeostasis and immunity. The majority of this literature is focused on cholesterol dynamics in the context of leukocyte immunobiology. However, the endothelium also plays an important role during the acute inflammatory response. Endothelial cells (ECs) rapidly respond to extrinsic signals, such as tissue damage or microbial infection, by upregulating factors to activate and recruit circulating leukocytes to the site of injury. Dysregulation or aberrant activation of ECs leads to disease, such as atherosclerosis. I studied the role of cholesterol and its master regulator, SREBP2, in the EC response to acute inflammatory stress. ECs treated with cytokines upregulated SREBP2 cleavage and classical cholesterol biosynthesis gene expression within the late phase of the acute inflammatory response. Furthermore, SREBP2 activation was dependent on NF-kB DNA binding and classical SCAP-SREBP2 processing. We used bacterial cytolysin probes to show that inflammatory stress significantly decreased accessible cholesterol, leading to dysfunctional sterol sensing and downstream SREBP2 cleavage. We also explored what role SREBP2 plays in the EC inflammatory response. Loss of SREBP2 in ECs treated with inflammatory cytokine altered EC phenotype, which was defined by decreased chemokine expression and increased type I inflammatory signaling. Interestingly, this effect on the EC inflammatory transcriptome could not be accounted by changes in cholesterol, but rather through SREBP2 binding to promoters of pro-inflammatory transcription factors. Preliminary results revealed that BHLHE40 and KLF6 are direct targets of SREBP2 and that loss of one of KLF6 could mimic the effect of SREBP2 knockdown on chemokine expression. This study is the first to provide an in-depth characterization of the relationship between SREBP2 and the endothelial acute inflammatory response.

overall_design: Comparative gene expression of early passage HUVECs treated with either siRNA to CTRL or KLF6 and treated with TNF for 16hrs

first: Joseph

first: Rong

last: Zhang

first: Nabil

last: Boutagy


title: Detection of transcriptome changes caused by overexpression of NeuroD4 in U251 glioblastoma cells

city: Wenzhou

first: hao

state: Zhejiang

address: Nanbaixiang, Ouhai District

institute: the First  Affiliated Hospital of Wenzhou Medical University

summary: We demonstrated that overexpression of NeuroD4 can reprogram GBM cells into neuron-like cells. In order to further explore the mechanism of NeuroD4 causing this phenomenon, we performed mRNA sequencing on U251 cells infected with GFP and GFP+NeuroD4.

overall_design: The mRNA changes of U251 cells infected with GFP and GFP+NeuroD4 were detected.

first: Hao


title: Slow-integrin dependent migration organizes networks of tissue-resident mast cells

status: Public on Jul 25 2022

city: Basel

first: Nadim

last: Aizarani

address: Maulbeerstrasse 66

country: Switzerland

institute: FMI

overall_design:
We performed single-cell RNA seqencing of mast cells from dermal skin using the mCEL-seq2 protocol.
CEL-Seq2 (Hasimshony et al. 2016, Genome Biology, DOI: 10.1186/s13059-016-0938-8)

first: Tim

last: Lämmerman

first: Sarah

last: Bambach

first: Dominic

last: Grün