title: Validation of a non-oncogene encoded vulnerability to Exportin 1 inhibition in pediatric renal tumors

status: Public on Mar 09 2022

city: New York

first: Prabhjot

middle: Singh

last: Mundi

state: NY

address: 1130 St. Nicholas Avenue

department: Medicine; Systems Biology

institute: COLUMBIA UNIVERSITY HEALTH SCIENCES

summary:
We identified XPO1 as an aberrantly activated, non-oncogene encoded targetable vulnerability in pediatric renal tumors (Wilms and malignant rhabdoid tumor [MRT]) using OncoTarget, a Master Regular-based precision cancer medicine tool.
We demonstrate significant anti-tumor activity of selinexor and eltanexor, two selective XPO1 inhibitors, in patient derived xenograft mice models of Wilms and MRT, and report on a case of successful treatment of a pediatric cancer patient.

overall_design: RNASeq profiles of MRT cell lines and PLATESeq profiles of selinexor (or DMSO control) perturbation in multiple MRT cell lines.

middle: S

first: Diego

last: Coutinho

first: Filemon

last: De laCruz

first: Andrea

last: Califano

first: Andrew

last: Kung


title: Genome-Scale CRISPR Knockout Screening Identifies BACH1 as a Key Regulator of Aflatoxin B1-Induced Oxidative Damage [CRISPR screening]

status: Public on Mar 25 2022

city: Wuhan

first: Shengsong

last: Xie

state: Hubei

address: 1st Shizishan Street, Hongshan

country: China

institute: Huazhong Agricultural University

summary: Aflatoxin B1 (AFB1) is amongst the mycotoxins commonly affecting human and animal health, raising global food safety and control concerns. The mechanisms underlying AFB1 toxicity are poorly understood. Moreover, antidotes against AFB1 are lacking. Genome-wide CRISPR/Cas9 knockout screening in porcine kidney cells identified the transcription factor BTB and CNC homolog 1 (BACH1) as a gene required for AFB1 toxicity. The inhibition of BACH1 expression in porcine kidney cells and human hepatoma cells resulted in increased resistance to AFB1. BACH1 depletion attenuates AFB1-induced oxidative damage via the upregulation of antioxidant genes.

overall_design: To systematically identify the host genes required for AFB1-induced cell death, we performed a genome-wide CRISPR KO screen in porcine kidney (PK)-15 cells stably expressing Cas9 (hereafter referred to as PK-15-Cas9), as described in previous work. We first performed three rounds of challenge with AFB1, using untreated PK-15-Cas9 cells as a negative control to confirm that cell death was attributable to AFB1 exposure in each round. Three rounds of AFB1 challenge were carried out with increasing doses of 0.2 µg/mL, 1 µg/mL, and 6 µg/mL, respectively. Since oxidative damage caused by AFB1 is a central mechanism of AFB1-induced cell death, we sought to identify the genes involved in AFB1-induced oxidative damage. Thus, the surviving cells in the second round were simultaneously exposed to hydrogen peroxide (H2O2), a classical model inducer of oxidative stress, and integrated small guide RNA (sgRNA) constructs were obtained from the cells that survived AFB1 and H2O2 by PCR and Illumina-based sequencing.

first: Shuhong

last: Zhao

first: Jinfu

last: Zhang

first: Changzhi


title: scRNA-seq of Chrna7+ bone marrow stromal cells in Chat-fl/fl and Cd19-Cre Chat-fl/fl mice

city: Boston

first: I-Hsiu

last: Lee

state: Massachusetts

address: 185 Cambridge Street

department: Center for Systems Biology

country: USA

institute: Mass General Hospital/Harvard University

type: Expression profiling by high throughput sequencing

summary: Examination of gene expression in FACS-purified Ter119- CD45- Chrna7+ bone marrow stromal cells as a function of B cell-derived acetylcholine

overall_design: Ter119- CD45- Chrna7+ bone marrow stromal cells were FACS purified from the bone marrow of Chat-fl/fl and Cd19-Cre Chat-fl/fl steady state mice followed by scRNA-seq analysis to identify differentially expressed genes and enriched gene sets.

first: Maximilian

middle: J

last: Schloss

first: Maarten

last: Hulsmans

first: Kamila

last: Naxerova

first: Matthias

last: Nahrendorf


title: RNA-seq of mature Chat+ and Chat- B cells in steady state murine bone marrow

summary: Examination of differentially expressed genes and GSEA analysis of FACS sorted Chat+ and Chat- mature B cells.

overall_design: Mature Chat+ and Chat- B cells were FACS sorted from the bone marrow of steady state Chat-GFP mice and underwent RNA-seq analysis for differentially expressed genes and GSEA.

first: I

middle: H


title: RNA Sequencing of a Phase Ib/II Study of Regorafenib and Paclitaxel in Patients with Beyond First-line Advanced Esophagogastric Carcinoma (REPEAT)

status: Public on Mar 11 2022

city: Amsterdam

first: Hanneke

last: van Laarhoven

address: Meibergdreef 9

department: Medical Oncology

country: Netherlands

institute: Amsterdam UMC, AMC

summary: We report the RNA sequencing data from the REPEAT study, in which patients with beyond first-line esophagogastric cancer were treated with regorafenib and paclitaxel. For the RNA sequencing, biopsies from metastatic lesions were obtained on baseline (n=21) and fifteen days following treatment initiation (n=13). PURPOSE: Regorafenib monotherapy, a multikinase-inhibitor of angiogenesis, tumor microenvironment, and oncogenesis, showed promising results in gastric cancer. We aimed to assess the tolerability of regorafenib and paclitaxel in advanced esophagogastric cancer (EGC) patients refractory to first-line treatment, and explore potential biomarkers.  METHODS: Patients received paclitaxel (80 mg/m2) on days 1, 8, and 15 of a 28-day cycle and regorafenib (80/120/160 mg) on day 1-21 in the dose-escalation cohort, and the maximum-tolerated dose (MTD) in the dose-expansion cohort. Exploratory, overall- (OS) and progression-free survival (PFS) were compared to a propensity-score matched cohort receiving standard second/third line systemic treatment. Paclitaxel pharmacokinetics were assessed using D1 and D15 samples. We performed ELISA measurements of galectin-1, RNA sequencing and shallow whole-genome sequencing of metastatic tumor biopsies for biomarker analyses.  RESULTS: In the dose-escalation cohort (n=14), the MTD of regorafenib was 120 mg. Thirty-four patients were enrolled in the dose-expansion cohort. Most common toxicities (all grades; grade ≥3) were fatigue (79%; 4%) and sensory neuropathy (63%; 4%). Best responses achieved were partial response (28%) and stable disease (54%). Median OS and PFS were 7.8 and 4.2 months, respectively (median follow-up 7.8 months). OS (p=0.08) and PFS (p=0.81) were not significantly improved compared to the matched cohort. Paclitaxel concentrations were significantly increased with regorafenib (D15) compared with paclitaxel only (D1; p<0.05); no associations were observed with toxicity or efficacy. An increase in circulating galectin-1 compared to baseline was associated with shorter OS (p<0.01). Enrichment of angiogenesis-related gene expression was observed in short-survivors measured by RNA sequencing. Chromosome 19q13.12-q13.2 amplification was associated with shorter OS (p=0.02) and PFS (p=0.02).   CONCLUSION: Treatment with regorafenib and paclitaxel is tolerable and shows promising efficacy in advanced EGC refractory to first-line treatment. Galectin-1 and chromosome 19q13.12-q13.2 amplification could serve as negative predictive biomarkers for treatment response.

overall_design: RNA sequencing data from 34 metastatic biopsies, obtained from patients with advanced esophagogastric cancer

first: Charlotte

middle: I

last: Stroes

first: Sandor

last: Schokker

first: Mohammed

last: Khurshed

first: Stephanie

middle: O

last: van der Woude

first: Ron

middle: A

last: Mathot

first: Marije

last: Slingerland

first: Judith

last: de Vos-Geelen

first: Massimo

last: Zucchetti

first: Cristina

last: Matteo

first: Erik

last: van Dijk

first: Bauke

last: Ylstra

first: Victor

last: Thijssen

first: Sarah

last: Derks

first: Tesfay

last: Godefa

first: Willemieke

last: Dijksterhuis

first: Gerben

middle: E

last: Breimer

first: Otto

middle: M

last: van Delden

first: Rob

last: Verhoeven

first: Sybren

middle: L

last: Meijer

middle: F

last: Bijlsma

middle: W


title: The confused cell identity is associated with aggressiveness in esophageal squamous cell carcinoma [bulkRNA-Seq]

status: Public on Mar 16 2022

city: Chengdu, Cihna

first: Xaingyu

last: Pan

state: Sichuan

address: No.17 Renming road section3

department: State Key Laboratory of Biotherapy, West China Hospital, Sihcuan University.

institute: Sichuan University

summary: Seven tumor samples and one distal normal sample from five pathologically confirmed ESCC patients were analyzed with 10X Genomics scRNA-seq. To better represent the squamous epithelial cells, we optimized the dissociation protocol. Total 44,206 cells were obtained, including 16,657 normal and malignant squamous epithelial cells. The squamous epithelial cells, glandular epithelial cells, immune cells, endothelial cells and other tumor microenvironmental cells were clearly separated and identified with classic markers.Seven tumor samples and one distal normal sample from five pathologically confirmed ESCC patients were analyzed with 10X Genomics scRNA-seq. To better represent the squamous epithelial cells, we optimized the dissociation protocol. Total 44,206 cells were obtained, including 16,657 normal and malignant squamous epithelial cells. The squamous epithelial cells, glandular epithelial cells, immune cells, endothelial cells and other tumor microenvironmental cells were clearly separated and identified with classic markers.

overall_design: The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer. Here, we report that esophageal squamous cell carcinoma (ESCC) cells display molecular features similar but distinct to all three types of normal esophageal epithelial cells, which we term as confused cell identity (CCI). CCI is an independent prognostic marker associated with poor prognosis in ESCC. Further, we identify tripomyosin 4 (TPM4) as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo. And TPM4 creates CCI through activating the JAK/STAT-SOX2 pathway. Thus, our study suggests a precedent unrecognized feature of ESCC cells, which might be of value for clinic prognosis and potential interference.

first: Xiangyu

first: Jian

last: Wang

first: Linjie

last: Guo

first: Jiajia

last: Du

first: Chong

last: Chen

first: Yu

last: Liu


title: Effects of VPA in P19KO embryos

status: Public on May 12 2022

city: Illkirch-Grafenstaden

first: Bill

last: Keyes

address: 1, rue Laurent Fries

department: Development and Stem Cells

country: France

institute: IGBMC

summary: To identify genes that are induced by Valproic acid in E8.5 mouse embryos, and how these genes are altered in p19-deficient embryos

overall_design: Forebrain+midbrain mRNA profiles of E8.75 embryos WT, WT+VPA, p19-/- and p19-/-+VPA, each 4 replicates

first: Muriel

last: Rhinn


title: single-cell RNA and TCR sequencing of TRM and ReCirulating CD8+ T cells sorted from 4 HGSOC tumors

status: Public on Mar 07 2022

city: Tampa

first: jiqiang

last: yao

address: 12902 USF Magnolia Drive

institute: moffitt cancer center

summary: Purpose: Characterization of the gene expression profile and TCR profile of CD8+ TILs (TRM and re-circulating) from HGSOC to understand the immunogenicity of ovarian cancer

overall_design: We FACs-sorted TRM and ReCirulating CD8+ T cells from 4 HGSOC disscociated tumors and performed 10X single-cell RNA and TCR sequencing

first: Carmen

last: Anadon

first: Xiaoqing

last: Yu

first: Jose

middle: R

last: Conejo-Garcia


title: single-cell RNA and TCR sequencing of TRM CD8+ T cells sorted from 8 HGSOC tumors

overall_design: We FACs-sorted TRM CD8+ T cells from 8 HGSOC disscociated tumors and performed 10X single-cell RNA and TCR sequencing


title: Bulk RNA sequencing of TRM and ReCirculating CD8+ T cells from 7 HGSOC tumors

summary: Purpose: Characterization of the gene expression profile of CD8+ TILs (TRM vs. re-circulating) from 7 HGSOC

overall_design: We FACs sorted TRM and ReCirculating CD8+ T cells from 7 HGSOC disscociated tumors and performed bulk RNA-seq

last: Anadon Anadon


title: Single-cell RNA/ATAC multiomic analysis of TRM and ReCirulating CD8+ T cells from HGSOC tumors

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Purpose: Evaluation of the BCR profile of HGSOC associated/infiltrated B cells

overall_design: We isolated  TRM and ReCirulating CD8+ T cells from X HGSOC disscociated tumors and performed 10X Multiome ATAC + Gene Expression


title: A Single Cell Transcriptome Atlas of The Domestic Pig II

status: Public on Mar 01 2022

city: Aarhus

first: Lin

last: Lin

address: Høegh-Guldbergs Gade 10

department: Department of Biomedicine

country: Denmark

institute: Aarhus University

summary: By leveraging single-cell/nuclei RNA sequencing, we generate the first single-cell transcriptome atlas of over 200,000 pig cells from 20 tissues/organs, as well as cultured ECs

overall_design:
In this study, we report the generation of a single-cell transcriptome atlas of 222,526 cells across twenty tissues of the domestic pig, and ECs from Aorta and lung by using scRNA-seq and single-nuclei RNA-sequencing (snRNAseq).

Please note that the processed data files have been replaced on Sep 29, 2022.
In the previous files, the mitochondria gene name in the gene matrix were with the "MT-" prefix. To be consistent with the pig Sus_scrofa11.1 genome assembly, the matrix has been updated with "MT-" prefix removed for the pig mitochondria genes.


title: Single cell RNA-sequencing in the suprafornical area of lateral hypothalamus

status: Public on Feb 22 2022

city: Ashburn

first: Scott

last: Sternson

state: VA

address: 19700 Helix Dr.

institute: Janelia Research Campus, HHMI

summary: The single-cell RNA sequencing was focused on the suprafornical LHA and its surrounding areas. For single cell dissociation and collection, we used transgenic animal Agrp-IRES-Cre × Ai9 crosses, where the tdTomato-labeled AGRP neurons extend a prominent set of axonal projections to the suprafornical region of the LHA and provide a useful signal for visually guided dissection of the targeting brain region. Single-cell cDNA libraries were prepared using the Smart-SCRB chemistry.

overall_design: Cells from 7 male Agrp-IRES-Cre × Ai9 mice (age 6-8 weeks) were hand-sorted and cDNA libraries were prepared using the Smart-SCRB chemistry. Barcoded cDNA libraries were then pooled and sequenced on a NextSeq 550 high-output flowcell with 27 bp in read 1 to obtain the barcode and UMI, and 125 bp in read 2 for cDNA.  PhiX control library (Illumina) was spiked in at a final concentration of 15% to improve color balance in read 1. Libraries were sequenced to an average depth of 135,025 ± 38401 (mean ± S.D.) reads per cell.

first: Fredrick

last: Henry

first: Andrew

last: Lemire

first: Lihua


title: The A to I editing landscape in melanoma and its relation to clinical outcome

status: Public on Mar 21 2022

city: Geneva

first: Phil

middle: Fang

last: Cheng

address: Rue Gabrielle-Perret-Gentil 4

department: Oncology

country: Switzerland

institute: Hopitaux universitaires de Geneve

summary: RNA editing refers to not transient RNA modifications that occurs after transcription and prior to translation by the ribosomes. RNA editing is more widespread in cancer cells than in non-transformed cells and is associated with tumorigenesis of various cancer tissues, however, RNA editing can also generate neo-antigens that expose tumour cells to host immunosurveillance. Global RNA editing in melanoma and its relevance to clinical outcome currently remains poorly characterized. The present study compared RNA editing as well as gene expression in tumour cell lines from melanoma patients of short or long metastasis-free survival, patients relapsing or not after immuno- and targeted therapy and patients harbouring BRAF or NRAS mutations.

overall_design: Single-end RNAseq of 72 melanoma cell cultures


title: Myxoma virus subdues type 1 interferon responses through a host range determinant

status: Public on Feb 14 2022

city: Little Rock

first: Jia

state: AR

department: Microbiology and Immunology

institute: University of Arkansas for Medical Sciences

summary: Evolutionarily successful poxviruses presented effective and diverse strategies to circumvent or overcome host defense mechanisms. Poxviruses encode many immunoregulatory proteins to evade host immunity for a productive infection and unique means of inhibiting DNA-sensing dependent type 1 interferon (IFN-I) responses is anticipated due to the biology of its dsDNA genome in nature and an exclusive cytoplasmic life cycle. We found the key DNA sensing inhibition by poxvirus infection was dominant during the early stage of poxvirus infection independent from DNA replication. In an effort of identifying poxvirus novel means to subdue antiviral proinflammatory responses e.g., IFN-I response, we focused on the function of one early gene that is the known host range determinant from the highly conserved poxvirus host range C7L superfamily, myxoma virus (MYXV) M062. Host range factors are unique features of poxviruses that determine the species and cell type tropism. Almost all sequenced mammalian poxviruses retain at least one homologue of the poxvirus host range C7L superfamily. In MYXV, a rabbit specific poxvirus, the dominant and broad-spectrum host range determinant of the C7L superfamily is the M062R gene. M062R gene product is essential for MYXV infection in almost all cells tested from different mammalian species and specifically inhibits the function of host Sterile α Motif Domain-containing 9 (SAMD9), as M062R-null (ΔM062R) MYXV causes abortive infection in a SAMD9-dependend manner. In this study we investigated the immunostimulatory property of the ΔM062R. We found that the replication-defective ΔM062R infection activated host DNA sensing pathway in the cGAS dependent fashion and knocking down SAMD9 expression attenuated proinflammatory responses. Moreover, transcriptomic analyses showed a unique feature of host gene expression landscape that is different from dsDNA stimulated inflammatory state. This study built a link between the anti-neoplastic SAMD9 and the regulation of the innate immune responses.

sample_organism:
Homo sapiens
Myxoma virus

platform_organism:
Homo sapiens
Myxoma virus

overall_design: THP-1 cell response to a mutant myxoma virus infection with wildtype infection and dsDNA stimulated responses as control

first: Steven

last: Conrad

first: Erich

last: Perterson

first: Jason

last: Liem

first: Richard

last: Connor

first: Bernice

last: Nounamo

first: Martin

last: Cannon


title: Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T-cells

first: jiqiang

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

overall_design: Refer to individual Series


title: Identification of the toxic 6mer seed consensus for human cancer cells

status: Public on Feb 16 2022

city: Chicago

first: Marcus

last: Peter

state: IL

address: 303 East Superior Street, Lurie 6-123

institute: Northwestern University Feinberg School of Medicine

summary: 6mer seed toxicity is a novel cell death mechanism that kills cancer cells by triggering death induced by survival gene elimination (DISE). It is based on si- or shRNAs with a specific G-rich nucleotide composition in position 2-7 of their guide strand. An arrayed screen of 4096 6mer seeds on two human and two mouse cell lines identified a consensus GGGGGC as the most toxic seed. We have now tested two additional cell lines, one human and one mouse, confirming the GGGGGC consensus as the most toxic average 6mer seed for human cells while slightly less significant for mouse cells. RNA Seq and bioinformatics analyses suggested that an siRNA containing the GGGGGC seed (siGGGGGC) is toxic to cancer cells by targeting GCCCCC seed matches in the 3' UTR of a set of genes critical for cell survival. We have identified several genes targeted by this seed and demonstrate direct and specific targeting of GCCCCC seed matches, which is attenuated upon mutation of the GCCCCC seed matches in these 3' UTRs. Our data show that siGGGGGC kills cancer cells through its miRNA-like activity and points at artificial miRNAs, si- or shRNAs containing this seed as a potential new cancer therapeutics

overall_design: PC3 or HeyA8 cells were transfected with different siRNAs at 1nM and 24 or 48hrs after transfection RNA was isolated and subjetced to lareg RNA Seq analysis

first: Monal

last: Patel

first: Elizabeth

middle: T

last: Bartom


title: Measuring transcription factor binding and gene expression using barcoded self-reporting transposon calling cards and transcriptomes

status: Public on Feb 04 2022

first: Matthew

last: Lalli

address: 1 Gustave L. Levy Pl

department: Psychiatry

institute: Icahn School of Medicine at Mount Sinai

summary: Calling cards technology using self-reporting transposons enables the identification of DNA-protein interactions through RNA sequencing . Here, we have drastically reduced the cost and labor requirements of calling card experiments in bulk populations of cells by introducing a DNA barcode into the calling card itself. An additional barcode incorporated during reverse transcription enables simultaneous transcriptome measurement in a facile and affordable protocol. We demonstrate that barcoded self-reporting transposons recover in vitro binding sites for four basic helix-loop-helix transcription factors with important roles in cell fate specification: ASCL1, MYOD1, NEUROD2, and NGN1. Further, simultaneous calling cards and transcriptional profiling during transcription factor overexpression identified both binding sites and gene expression changes for two of these factors. In sum, RNA-based identification of transcription factor binding sites and gene expression through barcoded self-reporting transposon calling cards and transcriptomes is an efficient and powerful method to infer gene regulatory networks in a population of cells.

overall_design: We performed mutagenesis of the terminal repeat region of the piggyBac transposon to identify sites that could accommodate or serve as a barcode for self-reporting transposon calling card expeirments. We identified 4 mutable nucleotides and used these sites as barcodes. We constructed barcoded self-reporting transposons encoding either puromycin resistance or tdTomato. We then used these barcoded constructs to identify binding sites for four transcription factors involved in cell fate decisions.

first: Robi

middle: D

last: Mitra


title: Single-cell RNA sequencing of OCI-Ly18 tumors treated with CART19 plus vehicle (DMSO) or CART19 plus Venetoclax

status: Public on Feb 03 2022

city: Philadelphia

first: Puneeth

last: Guruprasad

state: Pennsylvania

address: 3400 Civic Center Blvd

institute: University of Pennsylvania

summary: We performed single-cell RNA sequencing of a lymphoma (OCI-Ly18) subcutaneous tumor harvested from NSG mice two weeks after infusion with CART19 plus DMSO or CART19 plus Venetoclax (Suppl. Fig. 3A). Lymphoma cells with shared gene expression profiles were clustered using uniform manifold and approximation (UMAP) analysis. We identified six clusters characterized by different cell-cycle phases (Suppl. Fig. 3B), including one G1-dominant cluster, two S clusters, one G1/G2 cluster, one G2/M cluster, and an M cluster with high Ki67 expression. First, we observed a substantially lower proportion of cells assigned to G1-dom in the CART19/venetoclax-treated condition (8.4%) than in the CART19-treated condition (24%). These indicated a prevalent depletion of the G1-dom cluster by the addition of venetoclax (Suppl. Fig. 4C). In accordance with recent reports that venetoclax can induce cell cycle arrest and death in tumor cells in G1 39, these results suggest that venetoclax treatment also enhances CART’s anti-tumor efficacy by hindering the progression of cell cycle. Interestingly, the “G1-dominant (G1-dom)” and the additional “MKI67hi” cluster (high proliferative cells) showed significant enrichment of genes corresponding to interferon-gamma responsiveness, suggesting that the cells of these two clusters might have been interacting with CART cells (Suppl. Fig. 4D). Of note, by performing GO enrichment analysis with differentially expressed genes (DEGs) between CART19 and CART19/venetoclax combination in the MKI67hi cluster that represent a rapidly proliferating tumor subpopulation, we identified several pathways, including enrichment of the negative regulation of the G2/M phase transition in the CART19/venetoclax-treatment condition in the MKI67hi cluster (Suppl. Fig. 4E and 4F). Taken together, these data implicate that venetoclax treatment enhances CART-mediated tumor killing by promoting tumor apoptosis and inhibiting the cell cycle in cancer cells while also enhancing the interferon responses in neoplastic B-cells when engaging CART cells.

overall_design: Examination of OCI-Ly18 tumors two weeks after infusion of CAR19 or CAR19 with Venetoclax administration

first: Yong

middle: G

last: Lee

first: Marco

last: Ruella

first: Jonathan

last: Schug


title: Systematic profiling of synovial sarcoma transcriptome

status: Public on Feb 01 2022

city: shanghai

first: Geng

last: chen

address: 500 Dongchuan Road

institute: East China Normal University

summary: We systematically explored the transcriptome of 10 synovial sarcoma (SS) patients. We detected a large number of upregulated and downregulated genes in SS compared to normal tissues, which were mainly involved in cell cycle, metabolic and P53 signaling pathways. Moreover, we identified a multitude of differentially alternative spliced genes, indicating that the deregulation of alternative splicing could be one of main factors contribute to the tumorigenesis of SS. A set of tumor-specific gene fusion pairs were identified in SS. We also detected dozens of differentially expressed circRNAs and their parental genes were enriched in muscle related biological process. The interaction network constructed based on circRNAs, miRNAs and corresponding target genes showed that the differentially expressed circRNAs in SS have the potential to regulate the expression of a number of SS related genes. Collectively, we systematically investigated the abnormal expression profile of SS and gain insights into the molecular mechanism from different views of transcriptome expression changes.

overall_design: Investigation of the transcriptome changes of synovia sarcoma from different aspects.

first: Zhengwang

last: Sun

first: Wangjun

last: Yan

last: Chen


title: Single cell chromatin profiling of human cardiogenesis development and iPS derived cardiac cell types

status: Public on Jan 30 2022

city: Palo Alto

first: Laksshman

last: Sundaram

state: California

address: stanford

department: Computer science

institute: Stanford University

summary: In this study, we map chromatin accessibility  at single-cell resolution in the developing human heart and compare it with iPS derived cardiac cell types.

overall_design:
We generated single-cell ATAC-seq libraries from 3 samples of early-mid gestation human heart development, spanning19  weeks of development and 9 samples of iPS derived major cardiac cell types

**RAW data not provided due to patient privacy concerns**

first: Mohamed

last: Ameen

first: Meng

middle: C

last: Shen

first: Ioannis

last: Karakikkes

first: Kevin

last: Wang

first: Thomas

last: Quertermous

first: William

last: Greenleaf

first: Anshul

last: Kundaje


title: Expression data from human glioma tissues and corresponding adjacent non-tumor tissues

status: Public on Jan 26 2022

city: Wuhu

first: xiao

middle: long

last: zhu

state: Anhui

address: 2 Zheshan western road

institute: Yijishan Hospital

summary: We performed microarray expression profiling to analyze the differentially expressed genes between 19 human glioma tissues and corresponding adjacent non-tumor tissues.

overall_design: Glioma tissues and corresponding adjacent non-tumor tissues were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain highly expressed in glioma tissue.

first: Hui

last: Yang


title: Taro Raphide-Associated Proteins: Profilin, Allergens and Crystal Growth

status: Public on Feb 19 2022

city: Urbana

first: Dessiree

middle: Patricia

last: Zerpa Catanho

state: Illinois

address: 1201 W. Gregory Dr, 279 ERML

institute: University of Illinois at Urbana-Champaign

summary: Calcium oxalate raphide crystals are found in bundles in intravacuolar membrane chambers of specialized idioblasts cells of most plant families including many crop plants and are found in most tissues. Raphides are needle-shaped, often with barbed ends, and their morphology and biomineralization pattern have been a focus of much research. In the family Araceae, raphides have been proposed to cause acridity in crops such as taro (Colocasia esculenta (L.) Schott). Acridity is irritation that causes swelling of lips, mouth and throat, as well as itchiness and pain when raw or insufficiently cooked tissues are eaten; this response varies among taro consumers. Since raphides in some other foods do not cause acridity, and since acridity can be inactivated by cooking and/or protease treatment, it is possible that a toxin or allergen-like compound is associated with the crystals. Using two-dimensional (2D) gel electrophoresis and mass spectrometry (MS) peptide sequencing of selected peptides from purified raphides and the results from taro apex transcriptome sequencing, we have shown that profilins, known allergens, are present on raphides. One of the five raphide profilins genes was highly expressed in the apex and had a 17-amino-acid insert that significantly increased that profilin’s epitope peak. This insert was predicted to be coiled and exposed on the surface of the folded peptide. A second profilin had a 2-amino-acid insert that also had a greater B-cell epitope prediction. The taro profilins showed 83 to 92% similarity to known characterized profilins while other raphide peptides showed greater than 90% similarity to other higher plants. The presence on the raphides of peptides normally associated with mitochrondria (ATP synthase), chloroplasts (chaperonin cpn 60 kDa), cytoplasm (actin, profilin) and vacuole (V-type ATPase) indicates a multistage biocrystallation process ending with possible invagination of the tonoplast and addition of mucilage that may be derived from the Golgi. Actin might play a crucial role in the generation of the needle-like raphides. We also showed that commercial allergen test strips for hazelnuts, where profilin is a secondary allergen, have potential for screening in a plant breeding program to reduce acridity and during food processing to avoid over-cooking.

overall_design: Transcriptome of four taro samples from apex leaves were sequenced.

first: Robert

last: Paull

first: Ray

last: Ming

first: Ching

last: Wai

first: Dessireé

last: Zerpa-Catanho


title: RNA Sequencing on hippocampal tissue after ASO treatment overtime in MECP2 duplication mice

status: Public on May 26 2022

city: Houston

first: Yingyao

last: Shao

state: TX

address: 1250 Moursund St., Suite 1350

institute: Baylor College of Medicine

summary: To understand the response of MECP2-regulated genes to the ASO treatment, we performed RNA-sequencing at multiple timepoints on hippocampal tissue following ASO treatment. It shows that the abnormal transcriptomic profile of hDup mice is significantly rescued 2 weeks after the treatment. Long-term partial rescue of the gene expression was observed at 5 weeks and until 16 weeks after the treatment as the transcriptomic profile does not cluster with the control-ASO treated mice.

overall_design: Hippocampal mRNA profiles of 1) hGFP mice with control ASO, 2) hDup mice with control ASO, and3) hDup mice with MECP2-ASO and harvest at different time points after ASO treatment


title: Global changes of enhancer and chromatin accessibility due to microgravity in C2C12 myotubes

status: Public on Jan 14 2022

city: Chiba

first: Ichiro

last: Manabe

address: 1-8-1 Inohana, Chuo

country: Japan

institute: Chiba University


title: Med1 controls effector CD8+ T cell differentiation and survival through mediating the transcriptional regulation of C/EBPβ on T-bet

status: Public on Jan 17 2022

city: xian

first: Cangang

last: Zhang

state: State...

address: Yanta district, xi 'an city, shaanxi province

institute: xian jiaotong university

summary: Effector CD8+ T cells are crucial in adaptive immunity for effective protection against infectious pathogens. The regulatory mechanisms underlying CD8+ effector T cell development are incompletely understood. Here, we defined a critical role of mediator complex subunit 1 (Med1) in controlling effector CD8+ T cell differentiation and survival during acute infections. Mice with Med1 deletion in CD8+ T cells exhibited a significantly impaired effector cell expansion with large reduction of KLRG1+ terminally differentiated and Ly6c+ effector cell populations. Med1 deficiency led to enhanced cell apoptosis and expression of exhausted T cell associated inhibitory receptors (PD-1, Tim3, Lag3 and TIGHT). RNA-Seq analysis revealed the defects of T-bet and Zeb2 mediated transcriptional programs in effector differentiation. Overexpression of T-bet could rescue the Med1-deficient CD8+ effector T cell differentiation and survival. Mechanistically, transcription factor C/EBPβ promoted T-bet expression through interacting with Med1 in effector T cells. Collectively, our findings revealed a novel role of Med1 in regulating effector CD8+ T cell differentiation and survival during immune response.

overall_design: WT and KO CD8+ T cells were sorted from the spleens of recipient mice 7 days after LM-OVA infection in the co-transfer model.

first: Baojun

first: Anjun

last: Jiao


title: Urinary Exosome as a Potential Biomarker of Exercise-Induced Fatigue in Young Adult Males

status: Public on Jan 09 2022

city: Seoul

first: Suhong

last: Park

address: 1, Gwanak-ro, Gwanak-gu,

department: Exercise Science

country: South Korea

institute: Seoul National University

type: Non-coding RNA profiling by high throughput sequencing

summary: Exercise could stimulate the release of exosomes into the circulation, transferring signals between the cells. Exosomes are also found in urine, which is an emerging biomarker of several diseases. However, the characteristics of urinary exosomes and their contents after exercise remain poorly understood.  We used microarrays to identify the alteration of gene expression in urinary exosomes after exercise bout.

overall_design: We isolated exosomes from the urine samples of human after exercise. Then we analyzed changes in urinary exosome at three different time points (pre, post, post 1h).

first: Hyo

middle: Y

last: Moon


title: Transcriptome profiling of haloperidol treated mouse bone marrow LSK cells

status: Public on Jan 25 2022

city: Muenster

first: Hyun-Woo

last: Jeong

state: NRW

department: Dept. Tissue Morphogenesis

country: Germany

institute: Max-Planck-Institute for Molecular Biomedicine

summary: We performed RNA sequencing analyses of adult mouse bone marrow lineage-negative, Sca-1-positive, and c-kit-positive (LSK) hematopoietic stem/progenitor cell population. Especially, we investigated gene expression profiling of LSK cells before and after haloperidol treatment.

overall_design: Wildtype(B6) mice were injected with DMSO(vehicle) or Haloperidol for consecutive 3 days. Then the LSK cells were sorted by FACS. During FACS sorting, cells were still exposed to DMSO or haloperidol treatment. FACS sorted LSK cells were directly collected in RLT lysis buffer and processed for RNA-Seq.

first: Ralf

middle: H

last: Adams

first: Qi

last: Chen

first: Yang

last: Liu


title: Co-regulation of genome-wide gene expression by FluG and FluG-like protein A (FlrA) in Beauveria bassiana

status: Public on Jan 08 2022

city: Hangzhou

first: Chongtao

last: Guo

state: Zhejiang

address: 866 Yuhangtang Road

department: College of life science

institute: Zhejiang University

summary: Up to 1415 genes are co-upregulated (540) or co-downregulated (875) at similar levels in the flrA and fluG null mutants, highlighting similar regulatory roles for FlrA and FluG in the adaptation of B. bassian to insect-pathogenic lifecycle and environment.

overall_design: Trnascriptomes were constructed by RNA-seq based on three 3-day-old SDAY cultures (replicates) of flrA null mutant, fluG null mutant and wild-type strain.

first: Ming-Guang

last: Feng


title: Identification of distinct immune cell subsets associated with various clinical presentations, disease severity and viral persistence of SARS-CoV-2 infection

status: Public on Feb 17 2022

city: Xian

first: chengsheng

last: zhang

state: Shaanxi

address: 277 West Yanta Road, Xi'an, Shaanxi, P.R.China

department: precision medicine center

institute: First Affiliated Hospital of Xi 'an Jiaotong University

summary: The clinical presentations and outcomes of SARS-CoV-2 infection are highly variable, ranging from asymptomatic infections to severe conditions, and the underlying mechanisms remain largely unknown. In this study, we performed the single-cell RNA sequencing to examine the profiles of the peripheral blood mononuclear cells (PBMCs) from the healthy controls (HC), asymptomatic individuals (AS) and symptomatic COVID-19 patients (SM) with various clinical features and disease severity. We first identified nine major cell types, including T cells, B cells, monocytes, natural killer (NK) cells, dendritic cells (DC), platelets, neutrophils, plasma cells and stem cells from a total of 119,799 single cells captured and filtered for the final analysis, and then divided these cell types into separate cell clusters and sub-clusters, respectively. We revealed that SARS-CoV-2 infection resulted in profound alternations in various cellular compartments and identified a number of distinct immune cell subsets that were associated with various clinical presentations, disease severity and viral persistence of COVID-19. (NCAM1+CD160+) NK cells increased significantly in AS and SM individuals compared with the HC. SM patients showed a significant increase in (LAG3+CD160+CD8+) NKT cells and a decrease in (CD4-CD8-) double negative T cells compared with the AS subjects. (CD68-CSF1R-IL1BhiCD14+) classical monocytes were significantly higher in patients with severe disease (SD) than the patients with moderate disease (MD). (CD68-CSF1R-IL1BhiCD14+) classical monocytes and (CLEC10A-S100A9lo)pDC were positively and negatively correlated with the age-related disease severity of COVID-19 patients, respectively. Increases in (CD33-HLA-DMA-CD14+) classical monocytes and (CLEC10A-S100A9lo)pDC were associated with long-term nucleic acid test positive (LTNP) patients compared with the short-term nucleic acid test positive (STNP) individuals. Increases in (LAG3+CD160+CD8+) NKTcells and (FOXP3+IL2RA+IL7R+CD4+) Treg cells were observed in a patient lacking B cells and plasma cells. Dramatic increases in neutrophils, (CD33-HLA-DMA-CD14+) classical monocytes, and (CD68-CSF1R-IL1BhiCD14+) classical monocytes were detected at a later stage of a fatal patient. Our findings may enhance our understanding of the immune cell alternations involved in the pathogenesis of COVID-19 and the protective immune responses against SARS-CoV-2 infection.

overall_design: 53 peripheral blood mono-nuclear cell (PBMC) samples including 42 COVID-19 patients derived samples and 11 healthy controls (HCs) derived samples

first: Chengsheng


title: Non-canonical odor coding ensures unbreakable mosquito attraction to humans

status: Public on Jan 06 2022

first: Hongjie

last: Li

address: One Baylor Plaza

department: Huffington Center on Aging

summary: snRNA-seq was used to detect the expression of different chemoreciptors in the antenna and maxillary palp nuclei. Using snRNA-seq, we confirm the coexpression of different cheomreceptos in the same nuclei.

overall_design: single-nuclei RNA-seq

first: Tzu-Chiao

last: Lu


title: T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma

status: Public on Jan 13 2022

city: Stanford

first: Aaron

last: Newman

address: 265 Campus Drive

department: Institute for Stem Cell Biology and Regenerative Medicine, Department of Biomedical Data Science


title: 3D Chromatin Remodeling Potentiates Transcriptional Programs Driving Cell Invasion [ChIP-Seq]

status: Public on Jan 01 2022

city: Montreal

first: Michael

last: Witcher

state: Quebec

address: 3755 Chem. de la Côte-Sainte-Catherine

department: Experimental Medicine

country: Canada

institute: McGill University

summary: Epigenetic mechanisms often play an important role in driving tumor progression towards metastasis. It is less clear that deregulation of chromatin architecture, including topologically associated domains (TADS), contributes to cancer progression. CTCF is a central regulator of three dimensional chromatin structure that undergoes copy number loss in over half of all breast cancers, but the impact of this defect on epigenetic programming and chromatin architecture remains obscure. We find that the reduced pools of CTCF in hemizygous models potentiates cell invasion. Underlying this phenotype is the activation of oncogenic networks including the PI3K signaling cascade, which presents therapeutic vulnerabilities, especially to mTOR inhibitors. Deregulation of these oncogenic pathways is largely due to the loss of CTCF insulation, allowing a reorganization of long-range chromatin contacts at the subTAD level that is associated with aberrant programming of H3K27 acetylation at enhancer/promoter regions. Thus, lowered CTCF levels lead to chromatin reorganization facilitating pro-invasive transcriptional programs.

overall_design: Examination of mRNA expression, CTCF binding, H3K4me3, H3K27ac, DNA Methylation and chromatin conformation underlying the oncogenic phenotypes potentiated by CTCF LOH in mammalian breast epithelial cells.

first: Benjamin

last: Lebeau


title: Silencing of RNA binding protein, ZFP36L1, promotes epithelial-mesenchymal transition in liver cancer cells by regulating transcription factor ZEB2

city: Baton Rouge

first: Sonika

last: Patial

address: Baton Rouge, LA 70803

institute: Louisiana State University

summary: HCC cancer cells were knocked down of ZFP36L1 using siRNA and RNASeq was done.

overall_design:
RNA-seq after knockdown of nontarget control or ZFP36L1 in HCC cell line SNU475
in 4 independent experiments.

first: Jian

first: Yogesh

last: Saini


title: 3D Chromatin Remodeling Potentiates Transcriptional Programs Driving Cell Invasion [RNA-Seq]


title: 3D Chromatin Remodeling Potentiates Transcriptional Programs Driving Cell Invasion

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

overall_design: Refer to individual Series


title: Transcriptomic changes in bovine skeletal muscle cells after resveratrol treatment

status: Public on Dec 31 2021

city: Kongens Lyngby

first: Xiao

last: Wang

address: Bagsværdvej 103, ST

institute: Konge Larsen Aps

summary: Resveratrol (RSV) has been confirmed to benefit human health. Resveratrol supplemented in the feeds of animals improved pork, chicken, and duck meat qualities. In this study, we identified differentially expressed (DE) messenger RNAs (mRNAs) (n = 3,856) and microRNAs (miRNAs) (n = 93) for the weighted gene co-expression network analysis (WGCNA) to investigate the co-expressed DE mRNAs and DE miRNAs in the primary bovine myoblasts after RSV treatment. The mRNA results indicated that RSV treatments had high correlations with turquoise module (0.91, P-value = 0.01) and blue module (0.93, P-value < 0.01), while only the turquoise module (0.96, P-value < 0.01) was highly correlated with the treatment status using miRNA data. After biological enrichment analysis, the 2,579 DE genes in the turquoise module were significantly enriched in the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The top two GO terms were actin filament-based process (GO:0030029) and actin cytoskeleton organization (GO:0030036). The top two KEGG pathways were regulation of actin cytoskeleton (bta04810) and tight junction (bta04530). Then, we constructed the DE mRNA co-expression and DE miRNA co-expression networks in the turquoise module and the mRNA–miRNA targeting networks based on their co-expressions in the key module. In summary, the RSV-induced miRNAs participated in the co-expression networks that could affect mRNA expressions to regulate the primary myoblast differentiation. Our study provided a better understanding of the roles of RSV in inducing miRNA and of the characteristics of DE miRNAs in the key co-expressed module in regulation of mRNAs and revealed new candidate regulatory miRNAs and genes for the beef quality traits.

overall_design: Three cell cultures were treated with 20 μM resveratrol in differentiation medium for 4 days, whereas three other cell cultures treated with DMSO were used as control group.

first: Dan

last: Hao

first: Xiaogang

first: Bo

last: Thomsen

first: Hong


title: 3D Chromatin Remodeling Potentiates Transcriptional Programs Driving Cell Invasion [Hi-C]


title: The transcription factor Zfp335 promotes differentiation and persistence of memory CD8+ T cells by regulating TCF-1

first: Cangang

last: Zhang

summary: Memory CD8+ T cells play an essential role in providing effective and lifelong protection against pathogens. Comprehensive transcriptional and epigenetic networks are involved in modulating memory T cell development, but the molecular regulations of CD8+ memory T cell formation and long-term persistence remain largely unknown. Here, we show that zinc finger protein 335 (Zfp335) is indispensable for CD8+ T cell memory establishment and maintenance during acute infections. Mice with Zfp335 deletion in CD8+ T cells exhibit a significant reduction of memory T cells and memory precursor cells in the contraction phase.

first: Baojun

first: Haiyan


title: Paternal hypoxia exposure primes offspring for increased hypoxia resistance

city: Dunedin

first: Oscar

middle: Javier

last: Ortega-Recalde

state: Otago

address: 60 Hanover Street

department: Anatomy

country: New Zealand

institute: University of Otago

type: Methylation profiling by high throughput sequencing

summary: Environmental challenges experienced by an organism can have multiple effects at an individual level, with recent work also suggesting these challenges may affect their unexposed offspring. In a time of rapid environmental change, understanding whether environmental challenges experienced by organisms could increase the fitness of future generations to survive these same stressors, is critically needed. Low dissolved oxygen is a common environmental challenge that aquatic organisms encounter, resulting in numerous physiological, phenotypic, and epigenetic changes. In this study, we use zebrafish (Danio rerio) as a model to investigate how paternal hypoxia experience impacts subsequent progeny. Males were exposed to moderate hypoxia (11-13 kPA) for 2 weeks, bred to create an F1 generation, and progeny underwent an acute hypoxia (0-1 kPA) tolerance assay. Using time to loss of equilibrium and loss of equilibrium frequency as measured of hypoxia resistance, we show that paternal exposure to hypoxia endow offspring with a greater tolerance to acute hypoxia, compared to offspring of unexposed males, though there are strong family x treatment effects. In addition to phenotypic alternations, we also investigated changes in gene expression in offspring. We conducted RNA-Seq on whole fry and detected 91 differentially expressed genes, including two hemoglobin genes that are significantly upregulated by more than 4-fold in the offspring of hypoxia exposed males. Moreover, the offspring which maintained equilibrium the longest showed the greatest upregulation in hemoglobin expression. Paternal exposures to physiological challenges are thus able to impact the phenotype and gene expression of their unexposed progeny. We conducted whole genome bisulfite sequencing (WGBS) on the sperm of parental males to assess whether changes in progeny phenotype and gene expression are underpinned by changes in DNA methylation. While we observed coupling of methylation levels in the parental sperm and gene expression in progeny overall, we did not detect differential methylation at any of the differentially expressed genes, suggesting that another epigenetic mechanism is responsible for the observed changes in gene expression. Overall, our findings suggest that a ‘memory’ of past hypoxia exposure is maintained and that this environmentally induced information is transferred to subsequent generations, pre-acclimating progeny to cope with hypoxic conditions.

overall_design: Zebrafish males were exposed to moderate hypoxia (11-13 kPA) for 2 weeks and bred to create an F1 generation. To evaluate changes in gene expression, we conducted RNA-Seq on 20 day old fry from control and hypoxia treated males. Additionally, to evaluate changes in DNA methylation patterns we conducted whole genome bisulfite sequencing (WGBS) on the sperm of parental males.

first: Sheri

last: Johnson

first: Timothy

last: Hore

first: Alexandria

last: Ragsdale

first: Ludovic

last: Dutoit


title: Foxp3-dependent and -independent functions of peripherally-induced Treg cells

city: New York

first: Michail

last: Schizas

address: 1275 York ave

institute: Memorial sloan Kettering


title: Foxp3-dependent and -independent functions of peripherally-induced Treg cells [08075]

summary: Regulatory T (Treg) cells expressing the lineage-defining transcription factor Foxp3 are essential for the maintenance of immune tolerance. Foxp3 expression can be induced in a subset of developing self-reactive thymocytes to yield thymic Treg (tTreg) cells, critical for tolerance against self-antigens. Alternatively, activation of mature naïve T cells under non-inflammatory conditions can drive the differentiation of peripherally-induced Treg (pTreg) cells, thought to contribute to tolerance against commensal microbes and dietary antigens. While Foxp3 is indispensable for tTreg cell development and function, its role in pTreg cells has remained unknown. Here, we used a genetic fate mapping approach to characterize polyclonal pTreg cells induced by microbial colonization. We found that expression of a pTreg cell-specific gene expression program was initiated in the mesenteric lymph node (mLN) in a Foxp3-independent manner. Moreover, in contrast to Treg cells in secondary lymphoid tissues, colonic microbiota-dependent pTreg cells did not depend on Foxp3 for their fitness or lineage commitment and were capable of suppressing colonic effector T cell expansion in a Foxp3-independent manner. Rather, Foxp3 was required in a cell-intrinsic manner to limit IL-17 production and to prevent the expansion of intestinal mast cells. Our results suggest that, extrathymic Foxp3 induction likely acts as a mechanism to fine-tune the activity of Th17-like cells with Foxp3-independent regulatory functions.

overall_design: Foxp3DTR-GFP/Thy1.1CD4CreER/wtR26lsl-tdTomato/wt mice were bred and weaned on AVNM and an amino acid-defined diet. Extrathymic Foxp3- CD4 T cells were labeled by treating mice with tamoxifen and allowing ~3 weeks for thymocyte maturation while concomitantly treating mice with diphtheria toxin (DT). Following the labeling period, mice were switched to chow diet and colonized with SPF fecal microbiota. 12 days post-colonization tdTomato-GFP+, tdTomato-Thy1.1+, tdTomato+GFP+ and tdTomato+Thy1.1+ CD4 T cells cells were isolated from the mesenteric lymph nodes and double sorted into Trizol for RNA extraction, library preparation and sequencing.

first: Joris

last: van der Veeken

first: Clarissa

last: Campbell

first: Yuri

last: Pritykin

first: Wei

last: Hu

first: Zhong-Min

first: Jacob

last: Verter

first: Fanny

last: Matheis

first: Daniel

last: Mucida

first: Louis-Marie

last: Charbonnier

first: Talal

last: Chatila

first: Alexander

last: Rudensky


title: T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [scRNA-Seq]

first: Aaron

last: Newman

summary: Severe immune-related adverse events (irAEs) occur in up to 60% of melanoma patients treated with immune checkpoint inhibitors (ICIs). However, it remains unknown whether a common baseline immunological state precedes irAE development. Leveraging CyTOF, single-cell RNA sequencing, bulk RNA sequencing, and T cell receptor sequencing to analyze pretreatment blood from metastatic melanoma patients treated with ICIs, we investigated cellular factors associated with severe irAE development regardless of organ system involvement. Our results demonstrate circulating T cell characteristics associated with ICI-induced toxicity, with implications for improved diagnostics and clinical management.

overall_design:
To investigate cellular determinants of severe irAE development, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) obtained pretreatment from patients with metastatic melanoma treated with immune checkpoint blockade.
----------------------------------------
Authors state "raw data are not available due to patient privacy concerns".

middle: X

last: Lozano

first: Aadel

middle: A

last: Chaudhuri

first: Aishwarya

last: Nene


title: Multi-omics approaches reveal TNF-mediated inhibition of tissue reparative macrophages is via a gene-selective transcriptional mechanism (scRNA-Seq)

status: Public on Jan 11 2022

city: Martinsried

first: Assa

last: Yeroslaviz

state: Bavaria

address: Am Klopferspitz 18

department: computational Biology

institute: Max-Planck-Institute for biochemistry

summary: Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn’s Disease. Previously, we and others found that TNF blocks the emergence and function of alternatively-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balanced of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis and signaling pathway deconvolution. Our findings reveal that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way dependent on JNK signaling. We uncover principles of the selectively inhibition by TNF via the type 1 TNF receptor on specific populations of alternative activated macrophages.

overall_design: single cell RNA profiles of wild-type BMDMs stimulated with  IL4/IL13 or IL4/IL13 + TNF  from 2 separate mice.

first: Stefanie

last: Dichtl

first: David

middle: E

last: Sanin

first: Edward

middle: J

last: Pearce

first: Peter

last: Murray


title: Multi-omics approaches reveal TNF-mediated inhibition of tissue reparative macrophages is via a gene-selective transcriptional mechanism


title: Identification of the most toxic 6mer seed consensus and some of its targets in human cells

city: Chicago

first: Marcus

last: Peter

address: 303 East Superior Street, Lurie 6-123

institute: Northwestern University Feinberg School of Medicine

summary: We provide evidence that the 6mer seed GGGGGC is toxic in human cells by targeting GCCCCC seed matches in the 3' UTR oif a set of genes critical for cell survival thereby inducing DISE

overall_design: Samples of human ovarian cancer cell line HeyA8 generated by deep sequencing, using Illumina HiSeq4000.

first: Monal

last: Patel


title: Foxp3-dependent and -independent functions of peripherally-induced Treg cells [09748]

first: Michail

last: Schizas

overall_design: RNA-seq analysis of DTR-GFP+ wild-type Treg cells and Thy1.1+ reporter-null+ cells from colonic lamina propria of Foxp3DTR-GFP/loxp-Thy1.1-STOP-loxp-GFP mice.

first: Joris

last: van der Veeken

first: Clarissa

last: Campbell

first: Yuri

last: Pritykin

first: Wei

last: Hu

first: Zhong-Min

last: Wang

last: Verter


title: Development of gene expression signatures for mice with renal ischemia repurfusion injury.

status: Public on Dec 23 2021

city: Jinan

middle: Jinan

last: Huang

address: 44# Wenhua Xi Road

department: Department of Pharmacology

institute: School of Basic Medical Sciences, Shandong University

summary: Acute kidney injury (AKI) is a global public health concern associated with high morbidity and mortality, and currently no therapeutic interventions reliably limit injury or speed recovery after AKI. Therefore, strategies to augment endogenous repair processes and retard associated profibrotic responses are urgently required. Among them, macrophages are attractive therapeutic targets for AKI because of their critical roles in tissue homeostasis and inflammation. Despite the differentiation of macrophages into morphologically and functionally distinct phenotypes M1/M2 and their clearance of dead cells (efferocytosis) have been increasingly linked to renal inflammation and repair in AKI, the underlying mechanisms of macrophage phenotype switching and efferocytosis during AKI are largely unclear. Here, we found that JAML (junctional adhesion molecule-like protein) deficiency protected against renal AKI. By generation of bone marrow chimeric mice and tubular-specific JAML conditional knockout mice, we demonstrated macrophage JAML primarily contributed to AKI. Mechanistically, JAML mediated macrophage phenotype polarization and efferocytosis, at least in part, through a C-type lectin receptor Mincle-dependent mechanism. In addition, we also found that JAML could induce endogenous Mincle ligand such as SAP130 release from dead or dying renal tubular epithelial cells and subsequent Mincle activation in macrophages, thereby also slightly contributing to AKI. Importantly, we observed a higher expression of JAML in the kidney from subjects with AKI and the level of JAML was correlated with serum creatinine. Collectively, our studies for the first time explore new biological functions of JAML in macrophages and conclude that JAML is an important mediator and biomarker of AKI. Pharmacologic targeting of JAML-Mincle mediated signaling pathways may provide a novel therapeutic strategy for patients with AKI.

overall_design: The gene Jaml was knockd out in C57/6J background mice and was identified by western-blot and IHC,the results were showed in related articles. Three independent samples were performed for each group,after mice were anesthetized with an intraperitoneal injection of pentobarbital sodium (30 mg/kg body weight), a midline abdominal incision was made and bilateral renal pedicles were clipped for 40 minutes using microaneurysm clamps. At the end of the ischemic period, the vascular clamps were removed and the kidneys were observed for 5 minutes to ensure reflow process.

first: Fan

last: Yi


title: RNAseq of control and IL17D-expressing A549

status: Public on Dec 19 2021

city: Tianjin

first: Zhenzhen

last: Lin

address: 22 Qixiangtai Road

institute: tianjin medical university

overall_design: To study the effect of IL17D on lung cancer cells,  we overexpressed IL17D in A549 cells and performed RNA-seq.

last: Du


title: Diurnal 3D genome organization remodeling orchestrates rhythmic gene expression in rice [ChIP-Seq]

status: Public on Dec 24 2021

city: Wuhan

first: Baibai

last: Gao

address: 1 Shizishan Street, Hongshan District

institute: National Key Laboratory of Crop Genetic Improvement

summary: Genome-wide rhythmic modulation of RNAPII occupancy and histone acetylation modifications are highly coordinated with rhythmic gene expression, and dynamically modulates diurnal 3D genome architecture remodeling. The rhythmic genes at AM circadian phase and target genes of transcription factors (TFs) are enriched within limited spatial clusters, which forming subnuclear organization hubs to coordinate looping gene expression. Core circadian clock genes related chromatin connectivity networks suggested they co-localized within the same ?transcriptional factory? and define a distinct nuclear landscape and circadian outputs in the AM and PM. Our findings uncover novel diurnal fundamental genome folding principles in plants, and reveal a distinct higher-order chromosome organization that is crucial for coordinating diurnal dynamics of transcriptional regulation.

overall_design: Here, we generated genome-wide occupancy of RNA polymerase II (RNAPII) and histone modifications (H3K4me3, H3K9me2, H3K27ac, H3K27me3, H3K4me1 and H3K9ac) by ChIP-seq, whole-transcriptome by RNA-seq, chromatin accessibility by FAIRE-seq and DNA methylation by Bisulfite-seq throughout the six-time course. We also performed RNAPII long-read ChIA-PET from the same tissues used for ChIP-seq, RNA-seq, FAIRE-seq and Bissulfite-seq at 8:00 and 20:00. Together, we constructed comprehensive high-resolution dynamic chromatin architecture, and disected its effects on diurnal gene expression.

first: Li

last: Deng


title: P. syringae pv tomato DC3000 AlgU in planta regulon RNA-seq data

status: Public on Dec 18 2021

city: Athens

first: Brian

last: Kvitko

state: GA - Georgia

address: 120 Carlton St

department: Plant Pathology

institute: University of Georgia

summary: This RNA-seq dataset is from RNA sample collected using the physical seperation technique previously used in our lab (Lovelace 2018). The goal is to look at DC3000 AlgU regulon under pattern triggered immunity.

sample_organism: Pseudomonas syringae pv. tomato str. DC3000

overall_design: There are six samples in triplicate for a total of 18 samples. Two mutant strains of P. syringae pto DC3000 were used: ΔalgUmucAB (GS_00585 “3d“), and ΔalgUmucAB + AlgU complemented via pEM53 (pBAD promoter) plasmid (GS_00587 “3dA”). 5-week old A. thaliana were pre-treated 20hr in advance of inoculation with either Flg22 (“F”) or mock (water+DMSO, “M”).  Inoculum was prepared in 0.25mM MgCl2 from KB agar plates. Pellets (P) of both inoculums were saved as time-zero baseline examples. After 5hrs of infection, plants were vacuum-infiltrated with an RNA-later-like buffer (“M” or “F”) and were frozen in liquid nitrogen until RNA extraction.

first: Amy

last: Smith

first: Amelia

last: Lovelace

first: Haibi


title: Single-cell m6A profiling reveals mRNA methylation heterogeneity and unique cellular m6A signatures

city: Durham

first: Matthew

last: Tegowski

state: NC

address: 153 Research Dr.

department: Biochemistry

institute: Duke University

summary: We used DART-seq to map m6A methylation of RNA in single HEK293T cells. We also used DART-seq to map m6A from bulk RNA from HEK293T cells. Using the 10X Genomics and SMART-seq2 platforms, we sequenced a total of 19,533 experimental and control cells using the 10X Genomics platform, and 1,471 experimental and control cells using SMART-seq2.  We then used a Bullseye, a computational pipeline developed within the lab, to identify m6A sites from the C-to-U mutations in bulk and single-cell datasets. We find that most m6A methylation is highly heterogenous from cell-to-cell. RNAs containing m6A methylation, are infrequently methylated, and that most individual sites are rarely methylated within the population. Additionally, we are able to identify differentially methylated RNAs in different cellular states from within a single population, and use m6A methylation information to perform clustering of single cells to find a source of novel cellular heterogeneity.

overall_design: Bulk DART-seq: We performed bulk RNA-seq on RNA from HEK293T cells expressing APOBEC1-YTH. We also sequenced RNA from cells expressing APOBEC1-YTHmut, which serves as controls. There are 3 biological replicates included for each of these samples.  10x Genomics single-cell DART-seq: We performed 10x Genomics 3' end RNA-seq (3 biological replicates each, targeting ~80,000 reads per cell) on HEK293T cells expressing APOBEC1-YTH or APOBEC1-YTHmut (control cells). A total of 10,352 APOBEC1-YTH cells and 9,151 APOBEC1-YTHmut cells passed QC filters.  SMART-seq2 single-cell DART-seq: We generated SMART-seq libraries from single APOBEC1-YTH-expressing HEK293T cells and APOBEC1-YTHmut-expressing HEK293T cells (as controls). Cells were sequenced to a depth of about 5,000,000 reads per library using 150bp paired-end sequencing.

first: Mathieu

middle: N

last: Flamand

first: Kate

last: Meyer


title: Inhibiting ERK dimerization ameliorates BRAF-driven anaplastic thyroid cancer

status: Public on Dec 15 2021

city: Madrid

first: Miguel

middle: Angel

last: Zaballos

state: Madrid

address: Arturo Duperier, 4

country: Spain

institute: IIBm-CSIC

summary: Our findings establish that BRAF- and RAS-mutant thyroid cells respond differentially to DEL-22379, which cannot be explained by the previously described mechanism of action of the inhibitor. Nonetheless, DEL-22379 demonstrated significant anti-tumor effects in vivo with an apparent lack of toxicity, making it an interesting candidate for the development of combinatorial treatments. Thus, our data underscore the differences elicited by the specific driver mutation for thyroid cancer onset and progression, which should be considered for experimental and clinical approaches.

overall_design: We used a panel of four human anaplastic thyroid carcinoma (ATC) cell lines harboring BRAF or RAS mutations to analyze ERK dynamics and tumor-specific characteristics. We also analyzed the impact of DEL-22379 on the transcriptional landscape of ATC cell lines using RNA-sequencing, and evaluated its therapeutic efficacy in an orthotopic mouse model of ATC.

first: Adrián

last: Acuña-Ruiz

first: Garcilaso

last: Riesco-Eizaguirre

first: Piero

last: Crespo

first: Pilar

last: Santisteban


title: Diurnal 3D genome organization remodeling orchestrates rhythmic gene expression in rice [BiSulfite-seq]

summary: Genome-wide rhythmic modulation of RNAPII occupancy and histone acetylation modifications are highly coordinated with rhythmic gene expression, and dynamically modulates diurnal 3D genome architecture remodeling. The rhythmic genes at AM circadian phase and target genes of transcription factors (TFs) are enriched within limited spatial clusters, which forming subnuclear organization hubs to coordinate looping gene expression. Core circadian clock genes related chromatin connectivity networks suggested they co-localized within the same “transcriptional factory” and define a distinct nuclear landscape and circadian outputs in the AM and PM. Our findings uncover novel diurnal fundamental genome folding principles in plants, and reveal a distinct higher-order chromosome organization that is crucial for coordinating diurnal dynamics of transcriptional regulation.


title: RNAseq of polymicrobial S.aureus and E.coli macrocolonies

status: Public on Dec 11 2021

city: Singapore

first: Kelvin

last: Chong

address: 60 Nanyang Drive

department: SCELSE

country: Singapore

institute: Nanyang Technological University

summary: We report the transcriptome of macrocolonies taken from S. aureus and E. coli grown in single speicies or multispecies context.

sample_organism:
Escherichia coli
Staphylococcus aureus

platform_organism:
Escherichia coli
Staphylococcus aureus

overall_design: Examination of 2 different bacterial species macrocolonies

first: Wong

last: Jie

first: Benjamin

last: Ho

first: Kimberly

last: Kline


title: Investigation into the effect of cathelicidin on autoimmune CD4+ T cells

status: Public on Nov 14 2021

city: Edinburgh

first: Emily

last: Gwyer Findlay

address: 47 Little France Crescent

department: Centre for Inflammation Research

country: United Kingdom

institute: University of Edinburgh

summary: We have shown that, in acute models of vaccination, the antimicrobial peptide cathelicidin potentiates Th17 cell differentiation. TO examine this in long-term, chronic inflammation, here we studied T cells in the mouse model of Multiple Sclerosis. We examined T cells from wildtype mice and those lacking cathelicidin.

overall_design: Experimental autoimmune encephalomyelitis was induced in 8 week old female mice - 3 wildtype (WT) and 3 cathelicidin knockout (Camp-/-, KO). On day 7 draining inguinal lymph nodes were removed and RNA isolated from CD4+ T cells. The samples were run on a Nanostring mouse immunology chip.

first: Katie

last: Findlay


title: Comprehensive analysis of the transcriptome-wide m6A methylation in mouse pachytene spermatocytes and round spermatids

status: Public on Dec 13 2021

city: nantong

first: hong

last: shihao

address: 19 Qixiu Road

institute: Nantong university

summary: Spermatogenesis, an efficient and complex system in male germline development, requires a series of elaborately regulated genetic events in which diploid spermatogonia differentiate into haploid spermatozoa. N6-methyladenosine (m6A) is important for spermatogenesis. ALKBH5 is an m6A eraser, and knockout of ALKBH5 increases the level of total m6A methylation and causes male infertility.

overall_design: comprehensive analyses of MeRIP-seq and RNA-seq data revealed differences between wild-type (WT) and Alkbh5 knockout (KO) mice.

first: Shihao

last: Hong

first: Xiaozhong

last: Shen

first: Jinmei

last: Cheng

first: Hanyu

last: Tang

first: Fei

last: Sun


title: CD71+ HSC/MPP

status: Public on Dec 17 2021

city: Cambridge

first: Elisa

last: Laurenti

address: Jeffrey Cheah Biomedical Centre

department: Haematology

institute: University of Cambridge

summary: We describe the unique enrichment of erythroid-megakaryocyte primed CD71+ phenotypic HSC/MPPs in steady-state PB.

overall_design: Single CD71+ phenotypic HSC/MPPs (CD19-CD34+CD38-CD45RA-CD71+CD34lo) from healthy adult human PB (three different donors) were sequenced using the SmartSeq2 protocol.

first: Nicole

last: Mende

first: Hugo

middle: P

last: Bastos


title: Transcriptome of subsets of human haematopoietic stem cells from non-mobilised peripheral blood of healthy donors and CD71+ HSC/MPP

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

overall_design: Refer to individual Series


title: A Phase I/II Study of Ivaltinostat Combined with Gemcitabine and Erlotinib in Patients with Untreated Locally Advanced or Metastatic Pancreatic Adenocarcinoma

status: Public on Nov 29 2021

city: Seoul

first: Jung Hyun

last: Jo

state: --- Select ---

address: 50-1 Yonsei-ro

institute: Yonsei University Health System

summary: Histone deacetylase inhibitors (HDACi) are currently used as anticancer drugs; however, no clinical trials proved efficacy in pancreatic adenocarcinoma (PDAC). Ivaltinostat, a novel intravenous HDACi, presented cell growth inhibition and improved chemo-sensitivity in PDAC. This phase I/II study demonstrated ivaltinostat with gemcitabine and erlotinib can be administered safely to improve survivals in patients with untreated advanced PDAC. In addition, we proposed potential blood markers to predict response to ivaltinostat treatment based on correlative studies.

overall_design: To determine potential markers to predict the chemotherapy response to ivaltinostat, 6 patient samples were analyzed at the time of pretreatment(C1D1), on day 8 (C1D8) after treatment, and at the end of the trial (EOT) using antibody microarray analysis.

first: Dawoon

last: Jung

first: Jung

first: Si

last: Song


title: Diurnal 3D genome organization remodeling orchestrates rhythmic gene expression in rice

first: Baibai

last: Gao


title: Characterization of estrogen regulation in estrogen reseptor (ER)-positive breast cancer at the single cell level

status: Public on Dec 09 2021

city: Duarte

first: Shiuan

last: Chen

state: CA

address: 1500 E Duarte Rd

department: Cancer Biology-BRI

institute: City of Hope National Medical Center

summary: We performed the single-cell analysis to characterize estrogen regulation in ER-positive breast cancer using patient-derived xenograft (PDX) model (named SC31).

overall_design: Following a treatment that lasted 6 weeks using Placebo and estradiol (E2) (1mg) pellet, SC31-PDX tumors were harvested and digested into a single-cell.

first: Hitomi

last: Mori


title: whole blood RNA-Seq data of Japanese CNO patients and healthy controls

status: Public on Nov 05 2021

city: Tokyo

first: Koji

last: Yahara

address: Aoba-cho 4-2-1, Higashimurayama-shi

institute: National Institute of Infectious Diseases

summary: To explore new aspects of Chronic non-bacterial osteomyelitis (CNO) based on whole blood RNA sequencing (> 6Gb per sample)

overall_design: 11 patients and 9 healthy controls

first: Hiroko


title: Gene expression in CD14+ and CD16+ monocytes

status: Public on Oct 31 2021

city: Moscow

first: Polina

last: Vishnyakova

address: Oparina 4

country: Russia

institute: National Medical Research Center for Obstetrics, Gynecology and Perinatology

summary:
The aim of our work was to evaluate what happens to the two most polar subpopulations of peripheral blood monocytes in women diagnosed preeclampsia in comparison with physiological pregnancy.
We used microarrays for comparison of CD14+ and CD16+ monocytes from patients with preeclampsia and women with physiological pregnancy

overall_design: Peripheral venous blood samples were collected prior to the caesarian section in EDTA-treated tubes. CD14+ and CD16+ monocytes were isolated using magnetic sorting

first: Maria

last: Kuznetsova


title: RNA sequencing from hippocampal total lysates of the rTg4510 tauopathy mouse model.

status: Public on Oct 21 2021

city: Providence

first: Bess

last: Frost

state: RI

address: 185 Meeting St

institute: Center for Alzheimer’s Disease Research, Brown University

summary: RNA seqeuncing was perfomed to compare transcriptomic profiles of rTg4510 and control at three, six and nine month time points.

overall_design: Total RNA was isolated from hippocampi of rTg4510 and control mice at three, six and nine months. rRNA-depeleted total RNA was then sequenced using an Illumina HiSeq 4000 with 76 bp paired-end stranded reads at ~30 million reads per sample. The founder rTg4510 and non-transgenic control mice (mixed 129S6, FVB genetic background) were obtained from the Jackson Laboratory (IMSR_JAX:024854).

first: William

last: Ray

first: Virginie

last: Buggia-Prevot

first: Paul

last: Acton

first: Sunil

last: Goodwani

first: Mary

last: Hamby


title: Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptomes for advanced gastric cancer with different ferroptosis-related-scores

city: Harbin

first: Yingwei

last: Xue

address: 150, Haping St, Nangang District

department: Department of Gastrointestinal Oncology

institute: Harbin Medical University Cancer Hospital

summary: Gastric cancer is one of the leading causes of cancer mortality worldwide. We compared transcriptomic profiles of gastric cancer with different ferroptosis-related-scores to identify the prognostic significance of ferroptosis-related-score in gastric cancer.

overall_design: High-throughput sequence profiles from 231 gastric tumors and paired normal 230 gastric tissues from gastric cancer patients


title: Genome-wide gene expression changes in peripheral granulocytes and monocytes from TB patients

first: Kaibo

last: Duan

address: 8A Biomedical Grove, Immunos Building, Level 4

institute: Singapore Immunology Network

summary: Mycobacterium tuberculosis (Mtb) causes a wide spectrum of human disease ranging from asymptomatic latent infection to severe host pathology, but it remains unclear how Mtb influence on leukocyte gene expression differs between disease states.   We assessed mRNA expression in blood monocytes and granulocytes by next-generation sequencing in healthy controls and patients with active tuberculosis infection. We found genome-wide gene expression changes in granulocyte and monocyte which correlated with disease severity.

overall_design: We assessed mRNA expression in peripheral blood monocytes and granulocytes in healthy controls and patients with active tuberculosis infection.

first: Amit

last: Singhal

first: Bernett

last: Lee

first: Michael

last: Poidinger

first: Gennaro

last: De Libero


title: Selective recruitment of the AAA+ ATPase TnsC increases the fidelity of Type I-F CRISPR RNA-guided transposition

city: New York

first: Samuel

last: Sternberg

address: 701 W. 168th Street, HHSC 726

institute: Columbia University

summary: Bacterial transposons are pervasive mobile genetic elements that exploit distinct DNA binding proteins for their horizontal spread. For example, E. coli Tn7 homes to a specific attachment site using a TniQ family protein, whereas diverse Tn7-like transposons employ Type I or Type V CRISPR-Cas systems to insert downstream of target sites specified by a guide RNA. Despite this targeting pathway diversity, transposition invariably requires TnsB, a DDE superfamily transposase that catalyses DNA excision and insertion, and TnsC, a AAA+ ATPase that is thought to communicate between the transposase and targeting proteins. How TnsC mediates this communication and thereby regulates transposition fidelity has remained elusive. Here we apply chromatin immunoprecipitation sequencing (ChIP-seq) to monitor in vivo formation of the Vibrio cholerae RNA-guided transpososome, allowing us to unambiguously resolve distinct protein recruitment events prior to integration. DNA targeting by the TniQ-Cascade complex is surprisingly promiscuous, leading to binding at hundreds of genomic off-target sites, but only a subset of those sites are licensed for TnsC and TnsB recruitment, revealing a crucial proofreading checkpoint that controls transposition fidelity. To advance the mechanistic understanding of interactions responsible for transpososome assembly, we analysed V. cholerae TnsC by cryo-EM and found that TnsC forms ATP-dependent heptameric rings, which are likely to play a critical architectural role in positioning DNA substrates for downstream integration. Collectively, our results highlight the molecular specificity imparted by consecutive binding of distinct factors to genomic target sites during RNA-guided transposition, and provide a structural roadmap to guide future engineering efforts.

overall_design: E. coli genome ChIP-seq profiles for 5 proteins from the CRISPR type-IF-associated transposon. 31 samples were sequenced in total. The raw read files "Input_Cas8_crRNA_ChIP-seq_paired_raw" and "Input_Cas8_crRNA-287_ChIP-seq_paired_raw" are control samples which were used as reference samples for MACS3 peak calling. Replicate samples are indicated as "rep1" or "rep2". Samples that were re-sequenced in order to obtain more sequencing depth are named "[...]_more-depth".

first: Florian

middle: T

last: Hoffmann

first: Minjoo

last: Kim

first: Leslie

last: Beh

first: Jing

last: Wang

first: Phuc

middle: L

last: Vo

first: Diego

middle: R

last: Gelsinger

first: Christopher

last: Acree

first: Jason

last: Mohabir

first: Israel

middle: S

last: Fernandez


title: Transcriptomic profies in control or NCOR1 deficient vascular smooth muscle cells

status: Public on Oct 13 2021

city: Shanghai

first: Lin-Juan

last: Du

address: 115 Jinzun Rd

institute: Shanghai Jiao Tong University School of Medicine

summary: NCOR1  is a trancriptional coregulator  and has been demonstrated to modulate the acitivities of multiple transcription factors in many cell types. However, the function of NCOR1 in vascular smooth muscle cells (VSMCs) is unclear. We aimed to explore the effect of NCOR1 deficiency on gene expression in VSMCs and phenoypic modulation of VSMCs. Therefore, we constructed smooth-muscle specific NCOR1 knockout mice and isolated primary VSMCs for RNA-sequencing.

overall_design: Primary vascular smooth muscle cells (VSMCs) were isolated from three littermated control (LC) mice and three smooth muscle NCOR1 knockout mice and treated with 4-OHT to induce Ncor1 deletion.  VSMCs from 3 technical replicates per group were used to extract total RNA. Total RNA was then subjected to RNA-sequencing.

first: Sheng-Zhong


title: RNA sequencing of total RNA from spinal cord total lysates of the PS19 tauopathy mouse model.

status: Public on Oct 23 2021

first: Bess

last: Frost

summary: RNA seqeuncing was perfomed to compare transcriptomic profiles of PS19 and control mice at four and nine months.

overall_design: Total RNA was isolated from the spinal cord of PS19 and control mice at four and nine months. PolyA selected RNA was then sequenced using an Illumina HiSeq 6000 with 150b bp paired-end stranded reads at ~20 million reads per sample. The founder PS19 mice were obtained from the Jackson Laboratory (IMSR_JAX:008169). Heterozygotic offspring were bred and maintained at Baylor College of Medicine. Wild-type littermates were used as controls.

first: Wei

last: Cao

first: Gabriel

last: Chiu

first: Ethan

last: Roy


title: Gpr126 is essential for placental development

status: Public on Nov 30 2021

first: Jose Luis

last: de la Pompa

address: Melchor Fernández Almagro 3

institute: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC).

summary: Gpr126 is an adhesion G protein-coupled receptor (GPCR) that is expressed in the endocardium of the heart and its inactivation in mice leads to embryonic lethality and defective ventricular trabeculation. However, the mechanistic bases of this phenotype are unknown. We generated a series of standard, conditional loss- and gain-of-function alleles in mice and zebrafish, and found that cardiac abnormalities associated with global Gpr126 inactivation are secondary defects that arise as a result of placental insufficiency.

overall_design: Total RNA was extracted from E12.5 mouse embryonic hearts after removing atria and the valve region in sterile ice-cold PBS. 4 pools of Gpr126+/+ (WT) and 4 pools of Gpr126Δ7/Δ7 (KO) embryonic ventricles (4 ventricles per pool) were used. The tissue was homogenized in TRI ReagentTM Solution (Invitrogen, AM9738) using steel beads in the TissueLyser LT Adapter for 5 minutes at 50 Hz. For RNA extraction, the PicoPureTM RNA Isolation kit (Applied Biosystems, KIT0204) was used according to the manufacturer’s instructions. RNA was quantified and its purity checked with a NanoDrop ND-1000 spectrophotometer (Thermo Scientific). RNA integrity was verified with an Agilent 2100 Bioanalyzer instrument (Agilent Technologies).

first: Rebeca

last: Torregrosa

first: José Luis


title: Gene expression profiling of murine renal adenocarcinoma cells during recursive implantations

status: Public on Oct 27 2021

city: Liverpool

first: Kim

last: Clarke

address: Crown Street

institute: University of Liverpool

summary: The process of serial implantation of a cell line in vivo is a known method to render a cell line increasingly aggressive. In this study, we leveraged this technique to generate increasingly aggressive sub-lines of RENCA, a mouse renal carcinoma cell line. We used different implantation strategies to dissect the different stages of tumor progression and metastasis. Cell-line derived RNA and DNA were used to analyze transcriptional, DNA and methylome profiles of the cell types, and to generate signatures able to predict global, disease-free and progression-free survival time in human patients.

overall_design:
The mouse renal carcinoma cell line RENCA? were implanted orthotopically under the kidney capsule in female BALB/c mice. We adapted this model to produce new sub-cell lines with progressively enhanced aggressiveness and metastatic potential with differing characteristics. We serially passaged the cell lines using different implantation strategies designed to replicate different aspects of tumor development and metastasis. After each passage, primary tumor cells were purified from organ explant cultures to generate new sub-cell lines. The three injections modes were as follows:
(1) Orthotopic injection under the renal capsule leading to formation of a primary tumor (Kidney group). The primary tumor is explanted and cell lines purified for re-implantation into the kidney.
(2) Intravenous injection (tail vein group). Tumor cells are injected directly into the blood stream leading to formation of tumors in the lungs in the absence of a tumor in the kidney
(3) Orthotopic injection under the renal capsule followed by metastasis to the lungs (Lung group). Tumor cells are purified from the lung metastases and are re-implanted under the kidney capsule for the subsequent passage.
The sub-cell lines derived as described above were sequentially passaged 6 times in vivo using multiple mice per injection mode and per passage to give a total of 67 newly-derived sub-cell lines.

first: Andreas

last: Bikfalvi


title: SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline

city: Sagamihara

first: Toshiaki

last: Ito

state: Kanagawa

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

department: Biosciences

institute: Kitasato university

summary: Sexual reproduction involves the creation of sex-dependent gametes, oocytes and sperm. In mammals, sexually dimorphic differentiation commences in the primordial germ cells (PGCs) in embryonic gonads; PGCs in ovaries and testes differentiate into meiotic primary oocytes and mitotically quiescent prospermatogonia, respectively. Here, we show that the transition from PGCs to　sex-specific germ cells was abrogated in conditional knockout mice carrying a null mutation of Smarcb1 (also known as Snf5) gene, which encodes a core subunit of the SWI/SNF chromatin remodeling complex. In female mutant mice, failure to upregulate meiosis-related genes resulted in impaired meiotic entry and progression, including defects in synapsis formation and DNA repair. Mutant male mice exhibited delayed mitotic arrest and DNA hypomethylation in retrotransposons and imprinted genes, resulting from aberrant expression of genes related to growth and de novo DNA methylation. Collectively, our results demonstrate that the SWI/SNF complex is required for transcriptional reprogramming in the initiation of sex-dependent differentiation of germ cells.

overall_design: mRNA profiles of embryo day 15.5 (E15.5) Snf5 Ctrl and Snf5 CKO mice

first: Toshaki

first: Atsuki

last: Osada

first: Masami

last: Ohta

first: Kana

last: Yokota

first: Akira

last: Nishiyama

first: Yuichi

last: Niikura

first: Tomohiko

last: Tamura

first: Yoichi

last: Sekita

first: Tohru

last: Kimura


title: Comparing transcrional changes in Plasmodium yoelii infected to uninfected primary hepatocytes

status: Public on Oct 18 2021

city: Athens

first: Samarchith

last: Kurup

state: GA

address: 500 DW Brooks Dr, 330c Coverdell Center

department: CTEGD - Cellular Biology

institute: University of Georgia

summary: GFP expressing Plasmodium yoelii (Py-GFP) infected, or naïve cultured primary hepatocytes were FACS sorted and re-suspended in TRIzol and RNA purified with RNAeasy kit (Qiagen).RNA was assessed for purity and quality using an Agilent 2100 Bioanalyzer and transcriptome analysis performed on Affymetrix GeneChip Mouse Transcriptome array 1.0. Data output was analyzed and visualized using Affymetrix Expression Console 4.0.

overall_design: Infected hepatocytes were sorted based on the fluorescence signal from infecting Plasmodium yoelii (GFP) and compared to uninfected, sorted hepatocytes from an uninfected culture

first: Rahul

last: Vijay

first: John

last: Harty


title: Effects of NHE3 knockdown on the transcriptome of human colonic adenocarcinoma cells SK-CO15

status: Public on Sep 20 2021

city: Tucson

first: Pawel

middle: R.

last: Kiela

state: AZ

address: 1501 N. Campbell Ave.

department: Pediatrics

institute: University of Arizona

summary: NHE3 expression is downregulated in human colerectal cancer. This study evaluates the influence of of ca. 70% decrease in NHE3 expression on the transcriptomic profile of human colonic adenocarcinoma cells SK-CO15

overall_design: SK-CO15 cells stably transfected with a lentivirus carring scrambled shRNA or shRNA pool targeting SCL9A3 (NHE3) expression were grown to confluence. RNA was purified and used for microarray analysis using Affymetrix human HuGene-2_0-st arrays


title: Identification of differentially expressed genes in Streptococcus agalactiae following phagocytic uptake and survival in THP-1 macrophage cells.

status: Public on Sep 27 2021

city: East Lansing

first: Shannon

middle: D

last: Manning

state: MI

address: 1129 Farm Lane

department: Microbiology and Molecular Genetics

institute: Michigan State University

summary: The goal of this analysis was to identify genes that promote survival of S. agalactiae within macrophages.

overall_design: A total of 6 samples were examined. Two replicates are the controls (S. agalactiae grown in RPMI media), two replicates are for S. agalactiae following uptake by THP-1 cells after 1 hour, and two replicates are for S. agalactiae following uptake by THP-1 cells after 24 hours.

first: Michelle

last: Korir


title: Hsf3 governs intramitochondrial ROS homeostasis via regulating respiratory process

city: Shenyang City, Liaoning Province

first: XinDi

last: Gao

state: Liaoning

address: 89, North WenHua Road

institute: Northeastern university

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

overall_design: Refer to individual Series


title: TF ChIP-seq from HepG2 (ENCSR741TTE)

status: Public on Nov 04 2021

city: Stanford

first: ENCODE

last: DCC

address: 300 Pasteur Dr

institute: ENCODE DCC

summary:
ChIP-Seq on HepG2

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells

first: Wei

last: Yusheng

state: New York

address: 227,South Road of Chongqian,Shanghai,China

institute: Shanghai Jiao Tong University of Medicine

summary: we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and postinjury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with and thus inhibits the transcriptional activity of p53 in hematopoietic  cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from patients with chronic myelogenous leukemia (CML). Anp32b deletion enhances p53 transcriptional activity to impair LSC function in a murine CML model and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B and identify ANP32B as a potential therapeutic target in treating CML.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: RNA-seq data from wild type (WT) and Anp32b-KO LSK cells; RNA-seq data from KU812 cells with shNC and shANP32B infection.

first: Shuo

last: Yang

first: Yun

last: Yu


title: Hsf3 governs intramitochondrial ROS homeostasis via regulating respiratory process [ChIP-Seq]

summary: Mitochondrial quality control is essential in modulating intramitochondrial ROS (mtROS) homeostasis that is a critical determinant for many human disorders. Here we identified an atypical function of a heat shock factor, Hsf3, as an important mtROS regulator. Despite HSFs are nuclear proteins and master regulators of protein unfolded response (UPR) across taxa, we demonstrate that Hsf3 is a both nuclei and mitochondria targeting transcription factor that plays an irrelevant function in controlling UPR process. Instead, Hsf3 represses TCA cycle genes and simultaneously regulates electron transfer chain genes encoded from both nuclei and mitochondria. Moreover, both nuclear and mitochondrial targeting signal are required for promising Hsf3 function. Hsf3 regulation responds to multiple intramitochondrial stresses, which activates and ameliorates Hsf3 DNA binding via oxidation of the cysteine residue on DNA binding domain of Hsf3. Collectively, our findings reveal a previously unknown role of HSF family in modulation of mitochondrial function and damage.

overall_design: performed paired-end ChIP-seq of Hsf1-Flag-tagged and Hsf3-Flag-tagged cells were grown in YPD medium overnight and then subcultured to mid-log phase (OD600=0.8) at 40°C, in biological triplicates.

first: Chen

last: Ding


title: Hsf3 governs intramitochondrial ROS homeostasis via regulating respiratory process [RNA-Seq]

overall_design: performed paired-end RNA-seq of Cryptococcus neoformans H99s as Control group and hsf3∆ strains as in 100ml YPD broth  at OD600=0.8 at 30°C or 40°C, respectively in biological triplicates.


title: Cancer coopts differentiation of B-cell precursors into macrophages

city: Baltimore

first: Supriyo

last: De

state: Maryland

address: 251 Bayview Blvd

department: Laboratory of Genetics and Genomics

institute: NIA-IRP, NIH


title: Single cell transcriptomes of brain metastases and micrometastases derived from triple negative human breast cancer cell line in mouse model.

status: Public on Oct 05 2021

city: Seattle

first: Cyrus

middle: M

last: Ghajar

state: WA

address: 1100 Fairview Ave. N.

department: Public Health Sciences Division/Translational Research Program

institute: Fred Hutchinson Cancer Research Center

summary:
In order to gainan understanding of potential mechanisms by which dystroglycan could effect DTC quiescence signaling in brain, we took an unbiased approach.
We inoculated a series of mice with a tdTomato-positive, brain metastatic variant of T4-2 cells, and examined mice after 6-weeks in order to identify those with distinct brain metastases. Metastatic lesions were surgically dissected, digested and flow sorted to purify tdTomato+ cells (“Metastases”).
In parallel, the remaining uninvolved brain was digested, and residual tdTomato+tumour cells were purified from this digest via flow sorting (“Micromets”). These two populations were indexed, and the libraries were prepared following standard 10X Genomics protocols.

overall_design: In total, 1,779 micromet-derived DTCs (including both mVenus-p27+ and p27- cells from uninvolved brain) were subjected to single cell RNAseq. 4,032 mVenus-p27-  and 251 mVenus-p27+ (quiescent) cells from metastatic lesions were profiled.

first: JinXiang

last: Dai


title: B-cell derived macrophage in mouse and human breast cancer macrophage

first: Bongsoo

last: Park

department: Translational Gerontology Branch

institute: National Institute on Aging

summary: Cancer actively uses B cells to promote its progression and metastasis.  For example, it causes accumulation of bone marrow (BM) B-cell precursors in spleen to convert into immunosuppressive Breg cells. Here, we provide evidence that cancer also coopts differentiation BM CSF1R+ Pax5Lo B-cell precursors to generate macrophages (termed B-MF cells). To do this, cancer uses CSF1 to trigger Csf1r signaling and downregulate PAX5 in B-cell precursors by activating FOXO1. Although tumor-associated macrophages (TAMs) are primarily derived from BM monocytes, our data suggest that some of them may have B-cell origin. Unlike monocyte-derived TAMs, B-MF exhibit a higher M2 polarization, more efficiently phagocytize apoptotic cells, induce FoxP3+ Tregs and suppress T cells activity. We propose that the cancer-B-MF axis is a novel immune escape pathway, thus a therapeutic target.

overall_design: mouse ATAC-seq was performed to compare the open chromatin regions between Csf1r+ BM and Csf1r- BM/ Csf1r+Spleen and Csf1r- Spleen. We also performed scRNA-seq using invitro/invivo tumor macrophage samples.

last: Chen

first: Isabel

last: Beerman

first: Arya

last: Biragyn


title: Impaired bone fracture healing in type 2 diabetes is caused by defective functions of skeletal progenitor cells

status: Public on Oct 01 2021

city: Odense

first: Alexander

last: Rauch

address: Campusvej 55

department: Department of Clinical Research

institute: University of Southern Denmark and Odense University Hospital

summary: The mechanisms of obesity and type 2 diabetes (T2D)-associated impaired fracture healing are poorly studied. In a murine model of T2D reflecting both hyperinsulinemia induced by high fat diet (HFD) and insulinopenia induced by treatment with streptozotocin (STZ), we examined bone healing in a tibia cortical bone defect. A delayed bone healing was observed during hyperinsulinemia as newly formed bone was reduced by – 28.4±7.7% and was associated with accumulation of marrow adipocytes at the defect site +124.06±38.71%, and increased density of SCA1+ (+74.99± 29.19%) but not Runx2+osteoprogenitor cells. We also observed increased in reactive oxygen species production (+101.82± 33.05%), senescence gene signature (≈106.66± 34.03%) and LAMIN B1- senescent cell density (+225.18± 43.15%), suggesting accelerated senescence phenotype. During insulinopenia, a more pronounced delayed bone healing was observed with decreased newly formed bone to -34.9± 6.2% which was inversely correlated with glucose levels (R2=0.48, p<0.004) and callus adipose tissue area (R2=0.3711, p<0.01). Finally, to investigate the relevance to human physiology, we observed that sera from obese and T2D patients exerted inhibitory effects on osteoblastic and enhanced adipocyte differentiation of human bone marrow stromal stem cells. Our data demonstrate that T2D exerts negative effects on bone healing through inhibition of osteoblast differentiation of skeletal stem cells and induction of accelerated bone senescence and that the hyperglycaemia per se and not just insulin levels is detrimental for bone healing.

overall_design: mRNA profiles of primary bone marrow derived stromal cells that were differentiated to osteoblasts in vitro in the presence of serum from lean, obese or typ 2 diabtes subjects.

first: Florence

last: Figeac

first: Michaela

last: Tencerova

first: Dalia

last: Ali

first: Thomas

last: Andersen

first: Dan

last: Appadoo

first: Greet

last: Kerckhofs

first: Nicholas

last: Ditzel

first: Justyna

last: Kowal

first: Moustapha

last: Kassem