title: RNAseq of lymphocyte populations in Graft vs Host Disease

city: Maywood

first: Edward

last: Campbell

state: IL

address: 2160 S First Ave

department: Microbiology and Immunology

institute: Loyola University Chicago

summary: In this experiment we harvested donor T cells from recipient allogeneic mice and examined changes in gene expression in FLICA (caspase-1 activation) positive and negative T cell populations

overall_design: Splenocytes were harvested from the indicated donor mouse strain and T cells were isolated by negative selection using a negative isolation kit (EasySep Mouse T Cell Isolation kit; STEMCELL Technologies) or a cocktail of biotinylated antibodies (anti-B220 [RA3-6B2], anti-CD11b [M1/70], anti-CD11c [N418]), followed by incubation with magnetic nanoparticles conjugated to streptavidin (BD IMag Streptavidin Particles Plus; BD Biosciences) and magnetic isolation. Purity (>90%) was confirmed by flow cytometry staining for T cells (anti-CD3) (Fig. S1). 0.75-1x106 T cells + 1x107 BM cells were resuspended in PBS with heparin and intravenously injected into BALB/c recipient mice via tail vein injection. Human HLA-A2 negative PBMCs were isolated from adult healthy donors. 10 million PBMCs were resuspended in PBS with heparin and injected into NSG recipient mice. On the day of transplantation, BABL/c recipients received a total body lethal dose of irradiation (8 Gy) and NSG recipients received (2.5 Gy) from an X-ray source (RS 2000 Biological Research Irradiator). Body weights were recorded and clinical signs observed throughout the experiment. On day 7 (BALB/c) or day 10 (NSG), mice were sacrificed for ex vivo analyses. For survival experiments, experiments were carried out for 80 days. When mice reached weight loss >25% of their initial body weight or hit end of life criteria, mice were considered clinically dead.

first: Sarah

last: Talley


title: mRNA sequencing of brain and liver in multiple Alzheimer's Disease mouse models after treatment with either a Non-Targeting Control siRNA or an siRNA targeting mouse Apoe mRNA

status: Public on Oct 02 2023

city: Worcester

first: Samuel

last: Hildebrand

state: MA

address: 368 Plantation Street

department: RNA Therapeutics Institute

country: USA

institute: University of Massachusetts Medical School

type: Expression profiling by high throughput sequencing

summary: The most common genetic risk factor for late onset Alzheimer Disease (AD) is the APOE4 allele, with evidence for gain- and loss-of-function as a primary mechanism. ApoE knockout in mice abrogates AD phenotypes but causes severe atherosclerosis due to the role of liver ApoE in cholesterol homeostasis. Previous attempts to therapeutically block brain-specific ApoE in adult models of AD only modestly reduced ApoE expression and no significant impact on amyloid burden. Here, we optimized a divalent siRNA (di-siRNA) to selectively silence ApoE in brain (>2 months). By measuring transcriptomic changes upon knockdown of ApoE in the CNS in multiple mouse models of AD, we find that ApoE knockdown results in an upregulation of the innate immune response, likely through activation of microglia. Additionally, we find that the changes in the transcriptome were similar, but not identical, two weeks and two months post-treatment. We find that mild reduction of ApoE in the liver does not cause widespread transcriptomic changes, but near complete knockdown of ApoE in the liver results in the dysregulation of many lipid metabolism-related pathways.

overall_design: For the brain samples in each mouse model and each treatment (NTC or ApoE siRNA) timepoint (2 Weeks or 2 Months post-treatment) the sample size was 10-20 mice. For the liver samples in each treatment (NTC or ApoE siRNA, bilateral intracerebroventricular or subcutaneous injections) the sample size was 3-4 mice.

first: Chantal

middle: M

last: Ferguson

middle: R

first: Bruno

last: Godinho

first: Julianna

last: Buchwald

first: Dimas

last: Echeverria

first: Andrew

last: Coles

first: Anastasia

last: Grigorenko

first: Lorenc

last: Vanjielli

first: Jacquelyn

last: Sousa

first: Nicholas

last: McHugh

first: Matthew

last: Hassler

first: Pranathi

last: Meda

first: Jonathan

last: Watts

first: Evgeny

last: Rogaev

last: Khvorova


title: Macrophage Mannose receptor (MRC1) mediates uptake of dextran in murine bone-marrow derived macrophages via a receptor-mediated endocytic process

status: Public on Oct 01 2023

city: Brookings

first: Natalie

middle: W

last: Thiex

state: SD

address: 1390 College Ave

department: Biology & Microbiology

institute: South Dakota State University

summary: CRISPR/Cas9 whole genome screens identify regulators of dextran utpake

sample_organism:
Mus musculus
synthetic construct

platform_organism:
Mus musculus
synthetic construct

first: Jared

last: Wollman

first: Lu

last: Huang


title: MircroRNA-92b, a Novel Negative Regulator of the Transforming Growth Factor-β Signaling Pathway Targeting the Type I Receptor

city: Shenzhen

first: Shu

last: Yang

address: 1017 Dongmen North Road, Luohu District, Shenzhen

country: China

institute: shenzhen people's hospital

summary: Progressive renal disease is the consequence of destructive fibrosis. Renal fibrosis is a common outcome of many chronic kidney diseases, including diabetic kidney disease (DKD). Transforming growth factor-β1 (TGFβ1) has been identified as a major pathogenic factor underlying the development of DKD. It had been reported that the expression of miR-92b-3p had been reported to be reduced in the kidneys from diabetic mice and patients with DKD. However, the role of miR-92b-3p in the progress of renal fibrosis was remaining largely unknown. This study investigated the role of miR-92b-3p in the progression of renal fibrosis in unilateral ureteral occlusion (UUO) and unilateral ischemia-reperfusion injury (uIRI) mouse models, as well as explored its underlying mechanisms in human proximal tubular epithelial (HK2) cells. We found that renal fibrosis increased in UUO mice after miR-92b knockout, while reduced in miR-92b overexpressing mice. MiR-92b knockout aggravated renal fibrosis in unilateral ischemia-reperfusion injury. RNA-sequencing analysis, the luciferase reporter assay, qPCR analysis, and western blotting confirmed that miR-92b-3p directly targeted TGF-β receptor 1 (TGFBR1), thereby ameliorating renal fibrosis by suppressing the TGF-β/SMAD3 signaling pathway. Furthermore, we found that TGF-β suppressed miR-92b transcription through Snail family transcriptional repressors 1 (SNAI1) and SNAI2. Our results suggest that miR-92b-3p may serve as a novel therapeutic for mitigating fibrosis in chronic kidney disease.

overall_design: In this study, we identified the role of miR-92b-3p in renal fibrosis and observed that miR-92b-3p is significantly downregulated in mouse fibrotic kidneys. Mechanistically, we characterized miR-92b-3p as a key checkpoint for controlling TGF-β signaling and fibrogenesis. Global deletion of miR-92b-3p markedly aggravated the extent of renal fibrosis in fibrotic mouse kidney tissues induced by UUO and unilateral ischemia-reperfusion injury (uIRI). Importantly, we showed that renal TEC-specific overexpression of miR-92b-3p effectively ameliorated the development and progression of kidney fibrosis induced by UUO.

first: Kewei

last: Jiang

first: Lixing

last: Li

first: Jiaqing

last: Xiang

first: Yanchun

first: Lin

last: Kang

first: Guangyan

first: Zhen

last: Liang


title: RSK3 switches cell fate: from stress-induced senescence to malignant progression

city: Lyon

first: jean-michel

last: flaman

address: 28 rue Laennec

department: CRCL

country: France

institute: Inserm 1052

summary: TGFβ signaling induces several cell phenotypes including cellular senescence, a stable form of cell cycle arrest accompanied by a secretory program, and epithelial-mesenchymal transition (EMT) in normal epithelial cells. During carcinogenesis cells lose the ability to undergo senescence in response to TGFβ but they maintain an EMT, which can contribute to tumor progression and resistance. A screen with active kinases in HMECs upon TGFβ treatment identified that the serine threonine kinase RSK3, or RPS6KA2, reverted TGFβ-induced senescence. Interestingly, RSK3 expression decreased in response to TGFβ in a SMAD3-dependent manner, and its constitutive expression rescued SMAD3-induced premature senescence, indicating that decrease of RSK3 itself contributes to TGFβ-induced senescence. Mechanistically, using transcriptomic analyses and affinity purification coupled to mass spectrometry-based proteomics, we unveiled that RSK3 regulates senescence by inhibiting NF-κΒ pathway through the decrease in proteasome-mediated IκBα degradation. Strikingly, senescent TGFβ-treated HMEC display features of epithelial to mesenchymal transition (EMT) and during RSK3-induced senescence escape HMEC conserve EMT features. Importantly, RSK3 expression correlates with EMT and invasion, and anti-correlates with senescence and NF-κΒ in human claudin-low breast tumors and its expression accelerates formation of breast invasive tumors in the mouse mammary gland. We conclude that RSK3 switches cell fate from senescence to malignancy in response to TGFβ signals.

overall_design: hTERT-immortalized Human Mammary Epithelial Cells (HMECT) were transduced with either pWZL control or pWZL encoding RSK3 vectors and treated or not with TGFb. Three independent experiments have been performed.

first: Jean-Michel

last: Flaman

first: Anda

last: Huna

first: David

last: Bernard


title: Bulk RNA-seq of mouse ileum of Lactobacillus rhamnosus GG or Ruminococcus gnavus monoassociated mice.

city: Newark

last: Gao

state: NJ

address: 195 University Avenue

institute: Rutgers University

summary: Lacticaseibacillus rhamnosus GG (LGG) is a widely consumed probiotic whose potential beneficial effects in humans have been examined in over 250 clinical trials. However, the mechanisms by which LGG modulates host gut physiology remains unknown. R. gnavus is a pathobiont that is strongly associated with inflammatory bowel diseases. Germ free mice were mono-associated with L. rhamonosus (LGG) or R. gnavus (RG) for 21 days, ileum bulk RNA-seq were performed to compare the transcriptomic profiles of LGG or RG associated mice with the transcriptome of germ-free mouse ileum.

overall_design: Adult C57B/L6 germ-free mice were innoculated with LGG, RG or sterile PBS (as control). Successful colonization was confirmed by genomic PCR of fecal DNA using species specific primers. Twenty one days after inoculation, ilea were dissected from PBS (n=5), LGG (n=5) and RG (n=5) colonized mice. Bulk RNA-seq was performed to compare the transcriptomic profiles between germ-free (PBS) and LGG or RG colonized mice.

first: Juan

last: Flores

first: Iyshwarya

last: Balasubramanian

first: Sheila

last: Bandyopadhyay

first: Ronaldo

last: Ferraris

first: Panan

last: Suntornsaratoon


title: Revealing the developmental origin and lineage predilection of neural progenitors within human bone marrow via single cell analysis: Implications for regenerative medicine

city: Hong Kong

first: Hongfei

last: Wang

address: Pok Fu Lam

country: Hong Kong

institute: The University of Hong Kong

summary: Human bone marrow stromal cells (BMSCs) are an easily accessible and expandable progenitor population with the capacity to generate neural cell types in addition to mesoderm. Lineage tracing studies in transgenic animals have indicated Nestin+ BMSCs to be descended from the truncal neural crest. Single cell analysis provides a means to identify the developmental origin and identity of human BMSC-derived neural progenitors when lineage tracing remains infeasible. This is a prerequisite towards translational application. This study suggested BMSCs originating from truncal neural crest to be the source of cells within long bone marrow possessing neural differentiation potential. Unraveling the transcriptomic dynamics of BMSC-derived neural progenitors promises to enhance differentiation efficiency and safety towards clinical application in cell therapy and disease modelling.

overall_design: We attained transcriptomic profiles of embryonic long bone, adult human bone marrow, cultured BMSCs, and BMSC-derived neurospheres. Integrated scRNAseq analysis was supplemented by characterization of cells during culture expansion and following provision of growth factors and signaling agonists to bias lineage.

first: Changmeng

last: Zhang

first: Graham

middle: K

last: Shea


title: Murine Legionella pneumophilaInfection by Bioaerosol Inhalation in a Madison Aerosol Chamber Leads to Similar Disease Outcomes and Host Transcriptomic Responses as Intranasal Inoculation While Allowing for Bioaerosol Analysis

city: Cincinnati

last: Linz

state: Ohio

address: 26 Martin Luther King Dr W

institute: EPA

summary: Legionnaire’s Disease is a growing concern for the United States and Europe, with disease incidences rising 6-fold since 2002. These recorded cases are increasingly associated with antibiotic resistant Legionella pneumophila, the causative agent of Legionnaire’s Disease and overall Legionellosis. With this, the need to study L. pneumophilainfections has never been greater. Current methodology for Legionella pneumophila infection studies often revolves around either artificial administration using intranasal or intratracheal delivery, semi-authentic delivery using bioaerosols and individual delivery systems (i.e. nose cones), or the burgeoning field of authentic exposure scenarios using aerosol generating showerhead devices. Here, we developed an alternative method using a Madison Aerosol Chamber as a means of generating and delivering bioaerosols in mice. We show that bioaerosol delivery using the Aerosol Exposure Chamber is very effective at exposing mice to various doses of L. pneumophila. RNASeq analyses revealed a robust immune response to bioaerosol delivered L. pneumophila comprising of activations of classical markers of infection and inflammation, including Cxcl and Ccl family genes and Il-1β. Similar gene expression profiles were observed when animals were intranasally exposed to L. pneumophila. Intranasal delivery resulted in a shorter duration of activation of several genes, indicating a lack of realistic infection response. Taken together, this evidence shows that our system delivers similar, if not better, results than intranasal inoculation while allowing researchers to study bioaerosol generation and delivery mechanisms simultaneously, critical factors for studying Legionella pneumophila infection. Such a new approach will allow for more accurate investigations to understand the effects of inhaling to Legionella contaminated drinking water.

overall_design: To understand immune response in murine lung tissue after either intransal or aersosol-based delivery of Legionella pneumophila we exposed two cohorts of mice to either treatment at comparable L. pneumophila dosages. Aerosol based delivery was performed in a Madison aerosol chamber. After exposure animals were sacrificed after 1hr, 24hr, 48hr, or 72hr with biological replicates included in each subset. Intransal instillation was delivered via a bolus of 5ul to each nostril followed by a 5ul PBS wash. After exposure animals were sacrificed after 1hr, 24hr, 48hr, or 72hr with biological replicates included in each subset. From each individual in each treatment lung tissue was immediately harvested for transcriptomic profiling. Additionally, for each treatment, control animals were included and handled/treated identically to their treated counter-parts, but without L. pneumophila exposure.

first: Cameron

middle: T

last: McDaniel

first: Nathan

last: Sienkiewicz

first: Ian

last: Struewing

first: Kyle

last: McIntosh

first: Swinburne

last: Augustine

first: Tarsha

last: Eason

first: Michelle

last: Robillard

first: Eric

middle: N

last: Villegas

first: Jingrang

last: Lu


title: Single-cell transcriptome of stromal vascular fraction isolated from adipose tissue of lean and obese mice

city: Changsha

first: Limin

last: Xie

state: Hunan

address: No.139，Renmin Road Central Changsha, Hunan, China

institute: The second xiangya hospital of central south university

summary: Visceral white adipose tissue (VAT) is susceptible to inflammation as a result of obesity, and this inflammation contributes to the development of obesity-related diseases.   During the development of obesity, inflammatory immunocytes, including CD8+ T cells, Th1 cells, M1-like macrophages, neutrophils, and mast cells, accumulate in VAT.   While these profound changes in the immunocyte composition of VAT lead to local inflammation, the triggers of VAT inflammation remain poorly understood.   Therefore, a better understanding of the mechanisms underlying an early event of obesity-associated VAT inflammation will contribute to the development of novel therapies for obesity-related diseases. We utilized CellChat, which employs the expression of ligand-receptor pairs as indicators of intercellular communications, to examine the potential impact of these identified cell types within SVF on T cells. Our analysis revealed that ASCs exert the greatest influence on T cells in both lean and obese conditions.  Finally, we demonstrated that ASCs promote Tcell infiltration into WAT during the early stages of obesity.

overall_design: We performed single-cell sequencing （10X Genomics ）of stromal vascular fraction from the epididymal white adipose tissue (eWAT) of normal chow diet (NCD)-fed and 12-week high fat diet (HFD)-fed mice.

first: Tuo

last: Deng

first: Xiyan

last: Liao

first: Qin

last: Zeng


title: Single cell RNA sequencing of ischemia reperfused kidneys from Cre- and endothelial cell specific prolylhydroxylase 1, 2, and 3 knockout mice

city: Tampa

first: Ratnakar

last: Tiwari

state: FL

address: 560 Channelside Dr

department: Molecular Pharmacology & Physiology

institute: University of South Florida

summary: we performed scRNA sequening on day14 post renal IRI kidneys from a mutant mouse with acute inactivation of endothelial PHD1, PHD2 and PHD3 compared to control

overall_design: 8-10 week old Cre- and Cdh5-CreERT2;Phd1f/f, Phd2f/f, Phd3f/f mice were subjected to 25 minute ischemia reperfusion injury (IRI) at 37˚C. Cre-mediated inactivation was induced by four intraperitoneal (IP) injections of tamoxifen dissolved in 10% ethanol in corn oil at 20 mg/mL (3 mg/mouse) given every other day.On post IRI day 14, IR kidneys were isolated and processed for scRNA seq analysis.

first: Matthew

middle: J

last: Schipma

first: Pinelopi

middle: P

last: Kapitsinou


title: Comparative analysis of liver mitochondrial ncRNA in metabolic disease model mice.

city: Fukushima

first: Yoshimi

last: Homma

address: 1 Hikariga-oka

department: Biomolecular Research

country: Japan

institute: Fukushima Medical University School of Medicine

summary: ncRNA has been shown to be important for various biological processes including transcriptional regulation and protein complex formation. Mitochondoria were purified from the livers of normal mice and three metabolic model mice, and the RNA contained therein was analyzed by the next-generation sequencing method. Differential expression patterns of RNA species were detected in normal and three models, and some ncRNA were significantly up- or down-regulated in the metabolic models.

overall_design: Examination of liver mitochondrial ncRNA species in metabolic disease model mice.


title: Metabolic Model of Streptococcus suis reveals the Indispensability of catabolic ornithine carbamoyltransferase ArcB for Adapting to Anaerobiosis

city: Wuhan,Hubei

first: Hao

last: Tang

address: Shizishan Street 1

institute: Huazhong Agriculture University

summary: Pathogenic microorganisms have evolved various strategies to sense and respond to stress in order to establish infection and ensure survival within the host's complex environment. Hypoxia, a metabolic stress factor encountered by aerobic microorganisms during rapid growth, remains poorly understood in terms of pathogen adaptation. Streptococcus suis, a zoonotic pathogen causing meningitis and sepsis, exhibits remarkable adaptability to anaerobic conditions. Transcriptomic analysis reveals that anaerobic conditions significantly suppress carbohydrate metabolism in S. suis SC19 while differentially regulating genes related to toxins, metal uptake systems, and adhesion. A reconstructed genome-scale metabolic network (GSMM), constrained by transcriptomic information, was used to explore metabolic changes in SC19 under hypoxia. Anaerobic metabolism of SC19 is characterized by activation of the arginine deiminase (ADI) pathway and biosynthesis of branched-chain amino acids (BCAA). Enzymes ArcB and IlvH from these pathways were identified as potential targets and docked with drugs from the DrugBank database. Among the candidate inhibitors targeting ArcB, simvastatin and cis-(Z)-flupentixol demonstrated significant hypoxia-dependent inhibition of SC19 survival. Simvastatin was also found to attenuate virulence of SC19, proliferation, and pro-inflammatory capabilities in mice by inhibiting ArcB during the late stage of infection. This study unveils how Streptococcus suis adapts to low oxygen limitations by rewiring amino acid metabolism. A targeted antimicrobial strategy based on metabolic adaptability of pathogen is proposed to alleviate the pressure of developing new drugs against multidrug-resistant bacterial infections.

overall_design: To characterizing the impact of hypoxia on streptococcus suis SC19 growth, RNA-seq was utilized to monitor the global transcriptional regulation of SC19 at the mid-log phase (6 h) under oxygen limitation. A comparative analysis of gene expression between aerobic and anaerobic-cultivated SC19 cells revealed a global regulation of the transcriptome in response to hypoxia.

first: Lu

last: Li


title: RNA catabolism restricts ERV expression and functionalization [FKBP RNA-Seq]

city: New York

first: Robert

last: Sebra

state: New York

address: 1 Gustave L. Levy Place

institute: Icahn School of Medicine at Mount Sinai

summary: Endogenous retroviruses (ERVs) are remnants of ancient parasitic viral integrations and comprise a sizable portion of the genome in most organisms. Deregulated expression of ERVs in human is associated with a plethora of disease conditions, such as cancer and neurodegeneration. Epigenetic mechanisms silence most ERVs by generating a local repressive environment (heterochromatin) to prevent their expression. However, the mechanisms controlling the fate of ERVs residing in euchromatic regions of the genome (e.g. MERVL elements) are not well understood. Here, by integrating multidimensional epigenetic and genomic analyses, we demonstrate that silencing of euchromatic MERVL elements is achieved via transcription-coupled RNA degradation. Disrupting RNA catabolism promotes RNAPII elongation from MERVL promoters, increases MERVL expression and exonization, creating novel chimeric gene isoforms, and directing embryonic stem (ES) cells toward a terminal undifferentiated state.  Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards cell identity and potency, restricts MERVL functionalization and suppresses gene birth.

overall_design: Total RNA-Seq of mESCs undergoing rapid depletion of Exosc3 (dTAG-FKBP system) at 0hr, 6hr, 12hr. N=3 replicates per condition, 9 samples total.

first: D

last: Torre

first: Y

last: Fstkchyan

first: I

last: Marazzi


title: Targeting cis-regulatory elements of FOXO family is a novel therapeutic strategy for induction of leukemia cell differentiation

city: Kanazawa

first: Shin-ichi

last: Horike

state: Ishikawa

address: 13-1 Takaramachi

department: Research Center for Experimental Modeling of Human Disease

institute: Kanazawa University

summary: Differentiation therapy has been proposed as a promising therapeutic strategy for acute myeloid leukemia (AML); thus, the development of more versatile methodologies that are applicable to a wide range of AML subtypes is desired. Although the FOXOs transcription factor represents a promising drug target for differentiation therapy, the efficacy of FOXO inhibitors is limited in vivo. Here, we show that pharmacological inhibition of a common cis-regulatory element of forkhead box O (FOXO) family members successfully induced cell differentiation in various AML cell lines. Through gene expression profiling and differentiation marker-based CRISPR/Cas9 screening, we identified TRIB1, a complement of the COP1 ubiquitin ligase complex, as a functional FOXO downstream gene maintaining an undifferentiated status. TRIB1 is direct target of FOXO3 and the FOXO-binding cis-regulatory element in the TRIB1 promoter, referred to as the FOXO-responsive element in the TRIB1 promoter (FRE-T), played a critical role in differentiation blockade. Thus, we designed a DNA-binding pharmacological inhibitor of the FOXO-FRE-T interface using pyrrole-imidazole polyamides (PIPs) that specifically bind to FRE-T (FRE-PIPs). The FRE-PIPs conjugated to chlorambucil (FRE-chb) inhibited transcription of TRIB1, causing differentiation in various AML cell lines. FRE-chb suppressed the formation of colonies derived from AML cell lines but not from normal counterparts. Administration of FRE-chb inhibited tumor progression in vivo without remarkable adverse effects. In conclusion, targeting cis-regulatory elements of the FOXO family is a promising therapeutic strategy that induces AML cell differentiation.

overall_design: Comaprison between negative control cells and FOXO inhibitor (AS1842856) treated cells. There are three biological replicates for each conditions.

first: Kenta

last: Kurayoshi

first: Yusuke

last: Takase

first: Masaya

last: Ueno

first: Kumiko

last: Ohta

first: Kyoko

last: Fuse

first: Shuji

last: Ikeda

first: Takayoshi

last: Watanabe

first: Yuki

last: Nishida

first: Kazuyoshi

last: Hosomichi

first: Yuichi

last: Ishikawa

first: Yuko

last: Tadokoro

first: Masahiko

last: Kobayashi

first: Atsuko

last: Kasahara

first: Yongwei

last: Jing

first: Mahmoud

middle: I

last: Shoulkamy

first: Makiko

last: Meguro-Horike

first: Kensuke

last: Kojima

first: Hitoshi

last: Kiyoi

first: Hiroshi

last: Sugiyama

first: Hiroki

last: Nagase

first: Atsushi

last: Tajima

last: Hirao


title: Microarray gene expression data from RET siRNA-mediated knockdown in CDK4/6 inhibitor breast cancer resistant cells

city: Odense

first: Carlos

middle: Maria Lourenco

last: Alves

address: J.B. Winsløws vej 25 3.

country: Denmark

institute: SDU

summary:
RET is overexpressed in breast cancer cell lines resistant to combined CDK4/6i and endocrine therapy. siRNA-mediated knockdown of RET was performed to identify main pathways altered upon RET-knockdown.
We used microarrays to detail the global programme of gene expression following RET knockdown in 2 cell models resistant to combined CDK4/6 inhibitor palbociclib and fulvestrant (MPFR and TPFR). MPFR-ret and TPFR-ret were compared to MPFR-ctrl and TPFR-ctrl, respectively. The gene expression analysis revealed a significant number of genes altered in the knockdown (ret)  vs. ctrl

overall_design: Combined palbociclib and fulvestrant resistant cell lines were derived from MCF-7 and T47D cells by long-term treatment with hig concentration of palbociclib and fulvestrant. RET knockdown was performed by chemical transfection with lipofectime with siRNAs targeting RET and scramble siRNA as control. Total RNA from 3 biological replicates of RET-siRNA and control in MPFR and TPFR cells was extracted and arrayed separately in Human Transcriptome Array 2.0 (HTA, Affymetrix).

first: Alves

middle: L

last: Carla


title: VIGOR canine osteosarcoma tumor, cell line and skin samples

city: Minneapolis

first: Aaron

last: Sarver

state: MN

address: 425 East River Road

department: Masonic Cancer Center

institute: University of Minnesota

summary: VSV-IFNβ-NIS is a recombinant oncolytic vesicular stomatitis virus (VSV) that is being evaluated clinically for the treatment of advanced malignancies. As with other cancer immunotherapies, identifying biomarkers of response will be critical to the clinical advancement of this treatment approach. . RNAseq analysis showed that virtually all the long-term responders had increased expression of a CD8 T-cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS has an excellent safety profile and may provide a survival benefit for dogs with osteosarcoma whose tumors are permissive for immune infiltration.

overall_design: RNA-Seq of fresh frozen osteosarcoma tissues pre and post treatment with vesicular stomatitis virus (VSV)  as well as cell lines grown from tumors skin tissues from these samples.

first: Jaime

last: Modiano


title: Transcriptome data of rat ovarian tissue treated with Bushen Ningxin formula

city: Beijing

first: Shuang

last: Li

state: Beijing

address: Biomedical engineering

department: Biomedical engineering

institute: Beihang university

summary: mRNA and circRNA profiles of rat ovarian tissues were generated by the Arraystar rat circRNA Arrays V2 (8x15K, Arraystar)

overall_design: Twelve rats were divided into control group, model group and TCM treatment group. There were 3 rats in each group.

first: Wenjun

last: Chen


title: Transcriptome profile analyses of head kidney in roach (Rutilus rutilus), common bream (Abramis brama) and their hybrids: does infection by monogenean parasites in freshwater fish reveal differences in fish vigour among parental species and their hybrids?

city: Brno

first: Andrea

middle: Vetešníková

last: Šimková

address: Kamenice 5

department: Department of Botany and Zoology

country: Czech Republic

institute: Masaryk University

summary: Hybrid generations usually face either a heterosis advantage or a breakdown that can be expressed by the level of parasite infection in hybrid hosts. Hybrids are less infected by parasites than parental species (especially F1 generations) or more infected than parental species (especially post-F1 generations). We performed the experiment with blood-feeding gill parasite Paradiplozoon homoion (Monogenea) infecting leuciscid species, Abramis brama and Rutilus rutilus, their F1 generation, and two backcross generations. Backcross generations tended to be more parasitized than parental lines and the F1 generation. The number of differentially expressed genes (DEGs) was lower in F1 hybrids and higher in backcross hybrids when compared to each of the parental lines. The main groups of DEGs were shared among lines, however, Abramis brama and Rutilus rutilus differed in some of the top gene ontology (GO) terms. DEG analyses revealed the role of heme binding and erythrocyte differentiation after infection by blood-feeding P. homoion. Two backcross generations shared some of the top GO terms representing mostly downregulated genes associated with P. homoion infection. KEGG analysis revealed the importance of disease-associated pathways. The majority of them were shared by two backcross generations. Our study revealed the most pronounced DEGs associated with monogenean infection in backcross hybrids, potentially explained by hybrid breakdown. The gene expression of F1 hybrids was little affected by P. homoion, suggesting the hybrid advantage.

sample_organism:
Abramis brama
Rutilus rutilus
Rutilus rutilus x Abramis brama

overall_design:
Transcriptome profile analyses of head kidney in roach (Rutilus rutilus), common bream (Abramis brama), and their F1 and backcross hybrids to see if infection by monogenean parasites in freshwater fish does reveal differences in fish vigour among parental species and their hybrids.
Transcriptomic data includes the fish samples termed using three abbreviations, i.e., K – control samples (samples not exposed to parasite infection), OK - experiment with larval (termed oncomiracidia) infection of Paradiplozoon homoion, and PH – cohabitation experiment with P. homoion (see details below). Each of OK and PH representing independent experiment realized by two different methodologies using the same biological system - the infection by P. homoion (Monogenea) in Abramis brama, Rutilus rutilus and their two F1 generations (F1 generation with A. brama mtDNA, and F1 generation with R. rutilus mtDNA), and two backcross lines (backcross generation of F1 hybrid with A. brama mtDNA and paternal A. brama, and backcross generation of F1 hybrid with A. brama mtDNA and paternal R. rutilus).
We performed transcriptome assembly from all the samples of A. brama and R. rutilus, separately. Then, we used the R. rutilus transcriptome for RNA-seq data analyses, including differential expression and functional gene enrichment (GO, KEGG) analyses because it showed better results than the other transcriptome, and at the same time, we avoided complicated cross-referencing. Two experiments (termed OK and PH) with the same biological system were performed. The manuscript associated with the submitted RNA-seq data of both experiments focused, however, only on the analysis of the OK experiment.

first: Kristína

middle: C

last: Křížová

first: Kristýna

last: Voříšková

first: Lukáš

last: Vetešník

first: Vojtěch

last: Bystrý

first: Martin

last: Demko


title: scATAC-seq analysis using gastric mucosa with intestinal metaplasia

city: Tsukiji, Chuo-ku

first: Chihiro

last: Takeuchi

state: Tokyo

department: Division of Epigenomics

institute: National Cancer Center Research Institute

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Nucleosome positionings of gastric mucosa with intestinal metaplasia at single cell resolution

overall_design: We performed scATAC-seq using gastric mucosa with intestinal metaplasia and gastric normal mucosa.

first: Satoshi

last: Yamashita

first: Yu-Yu

last: Liu

first: Toshikazu

last: Ushijima


title: ChIP-seq analysis of H3K27acethylation using gastric mucosa with intestinal metaplasia

summary: Histone modification of H3K27acethylation in gastric mucosa with intestinal metaplasia

overall_design: We performed ChIP-seq for H3K27acethylation using gastric mucosa with intestinal metaplasia.


title: Genome-wide DNA methylation analysis using gastric crypts with intestinal metaplasia and NOS2-inducible cell lines

type: Methylation profiling by genome tiling array

summary: DNA methylation in gastric crypts with and without intestinal metaplasia, and NOS2-inducible cell lines

overall_design: Bisulfite converted DNA from the 26 samples were hybridised to the Infinium MethylationEPIC BeadChip Kit


title: Localized condensation of the cBAF remodeler is governed by ARID1A/B and is required for transcriptional activation [CUT&RUN]

city: Boston

first: Cigall

last: Kadoch

state: Massachusetts

address: 450 Brookline Avenue

institute: Broad Institute of MIT and Harvard, Harvard Medical School, Dana-Farber Cancer Institute

summary: Specifically, we find that the N-terminal disordered region of ARID1A/B and the DNA binding ARID domain are required for condensate formation and chromatin targeting.

overall_design: Cleavage Under Targets and Release (CUT&RUN) for BAF subunits ARID1A (HA-tagged), SMARCA4, SMARCC1, ARID1B (HA-tagged) as well as the histone modification H3K27ac in AN3CA cells.

first: Ajinkya

last: Patil

first: Clayton

last: Collings


title: Effects of metals on the gene expression of Cupriavidus basilensis SRS

city: Athens

first: He

last: Fu

state: GA

address: 120 Cedar St

department: Microbiology

institute: University of Georgia

summary: To investigate the molecular mechanisms of how Cupriavidus basilensis SRS may aid bioextraction of metals from ores, we exposed C. basilensis SRS to different metals, as well as natural ores

overall_design: Cupriavidus basilensis SRS was grown in media supplemented with 100 PPM Cerium, Lanthanum, Copper or 1g/ml Apatite or Phosphogypsum until mid-exponential phase; cells were saved in RNA-later before harvested for RNA extraction

first: Alex

last: Kugler

first: Amber

last: Depoy

first: Robin

last: Brigmon

first: Elizabeth

last: Ottenson


title: Transcriptomic profiling reveals differential cellular response of copper oxide nanoparticles and polystyrene nanoplastics in perfused human placenta

city: Tampere

first: Dario

last: Greco

address: Arvo ylpön Katu 34

department: Faculty of Medicine and Health Technology

country: Finland

institute: Tampere University

summary: Concerns about the potential risks to human health due nanoparticulate pollution have been emerging. However, the risks to sensitive populations, such as pregnant individuals and their unborn children are poorly characterised. With increasing evidence of environmental particles passing the placenta, their potential adverse effects of on pregnancy and fetal development need to be assessed. Here, we investigated the impact of copper oxide (CuO) and polystyrene (PS) nanoparticle exposure on gene expression in ex vivo perfused human placental tissue.

overall_design:
Human placentas from uncomplicated full term pregnancies were obtained from donors with written informed consent. The gene expression in the placental tissues were screened prior to any treatment (n = 8), and after 6 hours of perfusion with perfusion medium (control samples, n = 2), 6 hours of perfusion with 10 µg/mL of copper oxide (CuO) nanoparticles (n = 3), or 6 hours of perfusion with polystyrene (PS) nanoplastics (n = 3).
Please note that the experiments were technically as dual channel (eg, Cy3 and Cy5-labeled samples hybridized to the same array) but processed the results as though they are single channel (Cy3 and Cy5 signals are calculated). Therefore, each raw data file contains raw data for two samples (as indicated in the description field of the corresponding sample records).

first: S

last: Chortarea

first: G

last: Gupta

first: L

middle: A

last: Saarimäki

first: W

last: Netkueakul

first: P

last: Manser

last: Aengenheister

first: A

last: Gogos

last: Wichser

first: V

last: Fortino

last: Wick

first: D

first: T

last: Buerki-Thurnherr


title: Ceramide blockade in murine hematopoietic stem cells

city: philadelphia

first: Stephanie

last: Hurwitz

address: 3400 Spruce St

institute: University of Pennsylvania

summary: Hematopoietic stem and progenitor cells (HSPCs) rely upon cellular crosstalk, including extracellular vesicles (EVs) for lifelong niche occupancy and cellular function. Vesicle secretion is tightly linked to intracellular homeostasis; however, these mechanisms are poorly understood in HSPCs, particularly at the single-cell level. In this study, we target ceramide-dependent EV secretion by pharmacologic blockade in ex vivo expanded HSPCs. We use these cells to investigate single-cell resolution of short-term and delayed transcriptional changes induced by ceramide-EV inhibition.

overall_design: Single cell RNA sequencing of primary murine HSPCs grown in PVA-supported ex vivo expansion cultures at 24 and 120 hours following GW4869 treatment.

first: Seul

last: Jung

first: Peter

last: Kurre


title: FEM2  regulates the whole genome 24-nt siRNA accumulation and CHH DNA methylation in rice [Bisulfite-Seq]

city: Nanjing

first: Dachao

last: Xu

address: Weigang No.1

institute: Nanjing Agricultural University

type: Methylation profiling by high throughput sequencing

summary: To investigate the  function of FEM2 in regulation of DNA methylation, 18-day-old seedlings wer used for RNA-seq, BS-seq and sRNA-seq.

overall_design: whole genome wide DNA methylation data by bisulfite sequencing

first: Dong-Lei

last: Yang


title: FEM2 regulates the whole genome 24-nt siRNA accumulation and CHH DNA methylation in rice

type: Non-coding RNA profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Comparative Transcriptome Analysis of Peripheral Blood Mononuclear Cells Across Clinical Cohorts of Hepatitis B Virus Induced Hepatocellular Carcinoma and Chronic Asymptomatic Hepatitis B Infection in Nigeria

city: Ede

first: Oluwadamilola

middle: Gideon

last: Osasona

state: Osun

address: Akoda

department: Biological Sciences

country: Nigeria

institute: Redeemer's University

summary: Hepatitis B Virus (HBV) infection affects about 20 million Nigerians and its most fatal complications is the hepatocellular carcinoma (HCC). Chronic hepatitis B (CHB) infection progresses to HCC which lacks sensitive and specific biomarkers at early stage for detection and subsequent treatment. Efforts in this study is therefore to assess the differential gene expression across clinical cohorts of HBV infection to identify the potential biomarkers of early-stage HCC. Total RNA was extracted and the peripheral blood mononuclear cells (PBMC) in 12 samples were sequenced through the bulk RNA sequencing modality. This was followed by bioinformatic analysis for differential gene expression studies using GALAXY, Qiagen RNA-Sequencing Analysis and DAVID pipelines. Transcriptomic analysis of the PBMC identified a total of 66,726 genes and transcripts. Among patients with HBV-Induced HCC vs CHB, a total of 3,204 genes were differentially expressed with 76 and 272 genes significantly upregulated and downregulated respectively. Across the clinical cohorts of HBV-induced HCC vs healthy controls, 4561 were dysregulated with 370 and 375 genes significantly upregulated and downregulated respectively. Across the significantly upregulated genes of the cohort HBV-induced HCC vs healthy controls, 86 Gene ontology (GO) terms were identified, 19 clustered, 103 terms did not cluster, while across the downregulated cohort, 255 GO terms were identified, 63 clustered, 335 did not. The mitogen-activated protein kinase (MAPK) signalling pathway, cell division cycle and microRNA pathways in the HCC cohort were dysregulated

overall_design: To investigate the differential gene expression profiles across clinical cohorts of patients with HBV-induced hepatocellular carcinoma, chronic hepatitis B and healthy controls. We recruited 36 patients and subsequently divided the subjects into sequencing cohort (n=12) and validation cohort (n=24). We conducted gene expression profiling studies from data obtained from the HBV-induced HCC, chronic asymptomatic HBV patients and healthy controls. Differential gene expression profile analysis of the RNA-seq data from the 12 samples were studied using GALAXY and DAVID pipeline.

first: Osasona

last: Oluwadamilola Gideon

first: Onikepe

last: Folarin

first: Abiola

last: Arowosaye Opeyemi

first: Oguntoye

last: Oluwatosin Oluwagbenga


title: FEM2  regulates the whole genome 24-nt siRNA accumulation and CHH DNA methylation in rice [sRNA-Seq]

summary: To investigate the  function of FEM2 in regulation of 24-nt siRNA accumulation, 18-day-old seedlings wer used for RNA-seq, BS-seq and sRNA-seq.

overall_design: 24-nt siRNA expression analysis between fem2 mutant and WT.


title: Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids

city: Kamakura

first: Satoshi

last: Kondo

state: Kanagawa

address: 10-1 tebiro 6-chome

institute: Toray Industries,Inc.

summary: Fetal lung tissue fragments were implanted into adult lungs and miRNA expression at day 7 were compared. microRNA-487-3p, 374-5p, and 20b-5p expression changed by more than 2-fold in corticosteroid administration groups.

overall_design:
Fetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided in the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. For each group, microscopic alveolar space area, CT value, fluorescence immunostaining, and miRNA expression were compared.
MS-, fetal lung implantation into the adult left lung parenchyma; MS+,implantation with post-caval lobectomy; and DEX, implantation with post-caval lobectomy and corticosteroid administration.

first: Daisuke

last: Matsumoto

first: Hiroaki

last: Toba


title: Nanog mediates erasure of imprint-associated epigenetic marks via Prdm14

city: Cambridge

first: Laura

last: Biggins

address: Babraham Research Campus

department: Bioinformatics

country: United Kingdom

institute: The Babraham Institute

summary: Nanog’s target Prdm14 is upregulated in 2iL-ESCs and leads to loss of Zfp57 and epigenetic marks from imprinting control regions.

overall_design: Single cell bisulphite sequencing of primordial germ cells collected from Prdm14-null embryos at day 13.5 of gestation

first: Yael

last: Costa

first: Lawrence

middle: E

last: Bates

first: Elze

last: Lauzikaite

first: Charlotte

last: Handford

first: António

last: Galvão

first: Juan

last: Castillo-Fernandez

first: Mercedes

last: Barrero

first: Anna

last: Mallol

first: Imogen

last: Stockwell

first: Katsiaryna

last: Maskalenka

first: Harry

last: Leitch

first: Sabine

last: Dietmann

first: Mitinori

last: Saitou

first: Gavin

last: Kelsey

first: Bernhard

last: Payer

first: Irina

last: Mohorianu

first: José

last: Rebelo da Silva


title: Development of next-generation therapeutic antibodies using rapid mRNA immunization of humanized mice

city: West Haven

first: Sidi

last: Chen

state: CT

address: 850 West Campus Drive

institute: Yale University

summary: We generated LNP-mRNAs encoding B.1.1.529 SARS-CoV-2 spike, or single transmembrane protein CD22, or GPCR GPRC5D, respectively. Those LNP-mRNAs were intramuscularly administered in a human IgG and IgK knock-in mouse. Single cell VDJ-seq unveiled the sequences of human monoclonal antibodies targeting those target antigens.

overall_design: Three sets of B cells were isolated and processed from the spleen, lymph nodes, bone marrows, or peripheral blood of immunized mouse. Those B cells were subjected to scVDJ-seq, respectively.

first: Paul

last: Renauer


title: In-Depth Characterization of Cell Subculture Process based on Multi-Omics

first: Yunchao

last: Huang

address: Boxing 2nd Road

institute: Beijing Institute of Biological Products Company Limited

summary: To investegate the mechanism of physiological changes during cell digestion, we analyzed the levels of RNAs in cells treated with animal-based enzymes and animal origin-free enzymes.

overall_design: The Vero cells were divided into 3 groups. The first group (Group 1) was digested with trypsin at 37°C. The cells collected immediately after digestion were set to 0 h, and the digested cells were placed back in the cell incubator for 8 hours. After the cells were digested with non-enzymatic digestion solution and then collected for 8 h, the cells af-ter trypsinization at 37°C were further cultured for 24 hours, and the cells were di-gested with non-enzymatic digestion solution and collected for 24 h. The second group (Group 2) was digested with TrypLE at 37°C, then set the cells collected immediately after digestion as 0 h, place the digested cells back in the cell incubator for 8 hours, and digest the recovered cells with non-enzyme digestion solution. Set it to 8h, continue to culture the cells digested with TrypLE digestion solution at 37°C for 24 hours, and then digest the cells with non-enzyme digestion solution for 24h. The third group (Group 3) used 4°C TrypLE digestion solution at 25°C digestion, the cells collected immediately after digestion were set to 0 h, and the digested cells were placed back in the cell incu-bator for 8 hours, and the cells collected after digestion with non-enzyme digestion solution were set to 8 h, and digested with TrypLE digestion solution at 4°C. After the cells were cultured for 24 hours, the collected cells were digested with non-enzymatic digestion solution and set to 24 hours. In addition, Vero cells were digested with an enzyme-free digestion solution at 37°C, and the immediately harvested cells were set as the control group. Each sample has three biological replicates.

first: Shouzhi

last: Yu

first: Chongyang

last: Wu

first: Weibin

last: Fu

first: Hongyang

last: Liang

first: Chen

first: Yue

last: Cheng

first: Yancen

last: Guo

first: Ying

last: Zhang

first: Hui

last: Wang

first: Xiaoming

last: Yang


title: FEM2  regulates the whole genome 24-nt siRNA accumulation and CHH DNA methylation in rice [RNA-Seq]

first: Dachao

last: Xu

summary: To investigate the  function of FEM2 in regulation of gene expression, 18-day-old seedlings wer used for RNA-seq, BS-seq and sRNA-seq.

overall_design: Differential genes expression analysis between fem2 mutant and WT.

first: Dong-Lei


title: Effect of depletion of YY1 on gene expression in ESCC cells.

city: Jinan

first: chunyan

last: zheng

address: Jiyan Road

institute: Shandong Cancer Hospital and Institute

summary:
To investigate the role of YY1 in ESCC, we established  shYY1 ESCC cell lines in which target gene has been knocked down by shRNA.
We then performed gene expression profiling analysis using data obtained from RNA-seq of shNC and shYY1 cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq after interferring the expression of YY1.

first: Chunyan

last: Zheng

first: Baosheng

last: Li


title: Effect of ferroptosis of ACSL4, GPX4 and PTGS2 on gene expression during Acute osteofascial Compartment Syndrome of SD rats' skeletal muscle cells

city: NanNing

first: He

last: Ling

state: Guangxi

address: NO. 6 ShuangYong Road

institute: the First Affiliated Hospital of Guangxi Medical University

summary: To investigate the cooperative function ACSL4/GPX4/PTGS2 complex in the regulation of Acute osterfascial Compartment Syndrome, we established the Acute osterfascial Compartment Syndrome model of SD rats by ligation with low-elastic band on the knee joint of rats.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for ACS SD rats(especially ACSL4, GPX4 and PTGS2)

first: Zhao

first: Qingzhen

last: Lu

first: Dingquan

first: Tiejun

first: Junfeng

first: Jianwen

first: Jinmin

last: Zhao

first: Wei

last: Su


title: ALKBH5 Induces Fibroblast-to-Myofibroblast Transformation During Hypoxia to Protect Against Cardiac Rupture After Myocardial Infarction

city: Hangzhou

first: Rifeng

last: Gao

state: Zhejiang

address: No. 88 Jiefang Road

institute: Zhejiang University

summary: Objectives: To investigate the role of ALKBH5 in fibroblasts during post-myocardial infarction (MI) repair. Background: N6-methyladenosine (m6A) mRNA modification has been shown to play an important role in cardiovascular diseases. The RNA demethylase, AlkB homolog 5 (ALKBH5), is an m6A "eraser" that is responsible for decreased m6A methylation. However, its role in cardiac fibroblasts during the post-MI healing process remains elusive. Methods: MI was mimicked by permanent left anterior descending artery ligation in global ALKBH5-knockout, ALKBH5-knockin, and fibroblast-specific ALKBH5-knockout mice to study the function of ALKBH5 during post-MI collagen repair. Methylated RNA immunoprecipitation sequencing was performed to explore potential ALKBH5 targets. Results: Dramatic alterations in ALKBH5 expression were observed during the early stage post-MI and in hypoxic fibroblasts. Global ALKBH5 knockin reduced infarct size and improved cardiac function after MI. The global and fibroblast-specific ALKBH5-knockout mice both exhibited low survival rates along with poor collagen repair, impaired cardiac function, and cardiac rupture. Both in vivo and in vitro ALKBH5 loss led to impaired fibroblast activation and decreased collagen deposition. Additionally, hypoxia, but not TGF-β1 or Ang II, upregulated ALKBH5 expression in myofibroblasts in a HIF-1α-dependent transcriptional manner. Mechanistically, ALKBH5 promoted the stability of ErbB4 mRNA and the degradation of ST14 mRNA via m6A demethylation. Fibroblast-specific ErbB4 overexpression ameliorated the impaired fibroblast-to-myofibroblast transformation and poor post-MI repair due to ALKBH5 knockout. Conclusions: Fibroblast ALKBH5 positively regulates post-MI healing via post-transcriptional modification and stabilization of ErbB4 mRNA in an m6A-dependent manner. Targeting ALKBH5/ERBB4 may be a potential therapeutic option for post-MI cardiac rupture.

overall_design: To identify the m6A demethylation targets of ALKBH5 in response to acute MI, MeRIP-seq and RNA-seq were performed using RNA isolated from the infarct areas of ALKBH5-KO and WT mice 5 days after MI surgery (WT, n=3 vs. KO, n=3).

first: Kun

first: Aijun

last: Sun


title: Gasdermin D Mediates Endoplasmic Reticulum Stress via FAM134B to Regulate Cardiomyocyte Autophagy and Apoptosis in Doxorubicin-induced Cardiotoxicity

summary: These results suggest that GSDMD promotes autophagy and induces cardiomyocyte apoptosis by modulating the reaction of FAM134B and LC3, thereby promoting DIC injury. Targeted regulation of GSDMD may be a new target for the prevention and treatment of DIC.

overall_design: We used GSDMD knockout mice and control mice for DOX treatment.

first: Junbo

last: Ge

first: Yanan

last: Qu

first: Xiang

last: Wei


title: Translating ribosome affinity purification analysis of dopaminergic neurons of the mouse ventral midbrain with age and alpha-synuclein overexpression.

city: Oxford

first: Peter

last: Kilfeather

address: Biochemistry Building Phase II, South Parks Road

department: Department of Physiology, Anatomy and Genetics

institute: University of Oxford

summary:
To investigate the cell type-specific expression features of dopaminergic neurons in ventral midbrain, we generated DAT-TRAP mice.
We then performed gene expression profiling analysis using data obtained from RNA-seq of samples collected from 3- and 18-month old mice. OVX were also bred to overexpress human alpha-synuclein. Short and long-read sequencing were performed.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for DAT-TRAP  samples in 3- and 18-month old mice, with and without human alpha-synuclein overexpression.

first: Kilfeather

last: Peter

first: Wagner

last: Katharina


title: To compare the transcriptome expression of cumulus granulosa cells between PCOS patients with insulin resistance and women undergoing assisted reproduction for fallopian tube reasons

city: shijiazhuang

first: zhiming

last: zhao

state: hebei

address: 215 heping west road

institute: The second hospital of hebei medical university

summary:
Purpose
polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of childbearing age. It is characterized by follicular dysplasia and hyperandrogenemia. Insulin resistance plays an important role in the development of PCOS.However, the mechanism of regulation and interaction between insulin resistance and follicle development remains unclear.The aim of this study was to identify differential genes associated with follicle development in cumulus granulosa cells in PCOS patients with insulin resistance compared with controls.
Methods
In this study, RNA-seq, bioinformatics analysis and reverse transcription qPCR (RT-qPCR) were used to analyze the gene expression in cumulus granulosa cells.A total of seven cDNA libraries were constructed from three PCOS samples and four control samples.3 μg of RNA was used as starting material for each sample.Ribosomal RNA was removed using the Epicentre rigo-zero ™ Gold Kit (Epicentre, Illumina, Madison, WI, USA).
Results
Compared with the control group, there were 2233 DEGs in the PCOS group, including 1158 up-regulated genes and 1075 down-regulated genes. Some different expression patterns were observed in the two groups.The next series of experiments verified the effect of some genes on oocyte development.
Conclusion
Our study showed that the differential expression of transcriptome in cumulus granulosa cells could affect the growth, development and maturation of oocytes.Meanwhile, the results of RT-PCR and Elisa showed that the expression of renin angiotensin system was changed in PCOS patients with insulin resistance, and these changes could affect oocyte maturation and excretion through cumulus granulosa cells.

first: Zhiming

first: Yuanyuan

last: Liu


title: Localized condensation of the cBAF remodeler is governed by ARID1A/B and is required for transcriptional activation

first: Cigall

last: Kadoch


title: Localized condensation of the cBAF remodeler is governed by ARID1A/B and is required for transcriptional activation [ATAC-seq]

summary: This study investigates the role of the ARID1A/B subunits of the cBAF complex using in vitro and cell-based models. Specifically, we find that the N-terminal disordered region of ARID1A/B and the DNA binding ARID domain are required for condensation and proper orientation on chromatin respectively.

overall_design: Cleavage Under Targets and Tagmentation (CUT&Tag) for BAF subunits ARID1A (HA-tagged), SMARCA4, SMARCC1, ARID1B (HA-tagged) as well as the histone modification H3K27ac in AN3CA cells.

first: Ajinkya

last: Patil

first: Clayton

last: Collings


title: RNA catabolism restricts ERV expression and functionalization [ChIP-seq]

city: New York

first: Robert

last: Sebra

address: 1 Gustave L. Levy Place

institute: Icahn School of Medicine at Mount Sinai

summary: Endogenous retroviruses (ERVs) are remnants of ancient parasitic viral integrations and comprise a sizable portion of the genome in most organisms. Deregulated expression of ERVs in human is associated with a plethora of disease conditions, such as cancer and neurodegeneration. Epigenetic mechanisms silence most ERVs by generating a local repressive environment (heterochromatin) to prevent their expression. However, the mechanisms controlling the fate of ERVs residing in euchromatic regions of the genome (e.g. MERVL elements) are not well understood. Here, by integrating multidimensional epigenetic and genomic analyses, we demonstrate that silencing of euchromatic MERVL elements is achieved via transcription-coupled RNA degradation. Disrupting RNA catabolism promotes RNAPII elongation from MERVL promoters, increases MERVL expression and exonization, creating novel chimeric gene isoforms, and directing embryonic stem (ES) cells toward a terminal undifferentiated state.  Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards cell identity and potency, restricts MERVL functionalization and suppresses gene birth.

overall_design: Exosc3 cKO vs. control

first: D

last: Torre

first: Y

last: Fstkchyan

first: I

last: Marazzi


title: HR+/HER2- Breast Cancer Cell and Normal Breast Epithelial Cell  Derived Exosome RNA Expression

city: Shenyang

first: qi

last: zhou

address: No.155, Nanjing North Street, Heping District,

institute: CMU

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

summary: AS a key medium for intercellular communication, exosome plays an important role in the occurrence and development of various forms of cancers, including breast cancer. However, the RNA from breast cancer-derived exosome remains to be explored. The HR+/HER2− breast cancer is the most common subgroup of breast cancer, we collected and primary cultured breast cancer and normal breast epithelial cells from three HR+/HER2− breast cancer patients, isolated the supernatant and extracted RNA from exosomes, and then performed microarray assays.

overall_design: Three pairs of breast cancer tissues and normal breast tissues were collected at Tangshang people’s hospital for the establishment of primary cultures. Subsequently, the supernatant of the cell culture medium was collected, and the exosomes were extracted by differential ultracentrifugation. Total RNA was extracted from exosomes and used to assay gene expression patterns using microarrays.

first: Qi

last: Zhou

first: Feng

last: Jin


title: RNA catabolism restricts ERV expression and functionalization [bulk RNA-seq]


title: RNA catabolism restricts ERV expression and functionalization [TT-seq]


title: RNA catabolism restricts ERV expression and functionalization [Iso-seq]


title: Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [SM_CHOW_HFSC]

city: Valencia

first: Daniel

last: Perez-Cremades

state: Valencia

address: 15 Blasco Ibañez Avenue

department: Physiology Department

country: Spain

institute: University of Valencia

summary: We report transcriptomic changes in skeletal muscle of systemic miR-181a2b2 KO mice in response to chow and HFSC diet feeding and hindlimb ischemia

overall_design: RNA-sequencing on skeletal muscle of systemic miR-181a2b2 KO mice in response to chow and HFSC diet feeding and hindlimb ischemia

first: Henry

middle: S

last: Cheng

first: Rulin

last: Zhuang

last: Pérez-Cremades

first: Jingshu

last: Chen

first: Anurag

last: Jamaiyar

first: Aspasia

last: Tzani

first: Jorge

last: Plutzky

last: Henao-Mejia

first: Philip

last: Goodney

first: Mark

last: Creager

first: Marc

last: Sabatine

last: Bonaca

last: Feinberg


title: Localized condensation of the cBAF remodeler is governed by ARID1A/B and is required for transcriptional activation [CUT&Tag]

city: Boston

first: Cigall

last: Kadoch

address: 450 Brookline Avenue

institute: Broad Institute of MIT and Harvard, Harvard Medical School, Dana-Farber Cancer Institute

first: Ajinkya

last: Patil

first: Clayton

last: Collings


title: Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia

last: Perez-Cremades

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

overall_design: Refer to individual Series


title: Localized condensation of the cBAF remodeler is governed by ARID1A/B and is required for transcriptional activation [RNA-seq]

summary:
This study investigates the role of the ARID1A/B subunits of the cBAF complex using in vitro and cell-based models.
Specifically, we find that the N-terminal disordered region of ARID1A/B and the DNA binding ARID domain are required for condensation and proper orientation on chromatin respectively.

overall_design: Comparative gene expression profiling analysis of RNA-seq data using AN3CA cells expressing ARID1A WT or mutants.


title: YAP1 maintains active chromatin state in head and neck squamous cell carcinomas that promotes tumorigenesis through cooperation with BRD4 [RNA-seq]

first: Srinivas Vinod

last: Saladi

address: 20 Staniford St

institute: Harvard Medical School

summary: The conserved Hippo-YAP signaling pathway is involved in homeostasis and organ development through the regulation of cell growth and cell death. Its downstream effectors YAP1, WWTR1 (TAZ), and TEAD are transcriptionally active in the majority of human cancers, often as a result of copy-number variation or inactivating mutations of core components and upstream regulators. Analysis of The Cancer Genome Atlas and other published data of head and neck squamous cell carcinoma (HNSCC) reveals somatic alterations of the Hippo-YAP pathway in approximately 50% of HNSCC, making it the most altered pathway in these cancers. Unfortunately, highly specific inhibitors targeting the YAP1 transcriptional complex are not available, and better strategies to target this pathway are sought. Here, we show that FAT1 (FAT Atypical Cadherin 1), an upstream inhibitor of YAP1, is mutated either by missense or truncating mutation in 29% of HNSCC. Comprehensive proteomic and drug-screening studies across pan-cancer models confirm that FAT1-mutant HNSCC exhibit selective and higher sensitivity to BRD4 inhibition by JQ1. Epigenomic analysis reveals an active chromatin state in FAT1-mutant HNSCC cells that is driven by the YAP/TAZ transcriptional complex through recruitment of BRD4 to deposit active histone marks, thereby maintaining an oncogenic transcriptional state. This study reveals a detailed cooperative mechanism between YAP1 and BRD4 in HNSCC and suggests a specific therapeutic opportunity for the treatment of this subset of head and neck cancer patients.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for CAL33 cells with or without JQ1 treatment

first: Nana

first: Gabriel

last: Golczer

first: Michael

last: Lawrence

first: Srinivas

middle: V


title: Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [BM_CHOW]

first: Daniel

summary: We report transcriptomic changes in bone marrow cells of systemic miR-181a2b2 KO mice in response after chow diet feeding and hindlimb ischemia

overall_design: RNA-sequencing on bone marrow cells after chow diet feeding and hindlimb ischemia

first: Henry

last: Cheng

last: Zhuang

last: Pérez-Cremades

last: Chen


title: Activation of gp130 signaling in T-cells drives TH17-mediated multi-organ autoimmunity

city: Berlin

first: Francis

middle: G

last: Baumgartner

address: Hindenburgdamm 30

country: Germany

institute: Charité University Medicine Berlin

summary:
Purpose: Recently discovered activating Interleukin-6 receptor subunit beta (IL6ST, encoding glycoprotein 130 (gp130)) mutations, as well as germline Signal transducer and activator of transcription 3 (STAT3) gain-of-function mutations are associated with multi-organ autoimmunity, severe morbidity, and adverse prognosis, resulting in an unmet medical need.
Methods: To dissect crucial cellular subsets and disease biology involved in activated gp130 signaling, in this study we constitutively activated the gp130/JAK/STAT3 axis by means of a transgene, L-gp130, specifically targeted to T-cells.
Results: Activating gp130 signaling in vivo resulted in fatal early-onset multi-organ autoimmunity, resembling numerous clinical features of human STAT3 gain-of-function disease. We observed strong T-cell activation and effector differentiation, accompanied by TH17 expansion and interferon-gamma production. Transcriptome profiling of murine CD4+ and CD8+ T-cells revealed commonly dysregulated genes and a STAT3 gain-of-function signature that was used to discriminate between STAT3 gain-of-function and healthy control patients.
Conclusions: Hyperactive gp130/STAT3 signaling leads to strong TH17-mediated autoimmunity phenotypically resembling human STAT3 gain-of-function disease and identify TH17-cells as a key cellular subset for initiation and maintenance of autoimmunity

overall_design: Purified splenic CD4+ and CD8+ T-cell mRNA profiles of 5 weeks old CD4Cre+/− (control) and L-gp130fl/+;CD4Cre+/− mice

first: Stefanos

last: Bamopoulos

first: Ulrich

last: Keller


title: Methylation analysis of serum cfDNA pooled samples for the discovery of non-invasive biomarkers for colorectal cancer

city: Vigo

first: María

last: Gallardo-Gómez

address: Campus As Lagoas Marcosende

institute: Universidad de Vigo

summary: We explored the differential methylation patterns found in cfDNA between no neoplasia (NN; individuals with no colorectal findings, benign pathologies and non-advanced adenomas) and patients with advanced neoplasia (AN; advanced adenomas and colorectal cancer) using pooled samples, for the discovery of non-invasive methylation biomarkers for CRC screening. cfDNA was extracted from serum samples and methylation measurements were assessed with the Infinium MethylationEPIC BeadChip. Data was mainly preprocessed and analyzed with R/Bioconductor packages.

overall_design:
We explored the differential methylation patterns found in cfDNA between no neoplasia and advanced neoplasia using pooled samples.
cfDNA was extracted from 280 serum samples with a modifed phenol-chlorophorm protocol. A total of 28 cfDNA pooled samples were constructed using equal amounts of cfDNA from 5 men and 5 women with the same colorectal pathology as described in Gallardo-Gómez et al., Clinical Epigenetics 2018;10:53 (PMID: 29686738). cfDNA was bisulfite treated and was analyzed with the Infinium MethylationEPIC BeadChip microarray, covering over 850,000 CpG sites across the genome.

first: Loretta

last: De Chiara


title: Genome wide RNA-Seq of CsubMADS1 OX and wildtype Coccomyxa subellipsoidea C-169 cultures

city: Thiruvananthapuram

first: Saraswati

last: Nayar

state: Kerala

address: Thycaud Post, Poojappura

country: India

institute: Rajiv Gandhi Centre for Biotechnology

summary: To assess the significant downstream pathways affected by the overexpression of CsubMADS1 in Coccomyxa, transcriptome analysis was carried out using RNA sequencing of three biological replicates each from WT and CsubMADS1 OX at stationary phase (3h before dark phase). The stationary phase was chosen for the analysis because this is when the nutrients start depleting in the medium and starvation stress is induced.

overall_design: mRNA profiles of stationary phase cultures of CsubMADS1 OX and wild type Coccomyxa subellipsoidea


title: Expression data from Arabidopsis sid2.2 mutant (ICS1 mutant) and wild type (Col-0)

city: Versailles

first: Celine

last: Masclaux-Daubresse

address: Route de Saint Cyr

institute: IJPB INRAE

summary:
The sid2.2 mutant (Dewdney et al. 2000) with deletion/arrangement in exon 9 is deficient for salicylic acid synthesis.
We used Affymetrix microarrays to detail the global programme of gene expression underlying metabolic and cellular changes in the rosettes of the Arabidopsis sid2.2 mutant and wild type  grown under strong sulfate limitation.

overall_design: Two genotypes: wild type (Col-0) and sid2.2  mutant  were grown under low sulfate (S-)  60 days in short day condition. Three consecutive cultures (C1 C2 and C3) were performed at several month interval. For the three cultures and each genotype, rosettes of >6 plants were harvested  and mixed to extract RNA.

first: Céline

first: Christelle

last: Thibault


title: Bone marrow MiR-181a/b-CXCR4 signaling axis impairs hematopoiesis, monocytosis, and angiogenesis in diabetic critical limb ischemia [BM_HFSC]

summary: We report transcriptomic changes in bone marrow cells of systemic miR-181a2b2 KO mice in response after HFSC diet feeding and hindlimb ischemia

overall_design: RNA-sequencing on bone marrow cells after HFSC diet feeding and hindlimb ischemia

first: Rulin

first: Jingshu

first: Anurag

last: Jamaiyar

first: Aspasia

last: Tzani

first: Jorge

last: Plutzky

last: Henao-Mejia

first: Philip

last: Goodney

first: Mark

last: Creager

first: Marc

last: Sabatine

last: Bonaca

middle: W

last: Feinberg


title: Gene expression profile of  human leukemic cell line with cMyc mutations

city: Cincinnati

first: Kwangmin

last: Choi

state: Ohio

address: 333 Burnet Avenue

department: Experimental Hematology & Cancer Biology

institute: Cincinnati Children's Hospital Medical Center

summary: RNA-sequencing revealed that c-Myc-related gene signatures were negatively enriched in MV4;11(K148R) cells as compared to parental MV4;11, suggesting that lack of acetylation at K148 results in diminished c-Myc activity.  In contrast, MV4;11(K148Q) cells exhibit a positive enrichment of c-Myc-regulated gene signatures as compared to MV4;11(K148R) cells, confirming that loss of acetylation of c-Myc at K148 results in diminished transcriptional activity in AML cells

overall_design: mRNA profiles of MV4;11 cells with cMyc-WT, cMycK148R and cMyckK148Q

first: Tomoya

last: Muto

first: Choi

last: Kwangmin

first: Daniel

last: Starczynowski


title: Gene expression profile of  human leukemic cell line treated with TLR1/2 agonist.

summary: Treatment of MV4;11 cells with CU-T12-9 increased ubiquitination of c-Myc compared to control and correspondingly resulted in reduced K148 acetylation.  Chromatin immunoprecipitation coupled to high-throughput sequencing (Chip-Seq) revealed a significant loss of c-Myc occupancy in the genome following TLR1/2 activation with CU-T12-9.  As expected, diminished c-Myc binding resulted in gene downregulation of well-establish c-Myc targets.  These findings suggest that TLR-mediated K63-linked ubiquitination of c-Myc at K148 inhibits activation of c-Myc by interfering with its acetylation at the same residue.

overall_design: mRNA profiles of MV4;11 cells treated with CU-T12-9.


title: Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis

city: Harbin

first: Can

last: Wei

address: Baojian Road

department: Department of Pathophysiology

institute: Harbin Medical University


title: M6A-seq analysis of wild type and Mettl3-cKO liver tissues' transcriptomes

city: Xi'an

first: Xiang

last: Zhang

address: Changle west road #169

institute: the Fourth Military Medical University

summary: To investigate the role of METTL3-mediated m6A modification in liver, we performed m6A-sequencing to map the m6A modification in liver tissues of wild type (WT) and liver-sepcific Mettl3-KO mice.

overall_design: m6A-seq profiles of liver in 8 weeks wild type (WT) and liver-specific Mettl3-KO mice were generated by deep sequencing,with biologic replicates.

first: Zhang

last: Xiang

last: Rui


title: Next Generation Sequencing from small sizes of paired normal and glioblastoma patient tissues

city: Kaifeng

first: Xiong

last: Jin

state: Henan

address: Jin Ming Avenue

department: School of Pharmacy

institute: Henan University

summary: Although multi-omics studies of glioblastoma (GBM) have improved understanding of its biology nature and accelerated targeted therapy, data for paired adjacent normal tissues remains limited. Here, we report transcriptomes from 2 paired and 1 non-paired tumor and adjacent normal tissues (NAT) of glioblastoma (GBM) patients sequenced using Illumina Novaseq platform, and 150 bp paired-end reads were generated. This dataset provides a resource of paired GBM and normal tissues to identify novel tumor-specific oncogenes or tumor-suppressor genes.

overall_design: mRNA profiles of 2 paired and 1 non-paired GBM tissues and NAT

first: Jinlong

last: Yin


title: Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis [Ribo-seq]

summary: Oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC) represents an increasing problem in the global public health. OPSCC is the most frequent malignancy in oral cavity, with an overall increasing incidence and mortality. In view of its unclear exact mechanism and lack of optimized prevention and treatment methods, new biomarkers are needed to characterize the diversity of cancer and to explore effective treatment targets. This study combined translatomics and transcriptomics to analyze the differential genes in human oral cancer and adjacent tissues, in order to provide a new perspective for the prevention and treatment of OPSCC.

overall_design: Ribosome profiling sequencing of oral mucosa of human that divived into tumor tissue and paracancerous tissue of oral cavity carcinomas

first: Tao

last: Song


title: F. nucleatum-derived succinic acid induces tumor resistance to immunotherapy in colorectal cancer

city: Shanghai

first: Yile

last: Xie

address: 145 Middle Shandong Road

institute: Renji Hospital, Shanghai Jiao Tong University School of Medicine

summary: At present, the mechanisms underlying the association between gut microbiota metabolites and immunotherapy in CRC remain unknown. Here, we conducted a multiomics analysis of a cohort of patients with mCRC and found that F.nucleatum was more abundant in patients who did not respond to immunotherapy. We also found that F. nucleatum diminished the sensitivity to anti-PD-1 mAb through its metabolite succinic acid. Accordingly, patients with lower serum succinic acid levels achieved a better response to immunotherapy. Mechanistically, F.nucleatum-derived succinic acid suppressed the cGAS-interferon-β pathway, consequently dampening the antitumor response by limiting CD8+ T-cell trafficking to the tumor microenvironment in vivo. Treatment with metronidazole reduced intestinal F.nucleatum abundance and thereby decreased serum succinic acid levels, thus resensitizing the tumors to immunotherapy in vivo. Collectively, our findings indicate that F. nucleatum and its metabolite succinic acid induce tumor resistance to immunotherapy and offer new insights into microbiota-metabolite-immune crosstalk in CRC.

overall_design: We investigated the effect of Fusobacterium nucleatum on human colorectal cancer cell line LOVO. Sample1,2,3 were from PBS group; Sample 4,5,6 were from Fusobacterium nucleatum supernatant cocultured cells

first: Jing-Yuan

last: Fang

first: Shanshan

last: Jiang


title: Porin-mediated passage of negamycin across the outer membrane of Escherichia coli

city: Tübingen

first: Kay

last: Nieselt

state: DE

address: Sand 14

department: Department for Computer Science

institute: Institute for Bioinformatics and Medical Informatics

summary: The rise of antimicrobial resistant pathogens calls for new antibacterial treatments, but potent new compounds are scarce. Development of new antibiotics is difficult, especially against Gram-negative bacteria, as here uptake is strongly hindered by the additional outer membrane. Most antimicrobial agents against Gram-negatives use the porin mediated pathway to cross the outer membrane, which limits the choice of an antibiotic, as it has to fit by size, charge and hydrophilicity. In E. coli, the major porins OmpF and OmpC are associated with antibiotic translocation and therefore also with unspecific antibiotic cross-resistance. In this regard, alternative uptake routes are of interest. We were interested in the uptake opportunities of the small, natural product antibiotic negamycin and thereby found new uptake pathways across the outer membrane of E. coli. Besides OmpF and OmpC, we investigated the role of the minor porins OmpN and ChiP in negamycin translocation. We detected an effect of OmpN and ChiP on negamycin susceptibility and confirmed passage by electrophysiological assays. The structure of OmpN was resolved in order to analyze the negamycin translocation mechanism by computational simulations. As abundancy of these minor porins was low in E. coli, their transcript levels were analyzed by RNA-Seq. Increased transcripts levels of ompN and chiP were observed upon negamycin treatment, hinting at a role in antibiotic uptake. These new, additional uptake pathways across the outer membrane of E. coli highlight the antibiotic potential of negamycin, especially as resistance development is low due to availability of multiple uptake routes at both the outer and inner membranes

overall_design: Growth of wildtype Escherichia coli and three mutants (ΔompN, ΔchiP, ΔompNΔchiP) under no treatment and treatment with Negamycin (only wildtype) with 3 replicates each

last: Hörömpöli

first: Theresa

last: Harbig

first: Heike

last: Brötz-Oesterhelt


title: RNA Sequencing  of Wild Type and SENP8+/- BMDM Transcriptomes after Treated with CD47-coated Beads

city: Hangzhou

first: zhou

last: hui

address: no

institute: Zhejiang University

summary: Neddylation is coupled with tumor-cell survival by its well-characterized substrates Cullins. However, how neddylation impacts the tumor immune microenvironment is not clear. SENP8 deconjugates NEDD8 from non-Cullin targets to maintain the dynamic and reversible neddylation equilibrium. CD47 treated SENP8+/+ and SENP8+/- BMDMs were detected to show impacted gene transcription.

overall_design: Relative mRNA level inCD47-liganded WT and SENP8+/- BMDMs.

first: Yiqing

last: LI

first: Hui

last: Zhou

first: Yuehai

last: Ke


title: RNA-Seq of adenomas from Apc-Min mice with additional Tet1 and Tdg mutations

city: Philadelphia

first: Alfonso

last: Bellacosa

address: 333 Cottman Avenue

department: Cancer Signaling & Epigenetics

institute: Fox Chase Cancer Center

summary: Aberrant DNA methylation is frequently observed in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are poorly understood.  Ten-Eleven Translocation (TET) dioxygenases and Thymine DNA Glycosylase (TDG) are involved in active DNA demethylation by generating and removing novel oxidized cytosine species. TET1 and TDG mutations, and alterations of the levels of oxidized cytosines have been identified in human CRC. To clarify the biological significance of the TET-TDG demethylation axis in intestinal tumorigenesis, we generated ApcMin mice that are devoid of Tet1 and/or Tdg, and characterized the methylome and transcriptome of intestinal adenomas by DREAM and RNA sequencing, respectively. Tet1-deficient and Tet1/Tdg-double heterozygous ApcMin adenomas manifested increased adenoma size and features of erosion or invasion, whereas an increased number (>30) of adenomas was found in Tdg-mutant ApcMin mice.  Methylome analysis revealed progressive loss of global DNA hypomethylation in colonic adenomas from Tet1- and Tdg-deficient ApcMin mice, and hypermethylation of CpG islands in Tet1-deficient ApcMin mice.  In addition, RNA sequencing showed upregulation of genes in inflammatory, immune and interferon response in Tet1- and Tdg-mutant colonic adenomas compared to control ApcMin adenomas. The corresponding 135-gene inflammatory signature separated human colonic adenocarcinomas into four groups, closely aligned with their microsatellite or chromosomal instability profile, and characterized by different levels of DNA methylation and DNMT1 expression levels that anti-correlated with TET1 expression levels. These findings demonstrate a novel mechanism of epigenetic regulation during intestinal tumorigenesis by which TET1-TDG-mediated active DNA demethylation decreases not only methylation levels, but also inflammatory/interferon/immune response, which impinges on the intrinsic features of genomic instability of the tumors. This study establishes a novel link, via inflammatory response, between epigenomic and genomic instability.

overall_design: RNA sequencing (RNA-seq) was performed to determine the gene expression profile of adenomas (triplicates) from four-genotype groups: Tet1-/- Tdg+/+ ApcMin/+; Tet1+/- TdgN151A/+ ApcMin/+ ; Tet1+/+ TdgN151A/+ ApcMin/+; and Tet1+/+ Tdg+/+ ApcMin/+.

first: Rossella

last: Tricarico

first: Jozef

last: Madzo

first: Gabrielle

last: Scher

first: Shinji

last: Maegawa

first: Jaroslav

last: Jelinek

first: Rajeswari

last: Nagarathinam

first: Carly

first: Wen-Chi

last: Chang

first: Emmanuelle

last: Nicolas

first: Yan

first: Michael

last: Slifker

first: Karthik

last: Devarajan

first: Kathy

middle: Q

last: Cai

first: Pamela

last: Nakajima

first: Jinfei

last: Xu

first: Pietro

last: Mancuso

first: Valentina

last: Doneddu

first: Luigi

last: Bagella

first: Siddharth

last: Balachandran

first: Sergei

last: Grivennikov

first: Iuliia

last: Peshkova

first: Natalia

last: Kurilenko

first: Aleksandra

last: Mazitova

first: Ekaterina

last: Koltsova

first: Timothy

last: Yen

first: Jean-Pierre

last: Issa


title: Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics

city: Hamilton

first: Mickie

last: Bhatia

state: Ontario

address: 1200 Main Street West

department: Stem Cell and Cancer Research Institute (SCC-RI)

country: Canada

institute: McMaster University

summary: Natural products (NP) encompass a rich source of bioactive chemical entities. Hence, NPs-derived compounds represent the majority of drugs currently approved to treat cancer. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (SCCRI025044), capable of selectively inhibiting human CSC function vs. normal stem cell (SC) counterparts. Biochemical and molecular studies revealed that SCCRI025044 exerts inhibition on human CSCs through the small ubiquitin-like modifier (SUMO) cascade, found to be hyperactive in human CSCs. SCCRI025044 impedes SUMOylation pathway via direct targeting of the SAE1/2 complex. Treatment of patient-derived CSCs resulted in reduced levels of SUMOylated proteins and suppression of progenitor and stem cell capacity measured in vitro and in vivo. Our study overcomes a barrier in chemically inhibiting oncogenic SUMOylation activity and uncovers a unique role for SAE2 in human CSC biology.

overall_design: Duplicates of each drug treatment were compared to vehicle control (DMSO) for each cell type, also in duplicate.

first: Yannick

middle: D

last: Benoit

first: Ryan

middle: R

last: Mitchell

first: Wenliang

last: Wang

first: Luca

last: Orlando


title: Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis [RNA-seq]

first: Can

last: Wei

overall_design: Total RNA sequencing of oral mucosa of human that divived into tumor tissue and paracancerous tissue of oral cavity carcinomas

first: Tao

last: Song


title: Identification of translational microRNA biomarker candidates for nano-polystyrene induced brain injury using next-generation sequencing

city: Shijiazhuang

first: chu

last: chen

state: Hebei

address: 361 Zhongshan East Road

department: Department of Toxicology

institute: Hebei medical university

summary: The exposure to nano-plastics affects mammalian neurotoxic hazard characterization remains to be determined. Our aim was to investigate the neurotoxicity of nano-plastics in rodents. Animals were randomly divided into two groups: a control group and 50 mg/kg body weight PS NPs treatment groups. Before treatment, animals were fasted overnight. PS NPs were suspended into waters, vigorously stirred. The PS NPs via oral gavage once per day and for 6 months. The mice were treated with water in control group. We found that exposure to PS NPs caused cognitive decline. PS NPs exposure influenced the prefrontal cortex cells with more pathological alteration with increasing dosage. High-throughput RNA sequencing was conducted to explore miRNA expression in prefrontal cortex. Twenty-nine differentially expressed miRNAs were detected, including 12 upregulated and 17 downregulated miRNAs. This finding provided a reference for further studies on the development mechanisms of ncRNA during cognitive dysfunction.

overall_design: Mice exposure PS NPs for half year and identified of translational microRNA

first: Chu

last: Chen

first: Zhang

last: Rong


title: hPSC-derived Airway Organoids-based Screen Reveals the Role of HIF1/Glycolysis Axis in SARS-CoV-2 Infection.

city: New York

first: Shuibing

state: NY

address: A 827B, 1300 York Ave

department: Surgery

institute: Weill Cornell Medical College

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

overall_design: Refer to individual Series


title: hPSC-derived Airway Organoids-based Screen Reveals the Role of HIF1/Glycolysis Axis in SARS-CoV-2 Infection [scRNA-seq]

summary: SARS-CoV-2, the virus causing recently pandemic, primarily infects the respiratory tract. There is an urgent need to develop platforms using disease relevant human cells to dissect the molecular mechanism regulating SARS-CoV-2 infection and perform drug screen. Here, we derived airway organoids from human pluripotent stem cells (hPSC-AO). The hPSC-AOs, particularly ciliated cells, express ACE2 and are permissive to SARS-CoV-2 infection. Using hPSC-AOs, we performed a high content screen and identified GW6471, which blocks SARS-CoV-2 infection. RNA-seq analysis suggested that GW6471 blocking SARS-CoV-2 infection by inhibiting HIF1α, which is further validated by chemotin, another HIF1α inhibitor. Furthermore, metabolic profiling identified that the downregulation of glycolysis upon GW6471 treatment, which is further validated by RNA-seq. Finally, xanthohumol, a prenylated flavonoid suppressing fatty acid and cholesterol biosynthesis, blocks SARS-CoV-2 infection. Together, we applied the high content screen, RNA-seq and metabolic profiling to define the key role of HIF1α-glycolysis axis in SARS-CoV-2 infection, which provides a target pathway for anti-viral drug development.

overall_design: HPSCs were differentaited to airway organoids. The airway organoids were sequeneced using 10X platform.

first: Xiaohu

last: Duan

first: Tuo

last: Zhang


title: hPSC-derived Airway Organoids-based Screen Reveals the Role of HIF1/Glycolysis Axis in SARS-CoV-2 Infection [bulk RNA-seq]

overall_design: HPSCs derived airway organoids (AOs) or colonic organoids (COs) were treated with control or 10 uM GW6471 in the presence of SARS-CoV-2 infection.

first: Xiaohua


title: Bromodomain protein inhibition protects β-cells from cytokine-induced death and dysfunction via antogonism of NF-κB pathway

city: Pittsburgh

first: Vijay

last: Yechoor

state: PA

address: 200 Lothrop street,

department: Vascular Medicine Institute

institute: University of Pittsburgh

summary: We report that BET inhibitor (I-BET762) protect against cytokine induced pancreatic beta-cell apoptosis and did RNA-Seq to determine global transcriptome changes with the drug.

overall_design:
Rat insulinoma cell line (INS1) were treated with vehicle control (VC), I-BET762 (IB), ctyokine with vehicle control (CCVC) and cytokines with I-BET762 (CCIB) for 72h with cytokines added in last 24h.
contributor: Novogene

first: Vinny

last: Negi


title: Transcriptomic profiling of electrophysiologically characterized human iPSC-derived motor neurons having SOD1 A4V mutation

city: Boston

first: Seungkyu

last: Lee

state: MA

address: 3 Blackfan circle, CLS bldg. #12260

department: Neurobiology Dept.

institute: Boston Children's Hospital

summary: To find the molecular basis for abnormal excitability in human iPSC-derived motor neurons with the SOD1 A4V mutation and its involvement in risk of cell loss, we conducted a patch-seq, which combines genome-wide RNA sequencing and patch-clamp recording. This experiment enables excitability and gene expression to be measured simultaneously at a single cell level such that the links between the two could be explored.

overall_design: MNs differentiated from SOD1 A4V/+ iPSC lines and their isogenic controls were purified by introducing a GFP reporter under the control of the Hb9 promoter and GFP flow sorting. Three weeks after differentiation on P0-1 mouse cortical glial cells, whole cell current clamp recordings were made followed by single MN isolation for single cell Smart-seq2. Smart-seq2 analysis was performed on 192 neurons in two independent batches.

first: Ole

last: Wiskow

first: Sulagna

last: Ghosh

first: Bruce

last: Bean

first: Kevin

last: Eggan

first: Clifford

middle: J

last: Woolf


title: A to I editing of the 3'-UTR landscape regulates gene translation during retinal development

city: Guangzhou

first: Hongwei

last: Wang

state: Guangdong

address: No 7 Jinsui Rd, Research Building, Rm 301

department: Zhongshan Ophthalmic Center

institute: Sun Yat-Sen University

summary: We used parallel ribosome profiling and RNA sequencing to investigate the relationship between RNA editing and translation. Through systematically profiling mouse tissues from different developmental stages, we found dynamic changes in A-to-I RNA editome during retinal development. Further analysis revealed that altered translational efficiency in retinal development correlates with dynamics of A-to-I RNA editome.

overall_design: RNAseq and ribosome profiling were performed for 7 times during mouse retina development and two repllicates per time. A total of 28 barcoded libraries were pooled and single-end 51 bp and strand-specific pair-end 125bp sequencing was performed on an Illumina HiSeq 2500 for ribsome pforiling and RNAseq.

first: Yan

first: Zhi

last: Xie


title: Gene expression profile at single cell level of total dorsal dura mater cells

status: Public on Sep 30 2023

city: Helsinki

first: Salli

last: Antila

state: Uusimaa

address: Haartmaninkatu 8

department: Faculty of Medicine

institute: University of Helsinki, Wihuri Research Insitute

summary: This dataset was generated using adult wild-type mice and is part of a project profiling multiple different tissues. Single cell gene expression profiles were studied using 10x Genomics Chromium Single Cell 3’RNAseq platform.

overall_design: Dorsal dura mater pooled from 4 individual mice were pooled together and dissociated to single cells by mechanical dissociation and enzymatic digestion.

first: Kari

last: Alitalo


title: Embryonic incubation temperature has a long-term effect on the immune response of adult zebrafish

city: Bodø

first: Jorge

last: Fernandes

address: Universitetsalleen 11

department: Faculty of Biosciences and Aquaculture

country: Norway

institute: Nord University

summary: Zebrafish eggs were collected at 28 °C, and split into three embryonic incubation temperature groups (24 °C, 28 °C, 32 °C). When larvae reaching first feeding, the incubation temperature of larvae from 24 °C and 32 °C was gradually changed to 28 °C, and all fish were kept at 28 °C for later development until adulthood. At 100 d post-fertilization, 7 replicates from each temperature group were intraperitoneally (i.p.) injected with 2 μl of 50 mg/ml lipopolysaccharide (LPS) from Pseudomonas aeruginosa 10, while another 7 replicates were i.p. injected with 2 μl phosphate-buffered saline as control. At 12 h post-injection, the spleen was dissected, and total RNA was extracted. Five LPS-treated replicates and five controls were used for building RNA libraries and sequencing. The differential gene expression analysis were performed between fish from different embryonic incubation temperatures (24 °C vs 28 °C; 32 °C vs 28 °C), and between LPS treatment and control within each temperature group (24 °C LPS vs control; 28 °C LPS vs control; 32 °C LPS vs control). Totally, 251 differentially expressed genes (DEGs, 71 up-/180 down-regulated) were identified in fish from 24 °C embryonic incubation temperature compared to fish kept at constant 28 °C (DESeq2, adjusted p-value < 0.05, |fold change| > 1.5); and 660 DEGs (385 up-/275 down-regulated) were identified in fish from 32 °C embryonic incubation temperature compared to fish kept at 28 °C. By comparing LPS-treated fish to control, 567 DEGs (271 up-/296 down-regulated) were identified in fish from embryonic incubation temperature of 24 °C, 140 DEGs (80 up-/60 down-regulated) were identified in fish kept at constant 28 °C; and 49 DEGs (11 up-/38 down-regulated) were identified in fish from the 32 °C embryonic incubation temperature group.

overall_design: Thirty samples were analyzed, including five LPS-treated replicates and five controls from each of three embryonic incubation temperatures (24 °C, 28 °C, 32 °C).

first: Qirui

first: Igor

last: Babiak

middle: M


title: Embryonic incubation temperature effect adult zebrafish


title: Embryonic incubation temperature has a long-term effect on the microRNA transcriptome of adult zebrafish

summary: Zebrafish eggs were collected at 28 °C, and split into three temperature groups (24 °C, 28 °C, 32 °C) for incubation. When larvae reaching first feeding, the incubation temperature of larvae from 24 °C and 32 °C was gadually changed to 28 °C, and all fish were kept at 28 °C for later development until adulthood. At 100 d post-fertilization, seven replicates from each group were intraperitoneally (i.p.) injected with 2 μl of 50 mg/ml lipopolysaccharide (LPS) from Pseudomonas aeruginosa 10, while another seven replicates were i.p. injected with 2 μl phosphate-buffered saline as control. At 12 h post-injection, the spleen was dissected, and total RNA was isolated. Five LPS-treated replicates and five controls were used for building small RNA libraries and sequencing. A total of 112 novel miRNAs were identified using miRDeep2. By comparing fish from different embryonic incubation tmeperatures, 32 miRNAs (29 up-/3 down-regulated) were identified differentially expressed (DEmiRs, adjusted p-value < 0.05, |fold change| > 2.0, DESeq2) in fish from embryonic incubation temperature of 32 °C compared to fish kept at constant 28 °C, 3 DEmiRs (2 up-/1 down-regulated) were identified in response to LPS in fish kept at 28 °C. A total of 9,116 target genes were predicted using miRanda (v3.3a), including 8,224 genes targeted by 32 DE miRNAs and 892 genes targeted by 3 DE miRNAs.


title: Systematic compositional analysis of extracellular vesicles produced by cells undergoing apoptosis, necroptosis or necroptosis

city: Gosselies

first: Denis

middle: LJ

last: Lafontaine

state: Hainaut

address: Av Profs Jeneer & Brachet, 12

department: RNA Molecular Biology

country: Belgium

institute: Universite libre de Bruxelles

summary: Formation of extracellular vesicles (EVs) has emerged as a novel paradigm in cell-to-cell communication in health and disease. We performed a comparative analysis of steady-state (ssEVs) and cell death-associated EVs (cdEVs) following apoptosis (apoEVs), necroptosis (necEVs), and ferroptosis (ferEVs) using the same cell line. For each EV type, we systematically determined the biophysical and biochemical characteristics, the protein cargo, and the presence of methylated ribosomal RNA. The cell death EVs showed distinctive rRNA methylation patterns compared to ssEVs.

overall_design: RiboMethSeq analysis on EV-extracted RNA for the mapping and quantification of the ribosomal RNA 2'-O-methylations

first: Benjamin

last: Cappe

first: Bruno

last: Verstraeten

first: Eliza

last: Sack

first: Ludivine

last: Wacheul

first: Sara

last: Dufour

first: Julien

last: Franck

first: Francis

last: Impens

first: An

last: Hendrix

first: Peter

last: Vandenabeele

first: Franck

last: Riquet