title: Androgens show sex-dependent differences in myelination in immune and non-immune murine models of CNS demyelination

status: Public on Feb 19 2023

city: Le Kremlin-Bicêtre

first: Elisabeth

last: TRAIFFORT

address: 80 Rue du Général Leclerc

country: France

institute: Inserm

summary: Neuroprotective, anti-inflammatory and remyelinating properties of androgens are well-characterized in demyelinated male mice and men suffering from multiple sclerosis. However, androgen effects mediated by the androgen receptor AR, have been only poorly studied in females who make low androgen levels. Here, we show a predominant microglial AR expression in demyelinated lesions from female mice and women with multiple sclerosis, but virtually undetectable AR expression in lesions from male animals and men with multiple sclerosis. In female mice, androgens and estrogens act in a synergistic way while androgens drive microglia response towards regeneration. Transcriptomic comparisons of demyelinated mouse spinal cords indicate that, regardless of the sex, androgens up-regulate genes related to neuronal function integrity and myelin production. Depending on the sex, androgens down-regulate genes related to the immune system in females and lipid catabolism in males. Thus, androgens are required for proper myelin regeneration in females and therapeutic approaches of demyelinating diseases need to consider male-female differences.

overall_design: RNA-seq from male and female EAE mice treated with DHT or the corresponding vehicle

last: Traiffort

first: Carlos

last: Parras


title: The Impact of Biosynthesized ZnO Nanoparticles from Olea europaea (Common Olive) on Pseudomonas Aeruginosa Growth and Biofilm Formation

status: Public on Feb 18 2023

city: Zarqa

first: Hafez

last: Al-momani

address: Arab street

department: Microbiology, Pathology and forensic medicine

country: Jordan

institute: Hashemite university

summary: the impact of different concentration of ZnO NPs on the relative gene expression of QS-regulatory genes

overall_design: qPCR gene expression profiling.qRT-PCR was used, the total bacterial RNA was extracted at the middle of the log phase, corresponding to OD600 of 0.5-0.6, from PA subjected to a fairly low concentration (300 µg/ml) and high level (900 µg/ml) of ZnO NPs dispersed in the the MH mediumpooled prior to gene expression analysis.

first: H


title: Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation

city: Houston

first: An

last: Xu

state: TX

country: USA

institute: UThealth Houston

type: Expression profiling by high throughput sequencing

type: Methylation profiling by high throughput sequencing

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We report the application for high-throughput profiling of transcriptome, chromatin-associated proteins and histone-modifications on a genome-wide level in iPSC-derived family control astrocytes vs LFS (Li-Fraumeni Syndrome) patient astrocytes.

overall_design: RNA-seq, ChIP-seq, eCLIP-seq and m6Aseq are used to profile LFS patient derived astrocytes

first: Mo

last: Liu

first: Dung-Fang

last: Lee


title: The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression

status: Public on Feb 17 2023

city: CLEVELAND

first: Bibo

last: Li

state: OH

address: 2121 Euclid Avenue

department: Center for Gene Regulation in Health and Disease

institute: CLEVELAND STATE University

summary: Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. Its major surface antigen VSG is expressed from subtelomeric loci in a strictly monoallelic manner. We previously showed that the telomere protein TbRAP1 binds dsDNA through its 737RKRRR741 patch to silence VSGs globally. How TbRAP1 permits transcription of the single active VSG is unknown. Through NMR structural analysis, we unexpectedly identify an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. Assisted by the 737RKRRR741 patch, TbRAP1 RRM recognizes consensus sequences of VSG 3’UTRs in vitro and binds the active VSG RNA in vivo. Mutating conserved RRM residues abolishes the RNA binding activity, significantly decreases the active VSG RNA level, and derepresses silent VSGs. The competition between TbRAP1’s RNA and dsDNA binding activities suggests a novel mechanism of monoallelic expression, in which the active VSG’s abundant RNA antagonizes TbRAP1’s silencing effect, thereby sustaining its full-level transcription.

overall_design: High-throughput paired-end RNA sequencing on the Illumina platform was performed. Mutant T. brucei strain has one WT TbRAP1 allele flanked by loxP repeats (floxed) and a FLAG-HA-HA and an SV40 NLS- tagged TbRAP1-2FA&5A or a FLAG-HA-HA tagged TbRAP1-2FQ allele. Control T. brucei strain has one floxed and a WT TbRAP1 allele. Both mutant and control cells were induced for Cre induction for 30 hrs (to remove the floxed TbRAP1 allele) before total RNA was isolated. Three independent induction were performed for both mutants. RNA samples were sent to Novogene for subsequent experiments. Poly(A) RNA was purified for generating cDNA library and paired-end sequencing was done using Illumina. Gene expression profiles were compared between the mutant and control cells by differential gene expression analysis.

first: Amit

middle: K

last: Gaurav

first: Marjia

last: Afrin

first: Xian

last: Yang

first: Arpita

last: Saha

first: SK Abdus

last: Sayeed

first: Yanxiang

last: Zhao


title: MBD5 regulates NMDA receptor expression and seizures by inhibiting Stat1 transcription [RNA-Seq]

status: Public on Feb 16 2023

city: Chongqing

first: Feng-lin

last: Tang

address: No. 1, Youyi Road, Yuzhong District, Chongqing

department: Chongqing Key Laboratory of Neurology

country: China

institute: The First Affiliated Hospital of Chongqing Medical University

summary: Epilepsy is considered to result from an imbalance between excitation and inhibition of the central nervous system. Pathogenic mutations in the methyl-CpG binding domain protein 5 gene (MBD5) are known to cause epilepsy. However, the function and mechanism of MBD5 in epilepsy remain elusive. Here, we found that MBD5 was mainly localized in the pyramidal cells and granular cells of mouse hippocampus, and its expression was increased in the brain tissues of mouse models of epilepsy. Exogenous overexpression of MBD5 inhibited the transcription of the signal transducer and activator of transcription 1 gene (Stat1), resulting in increased expression of N-methyl-D-aspartate receptor (NMDAR) subunit 1 (GluN1), 2A (GluN2A) and 2B (GluN2B), leading to aggravation of the epileptic behaviour phenotype in mice. In contrast, overexpression of STAT1 reduced the expression of NMDARs and alleviated the epileptic behavioural phenotype of mice. Furthermore, the epileptic behavioural phenotype was relieved by the NMDAR antagonist memantine. These results indicate that MBD5 accumulation affects seizures through STAT1-mediated inhibition of NMDAR expression in mice. Collectively, our findings suggest that the MBD5-STAT1- NMDAR pathway may be a new pathway that regulates the epileptic behavioural phenotype and may represent a new treatment target.

overall_design: One month after injecting Mbd5 lentivirus (LV-MBD5) and its control virus (LV Control) into the hippocampus of mice, the model was made with kainic acid (KA). One month later, the mouse hippocampus was used for RNA sequencing (6, LV Control models; 6, LV-MBD5 models) and ChIP sequencing (LV-MBD5 model).

first: Ping-yang

last: Ke

first: Yuan-lin

last: Ma

first: Patrick

last: Kwan


title: MBD5 regulates NMDA receptor expression and seizures by inhibiting Stat1 transcription

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

overall_design: Refer to individual Series


title: An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis

status: Public on Feb 15 2023

city: SHANGHAI

first: xiaoxiao

last: zou

state: SHANGHAI

address: 280 SOUTHEAST CHONGQING ROAD

department: Department of Pathophysiology

institute: shanghaijiaotong university

summary: Dysfunction of cell cycle control and defects of primary ciliogenesis are two features of many cancers. Whether these events are interconnected and the driving mechanism controlling and coordinating these events remains largely unknown. Here we identified an actin branching surveillance system that alerts cells for the insufficiency of the actin branching network controlling the restriction point, cytokinesis， and primary ciliogenesis. We found that the ciliopathy protein Oral-Facial-Digital syndrome 1 (OFD1) functions as a previously undescribed class II NPF to promote Arp2/3 complex-mediated actin branching synergistically with class I NPF via its C-terminal acidic domain. Perturbation of actin branching promotes OFD1 degradation and inactivation via a liquid-to-gel transition at centriolar satellites. Elimination of OFD1 or disruption of OFD1-Arp2/3 interaction promotes ciliogenesis and drives proliferating, non-transformed cells into quiescence by an RB-dependent mechanism that is independent of ciliogenesis, senescence, or centrosome loss, which could be reversed by oncogene overactivation. Oncogene-transformed cells, as well as most cancer cells, bypass the G1/S checkpoint in the absence of OFD1 but fail to assemble actin filaments on the actomyosin ring, resulting in incomplete cytokinesis and irreversible mitotic catastrophe. Inhibition of OFD1 leads to marked suppression of pancreatic, colon, and triple-negative breast cancer cell growth in mouse xenograft models. Thus, cancer cells display a major difference from normal cells in their response to the OFD1-mediated actin branching surveillance system, and targeting this surveillance system provides a new direction for cancer therapy.

overall_design: Comparison of gene expression profiling analysis of RNA-seq data for hTERT-RPE1-TOShOFD1 cells (a lentivirus-delivered Tet-On inducible knockdown RPE1 cell line with doxycycline (DOX) induced initiation of short hairpin RNA (shOFD1) expression against OFD1) treated with 200 ng/mL Doxycycline for 72 hours or not.

first: Xiaoxiao

last: Zou

first: Muqing

last: Cao

first: Chaoyi

first: Zaiming

first: Qing

last: Zhong


title: MBD5 regulates NMDA receptor expression and seizures by inhibiting Stat1 transcription [ChIP-Seq]


title: Substrates of PRSS35 in PLC cells

city: Hefei

first: Ting

last: Wang

address: Huangshan

institute: University of Science and Technology of China

summary: Since PRSS35 only exhibited tumor suppressive effects in mice, but not in the cultured cells, we speculated that some factors in the microenvironment are affected by PRSS35. To explore this possibility, we performed SILAC proteomic analysis in conjunction with RNA sequencing to identify secreted proteins that decreased in accumulation, but not in transcription level, in the culture medium of PRSS35 overexpressing PLC cells.

overall_design: We performed gene expression profiling analysis using data obtained from RNA-seq of PLC cells expressing EV or PRSS35.

first: Shengqi

last: Shen


title: Effect of Mrps5 on gene expression in Mrps5 null heart at embryonic 12 days after Mrps5 knockout

status: Public on Feb 14 2023

city: Hang Zhou

first: Feng

last: Gao

state: Zhejiang

address: Kaixuan road 268

department: Department of Cardiology

institute: Second Afliated Hospital, Zhejiang University School of Medicine

summary:
To gain insight into the function of Mrps5 in cardiac development
We conducted RNA sequencing to profile the transcriptomes of Mrps5 fl/fl and Mrps5 fl/fl; cTNT-Cre mouse hearts at embryonic 12 days, prior to the onset of embryos lethality.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for  Mrps5 fl/fl and Mrps5 fl/fl; cTNT-Cre mouse hearts at embryonic 12 days. The ctrl group has 3 biological repeats, indicates as Ctrl_1, Ctrl_2, Ctrl_3, the cKO group has 3 biological repeats,indicates as cKO_1, cKO_2, cKO_3.

first: Tian

last: Liang

first: Jinghai

last: Chen

first: Da-Zhi


title: Myeloid, B, and T lineage regeneration from pluripotent stem cells by defined transcription factors

city: Guangzhou

first: Jinyong

state: GuangDong

address: 190 Kai Yuan Avenue, Science Park, Guangzhou, China

institute: Guangzhou Institutes of Biomedicine and Health (GIBH)

summary: Generating prolonged multi-lineage hematopoiesis from pluripotent stem cells (PSCs), an unlimited cell source, is a crucial aim for regenerative hematology. In this study, we used a gene-edited PSC line and revealed that simultaneous expression of three transcription factors, Runx1, Hoxa9, and Hoxa10, drove robust emergence of induced hematopoietic progenitor cells (iHPCs). The iHPCs engrafted successfully in wild type animals and repopulated abundant and complete myeloid, B, and T lineage mature cells in primary and secondary C57BL/6 recipients. The regenerative multi-lineage hematopoiesis distributed normally in multiple organs, persisted over six months, and eventually declined over time with no leukemogenesis. Transcriptome characterization of regenerative myeloid, B, and T cells at the single cell resolution further projected their identities to natural cell counterparts. Thus, we provide strong genetic evidence that co-expression of exogenous Runx1, Hoxa9, and Hoxa10 simultaneously leads to long-term reconstitution of myeloid, B, and T lineages using PSC-derived iHPCs as cell source.

overall_design: mRNA profiles of 76 single iHPCs. Single iHPCs were sorted from the iHPCs in vitro and were treated according to kit instructions of Discover-sc WTA Kit V2 (Vazyme) and TruePrepTM DNA Library Prep Kit V2 (Vazyme)

first: Qitong

last: Weng

first: Yunqing

last: Lin


title: Effect of Klf15 on gene expression in Mrps5 null heart at 14 weeks after Mrps5 gene knockout

summary:
To understand the molecular mechanisms by which Klf15 overexpression rescues the Mrps5 loss of function phenotype in the heart.
We conducted RNA sequencing to profile the transcriptomes of Mrps5cKO mice infected with AAV9-Klf15 or control AAV9-Luci.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Mrps5 fl/fl;MCM mouse hearts infected with AAV9 luci virus or klf15 virus at 14 weeks after tamoxifen induced Mrps5 gene deletion (7 weeks after AAV9 virus infection). The luci group has 3 biological repeats, indicates as Luci_1, Luci_2, Luci_3,  and the klf15 group has 4 biological repeats,indicates as Klf15_1, Klf15_2, Klf15_3, Klf15_4.


title: Expression data from mouse liver

city: MEXICO CITY

first: LORENA

last: AGUILAR ARNAL

address: TERCER CIRCUITO EXTERIOR, CU

department: BIOLOGIA CELULAR Y FISIOLOGIA

country: Mexico

institute: INSTITUTO DE INVESTIGACIONES BIOMEDICAS- UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO

summary: Circadian rhythms in NAD+ bioavailabity are present in many tissues.  Also, a pronounced depletion in NAD+ levels is observed in diet-induced obesity. This study was designed to investigate transcriptional responses triggered by a timed treatment with NAD+ which recovers heptaic NAD+ oscilations in obese mice, and ameliorates their metabolic dysfunction.

overall_design: Mice were fed either a normal diet (CD group) or a high fat diet (53% Kcal from fat) for eight weeks. Then, high fat-fed mice were divided in two groups, one was intraperitoneally (IP) injected with 50 mg/kg NAD+ at ZT11 (HFN group), and the other was injected with saline solution at ZT 11 (HF group), every day for three weeks under the same feeding conditions.  Livers for transcriptomic analyses were harvested either at ZT6 or at ZT 18 (n=3 animals per time point and group: CD, HF and HFN).

first: Ricardo

last: Orozco Solis

first: Lorena

last: Aguilar Arnal

first: Quetzalcoatl

last: Escalante Covarrubias


title: Arabidopsis TRB proteins function in H3K4me3 demethylation by recruiting the JMJ14 complex

status: Public on Feb 12 2023

city: Los Angeles

first: Zhenhui

address: 610 Charles E Young Dr East

department: Department of Molecular, Cell and Developmental Biology

institute: University of California, Los Angeles

summary: Histone marks H3K27me3 and H3K4me3 are mutual exclusive over plant genome, however, the underlying mechanism is not fully understood. Arabidopsis telomeric repeat binding factors (TRBs) are required for the deposition of H3K27me3 by recruiting Polycomb repressive complexes (PRCs). Here, we demonstrate that TRBs associate and colocalize with JUMONJI 14 (JMJ14) over gene body regions and trigger H3K4me3 demethylation. The trb1/2/3 triple mutant and jmj14-1 mutant show an increased level of H3K4me3 over TRB and JMJ14 binding sites, resulting in up-regulation of their targeting genes. Furthermore, tethering TRBs to the promoter region of genes with an artificial zinc finger successfully triggers target gene silencing. These results suggest that TRB proteins cooperate with PRC2 and JMJ14 complex to repress target gene by H3K4me3 demethylation and H3K27me3 deposition.

overall_design: This dataset includes ChIP-seq, RNA-seq, WGBS and BS-PCR to understand the molecular mechanism of Arabidopsis TRB proteins.

first: Ming


title: Bulk and single-cell transcriptome profiling of hESC-derived definitive endoderm cells induced by small molecules

city: Vancouver

first: Francis

middle: C

last: Lynn

state: BC

address: 950 28th Ave W

department: Surgery

country: Canada

institute: University of British Columbia

summary: Improving methods for human embryonic stem cell differentiation represents a challenge in modern regenerative medicine research. Using drug repurposing approaches, we discover small molecules that regulate the formation of definitive endoderm. Among them are inhibitors of known processes involved in endoderm differentiation (mTOR, PI3K, and JNK pathways) and a new compound, with an unknown mechanism of action, capable of inducing endoderm formation in the absence of growth factors in the media. Optimization of the classical protocol by including this compound achieves the same differentiation efficiency with a 90% cost reduction. The gene expression profile induced by the compound suggests that it is an inhibitor of the MYC pathway. The proposed in silico procedure for candidate molecule selection has broad potential for improving stem cell differentiation protocols.

overall_design:
This study characterizes the bulk and single-cell transcriptome profiling of hESC-derived definitive endoderm cells induced by small molecules.
Please note that the Single_cell_aggr_* and Single_cell_all.tar.gz files are assocated with  Single_cell_36h, Single_cell_Endo_72h, and Single_cell_Meso_72h samples.
Please note that the  "Bulk_all_cor_names.tsv" contains total 30 data columns.  Two sample data for 24 hours of N (N1-38038 and N1-38039) were removed  as they were used as controls (stem cells with no treatment) and redundant to include.

first: Gherman

last: Novakovsky

first: Shugo

last: Sasaki

first: Oriol

last: Fornes

first: Meltem

middle: E

last: Omur

first: Helen

last: Huang

first: Carmen

last: Bayly

first: Dahai

last: Zhang

first: Nathaniel

last: Lim

first: Artem

last: Cherkasov

first: Paul

last: Pavlidis

first: Sara

last: Mostafavi

first: Wyeth

middle: W

last: Wasserman


title: Blocking MAIT cell activation can modulate macrophage gene signature during liver fibrosis regression

status: Public on Feb 10 2023

city: Paris

first: Pierre

last: de la Grange

address: 29, rue du Faubourg Saint-Jacques

department: Paris Biotech Santé

institute: GenoSplice technology

summary: Exploratory RNA sequencing of pro-inflammatory (Ly6C high) and resolutive (Ly6C low) macrophages in mouse liver during fibrosis regression. Mice were treated with a MAIT antagonist or its control vehicle for 2 days after the last CCl4 injection. Ly6C high and Ly6C low macrophages were sorted by ARIA III.

overall_design: Pro-inflammatory and resolutive macrophage gene signature profile during liver fibrosis regression when MAIT cells are inhibited.

first: Sophie

last: Lotersztajn

first: Morgane

last: Mabire


title: Human Preadipocyte Response to PCB52 or 4-OH-PCB52

status: Public on Feb 13 2023

city: Iowa City

first: Aloysius

middle: John

last: Klingelhutz

state: IA

address: 3-604 BSB, 51 Newton Road

department: Microbiology and Immunology

institute: University of Iowa

summary: Purpose: The goal of this study was to perform an expression transcript profile over a timecourse of human preadipocytes that were treated with PCB52 or 4-OH-PCB52; Methods: Immortal human preadipocytes (NPAD) were treated with 10 uM PCB52 or 4-OH-PCB52 in PGM2 media containing 10%FBS for 9 hrs, 1 day, or 3 days. RNA was extracted with TriZol, DNase treated, and purified using a Qiagen column. RNAseq was used to assess gene expression. Bioinformatic analyses were used to determine differential gene expression between PCB52 or 4-OH-PCB52 treated and vehicle-treated at the same timepoint.

overall_design: RNAseq profile of differential gene expression over a timecourse caused by treatment of human preadipocytes with PCB52 or 4-OH-PCB52

middle: J


title: Spatial Transcriptomics Using Multiplexed Deterministic Barcoding in Tissue

status: Public on Feb 09 2023

city: München

first: Johannes

last: Wirth

address: Trogerstrasse 18

department: Institute of Pathology

country: Germany

institute: Technical University Munich

summary: In this study, we present a multiplexed version of Deterministic Barcoding in Tissue (xDBiT) to acquire spatially resolved transcriptomes of nine tissue sections in parallel. New microfluidic chips were developed to spatially encode mRNAs over a total tissue area of 1.17 cm2 with spots of 50 µm×50 µm. Optimization of the biochemical protocol increased read and gene counts per spot by one order of magnitude compared with previous reports. Furthermore, the introduction of alignment markers allows seamless registration of images and spatial transcriptomic spot coordinates. Together with technological advances, we provide an open-source computational pipeline to transform raw sequencing data from xDBiT experiments into the AnnData format. The functionality of xDBiT was demonstrated by the acquisition of 16 spatially resolved transcriptomic datasets from five different murine organs, including cerebellum, liver, kidney, spleen, and heart. Factor analysis and deconvolution of xDBiT spatial transcriptomes allowed for in-depth characterization of the murine kidney.

overall_design: Spatial transcriptomics samples of cerebellum, heart, liver, spleen and kidney from 3-month old mice.

first: Nina

last: Huber

first: Kelvin

last: Yin

last: Brood

first: Simon

last: Chang

first: Celia

middle: P

last: Martinez-Jimenez

first: Matthias

last: Meier


title: Effect of cardiac specific depletion of Mrps5 on gene expression in heart at 12 weeks after gene knockout

first: Feng

last: Gao

summary:
To understand the molecular mechanism underlying Mrps5 function in the heart, we performed RNA sequencing of Mrps5cKO and Mrps5fl/fl hearts 12 weeks after tamoxifen induction.
We chose this stage because the mutant hearts have just started to exhibit detectable defects and the changes in the transcriptome state would more accurately correlate with the onset of the phenotype.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Mrps5 fl/fl;MCM mouse hearts and Mrps5 fl/fl (control) hearts at 12 weeks after tamoxifen induced Mrps5 gene deletion. Each group has 3 biological replicates, the control group indicates as Ctrl_1, Ctrl_2, Ctrl_3,  and the cardiac specific Mrps5  knockout group indicates as cKO_1, cKO_2, cKO_3.

first: Tian

last: Liang

first: Jinghai

last: Chen

first: Da-Zhi

last: Wang


title: An interaction between Gβγ and RNA polymerase II regulates transcription in cardiac fibroblasts

city: Montreal

first: Terence

last: Hébert

state: Quebec

address: 3655 Promenade Sir William Osler

department: Pharmacology and Therapeutics

institute: McGill University

summary: Gβγ subunits are involved in an array of different signalling processes in various compartments of the cell, including the nucleus. To gain further insight into the functions of nuclear Gβγ, we investigated the functional role of Gβγ signalling in the regulation of GPCR-mediated gene expression in primary rat neonatal cardiac fibroblasts. Here, we demonstrate that following activation of the angiotensin II type I receptor in these cells, Gβγ dimers interact with RNA polymerase II (RNAPII). Our findings suggest that Gβ1 recruitment to RNAPII negatively regulates the fibrotic transcriptional response, which can be overcome by strong fibrotic stimuli. The Gβγ-RNAPII interaction was also investigated in HEK 293 cells and was regulated by signaling pathways that diverged from those operating in cardiac fibroblasts, suggesting that although it may be a conserved feature of transcriptional regulation, such regulation may be cell-specific. Taken together, our studies reveal a novel interaction between Gβγ subunits and RNA polymerase II and expand the role for Gβγ signalling in cardiac fibrosis.

overall_design: Gβ1 and RNAPII ChIP-seq from neonatal rat cardiac fibroblasts

first: Shahriar

middle: M

last: Khan

first: Ryan

middle: D

last: Martin

first: Sarah

last: Gora

last: Bouazza

first: Jace

last: Jones-Tabah

first: Andy

last: Zhang

last: MacKinnon

first: Phan

last: Trieu

first: Paul

middle: S

last: Clarke

first: Jason

last: Tanny


title: Hepatocytes demarcated by EphB2 contribute to the progression of non-alcoholic steatohepatitis

status: Public on Feb 08 2023

city: Philadelphia

first: Yang

last: Xiao

state: PA

address: 12-193 Smilow Translational Research Center, 3400 Civic Center Boulevard

institute: UNIVERSITY OF PENNSYLVANIA

summary: Current therapeutic strategies for treating non-alcoholic steatohepatitis (NASH) have failed to alleviate liver fibrosis, which is a devastating feature leading to hepatic dysfunction. Here, we integrated single-nucleus transcriptomics and epigenomics to characterize all major liver cell types during NASH development in mice and humans. The bifurcation of hepatocyte trajectory with NASH progression was conserved between mouse and human. At the non-alcoholic fatty liver (NAFL) stage, hepatocytes exhibited metabolic adaptation, whereas at the NASH stage, a subset of hepatocytes was enriched for the signatures of cell adhesion and migration, which was mainly demarcated by receptor tyrosine kinase EphB2. EphB2, acting as a downstream effector of Notch signaling in hepatocytes, was sufficient to induce cell-autonomously inflammation. Knockdown of Ephb2 in hepatocytes ameliorated inflammation and fibrosis in NASH. Thus, EphB2 expressing hepatocytes contribute to NASH progression and may serve as a potential therapeutic target.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Using unbiased genomic approaches including snRNA-seq and snATAC-seq on livers from mice fed a NASH promoting diet (modified ALIOS diet) for 3 months or 9 months, we comprehensively profiled transcriptomic and epigenomic changes of all major liver cell types during NASH progression. We identified receptor tyrosine kinase Ephb2 was specifically expressed in NASH hepatocytes. We confirmed this finding by performing snRNA-seq in human NASH livers. To determine the function of Ephb2, we performed bulk RNA-seq of the livers with forced expression of Ephb2 in hepatocytes.

first: Mitchell

middle: A

last: Lazar


title: Transcriptional profiling of Rat PFC after acute inescapable footshock stress (FS)

status: Public on Feb 07 2023

city: Brescia

first: Paolo

last: Martini

address: viale Europa 11

department: Department of Molecular and Translational Medicine

country: Italy

institute: University of Brescia


title: Transcriptional profiling of Rat PFC 2 hours after the beginnig of stress

summary:
We performed microarray transcriptional profiling of rat prefrontal cortex 2 hours after the beginnig of acute inescapable footshock (FS) stress
Samples were collected from rats exposed to FS stress and sacrificed 2 hours after the beginnig of 40-minutes stress section and from controls left undisturbed in their cage

overall_design: Microarray analysis was performed using N=6 PFC from stressed rats versus N=6 controls

first: Alessandro

last: Barbon


title: Transcriptional profiling of Rat PFC 24 hours after the beginnig of stress

summary:
We performed microarray transcriptional profiling of rat prefrontal cortex 24 hours after the beginnig of acute inescapable footshock (FS) stress
Samples were collected from rats exposed to FS stress and sacrificed 24 hours after the beginnig of 40-minutes stress section and from controls left undisturbed in their cage

overall_design: Microarray analysis was performed using N=5 PFC from stressed rats versus N=5 controls


title: Transcriptional profiling of Rat PFC after footshock stress

summary:
We performed microarray transcriptional profiling of rat prefrontal cortex after acute inescapable footshock (FS) stress
Samples were collected from rats exposed to FS stress and sacrificed immediately after the 40-minutes stress section and from controls left undisturbed in their cage

overall_design: Microarray analysis was performed using N=8 PFC from stressed rats versus N=8 controls


title: Liver X receptor controls follicular helper T cell differentiation via repression of TCF-1

status: Public on Feb 06 2023

city: Busan

first: Haeseung

last: Lee

address: 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu

department: College of Pharmacy

country: South Korea

institute: Pusan National University

summary: Liver X receptor (LXR) is a critical regulator of cholesterol homeostasis, and inhibits TCR-induced proliferation by altering intracellular sterol metabolism. However, the mechanisms by which LXR regulates helper T cell subset differentiation in vivo remains unclear. Here we demonstrate here that LXR is a crucial regulator of follicular helper T (Tfh) cells in vivo. Both mixed bone marrow chimera and antigen-specific T cell adoptive co-transfer studies show a specific increase in Tfh cells among LXRβ-deficient CD4+ T cell population in response to immunization and LCMV infection. Mechanistically LXRβ-deficient Tfh cells express increased levels of TCF-1 but comparable levels of Bcl6, CXCR5, and PD-1 in comparison with LXRβ-sufficient Tfh cells. Loss of LXRβ confers inactivation of GSK3β induced by either AKT/ERK activation or Wnt/β-catenin pathway, leading to elevated TCF-1 expression in CD4+ T cells. Conversely, ligation of LXR represses TCF-1 expression and Tfh cell differentiation in both murine and human CD4+ T cells. Treatment with an LXR agonist significantly diminishes Tfh cells and the levels of antigen-specific IgG upon immunization. These findings unveil a novel cell-intrinsic regulatory function of LXR in Tfh cell differentiation via controlling GSK3β-TCF1 pathway, which might be a promising target for pharmacological intervention in Tfh-mediated diseases.

overall_design: mRNA profiles of follicular helper T cells from wild type and Nr1h2-/- mice were generated by deep sequencing, singleplicate, using Illumina Truseq

first: Yeonseok

last: Chung


title: Spontaneously Evolved Progenitor Niches Escape Yap Oncogene Addiction in Advanced Pancreatic Ductal Adenocarcinomas

city: Washington

first: Chunling

last: Yi

state: DC

address: 3700 O St NW

department: Oncology

institute: Georgetown University

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

overall_design: Refer to individual Series


title: Diabetic Kidney Disease Induces Transcriptome Alterations Associated with Angiogenesis Activity in Human Mesenchymal Stromal Cells

city: Rochester

first: Nagaswaroop

last: Kengunte Nagaraj

state: Minnesota

address: 200 1st St SW

department: Quantitative Health Sciences

institute: Mayo Clinic

type: Non-coding RNA profiling by high throughput sequencing


title: Diabetic Kidney Disease Induces Transcriptome Alterations Associated with Angiogenesis Activity in Human Mesenchymal Stromal Cells [miRNA]

summary:
To explore the angiogenic activity of MSC in DKD, the transcriptome of adipose tissue-derived MSC obtained from DKD subjects was compared to age-matched controls without diabetes or kidney impairment.
Next-generation RNA sequencing was performed on MSC to identify differentially expressed messenger RNA and microRNA involved in angiogenesis.

overall_design: miRNA-seq data for MSC from DKD and control participants

first: LaTonya

last: Hickson

first: Sabena

last: Conley

first: XiaoHui

last: Bian


title: A novel approach uncovering the biological signal in Hi-C data affected by technical biases

status: Public on Feb 05 2023

city: Moscow

first: Victoria

last: Kobets

state: Moscow Oblast

address: Bolshoy Bulvar, 30. 1

country: Russia

institute: Skolkovo University of Science and Technology

summary: The chromatin interaction assays, particularly Hi-C, enabled detailed studies of chromatin architecture in multiple organisms and model systems, resulting in a deeper understanding of gene expression regulation mediated by epigenetics mechanisms. However, the analysis and interpretation of Hi-C data remain challenging due to technical biases, limiting direct comparisons of datasets obtained in  different experiments and laboratories. As a result, removing biases from Hi-C-generated chromatin contact matrices is a critical data analysis step. Our novel approach HiConfidence eliminates biases from the Hi-C data by weighing chromatin contacts according to their consistency between replicates so that low-quality replicates do not influence the result. The algorithm is effective for the analysis of global changes in chromatin structures such as compartments and TADs. We apply the HiConfidence approach to several Hi-C datasets with significant technical biases that could not be analyzed effectively using existing methods, and obtain meaningful biological conclusions. In particular, HiConfidence aids in the study of how changes in the histone acetylation pattern affect chromatin organization in Drosophila cells.

overall_design: Drosophila melanogaster Schneider-2 (S2) cells were treated to alter the level of histone acetylation. Depletion of histone deacetylase HDAC1 (HDAC-dep) and inhibition of histone deacetylases with trichostatin A (TSA) (HDAC-inh) increased histone acetylation level. Curcumin treatment inhibiting histone acetyltransferases (HAT-inh) was applied to reduce histone acetylation level. For each condition 2 replicates of treated samples and 2 replicates of control samples were obtained.

first: Sergey

last: Ulianov

first: Aleksandra

last: Galitsyna

first: Ekaterina

last: Khrameeva


title: DamID-Seq analysis of cutaneous squamous cell carcinoma cells

city: Edinburgh

first: Frederic

last: Li Mow Chee

address: Crewe Road

department: Edinburgh Cancer Centre

country: United Kingdom

institute: University of Edinburgh

summary: In this study, we interrogated the changes in the fibronectin-induced adhesome in cancer cells using patient-derived malignant keratinocytes from cutaneous squamous cell carcinoma (cSCC). We found that the human enabled homologue, Mena (encoded by ENAH; also known as hMena), an actin regulatory protein of the Ena/VASP family, is upregulated in the adhesome of metastatic cSCC cells compared to equivalent cells from the primary tumour. Using a network analysis approach, we found that Mena clusters within an actin-binding/regulatory module that is upregulated in metastatic keratinocytes. Our proteomic analysis connected Mena to the LINC complex component nesprin-2, and we uncovered a novel role for Mena at the perinuclear region of metastatic keratinocytes. We found that Mena locates adjacent to, and interacts with the C-terminal spectrin repeats of, nesprin-2 at the nuclear membrane. Mena loss results in the reduction of nesprin-2 interactions with actin and lamin A/C, affecting nuclear morphology. Moreover, Mena loss results in the reduction of emerin tyrosine phosphorylation and affects the regulation of PTX3 (which encodes pentraxin-3, an immunomodulatory component of the complement system) via the recruitment of its putative enhancer region to the nuclear lamina

overall_design: DamID sequencing analysis of Dam-lamin B1 and untethered Dam in Met4 and Met4 Mena-/- cutaneous squamous cell carcinoma cells

first: Yatendra

last: Kumar

first: Wendy

last: Bickmore

first: Margaret

last: Frame

first: Adam

last: Byron


title: A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination

status: Public on Feb 04 2023

city: beijing

first: lu

last: z

state: - 选择 -

address: beijing

institute: institution of microbology

summary: Ferroptosis is an iron-dependent programmed cell death caused by lipid peroxidation. Emerging evidence suggests several pathogens manipulate ferroptosis as a way for pathogen propagation, but the underlying mechanisms remain largely elusive. Here, we report that PtpA, secreted by intracellular pathogen Mycobacterium tuberculosis (Mtb), is a ferroptosis inducer during infection. Mechanistically, Mtb PtpA entries into the nucleus through the RaDAR pathway depending on the conserved cysteine 11 site, but not canonical ARs motif. Then, PtpA functions as an adaptor to increase the affinity between protein arginine methyltransferase 6 (PRMT6) with its substrate histone H3, thus promoting the asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a), leading to repression of GPX4 gene expression and the ensuing ferroptosis. Accordingly, disrupting nucleus entry site or PRMT6-interacting motif of PtpA markedly eliminates the PtpA-induced ferroptosis in host cells. These findings find a new motif involved in intracellular pathogens effectors for entering host nucleus, and reveal an unrecognized regulatory role of PtpA as an activator of methyltransferases PRMT6 to promote ferroptosis in host nuclear, providing fresh insights into the mechanism of Mtb-induced cell death.

overall_design: U937 cells infected with BCG or ptpA KO BCG at MOI of 10 for 24 h, and then were exacted RNA for RNA sequencing

first: Cuihua

last: Liu

first: Jing

last: Wang

first: Lihua

last: Qiang

first: Zhe

last: Lu


title: EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE [scRNA-Seq]

city: Munich

first: Gianluca

last: Santamaria

state: Germany

address: Ismaninger Strasse 22

department: Department of Medicine I

institute: Klinikum rechts der Isar – Technical University Munich

summary: Native human epicardial precursors are virtually inaccessible, as they appear in the embryo less than four weeks post-conception, at which point pregnancy may not yet be detected. Protocols have been established to generate epicardial cells and their progeny from human pluripotent stem cells in vitro. However, no current model is amenable to studying the many facets of human epicardial biology, notably epicardium formation, lineage heterogeneity, and functional crosstalk with other cardiac cell types during organ development and disease. Here, we generated human pluripotent stem cell-derived 3D heart organoids showing retinoic acid-dependent self-organization of the epicardium and myocardium, which we called epicardioids. Time course single-cell RNA sequencing revealed that epicardioids are formed through the specification of first heart field progenitors, a subset of which closely correspond to juxta-cardiac field (JCF) cells that have recently been identified in the embryonic mouse heart as novel common progenitors of myocardium and epicardium and have not yet been described and studied in humans. Analysis of chromatin accessibility by single-cell ATAC-seq additionally revealed key transcriptional programs guiding fate decisions along the epicardial lineage tree. Human epicardioids provide a unique model to gain fundamental insights into human epicardium biology and function during heart development, homeostasis, and disease.

overall_design:
single cell transcriptome analysis during timecourse differentiation (days 2,3,4,5,7,10,15, and 30) of hiPSC derived cardiac organoids (epicardioids)

Please note that the processed data files for the GSM5885681-GSM5885683 samples have been updated on April 19, 2023.

first: Dorota

last: Zawada

first: Anna

last: Meier


title: Single cell RNA-sequencing in the mouse central amygdala (CEA)

status: Public on Feb 03 2023

city: Ashburn

first: Yuhan

state: VA

address: 19700 Helix Dr

institute: Janelia Research Campus

summary: The central amygdala (CEA) is a brain region that consists of primarily GABAergic neurons. It has been widely investigated for its role in many innate and adaptive behaviors, such as appetitive and defensive behaviors. Despite the complex functions of CEA, the molecular diversity of CEA neurons has not been systemically examined. Here, we performed single-cell RNA-sequencing (scRNA-Seq) in the CEA to classify the molecularly defined neuron types in this region.

overall_design: Single-cell RNA sequencing was focused on the central amygdala (CEA). For visually guided dissection of the CEA, we used the fluorescent boundaries of the robust PBN to CEA axon projection. This specifically labels the CEA but not surrounding nuclei without directly expressing a transgene in neurons to be analyzed by scRNA-Seq. For this, male C57Bl/6J mice were bilaterally injected with AAV2/1-CAG-GFP into the parabrachial nucleus (PBN). Four weeks after PBN injection, mice were sacrificed, and the CEA was identified and dissected based on specific labeling of afferent fibers from the PBN. The manual single-cell sorting procedure to isolate non-fluorescent cell bodies from micro-dissected brain slices was similar to a previously described protocol (Hempel et al., 2007). Briefly, mice were deeply anesthetized with isoflurane and decapitated to collect 300 µm coronal brain slices. The CEA was manually dissected with spring scissors using the GFP signal as guidance. Two to three tissue sections from each animal were taken to cover the entire CEA and subjected to protease digestion, after which cells were dissociated. Intact neurons were manually selected into individual wells. Neurons collected from seven animals were pooled for sequencing.

first: Sabine

last: Krabbe

first: Fredrick

last: Henry

first: Andrew

middle: L

last: Lemire

first: Scott

last: Sternson


title: Gene expression profile at single cell level of immune cells and structural cells from the epithelial layer, and immune cells from the lamina propria layer of the small intestine

first: Calvin

last: Pan

address: 675 Charles Young Dr South

institute: UCLA

summary: The single-cell suspensions of two major intestinal compartments, the epithelium layer and lamina propria layer, were purified from C57BL/6J mice fed a chow diet and a HFHS diet for 10x Genomics Chromium scRNA-seq analysis.

overall_design: Small intestines were isolated from ten C57BL/6J mice fed a chow diet and ten mice fed a HFHS diet for 8 weeks. The single-cell suspensions of two major intestinal compartments, the epithelium layer and lamina propria layer, were purified and then subjected to FACS sorting. For intraepithelial and lamina propria immune cells, cells were sorted for CD45.2+ live cell population and then profiled utilizing droplet-based 10x Genomics Chromium scRNA-seq. For additional lamina propria immune cells, CD45.2+ live cells were sorted from the lamina propria layer of a new cohort of ten chow diet mice and ten HFHS diet mice, and then profiled using droplet-based 10x Genomics Chromium scRNA-seq. For structural cells, non-hematopoietic CD45.2- live cells were sorted from the epithelium layer of a new cohort of ten chow diet mice and ten HFHS diet mice, and then profiled using droplet-based 10x Genomics Chromium scRNA-seq.

first: Aldons

last: Lusis

first: Yuchen


title: Quantification and mapping of alkylation in the human genome reveal single nucleotide resolution precursors of mutational signatures

status: Public on Feb 01 2023

city: Zürich

first: Shana

last: Sturla

state: No

address: Schmelzbergstrasse 9

department: Department of Health Sciences and Technology

country: Switzerland

institute: ETH Zürich

summary: Benzo[a]pyrene (BaP) is a known human carcinogen (IARC Group 1) found in food, coal tar, as well as cigarettes and other smoke. Its diol-epoxide metabolites (Benzo[a]pyrene diol-epoxide [BPDE]) react with DNA forming DNA adducts, predominantly N2-BPDE-deoxyguanosine (N2-BPDE-dG). While the capacity of BPDEs to alkylate DNA and induce mutations is well known, little is known about how the genomic features influence the accumulation of DNA damage at a genome-wide level. To bridge this gap, we developed a single-nucleotide resolution damage sequencing method to map N2-BPDE-dG in a BPDE exposed human lung cell line, and combined this analysis with mass spectrometry to quantify the total absolute levels of the adduct in the genome. Comparing damage abundance with DNase hypersensitive sites, transcription levels, and other genome annotation data showed that although the overall adduct levels increased with increasing concentration of BPDE, the genomic distribution patterns of N2-BPDE-dG were stable and correlated with the genomic features related to chromatin state and transcriptional activities. In addition, we extracted the preferred local DNA sequence contexts for N2-BPDE-dG, i.e., its DNA damage signature, and found that it was highly similar to the mutational signatures identified from smoking-related lung cancers. These results suggest that genomic features and sequence contexts are important in shaping the landscape of DNA damage arising from chemical exposures and provide an effective strategy for linking single-nucleotide resolution damage sequencing data with cancer mutations.

overall_design: Sequencing of benzo[a]pyrene-diol-oxirane-dG (BPDE-dG) in naked DNA and cells that were exposed to various BPDE concentrations. Each condition includes three biological replicates.

first: Yang

last: Jiang

first: Cécile

last: Mingard


title: Impact of exercise on brain-bone marrow interactions in chronic stress: potential mechanisms preventing stress-induced hypertension

status: Public on Feb 02 2023

city: Inzai

first: Thu

middle: Van

last: NGUYEN

state: Other

address: Hirakagakuendai 1-1

country: Japan

institute: Juntendo University

summary: Brain-bone marrow interactions play a crucial role in stress response. However, it is not known whether the sustained increase in blood pressure caused by chronic stress is associated with changes occurring in these brain-bone marrow interactions. We, herein, examined the effect of chronic restraint stress on the molecular basis of the brain-bone marrow interactions, by especially focusing on the paraventricular nucleus (PVN) of the hypothalamus; a well-established blood pressure control center. Male Wistar rats were randomly assigned into control (Co) and restraint stress (St) groups. Furthermore, since daily exercise has been shown to exert anti-stress and anti-hypertensive effects, a stress + exercise (SE) group was also assessed. Bone marrow and hypothalamic gene expression profiles were examined through the undertaking of reverse transcription polymerase chain reaction and microarrays, respectively. The inflammatory blood cell population was investigated through flow cytometry. Moreover, through the use of immunohistochemistry, we examined the presence of bone marrow-derived C-C chemokine receptor type 2 (CCR2)-expressing microglial cells in the rat PVN. The gene expression levels of bone marrow inflammatory factors such as those of interleukin 1 beta and CCR2 were found to be significantly higher in both the St and the SE group rats (when compared with those of the Co group rats). The inflammatory blood cell population was significantly higher in the restrained groups (St and SE) compared with the Co group. Chronic restraint stress activated the recruitment of bone marrow-derived CCR2-expressing microglial cells into the PVN, whereas daily exercise prevented it. We identified 578 genes that were differentially expressed to a significant level (>1.5-fold difference; p<0.05) in the hypothalami of rats belonging to the three experimental groups. From those 578 genes, 49 genes were identified as differentially expressed between the St and the Co groups, 551 genes were identified as differentially expressed between the SE and the Co groups, and 153 genes were identified as differentially expressed between the St and the SE groups. A notable finding was that restraint stress upregulated the matrix metalloproteinase 3 gene (Mmp3) expression, and that daily spontaneous exercise managed to normalize it. Our findings provide new insights into the effects of restraint stress and of exercise on the regulation of cardiovascular homeostasis through brain-bone marrow interactions. A stress-induced increase of the hypothalamic Mmp3 expression was assumed to increase the permeability of the blood-brain barrier to bone marrow-derived CCR2-expressing microglial cells, which in turn may play a role in the onset of stress-induced hypertension. On the other hand, daily exercise may prevent these pathophysiological events via a downregulation of the Mmp3 expression in the rat hypothalamus.

overall_design: Three groups of male adult Wistar rats (5 weeks old) were formed : control (Co, n=6), stress (St, n=6) and stress rats combined with exercise (SE, n=6) for 4 weeks. Rats were sacrificed by decapitation, brains were extracted and hypothalami were dissected under microscope. Total RNAs were extracted and 200ng total RNAs from the hypothalamus of each rat were processed in the microarray experiment.

middle: V

last: Nguyen

first: Ko

last: Yamanaka

first: Keisuke

last: Tomita

first: Jasenka

last: Zubcevic

last: Gouraud

first: Hidefumi

last: Waki


title: Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy [bulkTCRseq]

city: Boston

first: Deepak

last: Rao

state: MA

address: 60 Fenwood Road

department: Division of Rheumatology, Inflammation, and Immunity

institute: Brigham and Women's Hospital

summary: Kidney transplant recipients are at particular risk for developing tumors, many of which are now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate transplant rejection. We utilized TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following ICI therapy. ICI therapy was associated with a sharp increase in circulating alloreactive CD8+ T cell clones, many of which were also detected in the rejected kidney but not at tumor sites. Longitudinal and cross-tissue TCR analyses revealed unintended expansion of alloreactive CD8+ T cells induced by ICI therapy for cancer, coinciding with ICI-associated organ rejection.

overall_design:
Bulk TCR sequencing was completed on fixed tissue samples and banked PBMCs to track identified alloreactive clones.
*** Submitter declares that the human samples require control for access and will be uploaded to dbGaP. ***

first: Garrett

last: Dunlap

first: Daniel

last: DiToro

first: Joel

last: Henderson

first: Sujal

last: Shah

first: Mike

last: Manos

first: Mariano

last: Severgnini

first: Astrid

last: Weins

first: Indira

last: Guleria

first: Patrick

last: Ott

first: Naoka

last: Murakami


title: Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy [Non-naive CD8 single-cell]

overall_design:
Non-naive CD8 T cells were sorted from PBMCs of 2 post-pembro timepoints, and analyzed using paired single-cell RNA and TCR sequencing.
*** Submitter declares that the human samples require control for access and will be uploaded to dbGaP. ***


title: Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy [MLR single-cell]

overall_design:
A mixed-lymphocyte reaction (MLR) was performed using donor splenocytes and recipient (post-pembro) PBMCs to identify alloreactive T cells, and paired single-cell RNA and TCR sequencing was used to link proliferative and transcriptomic states with TCR clone.
*** Submitter declares that the human samples require control for access and will be uploaded to dbGaP. ***


title: Differentially expressed genes in different aromatic grapes at ripening stage

status: Public on Jan 31 2023

city: Zhengzhou

first: Yongzhou

last: Li

address: No. 28, Gangwan Road, Guancheng District

institute: Chinese Academy of Agricultural Sciences Zhengzhou Fruit Research Institute

summary: In order to investigate what differences exist in the aroma-regulated genes of grape varieties with different aromas, we established different aromatic grape varieties at the ripening stage and looked for the differential genes and their expression.

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of 5 different aromatic grape at ripening stage.

first: Liping

last: guan

first: Sanjun

last: Liu

first: Liangliang

last: He


title: Characterization of radiation‑resistance mechanism  in Spirosoma montaniterrae DY10T in terms of transcriptional  regulatory system

city: seoul

first: Changyun

last: Cho

state: Not US or Canada

address: 1, Gwanak-ro, Gwanak-gu

institute: Seoul National University

summary: Spirosoma montaniterrae DY10T is an uncharacterized radiation-resistanct bacteria isolated from soil in South Korea. In order to identify the underlying mechanisms involved in UVC-resistance, we generated time-series transcriptome data with UVC radiation and analyzed data with computational methods.

overall_design: The bacterial strain DY10T (KCTC 23999T) was grown at 25ºC in liquid nutrient-rich medium tryptone glucose yeast extract (TGY; 1% tryptone, 0.1% glucose and 0.5% yeast extract) or TGY agar plates. For the UVC treatment, the early stationary phase cells on TGY agar plates were exposed to 600 JM-2 of ultraviolet using an ultraviolet crosslinker (UVP, CX-2000, CA, USA) at 254nm. The post-radiation cells of UVC were collected by centrifugation (17,500 × g for 5 min) at 5min, 1hr, 3hr and 12hr with washing and stored with RNAlater solution at -80ºC. Total RNA was isolated using the Ambion Ribopure-Yeast RNA kit, according to manufacturer's instructions.

first: Dohoon

last: Lee

first: Dabin

last: Jeong

first: Sun

last: Kim

first: Myung

first: Sathiyaraj

last: Srinivasan


title: Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [scRNA-seq]

city: San Francisco

first: Marcel

last: Arias Badia

address: 513 Parnassus Ave

institute: UCSF

summary: Gamma delta (γδ) T cells reside within human tissues including tumors, but their role in mediating anti-tumor response with immune checkpoint inhibition is unknown. Using single-cell approaches, we found that kidney cancers are infiltrated by diverse Vδ2- γδ T cells, with equivalent representation of Vδ1+ and Vδ1- cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2- T cells can express the transcriptional program of exhausted alpha beta (ab) CD8+ T cells as well as canonical markers of terminal T cell exhaustion including PD-1, TIGIT and TIM-3. While Vδ2- γδ T cells have blunted IL-2 production, they retain expression of cytolytic effector molecules and costimulatory receptors like 4-1BB. Exhausted Vδ2- γδ T cells are comprised of three distinct populations that lack TCF-7, are clonally expanded, express of cytotoxic molecules, and possess multiple Vδ2- TCRs. Human tumor-derived Vδ2- γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2- T cells in pre-treatment tumor biopsies predicted subsequent clinical responses to PD-1 blockade in vivo in cancer patients. Thus, Vδ2- γδ T cells within the tumor microenvironment can contribute to anti-tumor efficacy.

overall_design: Tumor samples were obtained from resection surgery from 6 adult patients with histologically confirmed renal cell carcinoma (RCC). Samples were minced and digested, then FACS-sorted for live gd, CD4, and CD8 T cells. Samples were then pooled by cell type (to be demultiplexed later via Demuxlet using separately constructed bulk RNA libraries). Libraries were constructed using 10x Genomics Chromium 5’ (v1) and 10x Genomics Chromium V(D)J kit (PN-1000005) and sequenced on an Illumina NovaSeq 6000.

last: Arias-Badia

first: Chiara

last: Rancan

first: Pranay

last: Dogra

first: Brandon

last: Chen

first: Dvir

last: Aran

first: Hai

last: Yang

first: Diamond

last: Luong

first: Arielle

last: Ilano

first: Jacky

first: Hewitt

last: Chang

first: Serena

last: Kwek

first: Li

last: Zhang

first: Lewis

last: Lanier

first: Maxwell

last: Meng

first: Donna

last: Farber

first: Lawrence

last: Fong


title: Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [bulk RNA-seq]

overall_design: Tumor samples were obtained from resection surgery from 6 adult patients with histologically confirmed renal cell carcinoma (RCC). Samples were minced and digested, then FACS-sorted for live gd, CD4, and CD8 T cells. Bulk RNA libraries were constructed using the Smart-seq2 protocol and sequenced on an Illumina HiSeq 4000. The sequenced data was used to generate a variant call format (VCF) file containing single-nucleotide polymorphism (SNP) data for each patient (used later by Demuxlet to demultiplex pooled scRNA data generated from the same tumor samples).

last: Li


title: GPCR-mediated calcium and cAMP signaling determines psychosocial stress susceptibility and resiliency

city: Kyoto

first: Shusaku

last: Uchida

state: Kyoto

address: 53 Kawaharamachi, Sakyo-ku

institute: Kyoto University

summary: We performed high-throughput profiling of gene expression in the anterior cingulate cortex of stress-vulnerable BALB/c mice subjected to social defeat stress. BALB/c mice were subjected to 5-day of social defeat stress and euthanized for tissue collection. We then conducted the transcriptomics analysis. Our study provided insights into the understanding of the molecular mechanisms underlying the behavioral response to stress.

overall_design: BALB/c mice were subjected to 5-day of social defeat stress. Total 2 groups were set up: mice received social defeat stress (smSDS) and non-stress (NS). Three replicates were used for each group.


title: Multi-organ single cell analysis of a mouse model of collagen-induced arthritis [subseries2]

city: Linköping

first: Sandra

last: Lilja

address: Sandbäcksgatan 7

department: BKV

country: Sweden

institute: Linköping University

summary: Prioratization of disease associated mechanisms in immune-mediated inflammatory diseases (IMIDs) is complicated by altered interactions across multiple organs and cell types. We have adressed these challenges by analyzing a multi-organ multicellular disease model (MO-MCDM) of a mouse IMID model, namely collagen-induced arthritis (CIA). In this pilot study, we sequenced at least one healthy and one CIA sample from each of the ten organs, joint, lung, muscle, skin, spleen, blood, draining lymph nodes, thymus, liver, and kidney. Sequencing data from liver and kidney never reached our defined quality cut-off, and were thus excluded from further comparisions.  Of the remaining organs, we found that joint, lung, muscle, skin, and spleen had the highest number of DEGs between CIA and healthy mice. We thus reason that these five organs shoult be most relevant to study disease associated changes on a systemic level, and prioritized those for further analyses.

overall_design: Organ samples were taken from male DBA1/J 6 CIA and 4 healthy mice. The CIA mice were immunized with 100 µg (50µL) bovine collagen II (BC-II, Chondrex, USA) emulsified with 50µL Complete Freund’s Adjuvant (CFA) (Sigma-Aldrich, USA) in 1:1 ratio, via intradermal injection near the base of the tail. A booster immunization was administered on day 20 with 100 µg of BC-II emulsion (prepared with 1:1 incomplete Freund’s adjuvant (IFA)) and injected at the base of the tail. The severity of each arthritic limb was scored on 0-4 scale, 0: Normal, 1: Swelling and redness in one digit, 2: Swelling and redness in more than one digits or swelling and redness in one digit, wrist joint and ankle, 3: Swelling and redness present in paw and digits, 4: maximum inflammation of limb involving all joints and digits. The total arthritis score was the sum score from all four limbs. For this pilot study, organ samples from at least one CIA and one healthy mice were taken for scRNA-seq.

first: Xinxiu

first: Martin

last: Smelik

first: Eun

last: Lee

first: Joseph

last: Loscalzo

first: Pratheek

last: Bellur Marthanda

first: Lang

last: Hu

first: Mattias

last: Magnusson

first: Oleg

last: Sysoev

first: Huan

first: Yelin

last: Zhao

first: Christopher

last: Sjöwall

first: Danuta

last: Gawel

first: Hui

last: Wang

first: Mikael

last: Benson


title: Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function

first: Marcel

last: Arias Badia

overall_design: Refer to individual Series


title: Multi-organ single cell analysis of a mouse model of collagen-induced arthritis


title: Multi-organ single cell analysis of a mouse model of collagen-induced arthritis [subseries1]

summary: Prioratization of disease associated mechanisms in immune-mediated inflammatory diseases (IMIDs) is complicated by altered interactions across multiple organs and cell types. We have adressed these challenges by analyzing a multi-organ multicellular disease model (MO-MCDM) of a mouse IMID model, namely collagen-induced arthritis (CIA). For all the five organs (joint, lung, muscle, skin, and spleen) we found highly complex and heterogenous expression changes due to disease, although, macroscopic and microscopic signs of inflammation could only be seen in joints. Based on the MO-MCDM, predicted molecular interactions within and between organs could be identified. The model supported that inflammation was switched on or off in different organs, by an altered balande between pro- and anti-inflammatory upstream regulators and downstream pathways. This on/off switch was validated in human IMIDs, by analyses of publically available data from 32 different samples of 10 different IMIDs. Additionally, it showed consistency with a general characteristic of both CIA and human IMIDs, namely variable organ involvement in disease.

overall_design: Organ samples were taken from male DBA1/J 6 CIA and 4 healthy mice. The CIA mice were immunized with 100 µg (50µL) bovine collagen II (BC-II, Chondrex, USA) emulsified with 50µL Complete Freund’s Adjuvant (CFA) (Sigma-Aldrich, USA) in 1:1 ratio, via intradermal injection near the base of the tail. A booster immunization was administered on day 20 with 100 µg of BC-II emulsion (prepared with 1:1 incomplete Freund’s adjuvant (IFA)) and injected at the base of the tail. The severity of each arthritic limb was scored on 0-4 scale, 0: Normal, 1: Swelling and redness in one digit, 2: Swelling and redness in more than one digits or swelling and redness in one digit, wrist joint and ankle, 3: Swelling and redness present in paw and digits, 4: maximum inflammation of limb involving all joints and digits. The total arthritis score was the sum score from all four limbs.

last: Zhang


title: STING suppresses the reactivation of dormant metastasis

status: Public on Jan 30 2023

city: New York

first: Jing

address: 417 E 68th St

institute: Memorial Sloan Kettering Cancer Center

summary:
Metastatic relapse frequently develops from disseminated cancer cells that remain dormant in distant organs after the apparently successful treatment of a primary tumor. Disseminated cancer cells fluctuate between immune evasive quiescent and cell cycle reentry states, which exposes them to elimination by the immune system. Little is known about the molecules that determine immune-mediated clearing of awakened metastatic cells and how this process could be therapeutically activated to eliminate residual disseminated disease in patients. Here, we use models of indolent metastasis to identify cancer cell-intrinsic determinants of immune reactivity during cancer cell exit from dormancy. Through in vivo genetic screens of tumor-intrinsic immune regulators, we identified the STING (stimulator of interferon genes) pathway as a suppressor of metastatic outbreak in dormant models of human and mouse lung adenocarcinoma metastasis. STING levels and signaling activity rise in metastatic progenitors that reenter the cell cycle and are dampened by STING enhancer hypermethylation in breakthrough metastases or enhancer chromatin repression in cells reentering dormancy in response to TGF-β. STING expression in cancer cells from spontaneous metastases suppresses their outgrowth in a NK cell- and CD8+ T cell-dependent manner. Systemic treatment of mice with pharmacologic STING agonists eliminates indolent metastatic cells and prevents spontaneous metastasis, both effects requiring cancer cell STING function. Thus, STING signaling represents a checkpoint against the progression of dormant metastasis and suggests a therapeutically actionable strategy for the prevention of disease relapse.
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modification markers H3K4me1, H3K4me3, H3K27ac in human lung cancer cells at different stages of metastasis and in cells treated with TGF-β or not.

overall_design: Jing Hu

first: Gabriela

middle: N

last: Johnson

first: Joan

last: Massagué


title: Signalling inhibition by ponatinib disrupts alternative lengthening of telomeres (ALT)

city: Singapore

first: Maya

last: Jeitany

address: 60 Nanyang Dr

country: Singapore

institute: Nanyang Technological University

summary: Analyses of gene expression changes in cells treated with ponatinib (experiment 1), and in cells either lacking JUN or overexpressing JUN (experiment 2).

overall_design: Experiment 1: RNA-seq on SAOS-2 or T1000 cells treated with either DMSO (as a control) or ponatinib (250nM for 24 hours); 2 replicates per condition.  Experiment 2: Identification of potential JUN transcription targets by RNA-seq in SAOS2 cells lacking JUN (cjun sg vs. LacZ sg as a control) or overexpressing JUN (JUN vs. CTRL (GFP overexpressing cells)); 3 replicates per condition


title: Activation of b-CATENIN in Fibro/Adipogenic Progenitors Leads to Muscle Mass Loss

city: Vancouver

first: Fabio

last: Rossi

address: 2222 Health Sciences Mall

department: School of Biomedical Engineering

institute: University of British Columbia

summary: We induced b-CATENIN transcriptional activity in MPs via inducible deletion of its ubiquitination site. As a result, we observed expansion of MPs in the absence of tissue damage, as well as rapid loss of muscle mass.

overall_design: To assess the role of b-CATENIN in mesenchymal progenitors (MPs), tamoxifen was injected in Hic1CREERT2 :b-CATENIN exon3 WTflox mice:Td.tomato mice. Tomato+ cells from skeletal muscle were sorted and subjected to RNA sequencing

first: Nasim

last: Kajabadi

first: Lin

last: Tung

first: Tara

last: Stach


title: Il-1/MyD88-Dependent G-CSF and IL-6 Secretion Mediates Post Burn Anemia

status: Public on Jan 29 2023

city: Cincinnati

first: Mike

last: Adam

state: Ohio

address: 240 Albert Sabin Way

department: CBDI

institute: Cincinnati Children's Hospital Research Foundation

overall_design: Single-cell RNA-seq was performed on post day 3 burn injured mouse skin

first: Jason

last: Gardner


title: Spatial epigenome-transcriptome co-profiling of mammalian tissues [Human ATAC-Seq]

city: New Haven

first: Di

state: CT

address: 55 Prospect St

department: Biomedical Engineering

institute: Yale University

summary: We present spatially resolved high-spatial-resolution genome-wide co-mapping of epigenome and transcriptome by simultaneously profiling of chromatin accessibility and gene expression (spatial-ATAC-RNA-seq), as well as histone modification and gene expression (spatial-CUT&Tag-RNA-seq) on the same tissue section at cellular level by combining the microfluidic deterministic barcoding strategy in DBiT-seq and the chemistry used in ATAC-seq/CUT&Tag.

overall_design:
Spatially resolved co-sequencing of epigenome and transcriptome in  Human hippocampus

*** Submitter declares that the raw data have not been submitted due to patient privacy concerns ***

first: Rong

last: Fan


title: Spatial epigenome-transcriptome co-profiling of mammalian tissues [spatial CUT&Tag]

overall_design: Spatially resolved co-sequencing of epigenome and transcriptome in mouse brains.


title: Spatial epigenome-transcriptome co-profiling of mammalian tissues

overall_design: Spatially resolved co-sequencing of epigenome and transcriptome in mouse embryos and mouse brains.


title: Spatial epigenome-transcriptome co-profiling of mammalian tissues [Human RNA-Seq]

overall_design:
Spatially resolved co-sequencing of epigenome and transcriptome in Human hippocampus

*** Submitter declares that the raw data have not been submitted due to patient privacy concerns ***


title: Diabetic Kidney Disease Induces Transcriptome Alterations Associated with Angiogenesis Activity in Human Mesenchymal Stromal Cells [mRNA]

city: Rochester

first: Nagaswaroop

last: Kengunte Nagaraj

address: 200 1st St SW

institute: Mayo Clinic

summary:
To explore the angiogenic activity of MSC in DKD, the transcriptome of adipose tissue-derived MSC obtained from DKD subjects was compared to age-matched controls without diabetes or kidney impairment.
Next-generation RNA sequencing was performed on MSC to identify differentially expressed messenger RNA and microRNA involved in angiogenesis.

overall_design: mRNA-seq data for MSC from DKD and control participants

first: LaTonya

last: Hickson

first: Sabena

last: Conley

first: XiaoHui

last: Bian


title: Spatial epigenome-transcriptome co-profiling of mammalian tissues [RNA-Seq]

first: Yanxiang

last: Deng


title: Spatial epigenome-transcriptome co-profiling of mammalian tissues [ATAC-Seq]


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


title: MicroRNA profile of drug resistant metaplastic breast cancer cell lines

city: London

first: Ernesto

last: Yague

address: Du Cane Road

department: Division of Cancer

institute: Imperial College London

summary: Breast cancer cells and two metaplastic breast cancer cell lines were used: a widely available, HS578T, and a novel line isolated from a metaplastic breast cancer tumor, BAS. Doxorubicin and paclitaxel resistant derivatives of these metaplastic lines were generated and miR profiling performed.

overall_design: Cells were treated with increasing concentrations of drug until they were able to survive and proliferate after a pulse of cytotoxic drug.  HS-TX: HS578T cells, 100 nM paclitaxel, 5 days pulse; HS-DOX: HS-578T cells, 100 nM doxorubicin, 3 days pulse; BAS-TX: BAS cells, 20 nM paclitaxe, 3 days pulse; BAS-DOX, BAS cells, 160 nM doxorubicin, 3 days pulse. For the array experiment, RNA isolated from three independent cultures was pooled and used for each condition.

first: E

first: U

last: Kumar


title: High-Throughput Screening for Myelination Promoting Compounds Using Human Stem Cell-derived Oligodendrocyte Progenitor Cells Identifies Novel Targets

status: Public on Jan 28 2023

city: Baltimore

first: Weifeng

last: Li

state: Maryland

address: 400 N Broadway

institute: Johns hopkins university

overall_design: The reporter hESCs were differentiated to OPCs by following the protocol described above. On day 30 of differentiation, neurospheres were plated on a 6-well culture dish to facilitate OPC migration from the plated spheres. 3 wells of day 80 differentiating cultures were treated DMSO as control and two wells each were treated with different small molecules for 10 days

first: Xitiz

last: Chamling

first: Donald

last: Zack


title: Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma

status: Public on Jan 27 2023

first: Navin

last: Chintala

state: NY

address: 417 E 68th Street, 4th Flr, Room 427D

department: Surgery

institute: MSKCC

summary: Regional delivery of oncolytic viruses has been shown to promote immune responses. Malignant pleural effusions comprise an immunosuppressive microenvironment, and the ability of oncolytic viruses to generate immune responses following regional delivery in patients with malignant pleural effusions is unknown. We conducted a phase I clinical trial that studied the intrapleural administration of oncolytic vaccinia virus to establish the safety and feasibility in patients with malignant pleural effusion due to malignant pleural mesothelioma or metastatic disease. In patients with malignant pleural mesothelioma, by correlative analysis of pre- and post-treatment tumor biopsies, we provide insight into tumor-specific viral uptake and associated immune responses.

overall_design: An open-label, dose-escalating, non-randomized, single-center phase I study was conducted to study the intrapleural administration of attenuated vaccinia virus (Olvi-vec) as a bolus. Olvi-vec was administered either as a single dose or as three consecutive daily doses to patients with a histologically or cytologically documented diagnosis of MPE.

first: Prasad

last: Adusumilli


title: A mixture of chemicals found in human amniotic fluid disrupts brain gene expression and behavior in Xenopus laevis

city: Paris

first: Evelyne

last: Duvernois-Berthet

address: 43 rue Cuvier

department: AVIV

institute: Museum national d'Histoire naturelle

summary: We hypothesized that embryonic exposure to a mixture of chemicals (containing phenols, phthalates, pesticides, heavy metals, and perfluorinated, polychlorinated, and polybrominated compounds) identified as commonly found in the human amniotic fluid (as calculated in Fini et al., ) could lead to altered brain development. We assessed its effect on TH signaling and neuro-development in an amphibian model (Xenopus laevis) highly sensitive to thyroid disruption. Fertilized eggs were exposed for eight days to either TH (thyroxine, T4 10 nM) or the amniotic mixture (at the actual concentration) until reaching stage NF47, where we analyzed gene expres-sion in the brains of exposed tadpoles using both RT-qPCR and RNA sequencing.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for brains of exposed tapoles to TH or the amniotic mixture compare to the control.

first: Michelle

last: Leemans

first: Petra

last: Spirhanzlova

first: Stephan

last: Couderq

first: Sébastien

last: Le Mével

first: Alexis

last: Grimaldi

first: Barbara

last: Demeneix

first: Jean-Baptiste

last: Fini


title: Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy

first: Deepak

last: Rao


title: Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice [RNA-Seq]

city: Duarte

first: Zhipeng

last: Fang

address: 1500 E Duarte Rd

institute: City of Hope

summary: Long non-coding RNAs (lncRNAs) are emerging important epigenetic regulators in metabolic processes. Whether they contribute to the metabolic effects of vertical sleeve gastrectomy (VSG), one of the most effective treatments for sustainable weight loss and metabolic improvement, is unknown. Herein, we identified a hepatic lncRNA Gm19619, which was strongly repressed by VSG but highly up-regulated by diet-induced obesity and overnight-fasting in mice. Forced transcription of Gm19619 in the mouse liver significantly promoted hepatic gluconeogenesis with the elevated expression of G6pc and Pck1. In contrast, AAV-CasRx mediated knockdown of Gm19619 in HFD-fed mice significantly improved hepatic glucose and lipid metabolism. Mechanistically, Gm19619 was enriched along genomic regions encoding leptin receptor (Lepr) and the transcriptional factor Foxo1, as revealed in chromatin isolation by RNA purification (ChIRP) assay and was confirmed to modulate their transcription in the mouse liver. In conclusion, Gm19619 may enhance gluconeogenesis and lipid metabolism in the liver.

overall_design: Performing polyA-enriched RNA-seq in mice liver following Vertical sleeve gastrectomy or sham operaion

first: Mingjie

last: Fan

first: Dongqiang

last: Yuan

first: Lili

last: Ding

first: Zhen

middle: B

last: Chen

first: Wendong

last: Huang


title: Single-cell clonal tracking of persistent T-cells in allogeneic hematopoietic stem cell transplantation

city: Berlin

first: Benedikt

last: Obermayer

address: Chariteplatz 1

department: Core Unit Bioinformatics

institute: Berlin Institute of Health

summary: The critical balance between intended and adverse effects in allogeneic hematopoietic stem cell transplantation (alloHSCT) depends on the fate of individual donor T‐cells. To this end, we tracked αβT‐cell clones during stem cell mobilization treatment with granulocyte-colony stimulating factor (G-CSF) in healthy donors and during immune reconstitution after transfer to transplant recipients. More than 250 αβT‐cell clones were tracked from donor to recipient. These clones consisted almost exclusively of CD8+ effector memory T cells (CD8TEM), which exhibited a different transcriptional signature with enhanced effector and cytotoxic functions compared to other CD8TEM. Importantly, these distinct and persisting clones could already be delineated in the donor. We confirmed these phenotypes on the protein level and their potential for selection from the graft. Thus, we identified a transcriptional signature associated with persistence and expansion of donor T-cell clones after alloHSCT that may be exploited for personalized graft manipulation strategies in future studies.

overall_design:
We designed our study to analyze peripheral blood lymphocytes of paired donor and recipient samples. We included five alloHSCT patients between December 2018 and May 2019 who received PB grafts from related donors at the Charité Universitätsmedizin Berlin. Patients were only included if the respective donors could be included as well. Blood samples were collected from donors before G-CSF mobilization and on the day of apheresis. Recipient samples were collected on days +90 and +180 post transplantation.
**RAW data not provided due to patient privacy concerns**

first: Luisa

last: Keilholz

first: Friedrich

last: Wittenbecher

first: Il-Kang


title: Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools

city: Munich

first: Gianluca

last: Santamaria

address: Ismaninger Strasse 22

institute: Klinikum rechts der Isar – Technical University Munich

summary: He we report a systematic analysis of RA impact on human cardiovascular progenitor specification in orchestry with other signaling cues during early mesoderm formation. To approach this, we used a single cell transciptome profiling to dissect heterogeneity within human heart field-like cell populations and their derivatives. Our analysis enable us to identify known as well as a novel population of cells that can in vitro differentaite towards myocytic as well as epicardial lineages.

overall_design: single cell transcriptome analysis of hESC in vitro derived human primitive streak-like cells (d1.5), cardiovascular progenitors (4 sorted samples at d4.5) and their derivatives (4 samples at d30)

first: Dorota

last: Zawada


title: Effect of HNRNPA2B1 inhibition in pulmonary arterial smooth muscle cell from pulmonary arterial hypertension

city: los angeles

first: Gregoire

last: Ruffenach

state: california

address: 650 charles E young street BH 550

department: Anesthesiology

institute: UCLA

summary: Investigate the effect of HNRNPA2B1 inhibition of the transcriptomic profile of PAH-PASMC

overall_design: Comparative gene expression profiling analysis of RNA-seq data for PAH-PASMC treated with Si-HNRNPA2B1 vs Si-Scrm.

first: Lejla

last: Medzikovic

first: Laila

last: Aryan

first: Min

last: Li

first: Mansoureh

last: Eghbali


title: Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice

first: Zhipeng

overall_design: Refer to individual Series


title: Linking chromatin acylation mark-defined proteome and genome in living cells

city: Beijing

first: Xiong

last: Ji

address: Yiheyuan Road

department: School of life science

institute: Peking University

summary: A generalizable strategy with programmable site-specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but challenging. We herein developed a Single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications, and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealed distinct crotonylation (e.g., H3K56cr) and β-hydroxybutyrylation (e.g., H3K56bhb) upon short chain fatty acids stimulation, and established linkages for chromatin acylation mark-defined proteome, genome and functions. This led to the identification of GLYR1 as a distinct interacting protein in modulating H3K56cr’s gene body localization as well as the discovery of an elevated super-enhancer repertoire underlying bhb-mediated chromatin modulations. SiTomics offers a platform technology for elucidating the “metabolites-modification-regulation” axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones.

overall_design: Hi-C was performed to explore the 3D genome changes caused by site-specific histone acylations

first: Fangfei

last: Qin

first: Boyuan


title: Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice [ChIRP-Seq]

last: Fang

overall_design: Chromatin isolation by RNA purification from mouse primary hepatocytes, followed by DNA-seq.

first: Mingjie

last: Fan

first: Dongqiang

first: Lili

first: Zhen


overall_design: RNA-Seq was performed to explore the distribution of genetic incorporated site-specific histone acylation marks in living cells and metabolites regulated gene expression


title: Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells

status: Public on Jan 26 2023

city: Lausanne

first: Valentina

last: Scandella

address: Rue du Bugnon 7

institute: University of Lausanne

summary: Cellular metabolism is important for adult neural stem/progenitor cell (NSPC) behavior. However, its role in the transition from quiescence to proliferation is not fully understood. We here show that the mitochondrial pyruvate carrier (MPC) plays a crucial and unexpected part in this process. MPC transports pyruvate into mitochondria, linking cytosolic glycolysis to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Despite its metabolic key function, the role of MPC in NSPCs has not been addressed. We show that quiescent NSPCs have an active mitochondrial metabolism and express high levels of MPC. Pharmacological MPC inhibition increases aspartate and triggers NSPC activation. Furthermore, genetic Mpc1 ablation in vitro and in vivo also activates NSPCs, which differentiate into mature neurons, leading to overall increased hippocampal neurogenesis in adult and aged mice. These findings highlight the importance of metabolism for NSPC regulation and identify an important pathway through which mitochondrial pyruvate import controls NSPC quiescence and activation.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MPC1 wt and MPC1 cKO NSPCs

first: Francesco

last: Petrelli

first: Sylvie

last: Montessuit

first: Nicola

last: Zamboni

first: Jean-Claude

last: Martinou

first: Marlen

last: Knobloch


title: Expression data from human fetal and adult neutrophils

city: Martinsried

first: Tobias

last: Straub

address: Großhadener Str. 9

department: Biomedical Center, Bioinformatics

institute: LMU Munich

summary:
Fetal neutrophils from early embryonic stages display a reduced capacity to react to inflammatory stimuli, therefore this study aimed to investigate the underlying molecular mechanisms regulating fetal neutrophil function during ontogeny.
Whole transcriptome analysis of human fetal cord blood-derived neutrophils from premature (<37 weeks of gestation) and mature (>37 weeks of gestation) infants, compairing their gene expression profiles to neutrophils from healthy adult donors

overall_design: Human fetal and adult neutrophils were purified, RNA was isolated and loaded on a Hgu133plus (Affymetrix, Santa Clara, CA).

first: Johannes

last: Altstatter

first: Markus

last: Sperandio

first: Matthias

last: Heinig


title: Actin-related protein 6 facilitates proneural protein-induced gene activation for rapid neural differentiation

city: Taoyuan City

first: Yun-Ling

last: Hsiao

state: Guishan Dist.

address: No. 259, Wenhua 1st Road

country: Taiwan

institute: Chang Gung University

summary: Actin-related protein 6 (Arp6), a core component of the H2A.Z exchange complex SWR1, interacts with proneural proteins and is crucial for efficient onset of proneural protein target gene expression.

overall_design: We performed gene expression profiling analysis using data obtained from RNA-seq of Drosophila S2 cells after dsRNA treatment and plasmid transfection.

first: Hui-Wen

last: Chen

first: Kuan-Han

first: Bertrand Chin-Ming

last: Tan

first: Chia-Hsiang

first: Haiwei

last: Pi


title: Hedgehog signaling affects platelet-derived growth factor signaling mediated alveolar septum formation during postnatal lung development [bulk RNA-seq]

city: New York City

first: Alireza

last: Khodadadi-Jamayran

address: 550 1st Ave, MSB 304

department: Division of Advanced Research Technologies (DART)

institute: New York University, NYU Langone Medical Center

summary: HH inhibition reproduces the lung phenotype of PDGF pathway knockout lungs and results in profound effects on differentiation and gene expression of Pdgfra-expressing alveolar mesenchymal cells, in particular myofibroblasts.

overall_design: Single cell lung suspensions of PgfraEGFP/+ reporter lungs (P8) from mice treated with anti-HH antibody 5E1 or control IgG at E18.5 were sorted based on endogenous EGFP fluorescence and were prepared for bulk RNA-seq.

last: Kugler


title: Plasticity and stereotypic rewiring of the transcriptome upon bacterial evolution of antibiotic resistance

city: Szeged

first: Gabor

last: Grezal

state: Csongrád

address: Temesvári krt. 62.

department: Institute of Biochemistry

country: Hungary

institute: Biological Research Centre

summary: Bacterial evolution of antibiotic resistance frequently has deleterious side effects on microbial growth, virulence, and susceptibility to other antimicrobial agents. However, it is unclear how these trade-offs could be utilized for manipulating antibiotic resistance in the clinic, not least because the underlying molecular mechanisms are poorly understood. Using laboratory evolution, we demonstrate that clinically relevant resistance mutations in Escherichia coli constitutively rewire a large fraction of the transcriptome in a repeatable and stereotypic manner. Strikingly, lineages adapted to functionally distinct antibiotics and having no resistance mutations in common show a wide range of parallel gene expression changes that alter oxidative stress response, iron homeostasis, and the composition of the bacterial outer membrane and cell surface. These common physiological alterations are associated with changes in cell morphology and enhanced sensitivity to antimicrobial peptides. Finally, the constitutive transcriptomic changes induced by resistance mutations are largely distinct from those induced by antibiotic stresses in the wild-type. This indicates a limited role for genetic assimilation of the induced antibiotic stress response during resistance evolution. Our work suggests that diverse resistance mutations converge on similar global transcriptomic states that shape genetic susceptibility to antimicrobial compounds.

overall_design: E. coli  BW 25113 single mutant lines carrying one of the following resistance mutations: (envZ[Ala396Thr], marR[Val84Glu], trkH[Thr350Lys], gyrA[Asp87Gly], phoQ[Gly384Cys], rpoC[Ala784Val], soxR[Leu139*]) were established using a highly precise allele replacement protocol (Toprak et al. 2012; Lázár et al. 2013; Nyerges et al. 2016). In addition, 3 ancestor lines were treated with lethal concentration of ciprofloxacin (50 ng/ml) for 120 minutes (CC*_120). Untreated samles were collacted immediatly after antibiotic treatment (0 minutes; CC*_0). Sample groups contain 3 biological replicates.

first: Gábor

last: Grézal

first: Réka

last: Spohn

first: Orsolya

last: Méhi

first: Anett

last: Dunai

first: Viktória

last: Lázár

first: Balázs

last: Bálint

first: István

last: Nagy

first: Csaba

last: Pál

last: Papp


title: Spatial epigenome-transcriptome co-profiling of mammalian tissues [CUT&TAG]

first: Di

last: Zhang

overall_design: Spatially resolved co-sequencing of epigenome and transcriptome in mouse brains.

first: Rong

last: Fan


title: Pharmacological intervention of PRMT5 links the E2F pathway with tumor associated antigens derived from the non-coding genome

city: St. Petersburg

first: Alexander

last: Kanapin

address: 7/9 University Emb.

department: Institute for Translational Biomedicine

institute: St Petersburg Universoty

summary: E2F activity impacts on an extensive gene network mediated in part by PRMT5-dependent arginine methylation which widens its functional role in gene expression control. We show here that the PRMT5-E2F1 axis has an additional and unexpected level of control through facilitating expression of the non-coding genome where long non-coding (lnc) genes are direct targets for PRMT5 and E2F1. The expression of some lncRNAs results in their translation into small proteins, which then give rise to peptides which populate the MHC class I antigen presentation machinery.  Pharmacological inhibition of PRMT5 alters the expression of lncRNA genes and thereby the repertoire lncRNA-derived peptides presented as MHC bound peptides. Delayed tumor growth upon PRMT5 inhibition reflects an influx of lncRNA peptide-specific cytotoxic CD8 T cells. When presented to the immune system as a stand-alone therapeutic vaccine, lncRNA-derived MHC-bound peptides are immunogenic and drive a potent anti-tumor T cell response with a significant delay in tumor growth. Our results show that the PRMT5 through its control of the E2F pathway influences expression of the non-coding genome and derived peptides presented to the immune system, which can subsequently be harnessed to deliver an effective stand-alone cancer vaccine. These results have important implications for deploying pharmacological intervention to manipulate gene expression and antigen presentation to the immune system and deploying new types of cancer vaccine. They also indicate that cell cycle control through the E2F pathway is intimately connected with immune recognition.

overall_design: Examination of expression profile of murine (CT26) colorectal cancer cells treated with DMSO (Control) or PRMT5 inhibitor (T1-44). In the experiment, the impact of PRMT5 inhibition on gene expression profiles was monitored.  The experiment had 2 samples (CT26 + DMSO, CT26 + T1-44) and was performed in biological triplicate.  CT26 + DMSO samples were used as the reference sample to which all others were compared.  An analysis was also performed on RNA extracted from tumor samples (Colon26 cells grown in situ in Balb/c mice, treated with DMSO or T1-44).  Again the experiment had two treatment conditions (DMSO and T1-44) and was performed in biological triplicate.  Tumor samples treated with DMSO were used as the reference sample to which all others were compared.

first: Wojciech

last: Barczak

first: Simon

last: Carr

first: Geng

last: Liu

first: Shonagh

last: Munro

first: Annalisa

last: Nicastri

first: Lian-Ni

last: Lee

first: Nicola

last: Ternette

first: Paul

last: Klenerman

first: Anastasia

last: Samsonova

first: Nicholas

last: La Thangue


title: The novel chloroplast glucose transporter pGlcT2 affects adaptation to extended light periods

status: Public on Jan 25 2023

city: Kaiserslautern

first: Benjamin

last: Pommerrenig

address: Paul-Ehrlich-Str. 22

department: Biology

institute: University of Kaiserslautern

summary: Intracellular sugar compartmentation is critically involved in plant development and acclimation to challenging environmental conditions. Sugar transport proteins are present in the plasma membrane and in membranes of organelles such as vacuoles, the Golgi apparatus and plastids. Here we report on a novel transporter of the Monosaccharide Transporter Family (MSF), that is the closest phylogenetic homolog to the chloroplast-localized glucose transporter pGlcT and that we therefore term plastidic glucose transporter 2 (pGlcT2). Its gene complemented glucose uptake deficiency of an Escherichia coli ptsG/manXYZ mutant strain and biochemical characterization revealed that this transporter specifically facilitates glucose transport, whereas other sugars do not serve as substrates. pGlcT2-GFP fusions located to the chloroplast envelope, and promoter activity analyses indicated that pGlcT2 is mainly produced in seedlings and in the rosette center of mature Arabidopsis plants. In the absence of additional sugars, pGlcT2-overexpression lines exhibited impaired germination. In conjunction with molecular and metabolic data we propose that pGlcT2 acts as a glucose importer that can limit cytosolic glucose availability in developing pGlcT2-overexpressing seedlings. Overexpression, as well as deletion of pGlcT2 resulted in impaired growth efficiency under long day and especially under continuous light conditions, suggesting that pGlcT2 contributes to a release of glucose derived from starch mobilization late in the light phase. These data thus indicate that the facilitator pGlcT2 changes its direction of glucose transport during plant development and suggest that the activity of pGlcT2 must be controlled spatially and temporarily, in order to prevent developmental defects during adaptation to periods of extended light.

overall_design: Comparative gene expression analysis of Arabidopsis thaliana lines overexpressing or lacking the pGLCT2 (At1g05030) gene under permanent light conditions

first: Valifard

last: Marzieh

first: Keller

last: Isabel

first: Pommerrenig

last: Benjamin

first: Neuhaus

last: H Ekkehard


title: Cancer-Associated Mesothelial Cell-Derived ANGPTL4 and STC1 Promote the early steps of Ovarian Cancer metastasis

city: Chicago

first: Hilary

last: Kenny

state: IL

address: 927 E 57TH STREET, ROOM W107K, CHICAGO, IL 60637

institute: University of Chicago

summary: Ovarian Cancer preferentially metastasizes in association with mesothelial cell-lined surfaces.We sought to determine if mesothelial cells are required for OvCa metastasis and detect alterations in mesothelial cell gene expression upon interaction with OvCa cells. To evaluate the OvCa-induced transcriptome changes in mesothelial cells, primary human mesothelial cells from 10 patients were treated with OvCa conditioned media or ascites and RNAseq analysis was performed.

overall_design: Comparative Gene expression profiling of RNAseq data for Human primary mesothelial cells treated with  ovarian cancer cell conditioned media, ascites or control media.

first: Bajwa

last: Preety

first: Kordylewicz

last: Kasjusz

first: Lengyel

last: Ernst

first: Kenny

last: Hilary


title: Commensal bacteria and the lung environment are responsible for Th2-mediated memory yielding natural IgE in MyD88-deficient mice

city: Noda

first: Hiroyasu

last: Aoki

state: Chiba

address: 2669 Yamazaki

department: Research Institute for Biomedical Sciences

institute: Tokyo University of Science

summary: IgE antibody is known as a common mediator of allergic responses, generally produced in type 2 immune responses to allergens. It is known that IgE binding to FcεRI without allergen binding promotes survival or proliferation of mast cells, basophils and other cells. Thus, spontaneously produced IgE, namely natural IgE, can increase an individual’s susceptibility to allergic diseases. Mice with a genetic defect in MyD88, a major signaling molecule downstream of Toll-like receptors, have a high level of serum natural IgE, the mechanism for which remains unknown. Here, we demonstrated that the maintenance of high serum IgE levels depends on memory B cells (MBCs). IgE from plasma cells and the sera from most of Myd88–/– mice, but none of Myd88+/– mice, recognized Streptococcus azizii (S. azizii), a commensal bacterium over-represented in the lung of Myd88–/– mice. IgG1+ MBCs from spleen also recognized S. azizii. The serum IgE levels declined by administration of antibiotics and were boosted by challenge with S. azizii in Myd88–/– mice. Moreover, bulk IgH repertoire analysis revealed that CDR3 sequences were highly shared between IgE+ PCs and IgG1+ or IgG2+ MBCs, indicating the contribution of S. azizii-specific IgG1+ MBCs to the natural IgE production.

overall_design: IgD- IgM- CD138- GL7- CD38+ CD19+ class-switched memory B cells or CD19- CD98+ CD138+ plasma cells (PCs) were sorted from spleen, mediastinal LN (medLN) or lung of unimmunized MyD88-deficient mice. Bulk IgH sequencing was performed for IgE, IgG1/2b/2c and IgG3 isotypes in these samples, and pairwise distances of the sequences were calculated based on the Morisita-Horn similarity index.

first: Shunsuke

last: Amano

first: Kei

last: Haniuda

first: Saori

last: Fukao

first: Satoshi

last: Ueha

first: Daisuke

last: Kitamura