title: Gene expression profile of HSCs and ANGPTL2 treated HSCs Transcriptomes

city: shanghai

first: wenqian

last: yang

address: 280 South Chongqing Road

institute: Shanghai Jiaotong University School of Medicine

summary: To identify the intracellular targets of ANGPTL2 that control HSC stemness, human cord blood CD34+ hematopoietic stem/progenitor cells (HSPCs) were stimulated with ANGPTL2 for 24 hr, followed by the extraction of total RNA and subjected to the RNA-sequencing.

overall_design: HSCs and ANGPTL2 treated HSCs from human cord blood were sorted to measure gene expression

first: J

last: Zheng

first: Z

last: Yu

first: W

last: Yang


title: Epigenetic Landscape Reveals MECOM As An Endothelial Lineage Regulator

status: Public on Mar 16 2023

city: Memphis

first: JIE

last: Lv

state: TN

address: 262 Danny Thomas Place

department: Department of Computational Biology

country: USA

institute: St Jude Children's Research Hospital

type: Expression profiling by high throughput sequencing

summary:
Background: A comprehensive understanding of the determinants of endothelial cell (EC) lineage specification will advance strategies for cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures specifically regulate cell identity genes, making it possible to systematically identify novel EC master regulators by leveraging extensive epigenomic datasets available for EC.
Methods: We developed a method to identify novel regulators of endothelial cell identity by integrating multiple epigenetic patterns. We verified MEOCM as a master EC lineage regulator using both in vivo and in vitro experiments. The mechanism of action of MECOM as EC lineage regulator was characterized by integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, scRNA-seq and bulk RNA-Seq data, as well as extensive molecular, cellular, and animal experiments.
Results: We identified MECOM to be the leading candidate as an EC lineage regulator. Single-cell RNA-Seq analysis further revealed that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide iPSC-ECs. We verified that MECOM was required for human endothelial differentiation, EC functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate EC identity genes. Specifically, we identified the VEGF signaling pathway to be a key downstream target of MECOM.
Conclusions: Our work provides new insights into epigenetic regulation of cell identity genes and uncovered MECOM as a master regulator of EC identity.

overall_design: RNA-Seq data of Control and MECOM KO (CRISPR-gRNA KO pools),  HUVECs

first: Jie

first: Lili

last: Zhang

first: Kaifu

last: Chen


title: Secretogranin II influences the assembly and function of MHC class I in melanoma

city: Heidelberg

first: Jochen

last: Utikal

address: Im Neuenheimer Feld 280

department: Clinical Cooperation Unit Dermato-Oncology

country: Germany

institute: German Cancer Research Center

summary: Melanoma is the deadliest form of skin cancer showing rising incidence over the past years. New insights into the mechanisms of melanoma progression contributed to the development of novel treatment options, such as immunotherapies. However, acquiring resistance to treatment poses a big problem to therapy success. Therefore, understanding the mechanisms underlying resistance could improve therapy efficacy. By conducting transcriptional analysis between SCG2-overexpressing (OE) and control melanoma cells, we detected a downregulation of components of the antigen presenting machinery (APM), which is important for the assembly of the MHC class I complex.

overall_design: Total RNA isolated from SCG2 overexpressing melanoma cell lines and its control cell lines

first: T

last: Steinfass


title: RNA sequencing of TA muscle in miR-501KO mice and control littermates at day 6 of CTX-induced muscle regeneration

city: Zurich

first: Alexandra

last: Fahrner

address: Rämistrasse 100

department: Division of Endocrinology, Diabetes and Clinical Nutrition

country: Switzerland

institute: University Hospital Zurich

summary: Adult muscle stem cells show a high transcriptional and clonal heterogeneity during ageing. Whether microRNAs contribute to this diversity is not known. Here we use global and tissue-specific genetic deletion of microRNA (miR)-501 that is highly enriched in activated myogenic progenitor cells 3 to address this question. Deletion of miR-501 reduced myofiber size and resilience of muscle fibers to injury and exercise in adult skeletal muscle. miR-501 elicits this effect by changing sarcomeric gene expression in newly built myofibers in vivo.

overall_design: We performed genome-wide identification of differentially expressed genes upon genetic deletion of miR-501. 5 Pax7Cre and 5 Pax7CremiR-501fl/Y (501KO) mice were subjected to cardiotoxin-induced muscle regeneration and TA muscles were assessed at day 6. Libraries were prepared using TruSeq Stranded mRNA Library Prep kit (Illumina) and samples were sequenced using NovaSeq 100bp single-end sequencing at the Functional Genomics Center Zurich.

first: Edlira

last: Luca

first: Jan

last: Krützfeldt


title: Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX MFN2 OE]

city: paris

first: Jerome

last: Tamburini

address: 22 rue mechain

country: France

institute: Cochin Institute

summary: Mitochondrial metabolism recently emerged as a critical dependency in acute myeloid leukemia (AML). The shape of mitochondria is tightly regulated by dynamin GTPase proteins, which drive opposing fusion and fission forces to consistently adapt bioenergetics to the cellular context. Here, we showed that targeting mitochondrial structure through the inhibition of mitochondrial fusion was a new vulnerability of AML cells, when assayed in patient-derived xenograft (PDX) models. Genetic depletion of mitofusin 2 (MFN2) or optic atrophy 1 (OPA1) or pharmacological inhibition of OPA1 (MYLS22) blocked mitochondrial fusion and had significant anti-leukemic activity, while having limited impact on normal hematopoietic cells ex vivo and in vivo. Mechanistically, inhibition of mitochondrial fusion disrupted mitochondrial respiration and reactive oxygen species production, leading to cell cycle arrest at the G0/G1 transition. These results nominate the inhibition of mitochondrial fusion as a promising therapeutic approach for AML.

overall_design: 8 conditions from patient-derived xenograft (PDX) AML samples (n=4, PDX1, PDX3, PDX4, PDX5) transduced with empty or MFN2 overexpression (OE) vectors

first: Clement

last: Larrue

first: Sarah

last: Mouche

first: Shan

last: Lin

first: Federico

last: Simonetta

first: Nastassja

middle: K

last: Scheidegger

first: Laury

last: Poulain

first: Rudy

last: Birsen

first: Jean-Emmanuel

last: Sarry

first: Kimberly

last: Stegmaier


title: Epigenetic misactivation of a distal developmental enhancer drives SOX2 overexpression in multiple cancer subtypes

city: Toronto

first: Jennifer

last: Mitchell

state: Ontario

address: 25 Harbord Street

department: Cell and Systems Biology

country: Canada

institute: University of Toronto

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We have investigated a distal regulatory region that drives SOX2 overexpression in multiple cancer subtypes

overall_design: WT and homozygous enhancer-deleted (dEnh) cells were submitted for ribo-depelted total RNA-seq and ATAC-seq in three replicates each.

first: Luis

middle: E

last: Abatti

middle: A


title: In vivo CRISPR screen identifies SNRPC as a regulator for facilitating triple-negative breast cancer progression [RNA-Seq]

status: Public on Mar 15 2023

city: Shanghai

first: Xin

last: Hu

address: No.688 Hong-Qu Road

country: China

institute: Fudan University Shanghai Cancer Center

summary: In this study, we employed an in vivo CRISPR screening and a TNBC progression model to identify potentially oncogenic RBPs. We identified the small nuclear ribonucleoprotein polypeptide C (SNRPC), a subunit of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), as a key modulator involved in TNBC progression. SNRPC was frequently upregulated and relevant to poor prognosis in TNBC patients. SNRPC ablation significantly impaired the proliferation, migration and invasion of TNBC cells in vitro and in vivo. In addition, SNRPC was essential for the stability of U1 snRNP and contributed to the RNA Pol II-controlled transcription program. Knockdown of SNRPC decreased RNA Pol II enrichment on some oncogenes (TNFAIP2, E2F2 and CDK4) and reduced their expression levels. We further confirmed that SNRPC deletion would inhibit TNBC progression partially through the TNFAIP2-Rac1-β-catenin signal.

overall_design: Comparative gene expression profling analysis of RNA-seq data for MCF10 CA1a cell and its SNRPC-KD dervative

first: Xunxi

last: Lu

first: Wenxiao

last: Yang


title: Expression data from a human primary syncytiotrophoblast model in response to double-stranded RNA

city: Setagaya

first: Kenichiro

last: Motomura

state: Tokyo

department: Allergy and Clinical Immunology

country: Japan

institute: National Research Institute for Child Health and Development

summary: Differentiated primary human cytotrophoblasts were stimulated with synthetic double-stranded RNA, poly I:C. Gene expression was profiled using Agilent microarray.

overall_design: The study included the data from differentiated cytotrophoblasts co-cultured with poly I:C or vehicle control. Total RNA from three different donors was pooled and analyzed by Agilent microarray.

first: Kenji

last: Matsumoto


title: Expression data from human peripheral blood mononuclear cells in response to double-stranded RNA

summary: Human peripheral blood mononuclear cells were stimulated with synthetic double-stranded RNA, poly I:C. Gene expression was profiled using Affymetrix Genechip.

overall_design: The study included the data from human peripheral blood monoculcear cells cultured with poly I:C or vehicle control. Total RNA was analyzed by Affimetrix genechip.


title: Combined disruption of T cell inflammatory regulators Regnase-1 and Roquin-1 enhances antitumor activity of engineered human T cells

city: Philadelphia

first: David

last: Mai

state: PA

address: 8-189 Smilow Center for Translational Research

institute: University of Pennsylvania

summary: To investigate the effect of Regnase-1 and/or Roquin-1 disruption in engineered primary human T cells, we produced CAR-T cells and TCR-T cells with single genetic disruption of Regnase-1, Roquin-1, or dual disruption of Regnase-1 and Roquin-1. We then performed differential gene expression analysis using data obtained from bulk RNA-seq of 3 different biological donors at baseline.

overall_design: Differential gene expression analysis of bulk RNA-seq data for primary human T cells transduced with either a mesothelin-targeting CAR or NY-ESO-1-targeting TCR, with genetic disruption of Regnase-1, Roquin-1, both Regnase-1 and Roquin-1, or mock control.

first: Omar

last: Johnson

first: Jordan

last: Reff

first: Ting-Jia

last: Fan

first: John

last: Scholler

first: Neil

middle: C

last: Sheppard

first: Carl

middle: H

last: June


title: Identification of dysregulated transcripts in egr-2(RNAi) planarians

city: Oklahoma

middle: J

last: Forsthoefel

state: OK

address: 825 NE 13th St

department: Genes and Human Disease Research Program

institute: Oklahoma Medical Research Foundation

summary: egr-2 is an injury-responsive gene that is upregulated in the anterior of planarian tail fragments and required for intestinal remodeling. The goal of this study was to identify differentially expressed transcripts in the anterior region of egr-2(RNAi) tail fragments relative to egfp(RNAi) control fragments.

overall_design: Total RNA was isolated from the anterior region of 0 hr, 2 day, and 4 day planarian tail fragments after egfp RNAi (control) or egr-2 RNAi (fed 6 times, 4 biological replicates per condition, tissue from 10 tail fragments per replicate). Library generation (NEB NEXT ULTRA) and RNA sequencing (2x150bp paired-end, Illumina HiSeq 4000) were conducted by Genewiz. Bioinformatic analysis was conducted using BBDuk, Bowtie2, and edgeR.

first: Vasileios

last: Morkotinis


title: The role and mechanism of R-spondin3 in pulmonary vascular barrier dysfunction induced by mechanical ventilation

first: hui

last: zhang

address: Kongjiang Road 1665

institute: Shanghai Jiao Tong University

summary: To investigate the effect of lowl tidal volume (LV) ventilation on the pathological development of severe lung injury, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to influence LV-induced lung injury. A mouse model of septic lung injury induced by cecal ligation and puncture was conducted, 24 h post-CLP,mice were exposed to LV (6ml/kg) for 12h

overall_design: To investigate the effect of small tidal volume ventilation on the pathological development of severe lung injury,we used a mouse model of septic lung injury induced by cecal ligation and puncture to observe the dynamic changes of lung pathology after small tidal volume ventilation for 12 h

first: Hui

last: Zhang

first: Dunfeng

last: Xu

first: Xiaoyan

last: Zhu

first: Lai

last: Jiang


title: In vivo CRISPR screen identifies SNRPC as a regulator for facilitating triple-negative breast cancer progression [ChIP-Seq]

first: Xin

last: Hu

overall_design: ChIP-sequencing of SNRPC, SNRPA, H3K4me3 and Pol II  in MCF10A and CA1a cells.

first: Xunxi

last: Lu

last: Yang


title: Dose- and type-dependent effects of ionizing radiation in genome-wide transcriptome changes of Chlamydomonas reinhardtii cells

city: Jeongeup-si

first: Jin-Hong

last: Kim

state: Jeonbuk-do

address: 29 Geumgu-gil

country: South Korea

institute: Korea Atomic Energy Research Institute

summary: The overall transcriptome changes were discriminated by the radiation dose rather than the radiation type and manifested mainly by DNA damage response (DDR) genes. Transcription levels of major DDR genes were found to increase in a dose-dependent manner but were rarely affected by the radiation type.

overall_design: To evaluate the genotoxic stress of X- or gamm-irradiation at two different doses proven to stimulate or inhibit cell growth, we compared the genome-wide transcriptomic profiles of Chlamydomonas reinhardtii by RNA-Seq analysis after X- or gamma-irradiation at doses of 6 and 50 Gy.

first: Shubham

last: Kumar Dubey


title: Urine-derived mesenchymal stem cells-derived exosomes enhances survival and proliferation of aging retinal ganglion cells

city: Chengdu

first: Li

last: Chen

state: Sichuann

address: No.17, South Renmin Road

institute: Sichuan University West China Hospital

summary: This study was designed to investigate to test the effect of exosomes from urine-derived mesenchymal stem cells (USCs) on the survival and viability of aging retinal ganglion cells (RGCs), and explored the preliminary related mechanisms. The sequencing outcomes demonstrated 117 upregulated genes and 186 downregulated genes in normal RGCs group vs aging RGCs group, 137 upregulated ones and 517 downregulated ones in aging RGCs group vs aging RGCs+USCs medium group. These DEGs involves in numerous positive molecular activities to promote the recovery of RGCs function.

overall_design: Moreover, gene sequencing and bioinformatics analysis were applied to analyze the genetic variation after medium treatment in RGCs along with the biological functions of differentially expressed genes (DEGs).

first: Qi-qin

last: Dan

first: Lan-Lan

last: shi

first: Xiu

last: Zhou

first: Ting-Hua

last: Wang

first: Hua

last: Liu


title: Epigenetic marks elucidate gene regulatory elements require for human inhibitory interneuron-like progenitors

city: Jerusalem

first: Tommy

last: Kaplan

address: Givat Ram Campus

department: School of Computer Science and Engineering

country: Israel

institute: Hebrew University

summary: Gene regulatory elements such as enhancers dynamically regulate gene expression in a tissue-specific manner. However, the transcriptional regulatory elements during human inhibitory interneuron differentiation and their role in neurodevelopmental disorders are unknown. Here, we generate gene regulatory element maps of human inhibitory-like interneurons derived from embryonic stem cells (H9-ESC), permitting large-scale annotation of previously uncharacterized regulatory elements relevant to inhibitory interneuron differentiation. Our analyses identify neuronal progenitor enhancers that likely regulate the expression of transcription factors that are essential for interneuron differentiation. Focusing on dynamic changes in chromatin organization, FOXG1 and ZEB2, where the chromatin organization is changed in interneuron progenitors compared to different stages during the differentiation. Using 4C-seq and an in vivo enhancer assay, we characterized neuronal enhancers at the FOXG1 locus that interact with the FOXG1 promoter region and showed activity patterns that resemble FOXG1 expression. Using CRISPR/Cas9 genome editing, we deleted FOXG1 enhancer/s that reduced FOXG1 expression in glioblastoma cells and altered cell proliferation. Furthermore, a microdeletion proximal to FOXG1 encompassing these neuronal FOXG1 enhancers was found in a patient with Rett-like syndrome, supporting the role of FOXG1 enhancers in this syndrome. Thus, our study elucidates the gene regulatory networks of human inhibitory interneurons. Furthermore, it provides a framework for understanding the impact of non-coding regulatory elements during inhibitory interneuron differentiation, and highlights novel mechanisms underlying neurodevelopmental disorders.

overall_design: Profiling histone modifications that are associated with enhancer activity during human ESC diffrentiation to interneuron progenitors

first: Reut

last: Eshel

first: Rawan

last: Alatawna

first: Shira

last: Strauss

first: Netanel

last: Loyfer

first: Einan

last: Farhi

first: Eva

last: D’haene

first: Sarah

last: Vergult

first: Idit

last: Dahan

first: Ramon

middle: Y

last: Birnbaum


title: In vivo CRISPR screen identifies SNRPC as a regulator for facilitating triple-negative breast cancer progression

first: Xin

last: Hu

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

overall_design: Refer to individual Series


title: YAP/TAZ-dependent expression of lncRNAs

city: Mannheim

first: Carsten

last: Sticht

address: Theodor-Kutzer-Ufer

department: ZMF

institute: University Heidelberg


title: Role of long non-coding RNA in regulatory network response to ‘Candidatus Liberibacter asiaticus’ in citrus

city: Lake Alfred

first: Xiaokang

last: Zhuo

state: Florida

address: 700 Experiment Station Rd

department: Citrus Research and Education Center

institute: University of Florida

type: Non-coding RNA profiling by high throughput sequencing

summary: The goals of this study are to reveal the transcriptional and regulatory dynamics of the lncRNAs in response to CLas infection and provide a reference for a better understanding of the role of lncRNAs involved in citrus HLB regulation. For the purpose, we obtained RNA-seq-based differential expression profile of the leave midrib of CLas- and mock-inoculated rough lemon and sweet orange at week 0, 7, 17, and 34 following infections with three biological replicates in the greenhouse. Approximately 2,523 million paired-end reads from 48 sample libraries were produced using Illumina HiSeq 2000. we systematically identified lncRNAs from rough lemon and sweet orange at four different time points of a greenhouse experiment and characterized their genomic transcriptional and regulatory dynamics. We predicted their potential regulatory genes and functions and constructed a co-expression network. Our study provides precious information and expands the knowledge of citrus lncRNA against HLB disease.

sample_organism:
Citrus sinensis
Citrus jambhiri

platform_organism:
Citrus sinensis
Citrus jambhiri

overall_design: mRNA profiles of the leave midrib of CLas- and mock-inoculated rough lemon and sweet orange at week 0, 7, 17, and 34.

first: Qibin

last: Yu

first: Riccardo

last: Russo

first: Yi

last: Zhang

first: Xu

last: Wei

first: Yuanzhi

middle: Z

first: Paige

last: Holden

first: Fred

middle: G

last: Gmitter


title: YAP/TAZ-dependent expression of lncRNAs [A549]

summary: Body fluids from cancer patients are informative regarding disease conditions in tumor tissues. Thus, biomarkers detected by liquid biopsy can guide clinicians in designing personalized therapies and may serve as a proxy for treatment success. However, biomarkers that predict the existence of druggable target structures cannot be reliably defined in blood samples due to genetic tumor heterogeneity and presence of molecules from non-tumorous cells. To test the applicability of RNA signatures as liquid biopsy biomarkers, expression data from hepatocellular carcinoma (HCC) cells after inhibition of Hippo pathway effectors is investigated. We show that the oncogene yes-associated protein (YAP) transcriptionally controls a panel of long non-coding RNAs (lncRNAs), which support HCC progression via tumor cell-intrinsic mechanisms. These lncRNAs are detectable and overexpressed in YAPS127A transgenic mouse livers as well as in a subgroup of human HCC tissue and serum samples. Using a machine learning algorithm, a 4 gene lncRNA signature is defined that correlates with the nuclear abundance of YAP in HCC tissues (CYTOR, SNHG1, SNHG17, MIR4435-2HG). Importantly, YAP accumulation in human HCCs is significantly associated with lncRNA signature serum abundance in two independent patient cohorts. Evaluation of expression data and confirmatory experiments illustrate that the lncRNA signature is a robust predictor for YAP activity in other tumor types such as lung adenocarcinoma.     Liquid biopsy-based detection of lncRNAs in cancer patients is informative for the activity of transcriptional regulators and can serve as diagnostic tool that guides clinicians in the design of targeted therapies.

overall_design: 2 different siRNA combinations targeting YAP and TAZ with 4 biological replicates

first: Fabian

last: Rose

first: Kai

last: Breuhahn


title: YAP/TAZ-dependent expression of lncRNAs [HLF]


title: Loss of Glo2 alters the glucose metabolism in zebrafish

summary: Glyoxalase 2 is the second enzyme of the glyoxalase system, catalyzing the detoxification of methylglyoxal to D-lactate via SD-Lactoylglutathione. Recent studies have suggested Glo2 as a regulator of glycolysis, but the physiological functions of Glo2 in vivo and organ specific functions of the enzyme have not yet been evaluated. Therefore, a CRISPR/Cas9 knockout of glo2 in zebrafish was created and analyzed. Consistent with its function in methylglyoxal detoxification, SD-Lactoylglutathione, but not methylglyoxal accumulated in glo2-/- larvae, with no change in longevity. Adult glo2‑/- livers developed an impaired insulin signaling, indicated by a reduced hepatic P70-S6-kinase activation and reduced hepatic hexose concentration. In contrast, glo2-/- skeletal muscle remained functionally intact, compensating for the dysfunctional liver through increased glucose uptake, thereby maintaining euglycemia and preventing damage of the retina and kidney. In conclusion, the data identified Glo2 to fulfill similar but unique functions compared to Glo1 and established Glo2 as a novel target in diabetes research, regulating hepatic insulin signaling.

overall_design: A CRISPR based knockout of Glyoxalase 2 was created in zebrafish. The development of the fish was analyzed, as well as organ specific glucose metabolism in skeletal muscle and liver. Imaging studies of Retina, kidney, liver and skeletal muscle were conducted. RNA sequencing was performed on adult liver tissue of glo2+/+ and glo2-/- fish by BGI in collaboration with the NGS Core facility in Mannheim, University of Heidelberg.

first: Christoph

middle: T

last: Tabler

first: Jens

last: Kroll


title: BRB-seq data of murine intestinal organoids treated with 100ng/ml of Egf, Ereg or Nrg1 ligand for 24 h

city: Helsinki

first: Toni

last: Lemmetyinen

address: Haartmaninkatu 8

country: Finland

institute: University of Helsinki

summary: Regeneration of the intestinal epithelium is a dynamic process requiring a transient Yap-dependent reprogramming of the epithelium into a fetal-like state. Adjacent stroma, including subepithelial fibroblasts, are believed to coordinate the process, but mechanisms are not well understood. Here, we identify Neuregulin 1 (NRG1) and Epiregulin (EREG) as fibroblast-derived EGF ligands in colon and intestine which are induced during regeneration and capable of supporting the growth of the intestinal epithelium. While EREG stimulated intestinal organoid growth similarly to EGF, NRG1 increased de novo crypt formation. The goal of this experiment was to observe the differences in gene expression profile of stromal-derived EGF ligands EREG and NRG1 on intestinal organoids compared to traditional used EGF. Organoids were derived from intestinal crypts of a WT mice C57BL/6J. To exclude the size differences observed in long term cultures of EREG and NRG1, we first cultured the organoids for three days in normal ENR media, removed exogenous EGF for 24h and added EGF, EREG or NRG1 to the culture medium for 24 hours prior to the RNA isolation. NRG1 treated organoids acquired a fetal/regenerative transcriptome including activation of the Yap pathway and induction of epithelial EGF ligand Ereg and Amphiregulin (Areg) expression, highlighting the dynamic orchestration of the EGF signaling during regeneration.

overall_design: Total of 18 samples from two experiments. The intestinal crypts were isolated from two different WT mice for organoid culture. Intestinal crypts were treated first 3 days in ENR, then 24h without any EGF ligand and 24h with either EGF,EREG or NRG1. Three replicates for each ligand.

first: Emma

middle: W

last: Viitala

first: Eva

last: Domenech-Moreno

first: Saara

last: Ollila


title: Evolutionary and functional analysis of DNA methyltransferases in micro-eukaryotes: Insights from the model diatom Phaeodactylum tricornutum

city: Nantes

first: LEILA

last: TIRICHINE

address: 2, rue de la Houssinière, BP 92208, Nantes

department: BIOLOGY

institute: Nantes Universte, CNRS UMR 6286

type: Methylation profiling by high throughput sequencing


title: Engineered Antibody Cytokine Chimera Synergizes with DNA-Launched Nanoparticle Vaccines to Potentiate Suppression of Melanoma Proliferation in vivo

first: Priyankara

last: Wickramasinghe

address: 3601 Spruce Street

department: Bioinformatics

institute: The Wistar Institute

summary: Cancer immunotherapy has demonstrated great promise with the checkpoint inhibitors being approved as the first-line therapy for some types of cancer, and engineered cytokines like Neo2/15 being evaluated in many studies. In this work, we designed Antibody Cytokine Chimera (ACC) scaffolding cytokine mimetics with full-length tumor-specific antibody. We characterized the pharmacokinetic (PK) and pharmacodynamic (PD) properties of first-generation ACC TA99-Neo2/15, which synergized with DLnano-vaccines in suppressing in vivo melanoma proliferation but caused significant systemic cytokine activation. A novel second-generation ACC TA99-HL2-KOA1, with retained IL-2Rβ/γ binding and attenuated but preserved IL-2Rα, caused significantly lower systemic cytokine activation and non-inferior protection in murine tumor studies. Transcriptomic experiment demonstrated up-regulation of Type I interferon responsive genes, particularly ISG15, in dendritic cells, macrophages and monocytes following TA99-HL2-KOA1 treatment. Characterization of additional ACCs in combination with cancer vaccines will likely be an important area of research for treating melanoma and other types of cancer.

overall_design: 10x single cell on the tumor-infiltrating lymphocytes

first: Daniel

last: Kulp

first: David

middle: B

last: Weiner

first: Ziyang

last: Xu


title: Evolutionary and functional analysis of DNA methyltransferases in micro-eukaryotes: Insights from the model diatom Phaeodactylum tricornutum [Bisulfite-Seq]

summary: DNA methylation has been associated with transcriptional repression of transposable elements. Here we describe the first DNA methylation deficient cell line of a diatom by generating DNMT5:KOs in Phaeodactylum tricornutum. These data show the extend of the loss of DNA methylation in DNMT5:KOs compared to the reference strain. All DNA methylation is lost in DNMT5:KOs.

overall_design: 3 conditions - 2 independent DNMT5:KOs -> DNMT5:KO line M23 ; DNMT5:KO line M25 + 1 reference strain "WT" Pt18.6. 1 replicate per condition.

first: Leila

last: Tirichine

first: Ouardia

last: Ait-Mohamed

first: Antoine

last: Hoguin


title: RNAseq of U87 treated with bulk control/0.5mM 8-cpt-cAMP/1nM MS275 or a combination

city: Guangzhou

first: liu

last: xincheng

address: zhongshan Road 74 Street

institute: sysu

summary: Transcriptomics revealed that the combination of 8-cpt-cAMP and MS275 could maximize the glioma differentation compared to control or use either drug alone

overall_design: U87 cells were treated with bulk control/0.5mM 8-cpt-cAMP/1nM MS275 or a combination for 48 hours. Total RNA was extracted from 1×10^6 cells with TRIzol Reagent (Thermo Fisher Scientific) and was sent for RNA sequencing

first: Xincheng

last: Liu


title: OTUB1 catalytic-independently deubiquitinates TGFBI and mediates the angiogenesis in infantile hemangioma by regulating glycolysis

status: Public on Mar 14 2023

city: Jinan

first: Mingyang

last: Li

state: --- Select One ---

address: 324 Jingwu Road, Jinan 250021, China

institute: Shandong Provincial Hospital Affiliated to Shandong First Medical University

summary: To investigate the role of Ubiquitination in the progression of infantile hemangioma. And to investigate the role of OTUB1 in infantile hemangioma

overall_design: detect the mRNA level of deubiquitinating enzymes in infantile. And comparative gene expression profiling analysis of RNA-seq data for Hemangioma endothelial cells and its KD derivatives

first: Xuan

last: Wang

first: Enli

last: Yang

first: Yiming

last: Geng

first: Shengyun

last: Huang

first: Dongsheng

last: Zhang

first: Haiwei

last: Wu


title: Effects of Th17 cytokines on microglial responses and the blood-brain barrier following recurrent intranasal Group A Streptococcus infections

city: New York

first: Charlotte

middle: Remy

last: Wayne

state: NY

address: 650 W 168th Street, BB310

department: Neurology

institute: Columbia University Irving Medical Center

summary: Peripheral infections can result in neuropsychiatric changes in many contexts, including after recurrent Group A Streptococcus (GAS) infections in children. To explore the underlying mechanisms, here we used an intranasal inoculation model to analyze more than 100,000 cells from the mouse olfactory bulb (OB) and nasal lymphoid tissue by single-cell RNA sequencing (scRNAseq). Upon repeated GAS inoculations, endothelial cells responded by downregulating blood-brain barrier (BBB)-specific genes, and microglia upregulated interferon-response, chemokine and antigen-presentation genes. To determine whether specific Th17 cytokines play distinct roles in producing this phenotype, we administered a neutralizing antibody against interleukin 17A (IL-17A), which decreased microglial expression of interferon-response and chemokine genes, but unexpectedly exacerbated levels of antigen presentation markers. Another Th17 cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF) rescued a different subset of microglial transcripts.

overall_design: Olfactory bulbs were isolated from P60 mice following five repeated inoculations with either a suspension of GAS or with vehicle (PBS), and profiled at 18 hours post-inoculation. After perfusion with cold PBS, tissue was finely chopped, then processed with a papain-based neural dissociation kit to create a single-cell suspension. Following bead-based myelin removal, cells were stained for CD31, CD11b and live/dead and collected by FACS. For analysis of nasal lymphoid tissue, the nasal-associated lymphoid tissue (NALT) and olfactory epithelium were dissected and combined for analysis.

middle: R

first: Dritan

last: Agalliu

first: Vilas

last: Menon


title: Impact of total years of play and AT8 in CTE

city: Boston

first: Adam

last: Labadorf

state: MA

address: 72 East Concord Street E301

institute: Boston University Medical School

summary: Total years of play and phospho tau (AT8) is associated for developing Chronic Traumatic Encelopathy (CTE). Seeking to study molecular markers associated with total years of play and AT8 in athlete cohorts with severe CTE, mild CTE and repetitive head injury.

overall_design: 56 CTE severe, 13 CTE mild and 10 with repetitive head injury

first: Thor

last: Stein

first: Filisia

last: Agus


title: Investigation of the anti-tumor mechanism of tirabrutinib, a highly selective Bruton’s tyrosine kinase inhibitor, by transcriptomics

city: Shimamoto-cho, Mishima-gun

first: Jun

last: Murai

state: Osaka

address: 3-1-1 Sakurai

department: Drug Discovery Technology

institute: Ono Pharmaceutical Co., Ltd.

summary:
Tirabrutinib is a highly selective BTK inhibitor for treating hematological malignancies. This study analyzed the anti-tumor mechanism of tirabrutinib with microarray analysis of ABC-DLBCL xenograft model tumors.
The comprehensive gene expression analysis revealed that tirabrutinib downregulated IRF-4, MYC, and mTORC1 pathway-related genes in TMD8, suggesting the crucial roles of these pathways in ABC-DLBCL.

overall_design: Vehicle, 3 mg/kg or 10 mg/kg of tirabrutinib were administered to TMD8 xenograft mice twice daily for 21 days. Tumors were collected from 8-9 replicates per group and analyzed with microarrays.

first: Ryohei

last: Kozaki

first: Hikaru

last: Kato

first: Tomoko

last: Yasuhiro


title: Spatial analysis of microglial and vascular responses following recurrent intranasal Group A Streptococcus infections

city: Worcester

first: Travis

middle: E.

last: Faust

address: 366 Plantation Street

department: Neurobiology

institute: University of Massachusetts Chan Medical School

summary: Peripheral infections can result in neurocognitive changes in many contexts, including after recurrent Group A Streptococcus (GAS) infections in children. To explore the underlying mechanisms, here we used an intranasal inoculation model to analyze nearly 200,000 cells from the mouse olfactory bulb (OB) by multiplexed error-robust fluorescent in situ hybridization (MERFISH). Upon repeated GAS inoculations, endothelial cells (ECs) responded by downregulating blood-brain barrier and extracellular matrix genes. Microglia upregulated response to interferon and antigen presentation genes and downregulated homeostatic microglia genes. We determined that microglia with higher expression of Streptococcus-responsive genes were localized to the outer glomerular layer of the OB, possibly due to their proximity to infiltrating CD4 T cells. Expression of homeostatic genes was correspondingly high in the inner granular layer of the OB.

overall_design: Brains were isolated from P53 mice following five repeated inoculations with either a suspension of Group A Streptococcus or with vehicle (PBS), and profiled at 24 hours post-inoculation. After perfusion with cold PBS, brains were embedded in OCT for sectioning onto specialized coverslips. Coronal sections of the olfactory bulb (around bregma 4.28) were collected for analysis by MERFISH

first: Violeta

last: Durán-Laforet

first: Dorothy

middle: P

last: Schafer


city: Chongqing

first: Peng

last: Xie

address: 1st, Youyi Street

institute: The first affiliated hospital of Chongqing medical university

summary: We performed high-throughput snRNA-seq on hippocampus (Hip) and prefrontal lobe cortex (PFC) tissue in mice (Mus musculus) to identify cell-type specific differentially expressed genes. Mice were divided into GF, SPF and CGF group.

overall_design: 10X Genomics Chromium snRNA-seq was performed on nuclei extracted from Hip and PFC of 3 GF mice, 3 SPF mice and 3 CGF mice at 8 week old. Cell-types were identified by unsupervised clustering and diffrential gene expression was performed between cases and controls for each cell-type cluster. The library preparation was performed with the Chromium Singel Cell 3’ Reagent Kits v2. Paired-end sequencing was performed on theIllumina NovaSeq 6000. FastQ files were produced with Cellranger v2.1.0 mkfastq. Alignments and gene counts were generated with Cellranger v2.1.0 count.

first: Yu


title: FUS modulates the level of ribosomal RNA modifications by regulating a subset of snoRNA expression [RiboMeth-Seq]

city: Copenhagen N

first: Sophia

middle: Julia

last: Häfner

address: Ole Maaløes Vej 5

department: Biotechnology Research and Innovation Centre (BRIC)

country: Denmark

institute: University of Copenhagen

summary: FUS is a nucleocytoplasmic protein involved in many processes such as RNA transport, translation, and metabolism as well as genomic maintenance. FUS mutations are found in several neurodegenerative diseases. We find that FUS knockout (KO) and FUS mutation affects the expression of many C/D box snoRNAs, H/ACA box snoRNAs and scaRNAs. snoRNAs notably serve as adaptors for the 2'-O-methylation (2'-O-me) and pseudouridylation of ribosomal RNA (rRNA).

overall_design: We carried out small RNA sequencing and analysed the impact on ribosomal RNA 2'-O-methylation and pseudouridylation using RiboMeth-Seq and HydraPsiSeq in FUS knock-out model cell lines (HEK293T FUS KO cells and SH-SY5Y (neuroblastoma) FUS KO cells as well as SH-SY5Y cells with FUS R495X mutation).

first: Kishor

last: Gawade

first: Dorota

last: Raczyńska


title: The role of NOX4 in skin fibroblasts

city: Geneva

first: Sylvain

last: LEMEILLE

address: 1 rue Michel-Servet

department: Department of Pathology and Immunology

institute: University of Geneva Medical School

summary: Differentiation of fibroblasts to myofibroblasts is governed by the transforming growth factor beta (TGF-β) through a mechanism involving redox signaling and generation of reactive oxygen species (ROS). Myofibroblasts synthesize proteins of the extracellular matrix and display a contractile phenotype. Myofibroblasts are predominant contributors of  wound healing and several pathological states, including fibrotic diseases and cancer. Inhibition of the ROS-generating enzyme NADPH oxidase 4 (NOX4) has been proposed to mitigate fibroblast to myofibroblast differentiation and to offer a therapeutic option for the treatment of fibrotic diseases. In this study, we addressed the role of NOX4 in physiological wound healing and in TGF-β-induced myofibroblast differentiation. We explored the phenotypic changes induced by TGF-β in primary skin fibroblasts isolated from Nox4-deficient mice by immunofluorescence, Western blotting and RNA sequencing. Mice deficient for Cyba, the gene coding for p22phox, a key subunit of NOX4 were used for confirmatory experiments as well as human primary skin fibroblasts. In vivo, the wound healing was similar in wild-type and Nox4-deficient mice. In vitro, despite a strong upregulation following TGF-β treatment, Nox4 did not influence skin myofibroblast differentiation. Nevertheless, up-regulation of the mitochondrial protein Ucp2 and the stress-response protein Hddc3, as well as down-regulation of Islr were observed in Nox4-deficient fibroblasts. Altogether, we provide extensive evidence challenging a profibrotic role of NOX4 in skin fibroblasts and show that Nox4 regulates Ucp2 and Hddc3 expression, suggesting the presence of a so far undescribed redox crosstalk between NOX4 and redox homeostasis in fibroblasts.

overall_design: WT and NOX4 KO primary mouse skin fibroblasts were stimulated with 10ng/ml TGF-beta 2 in three biological replicates, total 12 samples were analyzed

first: Aleksandra

middle: M

last: Siedlar

first: Vincent

last: Jaquet

first: Ali

last: Modarressi

first: Karl-Heinz

last: Krause


title: The transcriptome profiling analysis of intestines and kidneys in conventionally raised (CV) and germ-free (GF) wild type zebrafish embryos

city: Shanghai

first: Hongji

last: Li

state: Shanghai

address: Building 6, School of Pharmacy, Shanghai Jiao Tong University, No.800 Dongchuan Road, Minhang District, Shanghai

department: School of Pharmacy

institute: Shanghai Jiao Tong University

summary:
To investigate how the zebrafish embryos respond to the absence of the microbiota, the intestinal tissue-associated and the kidney tissue-associated gene expressions were examined at 5 dpf and 7 dpf respectively. 32,948 cDNAs of the zebrafish genome assembly were annotated after reads mapping for further analysis. For the 5 dpf intestinal tissue samples, 948 genes (4% of the total number of genes) were differentially expressed, 371 genes were up-regulated and 577 genes were down-regulated in the GF group . For the 7 dpf kidney tissue samples, 697 genes (3% of the total number of genes) were differentially expressed, 341 genes were up-regulated and 356 genes were down-regulated in the GF group. The enrichment analysis showed that the immune and cytokine related pathways were affected by the GF treatment in the wildtype embryos (both in intestines at 5 dpf and in kidneys at 7 dpf).
To investigate how the transcriptome changes in the chd8-/- zebrafish embryos, the intestinal tissue-associated and the kidney tissue-associated gene expressions were examined at 5 dpf and 7 dpf respectively.

overall_design:
Intestinal mRNA profiles of conventionally raised(CV) and germ-free(GF) embryos at 5 dpf,and renal (the location of their hematopoietic tissue) mRNA profiles of CV and GF embryos at 7 dpf.

Analysis of  mRNA profiles of intestines at 5 dpf and renal (the location of their hematopoietic tissue) at 7 dpf in chd8-/- embryos, and comparing the data with those from the wildtype embryos.

first: Dan

last: Zhong

first: Haowei

last: Jiang


first: Adam

last: Labadorf

summary: CTE RNASeq association with APOE and TMEM. It is known that APOE is a risk factor of CTE. This study will look at differences between CTE stages - mild and severe, including associations with age, APOE and TMEM.

overall_design: 136 samples were analyzed, 58 control samples, 17 mild CTE samples, and 61 severe CTE samples

first: Thor

last: Stein


title: Evolutionary and functional analysis of DNA methyltransferases in micro-eukaryotes: Insights from the model diatom Phaeodactylum tricornutum [RNA-seq]

first: LEILA

last: TIRICHINE

summary: Loss of DNA methylation is traditionally associated with transcriptional up-regulation of transposable elements. Here we describe for the first time expression changes upon loss of DNA methylation in diatoms using Phaeodactylum tricornutum as a model species. The loss of DNA methylation was obtained by generation of DNMT5 KOs, a divergent DNMT with SNF-like domains. Expression analysis confirm the loss of DNA methylation is associated with de-repression of transposable elements in Phaeodactylum tricornutum with indirect effects on protein coding genes.

overall_design: 3 conditions - 2 independent DNMT5:KOs -> DNMT5:KO line M23 ; DNMT5:KO line M25 + 1 reference strain "WT" Pt18.6. 2 replicates per condition.

first: Leila

last: Tirichine

first: Ouardia

last: Ait-Mohamed

first: Antoine

last: Hoguin


title: Genetically distinct parallel projection populations from ventral hippocampus to prefrontal cortex

city: London

first: Andrew

middle: F

last: MacAskill

state: England

address: Gower St

department: Neuroscience, Physiology and Pharmacology

country: United Kingdom

institute: University College London

summary: To investigate differential RNA expression in two populations of ventral CA1 neurons that project to PFC arising from the superficial and deep layers of the radial axis

overall_design: Comparative gene expression profiling analysis of RNA-seq data for superficial vs deep vCA1 neurons

first: Candela

last: Sánchez-Bellot


title: A two-step in vivo CRISPR screen unveils pervasive RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a therapeutic target

status: Public on Mar 13 2023

city: Toronto

first: Kristin

last: Hope

address: 101 College St.

institute: University of Toronto

summary:
Acute myeloid leukemia (AML) progression and relapse is fueled by self-renewing leukemic stem cells (LSCs) whose molecular determinants have been difficult to discern from normal hematopoietic stem cells (HSCs) or to uncover in screening approaches focused on general AML cell properties.
We have identified a unique set of RNA binding proteins (RBPs) that are enriched in human AML LSCs but repressed in HSCs. Using an in vivo two step CRISPR-Cas9-mediated screening approach to specifically score for cancer stem cell functionality, we found 32 RBPs essential for LSC propagation and self- renewal in MLL-AF9 translocated AML. Using knockdown or small molecule approaches we show that targeting key hit RBP ELAVL1 impaired LSC-driven in vivo leukemic reconstitution and selectively depleted primitive AML cells vs. normal hematopoietic stem and progenitors. Importantly, knockdown of Elavl1 spared HSCs while significantly reducing LSC numbers across genetically diverse leukemias. Integrative RNA-seq and eCLIP-seq profiling revealed hematopoietic differentiation, RNA splicing and mitochondrial metabolism as key features defining the leukemic ELAVL1-mRNA interactome with the mitochondrial import protein TOMM34 being a direct ELAVL1-stabilized target whose inhibition impairs AML propagation.

overall_design: Human primary AML cells (AML #4) were infected in triplicate with shScramble or shELAVL1 lentivirus (pLKO.1) at an MOI of 50. At 48h, 100k 7AAD-EGFP+ transduced cells were FACS-sorted per sample and RNA was extracted using TRIzolLS.

first: Ana

last: Vujovic

first: He

last: Chen

first: Mark

middle: D

last: Minden


title: Effects of Th17 cytokines on transcriptome of primary microglial cultures in vitro

first: Charlotte

last: Wayne

summary: Peripheral infections can result in neuropsychiatric changes in many contexts, including after recurrent Group A Streptococcus (GAS) infections in children. In a mouse model of intranasal GAS inoculation, we have previously demonstrated in vivo that mice lacking Th17 cells, or the key Th17 cytokines interleukin 17A (IL-17A) or granulocyte-macrophage colony-stimulating factor (GM-CSF), have altered microglial responses. As an attempt to determine whether these cytokines have direct effects on microglia, we cultured primary microglia and incubated them with either interferon gamma (IFNg), IL-17A or GM-CSF for 24 hours, then collected RNA for bulk sequencing. Microglia treated with IFNg or GM-CSF displayed striking transcriptional shifts, including upregulation of many inflammatory genes. IL-17A treatment did not have a noticeable effect on the microglial transcriptome, likely due to the in vitro absence of IL-17A receptors, which are expressed by microglia in vivo.

overall_design: Mixed glial cultures were obtained from forebrains of P0-P2 pups. After 7-14 days, microglia were obtained using a shake off protocol and cultured in serum-free media. Cultures were incubated with 100 ng/mL of either IFNg, IL-17A or GM-CSF for 24 hours. Cells were then collected into TRIzol reagent for bulk sequencing.

first: Dritan

last: Agalliu

first: Philip

middle: A

last: Feinberg

first: Dorothy

last: Schaefer


title: Multigenerational DNA methylation responses to copper exposure in Daphnia: potential targets for epigenetic biomarkers?

city: Aveiro

first: Guilherme

middle: de Abreu

last: Jeremias

address: Campus Universitário de Santiago

department: Biology Department

country: Portugal

institute: University of Aveiro

summary: Epigenetic mechanisms are moving to the forefront of environmental sciences, especially because environmentally induced epigenetic changes shape biological responses to contamination of chemicals. Moreover, such marks can be inherited by subsequent generations through epigenetic transgenerational inheritance, thus having long-term implications. In this work, we focused on Daphnia as a representative of the potentially threatened freshwater biota aiming to gain an insight on the involvement of epigenetic mechanisms in their response, eventually adaptation, to metal contamination. Copper induced DNA methylation changes, their potential transgenerational inheritance, and life-history traits were assessed. Organisms differing in their history of past exposure to copper were exposed to toxic levels of the element for one-generation (F0) and then monitored for three subsequent unexposed generations (F1, F2, and F3). Overall, methylation changes targeted important genes for counteracting the effects of metals and oxidative stress, including dynein light chain, ribosomal kinase and nuclear fragile X mental retardation-interacting protein. Also, contrasting overall and gene-specific methylation responses were observed in organisms differing in their history of exposure to copper, with different transgenerational methylation responses being also identified among the two groups, without apparent life-history costs. Taken together, these results demonstrate the capacity of copper to promote epigenetic transgenerational inheritance in a specific manner concerning past history of exposure, thereby supporting the potential of developing and incorporating epigenetic biomarkers in risk assessment frameworks.

overall_design: Comparison of transgenerational - 4 generations; F0, F1, F2 and F3 - DNA methylation patterns among daphnids with different life-histories of exposure to copper: 15 sequenced samples, treatments corresponding to F0 non-naïve daphnids (acclimated and exposed in F0 to a copper enriched medium - 3 replicates), F0 naïve daphnids (acclimated in blank ASTM and exposed in F0 to a copper enriched medium - 3 replicates), F0 control daphnids (cultured in blank ASTM), F3 non-naïve dapnids (cultured in blank ASTM - 3 replicates) and F3 naïve daphnids (cultured in blank ASTM - 3 replicates).

first: Telma

last: Veloso

first: Fernando

last: Gonçalves

first: Filip

last: Van Nieuwerburgh

first: Joana

middle: L

last: Pereira

first: Jana

last: Asselman


title: Expression data from Empty control, PMM1 wildtype and R150H mutation clones in Cal-27 cells

city: Taipei

first: Wei-Min

last: Chang

state: Not Applicable

address: 128 Academia Road, Section 2, Nankang,

country: Taiwan

institute: Academia Sinica

summary: To exmaine the PMM1-relative tumor suppression transcriptome in OSCC cells, we preformed the Affymetrix Human Genome U133 Plus 2.0 Array with empty vector, PMM1-wildtype and R150H mutation in Cal-27 cells

overall_design: Total RNA was collected from empty vector, PMM1-wildtype or PMM1-R150H expression in SAS cells

first: W

first: L

last: Lee

first: M

last: Hsiao


title: Effect of Diaph1 knockout on gene expression of mouse livers on western diet for 16 weeks

first: Richard

last: Friedman

address: 1130 St. Nicholas Av

department: Medicine

institute: Columbia University Irving  Medical Center

summary: Diaph1 was knocked out in Ldlr-/- mice on western diet for 16 weeks and the effect of gene expression in liver was measured.

overall_design:
a. WT mice on chow (n=4)
b.  Ldlr-/- mice on Western diet (n=4)
c.   Ldlr-/-Diaph1-/- mice on Western diet  (n=4)

first: Laura

last: Senatus

first: Lander

last: Egana-Gorrono

first: Raquel

last: Lopez-Diez

first: Sonia

last: Bergaya

first: Juan

last: Gomez

first: Jaume

last: Amengual

first: Boyan

last: Zhou

first: Liang

last: Guo

first: Daniela

last: Fuller

first: Aloke

middle: V

last: Finn

first: Renu

last: Virmani

first: Huilin

last: Li

first: Paul

last: Gugger

first: Edward

last: Fisher

first: Ravichandran

last: Ramasamy

first: Ann

last: Schmidt


title: Dysregulated Genes, Biological pathways, and Gastrocnemius Muscle Fiber Types Associated With Progression of Peripheral Artery Disease: A preliminary analysis

city: New Delhi

first: Sunil

middle: Kumar

last: Saini

state: Delhi

address: Ansari Marg

department: Department of Biophysics

country: India

institute: AIIMS, New Delhi

summary: We report the differentially expressed genes among people with PAD Progression, PAD no progression compared to non-PAD.

overall_design: Gastrocnemius muscle biopsies were obtained from 7 people with PAD progression, 6 with PAD- and no progression, and 7 people without PAD matched by sex and race. This study characterized differential gene expression in gastrocnemius muscle biopsies from people with PAD compared to those without PAD. Differences in gene expression were compared between people with PAD who had progression of disease over six months versus those without progression of disease over six months.

first: Daniel

last: Pérez-Cremades

first: Henry

last: Cheng

first: Kate

last: Kosmac

first: Charlotte

last: Peterson

first: Lingyu

first: Lu

last: Tian

first: Terence

last: Ryan

first: Robert

last: Sufit

first: Luigi

last: Ferrucci

first: Mary

last: McDermott

first: Christiaan

last: Leeuwenburgh

first: Mark

last: Feinberg


title: The immune checkpoint molecule, B7-H4/VTCN1, guides differentiation and suppresses proinflammatory responses and MHC class I expression in an embryonic stem cell-derived  model of primitive human trophoblast II

city: Durham

first: Jie

last: Zhou

state: North Carolina

address: The Chesterfield Building 701 W. Main Street, Suite 510

department: OBGYN

institute: Duke University

summary: VTCN1/B7-H4 is expressed in human embryonic stem cells (hESC) to an in vitro model of primitive trophoblast (TB) and first trimester but not term human placenta and that primitive trophoblast may be uniquely susceptible to certain pathogens.

overall_design: RNA-seq was performed on hESC derived trophoblast cells at 24, 48 and 72 h after VTCN1/B7H4 KD to better define pathways regulated by VTCN1/B7H4.

first: Ying

last: Qu

first: Danny

last: Schust


title: The immune checkpoint molecule, B7-H4/VTCN1, guides differentiation and suppresses proinflammatory responses and MHC class I expression in an embryonic stem cell-derived  model of primitive human trophoblast III


title: Cell-specific vulnerability to metabolic failure: the crucial role of parvalbumin expressing neurons in creatine transporter deficiency

city: San Juan de Alicante

first: Ángel

last: Márquez Galera

address: Av. Santiago Ramón y Cajal, s/n

country: Spain

institute: Instituto de Neurociencias

summary: Mutations in the solute carrier family 6-member 8 (Slc6a8) gene, encoding the protein responsible for cellular creatine (Cr) uptake, cause Creatine Transporter Deficiency (CTD), an X-linked neurometabolic disorder presenting with intellectual disability, autistic-like features, and epilepsy. The pathological determinants of CTD are still poorly understood, hindering the development of therapies. In this study, we generated an extensive transcriptomic profile of CTD showing that Cr deficiency causes perturbations of gene expression in excitatory neurons, inhibitory cells, and oligodendrocytes which result in remodeling of circuit excitability and synaptic wiring. We also identified specific alterations of parvalbumin-expressing (PV+) interneurons, exhibiting a reduction in cellular and synaptic density, and a hypofunctional electrophysiological phenotype. Mice lacking Slc6a8 only in PV+ interneurons recapitulated numerous CTD features, including cognitive deterioration, impaired cortical processing and hyperexcitability of brain circuits, demonstrating that Cr deficit in PV+ interneurons is sufficient to determine the neurological phenotype of CTD. Moreover, a pharmacological treatment targeted to restore the efficiency of PV+ synapses significantly improved cortical activity in Slc6a8 knock-out animals. Altogether, these data demonstrate that Slc6a8 is critical for the normal function of PV+ interneurons and that impairment of these cells is central in the disease pathogenesis, suggesting a novel therapeutic venue for CTD.

overall_design: snRNA-seq analysis of control and CrT-KO cells from the cerebral cortex.

first: Angel

last: Marquez-Galera

first: Carmen

last: Navarrón

first: Jose

last: Lopez-Atalaya

first: Laura

last: Baroncelli


title: Expression data from FAS knockout by CRISPR/Cas9 system in SAS cells

first: Wei-Min

last: Chang

summary: To exmaine the apoptosis independent function of FAS knockout transcriptome in OSCC cells, we preformed the Affymetrix Human Genome U133 Plus 2.0 Array with CRISPR/Cas9 control or FAS knockout in SAS cells

overall_design: Total RNA was collected from CRISPR/Cas9 control or FAS knockout expression in SAS cells

first: W

first: M

last: Hsiao


title: The immune checkpoint molecule, B7-H4/VTCN1, guides differentiation and suppresses proinflammatory responses and MHC class I expression in an embryonic stem cell-derived  model of primitive human trophoblast I

overall_design: RNA-seq was performed on hESC derived trophoblast cells at 24, 48 and 72 h after VTCN1/B7H4 KD to better define pathways regulated by VTCN1/B7H4. GSM7091566 has no raw data.


title: The dietary sweetener sucralose is a negative modulator of T-cell- mediated responses

first: Fabio

last: Zani

address: 1 Midland Rd,

institute: The Francis Crick Institute

summary: Sucralose is an artificial sweetener commonly used in food and drinks to increase food palatability and control total calorie content. While it is approved for human consumption by both the EFSA and the FDA, recent reports have questioned the safety of long-term consumption of s. in this study, we show that high doses of sucralose affect immune responses in different mouse models of autoimmunity, infection, and cancer. Similarly, sucralose impedes proper t cell proliferation and polarization in vitro. Mechanistically, sucralose dampens signals downstream the TCR resulting in decrease calcium flux upon TCR activation.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for primary murine T cells on either TCM, sucralose or saccharin exposed for 24 and 48 hours.

first: Karen

middle: H

last: Vousden

first: Julianna

last: Blagih

first: Pablo

last: Soro-Barrio


title: UNC0621, a novel small-molecule modulator of Ewing sarcoma chromatin accessibility, interacts with an RNA-associated macromolecular complex and influences RNA splicing

city: Chapel Hill

first: Ian

middle: J

last: Davis

state: NC

address: 450 West Drive

department: Genetics

institute: University of North Carolina at Chapel Hill

summary: Cancer genotyping projects have identified frequent mutations in epigenetic regulators. Ewing sarcoma is a pediatric tumor characterized by the critical translocation-associated fusion oncoprotein EWS::FLI and a low mutational burden. EWS::FLI targets characteristic genetic loci where it mediates aberrant chromatin and the establishment of de novo enhancers. Ewing sarcoma thus provides a model to interrogate mechanisms underlying chromatin dysregulation in tumorigenesis. Previously, we developed a high-throughput chromatin-based screening platform and demonstrated its utility in identifying small molecules capable of altering chromatin accessibility at EWS::FLI-bound loci. Here, we report the identification of UNC0621, a molecule with previously uncharacterized mechanism of action, as a small molecule modulator of chromatin state at sites of aberrant chromatin accessibility at EWS::FLI-bound loci. UNC0621 suppresses cellular proliferation of Ewing sarcoma cell lines by cell cycle arrest. Proteomic studies demonstrate that UNC0621 associates with RNA binding and splicing proteins as well as chromatin regulatory proteins. Surprisingly, interactions with chromatin and many RNA-binding proteins, including EWS::FLI fusion protein and its known interactors, were RNA-independent. Our findings suggest that UNC0621 affects EWS::FLI-mediated chromatin activity by interacting with and altering the activity of RNA splicing machinery and chromatin modulating factors. Genetic modulation of these proteins similarly inhibits proliferation and alters chromatin in Ewing sarcoma cells. The use of an oncogene-associated chromatin signature as a target represents a novel strategy to directly screen for modulators of epigenetic machinery and provides a framework for using chromatin-based assays for future therapeutic discovery efforts.

overall_design: Comparative gene expression and alternative splicing profiling analysis of RNA-seq data for EWS894 cells treated for 16 hours with 5 μM UNC0621 or vehicle control (DMSO).

first: Tamara

last: Vital


title: The impact of PD-1 antibody or G-CSF antibody on the immune system and the hematopoiesis of TNBC mice

last: Xie

address: 725 South Wanping Road, Shanghai

department: School of public Health

institute: Shanghai University of Traditional Chinese Medicine

summary: Triple negative breast cancer (TNBC) is the most intractable subtype of breast cancer. Inhibitors of programmed cell death protein-1 (PD-1) or its ligand PD-L1 have been considered as promising treatment for TNBC patients. However, only a minor subset of TNBC patients benefits from the monotherapy. An analysis of how PD-1/PD-L1 blockage affect immune activities in TNBC tumor-bearing mice could provide insights for it limitation. G-CSF was known to be highly elevated in TNBC cells, and affecting hematopoiesis and the immune system. Spleen is an immune organ and with extramedullary hematopoiesis in TNBC mice. Here we analyzed splenocyte gene expressions changed by administration of either PD-1 antibody or G-CSF antibody in both 4T1 tumor bearing mice and non-tumor control mice. TNBC tumor significantly changed gene expressions in splenocytes, which is consistent with a significant change in splenocyte composition. These genes were enriched in immune related pathways. Anti-PD-1 antibody treatment had limited impact on spleen immune cells composition and splenocyte gene expressions. The most affected genes were enriched in metabolism and extracellular matrix related pathways. Anti-G-CSF antibody treatment had higher impact on the splenocyte gene expression profile, making it more like the gene expression profile in the non-tumor control mice.

overall_design: Mammary pads of Balb/c female mice were orthotopically implanted with 4T1 cells on day 0 and mice were administered with G-CSF antibody, PD-1 antibody, or anti-IgG dissolved in PBS through intraperitoneal on day 18, day 21, day 24 at a dose of 10 mg/kg. At the endpoint of day 29, We collected splenocytes from mice bearing 4T1 tumor or not and performed RNA-seq by using Illumina NovaSpeq 6000 platform.

first: Mei

last: Ma

first: Xiaojuan

last: Yang

first: Feifei

last: Li

first: Meiling

last: Chu

first: Xiaodan

last: Hong

first: Lixia

last: Pei

first: Liyi

last: Ye

first: Ziwei

last: Jiang

first: Sheng

last: Liu

first: Hongmei

last: Cui


title: Murine N4 Ube3am-/p+ hippocampus:  Antagomir-134 vs Scramble (control)

city: Dublin

first: Albert

last: Sanfeliu

address: 123 St. Stephen's Green

country: Ireland

institute: Royal College of Surgeons in Ireland

summary: Transcriptional profiling of N4 Ube3am-/p+ mice ipsilateral hippocampi at 24h after the last audiogenic stimulus (at postnatal day 27; out of three stimulus) of mice pre-treated with either scramble or antagomir-134 (Ant-134; 0.5 nmol; ICV).

overall_design: Two-condition experiment, Scramble (control) vs Antagomir-134. Biological replicates: 4 scramble (controls) and 5 antagomir-134. Each biological replicate is the homogeneate of one ipsilateral hippocampus of the respective treated mouse. P21 mice received an ICV injection of scramble or Ant-134. At P22 24 hours later, they were subjected to an audiogenic seizure. This seizure was repeated at P24 and P26. At 24h later, brains were removed and microdissected for transcriptome analysis.

first: David

last: Henshall

first: Cristina

last: Ruedell Reschke

first: Aoife

last: Campbell

first: Ngoc

last: Thanh Nguyen


title: Steroidogenic factor 1 regulates transcription of the inhibin B co-receptor in pituitary gonadotrope cells

city: Los Angeles

first: Michel

last: Zamojski

state: California

address: 8700 Beverly Boulevard

department: Regenerative Medicine Institute

country: USA

institute: Cedars-Sinai Medical Center

summary: The inhibins control reproduction by suppressing follicle-stimulating hormone synthesis by pituitary gonadotrope cells. The recently discovered inhibin B co-receptor mediating this inhibition, TGFBR3L, is selectively and highly expressed in gonadotropes in both mice and humans. We sought to characterize mechanisms controlling cell-specific Tgfbr3l/TGFBR3L transcription. We identified two steroidogenic factor 1 (SF-1) cis-elements in the proximal Tgfbr3l promoter in mice.  Using single-nucleus ATAC-seq we find that gonadotrope-specific SF-1 (Nr5a1) knockout mice, which exhibit hypogonadotropic hypogonadism, display, contrary to controls, closed chromatin in the promoter region of theTgfbr3l gene in gonadotropes. These, and other, data collectively indicate that SF-1 directly regulates Tgfbr3l/TGFBR3L transcription, contributing to gonadotrope-specific expression of the gene.

overall_design: Chromatin accessibility profiles of adult mouse SF-1 control and cKO pituitary gonadotrope cells were generated using Chromium Single Cell ATAC from 10X Genomics and Illumina sequencing.

first: Yeu-Farn

last: Lin

first: Gauthier

last: Schang

first: Evan

last: Buddle

first: Hailey

last: Schultz

first: Thea

last: Willis

first: Frederique

last: Ruf-Zamojski

first: Natalia

last: Mendelev

first: Ulrich

last: Boehm

first: Stuart

middle: C

last: Sealfon

first: Cynthia

last: Andoniadou

first: Daniel

last: Bernard


title: Genome-wide analysis of miRNAs suggests a differential microRNAs signature associated with Normal and Diabetic limbal human corneas

first: Vasu

last: Punj

state: CA

address: Biggy Street

institute: USC

summary: Small non-coding RNAs, in  particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. Using deep sequencing analysis, we investigated miRNA expression profiles in central and limbal regions of normal and diabetic human corneas. We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type I (T1DM/IDDM) and type II (T2DM/NIDDM). Some miRNAs such as miR-10b that was upregulated in limbus vs. central corneas and in diabetic vs. normal limbus also showed significant increase in T1DM vs. T2DM limbus

overall_design: To study differntial expresssion profile of miRNAs in Normal and diabetic  limbus and central corneas.

first: Mangesh

last: Kulkarni

first: Aleksandra

last: Leszczynska

first: Gabbie

last: Wei

first: Michael

last: Winkler

first: Jie

last: Tang

first: Vincent

last: Funari

last: Deng

first: Zhenqiu

last: Liu

first: Sophie

middle: X

first: Alexander

last: Ljubimov

first: Mehrnoosh

last: Saghizadeh


title: Longitudinal transcriptomic analysis of mouse sciatic nerve reveals pathways associated with age-related muscle pathology

city: New York

first: Diane

middle: Berengere

last: Re

state: New York

address: 630 West 168th Street

department: Environmental Health Sciences

institute: Columbia University

summary:
Our objective was to identify early changes in gene expression related to the development of sarcopenia via transcriptomic profiling of aging sciatic nerves in vivo. Sciatic nerve mRNA profiles of C57BL/6JN mice aged 5 (n = 6), 18 (n = 5), 21 (n = 6), and 24 months (n = 5) old were generated by RNA sequencing using an Illumina HiSeq4000. The sequence reads that passed quality filters were mapped to the mouse reference genome using STAR and featureCounts. Differential expression analysis was performed using DESeq2. Differentially expressed genes were validated using quantitative reverse transcription PCR (qRT-PCR) using SYBR Green assays.

We detected 51 significant differentially expressed genes in sciatic nerve of 18-month-old mice compared to 5-month-old mice. These genes were associated with the AMPK signaling pathway, biosynthesis and metabolic pathways, and circadian rhythm. These early molecular changes shed a new light on biological processes in peripheral nerve that may be implicated in sarcopenia initiation and pathogenesis. Future studies are warranted to confirm the disease modifying and/or biomarker potential of the key changes we report here.

overall_design: Sciatic nerve mRNA profiles compared between C57BL/6JN mice aged 5 (n = 6), 18 (n = 5), 21 (n = 6), and 24 months (n = 5).

first: Nicole

last: Comfort

middle: B


title: Hepatic stellate cell-derived oxylipin activates leukotrine B4 receptor 2-β-catenin-YAP1 cascade to promote liver tumorigenesis

first: Hidekazu

last: Tsukamoto

address: 1333 San Pablo Street MMR414

department: Pathology

institute: University of Southern California

summary: Hepatocellular carcinoma (HCC) is the 3rd most deadly malignancy due to limited therapeutic options.  Activated hepatic stellate cells (aHSC) give rise to major cancer-associated myofibroblasts in HCC and considered a potential therapeutic target. Here we report that selective ablation of stearoyl CoA desaturase (Scd) in aHSC globally suppressed nuclear β-catenin (CTNNB1) and YAP1 in the tumor microenvironment and prevented liver tumorigenesis in mice. Tumor suppression was associated with reduced leukotriene B4 receptor 2 (LTB4R2) and its high affinity oxylipin ligand, 12-hydroxyheptadecatrienoic acid (12-HHTrE).  LTB4R2 ablation and pharmacological inhibition, recapitulated CTNNB1 and YAP1 inactivation and tumor suppression in vivo and in culture. Single cell RNA sequencing identified a unique subset of tumor-associated aHSC expressing Cyp1b1 but no other 12-HHTrE biosynthetic genes.  aHSC released 12-HHTrE in a manner dependent on SCD and their conditioned medium reproduced the LTB4R2-mediated tumor-promoting effects of 12-HHTrE in HCC cells.  CYP1B1-expressing aHSC were detected in proximity of LTB4R2-positive cancer cells in human HCC and the growth of patient HCC organoids was blunted by LTB4R2 antagonism or knockdown.  Collectively, our research identified a novel aHSC-initiated 12-HHTrE-LTB4R2-CTNNB-YAP1 pathway as a potential HCC therapeutic target.

overall_design: Scd2f/f;Col1a1-Cre vs. Scd2f/f mice subjected to the hepatic carcinogen DEN and fed Western alcohol diet

first: Sonal

last: Sinha

first: Satoka

last: Aizawa

first: Yibu

last: Chen

first: Meng

last: Li

last: Karin


title: Differential transcriptome responses in human THP-1 macrophages following exposure to T98G and LN-18 human glioblastoma secretions: a simplified bioinformatics approach to understanding patient-glioma-specific effects on tumor-associated macrophages

city: Clemson

first: Micaela

last: Scobie

state: SC

address: Clemson University

department: Biological Sciences

institute: Clemson University

summary:
We first describe a methods approach to differentiating THP-1 monocytes to macrophages with M0-like genotype.
Then we describe the effect that different glioblastoma supernatants have on the gene expression profiles of macrophages, suggesting gliomas should be considered different diseases.

overall_design: Differential gene expression analysis of RNA-seq data for THP-1 monocytes, differentiated macrophages, and those same macrophages treated with different glioma supernatants.

middle: R

first: Charles

last: Rice


title: MMP14 cleaves PTH1R in the chondrocyte derived osteoblast lineage, curbing signaling intensity for proper bone anabolism

city: Pok Fu Lam

first: Peikai

address: Sassoon Road 5

department: Faculty of Medicine

country: Hong Kong

institute: The University of Hong Kong

summary: Bone homeostasis is regulated by hormones such as parathyroid hormone (PTH). While PTH can stimulate osteo-progenitor expansion and bone synthesis, how the PTH-signaling intensity in progenitors is controlled is unclear. Endochondral bone osteoblasts arise from perichondrium-derived osteoprogenitors and hypertrophic chondrocytes (HC). We found, via single-cell transcriptomics, HC descendent cells activate membrane-type 1 metalloproteinase 14 (MMP14) and the PTH pathway as they transition to osteoblasts in neonatal and adult mice. Unlike Mmp14 global knockouts, postnatal day 10 (p10) HC lineage-specific Mmp14 null mutants (Mmp14ΔHC) produce more bone. Mechanistically, MMP14 cleaves the extracellular domain of PTH1R, dampening PTH signaling, and  consistent with the implied regulatory role,  in Mmp14ΔHC mutants, PTH signaling is enhanced. We found HC-derived osteoblasts contribute ~50% of osteogenesis promoted by treatment with PTH 1-34 and this response was amplified in Mmp14ΔHC. MMP14 control of PTH signaling likely applies also to both HC- and non-HC-derived osteoblasts because their transcriptomes are highly similar. Our study identifies a novel paradigm of MMP14 activity-mediated modulation of PTH signaling in the osteoblast lineage, contributing new insights into bone metabolism with therapeutic significance for bone-wasting diseases.

overall_design: We perforemed single-cell transcriptomics on mouse tibia at week 8 (P56) post natal, with cells pooled from three mice. All the mice had the genotype of MMP14 F/+; COL10A1cre; R26-tdT; Col1a1-2.3-GFP. The raw data was aligned to mouse genome mm10, and a reference of exogenenous RNAs, including GFP, tdTomato, and WPRE.

first: Anna

last: Yu

first: Kathryn

middle: S

last: Cheah


title: A genome-wide CRISPR activation screening identified that OCT4 and SOX2 co-regulate SIA-cIgG expression

city: Nanjing

first: Xinmei

last: Huang

address: Zhongshan Road

institute: Nanjing Drum Tower Hospital

summary: Misplaced IgG expression in cancer cells has been implicated in exacerbated malignancy and poor clinical prognosis. Accumulating evidence indicate that a non-conventional sialylation modification is critical for the function of cancer-derived IgG, rendering the name sialylated cancer IgG (SIA-cIgG). However, our knowledge remains rudimentary about the regulatory mechanism that controls the expression and function of SIA-cIgG. To investigate the regulatory mechanisms of SIA-cIgG expression in lung cancer stem cells, we performed a genome-wide CRISPR activation screen in NCI-H520 cells by expressing a lentiviral library of 70,290 CRISPR-activating gRNAs targeting 23,430 genes. We investigated that the stemness-related transcriptional factors OCT4 (Gene name: POU5F1) and SOX2 were both among the top genes enriched in SIA-cIgG high cells, suggesting that OCT4 and SOX2 may serve as key factors promoting SIA-cIgG expression.

overall_design: A genome-wide CRISPR activation sgRNA library was transduced in NCI-H520 cells and screened by FACS sorting of SIA-cIgG high and SIA-cIgG low cells before sequencing to determine sgRNA distribution.

first: Shenghua

last: Zhang

first: Jingshu

last: Tang

first: Liang

first: Xiaoyan

last: Qiu


title: A self-propagating c-Met-SOX2 axis drives cancer-derived IgG signaling that promotes lung cancer cell stemness [RNA-seq]

summary: Misplaced IgG expression in cancer cells has been implicated in exacerbated malignancy and poor clinical prognosis. Accumulating evidence indicate that a non-conventional sialylation modification is critical for the function of cancer-derived IgG, rendering the name sialylated cancer IgG (SIA-cIgG). However, our knowledge remains rudimentary about the functional role of SIA-cIgG in lung stemness maintenance. To investigate the mechanisms of SIA-cIgG in the regulation of lung stemness maintenance, we performed RNA-seq using established NCI-H520 cell lines sorted by FACS to have high or low expression of SIA-cIgG. This revealed that genes upregulated in SIA-cIgG high cells were associated with stem cell proliferation and maintenance.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for SIA-cIgG high/low NCI-H520 cells.


title: Single cell transcriptomic and VDJ sequencing of antibody-secreting cells (ASCs) from the bone marrow, spleen and thymus of young (3 months old) female and male mice.

city: Saskatoon

first: Peter

middle: Dion

last: Pioli

state: SK

address: 107 Wiggins Rd

department: Biochemistry, Microbiology and Immunology

institute: University of Saskatchewan

summary: Purpose: To examine the trasncriptional and VDJ repertoire differences that exist in ASCs based on factors such as tissue localiation and sex.

overall_design: ASCs were flow cytometrically purified from the bone marrow, spleen and thymus of young (3 months old) female and male Prdm1-eYFP mice. For each sort, pools of 3 mice were used. ASCs were sorted as B220+/- CD138HI IgD- CD90.2- Prdm1-eYFP+. Single cell gene expression and VDJ libraries were constructed via 10x Genomics technology.


title: RNA-seq and genome-wide CRISPR activation screening

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

overall_design: Refer to individual Series


title: Transcription shapes 3D chromatin organization by interacting with loop-extruding cohesin complexes

city: Vienna

first: Roman

last: Stocsits

address: Campus-Vienna-Biocenter 1

country: Austria

institute: IMP - Research Institute of Molecular Pathology

summary: Cohesin organizes mammalian interphase chromosomes by reeling chromatin fibers into dynamic loops. "Loop extrusion" is obstructed when cohesin encounters a properly oriented CTCF protein. It has been proposed that transcription relocalizes or interferes with cohesin, and that active transcription start sites function as cohesin loading sites, but how these effects, and transcription in general, shape chromatin is unknown. To determine whether transcription can modulate loop extrusion, we studied cells in which the primary extrusion barriers could be removed by CTCF depletion and cohesin’s residence time and abundance on chromatin could be increased by Wapl knockout. We found evidence that transcription directly interacts with loop extrusion through a novel "moving barrier" mechanism, but not by loading cohesin at active promoters. Hi-C experiments showed intricate, cohesin-dependent genomic contact patterns near actively transcribed genes, and in CTCF-Wapl double knockout (DKO) cells, genomic contacts were enriched between sites of transcription-driven cohesin localization ("cohesin islands"). Similar patterns also emerged in polymer simulations in which transcribing RNA polymerases (RNAPs) acted as "moving barriers" by impeding, slowing, or pushing loop-extruding cohesins. The model predicts that cohesin does not load preferentially at promoters and instead accumulates at TSSs due to the barrier function of RNAPs. We tested this prediction by new ChIP-seq experiments, which revealed that the "cohesin loader" Nipbl co-localizes with cohesin, but, unlike in previous reports, Nipbl did not accumulate at active promoters. We propose that RNAP acts as a new type of barrier to loop extrusion that, unlike CTCF, is not stationary in its precise genomic position, but is itself dynamically translocating and relocalizes cohesin along DNA. In this way, loop extrusion could enable translocating RNAPs to maintain contacts with distal regulatory elements, allowing transcriptional activity to shape genomic functional organization.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design:
ChIP-Seq; All antibodies used in this study are listed in Online Methods section 'Antibodies and Reagents'. 2 replicates for every experiment (except for suppl. PolII tracks)
Hi-C data were mapped to 1 kb resolution coolers using the mm9 genome assembly and distiller pipeline.

first: Edward

last: Banigan

first: Wen

first: Aafke

last: van den Berg

first: Gordana

last: Wutz

first: Jan-Michael

last: Peters

first: Leonid

last: Mirny


title: Anti-cancer action of imidazopyridine BAG1 compounds in steriod hormone receptor-positive breast and prostate cancer

city: Nantes

first: Victor

last: GOURAIN

address: 30 Bd Jean Monnet

country: France

institute: Centre de recherche en transplantation et immunologie

summary: Transcriptomics analyses to study the effect of the imidazopyridine X15695 on proliferation of estrogen receptor positive (ER+) breast and androgen receptor positive (AR+) prostate cancer cells. The effect of X15695 was analyzed on vehicle or steroid hormone-treated breast and prostate cancer cells.

overall_design: RNA-seq was carried out with breast cancer (MCF-7, T47D) and prostate cancer (LNCaP) cells treated with hormone and the compound X15695. MCF-7 and T47D cells were treated with 10 nM 17-β-estradiol (E2) or dihydrotestosterone (DHT) for the LNCaP cells, 1 µM X15695 (for the MCF-7 and T47D cells) or 5 µM for LNCaP cells and X15695 together with E2 or DHT for the breast or prostate cancer cells.

first: Andrew

last: Cato

last: Gourain

first: Mengwu

last: Pan


title: Maternal diet alters long-term innate immune cell memory in fetal and juvenile hematopoietic stem and progenitor cells in nonhuman primate offspring

city: Oklahoma city

first: Philip

last: ONeill

state: OK

address: 945 9th st

institute: OUHSC

summary: Maternal overnutrition increases inflammatory and metabolic disease risk in postnatal offspring. This constitutes a major public health concern due to the increasing prevalence of these diseases yet the mechanisms remain unclear. Here, using nonhuman primate models, we show that maternal Western-style diet (mWSD) exposure is associated with persistent pro-inflammatory phenotypes at the transcriptional, metabolic, and functional levels in bone marrow-derived macrophages (BMDMs) from 3-year-old juvenile offspring and in hematopoietic stem and progenitor cells (HSPCs) from fetal and juvenile bone marrow and fetal liver. mWSD exposure is also associated with increased oleic acid in fetal and juvenile bone marrow and fetal liver. ATAC-seq profiling of HSPCs and BMDMs from mWSD-exposed juveniles supports a model in which HSPCs transmit pro-inflammatory memory to myeloid cells beginning in utero. These findings demonstrate that maternal diet alters long-term immune cell developmental programming in HSPCs with proposed consequences for chronic diseases featuring altered immune/inflammatory activation across the lifespan.

overall_design: 3-year-old (3YO) juvenile Japanese macaque offspring were exposed to maternal control diet (mCD) or maternal western-style diet (mWSD) during gestation and lactation.  At weaning, offspring were fed a mCD. Bulk RNA-seq was run for fetal and juvenile column-enriched bone marrow CD34+ cells (HSPCs) for differential gene expression.  Chromatin changes assessed via ATAC-seq for genes in BMDM and HSPCs from mWSD and mCD for juveniles. Treatment/conditions represent: mCD= maternal CD (fetuses), mWSD = maternal WSD (fetuses), mCD/mCD = maternal CD and postweaning CD juveniles,  and mWSD/mCD = maternal WSD and postweaning CD juveniles.

first: Jacob

middle: E

last: Friedman

first: Michael

last: Nash

first: Stephanie

last: Wesolowski

first: Kenneth

last: Jones

last: O'Neill


title: aCGH of a pediatric acute lymphoblastic leukemia cohort

city: Utrecht

first: Judith

middle: M.

last: Boer

address: Heidelberglaan 25

country: Netherlands

institute: Prinses Maxima Centrum

type: Genome variation profiling by genome tiling array

summary: Array comparative genomic hybridization data for 372 diagnosis pediatric acute lymphoblastic leukemia samples.

overall_design: A large aCGH cohort with data from 372 diagnosis pediatric acute lymphoblastic leukemia samples was established. All samples are also included in GSE87070, using the same sample name.

first: Monique

last: den Boer

middle: M


title: miRNA profiling in human nonsteatotic and NAFLD livers

status: Public on Mar 12 2023

city: Guangzhou

first: Sijia

last: Liang

address: 74 Zhongshan 2 Rd

department: Pharmacology

country: China

institute: Sun Yat-Sen University

summary: To investigate the function of miRNAs in liver, we obtained liver tissues from nonsteatotic individuals and fatty livers from patients with nonalcoholic fatty liver disease (NAFLD). Patients due to excessive alcohol consumption, autoimmune liver disease, viral hepatitis and diabetes were excluded. Nonsteatotic livers were collected from the normal region of the livers from donors who received liver resection due to liver hemangioma, and were defined as those with NASH activity scores of 0  We then performed miRNA sequencing using livers from two NAFLD patients and two nonsteatotic individuals.

overall_design: Comparative miRNA level profiling analysis of liver tissues from human non-steatotic and NAFLD livers.

first: Si-Jia


title: EGFR activity addiction facilitates anti-ERBB based combination treatment of squamous bladder cancer

city: Aachen

first: Bernd

last: Denecke

state: NRW

address: Pauwelsstrasse 30

department: IZKF Aachen

country: Germany

institute: RWTH Aachen University

summary: Recent findings suggested a benefit of anti-EGFR therapy for basal-like muscle invasive bladder cancer (MIBC). However, impact on bladder cancer with substantial squamous differentiated (Sq-BLCA) and especially pure squamous cell carcinoma (SCC) remains unknown. Therefore, we comprehensively characterized pure and mixed Sq-BLCA (n=125) on genetic and protein expression level, and performed functional pathway and drug-response analyses with cell line models and isolated primary SCC (p-SCC) cells of the human urinary bladder. We identified abundant EGFR expression in 95% of Sq-BLCA without evidence for activating EGFR mutations. Both SCaBER and p-SCC cells were sensitive to EGFR tyrosine kinase inhibitors (TKIs: erlotinib and gefitinib). Combined treatment with anti-EGFR TKIs and varying chemotherapeutics led to a concentration-dependent synergism in SCC cells according to the Chou-Talalay method. In addition, siRNA knockdown of EGFR impaired SCaBER viability suggesting a putative ‘‘Achilles heel’’ of Sq-BLCA. The observed effects seem Sq-BLCA-specific since non-basal urothelial cancer cells were characterized by poor TKI sensitivity associated with a short-term feedback response by upregulating EGFR and ERBB3 expression. Hence, our findings give novel insights into a crucial, Sq-BLCA-specific role of the ERBB signaling pathway proposing improved effectiveness of combined anti-EGFR and chemotherapeutic regimens in squamous bladder cancers with wild-type EGFR-overexpression.

overall_design: Tumor tissue of an individual diagnosed with a pure SCC was obtained from the RWTH centralized biomaterial bank (RWTH cBMB) for SCC-tumor cell (p-SCC) isolation. Primary cells derived from pure SCC (p-SCC) tissue were established as a cell culture ex vivo model. p-SCC cells (n=1) were characterized and compared with the original tumor tissue (n=1) by whole transcriptomic analysis. SCaBER (n=1) and J82 cell lines (n=1) served as squamous and urothelial-like controls.

last: Rose

first: Nadine

middle: T

last: Gaisa


title: A necroptosis-independent function of RIPK3 promotes immune dysfunction and prevents control of chronic LCMV infection

city: Parkville

first: Alexandra

last: Garnham

state: Victoria

address: 1G Royal Parade

country: Australia

institute: Walter and Eliza Hall Institute of Medical Research

summary: Necroptosis is a lytic and inflammatory form of cell death that is highly constrained to mitigate detrimental collateral tissue damage and impaired immunity. These constraints make it difficult to define the relevance of necroptosis in diseases such as chronic and persistent viral infections and within individual organ systems. The role of necroptotic signalling is further complicated because proteins essential to this pathway, such as receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), have been implicated in roles outside of necroptotic signalling. We sought to address this issue by individually defining the role of RIPK3 and MLKL in chronic lymphocytic choriomeningitis virus (LCMV) infection. We  investigated if necroptosis contributes to the death of LCMV-specific CD8+ T cells or virally infected target cells during infection. We provide evidence showing that necroptosis was redundant in the pathogenesis of acute forms  of LCMV (Armstrong strain) and the early stages of chronic (Docile strain) LCMV infection in vivo. The number of immune cells, their specificity and reactivity towards viral antigens and viral loads are not altered in the absence of either MLKL or RIPK3 during acute and during the early stages of chronic LCMV infection. However, we identified that RIPK3 promotes immune dysfunction and prevents control of infection at later stages of chronic LCMV disease. This was not phenocopied by the loss of MLKL indicating that the phenotype was driven by a necroptosis-independent function of RIPK3. We provide evidence that RIPK3 signaling evoked a dysregulated type 1 interferone response which we linked to an impaired antiviral immune response and abrogated clearance of chronic LCMV infection.

overall_design: LCMV-specific CD8+ T cells were isolated from the spleen and pooled lymph nodes of mice 14 days post infection with LCMV docile. Paired-end RNA-seqeuencing data was then generated. Of these samples, 4 are wild type (WT) and 7 are Ripk3 knock-out (KO). Differential analyses were performed, identifying differentially expressed genes between the KO and WT groups.

first: Simon

last: Preston

first: Marcel

last: Doerflinger

first: Mark

last: Pellegrini


title: The role of miR-99a-5p in the immune regulation of host macrophages infected by Mycobacterium tuberculosis

city: Bei Jing

first: Yuting

last: Shi

address: No. 97 Ma Chang, Tongzhou District,Beijing of China

institute: Beijing Chest Hospital, Capital Medical University

summary: This study aims to identify the specific miRNA of mycobacterium tuberculosis (M.tb) infected THP-1 by next-generation sequencing, and further to explore the role of miRNA in innate immunity against M.tb infection.Comprehensive analysis of the next-generation sequencing results showed that the expression of miR-99a-5p was significantly lower in the MTB infected THP-1 cells.

overall_design: The miRNA expression profile in THP-1 cells with or without M.tb (H37Rv) infection was detected using Illumina HiSeq2500 next-generation sequencing platform.

first: Liping

last: Pan


title: Effect of TSP1 on gene expression  of mice mPFC

first: Shuang-Qi

last: Gao

address: tianhe road 600

institute: Third Affiliated Hospital of Sun Yat-sen University

summary: To investigate the role of TSP1 in the brain, we established the mPFC in mice after treatment with recombinant human thrombospondin-1 protein i.p.

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of 7 different mice.

first: Jun-Quan

last: Chen

first: Hai-Yun

last: Zhou

first: Lun

last: Luo

first: Bao-Yu

last: Zhang

first: Man-Ting

last: Li

first: Hai-Yong

last: He

first: Chuan

first: Ying

last: Guo


title: Single-cell sequencing of pleural effusion reveals immune response of COV2019 infection

city: GuangZhou

first: Jiangping

address: Kai yuan avenue 190

institute: Guangzhou Institutes of Biomedicine and Health (GIBH), CAS

overall_design:
We analyzed the single-cell transcriptome expression profiles(scRNA-seq)  for COVID-19 patient

***Raw data are not available due to patient privacy concerns***


title: The gene regulation landscape of MITF in lung adenocarcinoma

city: Taipei

first: Sung-Liang

last: Yu

address: Jen Ai Road Section1

department: Clinical Laboratory Sciences and Medical Biotechnology

institute: National Taiwan University

summary:
MITF is a transcription factor and identified as a oncoprotein in melanoma, but its role in lung adenoacrcinoma is still unknown. This study sought to investigate the effects of MITF on the biological behavior and global gene expression profiles in lung adenocacinoma cells.
We used expression microarrays to identify the global gene alterations in lung adenocacinoma cell line, CL1-0 cells after ectopic expressing three shRNA for knockdown MITF expression.

overall_design: Ectopic expressing three shMITF and scrembles in high-expressed MITF lung cancer cell line, CL1-0.

first: Yi-Jing

last: Hsiao


title: Defining TFAP4 transcriptional regulation in pre-leukemic Eμ-MYC pre-B lymphoma cells

first: Alexandra

summary: Many lymphoid malignancies arise from deregulated c-MYC expression in cooperation with additional genetic lesions. While many of these cooperative genetic lesions have been discovered and their functions characterised, DNA sequence data of primary patient samples suggest that many more do exist. However, the nature of their contributions to c-MYC driven lymphomagenesis have not yet been investigated. We identified TFAP4 as a potent suppressor of c-MYC driven lymphoma development in a previous genome-wide CRISPR knockout screen in primary cells in vivo. CRISPR deletion of TFAP4 in Eµ-MYC transgenic haematopoietic stem and progenitor cells (HSPCs) and transplantation of these manipulated HSPCs into lethally irradiated animals significantly accelerated c-MYC-driven lymphoma development. Interestingly, TFAP4 deficient Eµ-MYC lymphomas all arose at the pre-B cell stage of B cell development. This observation prompted us to characterise the transcriptional profile of pre-B cells from pre-leukaemic mice transplanted with Eµ-MYC/Cas9 HSPCs that had been transduced with sgRNAs targeting TFAP4.  This analysis revealed that TFAP4 deletion reduced expression of several master regulators of B cell differentiation, such as Spi1, SpiB and Pax5, which are direct target genes of both TFAP4 and MYC. We therefore conclude that loss of TFAP4 leads to a block in differentiation during early B cell development, thereby accelerating c-MYC-driven lymphoma development.

overall_design: Paired-end RNA-sequencing data was generated for 14 samples of primary mouse pre-leukemic Eµ-MYC/Cas9 B-cells. Of these samples, 6 are control and 8 are Tfap4 knock-out (KO).  Differential expression analyses were performed, identifying differentially expressed genes between the KO and control groups. This analysis included an adjustment for samples with the same FL ID.

first: Margaret

middle: A

last: Potts

first: Marco

last: Herold


title: Exploring the mechanism of Shoutai wan's intervention in recurrent miscarriage based on transcriptomics

city: Changsha

first: Kailin

last: Yang

state: Hunan

address: Xueshi Road No. 300

institute: Hunan University of Chinese Medicine

summary: Objective: To explore the mechanism of Shoutai Wan (STW) in treating recurrent miscarriage based on Transcriptomics.  Materials & Methods: The mice were divided into STW group, model group and normal group. After the intervention, Transcriptomics is then used to detect differential gene expression in decidual tissue and perform bioinformatics analysis.

overall_design: Comparative gene expression profiling analysis of RNA-seq data

first: Huiping

last: Liu

first: Guomin


title: Retrospective identification of cell-intrinsic factors that mark pluripotency potential in rare somatic cells (RNA-seq)

status: Public on Mar 11 2023

city: Philadelphia

first: Naveen

last: Jain

state: Pennsylvania

address: 415 Currie Boulevard

department: Bioengineering

institute: University of Pennsylvania

summary: Pluripotency can be induced in somatic cells by the expression of the four “Yamanaka” factors OCT4, KLF4, SOX2, and MYC. However, even in homogeneous conditions, usually only a rare subset of cells admit reprogramming, and the molecular characteristics of this subset remain unknown. Here, we apply retrospective clone tracing to identify and characterize the individual human fibroblast cells that are primed for reprogramming. These fibroblasts showed markers of increased cell cycle speed and decreased fibroblast activation. Knockdown of a fibroblast activation factor identified by our analysis led to increased reprogramming efficiency, identifying it as a barrier to reprogramming. Changing the frequency of reprogramming by inhibiting the activity of LSD1 led to an enlarging of the pool of cells that were primed for reprogramming. Our results show that even homogeneous cell populations can exhibit heritable molecular variability that can dictate whether individual rare cells will reprogram or not.

overall_design: Comparative gene expression profiling analysis of bulk RNA-seq data for hiF-T cells sorted by proliferation status or exposed to drug. Biological replicates are included and indicated.

first: Yogesh

last: Goyal

last: Dunagin

first: Christopher

last: Cote

first: Ian

last: Mellis

first: Benjamin

last: Emert

first: Connie

middle: L

last: Jiang

middle: P

last: Dardani

first: Sam

last: Reffsin

first: Arjun

last: Raj


title: The effect of DFMO on the gene expression in pro-inflammatory cytokine-treated human islets

city: Chicago

first: Raghavendra

last: Mirmira

state: IL

address: 900 E 57th St

institute: University of Chicago

summary: Inhibition of polyamine biosynthesis using α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), reduces β-cell stress and type 1 diabetes (T1D) incidence in preclinical models. However, underlying cellular and molecular mechanisms and the tolerability and effectiveness of polyamine depletion by DFMO in humans with T1D remain unknown. Transcriptomics and proteomics of cytokine-stressed human islets treated with DFMO reveal alterations in mRNA translation, nascent protein transport, and secretion. Collectively, our data suggest that inhibition of polyamine biosynthesis may preserve β-cell function in T1D via islet cell-autonomous responses to stress.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for human islets treated with DFMO in presence or absence of proinflammatory cytokines

first: Kulkarni

last: Abhishek

first: Mirmira

last: Raghavendra


title: Retrospective identification of cell-intrinsic factors that mark pluripotency potential in rare somatic cells (scRNA-Seq)

overall_design: Comparative gene expression profiling analysis of single-cell RNA-seq data for hiF-T cells, in some cases sorted by proliferation status, and induced pluripotent stem cells derived from hiF-T cells and exposed to drug. Biological replicates are included and indicated.