title: N7-Methylguanosine tRNA modification promotes hepatocellular carcinoma metastasis after insufficient radiofrequency ablation

status: Public on Nov 20 2022

city: Guangzhou

first: Shenghua

last: Zhu

address: 58 Zhong Shan Road 2

institute: The First Affiliated Hospital, Sun Yat-sen University

summary: Radiofrequency heat ablation is an ideal radical cure for HCC treatment; however, insufficient radiofrequency ablation (IRFA) could lead to a high recurrence rate. N7-methylguanosine (m7G) on tRNAs is a heat-responding modification that is critical for yeast survival under high temperature, while its function and mechanism in HCC recurrence after IRFA are unknown. Here, we found that IRFA significantly up-regulates the level of m7G tRNA modification and its methyltransferase complex components METTL1 and WDR4 in multiple systems including HCC patient-derived xenograft (PDX) mouse, HCC tissues of patients, sublethal-heat-treated models of HCC cell lines and organoids. Functionally, gain- or loss-of function assays showed that METTL1 mediated m7G tRNA modification promotes HCC metastasis under sublethal heat exposure both in vitro and in vivo. Mechanistically, we found that METTL1 and m7G tRNA modification enhance the translation of SLUG and SNAIL in a codon frequency dependent manner under sublethal heat exposure. Overexpression of SLUG and SNAIL rescued the malignant potency of METTL1 knockdown HCC cells after sublethal heat stress. Our study uncovers the important physiological functions of m7G tRNA modification in heat stress responses and HCC recurrence after IRFA and suggests that targeting METTL1-m7G-SLUG and SNAIL axis could be a promising strategy to prevent HCC metastasis after radiofrequency heat ablation treatment.

overall_design: Polyribosome associated mRNA sequencing was used to study the differential translated genes in METTL1 knockdown HCC cells with or without Heat treatment. TRAC-Seq was developed to identify the tRNA m7G methylome in the hepatocellular carcinoma cells with or without heat treatment.

first: Ming

last: Kuang


title: Knockdown of the long noncoding RNA PURPL induces apoptosis and sensitizes liver cancer cells to doxorubicin

status: Public on Nov 21 2022

city: Copenhagen

first: Kasper

middle: Thystrup

last: Karstensen

address: A. C. Meyers Vænge 15

country: Denmark

institute: Aalborg University

type: Expression profiling by high throughput sequencing

summary:
Liver cancer was the fourth leading cause of cancer-related deaths worldwide in 2018, of which Hepatocellular carcinoma accounts for 75-85% of all liver cancers and is therefore the most common type of liver cancer.
In this study, total RNA were extracted from sections of formalin-fixed paraffin embedded (FFPE) archival human liver biopsies from 24 patients, including ten HCV-associated HCC (HCV-HCC), ten virus-unrelated HCC (VU-HCC) and four normal liver patients.
By comparing the expression profiles of HCV-HCC and VU-HCC to that of the normal liver biopsies respectively, 18 lncRNAs were identified to be differentially expressed.

overall_design: Total RNA human liver tissue was sequenced from grouped FFPE archival samples.

first: Tsinat

last: Berhane

first: Anja

last: Holm

middle: T

first: Andreas

last: Petri

first: Henrik

last: Krarup

first: Mogens

last: Vyberg

first: Marianne

middle: B

last: Løvendorf

first: Sakari

last: Kauppinen


title: Inhibition of IL-17A Protects against Thyroid Immune-related Adverse Events while Preserving Checkpoint Inhibitor Anti-tumor Efficacy [RNA-seq (murine)]

city: Los Angeles

first: Melissa

middle: G

last: Lechner

state: CA

address: 10833 Le Conte Ave, CHS 57-154

department: Div of Endocrinology, Diabetes, and Metabolism

country: USA

institute: UCLA Geffen School of Medicine

summary: Checkpoint inhibitor (ICI) immunotherapy leverages the body’s own immune system to attack cancer cells but leads to unwanted autoimmune side effects in up to 60% of patients. Such immune related adverse events (IrAE) lead to treatment interruption, permanent organ dysfunction, hospitalization and premature death. Thyroiditis is one of the most common IrAE, but the cause of thyroid IrAE remains unknown. Here we present a novel mouse model in which checkpoint inhibitor therapy leads to multi-organ autoimmune infiltrates and show that activation and infiltration of Type 3 immune cells including IL17A+ RORgt+ CD4+ (T helper 17 or Th17) and gamma delta 17 (gdT17) T cells promote thyroid IrAE development. In parallel, Th17 and gdT17 cells were similarly expanded in cancer patients treated with ICI. Furthermore, antibody-based inhibition of IL-17A, a clinically available therapy, significantly reduced thyroid IrAE development in ICI-treated mice. Finally, combination of IL-17A neutralization with ICI treatment in a mouse tumor model did not reduce ICI anti-tumor efficacy and indeed showed a trend toward enhancement. These studies suggest that targeting Th17 and gd17 function may reduce IrAE without impairing ICI anti-tumor efficacy and may be a generalizable strategy to address IL17-mediated IrAE.

overall_design: This dataset contains a total of 5 single cell transcriptomes from thyroid infiltrating CD45+ immune cells, pooled from 16 NOD.WT mice treated for 4 weeks with twice weekly intraperitoneal injections of anti-mouse PD-1 and anti-mouse CTLA-4 (10mg/kg/dose), or treated with isotype control antibodies (n=10 mice).

first: Mandy

middle: I

last: Cheng

first: Anushi

middle: Y

last: Patel

first: Aline

last: Hoang

first: Natalie

last: Yakobian

first: Michael

last: Astourian

first: Marissa

middle: S

last: Pioso

first: Eduardo

middle: D

last: Rodriguez

first: Ethan

middle: C

last: McCarthy

first: Willy

last: Hugo

first: Trevor

last: Angell

first: Alexandra

last: Drakaki

first: Antoni

last: Ribas

first: Maureen

middle: A

last: Su


title: Screening for crucial biomarkers of tendon injury and repair in a rat model

city: beijing

first: yaonan

last: zhang

address: NO 1 Dahua Road, Dongdan, Beijing

country: China

institute: Beijing Hospital

summary: The rat tendon injury models were established and divided into three groups: normal control group, injury model group, and celecoxib + lactoferrin treatment group. Then, RNA sequencing and differential expression analysis were performed for samples from injury model group and celecoxib + lactoferrin treatment group on day 14. Next, autophagy/hypoxia/ferroptosis/pyroptosis-related genes retrieved from the corresponding databases and related literatures were downloaded to obtain the genes associated with autophagy/hypoxia/ferroptosis/pyroptosis. Subsequently, functional annotation, protein-protein interaction (PPI) network and transcriptional regulatory network construction for these genes were performed.

overall_design: The rat tendon injury models were established and divided into injury model group and celecoxib + lactoferrin treatment group.RNA sequencing and differential expression analysis were performed for samples from injury model group and celecoxib + lactoferrin treatment group on day 14

first: Y

last: Zhang


title: UCHL1 aggravates skin fibrosis through an IGF-1-induced AKT/mTOR/ HIF-1α pathway in keloid

first: chipeng

last: guo

address: Yanjiang Road

institute: Sun Yat-sen Memorial Hospital

summary: To investigate the function of UCHL1 in keloids, we established primary dermal fibroblasts in which the target gene has been overexpressed by lentiviral transfection.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for UCHL1 and empty vector transfected-fibroblasts

first: Chipeng

last: Guo


title: BRANCHED1-like gene CsTCP18a contributes to shoot branching and leaf development in cucumber

city: Shanghai

first: Renyi

last: Liu

state: Shanghai

address: 3888 Chenhua Road

department: Bioinformatics

institute: Shanghai Center for Plant Stress Biology

summary: Previous study we have reported the cucumber TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) family gene BRANCHED1 (CsBRC1) as a main transcription factor functions to regulate shoot branching. Here, we found CsBRC1 (CsTCP18b in this study) had a paralogous gene CsTCP18a. To investigate whether the function of CsTCP18a was same as CsTCP18b, we carried out biochemical experiments and genetic transformation. The Real-Time PCR and in situ hybridization showed that CsTCP18a displayed different expression patterns in cucumber compared with CsTCP18b. Ectopic expression of CsTCP18a in Arabidopsis tcp18 (brc1) mutants resulted in a decreased number of rosette branches and rosette leaves, whereas silencing CsTCP18a in cucumber only led to a deformed true leaf of seedling without influencing the shoot branching. RNA-seq analysis of wild-type plants and CsTCP18a-RNAi lines implicated that CsTCP18a regulated early leaf development of cucumber through affecting the transcripts of auxin and cytokinin related genes. Further studies indicated that CsTCP18a could directly interact with CsTCP10 and CsTCP18b in vitro and in vivo. Therefore, our data suggested that CsTCP18a had functional redundancy with CsTCP18b in inhibiting axillary buds outgrowth, and it could also regulate leaf development during cucumber seedling.

overall_design: Sequencing data of the first true leaf in wild-type and CsTCP18a-RNAi lines cucumber.

first: Junjun

last: Shen


title: Isosorbide fatty acid diesters have synergistic anti-inflammatory effects in cytokine-induced tissue culture models of atopic dermatitis

city: Dallas

first: William

middle: R

last: Swindell

state: TX

address: 6201 Harry Hines Blvd

department: Internal Medicine

institute: UT Southwestern Medical Center

summary: Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL+IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL+IDC led to synergistic down-regulation of inflammatory (IL1B, ITGA5) and neurogenic pruritus (TRPA1) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates.

overall_design: Microarray analyses were performed on reconstituted human epidermis (RHE) samples treated with caprylic/capric triglyceride vehicle only (CTL), cytokine cocktail (CYT), cytokines with 4% IDL (CYT+IDL), cytokines with 4% IDC (CYT+IDC) or cytokines with 2% IDL and 2% IDC (CYT+IDL+IDC) (n = 3 replicates per group).

first: Krzysztof

last: Bojanowski

first: Ratan

middle: K

last: Chaudhuri


title: Regulatory genomic profiling in pure iPSC-derived human cortical neurons

city: Palo Alto

first: Jingjing

last: Li

address: 3165 Porter Drive

institute: Stanford University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: For decades, technical and cost hurdles have prevented the systematic investigation of non-coding sequences in complex human diseases, and thus our knowledge about autism spectrum disorders (ASD) has been primarily obtained from analysis of protein-coding sequences. We have combined the analysis of whole genome sequencing with global studies of regulatory sequences of human cortical neurons to reveal the regulatory architecture of ASD. Analysis of de novo mutations from whole genome sequencing of 261 autism families revealed the physical proximity of ASD de novo mutations specifically to the cortical expression quantitative loci (eQTLs) of synaptic genes. We performed ATAC-Seq, ChIP-Seq, RNA-Seq and Hi-C experiments on human cortical neurons, which for the first time provided a paranormal view of the regulatory landscape in these cells. We found that ASD de novo mutations preferentially affect regulatory elements, and the associated genes are shared targets of two ASD syndromic factors, CHD8 and PTEN. Analyzing 15 chromatin states across 127 human tissue/cell types revealed a significant enrichment of ASD de novo mutations in active transcription start sites and the perturbed genes implicated in neuron functions; this distribution enabled us to develop a machine-learning algorithm to assess potential ASD risk for a given individual. Taken together, our study for the first time revealed the regulatory landscape in human neurons, demonstrated the importance of the non-coding genome in ASD and provides a general framework for analyzing regulatory mutations for other complex human diseases.

overall_design: We performed ATAC-SEQ, RNA-SEQ, in situ HI-C, ChIP-SEQ (H3K27AC and CHD8) in this neuron line, and also CHIP-SEQ for CHD8 in a postmortem brain sample (Brodmann Area 44)

first: Michael

last: Snyder


title: Interleukin-18 induced chromatin accessibility coupled to proteomic analysis by mass cytometry and ion beam imaging

city: Boston

first: Sizun

last: Jiang

state: MA

address: 3 Blackfan Circle

institute: BIDMC/Harvard

summary: Regulated chromatin states control genome accessibility and thus influence gene expression. Here we report an analysis pipeline termed ATAC-mass that capitalizes on isotopic labeling to detect the accessible genome by multiplexed ion beam imaging (MIBI) and mass cytometry. With MIBI the accessible genome can be visualized at approximately 100-nm resolution simultaneously with metabolic labeling to enable multi-parameter three-dimensional imaging of nuclear features. Extension of this approach to non-spatial mass cytometry enabled the simultaneous measurement of multiple parameters and total genome accessibility in millions of individual cells. We used ATAC-mass to analyze natural killer cells after stimulation with interleukin (IL)-12 or IL-18 -- demonstrating that IL-18 treatment leads to increased total genome accessibility. Analysis of the spatial organization of open chromatin suggest that IL-12 and IL-18 both induce an increase in chromatin accessibility in noncompacted DNA regions. Deep sequencing of the genomic distribution of open chromatin revealed that IL-18 increased the accessibility of quiescent enhancers whereas genomic loci that become more accessible by IL-12 stimulation are mainly localized in the active promoter regions. This integration of epigenomics, proteomics and high-resolution imaging at the single-cell level provides a tool that can enhance our appreciation of the molecular mechanisms underlying gene regulation.

overall_design:
ATAC-seq with MIBI compatible Tn5 and IL12/IL18 treated NKL cells

Each *bw file was generated from both rep1, rep2 and is linked to the corresponding rep1 sample records.
All the Cluster*.bed files were generated from the NK*.fastq.gz and NK*.bw files.
Please note that the ATAC-mass Tn5 samples were used for assay validation, with no unique processed files aside from basic alignment as described in the associated publication. It shows that the methodology works in comparison to the original ATAC paper [PMID 24097267].

first: Xinqi

last: Chen

first: Xavi

last: Rovira-Clave

first: Shih-yu


title: Real-time quantitative PCR analysis of mouse lungs after exposure to early SARS-CoV-2 bearing 614G, Kappa or Delta variant

city: Silver Spring

first: Hang

last: Xie

state: Maryland

address: 10993 New Hampshire Ave WO 52/72 Rm 1324

institute: US Food and Drug Administration, Center for Biologics Evaluation and Research

summary: Age-matched K18-hACE2 transgenic mice were passively transferred with human COVID-19 mRNA post-vaccination (post-vac) sera followed by the lethal challenge with different SARS-CoV-2 viruses via intranasal route, including (1) New York-PV09158/2020 (NY) of lineage B.1.3 bearing 614G, (2) Kappa (B.1.617.1) and (3) Delta (B.1.617.2).  Mouse lungs were harvested on 5 days post infection (dpi). Total RNA was extracted using QIAgen RNeasy Plus Mini Kit and was reverse transcribed using the High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific). Resultant cDNA was used as the template along with RT2 SYBR Green ROX qPCR Mastermix (Qiagen) to perform RT² Profiler™ PCR Array Mouse Hypoxia Signaling Pathway (Qiagen) real-time PCR in Stratagene MX3000p qPCR system.

overall_design: qPCR gene expression profiling.  Lung homogenates from 6 SARS-CoV-2 infected K18-hACE2 transgenic mice on dpi 5 were treated as indicated in the summary.  Total RNA extracted was analyzed individually.

first: Wei-chun

last: Tang


title: Transcriptomes of the metabolism inhibited mouse embryonic stem cells

city: Beijing

first: tongbiao

last: zhao

address: 1 Beichen West Road, Chaoyang District

institute: INSTITUTE OF ZOOLOGY, CHINESE ACADEMY OF SCIENCES

summary: The connection between bioenergetics and cell fate remains poorly understood. It is wildly accepted that pluripotent stem cells mainly on anaerobic glycolysis for energy production rather than oxidative phosphorylation (OXPHOS) compared with differentiated cells. However, mitochondria in PSCs still possess functional respiratory complexes. Here we generated the transcriptome profiling (RNA-seq) of OXPHOS inhibited ESC, glycolysis inhibited ESC and control ESC, presenting the variation of the global gene expression induced by metabolism inhibition

overall_design: ESC mRNA profiles of wild type (WT), low OXPHOS inhibition (1nM oligmycin treated for 48 hour ), high OXPHOS inhibition (10 nM oligmycin treated for 48 hour), low glycolysis inhibition (5mM 2-DG treated for 48 hour), and high glycolysis inhibition (10 mM 2-DG treated for 48 hour) were generated by deep sequencing, in triplicate, using  Illumina hiseqxten.

first: Jiani

last: Cao

first: Tongbiao

last: Zhao


title: Acute effects of liraglutides on gene expression in the hearts of mice with experimental myocardial infarction

city: Toronto

first: Chi Kin

last: Wong

address: 600 University Avenue

country: Canada

institute: LTRI

summary: Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce the rates of major cardiovascular events, including myocardial infarction in people with type 2 diabetes, and decrease infarct size while preserving ventricular function in preclinical studies. Nevertheless, the precise cellular sites of GLP-1R expression that mediate the cardioprotective actions of GLP-1 in the setting of ischemic cardiac injury are uncertain. Here, cardiac gene expression profiles regulated by liraglutide were examined using RNA-Seq to interrogate mouse atria and both non-infarcted and non-infarcted ventricular tissue after acute coronary artery ligation.

overall_design: Bulk RNA-seq was performed on the atria, and non-infarcted and infarcted regions of the left ventricle isolated from mice with experimental myocardial infarction.

first: Chi

first: Brent

last: McLean

first: Daniel

middle: J

last: Drucker


title: Reactive Metal Boride Nanoparticles Trap Lipopolysaccharide and Peptidoglycan for Bacteria-Infected Wound Healing

city: shanghai

first: yang

last: chen

address: siping road

institute: tongji university

summary: Bacteria and excessive inflammation are two main factors causing non-healing wounds. However, current studies have mainly focused on the inhibition of bacteria survival for wound healing while ignoring the excessive inflammation induced by dead bacteria-released lipopolysaccharide (LPS) or peptidoglycan (PGN). Herein, a boron-trapping strategy has been proposed to prevent both infection and excessive inflammation by synthesizing a class of reactive metal boride nanoparticles (MB NPs). Our results show that the MB NPs are gradually hydrolyzed to generate boron dihydroxy groups and metal cations while generating a local alkaline microenvironment. This microenvironment greatly enhances boron dihydroxy groups to trap LPS or PGN through an esterification reaction, which not only enhances metal cation-induced bacterial death but also inhibits dead bacteria-induced excessive inflammation both in vitro and in vivo, finally accelerating wound healing. Taken together, this boron-trapping strategy provides an approach to the treatment of bacterial infection and the accompanying inflammation.

overall_design: Pseudomonas aeruginosa treated with or without Nano-MgB2, each group has 3 samples

first: Yelin

last: Wu

first: Yun

last: Meng

first: Yang

first: Fan


title: Comparison of genome-wide DNA methylation between H446/DDP and H446

city: Shiyan

first: Fuyun

last: Ji

state: Hubei

address: South Renmin Road

department: Department of Medical Biology, School of Basic Medical Science

institute: Hubei University of Medicine

summary: Little has been known about the genome-wide methylation frameworks of the chemo-resistant cells of SCLC currently, which might provide prospective layouts to discover the genes and the signal pathways related with chemo-resistance of SCLC. Thus, this research reported for the first time the genome-wide abnormal methylation pattern of chemo-resistant H446/DDP cells of human SCLC induced by the cisplatin

overall_design: Illumina Infinium Human Methylation 450K bead chip

first: Ruiling

last: Guo

first: Xihua

first: Shilong

last: Yu

first: Yi

first: Liyuan

last: Song


title: Micropillar-based phenotypic screening platform uncovers involvement of HDAC2 in nuclear deformability

city: Bologna

first: Camilla

last: Luni

address: Via Terracini 28

department: DICAM

country: Italy

institute: University of Bologna

summary: Nuclear deformability is an essential feature of migratory cells. Intercellular movement and migration in the extracellular space requires cells to squeeze through constrictions up to an order of magnitude smaller than the average diameter of their biggest and stiffest organelle. One field of study in which aberrant nuclear shapes and deformability are of particular interest is cancer, with abnormal nuclear structures described as a hallmark of the disease and an indicator of pathological progression, while increased nuclear deformability correlates with increased metastatic potential. While most previous studies focused on the description of nuclear morphology in adaptation to different 3D geometries, and mechanistic investigations of nuclear deformation have been limited to contributions of the cytoskeleton, we tap for the first time into the potential of micropillared substrates to serve as drug screening platforms for compounds that influence nuclear deformability. To this end, we combine a micropillared culture substrate with image analyses to test the effect of various drugs on nuclear deformability and successfully identify histone deacetylases inhibitors (iHDACs) as active compounds in nuclear shape regulation on micropillars. Our experiments show that HDAC-activity as gene transcription regulators appears to activate a nuclear shape-rescue program in osteosarcoma cells, providing an excellent platform for identification of novel nuclear shape-determinants and possibly druggable targets for anti-cancer therapies.

overall_design: Examination of 4 replicates of SaOS-2 cells cultured for 48 h on flat or micropillared PDMS substrates. Each replicate represents a different cell passage within a paired design.

first: Sebastian

last: Martewicz

first: Xi

last: Zhu

first: Siqi

last: Qu

first: Meihua

last: Cui

first: Eleonora

last: Grespan

first: Biao

last: Jiang

first: Guang

last: Yang

first: Nicola

last: Elvassore


title: Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis [Hi-C]

city: Berlin

first: Irene

last: Mota-Gomez

address: Hannoversche strasse 28

country: Germany

institute: Max Delbruck Center

summary: Mammalian sex is determined by a network of antagonistic genes that are well characterized. However, its non-coding regulation is still largely unknown. Here we explore the 3D chromatin landscape of sex determination in vivo. We integrate Hi-C with ChIP-seq experiments using METALoci, a novel genome spatial auto-correlation analysis approach that identifies 3D regulatory hubs across the genome. We uncover a prominent rewiring of chromatin interactions during sex determination. By combining predictive approaches and validations in transgenic mice we identify a novel Fgf9 regulatory hub, which deletion results in male-to-female sex reversal.

overall_design: Hi-C experiments in FACS-sorted embryonic mouse gonadal populations.

first: Juan

last: Rodriguez

first: Shannon

last: Dupont

first: Oscar

last: Lao

first: Johanna

last: Jedamzick

first: Ralf

last: Kühn

first: Scott

last: Lacadie

first: Sara

last: Garcia-Moreno

first: Alicia

last: Hurtado

first: Rafael

last: Acemel

first: Blanche

last: Capel

first: Marc

last: Marti-Renom

first: Dario

last: Lupianez


title: DUSP5P1 promotes gastric cancer metastasis and platinum drug resistance [ChIRP-seq]

status: Public on Nov 18 2022

first: Xiaohong

last: Wang

address: Haidian district

institute: Peking university cancer hospital

summary: We elucidated the functional significance and molecular mechanisms of DUSP5P1 lncRNA (dual specificity phosphatase 5 pseudogene 1) in gastric carcinogenesis. We demonstrated that gastric cancer (GC) patients with high DUSP5P1 expression had shortened survival in two independent cohorts. DUSP5P1 promoted GC cell migration and invasion in vitro and metastasis in vivo. Mechanistically, DUSP5P1 activated ARHGAP5 transcription by directly binding to the promoter of ARHGAP5 with a binding motif of TATGTG. RNA-seq revealed that ARHGAP5 activated focal adhesion and MAPK signalling pathways to promote GC metastasis. DUSP5P1 also dysregulated platinum drug resistance pathway. Consistently, DUSP5P1 overexpression in GC cells antagonized cytotoxic effect of Oxaliplatin, and shDUSP5P1 plus Oxaliplatin exerted synergistic effect on inhibiting GC metastasis in vitro and in vivo. DUSP5P1 depletion also suppressed the growth of platinum drug-resistant PDO models. In conclusion, DUSP5P1 promoted GC metastasis by directly modulating ARHGAP5 expression to activate focal adhesion and MAPK pathways, serves as therapeutic target for platinum drug resistant GC, and is an independent prognostic factor in GC.

overall_design: Comparative Genome binding/occupancy profiling analysis of ChIRP-seq data for MGC803 ectopic expression derivatives (MGC803-DUSP5P1).

first: Lianhai

last: Zhang

first: Qiaoyi

last: Liang

first: Chi

last: Wong

first: Huarong

last: Chen

first: Hongyan

last: Gou

first: Yujuan

last: Dong

first: Weixin

last: Liu

first: Ziyu

last: Li

first: Jiafu

last: Ji

first: Jun

last: Yu


title: Super-enhancer driven MYST family histone lysine acetyltransferases are critical for nasopharyngeal carcinoma cell growth and survival

first: Sizun

last: Jiang

summary: Nasopharyngeal carcinoma (NPC) is causally linked to Epstein-Barr virus (EBV) infection, genetic predisposition and environmental factors. Early diagnosis is difficult due to lack of specific symptoms. Many patients have advanced disease at diagnosis and these patients respond to treatment poorly. To better understand the NPC molecular pathogenesis, genome-wide CRISPR screen was used to identify NPC dependency factors. These dependency factors were then linked to their enhancers using H3K27ac HiChIP. The screen identified MYST histone acetyl transferase complex, NF-kB signaling pathway, purine synthesis pathway, linear ubiquitination pathway, SLC2A1, MDM2, and PIK3C3 as NPC dependency factors/pathways. Importantly, H3K27ac HiChIP linked most of these dependency factors to super-enhancers. This study provided new insight to NPC pathogenesis and also identified novel potential targets for therapy.

sample_organism:
Homo sapiens
synthetic construct

platform_organism:
Homo sapiens
synthetic construct

overall_design: CRISPR screens and H3K27ac HiChIP were performed in EBV positive NPC cell lines (C666-1, C17) as well as the EBV negative NPC cell line (NP69)

first: Chong

first: Bo

last: Zhao


title: NUSAP1-LDHA-Glycolysis-Lactate feedforward loop promotes Warburg effect and metastasis in pancreatic ductal adenocarcinoma [ChIP-seq]

status: Public on Nov 19 2022

city: Hangzhou

first: Chen

last: Ming

state: Zhejiang

address: No. 79 Qingchun Road

institute: The First Affiliated Hospital, Zhejiang University School of Medicine

summary: To explore the genes regulated by Nusap1 protein in pancreatic ductal adenocarcinoma , chromatin immunoprecipitation followed by high-throughput sequencing (CHIP-Seq) were performed in AsPC1 cells.

overall_design: The fragments of genes pulled down by specific antibody (Nusap) was analyzed by high-throughput sequencing in  pancreatic ductal adenocarcinoma cells (AsPC1).

first: Ming


title: Role of Tim-3 on tumoral Treg cells

city: Pittsburgh

first: Binfeng

last: Lu

state: PA

address: 200 Lothrop St

department: Immunology

institute: University of Pittsburgh

summary: A gene profiling study revealed the requirement of Tim-3 in upregulation of effector Treg genes encoding immune inhibitory molecules, chemokine receptors for tissue residency, chemokines, and cytokines.

overall_design: Examination of 3 Tim-3 knockout samples and 3 Tim-3 sufficient samples for each group

first: Min

last: Yang

first: Chunyan

last: He

first: Yaoyu

last: Ying

first: Yi

last: Zhou

first: Sihan

first: Wensi

last: Zhai

first: Shaoxian

last: Wu

first: Bendong

last: Xue

first: Wenyan

first: Da


title: NUSAP1-LDHA-Glycolysis-Lactate feedforward loop promotes Warburg effect and metastasis in pancreatic ductal adenocarcinoma

summary: To explore the differential genes and signaling pathways regulated by NUSAP1 in pancreatic ductal adenocarcinoma, PANC1 cell line was transfected with siRNA or overexpressed plasmid targeted with NUSAP1. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for PANC1 cells and its derivatives (NUSAP1 was knockdowned by siRNA or overexpressed by flag-NUSAP1 plasmid).

last: Chen


title: Valine enhances intramuscular fat deposition through activating autophagy and fatty acid metabolism pathways in C2C12 myoblasts

city: 荆州市

first: 炳熙

last: 高

state: 湖北省

address: 湖北省荆州市荆秘路88号

department: 动物科学学院

institute: 长江大学

summary: The branched-chain amino acids (BCAA) are essential to animal growth and intramuscular fat deposition, and also metabolic health (circulating level elevated in obesity and diabetes). However, the molecular role and effect of valine on muscle growth and fat deposition were less explored. Valine supplementation significantly affected mouse muscle growth, increasing the abdominal fat but decreasing the back fat. In the leg muscle, the expression levels of genes related to autophagy and fat deposition were significantly disturbed. Furthermore, valine promotes lipid deposition in myoblasts in a dose-dependent manner, and co-treatment of valine and palmitic acid can act in concert to enhance lipid deposition in myoblast. Moreover, transcriptome sequencing on myoblasts revealed that the signaling pathways such as mTOR, PI3K-AKT and fatty acid metabolism were activated after valine treatment, and palmitic acid additionally stimulated signaling pathways related to lipid metabolism in myoblasts. Therefore, valine could independently activate the autophagy pathway, and the fatty acid metabolism pathway to enhance intramuscular fat deposition

overall_design: C2C12 cells of mice were taken as samples and sequenced and divided into control group (Control group), labeled C1-C6; 0.45 mM valine treatment group (Valine group), labeled as V1-V6; 0.45 mM+75 μ M Palmitic acid treatment group (Val+PA group), marked as VP1-VP6, randomly selected 3 samples from each group of six samples and sent them to the company for sequencing.

first: Cai-Xia

first: Zhi-Qiang

last: Du


title: Hippo signaling instructs ectopic but not normal organ growth

city: Leuven

first: Georg

last: Halder

address: Herestraat 49

department: VIB-KU Leuven Center for Cancer Biology

country: Belgium

institute: VIB-KU Leuven

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

sample_organism:
Drosophila melanogaster
Mus musculus

platform_organism:
Drosophila melanogaster
Mus musculus

overall_design: Refer to individual Series


title: Different expression profiles and bioinformatics analysis of circular RNAs between ST-elevation myocardial infarction and chronic artery syndroms.

city: Jinan

first: Jingbo

last: Xing

state: Shandong

address: No. 107, Wenhua West Road

institute: Shandong University

summary: We aimed to confirm the different expression profiles of circular RNAs (circRNAs) between ST-elevation myocardial infarction (STEMI) and chronic coronary syndromes (CCS) and identify the role of circRNAs in STEMI.

overall_design: We used sequence analysis of circRNAs in peripheral blood mononuclear cells (PBMCs) of 28 STEMI patients and 28 CCS patients.

first: Chenghu

last: Guo

first: Fangpu

first: Cheng

last: Zhang


title: MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing

first: Qiankun

last: Li

address: Fuxing Road

department: Department of Tissue Repair and Regeneration

institute: The First Medical Center Chinese PLA General Hospital

summary: Unhealable diabetic wounds need to be addressed with the help of newer, more efficacious strategies. Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment. Here, the engineered exosomes modified for efficiently loading miR-146a and attaching to silk fibroin patch were demonstrated to promote diabetic wound healing. The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment.

overall_design: Transcriptomics analysis GO enrichment and KEGG enrichment to the differentially expressed mRNAs of wounds treated with or without SGM-miR146a-Exo@SFP at day 3 and day 7 post-wounding.

first: Wenzhi

last: Hu


title: Comparative Computational RNA Analysis of Cardiac-Derived Progenitor Cells and Their Extracellular Vesicles

city: Atlanta

first: Michael

last: Davis

state: GA

address: 2015 Uppergate Dr

institute: Emory University

summary: We aimed to examine differences between c-kit+ progenitor cells (CPCs) and CPC-derived extracellular vesicles (EV) RNA content. We isolated CPCs from cardiac biopsies of patients with congenital heart disease using magnetic bead sorting. We expanded CPCs, reduced serum for 24hrs, and collected secreted EVs from conditioned media with sequential ultracentrifugation. We isolate RNA from CPCs and CPC-EVs and sequence total RNA and miRNA. Sequencing was performed in at two different facilities: "E" and "N".

overall_design: Examination of CPC and CPC-derived EV small RNA content

first: Jessica

last: Hoffman

first: Hyun-Ji

last: Park

middle: E


title: Transcriptomic profile of murine abdominal aorta allograft undergoing chronic rejection

city: Wuhan

first: Jie

address: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road 1277

department: Department of Cardiovascular Surgery

summary: Graft vascular disease (GVD) is a major problem limiting the long-term survival of grafts. To determine the underlying mechanisms of GVD during chronic phase, we performed murine abdominal aorta transplantation. Donor aortas from C57Bl/6 (H-2b) mice were transplanted into C57Bl/6 (H-2b) mice, and we call this group isograft (ISO). Donor aortas from BALB/c (H-2d) mice were transplanted into C57Bl/6 (H-2b) mice, and we call this group allograft (ALLO). In brief, donor abdominal aortas were isolated and the branch vessels were ligated, while the recipient vessels were cut from the midsection using microscopic scissors. The recipient and donor vessels were anastomosed with a cuff suture. 4 weeks after aorta transplantation, the mice were sacrificed for transcriptomic sequencing and analyzing of the aortic grafts.

overall_design: We designed the experiment to two groups. The aortic grafts tissue of ALLO and ISO group at 4 weeks post aorta transplantation (n=2 for both) were collected for transcriptome analysis.

first: Yanqiang

last: Zou

first: Heng

last: Xu


title: Hydrogel-based intramyocardial delivery of antimiR-195 after ischemia-reperfusion injury [UPyPEG_IR]

city: Utrecht

first: Eva

last: van Rooij

address: Uppsalalaan 8

country: Netherlands

institute: Hubrecht Institute

summary:
Background MicroRNAs are potent regulators of biology and disease. The miR-15 family  has been shown to regulate cardiomyocyte proliferation and antimiR-based inhibition induces a cardioprotective effect after myocardial infarction in mice. However, systemic delivery of antimiRs leads to accumulation in kidneys and liver, with relatively poor cardiac exposure. pH-responsive injectable hydrogels serve as a sustained-release drug delivery depot and could potentially be used to improve cardiac efficacy of antimiR therapeutics.

Objective Examine whether hydrogel can improve local delivery of antimiR-195 in ischemic hearts to increase cardiac efficacy and limit off-target effects.

Methods Study the effect of intramyocardial injections of hydrogel-formulated antimiR-195 under both baseline conditions and after ischemic injury.

Results Intracardiac injections of UPy-PEG induced a transient inflammatory response that was no longer present 7 days post-injection. In vitro experiments showed that antimiR-195 was released from the gel, and induced microRNA inhibition leading to downstream cardiomyocyte proliferation. In vivo, intramyocardial delivery of antimiR-195 in UPy-PEG enhanced cardiac target de-repression compared to PBS-dissolved antimiR-195, despite a low cardiac retention. After ischemic injury, this translated into a greater therapeutic effect by increasing both target de-repression and cardiomyocyte proliferation.

Conclusions UPy-PEG can be used as a cardiac delivery vehicle of antimiRs and intramyocardial injection of UPy-PEG formulated antimiR-195 is sufficient to improve cardiac efficacy of antimiR-195. Follow up experiments in large animals will enable us to assess the true added value of using UPy-PEG to increase cardiac exposure of antimiR therapies.

overall_design:
Healthy mice were subjected to cardiac ischemia-reperfusion injury (anesthesia, intubation, opening of thorax, ligation of LAD, reperfusion and intramyocardial injection (2x10µl) of Upy-PEG hydrogel; either with no drug or with antimiR-195. Hearts were harvested for RNA-analysis 3 days after injury injection.
There are 2 groups (Upy-PEG, UPy-PEG-antimiR) with 4 samples per group

first: Joep

last: Eding

first: Marta

last: Vigil Garcia

first: Marit

last: Vink

first: Charlotte

last: Demkes

first: Danielle

last: Versteeg

first: Lieneke

last: Kooijman

first: Maarten

middle: H

last: Bakker

first: Maaike

last: Schotman

first: Patricia

last: Dankers


title: N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling

city: Chongqing

first: Kang

last: Lu

address: Gaotanyanzheng street

institute: The Second Affiliated Hospital of Chongqing Medical University

summary: N-acetyl-L-cysteine (NAC) is a potent antioxidant. However, how NAC affects the biological functions of tendon stem/progenitor cells (TSPCs) and tendon repair has not been clarified.The effect of NAC on gene transcription in TSPCs was analyzed by transcriptomes and bioinformatics.

overall_design: We then performed gene expression bioinformatics analysis using data obtained from RNA-seq of 2 group  different cells after 7 days culturing.

first: Mei

last: Zhou

first: Liyuan

last: Wang

first: Yang

first: Hong

last: Tang

first: Huan

first: Chuyue

last: He

first: Wei

first: Kanglai

first: Yunjiao

first: Zhongliang

last: Deng


title: Targeting Bhlhe22-dependent MDSCs infiltration relieves the immunosuppressive bone TME and reduces the ICT resistance in bone metastatic Pca [PC-3]

city: Guangzhou

first: yin

last: chi

state: Guangdong Province

address: 58# Zhongshan 2rd Road

institute: 1st affliated hospital of Sun yat-sen university

summary: How to identify subgroups of PCa patients for immune checkpoint therapy (ICT) remains not fully understood. Basic helix-loop-helix family member e22 (Bhlhe22) is upregulated in bone metastatic PCa and drives an immunosuppressive bone TME. Tumoral Bhlhe22 mediates the high expression of colony stimulating factor 2 (CSF2), which results in the infiltration of myeloid-derived suppressor cells (MDSCs) and prolonged immunocompromised T cell status. Here, we reveal the immunosuppressive mechanism of tumoral Bhlhe22 and provide a prospective ICT combination therapeutic for Bhlhe22+ PCa patients.

overall_design: Differential gene expression profile between control (PC-3-Vector) cells and Bhlhe22 overexpression (PC-3-Bhlhe22) cells.

first: Chi

last: Yin

first: Min

first: Yuhu

last: Dai

first: Xinsheng

last: Peng


title: Effect of Upy-PEG hydrogel injection and delivery of antimiR-195 on left ventricular transcriptome [baseline]

first: Eva

last: van Rooij

overall_design:
Healthy mice were subjected to intramyocardial injections (anesthesia, intubation, opening of thorax, intramyocardial injection of 2x10µl) of PBS or Upy-PEG hydrogel or Upy-PEG hydrogel with antimiR-195. Hearts were harvested for RNA-analysis 3 days after injection.
There are 3 groups (PBS, Upy-PEG, Upy-PEG-antimiR) with 4 samples per group

first: Joep

last: Eding

first: Marta

last: Vigil Garcia

first: Marit

last: Vink

first: Charlotte

first: Danielle

first: Lieneke

first: Maarten

first: Maaike

first: Patricia


title: Hydrogel-based intramyocardial delivery of antimiR-195


title: DUSP5P1 promotes gastric cancer metastasis and platinum drug resistance [RNA-seq]

first: Xiaohong

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MGC803 cells and its ectopic expression derivatives (MGC803-DUSP5P1).

first: Lianhai

last: Zhang

first: Qiaoyi

last: Liang

last: Wong

first: Huarong

last: Chen

first: Hongyan

last: Gou

first: Yujuan

last: Dong

first: Weixin

last: Liu

first: Ziyu

last: Li

first: Jiafu

last: Ji

first: Jun

last: Yu


title: DUSP5P1 promotes gastric cancer metastasis and platinum drug resistance

last: Wang


title: RNA-sequencing from inflamed and normal synovial membrane after anterior cruciate ligament and/or meniscus injuries

first: Xiling

last: Xiao

address: No.1277, Jiefang Avenue

department: Department of Rehabilitation

institute: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

type: Non-coding RNA profiling by high throughput sequencing

summary:
Despite ample evidence demonstrating that anterior cruciate ligament (ACL) and meniscus tears are associated with the development of knee osteoarthritis (OA), the contributing factors remain unknown. Synovial inflammation has recently been recognized as a pivotal factor in the pathogenesis of OA. However, there is a lack of data on synovial profiles after ACL or meniscus injuries, which may contribute to posttraumatic OA (PTOA).
We performed RNA-seq of 3 inflamed synovial biopsy samples vs 3 normal synovial biopsy samples following ACL and/or meniscus injuries. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein–protein interaction (PPI) analyses were performed to investigate mRNAs with significant differences between the inflamed and normal groups.Next, competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses and quantitative real-time polymerase chain reaction (RT–PCR) results. The association of the identified DEGs with the levels of infiltrating immune cells was explored using Pearson correlation analysis in R software. We aimed to provide greater insights into molecular mechanisms and biologic pathways in synovitis that could regulate post-trauma osteoarthritis progression.

overall_design: Comparing lncRNAs, miRNA and mRNA expression profiling from inflamed and normal synovial tisssue following anterior cruciate ligament and/or meniscus injuries

first: Chunqing

last: Meng

first: Zhaohui

last: Yang


title: Targeting Bhlhe22-dependent MDSCs infiltration relieves the immunosuppressive bone TME and reduces the ICT resistance in bone metastatic Pca

first: yin

last: chi

overall_design: Differential gene expression profile between control (RM-1-Vector) cells and Bhlhe22 overexpression (RM-1-Bhlhe22) cells.

first: Chi

last: Yin

first: Min

first: Yuhu

last: Dai

first: Xinsheng

last: Peng


title: Flt3-ITD drives cooperating mutation-specific changes in cell identity and variable interferon dependence [RNA-seq dt2]

city: St Louis

first: Jeffery

last: Magee

state: Missouri

address: 660 South Euclid Ave

institute: Washington University In St Louis

summary: RNA-seq on NHD13/Flt3-ITD AML cells on Ifnar1 wildtype and kncokout backgrounds

overall_design: HPCs were from mice of the indicated genotypes

first: Jeffrey


title: Flt3-ITD drives cooperating mutation-specific changes in cell identity and variable interferon dependence [RNA-seq]

summary: Rna-seq analysis of wild type, Nup98-Hoxd13, Flt3-ITD and Runx1 mutant progenitors


title: Fed and fasted skeletal muscle of wildtype and PGC-1beta muscle specific knockout mice

city: Basel

first: Christoph

last: Handschin

address: Spitalstrasse 41

country: Switzerland

institute: Biozentrum, University of Basel

summary: The mechanistic underpinnings of the fasting response in skeletal muscle is still poorly understood. We therefore investigated the role of the transcriptional coactivator PGC-1beta (peroxisome proliferator-activated receptor gamma coactivator 1beta) in this context. To do so, the fasting response in quadriceps muscle was assessed in fed and 24 hours fasted mice and compared between wildtype and PGC-1beta muscle-specific knockout mice (both on a C57Bl6/J background). Morphological, functional and transcriptional parameters were determined. The results indicate that PGC-1beta significantly contributes to the metabolic remodelling of skeletal muscle to fasting by promoting catabolic pathways that help to improve energy production and sequester substrates for gluconeogenesis. Accordingly, muscle-specific knockouts for PGC-1beta exhibit mitigated protein degradation and muscle fiber atrophy. These findings contribute to our understanding of muscle plasticity in different metabolic contexts.

overall_design: Quadriceps muscle RNA-seq of wildtype and PGC-1beta muscle specific knockout mice, either fed or fasted for 24 hours, 4 groups, 5 or 4 replicates/mice per group

first: Svenia

last: Schmid


title: Obesity alters the endometrial transcriptome in a cell context-dependent manner

city: Grand Rapids

first: Ronald

middle: L

last: Chandler

state: Michigan

address: 400 Monroe Ave NW

institute: Michigan State University

summary: Obesity significantly impacts fertility, is positively correlated with endometrial cancer occurrence, and negatively correlated with endometriosis incidence. The endometrial epithelia often harbor disease driver-mutations, while the endometrial stroma are highly regulative of the neighboring endometrial epithelia. Two cohorts of CD-1 mice were fed high-fat diet or control diet ad libitum for 18 weeks, beginning at 8 weeks of age. Weight measurements were taken weekly and serum was collected bi-weekly. After 17 weeks, a glucose tolerance test was performed on all mice. After 18 weeks, uteri were collected. We profiled the transcriptomes of positively-enriched endometrial epithelia (cohorts 1 and 2) and macrophages (cohort 2), and epithelia- and macrophage-depleted stroma populations (cohort 2). Pieces of uterine tissue were saved for histological analysis. Purity of cell populations were confirmed by flow cytometry. RNA was isolated from each cell type and libraries were synthesized for RNA-seq. Mice fed a high-fat diet displayed significantly increased body mass compared to control diet mice after three weeks. High-fat diet mice developed glucose intolerance, hyperinsulinemia, and fatty liver. Obese mice displayed differential gene expression in the endometrial epithelia for 105 genes (FDR < 0.05), including factors related to innate immunity and leukocyte chemotaxis, such as calprotectin. The endometrial stroma of obese mice differentially expressed 141 genes (FDR < 0.05) including several factors related to circadian rhythm. Expression of many of these genes was significantly correlated with glucose tolerance or body mass (p < 0.05). We observed correlations between F4/80 macrophage marker, Cleaved Caspase 3 (CC3) apoptosis marker in the luminal epithelia and glucose intolerance. Among obese mice, we observed a subgroup with high CC3 staining in the luminal epithelium by immunohistochemistry. This subgroup displayed differential gene expression among all cell types, with pathways related to immune escape observed in epithelial and macrophage compartments, and pathways related to epithelial regulation observed in the stromal compartments. The endometrial macrophages of obese mice compared to control mice displayed differential gene expression of only one gene, although the abundance of F4/80+ macrophages was shown to be increased in the obese mouse uterus. There may be species-specific differences between humans and mice which limit interpretations. The results suggest an important role for differential response of both the epithelia and stroma in their response to obese phenotypes, while macrophages are dysregulated in the context of apoptotic epithelium. The obesity-related gene expression programs in cells found within the uterine microenvironment may influence the ability of the endometrium to function during pregnancy and contribute to endometrial cancer pathogenesis.

overall_design: EPCAM+ epithelia, F4/80+ macrophages and VIM+ stroma were isolated from the uteri of mice following 18 weeks on high-fat diet or control diet. RNA was collected from cels and used for RNA-seq analysis.

first: Mike

last: Wilson


title: Effects of allergen and airway constriction on gene expression in mouse lung

city: Weifang

first: Xiao

last: Niu

address: Baotong str. 7166

institute: Weifang Medicine University

summary: Airway hyperresponsiveness is found to be a heritable trait and the parents of respiratory patients often have this trait. To understand if airway constriction affects the lung and contributes to lung disease, we investigated the lungs that often occur airway constriction and compared those lungs with healthy lung and the lung with inflammation.

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different tracheal tissues of BABL/c mouse at two time points.


title: Lenalidomide-induced changes in gene expression profile of multiple myeloma cells

city: Shimotsuke

first: Yusuke

last: Furukawa

state: Tochigi

address: 3311-1 Yakushiji

department: Center for Molecular Medicine

country: Japan

institute: Jichi Medical University

summary: We identified lenalidomide-induced changes in gene expression profile to identify IKZF1-regulated genes in multiple myeloma.

overall_design: We cultured human myeloma cell lines KMS12 and MM.1S with lenalidomide and performed gene expression profiling using an Agilent GeneChip Array.

first: Jiro

last: Kikuchi


title: SARS-CoV-2 pseudovirus infection in BMMs

city: Shanghai

first: Junjie

last: Gao

address: 600 Yishan Road

institute: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

summary: Single-cell transcriptome analysis of SARS-CoV-2 pseudovirus infection in cultured BMMs that are derived from 1-month and 18-month mice

overall_design: Examination of SARS-CoV-2 pseudovirus infected cell types

first: Jia

last: Liu


title: Flt3-ITD drives cooperating mutation-specific changes in cell identity and variable interferon dependence [ATAC-seq]

summary: ATAC-seq analysis of wild type, Nup98-Hoxd13, Flt3-ITD and Runx1 mutant progenitors


title: Effect of FOXO3 on GR Signaling

city: Ulm

first: Giorgio

last: Caratti

address: Helmholzstraße 8/1

institute: University of Ulm

summary: To identify cross-talk between the transcription factors, glucocorticoid receptor and FOXO3 after activation of the glucocorticoid receptor with dexamethasone.Bone marrow derived macrophages lacking FOXO3 were exposed to vehicle, dexamethasone, a synthetic glucocorticoid.

overall_design: RNA-seq of BMDMs exposed to vehicle (DMSO), dexamethasone (100nM) for 24 hours before RNA isolation


title: Flt3-ITD drives cooperating mutation-specific changes in cell identity and variable interferon dependence [scRNA-seq]

summary: single-cell RNA-seq for indicated genotypes

overall_design: Lineage neg, Kit positive cells were isolated for CITE-seq


title: Total RNA sequencing of Skiv2l-deficient mouse epidermis

city: DALLAS

last: Yan

state: TEXAS

address: 6000 Harry Hines Blvd

institute: UT Southwestern Medical Center

summary: To identify differentially epxressed RNAs in Skiv2l-deficient mouse epidermis

overall_design: Two Skiv2l-deficient mouse epidermis (Skiv2lf/fl;K14-Cre) and two littermate controls (Skiv2l ctl) from P0 pups.

first: Kun


title: A single cell analysis of allograft rejection and tolerance using mouse solid organ transplantation models

city: Hangzhou

first: Fang

last: Ye

address: 866 Yuhangtang Rd

institute: Zhejiang University

summary: Solid organ transplantation in the mouse is a powerful research tool that has provided a pathway to find important mechanistic insights into the regulation of allograft injury, allograft immunopathology, and transplant rejection/tolerance, and that has unique advantages over transplantation in larger species, due to the well characterization of mouse genome and availability of genetically modified animals. However, setup of mouse liver, heart and kidney transplantation is a technically demanding surgical procedure, especially the orthotopic liver transplantation in mouse. Here, we performed Microwell-based single cell RNA-seq of three mouse organ transplantation models (liver, heart and kidney). Comparison of lymphocytes, parenchyma cells and peripheral blood mononuclear cells in liver, heart and kidney revealed distinct immune microenvironment at acute rejection and tolerance state respectively. Single-cell transcriptome analysis of mouse allograft without immunosuppressive drugs provided rich resources to help understand functioning solid-organ transplantation in human.

overall_design: Microwell datasets for three mouse tissues (heart, liver, kidney) at day 7 post allograft covering organ parenchyma cells, lymphocytes and peripheral blood mononuclear cells.

first: Yingying

last: Wang

first: Chengxuan

last: Yu

first: Jun

last: Pan


title: Flt3-ITD drives cooperating mutation-specific changes in cell identity and variable interferon dependence [ChIP-seq]

first: Jeffery

summary: Chipmentation analysis of wild type, Nup98-Hoxd13, Flt3-ITD and Runx1 mutant progenitors


title: Multiple signalling pathways converge on UHRF1 stability and activity

city: London

first: Gabriella

last: Ficz

state: Rest of the World

address: Centre for Haemato-Oncology

country: United Kingdom

institute: Barts Cancer Institute, Queen Mary University of London

summary: Propagation of DNA methylation through cell division relies on the recognition of methylated cytosines by UHRF1. We present an experimental system where regulation of global and site-specific demethylation can be dissected in great detail, which is part of the biology of stem cells transitioning to ground state pluripotency upon signal inhibition. In this study we begin to elucidate the signalling pathways that converge upon UHRF1 regulation by employing a high-throughput shRNA screen targeting genes of the mouse kinome, using UHRF1-GFP fluorescence as readout. Our screen identified a total of 251 genes, enriched in factors related to metabolic processes. We found that whilst all candidates tested rescued UHRF1 from proteasomal degradation, UHRF1 in Nags and Csnk2b knockdown prevented DNA methylation loss, whereas in Prpsap2 and Sephs2 knockdown cells UHRF1 activity was impaired leading to methylation loss. This study, therefore, provides a valuable resource for understanding the interface between signalling and its effect on the epigenome

overall_design: shRNA screen to identify kinases regulating UHRF1

first: Michael

last: Rushton


title: CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer

status: Public on Nov 17 2022

city: New York

first: Bic

last: MSKCC

state: NY

address: 1275 York Ave.

institute: Memorial SLoan-Kettering Cancer Center

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

overall_design: Refer to individual Series


title: Flt3-ITD drives cooperating mutation-specific changes in cell identity and variable interferon dependence

last: Magee


title: CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer [scRNA]

summary: We utilized cell surface expression of CD39 to demonstrate that this marker enriches for CD8+ T cells with features of exhaustion, proliferation and tumor reaxtivity.

overall_design: We sorted CD3+ T cells from four patients with lung cancer and submitted these samples for single cell CITE/TCR/RNA sequencing.

first: Andrew

last: Chow

first: Charles

middle: M

last: Rudin


title: miR expression microarray analysis on M2 macrophages treated with epigenetic modifiers

city: Daegu

first: Byungheon

last: Lee

state: Outside U.S. & Canada

address: 680 Guckchaebosang-ro, Jung-gu

department: School of Medicine

country: South Korea

institute: Kyungpook National University

summary:
Epigenetic regulation of gene expression involves DNA methylation, histone methylation or acetylation, and microRNA (miRNA)-mediated mRNA degradation.
We studied, if epigenetic modifiers namely 5-aza-2'-deoxycytidine and trichostatin A could remodulate the miR expression in M2 macrophage and enable M2-M1 reprogramming.

overall_design: Bone marrow cells were isolated from tibias and femurs of Balb/c mice and cultured in DMEM supplemented with 10 ng/mL of colony-stimulating factor-1 (CSF-1; Gibco, Carlsbad, CA, USA) and 10% FBS for 7 d. The culture medium was changed every other day. Next, the cells were incubated with 100 ng/mL of lipopolysaccharide and 20 ng/mL of recombinant mouse IFN-γ (R&D Systems, Minneapolis, MN, USA), for 24–48 h to achieve M1 polarization. For M2 polarization, BMDMs were incubated with 20 ng/mL of recombinant mouse IL-4 for 24–48 h. M2-polarized macrophages were treated with either 50 nM 5-aza-dC (Merck, Rahway, NJ, USA) for 72 h or 25 nM TSA (Merck) for 48 h. For treatment with the combination, M2-polarized macrophages were treated with 5-aza-dC for 24 h followed by treatment with 5-aza-dC and TSA for 48 h.RNAs for miRNA profiling were isolated using the miRNeasy® Mini Kit. Microarray analysis of miRNAs was performed using an Affymetrix GeneChip miRNA 4.0 array (Affymetrix, Santa Clara, CA, USA) by Macrogen (Seoul, Korea).

first: Poongkavithai

middle: V

last: Vadevoo

first: Gunassekaran

last: Gowry


title: CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer [VDJ]


title: CD39 Identifies Tumor-Reactive CD8 T cells in Patients With Lung Cancer [FB]


title: Epigenome Mapping in ING3-silenced pancreatic cancer cells

city: LOS ANGELES

first: MARINA

last: KOUTSIOUMPA

state: CA

address: 650 Charles E. Young Dr South, CHS 33-315

department: MEDICINE

institute: UCLA

summary: Epigenetic profiling in 4 cohorts of pancreatic cancer patients revealed reduced expression of the chromatin factor inhibitor of growth family member 3 (ING3). Furthermore, using mass spectrometry analysis we demonstrated that the linker Histone 1.2 (H1.2) is a direct binding partner of ING3. Thus, we reasoned to explore the Genome binding/occupancy profiling of H1.2 upon ING3 depletion by performing the Illumina NextSeq500 using single-end 75bp protocol.

overall_design: Chromatin fragments, derived from siControl and sING3 treated cells, were immunoprecipitated with antibody against Anti-Histone H1.2. After purification of DNA from cell lysate by functionalized magnetic particles, libraries for next generation sequencing were prepared and analyzed using standard procedures.

first: Dimitrios

last: Iliopoulos

first: Marina

last: Koutsioumpa


title: Genome-wide Expression Profiling in pancreatic cancer cells over-expressing ING3

summary: Differential gene expression profiling in ING3-overexpressing MIA PaCa-2 cells was performed using Human Genome U133 Plus 2.0 Array

overall_design: Expression profiles of MIA PaCa-2 cells from technical duplicates of control and ING3-overexpressing cells


title: RBP CELF2 regulates acute leukemia development via FAT10-mTORC1.

city: nanjing

first: tengxiao

last: guo

address: nanjing road

institute: State Key Laboratory of Experimental Hematology

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Transcriptomics of Rxfp4-expressing cells in mouse hypothalamus tissue

city: Cambridge

first: Fiona

last: Gribble

state: Cambridgeshire

address: Box 289 Addenbrooke's Hospital, Hills Road

department: Medical Research Laboratories

institute: University of Cambridge

summary: We purified Rxfp4-expressing cells from mouse hypothalamus by FACS and identified cell types distinguished by transcripts.

overall_design: Comparative transcriptomic study of cell populations by single cell RNAseq, pooled from 12x female biological replicates.

first: Jo

last: Lewis

first: Orla

last: Woodward

first: Christopher

last: Smith


title: RBP CELF2 regulates acute leukemia development via FAT10-mTORC1 [RIP-seq]

summary: We demonstrated that CELF2 regulates FAT10, and promotes mTORC1 signaling pathway activation in MLL-AF9-AML mice.

overall_design: K562 cells with either expression of 3xflag-HA-CELF2 or empty vector were seeded in 10 cm dishes and harvested. 5 μg of CELF2 antibody (or rabbit IgG (Sigma-Aldrich, 12-370, 3202364) was conjugated to protein A/G magnetic beads by incubation for 4 h at 4°C, and then wash three times with wash buffer and incubated with pre-cleared nuclear extraction in lysis buffer at 4°C overnight. After washing with wash buffer for three times, beads were resuspended in 50 μl PBS, followed by DNA digestion at 37°C for 15 min. Input and co-immunoprecipitated RNAs were recovered by TRIzol, extraction was analyzed RNA-seq. Input VC represented the RNA of input in k562 empty vector cells. Input OE represented the RNA of input in k562 3xflag-HA-CELF2 cells. CELF2 IP1 and CELF2 IP2 represented the co-immunoprecipitated RNAs with CELF2 in k562 3xflag-HA-CELF2 cells, in two replicates of the experiment.

first: Tengxiao

last: Guo

first: Yuxia

last: Wang


title: RBP CELF2 regulates acute leukemia development via FAT10-mTORC1 [RNA-seq]

overall_design:
Comparative gene expression profiling analysis of RNA-seq data for celf2 KO+MA9 mice and MA9 mice.
Celf2 conditional deletion mice were generated using the homologous recombination technique to selective knockout of exon 5 which causes in a frameshift mutation, resulting in a stop codon (as shown in the figure below). The mice were then mated with Vav1-Cre transgenic mice expressing Cre recombinase under the control of the Vav1 promoter to delete Celf2 in hematopoietic cells at the embryonic stage. As expected, half of the offspring were Celf2 wild-type, and the other half were Celf2 knockout mice. Continue breeding with Celf2fl/fl mice to obtain Vav1-Cre;Celf2fl/fl mice.


title: SWI/SNF chromatin remodeling complex coordinates the meiotic gene activation via promoter remodeling and Meiosin activation in female germline

city: Sagamihara

first: Toshiaki

last: Ito

state: Kanagawa

address: 1-15-1, Kitasato, Minami-ku

department: Biosciences

institute: Kitasato university

summary: In mammals, primordial germ cells (PGCs) enter meiosis and differentiate to primary oocytes in embryonic ovaries. Previously, we demonstrated that SWI/SNF chromatin remodeling complex is required for induction of the meiotic prophase genes and meiotic initiation in female germline, using conditional knockout (CKO) mice lacking the Smarcb1 (also known as Snf5) gene, which encodes a core subunit of the SWI/SNF complex. Here, we show that the meiotic prophase genes expressed at lower levels in the Snf5 CKO females can be classified into two groups, based on the promoter accessibility. The promoters of 74% of these genes showed lower accessibility in the mutant mice whereas those of remaining genes were opened equivalently in control and the mutant mice. The former genes include the Meiosin that encodes the transcription regulator essential for activation of the meiotic prophase genes. Furthermore, the promoters of the former and the latter genes were largely modified with H3K27me3/bivalent histone marks and H3K4me3, respectively. Collectively, we provide the mechanistic model by which SWI/SNF complex remodels the meiotic prophase genes repressed by polycomb repressive complex (PRC), including the Meiosin, and then MEIOSIN together with STRA8 activates the meiotic prophase genes in female germline.

overall_design: ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) data to profile chromatin accessibility of embryo day 15.5 (E15.5) Snf5 Ctrl and Snf5 CKO mice germ cells.

first: Masami

last: Ohta

first: Atsuki

last: Osada

first: Akira

last: Nishiyama

first: Kei-Ichiro

last: Ishiguro

first: Tomohiko

last: Tamura

first: Yoichi

last: Sekita

first: Tohru

last: Kimura


title: Ikaros-regulated microRNA networks in acute lymphoblastic leukemia

city: Burlington

first: Seth

last: Frietze

state: VT

address: 149 Beaumont Avenue

department: Biomedical and Health Sciences

institute: University of Vermont

summary: Purpose: miRNAs are important factors that are involved in the regulation cancer growth processes through the regulation of different biological processes. The purpose of the study was to investigate the differential expression pattern of miRNAs in IK1-induced B-ALL cells compared to controls.  Methods: In this study, we used two human B-ALL cell lines with IZF1 deletions and induced IK1 expression or controls for 24 hours, and then RNA samples were prepared for the analysis of miRNAs profiles using the Genechip miRNA 4.0 arrays. The Genechip miRNA 4.0 array provides a comprehensive coverage that is designed to interrogate all mature miRNA sequences in miRBase Release 20.  Result: The miRNAs expression microarray analysis showed that many miRNAs have been expressed differentially between IK1 and controls. These miRNAs might be involved in the different biological and physiological processes related to growth processes.  Conclusion: miRNAs might be an active player Ikaros tumor suppression.

overall_design: 2 independent B-ALL cell-lines were used each with TET-inducible expression of IK1 or a empty vector control (CON). For each cell-line independent cultures were used as replicates, totalling 4 IK1 and 4 CON samples.

first: Sophie

last: Kogut


title: CBP is required for establishing adaptive gene programs in the adult brain [CBPifKO]

city: San Juan de Alicante

first: Sergio

last: Niñerola

state: Alicante

address: Avenida Santiago Ramon y Cajal, s/n

department: Molecular Neurobiology and Neuropathology

country: Spain

institute: CSIC-Instituto de Neurociencias de Alicante

summary: We investigated the impact in transcription, chromatin acetylation and behavior of eliminating either CBP or p300 in excitatory neurons of the adult forebrain. The elimination of CBP reduced the expression of plasticity genes. The importance of CBP became more prominent in paradigms that involved a chronic or recurrent change in transcription, including kindling and neuroadaptation to environmental enrichment, in which CBP loss interfered with the establishment of activity-induced transcriptional and epigenetic adaptive changes in response to stimulus or experience. Comparative analyses in mice lacking CBP’s paralog p300 underscored the specificity of CBP function.

overall_design: Total RNA from hippocampi from 3- to 6-month-old mice. The recombination of floxed alleles was induced by 5 intragastrical administrations of tamoxifen (Sigma Aldrich, 20 mg/mL dissolved in corn oil) on alternate days (Fiorenza et al., 2016). In all our experiments with ifKOs, we used CaMKIIα-creERT2- littermates treated with tamoxifen as controls.

first: Michal

last: Lipinski

first: Jose

last: Lopez-Atalaya

first: Angel

last: Barco


title: CBP is required for establishing adaptive gene programs in the adult brain [p300]


title: CBP is required for establishing adaptive gene programs in the adult brain [ChIP-seq]

overall_design: ChIPseq from hippocampi from 3- to 6-month-old mice.  The recombination of floxed alleles was induced by 5 intragastrical administrations of tamoxifen (Sigma Aldrich, 20 mg/mL dissolved in corn oil) on alternate days (Fiorenza et al., 2016). In all our experiments with ifKOs, we used CaMKIIα-creERT2- littermates treated with tamoxifen as controls.


title: CBP is required for establishing adaptive gene programs in the adult brain [kindling]

overall_design: Total RNA from hippocampi from 3- to 6-month-old mice.  The recombination of floxed alleles was induced by 5 intragastrical administrations of tamoxifen (Sigma Aldrich, 20 mg/mL dissolved in corn oil) on alternate days (Fiorenza et al., 2016). In all our experiments with ifKOs, we used CaMKIIα-creERT2- littermates treated with tamoxifen as controls. We injected the mice with 45 mg/kg of pentylenetetrazol (PTZ) in alternate days and evaluated during 15 minutes by employing a modified Racine Scale. One week after kindling, mice were treated with the same dose of Saline(PTZ0) or PTZ(PTZ45) once again and 45 min later their hippocampi were extracted for RNA.


title: I3A Improves the Hepatic Mitochondrial Respiration Defects in NAFLD Disease Model

city: Qingdao

first: Chen

last: Zhang

address: Hefei Road 758

institute: Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University

summary: Recent evidences have linked indole-3-acetic acid (I3A), a gut microbiota-derived metabolite from dietary tryptophan, with the resistance to liver diseases. However, data supporting I3A-mediated protection against nonalcoholic fatty liver disease (NAFLD) remain incomprehensive. In this study, we verified that I3A definitely alleviates dietary-induced metabolic impairments, particularly glucose dysmetabolism and liver steatosis. Importantly, we expand the understanding of I3A further to enhancing mitochondrial respiration complex (MRC) capacity by RNA-seq. We found that I3A restored the deficiency of MRC capacity in palmitic acid (PA)-induced HepG2 in vitro. These changes were associated with complex I and III expression and their activities. In addition, pre-treatment of I3A guard against the deficiency of not only the MRC capacity but also ATP production due to the advanced protection effect on the expression and activity of complex V. In conclusion, our findings uncover that I3A increased expression and activity of hepatic oxidative phosphorylation subunits, contributing to mitochondrial respiration improvement in NAFLD mice.

overall_design: Liver mRNA profiles of HFD and HFD+I3A mice

first: Xiaoyun

last: Zhao


title: AXL and error-prone DNA replication confer drug resistance and offer strategies to treat EGFR-mutant lung cancer.

city: Rehovot

first: Yosef

last: Yarden

address: Herzl St 234

department: Biological Regulation

country: Israel

institute: Weizmann Institute of Science

summary: Anti-cancer therapies have been limited by emergence of mutations and other adaptations. In bacteria, antibiotics activate the SOS response, which mobilizes error‐prone factors that allow for continuous replication at the cost of mutagenesis. We investigated whether treatment of lung cancer with EGFR inhibitors (EGFRi) similarly engages hypermutators. In cycling drug-tolerant persister (DTP) cells and in EGFRi-treated patients presenting residual disease we observed upregulation of GAS6, while ablation of GAS6’s receptor, AXL, eradicated resistance. Reciprocally, AXL overexpression enhanced DTP survival and accelerated the emergence of T790M, an EGFR mutation typical to resistant cells. Mechanistically, AXL induces low-fidelity DNA polymerases and activates their organizer, RAD18, by promoting neddylation. Metabolomics uncovered another hypermutator, AXL-driven activation of MYC and increased purine synthesis that is unbalanced by pyrimidines. Aligning anti-AXL combination treatments with the transition from DTPs to resistant cells cured patient-derived xenografts. Hence, similar to bacteria, tumors tolerate therapy by engaging pharmacologically targetable endogenous mutators.

overall_design: AXL knock out PC9 cells were generatred. Single cells were sorted to a plate. From two cells, B11 and D11 cell culure were grown. Biological groups: control (3 replicates) and KO: B11 and D8 (2 replicates for each).

first: Ashish

last: Noronha

first: Diana

last: Drago-Garcia


title: Genetic analysis for the Grain shape and Grain weight heterosis of a super-hybrid rice WFYT025 combination

city: 南昌

first: Jianmin

last: Bian

state: 江西 (Jiāngxī)

address: 志敏大道1101

institute: 江西农业大学

summary: Purpose:The purpose of this study is to explore the transcriptome analysis of the heterosis of the grain type and grain weight of the super rice WFYT025 hybrid combination at the grain filling stage.

overall_design: RNA-seq of WFYT025 and its parents Changhui T025 and Wufeng B

first: Haohua

last: He


title: CBP is required for establishing adaptive gene programs in the adult brain [CBPifKO_EE]


title: CBP is required for establishing adaptive gene programs in the adult brain.


title: NLP7 transcription factor is a plant nitrate sensor

city: Boston

first: Jen

last: Sheen

state: MA

address: 185 Cambridge st. CPZN7620

department: Molecular Biology

institute: Massachusetts General Hospital

summary:
NLP1-9 are plant unique transcrition facotrs. To identify NLP1-9 target genes, we transiently expressed NLP1-9 in Arabidopsis mesophyll protoplasts and performed RNA-seq analysis. NLP1-9 individually  induced specific gene expression and co-activated nitrate responsive genes expression.
To study genome-wide transcriptional landscape modulated by NLP, we performed transcriptome analysis at 20 min after nitrate induction in wild type and nlp2,4,5,6,7,8,9.  All nitrate responsive genes were significant reduced in nlp2,4,5,6,7,8,9 indicated that NLP transcription factors are central regulators in PNR.

overall_design:
Genome-wide transcriptional profiling using RNA sequencing in the transient expressing NLP1-9 in mesophyll protoplasts. RNA-seq analysis of wild type and nlp2,4,5,6,7,8,9 mutant in response to nitrate
RNA-seq analysis of chl1-5 mutant in response to nitrate

first: Kun-hsiang

last: Liu


title: Transcriptome Analysis of PRC2 isogenic human MPNST cells with or without DNA demethylating therapy (RNA-Seq)

first: Ping

last: Chi

address: 417 East 68th Street

department: Human Oncology and Pathogenesis Program

institute: Memorial Sloan Kettering Cancer Center

summary: Goals of this study were to determine the effect of PRC2 loss or DNA demethylating therapy either alone or in combination on the Transcriptome

overall_design: Transcriptome analysis of SUZ12 isogenic M3 MPNST cells treated with either Vehicle, GSK862, or DAC.

first: Amish

last: Patel


title: CpG DNA methylation analysis of PRC2 isogenic human MPNST cells with or without DNA demethylating therapy (Methyl-Seq)

type: Methylation profiling by high throughput sequencing

summary: Goals of this study were to determine the effect of PRC2 loss or DNA demethylating therapy either alone or in combination on CpG DNA methylation genome wide

overall_design: SUZ12 isogenic M3 MPNST cells treated with either Vehicle, GSK862, or DAC.


title: G-Quadruplex in Long non-coding RNA 00273 acts as microRNA sponge to regulate Metastasis, Cancer Stemness, and Chemoresistance

city: Kolkata

first: Ananya

last: Roy

state: West Bengal

address: EN 80

department: Bio physics

country: India

institute: Bose Institute

summary: To investigate the role of upregulated LINC00273 in MDA-MB-231 triple negative breast cancer tumospheres.

overall_design:
We have performed whole transcriptomic expression profile upon LINC00273 over-expression and M2 treatment.
NGS analyses of LINC00273 overexpressed and M2 (10 μM)-treated samples were performed at Medgenome India Pvt. Ltd. using Illumina® HiSeq 4000/x platform to obtain 150-bp paired-end reads.

first: Pallabi

last: Sengupta

first: Subhrangsu

last: Chatterjee


title: A single cell-based computational platform to identify chemical compounds targeting desired sets of transcription factors for cellular conversion [Single-cell RNA-seq]

city: Beijing

first: Bingqing

last: Xie

address: No.5 Yiheyuan Road, Haidian District

institute: Peking University

summary: Conversion of cellular identity can be achieved safely, without genetic manipulation, by inducing signalling perturbations with chemical compounds to target cell fate-governing transcription factors (TFs). However, chemical-induced cellular conversion currently requires large-scale screening of small compounds, which is time- and labour-intensive. There are no existing computational approaches that facilitate chemical conversion of cell fate. Here, we develop a computational framework (SiPer) to systematically predict chemical compounds specifically targeting desired sets of TFs to direct cellular conversion. This framework integrates a large compendium of chemical perturbation datasets with a network model. We show that SiPer is generally applicable to diverse cellular conversion examples, recapitulating the known chemical compounds and their corresponding protein targets. Furthermore, using chemical compounds predicted by SiPer, we develop a highly efficient protocol for the generation of functional human induced hepatocytes (hiHeps). These results demonstrate that SiPer provides a valuable resource to efficiently identify chemical compounds for cellular conversion.

overall_design: 1 sample of hepatic progenitors were analyzed by single-cell RNA-seq.

first: Menglin

last: Zheng

first: Satoshi

last: Okawa

first: Soon

last: Liew

first: Hongkui

last: Deng

first: Antonio

last: Del Sol


title: A single cell-based computational platform to identify chemical compounds targeting desired sets of transcription factors for cellular conversion [Bulk RNA-seq]

summary: Cellular conversion can be induced by perturbing a handful of key transcription factors (TFs). Replacement of direct manipulation of key TFs with chemical compounds offers a less laborious and safer strategy to drive cellular conversion for regenerative medicine. Nevertheless, identifying optimal chemical compounds currently requires large-scale screening of chemical libraries, which is resource-intensive. Existing computational methods aim at predicting cell conversion TFs, however there are no methods for identifying chemical compounds targeting these TFs. Here, we develop a single cell-based platform (SiPer) to systematically prioritize chemical compounds targeting desired TFs to guide cellular conversions. SiPer integrates a large compendium of chemical perturbations on non-cancer cells with a network model, and predicted known and novel chemical compounds in diverse cell conversion examples. Importantly, we applied SiPer to develop a highly efficient protocol for human hepatic maturation. Overall, SiPer provides a valuable resource to efficiently identify chemical compounds for cell conversion.

overall_design: Total of 7 samples were analyzed, which included primary human hepatocytes, human liver tissue, human hepatic progenitor-like cells, 2 samples of human induced hepatocytes cultured in  Williams’ E medium with 2C (W2C) and 2 samples of Williams’ E medium with 6C (W6C). Global transcriptional profiles of these cells were analyzed by RNA-seq.


title: A single cell-based computational platform to identify chemical compounds targeting desired sets of transcription factors for cellular conversion

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

overall_design: Refer to individual Series


title: T cells and monocyte-derived myeloid cells mediate immunotherapy-related hepatitis in a mouse model II

status: Public on Nov 16 2022

city: San Diego

first: Richard

last: Virgen-Slane

address: 0777 Science Center Drive, CB4-2131, Pfizer La Jolla

department: Global Computational Safety Science, DSRD

institute: Pfizer

summary: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) which are more severe when ICIs are used in combination. A mouse model was developed to elucidate the molecular mechanisms of immune-related hepatitis, one of the common irAEs associated with ICIs. Molecular profiling by single cell RNA sequencing was performed on Pdcd1-/- mice treated with anti-CTLA4 and/or the IDO1 inhibitor epacadostat or a 4-1BB agonistic antibody. ICI combination-induced hepatitis and 4-1BB agonist-mediated hepatitis share similar features yet maintain distinct immune signatures. Both were characterized by an expansion of activated T cells. Single-cell transcriptomics revealed that the hepatitis induced by combination ICIs is associated with a robust immune activation signature in all subtypes of T cells and T helper 1 skewing. Expression profiling revealed a central role for IFNγ and liver monocyte-derived macrophages in promoting a pro-inflammatory T-cell response to ICI combination and 4-1BB agonism.

overall_design: Anti-CTLA4 antibody or isotype control was administered weekly to Pdcd1-/- mice. The IDO1 inhibitor, epacadostat, or vehicle control was administered by oral gavage twice daily. Anti-(4-1BB) agonistic antibody was administered intraperitoneally to mice twice weekly. Liver CD45+ cells were enriched with the Miltenyi liver dissociation kit and cells were analyzed on the 10X genomics platform.

first: Heather

last: Llewellyn

first: Changhua

last: Ji


title: Functional and molecular dissection of viral lncRNAs throughout HCMV life cycle

city: Seoul

first: Hyeshik

last: Chang

state: South Korea

address: Building 203 Room 525, School of Biological Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu

department: School of Biological Sciences

institute: Seoul National University


title: Activity dependent translation in astrocytes

city: St Louis

first: Joseph

last: Dougherty

address: 4566 Scott Ave, box 8232

department: Genetics and Psychiatry

institute: Washington University

summary: Protein coding gene expression requires two steps – transcription and translation – which can be regulated independently to allow nuanced, localized, and rapid responses to cellular stimuli.  Neurons are known to respond transcriptionally and translationally to bursts of brain activity, and a transcriptional response to this activation has also been recently characterized in astrocytes.  However, the extent to which astrocytes respond translationally is unknown.  We tested the hypothesis that astrocytes also have a programmed translational response by characterizing the change in transcript ribosome occupancy in astrocytes using Translating Ribosome Affinity Purification subsequent to a robust induction of neuronal activity in vivo via acute seizure. We identified a reproducible change in transcripts on astrocyte ribosomes, highlighted by a rapid decrease in housekeeping transcripts, such as ribosomal and mitochondrial components, and a rapid increase in transcripts related to cytoskeleton, motor activity, ion transport, and cell communication. This indicates a dynamic response, some of which might be secondary to activation of Receptor Tyrosine Kinase signaling. Using acute slices, we quantified the extent to which individual cues and sequela of neuronal activity can activate translation acutely in astrocytes. This identified both BDNF and KCl as contributors to translation induction, the latter with both action-potential sensitive and insensitive components. Finally, we show that this translational response requires the presence of neurons, indicating  the response is acutely or chronically non-cell autonomous.  Regulation of translation in astrocytes by neuronal activity suggests an additional mechanism by which astrocytes may dynamically modulate nervous system functioning.

overall_design: 6 mice, 3 per treatment, were used.

first: Darshan

last: Sapkota


title: Functional and molecular dissection of viral lncRNAs throughout HCMV life cycle [shortread]

summary: Small, compact genomes confer a selective advantage to viruses, yet human cyto-megalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~30 % and 50~60 % of to-tal and poly(A)+ viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the three abundantly expressed lncRNAs, appear to be es-sential in all infection states. Among these three lncRNAs, depletion of RNA2.7 and RNA4.9 results in the greatest defect in maintaining latent reservoir and promoting lytic replication, respectively. Moreover, we delineated the global post-transcriptional nature of HCMV lncRNAs by nanopore direct RNA sequencing and interactome analysis. We revealed that the lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth analysis demonstrated that m6A machineries stabilize HCMV lncRNAs, which could account for the over-whelming abundance of viral lncRNAs. Our study lays the groundwork for under-standing the viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.

overall_design: Comparative viral gene expression profiling of RNA-seq and DRS data for HCMV latency, reactivation, and lytic infection sample.

first: Sungwon

last: Lee

first: Hyewon

last: Kim

first: Ari

last: Hong

first: Jaewon

last: Song

first: Kwangseog

last: Ahn


title: Functional and molecular dissection of viral lncRNAs throughout HCMV life cycle [longread]


title: Deconvolution of drug screening data delineates drug sensitivity of stem-like cancer cells in Acute Myeloid Leukemia [scRNA-Seq]

city: Lausanne

first: Coudray

last: Alexandre

address: 25, Avenue Riant-Mont

department: SV

institute: EPFL

summary:
Ex-vivo drug sensitivity screening (DSS) only provides a readout on mixtures of cells, potentially occulting important information on clinically relevant cell subtypes. Here we developed a machine-learning framework to deconvolute bulk RNA expression matched with bulk drug sensitivity into cell subtype composition and cell subtype drug sensitivity.
We first determined that our method could decipher the cellular composition of bulk samples more accurately than current state-of-the-art methods. We then optimized an algorithm capable of estimating cell subtype- and single-cell-specific drug sensitivity, which we evaluated by performing in-vitro drug studies

overall_design: We generated in vitro pools containing various ratios of HL60, SUDHL4, K562, and THP1 human leukemic cells. We generated bulk RNA-seq for 6 mixtures of these cell lines, and 4 RNA-seq of the pure populations. To build the reference dataset, we peformed scRNA-seq on a mix of these four cell lines.

first: COUDRAY

last: ALEXANDRE

first: ROMAIN

last: FOREY

first: TRONO

last: DIDIER


title: Deconvolution of drug screening data delineates drug sensitivity of stem-like cancer cells in Acute Myeloid Leukemia [RNA-Seq]


title: Deconvolution of drug screening data delineates drug sensitivity of stem-like cancer cells in Acute Myeloid Leukemia


title: Transcriptomic analysis in human 3D skin model injected with resorbable hyaluronic acid fillers reveals foreign body response [RIVM]

city: Maastricht

first: Danyel

last: Jennen

address: Universiteitssingel 40

department: Toxicogenomics

institute: Maastricht University

summary: To unravel the molecular events caused by exposure to dermal fillers in a multi-cell type human 3D skin model and to link these events to the characteristics of the dermal fill-ers.

overall_design: The human Phenion® Full-Thickness Skin Model was injection with five experimental hyaluronic acid (HA) preparations with increasing cross-linking degree (RIVM1-5), and with the non-resorbable filler Bio-Alcamid®


title: Transcriptomic analysis in human 3D skin model injected with resorbable hyaluronic acid fillers reveals foreign body response [Perfectha]

summary: To unravel the molecular events caused by exposure to dermal fillers in a multi-cell type human 3D skin model and to link these events to the characteristics of the dermal fillers.

overall_design: The human Phenion® Full-Thickness Skin Model was injection with four commercial fillers from the Perfectha® product line differing in particulate size. This was done in triplicate, thus 3 biological replicates were obtained. For each biological triplicate 2 control samples were included (i.e. technical replicates). In total this would account for 18 samples. However for each of the controls only 1 technical replicate (with the best quality) was selected and  the Perfectha® Deep replicate 1 sample was excluded because it did not pass the quality criteria.


title: Transcriptomic analysis in human 3D skin model injected with resorbable hyaluronic acid fillers reveals foreign body response.


title: Transcriptome sequence of LN229 cells with UM-164 treatment

city: Shenyang

first: Huizhe

last: Xu

address: 44 Xiaoheyan Road Dadong District

institute: Liaoning Cancer Hospital & Institute

summary: Purpose: the goals of this study are to identify the regulated genes of glioma cells by UM-164

overall_design: The transcriptome sequence of LN229 cells with UM-164 treatment were generated by deep sequencing with two repeats using Illumina. The sequence reads that passed filters were mapped to human genome (ftp://ftp.ensembl.org/pub/release-101/fasta/homo_sapiens/dna/) using HISAT2 software. The differently expressed genes were identify by |log2(FoldChange)| > 0 & p < 0.05, and qRT–PCR validation was performed using SYBR Green assays.

first: Rui

last: Sui

first: Jia

last: Liu


title: Chemerin-induced down-regulation of placenta-derived exo-somal miR-140-3p and miR-574-3p promotes umbilical vein endothelial cells proliferation, migration, and tube formation in gestational diabetes mellitus

city: Hangzhou

first: Lixia

last: Zhang

address: 1 Bachelor Road

institute: Women's Hospital School of Medicine Zhejiang University

summary:
Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes and fetoplacental endothelial dysfunction; however, the underlying mechanisms are still unknown.
This study aimed to investigate the effect of placenta-derived exosomal miRNAs on fetoplacental endothelial dysfunction in GDM, and to further explore the role of chemerin to this end.
Placenta-derived exosomal miR-140-3p and miR-574-3p expression (next-generation sequencing, quantitative real-time PCR), its interactions with cell function (Cell Counting Kit-8, Transwell, tube formation assay), chemerin interactions (Western blotting), and placental inflammation (immunofluorescence staining, enzyme-linked immunosorbent assay) were investigated.
Placenta-derived exosomal miR-140-3p and miR-574-3p were downregulated in GDM.
Additionally, miR-140-3p and miR-574-3p inhibited the proliferation, migration, and tube formation ability of umbilical vein endothelial cells by targeting vascular endothelial growth factor.
Interestingly, miR-140-3p and miR-574-3p expression levels were negatively correlated with chemerin, which induced placental inflammation through the recruitment of macrophage cells and release of IL-18 and IL-1β.
These findings indicate that chemerin reduces placenta-derived exosomal miR-140-3p and miR-574-3p levels by inducing placental inflammation, thereby promoting the proliferation, migration, and tube formation of umbilical vein endothelial cells in GDM, providing a novel perspective on the underlying pathogenesis and therapeutic targets for GDM and its offspring complications.

first: Qi

last: Wu

first: Shuqi

last: Zhu

first: Yibo

last: Tang

first: Yanmin

last: Chen

first: Danqing

first: Zhaoxia

last: Liang


title: ATF3-activated CBS protects CRC from ferroptosis.

city: Xiamen

first: yongyou

last: zhang

state: Fujian

address: Xiang'an South Road

institute: Xiamen University

summary: We performed CUT&Tag to analyze the ATF3 binding gene regulatory element differences.

overall_design: SW480 cells were cultured between the full medium (FM) and cystine-restricted medium (CR) for 24 hrs.

first: Liu

last: Junjia


title: Genome-wide analysis of histone trimethylation in INMA cohort exposed to BPA revealed a global impact on telomeric binding proteins and histone acetyltransferase factors

city: Rennes

first: Fatima

last: SMAGULOVA

address: 9 av. Prof. Léon Bernard

country: France

institute: Irset - U1085

summary: This study was developed under the framework of the Human Biomonitoring for Europe Initiative (HBM4EU). We evaluated the possible impacts of BPA exposure in adolescent males from the INMA-Granada cohort (Spain) with the goal of identifying new biomarkers that could be useful in biomonitoring and epidemiological studies. Our hypothesis is that alterations in epigenetic regulation could lead to genetic instability in human subjects exposed to environmentally relevant doses of BPA.

overall_design: Methods: We used chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) technique and H3K4me3 antibody (Milipore, 07-4730). The experiments were done with material extracted from whole human blood with low (0.66-2.55) or high (10.07-42.64 microg/gram/creatinine) levels of BPA. The chromatin was fixed, shared and incubated with H3K4me3 antibody. The immunoprecipitated DNA was purified with MiniElute Reaction Clean-Up kit (Qiagen) and the DNA concentration was measured using QuantiFluor dsDNA system (Promega). A minimum of ~3 ng of DNA was recovered. Sequencing libraries were prepared using NEBNext Ultra DNA Library Prep Kit for Illumina (E7645S; NEB). Sequencing was performed on an Illumina HiSeq4000 sequencer using a single-end 50-base read in multiplexed mode. Reads were aligned to the human GRCh38 reference genome. Wig files were generated using with an in-house script (Variable step, span=25, reads were elongated to 200b).

last: Smagulova

first: Chunxiang

last: Hao

first: Louis

last: Legoff

first: Shereen

last: D'Cruz


title: Chronic Type I interferons signaling promotes lipid peroxidation-driven terminal CD8+T cell exhaustion and curtails anti-PD-1 treatment efficacy [RNA-Seq]

city: Hong Kong

first: Weixin

address: 21 Sassoon Road

country: Hong Kong

institute: The University of Hong Kong

summary: Identifying signals that govern the differentiation of tumor-infiltrating CD8 + T cells (CD8 + TILs) towards exhaustion can improve current therapeutic approaches for cancer. Here, we show that type I interferons (IFN-Is) act as environmental cues enhancing terminal CD8 + T cell exhaustion in tumors. We found enrichment of IFNIs-stimulated genes (ISGs) within exhausted CD8 + T cells (Tex cells) in patients across various cancer types, with heightened ISG levels correlating with poor response to immune checkpoint blockade (ICB) therapy. In preclinical models, CD8 + TILs devoid of IFN-Is signaling developed less exhaustion features, provided better tumor control and showed greater response to ICB-mediated rejuvenation. Mechanistically, chronic IFN-Is stimulation perturbed lipid metabolism and redox balance in Tex cells, leading to aberrant lipid accumulation and elevated oxidative stress. Collectively, these defects promoted lipid peroxidation, which potentiated metabolic and functional exhaustion of Tex cells. Thus, cell intrinsic IFN-Is signaling regulates the extent of CD8+ TIL exhaustion, and has important implications for immunotherapy.

overall_design: CD8+T cells were isolated using Human CD8+ T Cell Isolation Kit (Miltenyi Biotec) according to the manufacturers procedure. Purified CD8+T cells were then stimulated with anti-CD3/anti-CD28-coated microbeads (Dynabeads M-450 Epoxy, Invitrogen; bead to cell ratio of 1:1) in the presence of 10U/ml recombinant human IL-2 (PeproTech) in T cell medium (RPMI 1640 medium supplemented with 10% FBS, 50M -mercapteoethanol, 1M HEPES, 1X non-essential amino acids (NEAA), 100mM sodium pyruvate, and 1% penicillin-streptomycin). Surviving cells were passaged every 48 hours with fresh microbeads and IL-2 until day 8 to generate Tex cells. In these conditions, human universal Type I interferon (PBL Assay science) was added at 1000U/mL throughout the culture. Alive Tex cells were sorted through FACs with Influx (BD Biosciences). Their RNA was extracted using RNeasy Mini Kit (Qiagen) and submitted for paired-end RNA sequencing. Reads were mapped to UCSC human genome GRCh38/hg38 using STAR (version 2.6.1) and gene counts were quantified by featureCounts (version 1.6.4).

last: Teo

first: Siu

middle: W

last: Yau

first: Yee-Man

last: Wong

first: Chun-Nam

last: Lok

first: Chi-Ming

last: Che

first: Yuanhua

last: Huang

first: Asif

last: Javed

first: Stephanie

last: Ma

first: Guang

last: Ling