title: Daphnane diterpenoids as potent and tolerable importin-b1 inhibitors to treat castration-resistant prostate cancer [RNA-Seq]

summary: Importin-b1, a key member of karyopherins, is composed of 18-20 tandem repeats of the HEAT motif, each of which contains two antiparallel alpha helices linked by a turn. With the help of adaptor protein importin-α, importin-b1 recognizes cargo with NLS in the cytoplasm, and ferries the complex through the NPC into the nucleus. Several studies have shown that importin-b1 is overexpressed in some cancers, especially advanced prostate cancer, and is associated with poor prognosis and drug resistances.Here, the anti-CRPC (castration-resistant prostate cancer) screening of a natural diterpenoid library followed by target fishing led to the identification of a highly potent importin-b1 inhibitor, daphnane diterpenoid DD1.And the optimized analog is DD1-Br.To further dissect the influence of importin-b1 inhibitors on gene transcription programs, we analyzed RNA-seq transcriptomes of C4-2B cells with the treatment of DD1 (YDGY-3), DD1-Br (YDGY-3BR) or importazole (IPZ).

overall_design: C4-2B prostate cancer cells mRNA profiles of treatment with YDGY-3, YDGY-3BR or IPZ.

first: Sheng

last: Yin

first: Junjian

last: Wang


title: Daphnane diterpenoids as potent and tolerable importin-b1 inhibitors to treat castration-resistant prostate cancer [ChIP-Seq]

status: Public on Sep 01 2022

city: Guangzhou

first: Jialuo

last: Huang

address: 132# Waihuandong Road, Guangzhou University City

department: School of Pharmaceutical Sciences

country: China

institute: Sun Yat-sen University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Importin-b1, a key member of karyopherins, is composed of 18-20 tandem repeats of the HEAT motif, each of which contains two antiparallel alpha helices linked by a turn. With the help of adaptor protein importin-α, importin-b1 recognizes cargo with NLS in the cytoplasm, and ferries the complex through the NPC into the nucleus. Several studies have shown that importin-b1 is overexpressed in some cancers, especially advanced prostate cancer, and is associated with poor prognosis and drug resistances.Here, the anti-CRPC (castration-resistant prostate cancer) screening of a natural diterpenoid library followed by target fishing led to the identification of a highly potent importin-b1 inhibitor, daphnane diterpenoid DD1(YDGY-3).To further dissect the influence of importin-b1 inhibitors on gene transcription programs, we analyzed H3K27ac chip-seq of C4-2B cells with the treatment of DD1 (YDGY-3).

overall_design: Examination of H3K27AC modifications in prostate cancer cells treated with DMSO or YDGY-3


title: Mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (RNA-seq)

city: Milan

first: Stefano

last: Beretta

address: Via Olgettina, 60

country: Italy

institute: San Raffaele Telethon Institute for Gene Therapy

type: Expression profiling by high throughput sequencing

summary: Mesenchymal Stromal Cells (MSCs) have been employed in vitro to support HSPC expansion and in vivo to promote Hematopoietic Stem and Progenitor Cells (HSPCs) engraftment. Based on these studies, we developed an MSC-based co-culture system to optimize transplantation outcome of CRISPR-Cas9 gene-edited (GE) human HSPCs. We show that bone marrow (BM)-MSCs produce several hematopoietic supportive and anti-inflammatory factors capable to alleviate the proliferation arrest and mitigate the apoptotic and inflammatory programs activated in GE-HSPCs, improving their expansion and clonogenic potential in vitro. The use of BM-MSCs resulted in superior human engraftment and increased clonal output of GE-HSPCs contributing to the early phase of hematological reconstitution in the peripheral blood of transplanted mice. In conclusion, our work poses the biological bases for a novel clinical use of BM-MSCs to promote engraftment of GE-HSPCs and improve their transplantation outcome.

overall_design: Mesenchymal Stromal Cells (MSCs) expanded in culture and MSCs co-cultured with CRISPR-Cas9 gene-edited (GE)-HSPCs for 72 hours collected for RNA extraction from 5 patients, for a total of 10 samples (5 MSCs and 5 GE-HSPCs).

first: Stefania

last: Crippa

first: Anastasia

last: Conti

first: Valentina

last: Vavassori

first: Ivan

last: Merelli

first: Raffaella

last: Di Micco

first: Maria

middle: E

last: Bernardo


title: Serum is preferable to plasma for circulating exosomal microRNA biomarker discovery studies

city: Bedford Park

first: Damian

middle: James

last: Hussey

address: Flinders Drive

country: Australia

institute: Flinders University

summary: Exosomes were purified from 250 ul matched plasma and serum samples using ExoQuickTm. The presence of particles consistent in size with exosomes (60-150nm) was confirmed using a Nanosight LM10.   miRNA was extracted from exosomes  using an miRNeasy Serum/Plasma kit (Qiagen, #217184). miRNA was reversed transcribed using a TaqMan® microRNA Reverse Transcription Kit (Life technologies, #4366596). miRNA profiling was performed with a high throughput TaqMan® OpenArray® Human microRNA panel  (Life technologies, #4461104). The panel consisted of probes for 754 human miRNAs that are based on miRNA sequences derived from Sanger miRBase v14. MegaplexTM Primer Human Pool A v2.1 and Human Pool B v2.0 or v3.0

overall_design: OpenArray high throughput real time PCR of microRNAs purified from exosomes that were isolated from matched serum and plasma samples from 10 patients without oesophageal disease, and 10 patients with  locally advanced Oesophageal Adenocarcinoma.

first: Karen

last: Chiam

first: George

middle: C

last: Mayne

first: Tingting

first: David

middle: I

last: Watson

first: Tanya

middle: S

last: Irvine

first: Tim

last: Bright

first: Lorelle

middle: T

last: Smith

first: Imogen

middle: A

last: Ball

first: Joanne

middle: M

last: Bowen

first: Dorothy

last: Keefe

first: Sarah

middle: K

last: Thompson

middle: J


title: Histone-acetyl Epigenome Regulates TGF-β Pathway-associated Chemoresistance in Colorectal Cancer

city: Shanghai

first: Haoyan

last: Chen

state: Shanghai

address: 145 Shandong Road

institute: Renji Hospital

summary: The global up-regulation of histone acetylation modification after the activation of the TGF-β signaling pathway raised the possibility that the differential expression of specific histone acetyltransferases or histone deacetylases may involve in the modulation of TGF-β-associated chemoresistance in CRC. To test this hypothesis, high-throughput mRNA sequencing (RNA-Seq) was performed to compare the expression profile between SW480 cells treated with or without TGF-β1.

overall_design: RNA-seq was performed in SW480  colorectal cancer cells afterTGF-β1 treatment

first: Tian

last: Xianglong


title: RNA-seq analyses of liver samples in mice fed normal diet or subject to  60%  high fat diet for 23 weeks

city: Nanjing

first: John

middle: Zhong

last: Li

state: Jiangsu

address: 101 Longmian Avenue, Jiangning District

department: Biochemistry and Molecular Biology

institute: Nanjing Medical University

type: Non-coding RNA profiling by high throughput sequencing

summary: To systemically identify the long non-coding RNAs(lncRNAs) expression profile in the liver, specifically those involved in lipid metabolism, we generated a hyperlipemia model in mice. The hyperlipemia protocol was as follows:mice post natal 4 weeks fed normal diet or subjet to 60% high fat diet for 23 weeks, the mice were immediately sacrificed  for liver and plasma collection.

overall_design: In this study presented here,we separate mouse livers fed normal diet or subject to 60% high fat diet for 23 weeks and identified the genome-wide expression level of lncRNAs.

middle: Z

first: Xuan

last: Shen

first: Yajun

last: Zhang


title: Adaptation of Plasmodium falciparum to growth in medium lacking a lipids supplement is associated with mutations in the pfndh2 gene

city: Barcelona

first: Anastasia

last: Pickford

state: Barcelona

address: Carrer Rosselló 153

country: Spain

institute: ISGlobal

summary: The complex life cycle of the malaria parasite Plasmodium falciparum involves many different environments. Additionally, the parasite encounters fluctuating conditions within the same niche. For example, in the human blood parasites face variability in the host’s immune response, presence of antimalarial drugs or availability of nutrients, among others. Bet-hedging adaptive strategies, which involve population heterogeneity that precedes changes in the environment, play an important role in the adaptation of P. falciparum asexual blood stages to fluctuations in their environment. This is linked to clonally variant expression, regulated at the epigenetic level, of a large number of malarial genes. However, currently there are very few examples of fluctuation conditions to which adaptation by changes in the expression of clonally variant genes has been established. Here we studied the adaptation of P. falciparum cultures to grow in the absence of an external source of lipids. In three independent adaptation experiments, cultures were able to adapt to grow without lipids in the culture medium and this was linked to acquisition of deletions or non-sense mutations in the pfndh2 gene, a component of the mitochondrial electron transport chain. In contrast, full transcriptome analysis did not provide evidence for a role for bet-hedging strategies in the adaptation of parasites to grow in lipid-free medium. Therefore, adaptation to this type of stress involved metabolic rewiring achieved by inactivation of a gene involved the mitochondrial respiratory chains.

overall_design: Time-course transcriptomic analysis of 3D7-A parasites from two independent selections (Selection 2 and Selection 3) in which parasites (3D7-A-LF) were selected with lipid-free media supplemented with 0.5% bovine serum albumin (BSA) for 30 to 60 days and maintained in parallel with control parasites (3D7-A-Ctrl) that were in fully-supplemented 0.5% AlbuMAX II medium. Parasites were tightly synchronized to a 5 h age window by the means of a Percoll purification followed by a sorbitol lysis 5 h later. After the Percoll, 3D7-A-LF parasites were separated into two conditions: LF0 that was always maintained in lipid-free 0.5% BSA supplemented media and LFCM that was switched to 0.5% AlbuMAX II supplemented media for the duration of this experiment. 3D7-A-Ctrl parasites were always kept in 0.5% AlbuMAX II supplemented media. Samples for transcriptomic analysis were collected every 8 h at five different time points (8-13 hpi, 16-21 hpi, 24-29 hpi, 32-37 hpi and 40-45 hpi). The reference pool consisted of RNA from 3D7-A cultures throughout the asexual blood cycle. Total RNA was harvested using the Trizol method. A total number of 30 individual samples were analysed using the microarray design AMADID-085763 (GEO ID: GPL26985).

first: Lucas

last: Michel-Todó

first: Alfred

last: Cortés


title: RNA Sequencing Facilitates Quantitative Analysis of Control and GLUT1-HK2-PFKFB3 Overexpressed Transcriptomics in Mouse Skeletal Muscle

first: Cong

last: Xiang

state: JiangSu Province

address: 12 Xuefu Road, Pukou High-Tec District

institute: Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University

summary:
Purpose: RNA-Seq uses next-generation sequencing to analyze expression across the transcriptome, enabling to detect known or novel features and quantify RNA. The goal of this study is to compare transcriptome profiles between control and GLUT1-HK2-PFKFB3 overexpressed mouse skeletal muscle.
Methods: Total RNA was isolated from the gastrocnemius muscle of chow diet-fed M;G and control mice at the age of 3-month-old using RNAiso Plus (Takara Bio). Three independent pooled samples per group were analyzed. Sequencing libraries were generated using NEBNext® UltraTM RNA Library Prep Kit for Illumina® (NEB, USA) following manufacturer’s recommendations and index codes were added to attribute sequences to each sample. The clustering of the index-coded samples was performed on a cBot Cluster Generation System using TruSeq PE Cluster Kit v3-cBot-HS (Illumia) according to the manufacturer’s instructions. After cluster generation, the library preparations were sequenced on an Illumina Hiseq platform and 125 bp/150 bp paired-end reads were generated. Index of the reference genome was built using Hisat2 v2.0.5 and paired-end clean reads were aligned to the reference genome using Hisat2 v2.0.5. Fragments Per Kb of exon per Million mapped reads (FPKM) were calculated using featureCounts v1.5.0-p3.
Results: We mapped about 6 million sequence reads per sample to the mouse genome and identified 54533 transcripts in the gastrocnemius muscle of control and GLUT1-HK2-PFKFB3-overexpressed mice. RNA-seq data confirmed stable expression of 10 known housekeeping genes, and 7 of these were validated with qRT–PCR. A total 664 transtripts were differentially expressed in wildtype and GLUT1-HK2-PFKFB3 overexpressed skeletal muscle with a cutoff of 2.0-fold and p < 0.05 from RNA sequencing analysis. Altered expression of 15 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method.

overall_design: mRNA profiles of control and GLUT1-HK2-PFKFB3 overexpressed mouse gastrocnemius muscle

first: Geng

last: Liu


title: Recombinant human thrombomodulin treatment against endotoxemia-induced myocardial injury

city: Gifu

first: Hideshi

last: Okada

address: 1-1 Yanagido

department: Emergency and Disaster Medicine

country: Japan

institute: Gifu University Graduate School of Medicine

summary: We made LPS induced myocardial injury model mice, and determined the effect of recombinant human thrombomodulin against myocardial injury.

overall_design: Following 16-h starvation, mice were intraperitoneally injected with LPS (20 mg/kg; MilliporeSigma, Burlington, MA), and in some assays, with saline or recombinant human thrombomodulin (rhTM; Asahi Kasei Pharma Corporation, Tokyo, Japan) at 3 and 24 h post-LPS injection. Total RNA was extracted from mouse heart 30h after LPS injection.


title: Targeted RNA N6-Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells

first: Guoshi

last: Chai

address: No. 135, Xingang Xi Road

department: School Of Life Sciences

institute: SUN YAT-SEN UNIVERSITY

summary: Deficiency of the N6-methyladenosine (m6A) methyltransferase complex results in global reduction of m6A abundance and defective cell development in embryonic stem cells (ESCs). However, it’s unclear whether regional m6A methylation would affect cell fate decisions due to the inability to modulate individual m6A modification in ESCs with precise temporal control. Here, we develop a targeted RNA m6A erasure (TRME) system to achieve site-specific demethylation of RNAs in human ESCs (hESCs). TRME, in which a stably transfected, doxycycline-inducible dCas13a is fused to the catalytic domain of ALKBH5, can precisely and reversibly demethylate the targeted m6A site of mRNA and increase mRNA stability with limited off-target effects. We further demonstrate that temporal m6A erasure on a single site of SOX2 is sufficient to control the differentiation of hESCs. This study provides a versatile toolbox to reveal the function of individual m6A modification in hESCs, enabling cell fate control studies at the epitranscriptional level.

overall_design: Examination of m6A modification variation in the TRME hESCs treated with doxycycline or not.

last: Cao

first: Guanzheng

last: Luo

first: Jia

last: Wang


title: Expression Profile Analysis of Long non-coding RNAs in Mouse Liver

city: Houston

first: Liuqing

last: Yang

state: Texas

address: 1515 Holcombe Blvd.

department: Molecular and Cellular Oncology

country: USA

institute: The University of Texas MD Anderson Cancer Center

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

summary: In the present study, the lncRNA expression profile of mouse fetal and adult liver was analyzed by ArrayStar LncRNA Array 3.0. Differentially expressed LncRNAs with statistical significance were identified through Volcano Plot filtering between two groups. Pathway analysis and GO analysis were applied to determine the roles of these differentially expressed lncRNAs played in these biological pathways or GO terms. Finally, Hierarchical Clustering was performed to show the distinguishable LncRNAs expression pattern among samples.

overall_design: The total RNA from C57/BL6 mouse fetal (embryo-E18) and adult (2-months old) liver were extracted and RNA integrity was assessed by standard denaturing agarose gel electrophoresis and Bioanalyzer. For lncRNA array analysis, ArrayStar Mouse LncRNA Microarray V3.0 was employed. Three independent experiments were performed at each condition (liver-E18 vs. liver-2months). To identify differentially expressed LncRNAs with statistical significance, we performed a Volcano Plot filtering between the two groups (Fold Change >= 2.0, P-value <= 0.05).

first: Yajuan

first: Qingsong

last: Hu

first: Ke

last: Liang

first: Youqiong

last: Ye

first: Zhao

first: Yi-Chuan

first: Yaohua

first: Yinghong

last: Pan

first: Sujash

last: Chatterjee

first: Tina

last: Nguyen

first: Heidi

last: Hsiao

first: Peter

last: Park

first: Sergey

middle: D

last: Egranov

first: Nagireddy

last: Putluri

first: Arun

last: Sreekumar

first: Chandrashekar

middle: R

last: Ambati

first: David

middle: H

last: Hawke

first: Preethi

last: Gunaratne

first: Mien-Chie

last: Hung

first: Kuang-Lei

last: Tsai

first: Leng

last: Han

first: Chunru

last: Lin


title: Multifaceted functions of SiglecF expressing neutrohpils in the exacerbation of air pollutant-induced airway inflammation

city: Seoul

first: JAE WOO

last: SHIN

address: 103 Daehak-ro

department: Department of Biomedical Sciences

country: South Korea

institute: Seoul National University

summary: Diesel exhaust particles (DEPs) are the main component of traffic-related air pollution and implicated in asthma pathogenesis and exacerbation. However, the mechanistic link between DEP exposure and worsening asthma symptoms remains unclear. Here, we characterized a unique subset of neutrophils that express a high level of Sialic acid-binding, Ig-like lectin (Siglec)-F. DEP exposure instructs SiglecF expression on neutrophils by increasing P2X1 receptors sensing damage-associated molecular patterns (DAMPs) molecules, ATP. SiglecFhigh neutrophils stimulated by DEP release neutrophil extracellular traps (NETs) to cause tissue damage and IL-17A production, and potentiated type 2 cytokine production by producing cysteinyl leukotrienes. As a result, SiglecFhigh neutrophils worsen airway hyperresponsiveness (AHR) as well as airway inflammations. We also confirmed that siglec8, corresponding to murine SiglecF, expression increased in neutrophils from patients with asthma, and they correlated with the severity of the disease. Together, these translational findings suggest a novel SiglecF expressing neutrophils in the development of severe asthma by linking type 2 and type 3 responses.

overall_design: mRNA profiles of Eosinophils (1), SiglecFlow (2) and SiglecFhigh (2) neutrophils sorted from DEP exposed wild type lungs

first: Jae-Woo

last: Shin

first: Ji-Hyun

last: Kim

first: Tae-Young

last: Roh

first: Taesoo

first: Hye-Young


title: RNA-Seq of rhesus macaque macrophages generated by TET2-mutant hematopoiesis

city: Bethesda

first: Taehoon

address: 9000 Rockville Pike

institute: National Institutes of Health

summary: Gene expression profile of purified peripheral CD14+CD163+ macrophages was analyzed via RNA-Seq in the presence or absence of inflammatory stress to assess the impact of TET2 disruption on gene expression in macaque hematopoiesis.

overall_design: Mobilized CD34+ cells were treated with CRISPR/Cas9, followed by transplanted autologously to generate a non-human primate model of clonal hematopoiesis. Peripheral CD14+CD163+ macrophages were purified at early (4.5 months) and late (19 months) timepoints post-transplantation and incubated for 8 hours in the presence or absence of inflammatory stimulators, and then RNA was extracted and analyzed by high-throughput sequencing.

first: Kyung-Rok

last: Yu

first: Cynthia

last: Dunbar


title: CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis

city: Shijiazhuang

first: Zhan

last: Yang

state: Hebei

address: 215 Heping W Rd

institute: The Second Hospital of Hebei Medical University

summary: To study the differential expression of genes in prostate cancer tissue and benign prostatic hyperplasia

overall_design: Microarray hybridization analysis of mRNA expression in two PCa samples and two benign prostatic hyperplasia tissues were performed according to the manufacturer’s protocol (Arraystar, Inc., Rockville, MD, USA).

first: Chang-Bao

last: Qu


title: Neuronal activity induced by BDNF prompts chromatin remodeling at regulatory elements associated with neuropsychiatric traits [mouse]

city: Heidelberg

first: Dr. Kyung-Min

last: Noh

address: Meyerhofstrasse 1

department: Genome Biology

country: Germany

institute: EMBL Heidelberg

summary: Neuronal activity induced by Brain-Derived Neurotrophic Factor (BDNF) is crucial for neuronal survival, differentiation, synaptic plasticity, memory formation, and neurocognitive health. Molecular mechanisms of BDNF promoting cellular survival and synaptic plasticity have been intensely studied, yet its role in genome regulation is obscure. Here, through temporal profiling of chromatin accessibility and transcription in mouse primary cortical neurons upon BDNF treatment or depolarization (KCl), we identified BDNF-specific chromatin-to-gene expression programs. Our analyses revealed that enhancer activation is an early event in the regulatory control of BDNF treated neurons, where bZIP pioneered chromatin opening and co-regulatory transcription factors (Homeobox, EGRs, and CTCF) cooperate to induce fine-grained transcription. Deleting such cis-regulatory sequences decreased the BDNF mediated expression of Arc, a key regulator of synaptic plasticity. Furthermore, BDNF-induced accessible regions are linked to preferential exon usage of neurodevelopmental disorder related genes and heritability of neuronal complex traits. In conclusion, this work provides a comprehensive view of BDNF-mediated genome regulatory features and emphasizes the usage of genomic approaches on dissecting mammalian neuronal activity.

overall_design: Neuronal activity of mouse cortical neurons at embryonic day 15 (E15) with BDNF, KCl and unstimulated (control), at three timepoints (1, 6, and 10 hours), followed by RNA- and ATAC-seq library preparation.

first: Ignacio

middle: L

last: Ibarra

first: Vikram

last: Ratnu

first: Lucia

last: Gordillo

first: In-Young

last: Hwang

first: Luca

last: Mariani

first: Katrhyn

last: Weinand

first: Henrik

last: Hammarén

first: Martha

last: Bulyk

first: Mikhail

last: Savitski

first: Judith

middle: B

last: Zaugg

first: Kyung-Min


title: Expression profile of genes in CAMDI knockout mice brain compared with wild-type mice

city: Kamakura

first: Satoshi

last: Kondo

state: Kanagawa

address: Tebiro 6-10-1

department: New Projects Development Division

institute: Toray Industries,Inc.

summary: GeneChip analysis was performed on the cerebrums of CAMDI-KO mice at P0 to elucidate changes in the expression levels of genes related to psychiatric disorders.

overall_design: Experimental RNA samples were isolated from cerebrums of CAMDI-KO and WT mice at P0 using RNeasy (Qiagen) and analysed using Mouse Oligo chip 24K 3D-Gene (Toray).

first: Toshifumi

last: Fukuda

first: Shigeru

last: Yanagi


title: Gene expression data from sorted G1-G2/M phase of SLIMP knockdown and control cells.

first: Oscar

last: Reina Garcia

address: C/Baldiri Reixac 10

department: Biostatistics and Bioinformatics

institute: IRB Barcelona

summary: Drosophila melanogaster cells depleted of SLIMP showed a clear arrest in G2/M phase. The objective of this gene expression study was to determine the pathways involved in the phenotype of this cells.

overall_design: Drosophila S2 stable cell lines were induced with CuSO4 to induce the knockdown of SLIMP. G1 and G2/M phases of control cells and SLIMP depleted cells were then sorted using a FacsAria Fusion sorter. Cell cycle from live cells was obtained with the incubation with Vybrant DyeCycle Violet Stain (Thermofisher). Two replicates for the SLIMP depleted cells and three replicates for the control cells were analysed.

first: Albert

last: Antolin-Fontes

first: Lluís

last: Ribas de Pouplana


title: Frequent involvement of chromatin remodeler alterations in gastric field cancerization

status: Public on Aug 31 2022

city: Shinagawa-ku

first: Hideyuki

last: Takeshima

state: Tokyo

department: Institute for Advanced Life Sciences

institute: Hoshi University

summary: A field for cancerization, or a field defect, is formed by the accumulation of genetic and epigenetic alterations in normal-appearing tissues, and is involved in various cancers, especially multiple cancers.  Epigenetic alterations are frequently present in chronic inflammation-exposed tissues, but information on individual genes involved in the formation of a field defect is still fragmental.  Here, using noncancerous gastric tissues of cancer patients, we isolated 16 aberrantly methylated genes, and identified chromatin remodelers ACTL6B and SMARCA1 as novel genes frequently methylated in non-cancerous tissues.  SMARCA1 was expressed at high levels in normal gastric tissues, but was frequently silenced by aberrant methylation in gastric cancer cells.  Moreover, somatic mutations of additional chromatin remodelers, such as ARID1A, SMARCA2, and SMARCA4, were found in 30% of gastric cancers.  Mutant allele frequency suggested that the majority of cancer cells harbored a mutation when present.  Depletion of a chromatin remodeler, SMARCA1 or SMARCA2, in cancer cell lines promoted their growth.  These results showed that epigenetic and genetic alterations of chromatin remodelers are induced at an early stage of carcinogenesis and are frequently involved in the formation of a field defect.

overall_design: Genome-wide DNA methylation analysis was conducted by an Infinium HumanMethylation450 BeadChip array.

last: Yamashita

first: Toshikazu

last: Ushijima


title: A kinase-independent function of cyclin-dependent kinase 6 promotes outer radial glia expansion and neocortical folding

city: Memphis

first: Yong-Dong

last: Wang

state: TN

address: 262 Danny Thomas Pl, MS1135

institute: St. Jude Children's Research Hospital

summary: The neocortex, the center for higher brain function, first emerged in mammals and has become massively expanded and folded in humans, constituting almost half the volume of the human brain. Primary microcephaly, a developmental disorder in which the brain is smaller than normal at birth, mainly results from there being fewer neurons in the neocortex because of defects in neural progenitor cells (NPCs). Outer radial glia (oRGs), NPCs that are abundant in gyrencephalic species but rare in lisencephalic species, are thought to play key roles in the expansion and folding of the neocortex. However, how oRGs expand, whether they are necessary for neocortical folding, and whether defects in oRGs cause microcephaly remain important questions in the study of brain development, evolution, and disease. Here, we show that oRG expansion in mice, ferrets, and human cerebral organoids requires cyclin-dependent kinase 6 (CDK6), the mutation of which causes primary microcephaly via an unknown mechanism. In a mouse model in which increased Hedgehog signaling expands oRGs and intermediate progenitor cells and induces neocortical folding, CDK6 loss selectively decreased oRGs and abolished neocortical folding. Remarkably, this function of CDK6 in oRG expansion did not require its kinase activity, was not shared by the highly similar CDK4 and CDK2, and was disrupted by the mutation causing microcephaly. Therefore, our results indicate that CDK6 is conserved to promote oRG expansion; that oRGs are necessary for neocortical folding; and that defects in oRG expansion may cause primary microcephaly.

overall_design: RNA-sequencing data from E14.5 embryonic cortex: wildtype versus GFAP::Cre; SmoM2 mutant

first: Lei

first: Jun

middle: Y

last: Park

first: Fengming

last: Liu

first: Kristin

last: Olesen

first: Shirui

last: Hou

first: Jamy

last: Peng

first: Jordan

last: Infield

first: Anna

last: Levesque

first: Hongjian

last: Jin

first: Yiping

last: Fan

first: Jon

last: Connelly

first: Shondra

last: Pruett-Miller

first: Miaofen

middle: G

last: Hu

first: Philip

middle: W

last: Hinds

first: Young-Goo

last: Han


title: Histone chaperone CAF-1 is a synthetic lethal vulnerability in the context of ARID1A deficiencies [RNA-Seq]

city: Vienna

first: Christoph

last: Bock

address: Lazarettgasse 14

country: Austria

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

summary: Mutations in the BAF chromatin remodeling complex rank among the most frequent genetic alterations in human cancers, many of which result in a loss of function of the respective subunits. Recent genomic and chemical screens have revealed synthetic lethal interactions of BAF complex subunits with each other as well as with further chromatin modifiers. Using an epigenome-focused shRNA library, we identified loss of the histone chaperone complex CAF-1 (chromatin assembly factor 1) as a synthetic lethal vulnerability of ARID1A-deficient cells that is enhanced by the androgen receptor agonist testosterone. In line with antagonistic roles of the CAF-1 and BAF complexes in nucleosome deposition and remodeling, we show that knock-down of CAF-1 subunits results in a partial reversal of the transcriptional and chromatin accessibility effects caused by loss of ARID1A. Together, our findings identify a new functional partner of the BAF chromatin remodeling complex and represent a potential novel strategy for targeting ARID1A-deficient cancers.

overall_design: 36 RNA-seq samples for ARID1A knockout and WT HAP1 cells further perturbed with CHAF1A knockdown, degradation or EZH2 inhibitor or Testorsterone.

first: Bernd

last: Boidol

first: Sandra

last: Schick

first: André

middle: F

last: Rendeiro

last: Ringler

first: Kathrin

last: Runggatscher

first: Derya

last: Dönertas

first: Melanie

last: Hinkel

first: Michael

last: Schleicher

first: Guido

last: Boehmelt

first: Stefan

last: Kubicek


title: miRNome and proteome profiling of small extracellular vesicles secreted by human glioblastoma cell lines and primary cancer stem cells.

city: rome

first: andrea

last: sacconi

address: via elio chianesi

institute: regina elena cancer institute

summary: We investigated in parallel the miRNome and proteome of the small EVs (sEVs) released by two different human GBM established cell lines and by GBM primary cancer stem cell (CSC) lines, to explore the role of sEVs in their different tumor behavior and capacities, and to assess whether these different EVs that coexist in the tumor burden are functionally interrelated, and/or may together target distinct cellular pathways that converge on the same biological goals

overall_design: miRNA expression profiling of small extracellular vesicles (sEVs) secreted in the culture medium by two human glioblastoma (GBM) established cell lines, namely U373 MG-Uppsala and U87 MG, and GBM primary cancer stem cell (CSC) lines. Three samples, each in duplicate, were analyzed: U373-sEVs, U87-sEVs and CSC-sEVs.

first: Ingrid

last: Cifola

first: Federica

last: Fratini

first: Beatrice

last: Cardinali

first: Valentina

last: Palmieri

first: Giuliana

last: Gatti

first: Tommaso

last: Selmi

first: Sara

last: Donzelli

first: Andrea

last: Sacconi

first: Valeriana

last: Cesarini

first: Hany

middle: E

last: Marei

first: Massimilano

last: Papi

first: Giovanni

last: Blandino

first: Carlo

last: Cenciarelli

first: Germana

last: Falcone

first: Igea

last: D’Agnano


title: Exosomal miRNA profiling of plasma- and saliva-derived exosomes

city: Ulm

first: Linda

last: Hofmann

state: Deutschland

address: Frauensteige 14a, Haus 18

institute: University of Ulm

summary: Exosomes were isolated from plasma and saliva of healthy individuals and head and neck cancer (HNSCC) patients. miRNA profiling of plasma- and saliva-derived exosomes was performed using nCounter SPRINT system. Diagnostic panels were selected from the exosomal miRNA profile.

overall_design: Exosomal miRNA profiles from plasma and saliva of healthy individuals (n=5) and head and neck cancer patients (n=11) were analyzed regarding their diagnostic and prognostic potential, correlated to clinical data and integrated into network analysis.

first: Tsima

last: Abou Kors

first: Valentin

last: Medyany

first: Marie-Nicole

last: Theodoraki


title: A chromosome-level genome assembly provides insights into the environmental adaptability and outbreaks of Chlorops oryzae

city: Changsha

first: Ailin

last: Zhou

address: 1 Nongda Road, Furong District, Changsha City, Hunan Province

institute: Agricultural University Of Hunan

summary: Chlorops oryzae is a pest of rice that has caused severe damage to crops in major rice-growing areas in recent years. We generated a 447.60 Mb high-quality chromosome-level genome with contig and scaffold N50 values of 1.17 Mb and 117.57 Mb, respectively. Hi-C analysis anchored 93.22% scaffolds to 4 chromosomes. The relatively high expression level of Heat Shock Proteins (HSPs) and antioxidant genes in response to thermal stress suggests these genes may play a role in the environmental adaptability of C. oryzae. The identification of multiple pathways that regulate reproductive development (juvenile hormone, 20-hydroxyecdsone, and insulin signaling pathways) provides evidence that these pathways also play an important role in vitellogenesis and thus insect population maintenance. These findings identify possible reasons for the increased frequency of outbreaks of C. oryzae in recent years. Our chromosome-level genome assembly may provide a basis for further genetic studies of C. oryzae, and promote the development of novel, sustainable strategies to control this pest.

overall_design: Chlorops oryzae female adults were collected for genome analysis.

first: Cong

last: Huang

first: Yi

last: Li

first: Xinwen

first: Zhengbing

last: Zhang

first: Hualiang

last: He

first: Wenbing

last: Ding

first: Jin

last: Xue

first: Youzhi

first: Lin

last: Qiu


title: Localized mRNA translation mediated by Staufen is a novel mechanism regulating cytoskeletal reorganization in response to podocyte injury.

city: Boston

first: John

middle: N

last: Hutchinson

state: Massachusetts

address: 201 Wachusett Street

institute: Diamond Age Data Science

summary: Podocyte injury that compromises the glomerular filtration barrier is an initiating feature of chronic kidney disease.  Podocytes extend major cytoplasmic projections that ultimately subdivide into interdigitating foot processes to form a scaffold that supports the glomerular filtration barrier. We investigated whether podocytes, like other cell types that elaborate complex cytoplasmic projections, utilize RNA transport and local translation in order to synthesize proteins at sites distal from the cell body.  Here we show that mice deficient in the RNA binding proteins Staufen1 and 2 are significantly more sensitive to podocyte injury. Furthermore, Staufen2 associates with the podocyte cytoskeleton and is present in foot processes. After injury, Staufen2 and translating ribosomes increase markedly in areas of effacement adjacent to the glomerular basement membrane. Lastly, we found that Staufen2-bound RNAs are enriched in those encoding proteins mediating cytoskeletal assembly and cell-matrix adhesion. RNA transport and localized translation is identified as a crucial process for maintaining the glomerular filtration barrier.

overall_design: Pairwise comparison of two sample classes (control/input versus Staufen 2 RNA-IP) with 3 replicates per class.

first: Jessica

last: Harris

first: Valerie

last: Schumacher


title: Potent and selective PTDSS1 inhibitor targeting collateral lethality against cancer with PTDSS2 deletion [xeno_RNA-seq]

city: Tokyo

first: Hiroki

last: Goto

address: 1-16-13 Kitakasai, Edogawa-ku

institute: Daiichi Sankyo RD Novare

summary: To decipher the underlying mechanism governing selective growth arrest in PTDSS1-inhibited PTDSS2-depleted cancer cells, we analyzed the transcriptomic changes brought about by comparing vehecle treated and DS55980254 treated PTDSS2-KO HCT116 s.c. tumors.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for cancer xenograft models

first: Yohei

last: Yoshihama

first: Kazumi

last: Sato

first: Naoya

last: Wada


title: Transcriptomic analysis in cerebral microvessels from the brain of endothelial-specific Crif1 deficiency mouse

city: Daejeon

first: Min Joung

last: Lee

address: Munhwa-ro 266

department: Department of Biochemistry

institute: Chungnam National University School of Medicine

summary: Endothelial cells (ECs) in cerebral vessels are considered the primary targets in acute hemorrhagic brain injuries. EC dysfunction can aggravate neuronal injuries by causing secondary inflammatory responses and blood-brain barrier (BBB) disruption. ECs comprising the BBB are known to have a higher mitochondrial volume compared with peripheral ECs.   In previous study, we reported Tek-CRIF1-knockout (KO) mice, with EC-specific deletion of the mitochondrial OxPhos-related gene, Crif1, also known as Gadd45gip1 (encoding GADD45G-interacting protein 1), display profound BBB defects accompanied by reduced expression of junctional proteins in ECs. To identify signaling pathways involved in linking EC-specific mitochondrial dysfunction and BBB disruption, we first performed RNA sequencing using isolated cerebral vessels from Tek-CRIF1 mice. This transcriptome analyses of the Tek-CRIF1-KO mouse revealed significant changes in some signaling, a pathway intimately involved in BBB maintenance.

overall_design: RNA was isolated from cerebral microvessels from the brain of Tek- CRIF1-wild type mice (WT) and endothelial-specific Crif1 deletion mice, Tek-CRIF1-knockout mice (KO). (n=3 each per group)

first: Min

first: Jun

last: Heo


title: Effects of upregulated JAK/STAT signaling on gene expression in Drosophila airway epithelial cells

city: Weifang

first: Xiao

last: Niu

state: Shandong

address: Baotong str. 7166

institute: Weifang Medicine University

summary: Chronically activated JAK/STAT signaling leads to several lung diseases, including lung cancer, asthma, and chronic obstructive pulmonary disease. We used the fruit fly Drosophila melanogaster to elucidate the molecular processes which transform elevated JAK/STAT signaling in airway epithelial cells into pathology.

overall_design: We performed gene expression profiling analysis using data obtained from RNA-seq of 2 different tracheal tissues of Drosophila 3rd instar larvae at one time point.

first: Thomas

last: Roeder


title: Histone chaperone CAF-1 is a synthetic lethal vulnerability in the context of ARID1A deficiencies [ATAC-Seq]

first: Christoph

last: Bock

overall_design: 160 ATAC-seq samples for ARID1A knockout and WT HAP1 cells further perturbed with CHAF1A knockdown, degradation or EZH2 inhibitor or Testorsterone.

first: Bernd

last: Boidol

first: Sandra

last: Schick

first: André

last: Rendeiro

first: Anna

last: Ringler

first: Kathrin

last: Runggatscher

first: Derya

last: Dönertas

first: Melanie

last: Hinkel

first: Michael

last: Schleicher

first: Guido

last: Boehmelt

first: Stefan

last: Kubicek


title: Histone chaperone CAF-1 is a synthetic lethal vulnerability in the context of ARID1A deficiencies

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

overall_design: Refer to individual Series


title: Transcriptomic analysis of human Fragile X syndrome neurons reveals neurite growth modulation by the TGFβ/BMP pathway

city: Tel Aviv

first: Guy

last: Shapira

address: Chaim Levanon 30

country: Israel

institute: Tel Aviv University

summary:
Isogenic hESC clones with and without the FX mutation that share the same genetic background were in vitro differentiated into neurons. FX neurons present delayed neuronal development and maturation with full FMRP silencing. Following enrichment of neurons in the culture by MACS, transcriptome analysis by RNA sequencing at different time points during differentiation demonstrated dysregulation of the TGFβ/BMP signaling pathway and genes related to the extracellular matrix. FX neurons showed decreased neurite outgrowth that was rescued by inhibition of the TGFβ/BMP signaling pathway, this treatment did not affect the outgrowth of control neurons.
In FMRP expressing neurons the regulation of the TGFβ/BMP pathway allow typical neurite outgrowth and axonogenesis that will eventually result in normal neuronal network activity. In contrast, in FX neurons the lack of FMRP dysregulate members of the BMP signaling pathway associated with the ECM organization that in a yet unknown mechanism, reduces the guidance of axonal growth cones, leading to an aberrant neuronal network function. Overall, our results provide new insights into the molecular pathways by which loss of FMRP affects neuronal network development which probably leads to its aberrant function in FXS.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Isogenic human embryonic stem cells clones with and without the Fragile X mutation that share the same genetic background and its neuronal differentiation derivatives (neural precursor cells, glial cells and neurons).

first: Liron

last: Kuznitsov-Yanovsky

first: Lital

last: Gildin

first: Noam

last: Shomron

first: Dalit

last: Ben-Yosef


title: The mechanism of the Wenshenyang recipe in the treatment of infertility by transcriptome analysis and network pharmacology

city: Beijing

first: Lan

last: Xie

address: School of Medicine B410, Tsinghua University

institute: Tsinghua University

summary: The Wenshenyang recipe (WSYR) has the effect of treating infertility, but the mechanisms underlying this activity have not been fully elucidated. In this study, network pharmacology and RNA sequencing were combined, with database-based “dry” experiments and transcriptome analysis-based “wet” experiments used conjointly to analyse the mechanism of WSYR in the treatment of infertility. In the dry analysis, 43 active compounds in WSYR and 44 therapeutic targets were obtained through a database search, 15 infertility pathways were significantly enriched, and key targets, such as ESR1, TP53, AKT1, IL-6, and IL-10 were identified. In the wet experimental analysis, HK-2 cells were treated with the three herbs of WSYR. Using the transcriptome sequencing platform, the expression level changes in 412 genes from 15 infertility pathways were observed, and 92 DEGs were finally obtained. Additionally, key targets, such as ESR2, STAT1, STAT3, and IL6, were identified. RT-qPCR experiments further verified that WSYR played an anti-inflammatory role by upregulating IL-4 and IL-10. By building the molecular docking model of ESR1, ESR2 and screening compounds, it was further found that xanthogalenol in Drynaria fortunei (Kunze) J.Sm. (Gusuibu), arachidonate in Cistanche deserticola Y.C.Ma (Roucongrong), and anhydroicaritin in Epimedium brevicornu Maxim. (Yinyanghuo) have good affinity for estrogen receptors. These findings provide evidence that WSYR exerts an estrogen-regulating role. By integrating the results of dry and wet experiments, it was found that the WSYR treats infertility by regulating hormone levels and inflammatory responses.

overall_design: HK-2 cells were cultured in a 384-well plate for 24 hours and treated with the three herbal extracts for 24 hours. Grouped into Gusuibu_control group, Gusuibu_experiment group, Roucongrong_control  group,  Roucongrong_experiment group, Yinyanghuo_control group, Yinyanghuo_experiment group and then subjected to RNAseq for differentially expressed gene determination.In the Gusuibu transcriptome experiment, there were 16 samples in the control group and 3 samples in the experimental group; in the Roucongrong transcriptome experiment, there were 16 samples in the control group and 3 samples in the experimental group; in the Yinyanghuo transcriptome experiment, there were 16 samples in the control group sample, 3 samples in the experimental group.

first: Shuai

last: Zhao

first: Xiaoling

last: Zhang

first: Wenting

last: Huang

first: Liansheng

last: Qiao

first: Delin

last: Zhan

first: Chengmei

last: Ma

first: Wei

last: Gong

first: Honglei

last: Dang

first: Hua

last: Lu


title: Electroconvulsive Stimulation modulates Microglia.   Transcriptome analysis of Biozzi-ABH mice spinal-cord microglia following electroconvulsive-seizures.

city: Jerusalem

first: Smadar

last: Goldfarb

state: Israel

address: Hadassah Hospital

department: Department of Neurology

institute: Hadassah – Hebrew University Medical Center

summary: Neurostimulation by electroconvulsive therapy is highly effective in neuropsychiatric disorders by an unknown mechanism. Microglial toxicity plays a key role in chronic neuro-inflammatory brain diseases, where there is critical shortage in therapies. To investigate the direct effect of electroconvulsive seizures (ECS) on the CNS innate immune system, we performed transcriptome analysis on spinal microglia from ECS- and sham-treated naïve mice.

overall_design: Biozzi ABH mice received three ECS or sham treatments and sacrificed the next day, spinal cords were immediately dissociated and CD11b+ Cells were freshly isolated using magnetic beads. Transcriptome analysis (Illumina NextSeq 500) of three biological replicates per group (pool of five mice per replicate) were analyzed.

first: Tamir

last: Ben-Hur

first: Dan

last: Vershkov


title: Fibroadipogenic Progenitor Regulates Neuromuscular Junction by Secreting Novel Protein Granzyme E

city: Daegu

first: Ji Hwan

last: Park

state: Gyeongbuk

address: 333, Techno jungang-daero, Hyeonpung-eup, Dalseong-gun

department: Newbiology

institute: DGIST

summary: Muscle fibroadipogenic progenitor (FAP) cells, which are muscular mesenchymal cells that originate from lateral plate mesoderm have been proposed to act as a critical regulator for adult muscle homeostasis1–7, including the maturation and proper functioning of the neuromuscular junction (NMJ)3, Prx-Bap1 paper. However, the mechanism and intercellular crosstalk by which FAPs regulate the stability and functionality of neuromuscular system remains unknown. Here we show that FAPs not only locally but also systemically regulate the neuromuscular system through the secretion of a serine-type endopeptidase Granzyme E which may imply the previously unidentified endocrine function of FAPs. Local transplantation of wild-type FAPs into the neuromuscular disease model (Prrx1Cre;Bap1f/f, hereafter, cKO) can readily prevent neuromuscular defects, including degeneration of the neuromuscular junction and loss of motor neurons. These effects are found not only in transplanted hindlimb muscles but also in the contralateral hindlimb and even forelimb muscles. Notably, subcutaneous administration of microparticles encapsulating FAP-conditioned media into cKO mice was sufficient to restore normal neuromuscular functions. By analyzing the transcriptomic and secretomic profiles of FAPs, we identified a novel protein, Granzyme E, which is specifically expressed in and secreted by FAPs, and which indispensably regulates the structure and function of NMJ and motor neuron survival. Our study has defined a unique mechanism of Granzyme E-dependent, systemic control of the neuromuscular system by FAPs, which would provide a comprehensive understanding on the neuromuscular systems and their crosstalk with non-neuronal cells. These findings may provide a therapeutic benefit to treat NMJ-related diseases.

overall_design: Identification of downstream targets of Bap1 and Smn in FAP

first: Ji

first: Deahee

last: Hwang

first: Inkuk

first: Young-Yun

last: Kong


title: Transcriptional profile of NOMO1 knockout cell lines [RNA-seq]

city: Salamanca

first: Rogelio

last: González-Sarmiento

state: Salamanca

address: Alfonso X el Sabio, sn

department: Medicine

institute: University of Salamanca

summary: We report the data of high-troughput RNA sequencing of two different cell lines, HCT-116 (early-onset colorectal cancer; EOCRC) and HS-5 (bone marrow) in order to analyze the transcriptional profile generated after NOMO1 (Nodal Modulator 1) gene inactivation, a candidate biomarker in EOCRC. The generation of the NOMO1 knockout cell lines was performed using CRISPR/cas9 technology. The main objective was to identify whether the loss of NOMO1 generated a differential transcriptional profile in each cell line and whether it was possible to identify genes commonly deregulated in the two NOMO1-KO cell lines. RNA sequencing revealed a set of 592 differentially expressed genes (FDR<0.05) in common to the two cell lines as a consequence of NOMO1 inactivation.

overall_design: Examination of the transcriptional profile of HCT-116 and HS-5 NOMO1 knockout cell lines.

first: Jésica

last: Pérez García

first: Abel

last: Martel-Martel

first: Paula

last: García-Vallés

first: Luis

last: Corchete

first: Juan

last: García

first: Nerea

last: Gestoso-Uzal

first: Rosario

last: Vidal Tocino

first: Oscar

last: Blanco

first: Lucía

last: Méndez

first: Manuel

last: Sánchez-Martín

last: Fuentes

first: Ana

last: Herrero

first: Andreana

last: Holowatyj

first: José

last: Perea


title: Transcriptional profile of NOMO1 knockout cell lines [Affymetrix]

summary: We report the data of whole Gene expression of three different cell lines, HT-29 (early-onset colorectal cancer, EOCRC), HCT-116 (EOCRC) and HS-5 (bone marrow) in order to analyze the transcriptional profile generated after NOMO1 (Nodal Modulator 1) gene inactivation, a candidate biomarker in EOCRC. The generation of the NOMO1 knockout cell lines was performed using CRISPR/cas9 technology. The main objective was to identify whether the loss of NOMO1 generated a differential transcriptional profile in each cell line and whether it was possible to identify genes commonly deregulated in the three NOMO1-KO cell lines. The analysis revealed a set of differentially expressed genes in common to the three cell lines as a consequence of NOMO1 inactivation.

overall_design: Examination of the transcriptional profile of HT-29, HCT-116 and HS-5 NOMO1 knockout cell lines.


title: Pan-neuronal ribotagging in fasted C. elegans

city: Cambridge

first: Ian

middle: Gordon

last: McLachlan

state: MA

address: 77 Massachusetts Ave, 46-4243

department: Brain and Cognitive Sciences

institute: MIT

summary: mRNA-seq of adult C. elegans whole-animal and pan-neuronal ribotagging samples in fed or three-hour fasted animals.

overall_design: Three independent biological replicates, each with fed and three-hour fasted conditions. Each fed or fasted condition contains whole-animal input mRNA-seq data and pan-neuronal ribotagging mRNA-seq data.

first: I

first: S

last: Flavell


title: Genome-wide binding sites of RBM46 in mouse testes.

city: Nanjin

first: Baomei

last: Qian

address: Jiangning

institute: Nanjing Medical University

summary: We carried out RBM46 eCLIP-seq (enhanced cross-linking immunoprecipitation coupled with sequencing) in wild-type testes and reported genome-wide occupancy of RBM46 in mouse testes.

overall_design: Wild-type testes at P12-P14 were collected and eCLIP-seq of RBM46  was performed.We have biologically duplicates.

first: B

first: L

last: Ye


title: circRNA, lncRNA and mRNA profiles of umbilical cord blood exosomes from preterm newborns showing bronchopulmonary

city: Changzhou

first: huaiyan

last: Wang

address: Dingxiang Road

department: Department of Neonatology

institute: Changzhou Maternity and Child Health Care Hospital of Nanjing Medical University

summary: Purpose: The purpose of this study was to detect the expression profiles of circRNAs, lncRNAs and mRNAs in umbilical cord blood (UCB) exosomes from BPD infants. Methods:Microarray analysis was performed to compare the RNA profiles of UCB-derived exosomes from preterm newborn with and without BPD. Then, circRNA/lncRNA-miRNA-mRNA co-expression networks were built to determine their associations with BPD.Results:A total of 317 circRNAs, 104 lncRNAs, 135 mRNAs showed significant differential expression in UCB-derived exosomes from BPD preterm infants compared with the NBPD group. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for examining  differentially expressed exosomal circRNAs, lncRNAs and mRNAs. Our results showed the GO terms and KEGG pathways mostly involving differentially expressed exosomal RNAs were closely associated with endothelial or epithelial cell development. In addition, two networks were identified, including circRNA-circ_0086018/miR-762/MEN1 and lncRNA-BASP1-AS1/miR-20a-5p/DNAJC22 networks, which may take part in BPD.

overall_design: UCB specimens were obtained from the umbilical vein right after fetal delivery. Then, Microarray analysis was performed to compare the RNA profiles of UCB-derived exosomes from preterm newborn with and without BPD.

first: Huaiyan

first: Lin

last: Zhang

first: Yu

first: Xuan

first: Qiushi

last: Xu

first: Jiao

last: Yin


title: Human patients with influenza virus and bacterial infections

city: Münster

first: Klaus

last: Schughart

address: Von-Esmarch-Str 56

department: Virology

institute: University Münster

summary: Peripheral blood was collected from human patients infected with influenza A virus only or in addition with bacterial pathogens and at different days after hospital admission. For comparison, blood from healthy controls was collected. Gene expression differences were detected in influenza and bacterial infections compared to healthy controls, and at various days post infection.

overall_design: We recruited patients from 20 hospitals during the period 2009 to 2016. The eligibility criteria included (1) age greater than 18 years and (2) World Health Organization definition of influenza-like illness (fever of 38 C° or higher, cough and illness onset within the last ten days). Eligible patients were assessed by an admitting physician for likelihood of influenza infection. Patients with a high likelihood of infection, based on history and clinical features, were enrolled into the study. Collection of peripheral blood from human patients, preparation of RNA and gene expression analysis using microarrays was performed.

first: Benjamin

last: Tang


title: Potent and selective PTDSS1 inhibitor targeting collateral lethality against cancer with PTDSS2 deletion

first: Hiroki

last: Goto


title: Metabolic engineering reveals the relative importance of different sugar catabolic pathways during growth of Aspergillus niger on plant biomass

city: Utrecht

first: Ronald

last: de vries

state: Utrecht

address: Uppsalalaan 8

country: Netherlands

institute: westerdijkinstitute

summary: To evaluate the relative contribution of individual sugar catabolic pathways to the overall physiology of A. niger during growth on plant biomass, the A. niger sugar catabolic pathways involved in converting the most common monomers of plant biomass polysaccharides were blocked, and the phenotype as well as the transcriptomic response of these single-pathway deletion mutants was analysed on two distinct plant biomass substrates: wheat bran (WB) and sugar beet pulp (SBP). Deletion of all the above catabolic pathways were also combined in a single strain (?all), to evaluate whether other compounds of plant biomass could still support growth of A. niger when utilization of the major sugar components is blocked. On both WB and SBP, the strongest affected single-pathway deletion mutants were the PCP and glycolysis deficient mutants, delta-xkiA and delta-hxkA/delta-glkA, respectively. Especially on WB, which is a particularly rich substrate in pentose sugars, blocking PCP caused a significant effect in delta-xkiA with respect to both growth and transcriptomic response. However, delta-hxkA/delta-glkA was shown to be the most critically affected strain. On both substrates, combined deletion of hxkA and glkA resulted in the strongest growth reduction of all the single-pathway mutants, very similar to the multi-pathway deletion mutant delta-all. This result clearly pointed to glycolysis as the most essential and indispensable pathway for the survival of A. niger on these substrates. Since cellulose is not a preferred carbon source for A. niger, it seems that the double deletion of hxkA and glkA mostly affected the utilization of starch. (Note: A portion of this research was performed on a project award (10.46936/expl.proj.2019.51072/60006675) from the Environmental Molecular Sciences Laboratory, a DOE Office of Science User Facility sponsored by the Biological and Environmental Research program under Contract No. DE-AC05-76RL01830)

overall_design: mRNA profiling of five Aspergillus niger strains grown on wheat bran or sugar beet pulp at two time points.

first: Tania

last: Chroumpi

first: Mar

last: Cubertorer Navarro

first: Agata

last: Terebienic

first: Astrid

last: Mueller

first: Jiajia

last: Li

first: Mao

last: Peng

first: Meng

last: Markillie

first: Hugh

last: Mitchell

first: Carrie

last: Nicora

first: Chelsea

middle: M

last: Hutchinson

first: Vanessa

last: Paurus

first: Samuel

middle: O

last: Purvine

first: Chaevien

middle: S

last: Clendinen

first: Galya

last: Orr

first: Scott

last: Baker

first: Miia

last: Makela

middle: P

last: de Vries


title: Potent and selective PTDSS1 inhibitor targeting collateral lethality against cancer with PTDSS2 deletion [cell_RNA-seq]

first: Hiroki

last: Goto

summary: To decipher the underlying mechanism governing selective growth arrest in PTDSS1-inhibited PTDSS2-depleted cancer cells, we analyzed the transcriptomic changes brought about by comparing DMSO treated and DS07551382 treated wild type or PTDSS2-depleted cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for human cancer cell lines

first: Yohei

last: Yoshihama

first: Kazumi

last: Sato

first: Naoya

last: Wada


title: Transcriptional profile of NOMO1 knockout cell lines

first: Rogelio

last: González-Sarmiento


title: A specific JMJD6 inhibitor potently suppresses multiple types of cancers both in vitro and in vivo

city: Xiamen

first: Guosheng

last: Hu

state: Fujian

address: Xiang'an South Road, Xiang'an District

department: School of Pharmaceutical Sciences

institute: xiamen University

summary: Jumonji C-domain containing protein 6 (JMJD6), an iron (Fe2+) and a-ketoglutarate (a-KG)-dependent oxygenase, is expressed at high levels, correlated with poor prognosis, and considered as a therapeutic target in multiple cancer types. However, specific JMJD6 inhibitors that are potent in suppressing tumorigenesis have not been reported so far. We herein report that iJMJD6, a specific small-molecule inhibitor of JMJD6 with favorable physiochemical properties, inhibits the enzymatic activity of JMJD6 protein both in vitro and in cultured cells. iJMJD6 is effective in suppressing cell proliferation, migration, and invasion in multiple types of cancer cells in a JMJD6-dependent manner, while it exhibits minimal toxicity in normal cells. Mechanistically, iJMJD6 represses the expression of oncogenes including Myc and CCND1, in accordance with JMJD6 function in promoting the transcription of these genes. iJMJD6 exhibits suitable pharmacokinetic properties and suppresses tumor growth in multiple cancer cell line-and patient-derived xenograft models with safety. Furthermore, combination therapy with iJMJD6 and BET protein inhibitor (BETi) JQ1 or estrogen receptor antagonist fulvestrant exhibits synergistic effects in suppressing tumor growth. Taken together, we demonstrate that inhibition of JMJD6 enzymatic activity by using iJMJD6 is effective in suppressing oncogene expression and cancer development, providing a therapeutic avenue for treating cancers that are dependent on JMJD6 in clinic.

overall_design: ChIP-seq performed in this study was designed to investigate the effects of iJMJD6 on JMJD6-mediated demethylation in cancer cells

first: Wen

last: Liu

first: Rong-quan

last: Xiao

first: Guo-sheng


title: Transcriptomic alterations in mouse testis depleted of RBM46.

first: Baomei

last: Qian

state: Jiangsu

summary: This study aims to explore the expression changes in Neurog-cre/Rbm46fl/- mice at P10, when meiosis initiates. Testes were collected from Rbm46fl/+ and Neurog-cre/Rbm46fl/- mice at 10d. RNA-seq libraries were proformed in biologically duplicates.

overall_design: Total RNA was extracted from 10d testes of Rbm46fl/+ and Neurog-cre/Rbm46fl/-  at P10 using TRIzol reagent. For each group, we have biologically duplicates. Strand-specific libraries were prepared using the TruSeq Stranded Total RNA Sample Preparation kit (Illumina) according to the manufacturer's instructions.

first: B

first: L

last: Ye


title: PDX bank from urothelial cancer to guide precision medicine.

city: paris

first: Elodie

last: chapeaublanc

address: 26 rue d'ulm

department: UMR 144

country: France

institute: Institut Curie

summary: We developed preclinical PDX models, recapitulating the molecular heterogeneity of MIBCs and UTUC, which will represent an essential tool in therapy development. Pharmacological characterization of the PDXs suggested that upper urinary tract and bladder cancers (UCC/ SCC) with similar molecular characteristics could benefit from the same treatments, and showed a benefit for combined FGFR/EGFR inhibition in FGFR3-mutant PDXs, compared to FGFR inhibition alone.

overall_design: Integrated molecular and pharmacological characterization of patient-derived xenografts from bladder and ureteral cancers identifies new potential therapies.

first: François

last: Radvanyi

first: Isabelle

last: Bernard-Pierrot

first: Clémentine

last: Krucker

first: Urosphere

middle: T

last: France

last: Chapeaublanc


title: In vitro biocompatibility of Ti-Cp vs Ti-26Nb alloys on Saos-2 and THP-1 cells

city: NANCY

first: Laëtitia

last: CHEZEAU

address: Campus Artem, 2 allée André Guinier

department: Institut Jean Lamour

institute: Université de Lorraine

summary: This study assess the biocompatibility of Ti-26Nb compared to Ti-Cp, a reference in implantology, through the combination of conventional toxicological assay, morphological observations and transcriptomic analysis performed on two different cells line : Saos-2 and THP-1. The biocompatibility of Ti-Cp implants was evaluated in comparison with Ti-26Nb implants both having a mirror polished surface, studying cell proliferation (trypan blue and WST-1) and cell morphology/adhesion (SEM) on human THP-1 and Saos-2 cell lines. Finally, an evaluation of a potential toxicity of potassium niobiate powder KNbO3 was carried out by measuring metabolic activity and realizing a transcriptomic study on the THP-1 line (the first one) to deepen the results observed with Ti-26Nb discs. Indeed, niobiate ions are potentially released from implant in cellular acidic environnement. Concerning Saos-2 cells, our results suggest that Ti-26Nb and Ti-Cp discs do not impact proliferation and viability. Concerning THP-1 cell line, a decrease in proliferation and viability is observed in contact of Ti-26Nb discs (hypothesis of a cell-line effect ?, no biocompatibility study on monocyte/macrophage cell lines such as THP-1 actually available in literature). KNbO3 powder does not impact viability of THP-1 cells and does not induce changes at molecular level. Taken together, these data suggest a possible toxicity of Ti-26Nb toward THP-1 cells not directly related to the niobium but perhaps to the manufacturing process of Titane niobium alloy.

overall_design: Changes in gene expression in THP-1 cells (1,5 million) incubated without (control) or with 25 ug/mL of KNbO3 powder  for 24 h, were measured. Four biological replicates were performed as controls : T1 ; T2 ; T3 ; T4. Four biological replicates were performed in THP-1 cells exposed to 25 ug/mL of KNbO3 powder : E1 ; E2 ; E3 ; E4. A total of 8 samples (microarrays) was used.

last: Chézeau

first: Alex

last: Tchinda

first: Gaël

last: Pierson

first: Pierre

last: Brunet

first: Mohamed

last: Zaiou

first: Bertrand

last: Rihn

last: Bravetti


title: RBMS1 regulates breast cancer progression

city: Dalian

first: Wang

last: Yang

address: 9 Lvshun South Rd West Section, Lüshunkou District, Dalian, Liaoning, China

department: Institute of Cancer Stem Cell

institute: Dalian Medical University

summary: In order to profile the transcription events that were regulated by RBMS1, mRNA-seq was performed on plko_ctl and plko_s1 which based on MDA-MB-231 cells

overall_design: This study includes a total of 2 profiling samples, plko_S1 was generated as a RBMS1 knocked down breast cancer cells . plko_ctl was generated as a control breast cancer cells .

first: Wenjing

last: Zhang


title: ZNF384 fusion oncoproteins drive lineage aberrancy in acute leukemia [RNA-Seq]

city: MEMPHIS

first: QINGSONG

last: GAO

state: Tennessee

address: 262 DANNY THOMAS PLACE

institute: ST JUDE CHILDREN'S RESEARCH HOSPITAL

summary: RNA-seq of multiple models of ZNF384-rearrangments (transplanted human CD34 cells and transplanted mouse lineage negative cells) to determine differentially expressed genes.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: RNA-seq in GFP-sorted cells. CD34 cells had 5 fusion replicates and 1 wild type sample. ARF-null mouse tumors had at least 3 fusion replicates and 1 wild type sample. Mouse tumors had at least 2 fusion replicates, 3 NRAS G12D replicates, and 5 wild type replicates.

first: Kirsten

last: Dickerson

first: Charles

last: Mullighan


title: RBM46 in mouse testes.

first: Baomei

last: Qian

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

overall_design: Refer to individual Series


title: The expression of mRNA and lncRNA in peripheral blood mononuclear cells (PBMCs) of diabetes mellitus, diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) patients

city: Ningbo

first: Jin

last: Xu

address: 818 Fenghua Road

institute: Ningbo University

summary:
DR, DPN and DN are common complications in diabetes, and the differentially expressed mRNAs and lncRNAs in these diabetic complications may help to identify the molecular markers for the onset and progression of diseases.
In our study, high-throughput sequencing technique was used to analyze the expression profile of mRNA and lncRNA in the peripheral blood of health control, T2DM, DR, DPN and DN patients, in order to determine the
differentially expressed  transcriptomic profiles changes in diabetic complications and identify the shared and specific biological signaling pathways related to DR, DPN and DN.

overall_design: mRNA and lncRNA transcriptional spectrums of peripheral blood mononuclear cells in health control, T2DM, DR, DPN and DN patients were obtained through high-throughput sequencingene technology.

first: Hui

last: Zhu


title: Chromatin accessibility landscapes of WT (Rag1-/-) and BATF KO (Rag1-/-Batf-/-) ILC3s sorted from small intestine [ATAC-seq]

city: Chicago

first: Weiguo

last: Cui

state: IL

address: 303 E Chicago Ave

department: Pathology

institute: Northwestern University

summary: Group 3 innate lymphoid cells (ILC3s) are crucial for the maintenance of host-microbiota homeostasis in gastrointestinal mucosal tissues. The mechanisms that maintain lineage identity of intestinal ILC3s, and ILC3s-mediated orchestration of microbiota and mucosal T cell immunity are elusive. Here, we identified BATF as a gatekeeper of ILC3s homeostasis in the gut. Depletion of BATF in ILC3s resulted in excessive interferon-γ production, dysbiosis, aberrant T cell immune responses and spontaneous inflammatory bowel disease (IBD), which was considerably ameliorated by removal of adaptive immunity or antibiotic treatment. Mechanistically, BATF directly regulates ILC3s identity by globally shapes chromatin landscape of ILC3s. BATF directly binds to the cis-regulatory elements of type 1 effector genes, restrains their chromatin accessibility and inhibits their expression. Conversely, BATF promotes chromatin accessibility of genes involved in MHCII antigen processing and presentation pathways. Collectively, our findings reveal BATF is a promising candidate to maintain ILC3s stability and coordinate ILC3s–mediated control of intestinal homeostasis.

overall_design: ATACseq, 2 samples (WT and Batf-/- ILC3s), 2 biological replicates per sample, from small intestine.

first: Xiaopeng

last: Wu


title: ZNF384 fusion oncoproteins drive lineage aberrancy in acute leukemia [HiChIP]

summary: We report no global changes in H3K27Ac upon expression of ZNF384 fusions but 47 loci with increased H3K27Ac. Therefore we performed HiChIP H3K27Ac to determine if those loci are enhancers. We did not observe any differential looping.

overall_design: 2 replicates of H3K27Ac HiChIP in fusion-expressing or ZNF384 ARF-null pre-B cells.


title: ZNF384 fusion oncoproteins drive lineage aberrancy in acute leukemia [scRNA-Seq]

summary: Expression of ZNF384 fusions results in lineage abberancy and leukemia development. Here we report the gene expression changes that occur in the hematopoietic system when Ep300-Zfp384 is expressed in a transgenic mouse model.

overall_design: Single cell RNAseq using 10X 3' v3.1


title: Characterization of small intestine innate lymphoid cells of WT (Batf fl/fl) and cKO (Batf fl/fl Plzf cre+) mice using single cell RNA sequence [scRNA-seq]

overall_design: Two samples (WT and cKO) were prepared using 10x Genomics Chromium platform


title: The WNT-dependent gating of MYC requires non-canonical functions of a distal CTCF binding site

city: Stockholm

first: Anita

last: Göndör

address: Nobels väg 16, KI Solna Campus, Karolinska Institutet, Box 280

department: MTC

country: Sweden

institute: Karolinska Institutet

summary: Abnormal WNT signaling increases MYC expression in colon cancer cells in part via oncogenic super-enhancer-(OSE)-mediated gating of the active MYC to the nuclear pore in a poorly understood process. We show here that that the principal tenet of the WNT-regulated MYC gating, facilitated nuclear export of the MYC mRNA, converged on a single CTCF binding site (CTCFBS) within the OSE to confer increased growth advantage. To achieve this, the CTCFBS directed in a stepwise manner the WNT-dependent trafficking of the entire OSE to the nuclear pore from intra-nucleoplasmic positions. Once the OSE reached a perinuclear position, triggered by CTCFBS-mediated CCAT1 eRNA activation, its final stretch (<1micrometer) to the nuclear pore required the recruitment of AHCTF1, a key nucleoporin, to the CTCFBS. Thus, a novel WNT-CTCF-eRNA circuit converges on the ability of the OSE to promote pathological cell growth by coordinating the trafficking of MYC within the 3D nuclear architecture.

overall_design: Examination of CTCF binding in D3, E4 and WT. All the cell line is HCT-116. D3 and E4 are two clones of CTCF mutation.


title: Effect of depletion of OsPIN1c, OsPIN1d, and OsPID on gene expression in leaf primordia during vegetative growth

city: nanjing

first: Jiajun

last: Liu

address: Weigang no.1, Xuanwu District, Nanjing City, Jiangsu Province

institute: Nanjing Agricultural University

summary: To explore the molecular mechanisms of leaf development mediated by OsPIN1c, OsPIN1d, and OsPID, we established ospin1c ospin1d and ospid mutant lines, and then examined the gene expression profiles in vegetative leaf primordia of WT, ospin1c ospin1d, ospid C1, and ospid C2.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Nipponbare (WT) and several mutant lines (ospin1c ospin1d, ospid C1, and ospid C2).

first: Xi'an

last: Shi

first: Wanrong

last: Jie

first: Chengqiang

last: Ding


title: A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production

city: Stanford

first: Maria

last: Barna

state: California

address: 279 Campus Drive, Beckman Center B309

institute: Stanford University

summary: Recent findings suggest that the ribosome itself modulates gene expression. However, whether ribosomes change composition across cell types or control cell fate remains unknown. Here, employing quantitative mass spectrometry during human embryonic stem cell differentiation, we identify dozens of ribosome composition changes underlying cell fate specification. We observe upregulation of RPL10A/uL1-containing ribosomes in the primitive streak followed by progressive decreases during mesoderm differentiation. An Rpl10a loss-of-function allele in mice causes striking early mesodermal phenotypes, including posterior trunk truncations, and inhibits paraxial mesoderm production in culture.  Ribosome profiling in Rpl10a loss-of-function mice reveals decreased translation of mesoderm regulators, including Wnt pathway mRNAs, which are also enriched on RPL10A/uL1-containing ribosomes. We further show that RPL10A/uL1 regulates canonical and non-canonical Wnt signaling during stem cell differentiation and in the developing embryo.  These findings reveal unexpected ribosome composition modularity that controls differentiation and development through the specialized translation of key signaling networks.

overall_design: Ribosome profiling from E8.5 Rpl10a +/+ and Rpl10a LOF/LOF embryos (N=3 of each genotype)

first: Naomi

last: Genuth

first: Zhen

first: Koshi

last: Kunimoto

first: Victoria

last: Hung

first: Adele

first: Craig

last: Kerr

first: Gerald

middle: C

last: Tiu

first: Juan

middle: A

last: Oses-Prieto

first: Rachel

last: Salomon-Shulman

first: Jeffrey

middle: D

last: Axelrod

first: Alma

last: Burlingame

first: Kyle

last: Loh


title: BATF is a promising candidate to maintain ILC3s stability and to coordinate ILC3s-meditaed control of intestinal homeostasis

first: Weiguo

last: Cui


title: GCN2 suppresses TOP mRNA translation via LARP1

first: Soroush

last: Tahmasebi

address: 909 S Wolcott Ave

department: Department of Pharmacology and Regenerative Medicine

institute: University of Illinois at Chicago

summary:
La-related protein 1 (LARP1) has been identified as a key translational inhibitor of terminal oligopyrimidine tract (TOP) mRNAs downstream of the nutrient sensing protein kinase complex, mTORC1. LARP1 exerts this inhibitory effect on TOP mRNA translation by binding to the mRNA cap and the adjacent 5’TOP motif, resulting in the displacement of the eIF4E complex from TOP mRNAs. In the present study, we identify a second nutrient sensing kinase GCN2 that converges on LARP1 to control TOP mRNA translation. GCN2 inhibits TOP mRNA translation via ATF4-dependent transcriptional induction of LARP1 mRNAs and GCN1-mediated recruitment of LARP1 to stalled ribosomes.
We performed ATF4 ChIP-seq experiments in both WT and GCN2 KO MEFs with or without leucine deprivation.

overall_design: WT and GCN2 KO MEFs were cultured in DMEM with or without Leucine for 24h prior to crosslinking and ATF4 ChIPs.

first: Catherine

middle: R

last: Dufour

first: Eloi

last: Mercier

first: Guillaume

last: Bourque

first: Vincent

last: Giguère


title: Impact of exposures to persistent endocrine disrupting compounds on the sperm methylome in regions associated with neurodevelopmental disorders

city: Washington

first: Valerie

middle: Wailin

last: Hu

state: DC

department: Biochemistry and Molecular Medicine

institute: The George Washington University School of Medicine and Health Sciences

type: Methylation profiling by high throughput sequencing

summary: Although autism spectrum disorder (ASD) is among the most heritable of neurodevelopmental disorders, the rapidly rising prevalence of ASD suggests that environmental factors may interact with genetic risk for ASD. Environmental factors may impact both gene expression and phenotypes in ASD through epigenetic modifications that, in turn, could lead to intergenerational effects influencing risk for ASDs. Endocrine disrupting compounds (EDCs), such as the long-lived organochlorines, are of particular interest with respect to risk for autism because of their ability to interfere with sex hormones that have been implicated in the regulation of RORA, a dysregulated gene in ASD that is a master regulator of many other ASD risk genes. The specific aims of this study are to: 1) investigate whether high versus low exposures to the persistent organochlorine 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) are associated with differentially methylated  regions (DMRs) in sperm from a Faroese cohort whose natural diet of pilot whale meat and blubber exposes them to higher than average levels of organic pollutants; 2) determine if genes associated with DDE DMRs are enriched for ASD risk genes; 3) identify pathways and functions over-represented among genes associated with DMRs. Whole genome bisulfite sequencing (WGBS) was used to identify genome-wide DMRs in sperm from individuals divided by high and low exposure levels. Gene ontology and pathway analyses were used to determine enrichment in functional relationships to ASD. Genes in DMRs not only could discriminate between high and low exposures to DDE, but also were enriched in autism risk genes. Gene ontology and pathway analyses of these genes show significant enrichment for neurodevelopmental processes frequently impacted by ASD. Results of this study show that elevated exposure to certain organochlorines is associated with genome-wide DNA methylation patterns in sperm affecting genes involved in neurological functions and developmental disorders, including ASD.

overall_design: DNA methylation in sperm from a cohort of men from the Faroe Islands (Denmark) was investigated using whole genome bisulfite sequencing. This cohort was selected based on their higher than average exposure to persistent organochlorine compounds based on their diet of pilot whale meat and blubber.  Semen samples from 52 men were divided into two exposure groups for comparison of methylation profiles; these were the high (26 samples] and low (26 samples) exposure groups based on the highest and lowest tertiles of serum levels of the organochlorine 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), which correlated well with the levels of several other organochlorines (e.g., PCBs) in the respective sera.


title: ZNF384 fusion oncoproteins drive lineage aberrancy in acute leukemia [ChIP-seq]

first: QINGSONG

last: GAO

summary: We report changes in chromatin occupancy dependent on TCF3-ZNF384 splicing isoform usage. The isoform including exon 8, which encodes 2 zinc finger domains, has increased binding near genes important for nomal hematopoiesis. We report no global changes in H3K27Ac upon expression of ZNF384 fusions but 47 loci with increased H3K27Ac.

overall_design: 4 replicates of HA-tagged fusion proteins expressed in ARF-null pre-B cells or 2 replicates of H3K27Ac in fusion-expressing or wildtype expressing cells.

first: Kirsten

last: Dickerson

first: Charles

last: Mullighan


title: Transcriptional regulation of ICAM-1 in human retinal endothelial cells (HREC)

city: Adelaide

first: Feargal

middle: J

last: Ryan

state: Adelaide

address: North Terrace

institute: SAHMRI

summary: Total RNASeq of 5 HREC donors exposed to TNF-alpha and IL1-beta. Here we seek to investigate the transcriptional regulation of ICAM-1 in human retinal endothelial cells (HREC). In order to do this we have collected primary isolates from 5 HREC donors and exposed them to Tumour Necrosis Factor alpha and Interleukin-1. Total RNA was sequenced on a NovaSeq to 1.2 illion 150bp read pairs per sample. Samples here cluster primarily by donor and then by time (60 minutes vs 24 hours).

overall_design:
Total RNA-Seq of human retinal endothelial cells (HREC)
5 donors, with 3 samples from each at two timepoints. 30 samples total: Control, TNF and IL1 treated groups.

first: David

last: Lynn

first: Justine

last: Smith


title: Using DMS-MaPseq to dissect structural differences of ribosomal RNA in different SSU Processome intermediates

city: Jupiter

first: xin

last: liu

state: FL

address: 130 Scripps Way

institute: The Scripps Research

summary: Ribosomes are among the largest folded RNAs, whose function depends on their structure. Nonetheless, in vitro studies indicate a propensity of rRNAs to misfold. We use a combination of DMS-MaPseq, structural analyses, biochemical experiments, and yeast genetics to dissect the final RNA folding steps of the small ribosomal subunit head.

overall_design: SSU Processome are purified from Has1-WT or Has1-H375A cells are purified via Utp10-TAP.  Each sample has DMS treated and its untreated control. There are 4 biological replicates.

first: Xin

last: Liu

first: Katrin

last: Karbstein


title: ZNF384 fusion oncoproteins drive lineage aberrancy in acute leukemia


title: Nanostring derived microRNA of rats treated with lithium alone and in combination with amiloride for 6 months

city: Dunedin

first: Paulomi

last: Mehta

state: Otago

address: 56 Hanover street

department: Department of Pathology

country: New Zealand

institute: University of Otago

summary: Differential analysis of microRNA in response to treatment with lithium and amiloride

overall_design: MicroRNA quantification of all samples using Nanostring nCounter Rat miRNA Assay on Nanostring nCounter GEN2 Digital Analyzer.


title: Expression data from  CHST11 over-expression in A-549 or NCI-H358 cells

city: Taipei

first: Wei-Min

last: Chang

state: Not Applicable

address: 128 Academia Road, Section 2, Nankang,

country: Taiwan

institute: Academia Sinica

summary:
To examine the CHST11 controls transcriptome in NSCLC cells, we preformed the Affymetrix Human Genome U133 Plus 2.0 Array with empty vector or CHST11 expression vector in A-549 or NCI-H358 cells
Then the transcriptome were compared with each other to see the CHST11-regulating gene in NSCLC cells

overall_design: Total RNA was collected from empty vector or CHST11 expression in A-549 and NCI-H358 cells

first: Michael

last: Hsiao


title: Telomere Shortening Impairs PGC Fate Decision [ATAC-seq]

city: Munich

first: Chenglei

last: Tian

address: Ingolstädter Landstraße 1

institute: Helmholtz Munich

summary: We asked whether telomere shortening impairs differentiation of ESCs into germ cell lineage. Terc-/- ESCs were used to investigate the effects of short telomeres on germ cell specification by in vitro differentiation. Short telomeres greatly reduced induction of PGCLCs from ESCs. Mechanistically, short telomeres resulted in excessive chromatin accessibility, which in turn activated the genes regulated by chromatin. Notably, Fst overexpression reduced BMP-Smad signaling and thus induction of PGCLCs, meanwhile upregulation of MAPK signaling pathway increase somatic lineage differentiation in short telomeres sampels. Moreover, knockin of Terc gene by CRISPR/Cas9 in Terc-/- ESCs restored telomere length and normal gene expression profile, and rescued PGCLC induction, revealing important roles of telomeres in PGC fate decision.

overall_design: We used long telomere (LT), short telomere (LT) and telomere length rescued (RT) 1dEBs, PGCLCs and 1dMeiLCs differention from ESCs to do ATAC-seq for analysis the chromatin accessibility of global genome, PGC genes, somatic lineage genes, meiosis-related genes and genes invovled in MAPK and TGF-beta signaling pathways.


title: Differential gene expression changes to oral immunotherapy by a multi-antigenic peptide at different time points of atherosclerotic disease progression

city: BANGALORE

first: V L NARASIMHA RAO

last: THOTA

state: KARNATAKA

address: 258/A NARAYANA HRUDAYALAYA, BOMMASANDRA

country: India

institute: Thrombosis Research Institute

summary: To understand the changes in gene expression by oral immunotherapy to a multi-antigenic construct consisting AHC (ApoB, HSP60 and chlamydia pneumonia outer membrane protein) at different stages of atherosclerotic development, double knock out Apobtm2Sgy/Ldltm1Her mice were fed with high-fat after 5 oral doses with respective highfat diet alone controls at 0,6,18 and 30 weeks.

overall_design: Double knockout mice treated with AHC and untreated were fed on high cholesterol diet were sacrificed after 0, 6, 8, 18 and 30 weeks and RNA was extracted for Microarray analysis from the ascending aorta of the animals.

first: Lakshmi

last: Thota

last: Mundkur


title: RBM45 is an m6A-binding protein that affects neuronal differentiation and the splicing of a subset of pre-mRNAs VII

status: Public on Aug 30 2022

city: D

first: Kate

last: Meyer

state: NC

address: 307 Research Drive Box 3711

department: Biochemistry

institute: Duke University School of Medicine

summary: Here, we identify RNA-binding motif containing protein 45 (RBM45) as a novel m⁶A reader, enriched in the brain, and highly expressed during embryonic neurodevelopment. We demonstrate that RBM45 recognizes intronic m⁶A and that its primary role is as a direct regulator of pre-mRNA splicing for its target genes, many of which are associated with neurodevelopment. Furthermore, we show that RBM45 is absolutely required for proper differentiation in cultured SH-SY5Y neuroblastoma cells, and that RBM45 regulates splicing of neurodevelopmental target genes central to the activation of gene expression programs that regulate differentiation in vitro.

overall_design: Transcriptomic profiling of RBM45 binding sites and target genes (CLIP-seq) in control (DMSO-treated) and differentiated (10 µM RA-treated) SH-SY5Y stable cells expressing FLAG-HA-RBM45

first: Seung

middle: H

last: Choi


title: Inter-gastruloid heterogeneity revealed by single cell transcriptomics time course: implications for organoid based perturbation studies

city: Hinxton

first: Leah

middle: Ursula

last: Rosen

address: Wellcome Genome Campus

country: United Kingdom

institute: EMBL-EBI

summary: Recent advances in organoid and genome editing technologies are allowing for perturbation experiments at an unprecedented scale. However, before doing such experiments it is important to understand the gene expression profile in each of the organoid’s cells, as well as how much heterogeneity there is between individual organoids. Here we characterise an organoid model of mouse gastrulation called gastruloids using single cell RNA-sequencing of individual organoids at half-day intervals between day 3 and day 5 of differentiation (roughly corresponding to E6.5-E8.75 in vivo). Our study reveals multiple differentiation trajectories that have hitherto not been characterised in gastruloids. Intriguingly, we observe that individual gastruloids displayed a strong bias towards producing either mesodermal (largely somitic) or ectodermal (specifically neural) cell types. This bifurcation is already seen at the earliest sampled time point, and is characterised by increased activity of WNT-associated pathways in mesodermally-biased gastruloids as compared to neurally-biased gastruloids. Notably, at day 5, mesodermal gastruloids show an increase in the proportion of neural cells, while neural gastruloids do not produce notably more mesodermal cells. This is in line with previous studies on how the balance between these cell types is regulated. We demonstrate using in silico simulations that without proper understanding of the inter-organoid heterogeneity, perturbation experiments have either very high false positive or negative rates, depending on the statistical model used. Thus in future studies, modelling of inter-organoid heterogeneity will be crucial when designing organoid-based perturbation studies.

overall_design: MULTI-seq (10X + individual gastruloid barcoding) for gastruloids between day 3 and day 5 of differentiation at half day intervals. A total of 4 experiments were performed. In the first experiment, day 3 and day 4 gastruloids were sequenced using 10X without MULTI-seq. The first MULTI-seq experiment involved 24 day 5 gastruloids spread over 3 10X lanes. The second MULTI-seq experiment involved 3 pools of day 3 and day 3.5 gastruloids (“exp2A_d3_d3.5”, “exp2C_d3_d3.5”, “exp2D_d3_d3.5”; note pools B and D were not sent for 10X sequencing), as well as 3 pools of day 4 and day 4.5 gastruloids (“exp3A_d4_d4.5”, “exp3B_d4_d4.5”, “exp3C_d4_d4.5”). Unfortunately, the day 3 and day 3.5 gastruloid data quality was too poor and these data were excluded in downstream processinng. For the day 4 and day 4.5 gastruloids, out of the 3 pools (pool A, B, and C), only pools B and C were sequenced, and from these only lanes (samples) 2 and 3 from pool B, and lanes 1 and 2 from pool C. The third experiment involved 1 pool of 24 day 3 gastruloids, spread across 2 10X lanes (“exp4_d3”), as well as one pool of 16 day 3.5 and 16 day 4 gastruloids, spread across 4 10X lanes (“exp5_d3.5_d4”), and finally 16 day 4.5 and 16 day 5 gastruloids, spread across 3 10X lanes (“exp6_d4.5_d5”). The MULTI-seq barcodes for this third experiment were additionally resequenced at higher depth and using 16 PCR amplification cycles during library preparation due to low yield.

middle: U

first: L

last: Stapel

first: Ricard

last: Argelaguet

first: Charlie

middle: G

last: Barker

first: Wolf

last: Reik

first: John

last: Marioni


title: ChIP-seq analysis of BATF in ILC3s sorted from small intestine of Rag1-/- mice [CUT&TAG ChIPseq]

first: Weiguo

last: Cui

summary: Group 3 innate lymphoid cells (ILC3s) are crucial for the maintenance of host-microbiota homeostasis in gastrointestinal mucosal tissues. The mechanisms that maintain lineage identity of intestinal ILC3s, and ILC3s-mediated orchestration of microbiota and mucosal T cell immunity are elusive. Here, we identified BATF as a gatekeeper of ILC3s homeostasis in the gut. Depletion of BATF in ILC3s resulted in excessive interferon-γ production, dysbiosis, aberrant T cell immune responses and spontaneous inflammatory bowel disease (IBD), which was considerably ameliorated by removal of adaptive immunity or antibiotic treatment. Mechanistically, BATF directly regulates ILC3s identity by globally shapes chromatin landscape of ILC3s. BATF directly binds to the cis-regulatory elements of type 1 effector genes, restrains their chromatin accessibility and inhibits their expression. Conversely, BATF promotes chromatin accessibility of genes involved in MHCII antigen processing and presentation pathways. Collectively, our findings reveal BATF is a promising candidate to maintain ILC3s stability and coordinate ILC3s–mediated control of intestinal homeostasis.

overall_design: BATF CUT&TAG ChIPseq, 2 samples (anti-BATF and Rabbit normal serum IgG1 was used as a control. ), 2 biological replicates for IgG control and 3 biological replicates for BATF antibody, ILC3s sorted from small intestine and then cultured in vitro for expansion for 2 weeks.

first: Xiaopeng

last: Wu

first: Yao

last: Chen


title: Telomere Shortening Impairs PGC Fate Decision

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

overall_design: Refer to individual Series


title: RBM45 is an m6A-binding protein that affects neuronal differentiation and the splicing of a subset of pre-mRNAs IV

overall_design: in vitro DART-seq m⁶A profiling on subcellular fractionated RNAs (chromatin associated (CA), nuclear, and cytoplasmic RNA) from immortalized mouse hippocampal neurons (mHiPPoE-2)

first: Huanyu

last: Zhu

first: Mathieu

last: Flamand


title: Treadmill physical exercise on postarthritic phase of collagen induced arthritis in DBA1 mice_transcriptome responses on tarsal joint

city: Chihuahua

first: Susana

middle: Aideé

last: González-Chávez

state: Chihuahua

address: Circuito Universitario Campus II

department: Facultad de Medicina

country: Mexico

institute: Universidad Autónoma de Chihuahua

summary: Gene expression profiles in the tarsal joints of DBA/1 mice whit collagen-induced arthritis that performed treadmill exercise in the post-arthritic phase vs. those who were not exercised were compared. Exercise induced the upregulation of inflammatory genes and signaling pathways.

overall_design: Pools of total RNA were made per study group (eight mouse per group): CIA exercised mice (test group) and CIA non-exercised mice (reference). The reverse transcription polymerase chain reaction (RT-PCR) was performed and the resulting complementary DNAs were labeled with Cy5 (CIA exercised mice) or Cy3 (CIA non-exercised mice). Hybridation analysis used the mouse 65-mer oligo library from Sigma-Genosys to compare the expression of 23,232 gene-specific oligonucleotide probes for mouse.

first: César

last: Pacheco-Tena


title: RNA-Seq of transgenic plasma cells from the described subgroup-specific MM mouse models

city: Berlin

first: Wiebke

last: Winkler

address: Robert-Rössle-Straße 10

institute: Max-Delbrück-Centrum for Molecular Medicine in the Helmholtz Association

summary: RNA expression profiling of control, single mutant (Ccnd1, MMSET or Ikk2ca) and double mutant (Ccnd1/Ikk2ca or MMSET/Ikk2ca) bone marrow plasma cells

overall_design: Comparison of transcriptional profiles of (reporter+) CD138+TACI+ bone marrow plasma cells of the Ccnd1 (D) cohort; i.e. control(D) (n=4), Ccnd1 (n=4), Ikk2ca(D) (n=4), Ccnd1/Ikk2ca (n=6); and the MMSET (M) cohort, i.e. control(M) (n=4), MMSET (n=4), Ikk2ca(M) (n=4), MMSET/Ikk2ca (n=6)

first: M

last: Janz

first: Klaus

last: Rajewsky

first: Eric

last: Blanc


title: Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps

city: Seattle

first: Tyler

last: Hether

state: WA

address: 530 Fairview Ave N

department: Translational Sciences

institute: NanoString Technologies, Inc.

summary: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 100 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS) remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, which are a function both of viral load (high vs. low) and transcriptional signatures (splicing isoforms, T-cell receptor expression, cell state regression). These findings reveal a massive disruption of cellular and transcriptional pathways from COVID-19 that can inform subsequent studies on the pathophysiology SARS-CoV-2 as well as other viruses.

sample_organism: Severe acute respiratory syndrome coronavirus 2

overall_design: The molecular mechanisms and clinical manifestations of COVID-19 are still poorly understood, especially in terms of the differences between COVID-19, influenza virus, Acute Respiratory Distress Syndrome (ARDS), and other viral infections. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections (regions of interest, ROIs) with 373 areas of interest (i.e., samples). Note that 1 or more AOIs can be found in a given ROI. The dataset comprises the GeoMx data samples only. Specifically, there are five groups (Covid-19_High, Covid-19_Low, Non-viral [ARDS],  Flu, and Normal). The breakdown of Patients, ROIs, and AOIs are as follows: Covid-19_High, 4 patients and 86 AOIs within 86 ROIs; Covid-19_Low, 4 patients and 94 AOIs within 94 ROIs; Non-viral, 3 patients and 67 AOIs within 63 ROIs; Flu, 2 patients and 46 AOIs within 42 ROIs; Normal, 3 patients and 64 AOIs within 60 ROIs. For each AOI (sample), digital spatial profiling was performed using NanoStiring's Cancer Transcriptome Atlas (CTA) with Covid-19 spike-in genes.

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