title: Genetic Rescue of X-Linked Retinoschisis Mouse (Rs1-/y) Retina Induces Quiescence of the Retinal Microglial Inflammatory State Following AAV8- RS1 Gene Transfer and Identifies Gene Networks Underlying Retinal Recovery

city: Bethesda

first: Matthew

last: Brooks

state: MD

address: 6 Center Dr Bldg 6, Rm 303

department: NEI

institute: NIH

summary: To understand RS1 gene interaction networks in the X-linked retinoschisis (XLRS) mouse retina (Rs1-/y), we analyzed the transcriptome by RNA sequencing before and after in vivo expression of exogenous retinoschisin (RS1) gene delivered by AAV8. RS1 is a secreted cell adhesion protein that is critical for maintaining structural lamination and synaptic integrity of the neural retina. RS1 loss-of-function mutations cause XLRS disease in young boys and men, with splitting ("schisis") of retinal layers and synaptic dysfunction that cause progressive vision loss with age. Analysis of differential gene expression profiles and pathway enrichment analysis of Rs1-KO (Rs1-/y) retina identified cell surface receptor signaling and positive regulation of cell adhesion as potential RS1 gene interaction networks. Most importantly, it also showed massive dysregulation of immune response genes at early age, with characteristics of a microglia-driven proinflammatory state. Delivery of AAV8-RS1 primed the Rs1-KO retina toward structural and functional recovery. The disease transcriptome transitioned toward a recovery phase with upregulation of genes implicated in wound healing, anatomical structure (camera type eye) development, metabolic pathways, and collagen IV networks that provide mechanical stability to basement membrane. AAV8-RS1 expression also attenuated the microglia gene signatures to low levels toward immune quiescence. This study is among the first to identify RS1 gene interaction networks that underlie retinal structural and functional recovery after RS1 gene therapy. Significantly, it also shows that providing wild-type RS1 gene function caused the retina immune status to transition from a degenerative inflammatory phenotype toward immune quiescence, even though the transgene is not directly linked to microglia function. This study indicates that inhibition of microglial proinflammatory responses is an integral part of therapeutic rescue in XLRS gene therapy, and gene therapy might realize its full potential if delivered before microglia activation and photoreceptor cell death.

overall_design: Mouse retinas from wild-type and Rs1-KO mice at ages post-natal day 12 and 21 were obtained in triplicate for stranded mRNA-seq library construction. In addition, gene therapy delivery of human RS1 gene and null vector, via AAV8 in mouse post-natal day 14 Rs1-KO retina, were performed and retinas obtained in quadruplicate from day 7 and 35 post-delivery and were used for stranded mRNA-seq library construction.

first: Vijayasarathy

last: Camasamudram

first: Yong

last: Zeng

first: Robert

last: Fariss

first: Paul

last: Sieving


title: CRAC of yeast RNA polymerase II in the absence or upon depletion of Xrn1

status: Public on Jun 22 2021

city: Montpellier

first: Domenico

last: Libri

address: 1919 route de Mende

country: France

institute: IGMM - CNRS

type: Expression profiling by high throughput sequencing

summary: We report  RNA polymerase II occupancy profiles across the genome of S.cerevisiae  strains deleted or depleted for the protein Xrn1. This allowed investigating the role of Xrn1 in RNA polymerase II transcription.

overall_design: Xrn1 was depleted from the cell using the auxin-degron method. Nuclear depletion was also studied, using the anchor away methodology. In both cases several time points of depletion have been analyzed, including no addition of auxin (auxin-degron method) or rapamycin (anchor-away technique).  An xrn1∆ strain was also studied. The nascent RNA was crosslinked to RNAPII and sequenced after purification of the HTP-tagged large subunit Rpb1 under stringent and denaturing conditions. This reveals the position of the polymerase at the nucleotide resolution level.

first: Drice

last: Challal

first: Mara

last: Barucco


title: Transcriptional analyses of different Chrysodeixis includens larvae (Lepidoptera: Noctuidae) unveil molecular resistance mechanism for pyrethroid resistance in Brazil

status: Public on Jun 23 2021

city: Davis

first: Joanna

middle: C.

last: Chiu

state: California

address: One shield Av

country: USA

institute: University of California

summary:
Purpose: To investigate resistance mechanisms among individuals that tolerate high doses of insecticides, we performed high-throughput RNA sequencing on two Brazilian populations of C. includens, that differ in susceptibility to pyrethroid λ-cyhalothrin.
Methods: Two replicates of pool 4 larvae (third instar) of each population, susceptible (LAB) and resistant (MS), were dissected into two parts: head (enriched with neural tissue) and body (enriched with adipose and gut tissues). Paired-end libraries of head and body tissues, with an approximate average insert length of 300 bp, were sequenced on an Illumina HiSeq platform with 150 bp paired-end sequencing. Trimmed RNA-Seq reads from transcriptomes of head and body larvae were used to alings the reads in the reference transcriptome (GSE121104), using TopHat. Expression analysis between LAB and MS population and between tissues were performed on Cufflinks, where the FPKM (fragments per kilobase per million mapped reads) between transcriptomes were estimated.
Results: . Our results revealed several potential molecular mechanisms that underlie their low susceptibility to pyrethroids. We identified 10 synonymous and five non-synonymous mutations within the coding region of the voltage-gated sodium channel in the resistant population, specifically in domains II, III, and IV. Additionally, we observed overexpression of metabolic enzymes including Cyp, Gst, Est, and Ugt. Some of these enzymes were up-regulated in the head as well as the abdomen of the resistant population, suggesting a detoxification process that begins in the mouth parts and continues through the gut.
Conclusions: The complexity of altered gene expression and nonsynonymous mutations can effectively be assessed with RNA sequencing in order to implement integrated pest management strategies and insecticide resistance management.

overall_design: Libraries of two replicates of pool 4 larvae (third instar) from head and body tissues were sequenced.

first: Frank

middle: G

last: Zalom

first: Jerson

middle: V

last: Guedes


title: Loss of Musashi-1 inhibits breast cancer metastasis via regulation of Timp3/Mmp9

city: beijing

first: xueyun

last: bi

address: 2 yuanmingyuan west road, haidian district, Beijing, China

country: China

institute: China Agricultural University

summary: To investigate the molecular mechanism of Msi1 in breast cancer metastasis, we performed transcriptome profiling at 16 weeks of primary tumor samples between ctrl and Msi1 cko mice, We performed a pathway enrichment analysis of the transcriptome data, the enriched KEGG pathways are mostly related to cellular adhesion, such as Focal adhesion, cell adhesion molecular (CAM), ECM-receptor interaction and regulation of actin cytoskeleton, which are closely related to the formation of invadopodia.

overall_design: mammary tumor mRNA profiles of 16 weeks of ctrl and Msi1 cko mice were generated by deep sequencing,  using Illumina NovaSeq 6000 platform.

first: Xueyun

last: Bi

first: Zhengquan

last: Yu


title: Macaque prenatal lung development

city: Cincinnati

first: Yan

last: Xu

state: OH

address: 3333 Burnet Ave

institute: Cincinnati Children's Hospital Medical Center

summary: Bulk RNA-seq of macaque prenatal lung at GA105, GA130, and GA150

overall_design: Total 7 samples were obtained at 3 different gestational ages of GA105 (2 replicates), GA130 (2 replicates), and GA150 (3 replicates).

first: Jeffrey

last: Whitsett

first: Alan

last: Jobe

first: Yina

last: Du


title: Identification of SAT1 regulated genes in GBM cells by microarray

city: Miami

first: Scott

last: Welford

state: FL

address: 1550 10th Avenue, Pap 503

institute: University of Miami

summary: We aimed to identify SAT1 regulated genes in U87MG cell by knockdown of SAT1 with two different shRNAs, and then compared knockdown cells to control cells with shGFP

overall_design: U87 cells were infected with shRNA lentifirus from the Broad Institute (TRCN0000035250 and TRCN0000035252), then RNA was harvested and analyzed with Affymetrix HTA-2_0 chips.

first: Welford

last: Scott

first: Thakur

last: Vijay


title: Transcriptomic data of parent and NAPE-PLD deteled Caco-2 cells

city: Fuchu-City

first: Miki

last: Igarashi

state: Tokyo

address: 3-5-8 Saiwai

country: Japan

institute: Tokyo University of Agriculture and Technology

summary: PURPOSE: We generated NAPE-PLD-deleted Caco-2 cells, which is a model of intestinal epithelial cells, using genome editing with the CRISPR/Cas9 system. To explore the molecular events following the deletion of NAPE-PLD in Caco-2 cells, we examined the transcriptomic changes in the NAPE-PLD deleted clone 35 compared with Caco-2 parent cells by RNA-seq. METHODS: mRNA profiles of parent and NAPE-PLD deleted Caco-2 cells were generated using Illumina HiSeq4000 (n=2/each cell). Those raw sequence data were then mapped to the human hg38 reference genome using a custom MOIRAI pipeline with STAR 2.51 for alignment. Then, read counts for each transcript were obtained using featureCounts, and the raw count data were directly analyzed for differential gene expression by using edgeR 3.20.9. RESULTS: Approximately 40 million reads per sample were obtained as raw data. Among a total of 12,331 genes detected in at least in one cell type, 1,019 genes were up-regulated (FDR < 0.01, logFC > 1) and 827 genes were down-regulated (FDR < 0.01, logFC > 1) in clone 35 compared with the parental cells.

overall_design: mRNA profiles of parent and NAPE-PLD deleted Caco-2 cells were generated using Illumina HiSeq4000.

first: Kazuhide

last: Watanabe


title: Chromatin Occupancy of AR, BRD4, and H3K27Ac in MR42D Cells in response to Enzalutamide [ChIP-seq]

city: Portland

first: Zheng

last: Xia

state: Oregon

address: 3181 SW Sam Jackson Park Rd

department: Department of Biomedical Engineering

institute: Oregon Health & Science University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: In order to identify AR-repressed genes that are activated by enzalutamide in t-NEPC cell lines, we cultured enza-resistant MR42D cells in the absence of enzalutamide for 72 hours, then added back either enzalutamide or vehicle and cultured for an additional 24 hours. Then we performed chromatin immunoprecipitation sequencing (ChIP-seq) pulling down AR, BRD4, and H3K27Ac. To identify potential NEPC genes suppressed by the AR, we compared AR DNA occupancy from the vehicle and enzalutamide treatments to identify regions where AR was evicted in response to enzalutamide. Similarly to determine the role of histone acetylation on NEPC gene activation in t-NEPC lines, we examined differential DNA-binding of the BRD4 acetylated lysine reader, and differential acetylation of the active enhancer mark H3K27Ac in response to enzalutamide treatment.

overall_design: MR42D cells were grown in the absence of enzalutamide for 72 hours, then the AR-antagonist Enzalutamide (MDV) or Vehicle (DMSO) were added to the media and cells were cultured an additional 24 hours. After treatment, nuclear extracts were subjected to chromatin immunoprecipitation sequencing (ChIP-seq) pulling down either AR, BRD4, or H3K27Ac.

first: Dae-Hwan

last: Kim

first: Duanchen

last: Sun

first: Katherine

last: Welker-Leng

first: Joshua

last: Urrutia

first: Joshi

last: Alumkal


title: Transcriptome comparison of balding and non-balding dermal papilla aggregates from NHEK co-culturing

city: Cologne

first: Axel

last: HILLMER

address: Kerpener Str. 62

department: Institute of Pathology

country: Germany

institute: University of Cologne

summary: Androgenetic alopecia (AGA, male patterned baldness) is a prevalent hair loss condition in males that develops due to the influence of androgens and genetic predisposition. The keratinocytes-surrounded spheroid dermal papilla (DP) at the base of the hair follicle is essential in hair morphogenesis and cycling. With the aim of elucidating genes involved in AGA pathogenesis, we co-cultured immortalised balding and non-balding human DP cells (DPC) derived from male AGA patients with epidermal keratinocyte (NHEK) using multi-interfacial polyelectrolyte complexation (MIPC) technique, and compared gene expression using RNA-seq between isolated balding and non-balding DP aggregates.

overall_design: Examination of transcriptome difference between isolated balding and non-balding dermal papilla cell aggregates, technical triplicate.

middle: M

last: Hillmer


title: Investigations of the roles of epigenetic regulator KAT2A in ccRCC

city: Shanghai

first: Li

last: Chen

address: 966 Middle Huaihai Road

department: Department of Pharmacy

institute: Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University

summary: We systematically described the oncogenic functions of KAT2A in ccRCC

overall_design: RNA-seq of WT and KAT2A KO ccRCC cells.


title: Reversal of emphysema by restoration of pulmonary endothelial cells

city: New York City

first: Balvir

last: Kunar

state: New York

address: 1300 York Ave

department: Regenerative Medicine; Physiology, Biophysics, & Systems Biology

institute: Weill Cornell Medical College

summary: Chronic obstructive pulmonary disease (COPD) is a heterogenous disorder marked by small airway inflammation and distal airspace enlargement (emphysema) leading to progressive airflow obstruction and eventual respiratory failure. Current therapies are limited in their ability to halt the pathogenesis of COPD merely relieving symptoms of dyspnea and airflow limitation. Microvasculature dysfunction, an understudied area of investigation, is associated with the severity of COPD. However, it is not known if abnormal lung endothelium drives COPD pathology and/or if correcting endothelial dysfunction has therapeutic potential. Here, we show the centrality of specialized pulmonary endothelial cells to lung pathogenesis in an elastase-induced murine model of COPD. Airspace disease was marked by aberrant endothelial cell loss and dysfunction, which was rescued by intravenous delivery of healthy lung endothelial cells. Airspace injury triggered regulation of a distinct module of maladaptive endothelial transcripts comprising lost endothelial cell function. Endothelial leucine-rich alpha-2-glycoprotein-1 (LRG1) was identified as a key driver of the emphysematous pathology and selective deletion of Lrg1 from endothelial cells rescued elastase-induced defects of pulmonary parenchymal destruction. Hence, targeting lung endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent novel therapeutic strategies of immense potential for the treatment of emphysema.

overall_design:
RNA sequencing of mouse lung endothelial cells after one and six months of whole body smoke compared to controls at room air.
Expression profiling by high throughput sequencing data; Illumina HiSeq 4000 (Mus musculus).

first: Shu

last: Hisata

first: Alexandra

last: Racanelli

first: Sean

last: Houghton

first: Suzanne

last: Cloonan

first: Shahin

last: Rafii

first: Augustine

last: Choi


title: RNA-Seq of potato tubers after cut-wounding

city: Guangzhou

first: Wang

last: Li

address: Wushan road, Tianhe district

institute: Guangdong Academy of Agricultural Sciences

summary: Transcriptome sequencing was performed to reveal the physiological changes of potato tubers after injury at the transcriptome level

overall_design: mRNA profiles of potato tubers after cut-wounding

last: Wang

first: Xingyao

last: Xiong


title: Gene expression profiling of two subclones of HN9-S and HN9-R isolated from patient-derived HN9 cancer cells

city: SEOUL

first: Kyung-Chul

address: Sonpa-gu

department: Biomedical Sciences

country: South Korea

institute: University of Ulsan college of Medicine

summary:
Purpose: The goals of the study are to understand phenotypically different characteristics of two single clones, HN9-R and HN9-S isolated from primary Head and Neck Carcinoma HN9 and to compare transcriptome profiling to genome-wide analytic approach performed by next-generation sequencing (NGS) analysis.
Methods: mRNA profiles of two single clones, HN9-R and HN9-S, were generated by sequencing using Illumina NextSeq 500 software. Sequenced reads were trimmed for adaptor sequence then mapped to hg19 whole genome using STAR (version 2.5.0) with parameters -outFilterIntronMotifs RemoveNoncanonicalUnannotated. Fragments Per Kilobase of exon per Megabase of library size (FPKM) were calculated by Cufflinks packages (version 2.2.1). Differentially expressed genes were detected using Cuffdiff (version 2.2.1) against Ensemble genes.
Results: We find total 337 DEGs (differentially expressed genes) between HN9-R and HN9-S (FPKM value of > 1, log2. Fold-change > 2, and Padj < 0.05) and that there were 178 and 159 genes of significantly increased or reduced transcripts, respectively. The level of gene expression was validated by quantitative real-time PCR using SYBR Green assay and western blotting analysis.
Conclusion: The results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cells. This study provides a framework for the dissection of biological functions towards characterization of two sub-clones co-existed within a primary cancer cells.

overall_design: Gene expression profiles of two clones (HN9-R and HN9-S) isolated from Head and Neck Cancer cells HN-9 were generated by sequencing, in triplicate, using Illumina NextSeq 500.

first: Seong

middle: W

last: Kim

first: Hae

middle: Y

last: Nam


title: Sonic Hedgehog inhibitors cyclopamine and GANT61 effect on HT-29 cells

city: NANCAHNG

first: Shiwen

last: Luo

state: JiangXi

address: 17 Yong Wai street

department: Center for experimental medicine

institute: The Frist Affiliated Hospital of Nanchang University

summary: Analysis of gene expression levels in response to inhibition of Hh signaling in HT-29 cells using a cDNA microarray technique. Microarray analyses revealed that different genes after treatment with both cyclopamine (an antagonist of SMO) and GANT61 (a specific, small-molecular molecule inhibitor of Glis).

overall_design: HT-29 cells were treated with GANT61 (20 μM for 48 hr), Cyclopamine (20μM for 48 hr) and control vehicle DMSO, Tomatidine, respectively.

first: S


title: An integrated epigenome and transcriptome analysis to clarify the effect of epigenetic inhibitors in gastrointestinal stromal cells

status: Public on Jun 21 2021

city: Sapporo

first: Hiromu

last: Suzuki

state: Hokkaido

address: S1, W17, Chuo-ku

department: Department of Molecular Biology

institute: Sapporo Medical University

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

overall_design: Refer to individual Series


title: Gene signature profiles in bronchial tissues from severe asthma patients treated with bronchial thermoplasty

city: TSUKUBA

first: Masashi

last: Matsuyama

state: IBARAKI

address: 1-1-1 AMAKUBO

department: respiratory medicine

institute: Tsukuba university

summary: Bronchial thermoplasty (BT) is an endoscopic therapy employed for the treatment of refractory asthma. However, no predictive factors are available that determine the effectiveness of BT in treating asthma patients. The present study aimed to comprehensively analyze RNA samples from the airway bronchial tissues of 8 patients with severe asthma treated by BT, and to characterize each patient as a BT responder or non-responder. Total 24 RNA samples (three per patient prior to BT1 [baseline], prior to BT2 [after 1st time treatment], and prior to BT3 [after 2nd time treatment]) were obtained. There were 975 differentially expressed (DE) genes in the bronchial tissues of 8 patients between prior to BT1 (baseline) and prior to BT2 (after 1st time treatment), with significant differences (FDR-adjusted P<0.05). Subjects with an Asthma Quality of Life Questionnaire score change of >0.5 for a period of 12 months were considered BT responders. Non-responders exhibited a score change of <0.5 for 12 months. Transcriptome analysis at baseline identified 67 genes that were differentially expressed between responders and non-responders, including SLPI, MMP3, and MUC19 which were upregulated in responders.

overall_design: We prospectively studied 8 patients with severe asthma treated with Bronchial thermoplasty (BT). We underwent three sessions of BT (BT1, BT2, and BT3) at least every 3 weeks.   Total RNA was extracted from homogenized bronchial tissues using TRIzol reagent.  Total 24 RNA samples (three per patient prior to BT1 [baseline], prior to BT2 [after 1st time treatment], and prior to BT3 [after 2nd time treatment]) were obtained.

first: Satoshi

last: Ano

first: Yukio

last: Ishii

first: Masayuki

last: Nakajima

first: Nobuyuki

last: Hizawa


title: Sphingosine kinase 1 regulates the pulmonary vascular immune response

city: Indianapolis

first: Robert

last: Stearman

state: IN

address: 950 W Walnut St

department: Medicine/Pulmonary

institute: Indiana Univeristy School of Medicine

summary: Aberrant proliferation of pulmonary arterial smooth muscle (PASMCs) cells are a defining characteristic of pulmonary arterial hypertension (PAH) and leads to increased vascular resistance, elevated pulmonary pressure, and right heart failure. The Sphingosine kinase 1 (SPHK1)/Sphingosine-1 phosphate/ Sphingosine-1 phosphate receptor 2 pathway promotes vascular remodeling and induces PAH. The aim of this study was to identify genes and cellular processes that are modulated by over-expression of SPHK1 in human PASMCs (hPASMCs). RNA was purified and submitted for RNA sequencing to identify differentially expressed genes. Using a corrected p-value threshold of <0.05, there were 294 genes significantly up-regulated while 179 were significantly down-regulated. Predicted effects of these differentially expressed genes was evaluated using the freeware tool Enrichr to assess general gene set over-representation (enrichment) and Ingenuity Pathway Analysis (IPA™) for upstream regulator predictions. We found a strong change in genes that regulated the cellular immune response. IL6, STAT1, and PARP9, were elevated in response to SPHK1 over-expression in hPASMCs. The gene set enrichment mapped to a few immune modulatory signaling networks, including IFNG. Furthermore, STAT1 protein was elevated in primary hPASMCs isolated from PAH patients. In conclusion, these data suggest a role of Sphk1 regulates pulmonary vascular immune response in PAH.

overall_design: Determine change in hPASMC transcriptome after SPHK1 over-expression. Two groups- vector control and SPHK1 over-expression run in triplicate (6 samples total)

first: Yang

last: Bai

first: Angelia

middle: D

last: Lockett

middle: S

first: Roberto

middle: F

last: Machado


title: Molecular design of the γδ T cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing

city: Boston

first: Jonathan

middle: S.

last: Duke-Cohan

state: MA

address: 450 Brookline Ave

department: Medical Oncology

institute: Dana-Farber Cancer Institute

summary: High acuity αβT cell receptor (TCR) recognition of peptides bound to MHC molecules (pMHC) requires mechanosensing, a process whereby piconewton (pN) bioforces exert physical load on αβTCR-pMHC bonds to dynamically alter their lifetimes and foster digital sensitivity cellular signaling. While mechanotransduction is operative for both αβTCRs and preTCRs within the αβT-lineage, its role in γδT cells is unknown. Here we show that the human DP10.7 γδTCR specific for the sulfoglycolipid sulfatide bound to CD1d only sustains significant load and undergoes force-induced structural transitions when the binding interface-distal γδ constant  domain (C) module is replaced with that of αβ. The chimeric γδ-αβTCR also signals more robustly than the wild-type γδTCR as revealed by RNA-seq analysis of TCR-transduced Rag2-/- thymocytes, consistent with structural, single molecule and molecular dynamics studies reflective of γδTCRs as mediating recognition via a more canonical immunoglobulin-like receptor interaction. Absence of robust, force-related catch bonds as well as γδTCR structural transitions implies that γδT cells do not use mechanosensing for ligand recognition. This distinction is consonant with the fact that their innate-type ligands, including markers of cellular stress, are expressed at high copy number relative to sparse pMHC ligands of αβT cells arrayed on activating  target cells. We posit that mechanosensing emerged over ~200 million years of vertebrate evolution to fulfill indispensable adaptive immune recognition requirements for pMHC in the αβT cell lineage that are unnecessary for the γδ T cell lineage mechanism of non-pMHC ligand detection.

overall_design: Comparison of a native γδTCR with a chimeric γδTCR where the constant domains have been replaced with those of an αβTCR, focusing on signaling properties during the DN3 and DN4 stages of thymocyte development. 2 receptors (γδTCR, γδ/αβTCR) x 2  stages (DN3, DN4) x 2 signaling environments (control, +sulfatide/CD1d agonist) x 3 replicates (except for 2 samples with 2 replicates) = 22 libraries

middle: J

last: Mallis

first: Ellis

middle: L

last: Reinherz


title: LSD1 promotes secretory cell specification to drive BRAFmutant colorectal cancer

last: Policastro

state: Massachusetts

address: 451 D St Unit #600

institute: Ensoma Inc.

summary: Despite the connection to distinct mucus-containing colorectal cancer (CRC) histological subtypes, the role of secretory cells, including goblet and enteroendocrine (EEC) cells, in CRC progression has been underexplored. Analysis of TCGA and single cell RNA sequencing data demonstrates that multiple secretory progenitor populations are enriched in BRAF-mutant CRC patient tumors and cell lines. Enrichment of EEC progenitors in BRAF-mutant CRC is maintained by DNA methylation and silencing of NEUROD1, a key gene required for differentiation of EECs. Mechanistically, secretory cells and the factors they secrete, such as Trefoil factor 3, are shown to promote colony formation and activation of cell survival pathways in the entire cell population. We further identify LSD1 as a critical regulator of secretory cell specification in vitro and in a colon orthotopic xenograft model, where LSD1 loss reduces tumor growth and metastasis. This work establishes EEC progenitors, in addition to goblet cells, as targetable populations in BRAF-mutant CRC and identifies LSD1 as a therapeutic target in secretory lineage-containing CRC.

overall_design: scRNA-seq of empty vector control and LSD1 knockdown CRC cell lines

first: Heather

last: O'Hagan

first: Samuel

middle: A

last: Miller


title: Chromatin Occupancy of AR, BRD4, and H3K27Ac in MR42D Cells in response to Enzalutamide [ATAC-seq]

first: Zheng

last: Xia

summary: In order to look at global chromatin accessibility in enzalutamide sensitive (V16D) and enzalutamide-resistant t-NEPC lines (MR42D), we treated these lines with enzalutamide or vehicle and performed an Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq). Hyperaccessible regions in V16D were associated with metabolic pathways, whereas hyperaccesible regions in MR42D were associated with neuronal pathways, indicating that the chromatin conformation in these enzalutamide resistant cells is conducive to transdifferentiation to a neuronal t-NEPC phenotype.

overall_design: MR42D cells were grown in the presence of enzalutamide (Maintenance_MDV conditon) for 96 hours, or in the absence of enzalutamide for 72 hours, then enzalutamide (Washout_MDV) or Vehicle (Washout_Veh) was added back to the media and cells were cultured an additional 24 hours. Biological duplicates of the MR42D treatments were subjected to Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq). V16D cells were treated with enzalutamide or vehicle for 24 hours, and biological triplicates for each treatment were subjected to ATAC-seq.

first: Dae-Hwan

last: Kim

first: Duanchen

last: Sun

first: Katherine

last: Welker-Leng

first: Joshua

last: Urrutia

first: Joshi

last: Alumkal


title: Gene expression analysis of inositol hexakisphospahte kinase 1 (Ip6k1) knockout testes in juvenile mice

status: Public on Jun 20 2021

city: Bangalore

first: Genotypic

last: technology

state: Karnataka

address: 259, Apoorva 4th cross,80 feet Road,RMV 2ND STAGE

country: India

institute: Genotypic Technology

summary: Ip6k1 knockout male mice are infertile and display a delay in the first wave of spermatogenesis. To understand the underlying basis of this delay, we compared the gene expression profiles of whole testes from 17 days postpartum (17dpp) and 26 days postpartum (26dpp) Ip6k1 wild type (Ip6k1+/+) and Ip6k1 knockout (Ip6k1-/-) mice. We observed deregulation of several biological processes in Ip6k1-/- testes compared with Ip6k1+/+ testes.

overall_design: Two biological replicates each of 17dpp and 26dpp Ip6k1+/+ and Ip6k1-/- mice.

first: Aushaq

last: Bashir Malla

first: Vineesha

last: Oddi

first: Sameer

last: Ahmed Bhat

first: Rashna

last: Bhandari


title: TRAP analysis of somatic muscle populations in Drosophila embryos

city: clermont ferrand

first: yoan

last: renaud

address: place henri dunand

institute: igred

summary: Microarray profiling of mRNA engaged in translation from 3 populations of somatic muscle at 3 different time points. The goal is to compare within a same population at different time points and between population the translatome present in these cell types in order to define specific properties giving rise to functional muscles

overall_design: 3 IP samples replicates and 3 Input for each 3 tested conditions and for 3 muscle populations

first: Benjamin

last: Bertin

first: Guillaume

last: Junion


title: Phase I Dose Escalation Study of ATRA Combined with the LSD1 inhibitor Tranylcypromine in AML and MDS

first: Ramin

last: Shiekhattar

state: Florida

address: 1501 NW 10th Avenue

department: Department of Human Genetics

institute: University of Miami - Sylvester Comprehensive Cancer Center

summary: Preclinical studies have shown that combining the LSD1 inhibitor tranylcypromine (TCP) with all-trans retinoic acid (ATRA) induces differentiation and impairs survival in non-APL acute myeloid leukemia (AML). We conducted a Phase 1 clinical trial (NCT02273102) to evaluate the safety and preliminary activity of ATRA in combination with TCP in patients with relapsed/refractory AML and myelodysplasia (MDS). Seventeen patients (11 AML and 6 MDS) received ATRA-TCP therapy with ATRA (45 mg/m2 daily in divided doses) and TCP (3 dose levels: 10 mg twice-daily [BID], 20 mg BID, and 30 mg BID). ATRA-TCP had an acceptable safety profile. The maximum tolerated dose of TCP was 20 mg BID. There were 3 DLTs: dizziness (20 mg BID), asthenia (30 mg BID), and nausea/vomiting (30 mg BID). Best evaluable responses included 1 morphologic leukemia-free state (MLFS), 1 marrow complete remission (CR) with hematologic improvement, 2 stable disease with hematologic improvement, and 2 stable disease. In 13 response-evaluable patients, the overall response rate was 30.8% and clinical benefit rate 46.2%. Gene expression profiling of patient blasts showed that responding patients had a more dormant phenotype compared to non-responders at baseline. In human AML cell lines, we showed that treatment with ATRA-TCP increases differentiation capacity and/or cell death, and that ATRA-TCP regulates the in vitro expression of genes that segregate primary patients by their clinical response. These data indicate that LSD1 inhibition sensitizes AML cells to ATRA-induced differentiation and cell death and may restore clinical responsiveness in subsets of MDS and AML patients.

overall_design: Total RNA-seq of purified CD34+ cell isolated from bone marrow of Relapsed/refractory AML and MDS patients before/after treatment with ATRA-TCP (phase-I clinical trial, NCT02273102). Total RNA-seq of  ATRA-treated, TCP-treated, and ATRA-TCP treated or vehicle control in U-937 and SKNO-1 cell lines in duplicates.

first: Mina

last: Tayari

first: Helena

last: Gomes Dos Santos

first: Deukwoo

last: Kwon

first: Terrence

last: Bradley

first: Amber

last: Thomassen

first: Charles

last: Chen

first: Yvonne

last: Dinh

first: Aymee

last: Perez

first: Arthur

last: Zelent

first: Lluis

last: Morey

first: Luisa

last: Cimmino

first: Ronan

middle: T

last: Swords

first: Shiekhattar

last: Ramin

first: Justin

last: Watts


title: SWI3B and HDA6 interact and are required for transposon silencing in Arabidopsis

city: Taipei

first: Pao-Yang

address: 128 Sec. 2, Academia Rd, Nankang,

department: Institute of Plant and Microbial Biology

country: Taiwan

institute: Academia Sinica

type: Methylation profiling by high throughput sequencing

summary: Although the interplay of covalent histone acetylation/deacetylation and ATP-dependent chromatin remodeling is crucial for the regulation of chromatin structure and gene expression in eukaryotes, the underlying molecular mechanism in plants remains largely unclear. Here we show a direct interaction between Arabidopsis SWI3B, an essential subunit of the SWI/SNF chromatin-remodeling complex, and the RPD3/HDA1-type histone deacetylase HDA6 both in vitro and in vivo. Furthermore, SWI3B and HDA6 co-repress the transcription of a subset of transposons. Both SWI3B and HDA6 maintain transposon silencing by decreasing histone H3 acetylation but increasing histone H3 lysine 9 di-methylation, DNA methylation and nucleosome occupancy. Our findings reveal that SWI3B and HDA6 may act in the same corepressor complex to maintain transposon silencing in Arabidopsis.

overall_design: To  investigate the role of SWI3B and HDA6 on transposon silencing, we conducted whole genome bisulfite sequencing (WGBS) from wild-type (Col), swi3b and sil1 mutant plants

first: Jie

last: Yang

first: Lianyu

last: Yuan

first: Ming-Ren

last: Yen

first: Tao

last: Peng

first: Dachuan

last: Gu

first: Rujun

last: Ji

first: Songguang

first: Yuhai

last: Cui

first: Keqiang

last: Wu

first: Xuncheng

last: Liu


title: Antitumor Effects of 3-bromoascochlorin on Small Cell Lung Cancer via Inhibiting MAPK Pathway

city: guangzhou

first: zhang

middle: zhen

last: hua

state: guangdong

address: xiaoguwei

department: college of pharmacy

institute: Sun Yat-Sen University

summary: Small cell lung cancer (SCLC) was defined as a recalcitrant cancer, and novel therapies are urgently needed. Marine natural products (MNP) may bring continuing hope for treatment of SCLC. In this study, 3-bromoascochlorin (BAS), an MNP isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, was primarily screened out with antiproliferative activity towards SCLC cell lines. Then Western blotting (WB) and flow cytometry were conducted, and we found BAS could induce the apoptosis of H446 and H69AR cells. Besides, BAS could suppress the invasion and migration of H446. In a SCLC xenograft mice model, BAS inhibited the growth of tumor without affecting the body weight of mice. Finally, the underlying mechanisms were preliminarily explored. According to the results of RNA-seq, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and WB, we draw the conclusion that BAS exerted antitumor activity via inhibiting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway. In short, we discovered an MNP as a potential drug lead against SCLC.

overall_design: H446 cells were treated with vehicle or the small molecule BAS (5 μM) and BAS (10 μM), for 48 h before RNA extraction. RNA-seq libraries were from 1 μg total RNA which was extracted using the total RNA isolation kit (Tiangen, BJ, China) and reverse transcribed with reverse transcriptase M-MLV (Takara, DL, China), according to the manufacturer's instructions. Libraries were validated with an Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA).

first: Zhenhua

last: Zhang

first: Chunju

first: Xiaowei

last: Luo


title: An integrated epigenome and transcriptome analysis to clarify the effect of epigenetic inhibitors in gastrointestinal stromal cells (ChIP-Seq)

first: Hiromu

last: Suzuki

summary: Epigenetic alterations play an important role in the pathogenesis of gastrointestinal stromal tumors (GISTs). To obtain better insight into the GIST epigenome, we analyzed genome-wide histone modification and DNA methylation in GIST cells. Trimethylation of histone H3 lysine 3 (H3K4me3), DNA methylome, and transcriptome in GIST-T1 cells were analyzed by chromatin immunoprecipitation-sequencing (ChIP-seq), Infinium HumanMethylation450 BeacChip, and gene expression microarray. Enrichment of H3K4me3 at transcription start sites (TSSs) is positively correlated with gene expression, while DNA methylation is negatively associated with gene expression in GIST-T1 cells. We found that treatment with a DNA methyltransferase inhibitor and a histone deacetylase inhibitor not only upregulated genes with DNA methylation, but also activated a number of interferon signaling-related genes. ChIP-seq analysis revealed that the drug treatment significantly upregulated H3K4me3 levels at TSS regions as well as retrotransposons including endogenous retroviruses (ERVs). Finally, by utilizing the omics data, we screened epigenetically silenced long non-coding RNA genes, and found that hypermethylation of MEG3 is a frequent event and an indicator of worse outcome in GIST patients. Our data suggest that epigenetic inhibitors may activate interferon signaling via viral mimicry in GIST cells. We also show that epigenome data obtained in this study could be a useful resource to identify novel GIST-related genes.

overall_design: GIST-T1 cells were treated with 2 μM 5-aza-2’-deoxycytidine (5-aza-dC; Sigma-Aldrich) for 72 hours and then treated with or without 3 mM 4-phenylbutyric acid (4-PBA; Sigma-Aldrich) for an additional 48 hour, replacing drug and medium every 24 hours.

first: Takeshi

last: Niinuma


title: miR-579-3p controls hepatocellular carcinoma formation by regulating the PI3K-AKT pathway in chronically inflamed liver (mRNA expression)

city: Basel

first: Matthias

middle: Sebastian

last: Matter

state: BS

address: Schönbeinstrasse 40

country: Switzerland

institute: University of Basel

summary: Background & Aims: Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas, the ten-year incidence for HCC in cirrhotic patients is approximately 20%, many cirrhotic patients remain tumor-free for their entire lives. Therefore, we wanted to clarify the mechanisms defining the different outcomes of chronic liver inflammation. Methods: We designed a longitudinal study comparing the mRNA and miRNA expression profiles in matched non-tumoral liver tissue from patients developing HCC (n = 30) versus patients remaining tumor-free (n = 27). The liver parenchyma was analyzed before and after HCC development in the same patient. Cirrhotic patients remaining tumor-free within a similar time frame served as a control cohort. mRNA expression of genes associated with cancer development and miRNAs were examined by the nCounterNanostring technology. The role of the identified genes involved in HCC development was evaluated by immunohistochemistry and in vitro assays. Results: Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed activation of NF-B, Insulin receptor and PI3K-AKT pathways, in parallel with increased hepatocyte proliferation and damage. Furthermore, downregulation of miR-579-3p was found as an early step in HCC development. MiR-579-3p directly attenuated PIK3CA expression and consequently AKT and pAKT. In vitro analyses confirmed that miR-579-3p controlled cell proliferation, migration and colony formation. Conclusions: Liver tissues from patients developing HCC revealed a more severe damage to the parenchyma with elevated hepatocyte proliferation. Moreover, miR-579-3p was identified as a potential novel tumor suppressor regulating PI3K-AKT signalling at the early stages of HCC development.

overall_design: In the study we analyzed mRNA expression by the nCounterNanostringPanCancer Pathways panel containing 730 cancer-associated genes in sequential liver biopsies from the same patient at two points in time: once when no hepatocellular carcinoma was present in the liver (1st biopsy) and once a hepatocellular tumor was present in the liver (2nd biopsy), in parallel we analyzed sequential biopsies from cirrhotic patients which remained tumor-free over a similar time free. 25 patients which developed hepatocellular carcinoma and 24 patients which remained tumor-free were included.

first: Cristina

middle: C

last: Quintavalle


title: miR-579-3p controls hepatocellular carcinoma formation by regulating the PI3K-AKT pathway in chronically inflamed liver (miRNA expression)

overall_design: In the study we analyzed miRNA expression in sequential liver biopsies from the same patient at two points in time: once when no hepatocellular carcinoma was present in the liver (1st biopsy) and once a hepatocellular tumor was present in the liver (2nd biopsy), in parallel we analyzed sequential biopsies from cirrhotic patients which remained tumor-free over a similar time free. 23 patients which developed hepatocellular carcinoma and 26 patients which remained tumor-free were included.


title: An integrated epigenome and transcriptome analysis to clarify the effect of epigenetic inhibitors in gastrointestinal stromal cells (Expression)

overall_design: Trimethylation of histone H3 lysine 3 (H3K4me3), DNA methylome, and transcriptome in GIST-T1 cells were analyzed by chromatin immunoprecipitation-sequencing (ChIP-seq), Infinium HumanMethylation450 BeacChip, and gene expression microarray. To restore epigenetic silencing, GIST-T1 cells were treated with a DNA methyltransferase inhibitor and a histone deacetylase inhibitor.


title: An integrated epigenome and transcriptome analysis to clarify the effect of epigenetic inhibitors in gastrointestinal stromal cells (Methylation)


title: RPRD PROTEINS CONTROL TRANSCRIPTION IN HUMAN CELLS

status: Public on Jun 19 2021

city: BIRMINGHAM

first: Hurmuz

last: CEYLAN

address: School of Biosciences, University of Birmingham,, Edgbaston B15 2TT

country: United Kingdom

institute: University of Birmingham

summary: Regulation of transcription is an essential process that allows the cell to respond to various internal and external signals. RNA Polymerase II (Pol II) activity is controlled by a number of factors which bind to the C-terminal domain (CTD) of its largest subunit, RPB1, and stimulate or supress RNA synthesis. Here, we demonstrate that members of the RPRD family of CTD-interacting proteins, RPRD1A, RPRD1B and RPRD2, act as negative regulators of transcription. We show they form mutually exclusive complexes with Pol II, coordinating this way their roles in transcription control. Our data indicate that the main alterations in gene expression patterns are driven by RPRD2, which results in further consequences during the cellular stress response, cell cycle and cell growth.

overall_design: Investigation the role of RPRD proteins on accumulation of steady-state RNA.

first: Kinga

last: Winczura

last: Ceylan

first: Monika

last: Sledziowska

first: Matt

last: Jones

first: Holly

last: Fagarasan

first: Jianming

last: Wang

first: Marco

last: Saporano

first: Daniel

last: Hebenstreit

first: Roland

last: Arnold

first: Pawel

last: Grzechnik


title: Set2-mediated H3K36 methylation states redundantly repress the production of antisense transcripts:: role in transcription regulation

city: wuhan

first: yuchao

last: Mei

address: Bayi Road

department: Colleage of Life Science

institute: Wuhan University

summary: Histone H3K36 can be added up to three methyl groups to form mono-, di-, and tri-methylation states. Recent study has shown that Set2 can suppress a specific group of antisense transcripts, which largely depends on the presence of H3K36 methylation. However, whether different methylation states possess distinct regulatory mechanisms on antisense transcripts is still unclear. In this study, we identified two yeast mutants that lack H3K36 di-methylation and tri-methylation, respectively. We also identified novel antisense transcripts in the absence of Set2 with own bioinformatics pipeline. Our study showed that the expression of these antisense transcripts does not affect the expression of corresponding sense genes. Different H3K36 methylation states (me2/me3) are not specific for the regulation of antisense expression, implying a co-regulation mechanism between them. Altogether, our study developed a method to identify new antisense transcripts, examined the potential effect of H3K36 di-methylation and tri-methylation on production of antisense transcripts. This study would shed light on the mechanism underlying how H3K36 methylation functions in the production of antisense transcripts.

overall_design: RNA-seq analysis of antisense expression in set2-delta, set2-Y149F and set2-Y236F cells of Saccharomyces cerevisiae.

first: Yu

first: Jiang

middle: P

last: Feng

first: Fei

last: He

last: Li

first: Ya

last: Liu

first: Feng

last: Chen

first: Hai

middle: N

last: Du


title: Aberrant expression of TRIM24 develops carcinosarcoma in vivo: a relevant model to study human metaplastic breast cancer

city: Houston

first: Abhinav

middle: K

last: Jain

state: TX

address: 1515 Holcombe Blvd

department: Epigenetics and Molecular Carcinogenesis

institute: The UT MD Anderson Cancer Center

summary: To identify chromatin accessibility in TRIM24-driven carcinosarcomas, we performed ATAC-Seq in primary cell line derived from TRIM24-driven mouse model.

overall_design: 2 replicates for TRIM24-driven primary carcinosarcoma cell line (897) and control MMTV-Cre expressing cell line (823) were subjected to ATAC-Seq.

first: Vrutant

last: Shah

first: Michelle

last: Barton


title: Changes in gene expression over time in cells expressing t(4;11) fusion proteins

city: Frankfurt am Main

first: Lukas

last: Jost

address: Altenhöferallee 3

institute: GenXPro GmbH

summary: We have used a constitutive MLL-AF4 fusion gene together with a inducible AF4-MLL fusion gene to investigate the power of theses fusion proteins. All transgenes were stably or transiently transfected.

overall_design: Fusion genes were constructed by fusing distinct cDNA portions of MLL/KMT2A with corresponding AF4 fragment.

first: Rolf

last: Marschalek


title: Mechanisms underlying strikingly divergent responses of genetically distinct macrophages to IL-4 [HiChIP]

city: La Jolla

first: Christopher

last: Glass

state: CA

address: 9500 Gilman Drive

department: CMM

institute: University of California, San Diego

summary: Mechanisms by which non-coding genetic variation influences gene expression remain only partially understood but are considered to be major determinants of phenotypic diversity and disease risk. To investigate these mechanisms with respect to signal-dependent gene expression, we evaluated effects of > 50 million SNPs and InDels provided by five inbred strains of mice on the responses of macrophages to the anti-inflammatory cytokine IL-4. Remarkably, of the > 600 genes observed to be induced >2-fold across the five strains after 24 hours of IL-4 treatment, only 26 genes reached this threshold in all strains and more than half of the induced genes were observed in only a single strain. By examining the effects of SNPs and InDels on transcription factor binding and enhancer activity under basal and IL-4 treatment conditions, we identified dominant collaborative roles of the signal-dependent transcription factors (SDTFs) STAT6, PPARg and EGR2 in driving late enhancer activation that were dependent on general macrophage lineage determining factors (LDTFs). As expected, SNPs and InDels that affected the relative affinities of SDTFs primarily influenced the ability of enhancers with similar basal activities to respond to IL-4. In contrast, SNPs and InDels that altered the relative binding affinities of macrophage LDTFs had divergent effects on basal and activated enhancer activity. Variants resulting in strong reductions in LDTF binding affinity were associated with low basal enhancer activity and failure to recruit SDTFs, whereas variants that increased LDTF binding affinities were associated with constitutively high levels of enhancer activity and a blunted response to SDTF recruitment. Together, these studies reveal mechanisms by which noncoding genetic variation influences absolute levels of enhancer activity and their dynamic responses to IL-4, thereby contributing to strain-specific patterns of gene expression and phenotypic diversity.

overall_design: HiChIP-seq for BMDMs (bone marow-derived macrophages) from C57BL/6J mice with IL-4 treatment

first: Marten

last: Hoeksema

first: Zeyang

last: Shen


title: mRNA Sequencing Analysis of Subcutanous White Adipose Tissue Transcriptomes from Vertical Sleeve Gastrectomy and Sham-operated WT-Mice

city: Lübeck

first: Henrik

last: Oster

address: Ratzeburger Allee 160

department: Institute of Neurobiology

institute: University Lübeck

summary:
Purpose: VSG has leads to a restructuring of WAT anantomy and physiology. The study aimed to understand how the (rhythmic) transcriptome is affected by these changes, especially in regard to metabolism and circadian clock genes.
Methods: Animals were fed HFD for approx. 10 weeks to be considered overweight (ca. 35g body weight). 32 animals underwent either sham or VSG surgery. After 3-4 days of postoperative care with liquid diet and analgetic treatment, subcutanous WAT biopsies from Zeitgeber time 1, 7, 13, and 19 were collected 9 days after surgery. mRNA sequencing was conducted with Illumina HiSeq 2000 and rhythm analysis of filtered genes performed with JTK_CYCLE.
Results: We found a reduction of cycling genes after VSG (sham: 2,493 vs. VSG: 1,013) in parallel to a reduced amplitude of cycling genes shared between VSG and sham animals (paired t-test p < 0.05) independent of the expression of core clock genes. Genes associated with lipid metabolic pathways (fatty acid breakdown and lipogenesis) showed altered circadian regulation.
Conclusions: We found VSG to reorganize WAT rhythmic transcriptome in a specific manner independent of the core clock machinery.

overall_design: White adipose tissue mRNA profiles 9 days after surgical intervention at 4 time points across the day with each 4 animals per group (n = 16 / group)

first: Anne-Marie

last: Neumann

first: Cathleen

last: Geißler

first: Violetta

last: Pilorz

first: Iwona

last: Oleijniczak

first: Aflor

middle: G

last: Lewis

first: Randy

last: Seeley

first: Orr

last: Shomroni

first: Gabriela

last: Salinas

first: Henriette

last: Kirchner


title: Affymetrix SNP array data for a Diffuse Large B-cell Lymphoma case with a TERT promoter variant who later developed Chronic Myelomonocytic Leukemia

city: Perugia

first: Cristina

last: Mecucci

address: Piazzale Menghini n.9

department: Department of Medicine, Hematology and Bone Marrow Transplantation Unit

country: Italy

institute: University of Perugia

summary: TERT promoter variants are well known in solid tumors. However, less is known in hematological malignancies, thus we screened a large series of MDS and MDS/MPN.

overall_design: Copy number analysis (400Kb) and cnLOH (10Mb) of Affymetrix SNP arrays was performed for one Diffuse Large B-cell Lymphoma case with a TERT promoter variant who later developed Chronic Myelomonocytic Leukemia

first: Silvia

last: Arniani

first: Valeria

last: Nofrini

first: Caterina

last: Matteucci


title: Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4 [ATAC-seq]

first: Christopher

last: Glass

summary: Mechanisms by which noncoding genetic variation influences gene expression remain only partially understood but are considered to be major determinants of phenotypic diversity and disease risk. Here, we evaluated effects of >50 million single-nucleotide polymorphisms and short insertions/deletions provided by five inbred strains of mice on the responses of macrophages to interleukin-4 (IL-4), a cytokine that plays pleiotropic roles in immunity and tissue homeostasis. Of >600 genes induced >2-fold by IL-4 across the five strains, only 26 genes reached this threshold in all strains. By applying deep learning and motif mutation analyses to epigenetic data for macrophages from each strain, we identified the dominant combinations of lineage-determining and signal-dependent transcription factors driving IL-4 enhancer activation. These studies further revealed mechanisms by which noncoding genetic variation influences absolute levels of enhancer activity and their dynamic responses to IL-4, thereby contributing to strain-differential patterns of gene expression and phenotypic diversity.

overall_design:
ATAC-seq for BMDMs (bone marow-derived macrophages) from five mouse strains with IL-4 treatment

**Please note that
[1] the processed data generated from all replicates is linked to the corresponding rep1 sample records
[2] raw data for human sample is not provided due to privacy concerns.


title: Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4 [RNA-seq]

overall_design:
RNA-seq for BMDMs (bone marow-derived macrophages) from five mouse strains with IL-4 treatment

**Please note that
[1] the RNA_TPM_F1.tsv was prepared for the RNA-seq data generated from F1 mice, and  during data preprocessing, those data were mapped to two different genomes labeled as  "C57" and "SPRET".
[2] raw data for human sample is not provided due to privacy concerns.

first: Marten

last: Hoeksema


title: Genome-wide maps of nuclear lamina interactions in AML12 cells upon G9a/GLP inhibition [DamID]

city: Shanghai

first: Luzhang

last: Ji

address: 1239 Siping Rd.

institute: Tongji University

type: Genome variation profiling by genome tiling array

summary: In differentiated cells, inhibition of methyltransferases G9a and GLP eliminated H3K9me2 predominantly at A-type genomic compartments, and the remaining H3K9me2 marks were strongly associated with B-type compartments and lamina-associated domains (LADs). However, inhibition of G9a/GLP in mouse embryonic stem cells (ESCs) removed most of the H3K9me2 modifications in both A and B compartments. Furthermore, chemical inhibition of G9a/GLP in mouse hepatocytes decreased chromatin-nuclear lamina (NL) interactions, increased the degree of genomic compartmentalization and the boundary strength of topologically associating domains (TADs) between A and B compartments, and altered the expression of hundreds of genes that were associated with alterations of chromatin structure.

overall_design: LAMINB1 DamID data in DMSO and UNC0638 treated AML12 cells.


title: Integrative transcriptomic and proteomic analyses reveal that 15,16-dihydrotanshinone I inhibits  infantile hemangioma by interfering in posttranscriptional processing of hypoxia-inducible factor 1

status: Public on Jun 30 2021

first: Ding

last: Yu

address: Number 953 Jianchuan Road

institute: Newcore biotechnology

summary: Our team found that 15,16-dihydrotanshinone I (DHTS) was significantly effective at inhibiting infantile hemangioma proliferation in vitro and in vivo. To investigate the underlying mechanism by which DHTS inhibits hemangioma, we compared the transcriptomes of control and DHTS-treated hemangioma cells.

overall_design: mRNA profiles of control EOMA cells(treated by DMSO) and DHTS-treated EOMA cells

first: Peiwen

last: Duan

first: Yingying

last: Huang

first: Kai

last: Chen

first: Cheng

last: cheng

first: Yeming

last: Wu

first: Zhixiang


title: RNA-seq in normal human dermal fibroblast cells for understanding protective effects of visible red light (660nm) in response to UVB (312nm) exposure

city: Goyang-si

first: Young Rok

last: Seo

address: Dongguk-ro 32

department: Life science

institute: Dongguk University

summary: The aim of this study is identifying potential signaling pathways involve with visible red light induced photoprotective effect against skin damage by UVB exposure, using transcriptomic analysis

overall_design: Light treatment with UVB (312nm) 0.1J/㎠ and visible red light (660nm) 60J/㎠ in Normal Human Dermal Fibroblast cells. There are two of experimental tries with differentiated post incubation time after UVB treatment. 1) (n=3) : Control, Red (660nm red light 60J/㎠ treatment and post incubation for 1h), UV 1h (312nm UVB 0.1J/㎠ treatment and post incubation for 1h) , Pre-Red 1h (pre-treatment of red light before UVB treatment, post incubation for 1h after UVB treatment). 2) (n=3) : Control, Red (660nm red light 60J/㎠ treatment and post incubation for 1h), UV 4h (312nm UVB 0.1J/㎠ treatment and post incubation for 4h), Pre-Red 4h (pre-treatment of red light before UVB treatment, post incubation for 4h after UVB treatment).

first: H

last: Kim

first: Y

first: S

first: D

last: Kang

first: T

last: Lee

last: Shin


title: miR-579-3p controls hepatocellular carcinoma formation by regulating the PI3K-AKT pathway in chronically inflamed liver

first: Matthias

last: Matter

department: Institute of Pathology

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

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

overall_design: Refer to individual Series


title: Transcriptomic analysis of dorsal and ventral subiculum after induction of acute seizures by electric stimulation of the perforant pathway in rats

status: Public on Jun 18 2021

city: Campinas

first: Andre

last: Schwambach Vieira

state: SP

address: Rua Monteiro Lobato, 255 - Bloco J - 1 piso - Sala 3

country: Brazil

institute: State University of Campinas

summary:
Purpose: This study aims to characterize gene expression changes in dorsal and ventral subiculum after the induction of acute seizures by electrical stimulation of the Perforant Pathway (PP) in rats.
Methodolody: The dorsal (dSub) and  ventral (vSub) subiculum regions were collected by laser- microdissection laser 24 hours after preconditioning protocol, RNA was extracted using Trizol, RNA sequencing was performed in a Hiseq 4000 platform. Reads were aligned to the Rattus norvegicus Ensembl Rnor 5.0 assemble genome using the STAR, DESEq2 statistics package was used to estimate gene expression and for statistical analysis.
Results: We identified a total of 1176 differentially expressed genes, in which 204 genes were differentially expressed in dSub and 972 differential expression genes in vSub comparing control to preconditioning samples. The gene ontology enrichment analysis showed that the most significant common enrichment pathway considering up-regulated genes in dSub and vSub was Cholesterol Biosynthesis, while the most significant enrichment pathway considering down-regulated genes in vSub was Axon guidance. Moreover, we found GFAP, C3 and GAD2 up-regulated in dSub and vSub, downregulation of GLS2 in dSub and vSub, and downregulation of GAT-1 in vSub.
Conclusion:  These findings suggest preconditioning by PP electrical stimulations might induce synaptic reorganization, complement system activation, decreased glutamatergic transmission, and increased GABA transmission in subiculum areas. In the ventral subiculum, the down-regulation of proapoptotic genes and axon guidance indicates that preconditioning induces a neuroprotective environment in this region.

overall_design: Dorsal and Ventral subiculum mRNA profile 24 hours after preconditioning protocol compared to Control dorsal and ventral subiculum mRNA profile

first: Beatriz

middle: B

last: Aoyama

first: Gabriel

last: Zanetti

first: Elayne

middle: V

last: Dias

first: Maria

last: Athié

first: André

last: Vieira


title: RNA-Seq analysis SIRT1 knockdown effect on pancreatic cancer cell line

city: beijing

first: yan

last: wang

address: 17 panjiayuan nanli, chaoyang district, Beijing, China

country: Zimbabwe

institute: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences

summary: Pancreatic cancer is a common malignant tumor with poor prognosis. Accumulating evidence indicates that sirtuin 1 (SIRT1) exerts biological functions in various cancers.SIRT1 plays an important role in tumorigenesis, development, and drug resistance by blocking aging and apoptosis, also promoting cell growth and angiogenesis.However, how SIRT1 functions in the development of pancreatic cancer stem cells (CSCs) is currently poorly understood. Here, we showed that SIRT1 is involved in regulating various pathways closely related to tumor growth, autophagy and stemness, as well as promoting pancreatic CSC development.

overall_design: siSIRT1 or controls were transfected into PANC-1 cells (n=2 for each group) for 48 hours. Total RNA was isolated using Trizol reagent (Invitrogen, USA). Agilent 2100 Bioanalyzer (Agilent Technologies, USA) was used to evaluate the RNA quality.

first: Shuai

last: Leng

first: Yan

last: Wang


title: Expression data from glioblastoma stem cells after knockdown of PUS7

city: Duarte

first: wei

last: chen

address: 1500 E Duarte Rd

department: Cancer Biology-BRI

institute: City of Hope National Medical Center

summary: PUS7, a pseudouridine synthase, plays a critical role in growth, self-renewal, and tumorigenesis of glioblastoma stem cells. We used RNA-seq to investigate the global gene expression regulated by PUS7 and identified downstream pathway of PUS7 in glioblastoma stem cells.

overall_design: Glioblastoma stem cells were treated with lentivurs expressing constrol sgRNA or target (PUS7) sgRNA to knockdown the expression of PUS7.

first: Qi

last: Cui

first: Yanhong

last: Shi

first: Xiwei


title: The expression profiles of AMG510-resistant cancer cells

first: Yung-Ming

last: Jeng

address: No.7, Zhongshan S. Rd., Zhongzheng Dist.

institute: National Taiwan University Hospital

summary: AMG510 is a covalent inhibitor of G12C mutated KRAS. To identify the mechanism of resistance to AMG510, we treated MIA-PaCa2 cells with increasing dose of AMG510 for 2 months and established two population of cells that are resistant to 5 uM AMG510. RNA sequencing was used to extermine the expression profile.

overall_design: MIA-PaCa2 cells were treated with increasing dose of AMG510 for 2 months and established two population of cells that are resistant to 5 uM AMG510. RNA sequencing was used to extermine the expression profiles of the two populations of cells and two untreated control cell populations.

first: Chien-Hui

last: Chan

first: Li-Wen

last: Choiu

first: Yun-Ru

last: Liu

first: Tsung-Han

last: Hsieh


title: Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4 [ChIP-seq]

first: Christopher

last: Glass

overall_design:
ChIP-seq for BMDMs (bone marow-derived macrophages) from five mouse strains with IL-4 treatment

**Please note that
[1] each processed data (linked as Series supplementary files) was generated from multiple samples as indicated in the corresponding sample description field.
[2] raw data for human sample is not provided due to privacy concerns.

first: Marten

last: Hoeksema

first: Zeyang

last: Shen


title: Gene expression profiling of newly-diagnosed DLBCL samples with the NanoString nCounter technology

city: Fukuoka

first: Kohta

last: Miyawaki

address: 3-1-1, Maidashi, Higashi-ku

institute: Kyushu University

summary: Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy with varying prognosis after the gold standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Several prognostic models have been established by focusing primarily on characteristics of lymphoma cells themselves, including cell-of-origin, genomic alterations, and gene/protein expressions. However, the prognostic impact of the lymphoma microenvironment and its association with characteristics of lymphoma cells are not fully understood. Using highly-sensitive transcriptome profiling of untreated DLBCL tissues, we here assess the clinical impact of lymphoma microenvironment on the clinical outcomes and pathophysiological, molecular signatures in DLBCL. The presence of normal germinal center (GC)-microenvironmental cells, including follicular T cells, macrophage/dendritic cells, and stromal cells, in lymphoma tissue indicates a positive therapeutic response. Our prognostic model, based on quantitation of transcripts from distinct GC-microenvironmental cell markers, clearly identified patients with graded prognosis independently of existing prognostic models. We observed increased incidences of genomic alterations and aberrant gene expression associated with poor prognosis in DLBCL tissues lacking GC-microenvironmental cells relative to those containing these cells. These data suggest that the loss of GC-associated microenvironmental signature dictates clinical outcomes of DLBCL patients reflecting the accumulation of “unfavorable” molecular signatures.

overall_design: In the study presented here, a well-defined cohort of 170 DLBCL cases was used to acquire expression profiles of 447 genes

first: Takeshi

last: Sugio


title: Identification of ARGLU1 as a potential therapeutic target for gastric cancer based on genome-wide functional screening data

first: Li

last: Fangyuan

state: Shanghai

address: Ruijin Er road

institute: Shanghai Jiao Tong University

summary: Chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-Seq) in HGC27 cells using anti-ARGLU1 antibody

overall_design: Examination of ARGLU1 binding DNA sequence in gastric cancer HGC27 cells

first: Fangyuan

last: Li


title: Comparison of transcriptional profiles from 2W1S-specific CD4+ T cells during 2W1S-expressing Salmonella and Strongyloides ratti infections reveals that infectious context drives effector CD4+ T cell function

city: Philadelphia

first: De'Broski

last: Herbert

state: PA

address: 3900 Spruce Street

department: Pathobiology

institute: University of Pennsylvania

summary: Approximately one-third of the world is infected with parasitic helminths, and there are no available vaccines. Helminths induce robust type 2 immune responses and host CD4+ T cells are required for clearance, but how helminth-specific CD4+ T cells are generated and whether they adopt prototypical features of effector Th2 cells is entirely unknown. We generated a novel transgenic line of Strongyloides ratti to track and study  helminth-specific T cells. This transgenic line, termed Hulk, stably expresses immunodominant T cell epitope 2W1S as a fusion protein with FLAG and green fluorescent protein (GFP). We consistently observe expansion of CD44hiCD11ahi 2W1S-specific CD4+ T cells in the lungs of Hulk-infected C57BL/6 mice. Surprisingly, these cells do not exhibit a Th2 or regulatory T cell (Treg) phenotype, and their expansion is minimal compared to expansion following 2W1S-peptide immunization. In order to more thoroughly interrogate the phenotype and function of 2W1S-specific CD4+ T cells during Hulk infection, we performed mRNA sequencing on 2W1S-specific CD4+ T cells from both Hulk-infected and 2W-Salmonella-infected mice. Interestingly, whereas 2W1S-specific CD4+ T cells that expand during 2W-Salmonella infection express canonical pro-inflammatory genes, 2W1S-specific CD4+ T cells from Hulk-infected mice preferentially upregulate genes associated with immune suppression and wound healing. Altogether, these data suggest that helminth antigen specific CD4+ T cells may comprise an unconventional subset that mediates immunosuppression and tissue repair following helminth infection and not necessarily type 2 cytokine responses.

overall_design: Mice were infected with 2W1S-expressing S. ratti (Hulk, 15 mice) or Salmonella (Salm, 10 mice). Activated, 2W1S+CD62Llo CD4+ T cells (2W) were electronically sorted from mice in each group and pooled into 3 biological replicates for mRNA sequencing. Naive, 2W1S-CD62Lhi CD4+ T cells (N) were isolated in the same manner from mice in each group as internal naive controls and were pooled into 3 biological replicates in the same manner as the 2W samples for mRNA sequencing.

first: Bonnie

last: Douglas

first: Annabel

last: Ferguson


title: Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4


title: Genome-wide maps of chromatin state in PANC-1 cells.

first: yan

last: wang

summary: To investigate functional associations between SIRT1 and CUL4B, we  used ChIP-seq to analyze genome-wide SIRT1/CUL4B complex transcriptional targets. ChIP experiments were performed first in PANC-1 cells using antibodies against SIRT1 or CUL4B. Next, SIRT1- or CUL4B-associated DNA was amplified using non-biased conditions, labeled, and sequenced. Using Illumina HiSeq2000, we found lots of SIRT1- and CUL4B-specific binding peaks, respectively, representing the ChIP-seq peak. We found that strong  enrichment on the promoters of selected genes involved in classical pathways. This study gave us a new understanding of the role of SIRT1/CUL4B in chromatin status and gene transcription.

overall_design: Examination of  SIRT1 and CUL4B  target genes in PANC-1 cell line

first: Shuai

last: Leng

first: Yan

last: Wang


title: RNA-seq analysis of A549 cells based on DSTY knockdown

city: Changsha

first: yuan

middle: yu

last: zi

address: Changsha Xiangya Road

institute: Xiangya hospital

summary: Purpose: Analysis of the regulatory network involved in DSTY in lung cancer cells.  Methods: mRNA profiles of A549 knockdown cell group and A549 NC group were generated by deep sequencing, using Illumina Novaseq platform. Index of the reference genome was built using Hisat2 v2.0.5 and paired-end clean reads were aligned to the reference genome using Hisat2 v2.0.5. featureCounts v1.5.0-p3 was used to count the reads numbers mapped to each gene. And then FPKM of each gene was calculated based on the length of the gene and reads count mapped to this gene. Differential expression analysis of two conditions/groups (two biological replicates per condition) was performed using the DESeq2 R package (1.16.1). The resulting P-values were adjusted using the Benjamini and Hochberg’s approach for controlling the false discovery rate .Genes with an adjusted P-value <0.05 found by DESeq2 were assigned as differentially expressed. Clusterprofiler software was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis of the differential gene sets.  Results: We identified 2555 differential genes, of which 1444 were up-regulated and 1111 were down-regulated in A549 sh1 VS NC. In GO enrichment analysis,the biological process is mainly in the cell ions homeostasis and the molecular function is mainly in inflammation response,chemotaxis,innate immune response, and extracellular matrix. KEGG analysis shows that differential genes are enriched in cytokine-cytokine receptor interaction ,JAK-STAT signaling pathway and PI3K-Akt signaling pathways.We identified 2600 differential genes, of which 1523 were up-regulated and 1077 were down-regulated in A549 sh4 VS NC. In GO enrichment analysis,the biological process is mainly in the cell ions homeostasis and the molecular function is mainly in chemokine receptor binding,nic hydroxy compound metabolic process,alcohol metabolic process, and extracellular matrix. KEGG analysis shows that differential genes are enriched in cytokine-cytokine receptor interaction ,glutathione metabolism and chemical carcinogenesis.  Conclusion: Based on RNA-seq analysis, the regulatory network involved in DSTY in Lung cancer .

first: Chenxi

last: Zhong


title: Transcriptomic of hrdB regulatory strain in the Streptomyces lividans TK24 secdonary metabolism.

city: shanghai

first: Ming

last: Zhao

address: 130 Meilong Road, Xuhui District

institute: East China University of Science and Technology

summary: To avoid the complex switches and to reduce the limitations of different metabolic stages on the synthesis of metabolites, we designed a Streptomyces self-sustained system (StSS) that contains two functional modules, the primary metabolism module (PM) and the secondary metabolism module (SM). Here, the transcriptomic of hrdB regulatory strain in the secondary metabolism was analyzed.

overall_design: mRNA profiles of 84 h  PM egulatory strain and SM egulatory strain

first: Feng-Qing


title: ATAC-seq of embryonic motor neurons

city: Cambrdige

first: Jennifer

last: Hammelman

address: 32 Vassar Street

institute: MIT

summary: ATAC-seq of Hb9:GFP e10.5 spinal motor neurons from C57/Bl6 mice

first: Michael

last: Closser

first: Hynek

last: Wichterle


title: Transcriptome sequencing (RNA-Seq) of ACHN cells upon treatment of the 25nM,50nM Piericidin A or DMSO(0.1%) for exploring the mechanism of Piericidin A against the renal cell carcinoma

city: Guangzhou

first: Lan

last: Tang

state: Guangdong

address: 1838  Guangzhou North Ave,

department: School of Pharmaceutical Science

institute: Southern Medical University

summary: Piericidin A (PA), the most common member of the family of piericidins, is fermented from Streptomyces#sp.HBERC#58855. We have found that PA had significant cytostatic activity against the ACHN cells, which can be used as a potential drug against renal cell carcinoma (RCC). Therefore, we used the second-generation transcriptome sequencing (RNA-seq) to determine the expression changes of various genes in ACHN cells treated with PA (25nM,50nM) or DMSO (0.1%), so that we can investigate the molecular mechanism of PA against the RCC.

overall_design: mRNA profiles of ACHN cells upon treatment of the 25nM,50nM Piericidin A or DMSO(0.1%) were generated by deep sequencing, using Illumina HiSeqTM 4000


title: Early or Late Gestational Exposure to Maternal Immune Activation Alters Neurodevelopmental Trajectories in Mice: An Integrated Neuroimaging, Behavioral, and Transcriptional Study

city: Montreal

first: Mallar

last: Chakravarty

state: Quebec

address: 6875, boulevard LaSalle

country: Canada

institute: McGill

summary:
Background:
Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental disorders later in life. The impact of the gestational timing of MIA exposure on downstream development remains unclear.

Methods:
We characterized neurodevelopmental trajectories of mice exposed to the viral mimetic poly I:C (polyinosinic:polycytidylic acid) either on gestational day 9 (early) or on day 17 (late) using longitudinal structural magnetic resonance imaging from weaning to adulthood. Using multivariate methods, we related neuroimaging and behavioral variables for the time of greatest alteration (adolescence/early adulthood) and identified regions for further investigation using RNA sequencing.

Results:
Early MIA exposure was associated with accelerated brain volume increases in adolescence/early adulthood that normalized in later adulthood in the striatum, hippocampus, and cingulate cortex. Similarly, alterations in anxiety-like, stereotypic, and sensorimotor gating behaviors observed in adolescence normalized in adulthood. MIA exposure in late gestation had less impact on anatomical and behavioral profiles. Multivariate maps associated anxiety-like, social, and sensorimotor gating deficits with volume of the dorsal and ventral hippocampus and anterior cingulate cortex, among others. The most transcriptional changes were observed in the dorsal hippocampus, with genes enriched for fibroblast growth factor regulation, autistic behaviors, inflammatory pathways, and microRNA regulation.

Conclusions:
Leveraging an integrated hypothesis- and data-driven approach linking brain-behavior alterations to the transcriptome, we found that MIA timing differentially affects offspring development. Exposure in late gestation leads to subthreshold deficits, whereas exposure in early gestation perturbs brain development mechanisms implicated in neurodevelopmental disorders.

overall_design:
mRNA profile of exposure to prenatal maternal immune activation generated across 3 different brain regions (anterior cingulate cortex, dorsal hippocampus, ventral hippocampus), with a sample size of 6 males and 6 females per group (MIA-exposed and vehicle-exposed).

RNA-Seq was performed on mice at timepoint PND38, their mothers have been exposed to the viral mimetic poly I:C (polyinosinic:polycytidylic acid) on day GD9. We did the MRI and behavior on GD9 and GD17 exposed mice.

For the sample titles, 09, 13, 15 are the individual mouse numbers, and the second number is the litter number, so for example 01_09 is mouse 01 (individual number) from littler 9.

first: Elisa

last: Guma

first: Pedro

middle: d

last: Bordignon

first: Rosemary

last: Bagot


title: Analysis of Bone Morphogenetic Protein 15 (BMP15)-induced transcriptome in human granulosa cells for the identification of novel candidate genes for Primary Ovarian Insufficiency

status: Public on Jun 17 2021

city: CUSANO MILANINO

first: Raffaella

last: Rossetti

state: Italy

address: VIA ZUCCHI 18

institute: IRCCS ISTITUTO AUXOLOGICO ITALIANO

summary: Analysis of primary cultures of human granulosa cells (hGCs) stimulated with recombinant human BMP15 (rhBMP15) at gene expression level. The hypothesis tested in the present study was that rhBMP15 regulates genes and processes of maturation and differenti

overall_design: Total RNA obtained from primary cultures of hGCs stimulated with rhBMP15 for 2 and 6 hours compared to Not-stimulated control hGCs.

first: Marco

last: Fornili


title: Gene expression pattern analysis of rat articular cartilage and xiphoid cartilage

city: Changchun

first: Baojin

last: Yao

address: 1035 Boshuo Road

institute: Changchun University of Chinese Medicine

summary: We performed RNA-Seq analysis to investigate the gene expression patterns of rat articular cartilage and xiphoid cartilage.

overall_design: mRNA profiles of rat articular cartilage and xiphoid cartilage.

first: Zhenwei

last: Zhou

first: Xiangyang

first: Daqing


title: Species-dependent in vivo mRNA delivery and cellular response to nanoparticles

city: Atlanta

first: James

last: Dahlman

state: ga

address: 311 Ferst dr

institute: Georgia Institute of Technology

summary: Delivery of LNPs in humanized mice to determine transcriptional differences in human cells.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Humanized mice were administered ether pooled LNP libraries or PBS as a control using IV injection. Livers were digested with Collagenase and hepatocytes were sorted with FACS. In JD69 samples 3 mice per group were pooled prior to RNA-seq library prep. For the remaining samples mice were kept separate for biological replicates. Library prep was performed using modified SMART-seq protocol for 1000 cells.

first: Marine

last: Hatit

first: Curtis

last: Dobrowolski


title: Next Generation Sequencing of DIO intestine DMSO vs NCT (HNF4a agonist)

city: San Diego

first: Brian

middle: Patrick

last: James

address: 10901 North Torrey Pines Road

department: Genomics

institute: Sanford Burnham Prebys Medical Discovery Institute

summary: Mice rendered obese with high fat diet were treated by IP injection with N-trans caffeoyltyramine (NCT) (200 mg/kg bid) for 14 days, followed by harvesting of the intestine for analysis, including RNA isolation.

overall_design: Intestine of high fat diet induced non-alcoholic fatty liver (NAFLD) model treated with DMSO or NCT compound.

first: Fred

last: Levine


title: Hypoxia-induced ncRNA transcriptome in TNBC cells

city: Dallas

first: Weibo

last: Luo

state: Texas

address: 5323 Harry Hines Blvd.

department: Pathology

institute: UT Southwestern Medical Center

summary: Whole transcriptome sequencing was performed to identify ncRNA transcriptome in two human TNBC cell lines under normoxia and hypoxia

overall_design: MDA-MB-231 and SUM159 cells were exposed to 20% or 1% O2 for 24 hrs and subject to whole transcriptome sequencing.

first: Yanling

last: Niu


title: Differential gene expression in CD137HI vs CD137LO human healthy donor monocytes

city: Erlangen

first: Andrej

last: Stoll

address: Schwabachanlage 12

department: Department of Medicine 5 - Hematology and Oncology

institute: Friedrich-Alexander University Erlangen Nuremberg

summary: The cell surface glycoprotein CD137, which is also known as 4-1BB, belongs to the group of co-stimulatory immune receptors and is a member of the TNF receptor superfamily (TNFRSF). It is preferentially found on activated T-cells and regulatory T-cells but also innate immune cells such as natural killer cells, neutrophils, and monocytes can express CD137. In order to delineate properties of monocytes expressing CD137, RNAseq of CD137HI vs CD137LO expression monocytes was performed.

overall_design: Monocytes from three different healthy donors were purified via MACS and subsequently FACS-sorted into CD137HI and CD137LO populations followed by RNAseq analysis.

first: Maximilian

last: Fuchs

first: Meik

last: Kunz

first: Dimitrios

last: Mougiakakos


title: Transcriptome-wide Gene Expression Analysis in Peri-Implantitis Reveals Candidate Cellular Pathways

city: San Antonio

first: Georgios

last: Kotsakis

address: 7703 Floyd Curl Dr.

department: Periodontics

institute: UT Health San Antonio

summary:
Transcriptome analysis of oral tissue samples taken from peri-implantitis and healthy control patients
Peri-implantitis is a condition resulting in destructive inflammation in the peri-implant soft tissue barrier. Clinically, it demonstrates vast clinical differences to periodontitis that suggests distinct inflammatory mechanisms. Implant-derived Titanium particles (i-TiPs) frequently found around diseased implants appear to alter the microenvironment and confer resistance to antibiotic treatments. Studies in orthopedic implants have demonstrated a strong inflammatory response to i-TiPs, involving a variety of cell types, in aseptic conditions. Nonetheless, the genetic programs of cells surveilling and supporting the peri-implant soft tissue barrier in response to the combined challenges of biomaterial degradation products and oral bacteria are poorly defined. Thus, we studied gene expression specific to oral peri-implant inflammatory disease. We found that certain cellular pathways were highly upregulated in diseased tissues. Upregulated pathways provided insight into important physiological pathways that might play a role in peri-implant pathology. These findings could potentially contribute to the production of more targeted and effective therapeutics for the disease.

overall_design:
We performed transcriptomic analysis on peri-implant soft tissue from 3 healthy implant controls and 4 peri-implantitis patients.  Array data was processed by Affymetrix Exon Array Computational Tool with the use of the Summarization Signal Space Transformation - Robust Multichip Analysis (SST-RMA) algorithm.
----------------------------------------------
CHP file not provided for Well A12 Sample

first: Martin

last: Alexander

first: Kotsakis

last: Georgios

first: Zhou

last: Peng


title: RNA-Seq analysis SIRT1 overexpression effect on pancreatic tumor tissue in NOD/SCID mice

first: yan

last: wang

address: 17 panjiayuan nanli, chaoyang district, Beijing, China

institute: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences

summary: Pancreatic cancer is a common malignant tumor with poor prognosis. Accumulating evidence indicates that sirtuin 1 (SIRT1) exerts biological functions in various cancers.SIRT1 plays an important role in tumorigenesis, development, and drug resistance by blocking aging and apoptosis, also promoting cell growth and angiogenesis.However, how SIRT1 functions in the development of pancreatic cancer stem cells (CSCs) is currently poorly understood. Here, we showed that SIRT1 inhibits the differentiation of cancer cells by inhibiting  various genes expression , including GRHL3, thus promoting the stemness and tumorigenesis of pancreatic cancer.

overall_design: PANC-1 cells transfected with stable expression of  vector or  SIRT1.  These cells were injected subcutaneously into the groin of 6-week-old female NOD/SCID mice under limiting dilutions. We further extracted tota RNA using Trizol reagent (Invitrogen, USA) from tumor samples 4 weeks after injection. Agilent 2100 Bioanalyzer (Agilent Technologies, USA) was used to evaluate the RNA quality.

first: Shuai

last: Leng

first: Yan

last: Wang


title: Identification of chromatin states during zebrafish gastrulation using CUT&RUN and CUT&Tag

city: Athens

first: Mary

last: Goll

state: GA

address: 120 East Green Street

department: Genetics

institute: University of Goergia

summary: Here we describe successful implementation of CUT&RUN for profiling protein-DNA interactions in zebrafish embryos. We apply modified a CUT&RUN method to generate high resolution maps of enrichment for H3K4me3, H3K27me3, H3K9me3, and RNA polymerase II during zebrafish gastrulation. Using this data, we identify a conserved subset of developmental genes that are enriched in both H3K4me3 and H3K27me3 during gastrulation, and we demonstrate the increased effectiveness of CUT&RUN for detecting protein enrichment at repetitive sequences with reduced mappability.  Our work demonstrates the power of combining CUT&RUN  with the strengths of the zebrafish system to better understand the changing embryonic chromatin landscape and its roles in shaping development.

overall_design: CUT&RUN in 6hpf zebrafish embryos for H3K27me3, H3K4me3, H3K9me3, and pol-II. Experiments performed in duplicate with an IgG control.

first: Bagde

last: Akdogan-Ozdilek

first: Katherine

last: Duval


title: Regulation of hypoxia-inducible factor activity by CHD4

summary: CHD4 coactivates a subset of HIF target genes in breast cancer MDA-MB-231 cells.

overall_design: MDA-MB-231 cells were exposed to 20% or 1% O2 for 24 hrs and subjected to mRNA-seq.

last: Chen


title: The role of RAB11B-AS1 in gene regulation under hypoxia

last: Luo

summary: RAB11B-AS1 is induced by hypoxia and controls gene expression in breast cancer cells under hypoxia

overall_design: MDA-MB-231-EV and -RAB11B-AS1 cells were exposed to 20% or 1% O2 for 24 hrs and subjected to mRNA-seq. MDA-MB-231 cells were exposed to 1% O2 for 24 hrs and subjected to ChIP-seq.

first: Lei

last: Bao


title: Comparing mRNA and sncRNA profiles during the maternal-to-embryonic transition in bovine  IVF and scNT embryos

city: Logan

first: Abby

middle: D

last: Benninghoff

state: UT

address: 4815 Old Main Hill

department: Animal, Dairy and Veterinary Sciences

institute: Utah State University

type: Non-coding RNA profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Effect of CD137 (4-1BB) triggering on human monocytes

last: Stoll

summary: The cell surface glycoprotein CD137, which is also known as 4-1BB, belongs to the group of co-stimulatory immune receptors and is a member of the TNF receptor superfamily (TNFRSF). It is preferentially found on activated T-cells and regulatory T-cells. In T-cells, CD137-crosslinking delivers a potent co-stimulatory signal as it promotes T-cell proliferation, formation of memory cells and enhances survival. Despite numerous studies investigating the effects of co-stimulatory CD137 in T-cells, little is known regarding the role of CD137 in human monocytes/macrophages. To investigate the effect of CD137 triggering on human monocytes, monocytes were isolated and treated with an agonistic CD137 mAb and subsequently analyzed by RNA-seq.

overall_design: Monocytes from three different healthy donors were cultured with or without agonistic CD137 mAb followed by RNAseq analysis.


title: Genome-wide DNA methylation analysis of HER2-positive breast cancer and stroma

status: Public on Jun 16 2021

city: Chuo-ku

first: Satoshi

last: Yamashita

state: Tokyo

address: Tsukiji 5-1-1

institute: National Cancer Center Research Institute

summary: DNA methylation in HER2-positive breast cancers

overall_design: Multi-omics screening was conducted using laser capture microdissection-purified samples to explore response markers of HER2‑positive breast cancer to HER2‑directed therapy.

last: Fujii

first: Takeshi

last: Yamaguchi

first: Masato

last: Takahashi

first: Yasuo

last: Hozumi

first: Toshikazu

last: Ushijima

first: Hirofumi

last: Mukai


title: IGF2 Mediates Resistance to Isoform-Selective-Inhibitors of the PI3K in HPV Positive Head and Neck Cancer

city: Beer Sheva

first: Moshe

last: Elkabets

address: Ben-Gurion

country: Israel

institute: Ben-Gurion University

summary: In the current study, we delineate the molecular mechanisms of acquisition of resistance to two isoform-selective inhibitors of PI3K (isiPI3K), alpelisib and taselisib, in human papillomavirus positive head and neck cell lines. By comparing RNA sequencing of isiPI3K-sensitive tumor cells and their corresponding isiPI3K-acquired-resistant tumor cells, we found that overexpression of insulin growth factor 2 (IGF2) is associated with the resistance phenotype. We further demonstrated by gain and loss of function studies that IGF2 plays a causative role in limiting the sensitivity of human papillomavirus-positive head and neck cell lines. Moreover, we show that blocking IGF2 stimulation activity, using an inhibitor of the IGF1 receptor (IGF1R), enhances isiPI3K efficacy and displays a synergistic anti-tumor effect in vitro and superior anti-tumor activity ex vivo and in vivo.

overall_design: we generated two acquired-resistant cell line models from UM-SCC47 and UT-SCC60A cells.UM-SCC47 and UT-SCC60A tumor cell lines were exposed to increasing concentrations of either GDC0032 or BYL719, respectively, for four to eight months, until resistance developed. We mapped the transcriptional landscape of isiPI3K-sensitive and isiPI3K-resistant cell lines by RNA sequencing (RNAseq). Specifically, we used the parental UM- SCC47 and UT-SCC60A and their corresponding acquired resistance models, UM- SCC47-Res2 and UT-SCC60A-Res2. Importantly, RNA extraction from the resistant cells was performed following 48 h of drug-free culture.

first: Mai

last: Badarni


title: Analysis of gene expression in primary murine OPC isolated from cerebrum and spinal cord to identify differentially regulated genes important for OPC migration

city: Münster

first: Julia

last: Ghelman

address: Pottkamp 2

department: Institute of Neuropathology

institute: University Hospital Münster

summary: Recent studies indicate that the oligodendroglial cell population is heterogeneous on transcriptional and functional level depending on the location in the CNS. Here, we compared primary murine OPC from spinal cord and brain on transcriptional level using whole-genome microarray. Identified up- and downreggulated genes may indicate intrinsic differences between those two populations

overall_design: Total RNA was obtained from primary murine OPC cultivated for 7 days in vitro under proliferating conditions. Three biological replicates were used and corresponding samples (n1 to n3) indicate isolated cells from one cell preparation (a pool of 3-4 mouse pups at P6-8)

first: Tanja

last: Kuhlmann


title: A transcriptomic analysis of  EDN1 overexpression in HepG2 cells.

city: Daejeon

first: Sang-Min

last: Park

address: Youseong-Daero

department: College of Pharmacy

institute: Chungnam National University

summary: We performed RNA sequencing analysis of two Hepatocellular carcinoma (HCC) cell lines (HepG2_Mock and HepG2_EDN1 O/E).

overall_design: Expression profiles of HepG2_Mock and HepG2_EDN1 O/E cells were generated by RNA sequencing, in quadruplicate, using Illumina NextSeq 500.

first: ChaeYoung

last: Hwang

first: Soobeom

last: Lee

first: Kwang-Hyun

last: Cho


title: WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [zebrafish RNAseq]

city: Shanghai

first: Chen

last: Lin

address: NO.2005 Songhu road

institute: Fudan university

summary: Granulomas are the pathological hallmark of tuberculosis (TB). In individuals latently infected with Mycobacterium tuberculosis (M. tb), the bacteria are thought to reside within the granulomas in a nonreplicating dormant state due to the lack of oxygen and nutrients. However, a portion of these individuals will develop active TB and little is known on the bacterial mechanisms/factors involved in this process. In this study, we found that WhiB4, an oxygen sensor and a transcription factor, plays a critical role in disease progression and reactivation of Mycobacterium marinum (M. marinum) infection in zebrafish. We show that the whiB4 mutant of M. marinum caused latent infection in adult zebrafish, which is characterized by the stable bacterial loads, constant number of non-necrotized granulomas in fewer organs, and reduced immune responses compared to zebrafish infected with the wild type bacteria or the complemented strain. The mutant bacteria in zebrafish were also less responsive to antibiotic treatments. Moreover, the whiB4 mutant was defective in resuscitation from hypoxia-induced dormancy and that the DosR regulon was dysregulated in the mutant. Taken together, our results suggest that WhiB4 is a major driver of reactivation from latent infection and that WhiB4 is an attractive target for the development of novel therapeutics, which may help to prevent the reactivation of latent infection thereby reducing the incidences of active TB.

overall_design: mRNA profiles of zebrafish kidney infected with whiB4 mutant strain and wild type;a total of 6 samples were analyzed, 3 relicates were included for control and experiment samples.

first: Lu

last: Zhang

first: Jun

last: Liu


title: Selective dysregulation of ROCK2 activity promotes aberrant transcriptional networks in ABC diffuse large B cell lymphoma

city: New York

first: Akanksha

last: Verma

state: New York

address: 1300, York Avenue

department: Department of Physiology and Biophysics

institute: Weill Cornell Medical College

summary: We have found that ROCK2 regulates a transcriptional program in U2932, an ABC-DLBCL cell line by RNA-seq analysis.

overall_design: U2932 cells were lentivirally infected with shRNA constructs targeting ROCK2 or a scrambled shRNA control. Stable cell lines were generated using sorting and puromycin-selection techniques. Total RNA was harvested from stable cell lines and used for transcriptional profiling via RNA-seq.

first: E

last: Ricker

first: A

first: O

last: Elemento

last: Pernis


title: The cholesterol metabolite 27-hydroxycholesterol increases the secretion of extracellular vesicles which promote breast cancer progression

city: Urbana

first: Erik

last: Nelson

state: Illinois

address: 407 S Goodwin Ave

department: Molecular and Integrative Physiology

institute: University of Illinois at Urbana Champaign

summary: Mice bearing Met1 tumors were treated with extracellular vessicles (EVs) isolated from neutrophils treated with vehicle (DMSO) or 27-hydroxycholesterol. RNAseq was performed on harvested tumors.

first: Amy

middle: E

last: Baek

first: Natalia

last: Krawczynska

first: Anasuya

last: Gupta

first: Svyatoslav

last: Dvoretskiy

first: Sixian

last: You

first: Jaena

first: Yu-Heng

last: Deng

first: Janet

last: Sorrells

first: Brandi

last: Smith

first: Liqian

last: Ma

first: Adam

first: Hannah

last: McDowell

first: Ashabari

last: Sprenger

first: Madeline

last: Henn

first: Zeynep

last: Madak-Erdogan

first: Hyunjoon

last: Kong

first: Stephen

last: Boppart

first: Marni

middle: R


title: Gene expression analysis of cultured bone marrow-derived eosinophils in response to GM-CSF and IL-10 stimulation

city: Zürich

first: Miquel

last: Anglada Girotto

address: Cäsar-Ritz-Strasse, 5/560

institute: Functional Genomics Center Zurich

summary: gene expression analysis through RNA sequencing of cultured bone marrow-derived WT, IRF5-/- or Csf2ra-/- eosinophils that were exposed or not to recombinant GM-CSF, IL-10 ot both overnight.

overall_design: Examination of 3 different eosinophil genotypes in 4 different treatment settings

first: Anne

last: Müller

first: Isabelle

last: Arnold


title: Infinium MethylationEPIC BeadChip array data for HGSOC PH039 PDXs at baseline and treated with cycles of 100 mg/kg niraparib for 21 days for four treatment rounds and murine sample.

city: Rochester

first: Hu

last: Li

state: MN

address: 200 First Street, Gonda Building G19-408

department: Molecular Pharmacology & Experimental Therapeutics

institute: Mayo Clinic

type: Methylation profiling by genome tiling array

overall_design:
Infinium MethylationEPIC BeadChip data of 8 samples: Niraparib arm (n=4 over three treatment cycles) or source tumor arm passaged without drug (n=4) passaged ).
HGSOC= high grade serous ovarian cancer
PDX= personalized derived xenograph

first: Scott

last: Kaufmann

first: Ee

last: Ming Wong

first: Melissa

last: Southey

first: Nesic

last: Ksenija

first: Olga

last: Kondrashova

first: Matthew

last: Wakefield

first: Clare

last: Scott


title: Gene expression profile of A549 cells treated with TGF-beta

city: Suita

first: Sho

last: Tabata

state: Osaka

address: 3-2 Yamadaoka

department: Institute for Protein Research,ces

institute: Osaka University

summary: Epithelial–mesenchymal transition (EMT) is a plastic process that converts epithelial cells into migratory and invasive cells. Accumulating evidence indicates that EMT is a key event for metastasis in several types of cancer, including non-small cell lung cancer (NSCLC). Especially, transforming growth factor-beta (TGF-beta) acts as a potent inducer of EMT and contributes to cancer progression. Emerging studies suggest that a metabolic reprograming is essential to acquire the EMT phenotype in cancer cells. However, a comprehensive understanding of metabolism in cancer EMT remains largely unexplored. Here, we analyzed metabolic changes during TGF-beta-induced EMT in NSCLC A549 cells using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). At the same time, we examined the expression of metabolic-related genes using microarray analysis.

overall_design: Gene expression in A549 cells treated with TGF-beta for 72 h was measured.