title: Acetate supplementation rescues social deficits and alters transcriptional regulation in prefrontal cortex of  Shank3  deficient mice

city: New York

first: Aya

last: Osman

state: NY

address: 109 east 102nd street, apartment 3c

department: Neurology

institute: Icahn School of Medicine Mount Sinai

summary: Autism spectrum disorder (ASD) is a heterogenous neurodevelopmental disorder with complex pathophysiology including both genetic and environmental factors. Recent evidence demonstrates the gut microbiome and its resultant metabolome can influence brain and behavior and have been implicated in ASD. To investigate gene by microbiome interactions in a model for genetic risk of ASD, we utilize mutant mice carrying a deletion of the ASD-associated Shank3 gene (Shank3KO). Shank3KO have altered microbiome composition and function at baseline in addition to social deficits. Further depletion of the microbiome with antibiotics exacerbates social deficits in Shank3KO, and results in transcriptional changes in the frontal cortex. Supplementation with the microbial metabolite acetate leads to reversal of social behavioral phenotypes even in mice with a depleted microbiome, and significantly alters transcriptional regulation in the prefrontal cortex. These results suggest a key role for the gut microbiome and the neuroactive metabolite acetate in regulating ASD-like behaviors.

overall_design: Comparative gene expression profiling analysis of RNA-seq data from Wt and Shank3 deficient mice treated with water as controls, antibiotics, antibiotics plus acetate and acetate only

first: Drew

last: Kiraly

first: Michael

middle: S

last: Breen

first: Joseph

last: Buxbaum

first: Christoph

last: Thaiss

first: Jasleen

last: Gill

first: Lev

last: Litichevskiy

first: Elodie

last: Drapeau

first: Ariela

middle: B

last: Grice

first: Kenny

last: Chan

first: Scott

last: Tyler

first: Katherine

last: Meckel

first: Rebecca

last: Pollak

first: Gilllian

last: Zipursky

first: Tanner

last: Euston

first: Ana

middle: N

last: Strat

first: Nicolas

last: Mervosh


title: Nrf2-regulated L-2-hydroxyglutarate sensitizes erythroid cells to ferroptosis in sickle cell disease [ChIP-seq]

status: Public on Mar 02 2023

city: Augusta

first: Xingguo

last: Zhu

state: Georgia

department: Cancer Center

country: USA

institute: Augusta University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: SCD had hemolysis with elevated levels of heme and iron, which induced ferroptosis. Here, we found Nrf2 knockout in SCD mice accumulated the levels of the metabolite L-2-hydroxyglutarate (L2HG), which impaired ferroptosis stress response to exacerbate SCD symptom. Mechanistically, L2HG was found to regulate the expression of genes involved in the iron and heme metabolism via histone epigenetic hypermethylation. Our findings indicate an important role of Nrf2/L2HG in SCD for ferroptosis response.

overall_design: Comparison of the genome-wide distribution of histone lysine 27 trimethylation in bone marrow erythroid cell of sickle cell disease Nrf2 WT (3 samples) and Nrf2 KO mice (3 samples) at 2-3 month of age.

first: Caixia

last: Xi

first: Junfeng

last: Pang


title: Pyruvate dehydrogenase fuels a critical citrate pool that is essential for Th17 cell effector functions (RNA-Seq II)

city: Esch-sur-Alzette

first: Joseph

last: Longworth

state: Luxembourg

address: 29, rue Henri Koch

department: Department of Infection and Immunity

country: Luxembourg

institute: LIH

type: Expression profiling by high throughput sequencing

summary: Pyruvate dehydrogenase (PDH) is the central enzyme connecting glycolysis and the tricarboxylic acid (TCA) cycle. The importance of PDH function in Th17 cells is unknown. Here, we show that PDH is essential for the generation of a unique glucose-derived citrate pool needed for Th17 cell proliferation, survival and effector function. In vivo, mice harboring a T cell-specific deletion of PDH were less susceptible to developing experimental autoimmune encephalomyelitis. Mechanistically, the absence of PDH in Th17 cells increased glutaminolysis, glycolysis, and lipid uptake in an mTOR-dependent manner. However, cellular citrate remained critically low in mutant Th17 cells, which interfered with oxidative phosphorylation (OXPHOS), lipid synthesis and histone acetylation crucial for the transcription of Th17 signature genes. Increasing cellular citrate in PDH-deficient Th17 cells restored their metabolism and function, identifying a metabolic feedback loop within central carbon metabolism that may offer possibilities for therapeutically targeting Th17 cell-driven autoimmunity.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Th17 cells with and without PDH knockout as well as with and without treatmnt with Acetate each with 4 replicates.

first: Leticia

last: Soriano-Baguet

first: Dirk

last: Brenner


title: Pyruvate dehydrogenase fuels a critical citrate pool that is essential for Th17 cell effector functions

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

overall_design: Refer to individual Series


title: Pyruvate dehydrogenase fuels a critical citrate pool that is essential for Th17 cell effector functions (RNA-Seq I)

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Th17 cells with and without PDH knockout with 3 replicates.


title: Pyruvate dehydrogenase fuels a critical citrate pool that is essential for Th17 cell effector functions (ATAC-Seq)

overall_design: ATAC

first: Sergio

last: Helgueta

first: Deborah

last: Gérard

first: Lasse

last: Sinkkonen


title: CCN2 deficiency in smooth muscle cells triggers cell reprogramming and aggravates aneurysm development

city: Atlanta

first: Qian

last: Xu

state: GA

address: 101 Woodruff Circle

institute: Emory University

summary: Vascular smooth muscle cell (VSMC) phenotypic switching is widely recognized as a key mechanism responsible for the pathogenesis of several aortic diseases such as aortic aneurysm. Cellular communication network factor 2 (CCN2), often upregulated in human pathologies and animal disease models, exerts a myriad of context-dependent biological functions. However, current understanding of the role of SMC-CCN2 in SMC phenotypic switching and its function in the pathology of abdominal aortic aneurysm (AAA) is lacking. Here we report the effect of  SMC-restricted CCN2 deficiency of hypercholesterolemic mice on gene expression in infrarenal aorta with or without angiotensin II (Ang II)-infusion.

overall_design: CCN2-floxed mice were crossed with Myh11-Cre-ERT2 transgenic mice to generate male CCN2-floxed mice harboring SMC-specific Cre (CCN2fl/fl-Myh11-Cre-ERT2). Smooth muscle cell (SMC)-specific deletion of CCN2 was achieved by intraperitoneal (IP) injection of five consecutive doses of tamoxifen to 8 weeks old male CCN2fl/fl-Myh11-Cre-ERT2 mice. Age-matched male CCN2-floxed mice without Cre expression subjected to the same tamoxifen regimen were used as controls. After two-week washout period, SMC-specific CCN2-knockout mice, henceforth CCN2SMC∆ mice and CCN2-floxed control mice, henceforth CCN2fl/fl mice were used for the modeling of AAA (Ang II infusion via mini-osmotic pumps at the dose of 500 ng/kg/min for 7 days)

first: Yu

last: Wang

first: Xuesong

last: Liu

first: Wei

first: Xianming

last: Zhou

first: Zhiyong

last: Lin


title: Single-cell RNA Sequencing Reveals Immunosuppressive Myeloid Cell Diversity During Malignant Progression in a murine model of glioma

first: Yang

last: Hu

address: 1305 York Avenue Y-1322

institute: Weill Cornell Medicine

summary: Low grade gliomas (LGG) account for about two-thirds of all glioma diagnoses in adolescents and young adults (AYA) and malignant progression of these patients leads to dismal outcomes. Recent studies have shown the importance of the dynamic tumor microenvironment in high-grade gliomas (HGG), yet its role is still poorly understood in low-grade glioma malignant progression. Here, we investigated the heterogeneity of the immune microenvironment using a platelet-derived growth factor (PDGF)-driven RCAS (replication-competent ASLV long terminal repeat with a splice acceptor) glioma model that recapitulates the malignant progression of low to high-grade glioma in humans and also provides a model system to characterize immune cell trafficking and evolution. To illuminate changes in the immune cell landscape during tumor progression, we performed single-cell RNA sequencing on immune cells isolated from animals bearing no tumor (NT), LGG and HGG, with a particular focus on the myeloid cell compartment, which is known to mediate glioma immunosuppression. LGGs demonstrated significantly increased infiltrating T cells, CD4 T cells, CD8 T cells, B cells, and natural killer cells in the tumor microenvironment, whereas HGGs significantly abrogated this infiltration. Our study identified two distinct macrophage clusters in the tumor microenvironment; one cluster appeared to be bone marrow-derived while another was defined by overexpression of Trem2, a known anti-tumor immunity marker in myeloid cell subpopulations. Our data demonstrates that these two distinct macrophage clusters show an immune-activated phenotype (Stat1, Tnf, Cxcl9 and Cxcl10) in LGG which evolves to an immunosuppressive state (Lgals3, Apoc1 and Id2) in HGG that restricts T cell recruitment and activation. We identified CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Interestingly, these results were mirrored by our analysis of the TCGA dataset, which demonstrated a statistically significant association between CD74 overexpression and decreased overall survival in AYA patients with grade II LGGs.   Targeting immunosuppressive myeloid cells and intra-tumoral macrophages within this therapeutic window may ameliorate mechanisms associated with immunosuppression before and during malignant progression.

overall_design: Immune cells isolated from animals bearing no tumor (NT), LGG and HGG, from the brain’s right hemisphere, with a particular focus on the myeloid cell compartment, which is known to mediate glioma immunosuppression

first: Sakthi

last: Rajendran

first: Alessandro

last: Canella

first: Clayton

last: Peterson

first: Amy

last: Gross

first: Maren

last: Cam

first: Matthew

last: Nazzaro

first: Abigail

last: Haffey

first: Akdes

last: Serin-Harmanci

first: Rosario

last: Distefano

first: Giovanni

last: Nigita

first: Wesley

first: Daniel

last: Kreatsoulas

first: Zihai

last: Li

first: Jesse

middle: A

last: Sepeda

first: Andrew

last: Sas

first: Mark

middle: E

last: Hester

first: Katherine

last: Miller

first: Olivier

last: Elemento

first: Ryan

middle: D

last: Roberts

first: Eric

middle: C

last: Holland

first: Ganesh

last: Rao

first: Elaine

middle: R

last: Mardis

first: Prajwal

last: Rajappa


title: Changes in carbohydrate metabolism in alveolar epithelial type II cells in Ub-Cre and Hif1a loxp/loxp Ub cre mice in respnse to injurious mechanical ventilation (IMV)

city: Aurora

first: Christine

last: Vohwinkel

state: COLORADO

institute: University of Colorado

summary:
IMV induces transcription of key glycolytic enzymes in alveolar epithelial type II mice
IMV induced transcription of key glycolytic enzymes is HIF1A dependent

overall_design: Mice  were subjected to IMV (peak inspiratory pressure 45, PEEP 3, RR 80, FiO2 100%) or control ventilation  (peak inspiratory pressure 12, PEEP 3, RR 80, FiO2 100%) , duration of mechanical ventilation 4 hours. After that alveolar type II epithelial cells were isolated form lungs


title: MicroRNAs in adipocyte-derived extracellular vesicles in maternal and cord blood are related to neonatal adiposity

city: Pune

first: Chittaranjan

middle: Sakerlal

last: Yajnik

state: Maharashtra

address: Sardar Moodliar Road, Rasta Peth

department: Diabetes Unit

country: India

institute: King Edward Memorial Hospital Research Centre, Pune

summary:
Maternal body size, nutrition, and hyperglycemia contribute to neonatal body size and composition. There is little information on maternal-fetal transmission of messages which influence fetal growth. We analyzed adipocyte-derived small extracellular vesicular (ADsEV) microRNAs in maternal and cord blood to explore their adipogenic potential.
Differential expression (DE) of ADsEV miRNAs in adipose vs. lean neonates was studied before and after adjustment for maternal gestational diabetes mellitus (GDM), adiposity, and vitamin B12-folate status.

overall_design: Adipocyte derived extracellular vescicular microRNAs were profiled from maternal plasma and cord blood samples of their neonates (N=127 pairs)

first: Pooja

last: Kunte

first: Matthew

last: Barberio

first: Pradeep

last: Tiwari

first: Krishna

last: Sukla

first: Brennan

last: Harmon

first: Samuel

last: Epstein

first: Dattatray

last: Bhat

first: Kayla

last: Authelet

first: Madeleine

last: Goldberg

first: Sudha

first: Hemant

last: Damle

first: Robert

middle: J

last: Freishtat


title: Pre-clinical evaluation of the hypomethylating agent decitabine for the treatment of T-cell acute lymphoblastic lymphoma

city: Gent

first: Lien

last: Provez

address: Corneel Heymanslaan 10 - MRB2

department: Biomolecular Medicine

country: Belgium

institute: Ghent University

summary: T-cell acute lymphoblastic lymphoma (T-LBL) is a rare and aggressive blood cancer, most often diagnosed in teenagers and young adults. Patients are usually treated with intensive chemotherapy which causes many side effects and relapse still occurs. Therefore, the search toward less toxic anti-leukemic therapies is ongoing. In line with this, we here focused on targeting a recently described perturbed DNA methylation profile in T-LBL. This aberrantly methylated DNA can serve as a new therapeutic target for DNA hypomethylating epidrugs like decitabine. We evaluated the anti-leukemic properties and downstream effects of decitabine using T-LBL patient derived xenograft (PDX) models. Interestingly, decitabine treatment resulted in prolonged leukemia-free survival in all T-LBL PDX models, which was mediated by i.a. downregulation of the oncogenic MYC pathway. However, some PDX models had more benefit of being treated with decitabine compared to others. Remarkably, differentially methylated CpG islands regions resulted in significantly more differentially expressed genes in open chromatin in the more sensitive group. This resulted in i.a. stronger downregulation of cell cycle genes and upregulation of immune response activating genes. Furthermore, we suggested a gene signature for high decitabine sensitivity. In conclusion, we delivered pre-clinical data of the potential of decitabine to act as a new therapeutic agent in T-LBL.

overall_design: Gene expression profiling analysis of RNA-seq data for 5 T-LBL PDX models treated with decitabine or vehicle (at least 3 replicates/condition).

first: Tom

last: Putteman

first: Mattias

last: Hofman

first: Sofie

last: Degerman

first: Renate

last: De Smedt

first: Pieter

last: Van Vlierberghe


title: Next Generation Sequencing Facilitates Analysis of Propafenone Treatment and Control Sample Transcriptomes

city: Shanghai

first: Jinlian

last: Wei

state: Shanghai

address: Meilong Road 130

country: China

institute: EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY

summary: Conjunctival melanoma (CM), a rare and fatal malignant ocular tumor, lacks proper diagnostic biomarkers and therapy. Herein, we revealed the novel application of Propafenone, an FDA-approved antiarrhythmic medication, which was found effective in inhibiting CM cells growth and homologous recombination pathway.

overall_design: Examination of  Propafenone  treatment and control samples in CM-AS16 cells by RNA-seq, in triplicate.

first: Yongyun

last: Li

first: Jian

first: Renbing

last: Jia


title: Electroacupuncture Alleviates Perioperative Hypothalamus-Pituitary-Adrenal Axis Dysfunction via CircRNA-miRNA-mRNA Networks [circRNA]

first: Wei

last: Hu

address: Dongan Road 130

institute: Fudan university

type: Non-coding RNA profiling by high throughput sequencing

summary: Electroacupuncture (EA) has long been used to treat surgery-induced hypothalamic-pituitary-adrenal (HPA) axis dysfunction. However, its target gene expression profiles in the brain remain unclear. Thus, the aim of the present study was to clarify the potential targets of EA based on RNA sequencing techniques (RNA-seq). Rats were randomly divided into normal control, hepatectomy surgery (HT), HT+EA, and HT+sham EA groups followed by RNA-seq of two representative nuclei in the hypothalamus and amygdala.

overall_design: mRNA, miRNA, circRNA profiling analysis of mouse hypothalamus and amygdala with modeling of normal control, hepatectomy surgery (HT), HT+EA, and HT+sham EA

first: Tao

last: Xu

first: Ning

last: Jiang

first: Mingquan

last: Chen


title: Electroacupuncture Alleviates Perioperative Hypothalamus-Pituitary-Adrenal Axis Dysfunction via CircRNA-miRNA-mRNA Networks [mRNA]


title: LncRNA expression profile and their possible regulatory role in the HSOS induced by monocrotaline in rats

city: Nanjing

first: Lixin

last: Sun

address: 24 Tong Jia Xiang

institute: China Pharmaceutical University

summary: Aims: Long noncoding RNA (lncRNAs) contribute in regulating vital physiological processes and pathogenesis of many diseases. Monocrotaline can cause large-scale outbreaks of toxic liver disease in humans and animals as hepatic sinusoidal obstruction syndrome (HSOS). This research aimed to study the lncRNA-mRNA regulation network in MCT-induced HSOS in rats.  Main methods: We established MCT-induced HSOS, and then carried out microarray to liver tissues of SD rat of an early HSOS model (MCT-12h treated and control groups) to investigate the differentially expressed lncRNAs and mRNAs in the early hepatotoxicity, followed by RT-PCR for selected lncRNAs, which were markedly changed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome analysis were also conducted Key findings. According to analysis, LncRNAs might play an essential role in the hepatotoxicity mechanism.  Significance: This study provides a basis for further researches on the molecular mechanisms, and treatment of MCT-induced hepatotoxicity, especially in the early stage, which is pivotal to treat it successfully before irreversible liver damage occur.

overall_design: Microarray analysis was performed on colonic tissues from the Control and MCT (160mg/kg MCT, i.g.) groups (n=3)

first: Mohammed

last: Ismail

first: Xi

last: Zhang


title: Electroacupuncture Alleviates Perioperative Hypothalamus-Pituitary-Adrenal Axis Dysfunction via CircRNA-miRNA-mRNA Networks [miRNA]


title: Electroacupuncture Alleviates Perioperative Hypothalamus-Pituitary-Adrenal Axis Dysfunction via CircRNA-miRNA-mRNA Networks


title: SigB modulates expression of novel SigB regulon members via Bc1009 in non-stressed and heat-stressed cells revealing its alternative roles in Bacillus cereus

city: Wageningen

first: Jeroen

middle: Steven

last: Koomen

address: Bornse Weilanden 9

country: Netherlands

institute: Wageningen University

summary: Background: The Bacillus cereus Sigma B (SigB) dependent general stress response is activated via the two-component RsbKY system, which involves a phosphate transfer from RsbK to RsbY. It has been hypothesized that the Hpr-like phosphocarrier protein (Bc1009) encoded by bc1009 in the SigB gene cluster may play a role in this transfer, thereby acting as a regulator of SigB activation. Alternatively, Bc1009 may be involved in the activation of a subset of SigB regulon members. Results: We first investigated the potential role of bc1009 to act as a SigB regulator but ruled out this possibility as the deletion of bc1009 did not affect the expression of sigB and other SigB gene cluster members. The SigB-dependent functions of Bc1009 were further examined in B. cereus ATCC14579 via comparative proteome profiling  (backed up by transcriptomics) of wt, Δbc1009 and ΔsigB deletion mutants under heat stress at 42°C. This revealed 284 proteins displaying SigB-dependent alterations in protein expression levels in heat-stressed cells, including a subgroup of 138 proteins for which alterations were also Bc1009-dependent. Next to proteins with roles in stress defense, newly identified SigB and Bc1009-dependent proteins have roles in cell motility, signal transduction, transcription, cell wall biogenesis, and amino acid transport and metabolism. Analysis of lethal stress survival at 50°C after pre-adaptation at 42°C showed intermediate survival efficacy of Δbc1009 cells, highest survival of wt, and lowest survival of ΔsigB cells, respectively. Additional comparative proteome analysis of non-stressed wt and mutant cells at 30°C revealed 96 proteins with SigB and Bc1009-dependent differences in levels, 51 were also identified under heat stress, and 45 showed significant differential expression at 30°C, including proteins with roles in carbohydrate/ion transport and metabolism. Overlapping functions at 30°C and 42°C included proteins involved in motility, and ΔsigB and Δbc1009 cells showed reduced motility compared to wt cells in swimming assays at both temperatures. Conclusion: our results extend the B. cereus SigB regulon to >300 members,  with a novel role of SigB-dependent Bc1009 in the activation of a subregulon of >180 members, conceivably via phosphotransfer-based interactions with other transcriptional regulatory networks.

overall_design: Seven comparisons were performed: WT over ΔsigB at 30°C and 42°C, WT over Δbc1009 at 30°C and 42°C, WT 30°C over WT 42°C,  ΔsigB 30°C over ΔsigB 42°C, Δbc1009 30°C over Δbc1009 42°C (all biological duplicate, and Cy5-Cy3 dye-swapped). Strains were grown in BHI at 30 degrees C until an OD600nm ~0.4 followed by exposure in the same media at 30 degrees C or 42 degrees C, while shaken at 160 rpm, and harvested after 20 minutes.

first: Kah

middle: Y

last: Yeak

first: Marcel

middle: H

last: Tempelaars

first: Jia

middle: L

last: Wu

first: Wouter

last: Westerveld

first: Alexander

last: Reder

first: Stephan

last: Michalik

first: Vishnu

middle: M

last: Dhople

first: Uwe

last: Völker

first: Jan

last: Pané-Farré

first: Marjon

last: Wells-Bennik

first: Tjakko

last: Abee


title: ESRG, a novel target of OCT4, maintains self-renewal and pluripotency of human pluripotent stem cells in collaboration with MCM2

city: Wenzhou

first: dandan

last: Fan

address: 270 Xueyuan West Road

institute: Wenzhou Medical University

summary: Long non-coding RNA ESRG was first identified in our previous study, but its physiological function, regulatory and action mechanisms in human pluripotent stem cells (hPSCs) remain largely unexplored. Here, we found that ESRG is specifically and highly expressed in hPSCs, and its transcription is directly regulated by OCT4, suggesting that ESRG may be an integral component of the core regulatory circuit regulating the pluripotent state of hPSCs. Knockdown of ESRG induces hPSC differentiation, cell cycle arrest, and apoptosis. Mechanistically, ESRG binds to minichromosome maintenance protein 2 (MCM2), a replication-licensing factor, to sustain its steady-state level and nuclear translocation, safeguarding error-free DNA replication. Further study showed that inhibition of the interaction bewteen ESRG and MCM2 results in DNA damage and activation of p53 signaling pathway, ultimately deregulates deregulates pluripotency and self-renewal of hPSCs. In sum, our observations suggest that ESRG, as a novel target of OCT4, plays an essential role in maintaining the pluripotency and self-renewal of hPSCs in collaboration with MCM2 to suppress p53 signaling. These findings provide critical insights into the mechanisms underlying the maintenance of self-renewal and pluripotency in hPSCs.

overall_design: Gene Expression Profiling of human embryonic stem cells (H9) treated by siControl and siESRG for 48h were characterized using Illumina Human HT-12 v4 array.

first: Shasha

last: Li

first: Hui

last: Liu

first: Hecheng

last: Zhu

first: Ming

last: Zhao

first: Longlong

last: Luo

first: Weidong

first: Lei

last: Wang

first: Bin

first: Wen

last: Xie

first: Cong

first: Yao

last: Zhou

first: Xingjun

last: Jiang

first: Caiping

last: Ren


title: TFEB and TFE3 are required for efficient cellular response against beta-coronavirus [RNA-seq]

city: Bethesda

first: Pablo

last: Tapia

state: Maryland

address: 50 South Dr

department: Cell Biology and Physiology Center, National Heart, Lung, and Blood

institute: National Institutes of Health

summary: The transcription factors EB and E3 (TFEB and TFE3) promote lysosomal biogenesis and autophagy in response to a variety of stress conditions. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the ß-coronaviruses family. Recent studies have shown that ß-coronaviruses use lysosomes to egress the cell. The aim of this work is to analyze if ß-coronavirus infection promotes TFEB/3 activation and to evaluate the contribution of these transcription factors to the cellular response upon viral infection.

overall_design: Analysis of mRNA expression under Mouse Hepatitis Virus (MHV) infection in HeLa-mCC1a cells with siControl or siTFEB/TFE3

last: Contreras

first: Eutteum

last: Jeong

first: Nihal

last: Altan-Bonnet

first: Rosa

last: Puertollano


title: p53 Promotes Peroxisomal Fatty Acid β-oxidation to Repress Purine metabolism and Mediate Tumor Suppression

city: wuhan

first: jianhong

last: zhao

address: 115 Donghu Road, Wuhan, Hubei, China

institute: wuhan university

summary: Several studies suggested that p53 controls multiple metabolic pathways and their contribution to its tumor-suppressive functions. To investigate whether p53 might involve some unexplored metabolic pathways, Trp53fl/fl mice were crossed with Pvillin-Cre mice to generate Pvillin-Cre + Trp53fl/fl (VP) mice, and colorectal tumor model was induced by AOM/DSS. We analyzed the CRC tumor tissues from Trp53fl/fl and VP mice by RNA-seq.

overall_design: Trp53fl/fl mice were crossed with Pvillin-Cre mice to generate Pvillin-Cre + Trp53fl/fl (VP) mice, and colorectal tumor model was induced by AOM/DSS. And RNA-seq was sequenced at Majorbio (Shanghai,China) on the Illumina novaseq6000 platform.

first: Jianhong

first: Youjun


title: TFEB and TFE3 are required for efficient cellular response against beta-coronavirus [ChIP-Seq]

overall_design: Analysis of TFE3 binding to promoter of genes under Mouse Hepatitis Virus (MHV) infection in HeLa-mCC1a cells


title: TFEB and TFE3 are required for efficient cellular response against beta-coronavirus


title: single-cell RNA sequencing reveals the lymph node atlas of breast cancer metastases

first: kun

last: xu

address: 300 Guangzhou Road

institute: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University

summary: To obtain more information about the lymph node metastasis of breast cancer cells, we selected the  positive lymph nodes (PL) of the two patients to perform integrated analysis. The two PL samples were analysed with single-cell RNA sequencing.

overall_design: The positive lymph nodes (PL) were analysed with single-cell RNA sequencing.

first: Kun

last: Xu


title: Analysis of Cellular Resistance to Clostridioides difficile TcdB2 Reveals Regulators of Chondroitin Sulfate Proteoglycan 4

city: Oklahoma City

first: Jason

last: Larabee

state: OK

address: 940 Stanton L. Young Blvd. BMSB 1062

institute: OUHSC

summary: RNA-seq data comparing parental HeLa cells to TcdB2-resistant HeLa cells  (termed HeLa R5).  The transcript signatures were used to determine differences between these cell lines in order to determine mechanisms of TcdB2 resistance and CSPG4 expression.

overall_design: Two biological replicates for the TcdB2-resistant HeLa cells.

first: Jimmy

last: Ballard


title: RNA-Seq of young and senescent cells with empty vector, TRF2 overexpression or LMNB1 downregulation

city: Nice

first: Melanie

last: Pousse

address: Faculty of Medicine - Pasteur tower - 28, av. Valombrose

department: Bioinformatics

country: France

institute: IRCAN

summary: Telomeres, the nucleoprotein structures located at the end of eukaryotic DNA, protect chromosomal integrity. These structures undergo changes during development and aging, including length shortening and alterations in the levels of the proteins associated to them called shelterin, all this affecting genome stability as the cells age. However, telomeres also behave as transcriptional regulators acting not only on genes present at subtelomeres but also on more distantly located genes presented throughout the genome. This process is referred as Telomere Position Effect (TPE). Here we set to determine whether telomere shortening in senescent cells impact TPE and senescent cells transcriptome. We also investigate whether TRF2 (a shelterin protein) and Lamin B1 (a member of nuclear lamina) are involved in TPE by doing RNA sequencing of young and senescent cells in which we modulated TRF2 and Lamin B1 expression.

overall_design: RNA-Seq performed on triplicates on young and senescent MRC-5 cells with empty or TRF2 expressing lentivirus and with siRNA control or siRNA Lamin B1.

first: Martin

last: Rey-Millet

first: Aaron

last: Mendez-Bermudez

first: Eric

last: Gilson


city: Paris

first: Pierre

last: de la Grange

address: 29, rue du Faubourg Saint-Jacques

department: Paris Biotech Santé

institute: GenoSplice technology

summary: Human serum albumin (HSA) is an emerging treatment for preventing excessive systemic inflammation and organ failure(s) in patients with acutely decompensated (AD) cirrhosis. Here, we investigated the molecular mechanisms underlying the immunomodulatory properties of HSA. Administration of HSA to patients with AD cirrhosis with elevated circulating bacterial DNA (CpG-DNA) was associated with reduced plasma cytokine levels. In isolated leukocytes, HSA abolished CpG-DNA-induced cytokine expression and release independently of its oncotic and scavenging properties. Similar anti-inflammatory effects were observed with recombinant human albumin. HSA exerted widespread changes on the immune cell transcriptome, specifically in genes related to the endosomal compartment involved in cytosolic DNA sensing and type I interferon responses. Flow cytometry and confocal microscopy analyses revealed that HSA was taken up by leukocytes and internalized in vesicles positively stained with EEA1, a marker of early endosomes. Indeed, HSA and CpG-DNA colocalized in endosomes, the compartment where CpG-DNA binds to TLR9, its cognate receptor. Furthermore, HSA also inhibited poly-(I:C)- and LPS-induced IRF3 phosphorylation and TRIF-mediated responses, which are exclusive of endosomal TLR3 and TLR4 signaling, respectively. The immunomodulatory actions of HSA did not compromise leukocyte defensive mechanisms such as phagocytosis, efferocytosis and intracellular ROS production. The in vitro immunomodulatory effects of HSA were confirmed in vivo in analbuminemic humanized FcRn transgenic mice. In conclusion, these findings indicate that HSA internalizes in immune cells and modulates their responses through interaction with endosomal TLR signaling, thus providing a mechanism for the benefits of HSA infusions in patients with cirrhosis.

overall_design:
Microarray of PBMC from patients with decompensated cirrhosis (AD) and ACLF stimulated with CpG-DNA and treated with human serum albumin (HSA).
PBMC were isolated from 20 ml of EDTA blood using a ficoll-Hypaque density gradient separation method. PBMC were seeded at a density of 1.0x10e6 cells/mL and incubated with HSA (15 mg/ml) for 24 h in the presence of CpG-DNA (4 µM) or vehicle for the last 4 hours. Cells were collected and RNA was isolated using TRIzol reagent and quantified with nanodrop. RNA integrity was re-checked in the Bioanalyzer 2100 before performing microarray hybridization. The average RIN value of total RNAs was 9.05 (from 8 to 9.5 range). Processing of RNA samples, fragmentation and labelling of single-stranded-cDNA were prepared according to Affymetrix WT PLUS Reagent Kit user guide in an automated system (Beckman FX robot). Following fragmentation and terminal labeling, single-stranded-cDNAs were hybridized for 17 hours at 45ºC on the GeneChip Human gene 2.1ST 24 - array plates, using the automated GeneTitan System, which includes the hybridization oven, the fluidic station and the scanner.

first: Mireia

last: Casulleras

first: Roger

last: Flores-Costa

first: Marta

last: Duran-Güell

first: José

last: Alcaraz-Quiles

first: Silvia

last: Sanz

first: Esther

last: Titos

first: Cristina

last: López-Vicario

first: Javier

last: Fernández

first: Raquel

last: Horrillo

first: Montserrat

last: Costa

first: Richard

last: Moreau

first: Vicente

last: Arroyo

first: Joan

last: Clària


title: Aberrant JAK-STAT pathway confers resistance to the HDAC inhibitor chidamide in Natural Killer/T-cell lymphoma through chromatin remodeling

city: Guangzhou

first: jinghong

last: Chen

address: Panyu

institute: SYSUCC

summary: Natural Killer/T-cell lymphoma (NKTL) is a rare type of aggressive and heterogeneous non-Hodgkin's lymphoma (NHL) with poor prognosis and limited therapeutic options. Here, we demonstrate that chidamide, a novel histone deacetylase (HDAC) inhibitor, is effective in treating relapsed/refractory NKTL patients, achieving an overall response rate of 39.3%, with 17.9% complete response rate. However, the clinical response to chidamide remains variable as more than half of the patients exhibit primary resistance, limiting its utility in NKTL treatment. To unravel the resistance mechanisms of chidamide, we performed integrative transcriptomic and chromatin profiling of sensitive and resistant NKTL cells. Our results revealed that aberrant JAK-STAT signaling remodels the chromatin and confers resistance to chidamide. Subsequently, inhibition of JAK-STAT activity could overcome resistance to chidamide by reprogramming the chromatin from a resistant to sensitive state, leading to synergistic anti-tumor effect. More importantly, our clinical data demonstrated that combinatorial therapy with chidamide and JAK inhibitor ruxolitinib is effective against chidamide-resistant NKTL. In addition, we identified TNFRSF8 (CD30), a downstream target of JAK-STAT pathway, as a potential biomarker that could predict NKTL sensitivity to chidamide. Collectively, our study suggests that chidamide, in combination with JAK-STAT inhibitors, can be a novel targeted therapy in the standard of care for NKTL.

overall_design: 1. Chromatin immunoprecipitation sequencing (ChIP-Seq) for H3K27ac and H3K4me3  was performed in two resistant cell lines (HANK1 and SNK6) and two sensitive cell lines (KHYG1 and MEC04) to chidamide. 2. RNA-seq was performed in three resistant cell lines (SNT8, SNK6 and HANK1) and three sensitive cell lines (KHYG1, MEC04 and NK92)  to chidamide. 3.RNA-seq for HANK1 treated with DMSO, tofacitinib or ruxolitinib was performed (duplicate).

first: Jinghong

first: Zhixiang

last: Zuo

first: Yan

last: Gao

first: Huiqiang

last: Huang

first: Choon

middle: K

last: Ong

first: Jing

last: Tan


title: TiO2 nanoparticles' library toxicity (UV and non-UV exposure) – High-throughput in vivo transcriptomics reveals mechanisms

city: Aveiro

first: Susana

middle: Isabel Lopes

last: Gomes

address: Campus Universitário de Santiago, Departement of Biology, University of Aveiro

department: Biology

country: Portugal

institute: CESAM & University of Aveiro

summary: Ecotoxicological studies with NPs are nearly all focused on testing one or few NPs. A more systematic approach to compare effects across many NMs with identified different but related characters/descriptors (e.g. different aspect-ratios or surface activities) are only sparsely reported especially in ecotoxicology. There is an urgent need to provide tools that allow us to fast develop an (eco)toxicological dataset containing comprehensive toxicity information relating to a diverse spectra of NPs characters, thus allowing the extrapolation of acquired information across NMs. NM libraries are an excellent tool for alternative testing and modeling. In the present study a custom-designed Fe doped TiO2 NM library was used covering of a wide spectrum of properties. Enchytraeus crypticus (Oligochateta) was used as test species since it is both environmentally relevant (as an important soil representative oligochaete and is also a standard species in soil ecotoxicology studies) and also a genomic model, with a high-throughput (HTP) genomic library. Effects were assessed at the organism (survival, reproduction) and gene level (differential gene expression, microarray).

overall_design: Gene expression profile of Enchytraeus crypticus was analysed after 5 days of exposure to: i) TiO2 NMs under standard lab illumination (No-UV) and ii) TiO2 NMs + UV radiation. To maximise exposure, the test media was reconstituted water (ISO 1). The treatments selected (concentration/NM) were based on previous known effects on reproduction (3 weeks) after transference to clean LUFA 2.2 soil; and the treatments were selected to cover a wide range of NM characteristics and different effects. Three biological replicates per test treatment and controls (standard laboratory light or UV) were used.

middle: I

first: Carlos

middle: P

last: Roca

first: Janeck

last: Scott-Fordsmand

first: Mónica

last: Amorim


title: Gene Expression Profiles Associated with Radio-Responsiveness in Locally Advanced Rectal Cancer

status: Public on Mar 01 2023

city: Seoul

first: Kwang Seok

last: Kim

address: 75 Nowon-gil, Nowon-gu

department: Division of Fusion Radiology Research

country: South Korea

institute: Korea Institute of Radiological and Medical Sciences

summary: locally advanced rectal cancer (LARC) patients were sorted according to their radio-responsiveness. Patients were categorized into two groups—complete response (n = 3) and poor response (n = 3)—based on the tumor regression grade. Expression profiles for each group were obtained using RNA-seq on a HiSeq 4000 system (Illumina).

overall_design: Colon cancer patients have different responses during radiotherapy. It results from different genetic backgrounds between individuals. Therefore, total RNA was obtained from the six patient-derived organoids and analyzed through RNA sequencing.

first: Eunju

last: kim

first: UiSup

last: Shin

first: Kwang

last: S Kim

first: Jiyong

last: Lee


title: Genome activity during the emergence of mouse embryonic totipotency

city: Regensburg

first: Xin

last: Lu

address: Universitätsstraße 31

country: Germany

institute: University of Regensburg

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

overall_design: Refer to individual Series


title: Genome activity during the emergence of mouse embryonic totipotency (time course)

summary: Fertilization transforms sperm and egg into a totipotent embryo but the underlying mechanisms are unknown. We here report that gene expression initiates during the gamete-to-embryo transition in mouse embryos. Meiotic exit induced by sperm entry enhances a transcriptionally-permissive epigenetic landscape. Time-course analysis of single embryos revealed a succession of genome-wide transcription 'ripples' initiating within 2 hours. Disrupting key pluripotency transcription factor levels prior to sperm entry had little immediate effect, indicating that different mechanisms engender pluripotent and totipotent states. These findings suggest that a hierarchical gene expression program characterizes the emergence of totipotency during the gamete-to-embryo transition, with broad mechanistic implications for the reprogramming of cellular potency.

overall_design: 2h interval time course after ICSI produced mouse single embryo: Biological replicates: 3 replicates at 0h, 3 replicates at 2h, 4 replicates at 4h, 3 replicates at 6h, 3 replicates at 8h, 4 replicates at 10h, 4 replicates at 12h

first: A

last: Perry


title: Effects of the absence of ACLY or Pdca1 on the transcriptome of T cells activation

city: Utrecht

first: Enric

last: Mocholi Gimeno

state: Utrecht

address: Heidelberglaan 100

department: CMM

institute: UMC Utrecht

summary: T cell activation is known to require a metabolic shift towards glycolysis, triggered by TCR-engagement . To evaluate the role of ACLY or PDH in transcriptional reprogramming. T cell-specific Pdha1 knockout mouse by crossing Pdha1fl/fl mouse with CD4CreERT2 and CD4+ T cells from conditional knockout mice with T cell-specific ablation of Acly (CD4-Cre Aclyfl/fl).

overall_design: mice  CD4+ deficients of ACLY or Pdha1cells were activated with CD3/CD28 during 24h


title: ATAC-seq in wild-type and XAF1 knockout HT29 cells after vesicular stomatitis virus infection

city: Beijing

first: Ming

last: Kuang

address: Xueyuan Road 38 #, Haidian District

institute: Peking University

summary:
To investigate the function of XAF1 in chromatin openning. Wild-type or XAF1 knockout HT29 cells were infected with  VSV  for 0 or 3 hours,ATAC-seq was performed.
Examination of chromatin openness in Wild-type or XAF1 knockout HT29 cells.

overall_design: Chromatin openness analysis of ATAC-seq data for  WT or XAF1 knockout HT29 cells that were infected by VSV for 0 or 6 hours.


title: Genome activity during the emergence of mouse embryonic totipotency (morpholino)

overall_design: Two-condition experiment in each Morpholino and cRNA mII injected mouse embryos, Morpholino control vs. Morpholino Oct4A and mcherry cRNA vs Oct4A-mcherry cRNA.  Biological replicates: 8 control replicates, 12 Morpholino Oct4A replicates, 12 control cRNA replicates, 11 Oct4A-mcherry cRNA replicates.


title: A Multi-omic and Multi-Species Analysis of Right Ventricular Failure

city: Minneapolis

first: Lauren

last: Mills

state: MN

address: 420 Delaware St SE

department: Department of Pediatrics

institute: University of Minnesota

summary: Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no approved RV-targeted treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Here, we used transcriptomics and proteomics analyses to define the molecular pathways associated with cardiac MRI-derived values of RV hypertrophy, dilation, and dysfunction in pulmonary artery banded (PAB) piglets. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare the three species. Transcriptomic and proteomic analyses identified changes in multiple metabolic pathways in the RV of PAB pigs, and pathway alterations that were conserved between species. However, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across species. FAO and ETC proteins and transcripts were mostly downregulated in rats, but were predominately upregulated in PAB pigs. When compared to humans, the pig PAB molecular signature was more similar to patients with RVF than rodents. These data suggest there are divergent molecular responses of RVF across species, and pigs more accurately recapitulate the metabolic molecular signature of human RVF.

overall_design: RNA from bulk RV free wall tissue from control pigs and pulmonary artery banded pigs

first: Jenna

middle: B

last: Mendelson

first: Jacob

last: Sternbach

first: Michelle

last: Doyle

first: Lynn

last: Hartweck

first: Walt

last: Tollison

first: John

last: Carney

first: Matthew

middle: T

last: Lahti

first: Richard

middle: W

last: Bianco

first: Rajat

last: Kalra

first: Felipe

last: Kazmirczak

first: Charles

last: Hindmarch

first: Stephen

last: Archer

first: Kurt

last: Prins

first: Cindy

last: Martin


title: Long noncoding RNA microarray profile in the plasma of mild cognitive impairment due to Alzheimer's disease

city: shanghai

first: wei

last: zhang

address: 600 South Wan Ping Road

department: Geriatric Psychiatry

institute: Shanghai Mental Health Center

summary: To explore the lncRNAs associated with pathology of early Alzheimer's disease, we detected the lncRNA profiles in the plasma of subjects with mild cognitive impairment due to Alzheimer's disease and gender-, age-, education-matched normal control elderly.

overall_design: We recruited five mild cognitive impairment due to Alzheimer's disease subjects and five gender-, age-, education-matched normal aging elderly. Blood samples of all participants were collected after fasting for 12 hours. Then plasma was saperated, and the RNA was extracted for the microRNA microarray analysis.

first: Wei

last: Zhang

first: Tao

last: Wang


title: Effect of sub-MIC tobramycin treatment on E. coli MG1655 WT and NCM3416

first: Zeynep

last: Baharoglu

address: 28 Rue du Docteur Roux

department: Génomes et Génétique

institute: Institut Pasteur

summary: Effect of sub-MIC tobramycin treatment on E. coli MG1655 WT (strain classically used as WT strain) and NCM3416 (corrected rph strain). Comparison of genes expression without treatment (MH) in E. coli MG1655 WT and NCM3416.

sample_organism: Escherichia coli str. K-12 substr. MG1655

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

first: Manon

last: Lang

first: Elodie

last: Turc

first: Laure

last: Lemée

first: Thomas

last: Cokelaer


title: Transcriptome analysis of the CBX3-depleted 143B osteosarcoma cell line.

city: Shaoxing, China

first: Di

last: Qiao

address: Shaoxing , Zhejiang, China.

institute: School of Medicine, Shaoxing University

summary: To investigate the role of CBX3 in the progression of osteosarcoma, we performed a transcriptome analysis of the CBX3-depleted 143B cell line and a matched normal 143B cell line.Differential gene enrichment revealed activation of the anti-DNA damage pathway and activation of the apoptotic and P53 pathways.

overall_design: The mRNA profiles of 143B osteosarcoma cells without targeting gene small interfering RNA and targeting CBX3 small molecule interfering RNA were generated by deep sequencing using a Novaseq 6000 sequencer (Illumina).


title: Gene expression profiling of the duodenum and ileum of mice lacking enteroendocrine cells and fed a high fat diet

city: Illkirch

first: Gérard

last: Gradwohl

address: 1 rue Laurent Fries

institute: IGBMC

summary: Background and aims: Enteroendocrine cells (EECs) and their hormones are essential regulators of whole-body energy homeostasis. EECs sense luminal nutrients and microbial metabolites and subsequently secrete a variety of hormones acting locally or at distance. Impaired development of EECs during embryogenesis is life-threatening in newborn mice and humans due to compromised nutrient absorption. However, the physiological importance of the EEC system in adult mice has not been directedly studied. Herein, we aimed to determine the long-term consequences of a total loss of EECs in healthy adults on energy metabolism, intestinal transcriptome and microbiota.   Methods: We depleted intestinal EECs by tamoxifen treatment of adult Neurog3fl/fl; Villin-CreERT2 male mice. We studied intestinal cell differentiation, food efficiency, lipid absorption, microbiota composition, fecal metabolites and transcriptomic responses in the proximal and distal small intestine of mice lacking EECs. We also determined the high-fat diet induced transcriptomic changes in sorted Neurog3eYFP/+EECs.   Results: Induction of EECs deficiency in adults is not life-threatening unless fed with a high-fat diet. Under a standard chow diet, mice lose 10% of weight due to impaired food efficiency. Blood concentrations of cholesterol, triglycerides, and free fatty acids are reduced and lipid absorption is impaired and delayed to the distal small intestine. Genes controlling lipogenesis, carbohydrate metabolism and neoglucogenesis are upregulated. Microbiota composition is rapidly altered after ECCs depletion and characterized by decreased alpha-diversity. Bacteroides and Lactobacillus were progressively enriched while Lachnospiraceae declined without impacting fecal short chain fatty acid concentrations.   Conclusions: EECs are dispensable for survival in adult male mice under a standard chow diet. The absence of EECs impairs intestinal lipid absorption leading to transcriptomic and metabolic adaptations and remodeling of the gut microbiota.

overall_design: Samples are from duodenum of Neurog3f/f; villin-CreERT2 (n=4) and control Neurog3f/f (n=4) mice and from ileum of  Neurog3f/f; villin-CreERT2 (n=4) and control Neurog3f/f (n=4) mice fed a high fat diet.

first: Florence

last: Blot

first: Adèle

last: de Arcangelis

first: Céline

last: Keime


title: Promoter CpG content regulates DNMT-dependent silencing dynamics

city: Pasadena

first: Yitong

last: Ma

state: CA

address: 1200 E California Blvd

department: Division of Biology and Biological Engineering

institute: Caltech

type: Methylation profiling by high throughput sequencing

summary: Effect of how CpG density on the promoter affects the gene silencing and DNA methylation rate of a promoter

sample_organism:
Escherichia coli
Cricetulus griseus

platform_organism:
Escherichia coli
Cricetulus griseus

overall_design:
We constructed a library of promoter based on the synthetic pEF1s promoter, with varying CpG density. Then we recruited an ectopically expressed DNMT3b to the locus.
The cells are sorted into high, med and low expression at different day after DNMT3b recruitment, and subjected to targeted, methylation specific, enzymatic based sequencing analysis (NEB EM-Seq).

first: Mark

last: Budde

first: Junqin

last: Zhu

first: Michael

last: Elowitz


title: RNA-seq analysis of mouse bone marrow-derived macrophages overexpressing miR-204-3p

first: Sijia

last: Liang

address: 74 Zhongshan 2 Rd

department: Pharmacology

institute: Sun Yat-Sen University

summary: Bone marrow-derived macrophages were transfected with miRNA-204-3p mimics or mimics negative control for 24 hours. RNA-seq was performed to compare miR-204-3p overexpression versus control cells.

overall_design: RNA-seq was performed to compare the mRNA expression level between miR-204-3p mimics- and mimics negative control-treated bone marrow-derived macrophages.

first: Si-Jia


title: The deubiquitinase OTUD4 inhibits the expression of antimicrobial peptides in Paneth cells to support intestinal inflammation and bacterial infection

city: Wuhan City

first: Keying

last: Yu

state: Hubei Province

address: 299 Bayi Road, Wuchang District

institute: Wuhan University, China

summary: The intestinal epithelial barrier plays critical role in the intestinal homeostasis and dysfunction of the epithelial barrier causes microbial invasion that would lead to inflammation in the gut. Antimicrobial peptides (AMPs) are essential components of the epithelial barrier to inhibit bacterial invasion. The regulatory mechanisms of the expression of AMPs are not fully characterized. Here, we report a cell-type-specific role of ovarian tumor family deubiquitinase 4 (OTUD4) in experimental colitis and bacterial infection. OTUD4 is upregulated in the inflamed mucosa of IBD patients and in the colon of mice treated with dextran sulfate sodium salt (DSS). Knockout of OTUD4 in intestinal organoids promotes the expression of AMPs after the stimulation with lipopolysaccharide (LPS), peptidoglycan (PGN), or Salmonella typhimurium (S.t.). In addition, the expression of AMPs was upregulated in intestinal epithelial cells (IECs) after DSS treatment or S.t. infection. Consistently, Vil-Cre;Otud4fl/fl mice and Def-Cre;Otud4fl/fl mice exhibit hyper-resistance to DSS-induced colitis and S.t. infection compared to Otud4fl/fl mice. Mechanistically, Knockout of OTUD4 results in hyper K63-linked ubiquitination of MyD88 and increases the activation of the NF-κB signaling pathway and MAPK signaling pathway to promote the expression of AMPs. These finds collectively highlight an indispensable role of OTUD4 in paneth cells to modulate AMPs production, indicating OTUD4 as a promoter and potential druggable target for gastrointestinal inflammation and bacterial infection.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for small intestinal epithelial cells (IECs) from two groups of Otud4fl/fl (n=2) and Vil-Cre;Otud4fl/fl (n=2) mice that were given 2.5% DSS in drinking water for 2 d

first: Yuyao

last: Guo

first: Bo

last: Zhong

first: Dandan

last: Lin


title: Gene expression profile at single cell level of astrocytes from group housing and single housing mice

city: Houston

first: Yi-Ting

last: Cheng

state: TX

address: 1 Baylor Plaza

institute: Baylor College of Medicine

summary: Astrocytes are heterogenous, so we used single cell RNA sequencing (scRNA-seq) to profiling astrocytes a the singel cell resolution.

overall_design: Hippocampal tissue were dissociated from either group housing or single housing mice and then astrocytes were isolated by FACS sorting based on fluorescence in astrocytes

first: Benjamin

last: Deneen


title: Autoantibody repertoire characterization provides insight into the pathogenesis of dissimilar autoimmune diseases

city: Billerica

first: Andrew

last: Bender

state: MA

address: 45A Middlesex Turnpike

institute: EMD Serono

summary:
To investigate the differences between disease types, RNA was isolated from healthy, SjS and SLE blood samples.
We then performed gene expression profiling analysis using data obtained from RNA-seq.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for SLE, SjS, and healthy control samples

first: Thomas

last: Clarke


title: Transcriptomic and Genetic Analysis of Seed Germination Vigor under Low Temperature in Weedy Rice WR04-6

city: Hangzhou

first: wenjia

last: wang

address: No. 198, Shiqiao Road, Hangzhou, Zhejiang Province

institute: Zhejiang Academy of Agricultural Sciences

summary: Low temperature is one of the major factors affecting rice germination, and low tempera-ture germination (LTG) is an important agronomic trait. Although genetic variation is abundant in rice germplasm resources, the molecular mechanism of LTG remains poorly understood. In this study, we first proved that weedy rice WR04-6 had significantly better low-temperature germination (LTG) ability at 10°C than the cultivated rice Qishanzhan (QSZ). RNA-seq was used to investigate the gene expression of WR04-6 and QSZ at 10, 12 and 14 days of seed germination at 10°C. The results of GO enrichment and KEGG en-richment revealed that the differentially expressed genes between WR04-6 and QSZ were mainly concentrated on the response to starch catabolic processes and the response to ab-scisic acid. This is consistent with the results of α-amylase activity, ABA and GA treat-ment. A recombinant inbred line (RIL) population derived from a cross between WR04-6 and QSZ and its high density SNP genetic map were used to detect quantitative trait loci (QTL) for low temperature germination rates at 10°C for 14 days. The results showed that two new QTLs were located on chromosome 3 and chromosome 12. Combined with the mapped QTLs and RNA-seq differential genes (DEGs), sixteen candidate genes potentially associated with LTG were identified. Validation of expression of the candidates by qRT-PCR were consistent with the RNA-seq data. These results will enable us to under-stand the genetic basis of LTG in weedy rice and provide new genetic resources for gener-ation of rice germplasm with LTG.

overall_design: An RNA-seq analysis was performed to further investigate difference between WR04-6 and QSZ. Low temperature (10°C) germinating seed of WR04-6 and QSZ were collected at 10, 12 and 14 days after imbibition, with three biological replications.

first: Wenjia

last: Wang

first: Ruizhi

last: Huang

first: Gengwei

last: Wu

first: Jian

last: Sun

first: Ying

first: Hua


title: Multi-omics approaches for revealing the epigenetic regulation of histone H3.1 during spermatogonial stem cell differentiation in vitro

city: Nanjing

first: Yan

last: Yuan

address: 101 Longmian Avenue

institute: Nanjing Medical University

summary: Epigenetic regulation, particularly histone post translational modification (PTM), participates in spermatogonial stem cells (SSCs) differentiation. However, prior research is still limited to a single PTM. Herein, we constructed over 100 histone H3.1 targeted modification peptides, in combination with histone H3.1 modification binding protein identification, and RNA-Seq. We identified 7 differentially expressed histone H3.1 modifications. In addition, we selected H3K9me2 and H3S10ph for subsequent biotinylating peptide pull-down experiments, and identified a series of transcription factors, such as, GTF2E2 and SUPT5H, which appear to be crucial for the early SSC differentiation process.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for three stages of SSCs cells differentiated in vitro.

first: Li

last: Liu

first: Mengjie

first: Haojie

last: Li

first: Xiangzheng

last: Zhang

first: Xuejiang

first: Jiahao

last: Sha


title: Gene expression profiling of the duodenum and ileum of mice lacking enteroendocrine cells

first: Gérard

last: Gradwohl

summary: Background and aims: Enteroendocrine cells (EECs) and their hormones are essential regulators of whole-body energy homeostasis. EECs sense luminal nutrients and microbial metabolites and subsequently secrete a variety of hormones acting locally or at distance. Impaired development of EECs during embryogenesis is life-threatening in newborn mice and humans due to compromised nutrient absorption. However, the physiological importance of the EEC system in adult mice has not been directedly studied. Herein, we aimed to determine the long-term consequences of a total loss of EECs in healthy adults on energy metabolism, intestinal transcriptome and microbiota.   Methods: We depleted intestinal EECs by tamoxifen treatment of adult Neurog3fl/fl; Villin-CreERT2 male mice. We studied intestinal cell differentiation, food efficiency, lipid absorption, microbiota composition, fecal metabolites and transcriptomic responses in the proximal and distal small intestine of mice lacking EECs. We also determined the high-fat diet induced transcriptomic changes in sorted Neurog3eYFP/+EECs.   Results: Induction of EECs deficiency in adults is not life-threatening unless fed with a high-fat diet. Under a standard chow diet, mice lose 10% of weight due to impaired food efficiency. Blood concentrations of cholesterol, triglycerides, and free fatty acids are reduced and lipid absorption is impaired and delayed to the distal small intestine. Genes controlling lipogenesis, carbohydrate metabolism and neoglucogenesis are upregulated. Microbiota composition is rapidly altered after ECCs depletion and characterized by decreased -diversity. Bacteroides and Lactobacillus were progressively enriched while Lachnospiraceae declined without impacting fecal short chain fatty acid concentrations.   Conclusions: EECs are dispensable for survival in adult male mice under a standard chow diet. The absence of EECs impairs intestinal lipid absorption leading to transcriptomic and metabolic adaptations and remodeling of the gut microbiota.

overall_design: samples are from duodenum of Neurog3f/f; villin-CreERT2 (n=4) and control Neurog3f/f (n=4) mice and from ileum of  Neurog3f/f; villin-CreERT2 (n=4) and control Neurog3f/f (n=4) mice.

first: Florence

last: Blot

first: Adèle

last: de Arcangelis

first: Céline

last: Keime


title: Whole transcriptome sequencing explored the anti-aging and anti-obesity effect of naringin on high glucose induced Caenorhabditis elegans.

city: Zhengzhou

first: Panpan

address: 郑州市高新区科学大道100号郑州大学

department: College of Public Health

institute: 郑州大学

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

overall_design: Refer to individual Series


title: Whole transcriptome sequencing explored the anti-aging and anti-obesity effect of naringin on high glucose induced Caenorhabditis elegans [microRNA].

address: 郑州市高新区科学大道100号郑州大学

summary:
Purpose: Naringin (Nar) is a dihydroflavonoid compound, which is widely found in Chinese herbal medicine and citrus fruit. As one of the phytochemicals, it acts as a dietary supplement and can delay aging and prevent aging-related disease, such as obesity and diabetes. However, the exact mechanism still partially remained unclear.
Methods: In this study, the high-glucose induced (HGI) Caenorhabditis elegans model was used to evaluate the anti-aging and anti-obesity effects of Nar.
Results: It indicated that the mean lifespan and fast movement span of HGI worms were extended roughly 24% and 11% by Nar treatment, respectively. Oil red O staining revealed the significant reduction of fat accumulation (P<0.05) and the dFP::LGG labeled worms showed the promotion of autophagy. Additionally, the whole transcript sequencing and gene set variation analysis algorithm suggested that Nar improved the lipid biosynthesis and metabolism pathways, as well as the TGF-β, Wnt and longevity signaling pathway. The PPI network was applied to screen out hub genes in the above-mentioned pathways for further analysis. The expression levels of hub genes fat-7 and ech-6 were down-regulated, as well as aak-2, nhr-49, acs-2, hlh-30, lgg-1, unc-51, pha-4, skn-1 and yap-1 were up-regulated. Then, mutant worms and RNA interference were used to study the mechanism. It revealed that suppression of the expression of autophagy related genes including hlh-30, lgg-1, unc-51, pha-4, skn-1 and yap-1 could disable the fat-lowering, lifespan-prolonging, and health-promoting properties of Nar. Finally, a competing endogenous RNAs network was constructed to profoundly understand the beneficial mechanism caused by Nar.
Conclusions: our findings elucidate that Nar plays the important role to alleviate HGI aging and anti-obesity effects by reducing fat accumulation and promoting autophagy.

overall_design: Examination of the change of RNA after naringin treatment in high glucose induced Caenorhabditis elegans.

first: Peisen

last: Guo


title: Whole transcriptome sequencing explored the anti-aging and anti-obesity effect of naringin on high glucose induced Caenorhabditis elegans [RNA-seq]

address: 郑州市高新区科学大道100号郑州大学


title: Microglia-mediated T cell Infiltration Drives Neurodegeneration in Tauopathy

city: St Louis

first: Maxim

last: Artyomov

state: Missouri

address: 425 S Euclid Ave

department: Pathology and Immunology

institute: Washington University in St.Louis

summary: Extracellular amyloid-β (Aβ) deposition as neuritic plaques and intracellular accumulation of hyperphosphorylated, aggregated tau as neurofibrillary tangles (NFT) are two of the characteristic hallmarks in Alzheimer’s disease (AD). The regional progression of brain atrophy in AD highly correlates with tau accumulation but not amyloid deposition  and the mechanisms of tau-mediated neurodegeneration remain elusive. Innate immune responses represent a common pathway for the initiation and progression of some neurodegenerative diseases. To date, little is known about the extent or role of the adaptive immune response in the presence of Aβ or tau pathology. We systematically compared the immunological milieus in the brain of mice with amyloid deposition or tau aggregation and neurodegeneration. We found that mice with tauopathy but not amyloid, developed a unique innate and adaptive immune response and that depletion of microglia or T-cells blocked tau-mediated neurodegeneration. T cells, especially cytotoxic T cells, were markedly increased in areas with tau pathology in mice with tauopathy and in the AD brain. T cell numbers correlated with the extent of neuronal loss, and dynamically transformed their cellular characteristics from activated to exhausted states along with unique TCR clonal expansion. Inhibition of IFN-γ and PD-1signaling both significantly ameliorated brain atrophy. Our results thus reveal a tauopathy and neurodegeneration-related immune hub involving activated microglia and T cell responses, which could serve as therapeutic targets for preventing neurodegeneration in AD and primary tauopathies.

overall_design: Exploration the immunological mileus in the brain drive neurodegenration

first: Xiaoying

last: Chen

first: Ekaterina

last: Aladyeva

first: Maria

last: Firulyova

middle: N

first: Jason

middle: D

last: Ulrich

first: David

last: Holtzman


title: Genomic and epigenomic profiling of GATA2 deficiency reveals aberrant hypermethylation pattern in Bone Marrow and Peripheral Blood

city: Esplugues de Llobregat

first: Maximiliano

last: Distefano

state: Barcelona

address: Passeig de Sant Joan de Déu, 2

department: Department of Hematology and Oncology

country: Spain

institute: Hospital Sant Joan de Deu

type: Methylation profiling by genome tiling array

summary: The majority (72%) of adolescents with myelodysplastic syndrome and monosomy 7 carry an underlying GATA2 deficiency. Nowadays, chemotherapy and allogenic hematopoietic stem cell transplantation (HSCT) are the only cure, pointing out the urgent need to develop reliable predictive tools.    Familial cases carrying the same mutation in the GATA2 gene develop the disease at different age. The trigger of the disease is still unknown. Therefore, it is needed to understand the genetic mechanisms (mutations) and epigenetic mechanism, such as, DNA methylation, a cellular mechanism to control gene expression. Abnormal DNA methylation has been linked to several adverse outcomes, including human diseases.    In this study, we deeply characterized 20 Spanish GATA2 deficient patients; study the presence of secondary mutations, clinical phenotype and DNA methylation. We have found that the most frequent secondary mutations are in STAG2 and ASXL1 genes, detected in 30% and 20% of the patients, respectively, a similar ratio has been described in a bigger cohort, showing that our 20-patient cohort is representative of the GATA2 deficiency scenario.    For the first time, we found a specific hypermethylated signature in GATA2 patients, opening a novel point of view in the GATA2-patient diagnostic and facilitating the risk estimation of themselves. Furthermore, whether the methylation profiling is accurate enough, it will be useful to predict the onset of the disease progression.

overall_design: Bisulphite converted DNA from 28 samples (bone marrow and peripheral blood from gata2 mutant patients and healthy donors) were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

first: Oskar

last: Marin-Bejar

first: Damia

last: Romero-Moya

first: Javier

last: Rodriguez-Ubreva

first: Francesca

last: Lessi

first: Paolo

last: Aretini

first: Alessandro

last: Liquori

first: Julio

last: CastanÌƒo

first: Emilia

last: Kozyra

first: Lili

last: Kotmayer

first: Clara

last: Bueno

first: Jose

last: Cervera

middle: C

last: Rodriguez-Gallego

first: Josep

middle: F

last: Nomdedeu

first: Cristina

last: DiÌaz de Heredia

first: Antonio

last: MartÃnez

first: Felix

last: Cadenas

first: Carolina

last: MartiÌnez-Laperche

first: Nieves

last: Dorado

first: Francisco

last: Marco

first: Felipe

first: Pablo

last: Menendez

last: ValcÃ¡rcel

first: Esteban

last: Ballestar

first: Csaba

last: BÃ¶dÃ¶r

first: Anna

last: Bigas

first: Albert

last: CatalaÌ

first: Marcin

last: Wlodarski

first: Alessandra

last: Giorgetti


title: RNA-seq data of T47D overexpressing prolactin and the control

city: Shang hai

first: Jiawei

last: Zhang

address: 上海交通大学药学院6号楼202

institute: Shanghai Jiao Tong University

summary: The exact role of prolactin on breast cancer still remains unclear. Clues supportive or unsurpportive for prolactin to be cancer driver are confusing. To clarify the role of autocrine prolactin of breast cancer cells on cancer development, we construct T47D cells overexpressing prolactin.

overall_design: Using 2nd PLVX-puro lentivirus system, we construct T47D-PRL cells. After screening, we extract RNA from T47D-PRL and T47D-PLVX and conduct RNA-seq. Each samples have three biological replicates.

first: Jianwei

last: Zhu


title: Maternal Serum tRNA-derived Fragments (tRFs) as Potential Candidates for Diagnosis of Fetal Congenital Heart Disease

city: 南京

first: Enkang

last: Lu

address: 江苏省南京市鼓楼区江东北路368号

institute: Nanjing medicine university

summary: Background: Congenital heart disease (CHD) is one of the most predominant birth defects that cause infant death worldwide. The timely and successful surgical treatment of CHD on newborns after delivery requires accurate detection and reliable diagnosis during pregnancy. However, there are no biomarkers that can serve as an early diagnostic factor for CHD patients. tRNA-derived fragments (tRFs) have been reported to play an important role in the occurrence and progression of numerous diseases, but their roles in CHD remains unknown. Methods: High-throughput sequencing was performed on the peripheral blood of pregnant women with abnormal fetal heart and normal fetal heart, and 728 differentially expressed tRFs/tiRNAs were identified, among which the top 18 tRFs/tiRNAs were selected as predictive biomarkers of CHD. Then, quantitative reverse transcriptase polymerase chain reaction verified the expression of tRFs/tiRNAs in more clinical samples, and the correlation between tRFs/tiRNAs abnormalities and CHD was analyzed. Results: tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2 may be promising biomarkers. Through further bioinformatics analysis, we predicted that TRF-58:744-GLy-GCC-1 could induce CHD by influencing biological metabolic processes. Conclusions: our results provide a theoretical basis for the abnormally expressed tRF-58:74-Gly-GCC-1 in maternal peripheral blood as a new potential biomarker for the accurate diagnosis of CHD during pregnancy.

overall_design: Comparative gene expression profiling analysis of tRFs-seq data for pregnant women whose fetal diagnosis of CHD and pregnant women with normal fetal heart

last: LU

first: Lijun

last: Wu

first: Bin

last: Chen

first: Haitao

last: Gu


title: Differential regulation of primary root growth during water-deficit stress in cotton

city: Columbia

first: Sidharth

last: Sen

address: Agriculture Bldg, University of Missouri

department: The Division of Plant Sciences and Technology

institute: University of Missouri

summary: Cotton seedlings were subjected to water-deficit stress along with control condition for 24 hours or 48 hours and tissues emcompassing the elongation zone of primary roots were analysed for differential accumulated transcripts compared to control.

overall_design: Cotton seedlings were subjected to water deficit for 24 and 48 hours and primary root tips were collected in liquid nitrogen. Total RNA was isolated and mRNA profile were generated by sequencing using Illumina NextSeq 500.

first: Jian

last: Kang

first: Robert

middle: E

last: Sharp

first: Melvin

middle: J

last: Oliver


title: Differential regulation of primary root growth during water-deficit stress

sample_organism:
Gossypium hirsutum
Zea mays

platform_organism:
Gossypium hirsutum
Zea mays


title: Differential regulation of primary root growth during water-deficit stress in maize

summary: Maize seedlings were subjected to water-deficit stress along with control condition for 24 hours or 48 hours and tissues emcompassing the elongation zone of primary roots were analysed for differential accumulated transcripts compared to control.

overall_design: Maize seedlings were subjected to water deficit for 24 and 48 hours and primary root tips were collected in liquid nitrogen. Total RNA was isolated and mRNA profile were generated by sequencing using Illumina NextSeq 500.


title: Analysis of the roles of AP4 and p53 downstream of c-MYC activation in breast cancer cells.

city: Munich

first: Markus

last: Kaller

address: Thalkirchner Strasse 36

department: Institute of Pathology

institute: Ludwig-Maximilians-University Munich

summary: Deregulated expression of the c-MYC oncogene induces unscheduled DNA replication, DNA damage, and activation of the p53 tumor suppressor. The AP4 transcription factor is a direct c-MYC target gene involved in cell proliferation, epithelial-mesenchymal transition, and stemness, as well as suppression of DNA damage and senescence. Here, we analyzed the role of AP4 and p53 downstream of c-MYC activation using a CRISPR/Cas9-approach in MCF-7 cells.

overall_design: Cells were pre-treated with ICI for 72 hours. Ectopic expression of c-MYC was induced with DOX for 48 hours in the presence of ICI. For each genotype, RNAs from three biological replicates (48 DOX treatment and ICI-only treated controls) were obtained.

first: Heiko

last: Hermeking


title: p53 dimers elicit unique tumor suppressive activities through an altered metabolic program [scRNA-seq]

first: Yuan

last: Qi

address: 1400 Pressler St

department: Bioinformatics & Computational Biology

institute: University of Texas M.D. Anderson Cancer Center

summary: Cancer-related alterations of the p53 Tetramerization Domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers. These are also normal p53 states under basal cellular conditions. However, their physiological relevance is not well understood. We have established in vivo models for monomeric and dimeric p53 which model Li-Fraumeni Syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and inhibition of CD8+ T-cell accumulation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.

overall_design: Comparison of cell populations in 4-week old thymus from WT, AD and  p53-null  mice

first: J

last: Gencel-Augusto

first: G

last: Lozano


title: p53 dimers elicit unique tumor suppressive activities through an altered metabolic program [RNA-seq]

overall_design: Investigate transcriptome differences in stressed and basal tissues from mutant p53 vs p53-null mice


title: Fecal Microbiome Transplantation and Butyrate Improves Early Cardiac Dysfunction and Modifies the BCAA Metabolic pathway in a Diet induced pre-HFpEF Mouse Model.

city: Maywood

first: Gregory

last: Aubert

state: IL

address: 2160 S 1st Ave

institute: Loyola University Chicago

summary: To investigate the effect of butyrate on cardiac transcripts in western-diet induced pre-HFpEF

overall_design: Comparative gene expression profiling analysis of RNA-seq data for 15 weeks western-diet fed mice treated with tributyrin or PBS (n=3 per group)

first: Jomana

last: Hatahet

first: Tyler

last: Cook

first: Raiza

middle: R

last: Bonomo

first: Nadia

last: Elshareif

first: Chaitanya

last: Gavini

first: Chelsea

last: White

first: Jason

last: Jesse

first: Virginie

last: Mansuy-Aubert


title: p53 dimers elicit unique tumor suppressive activities through an altered metabolic program [ChIP-seq]

overall_design: ChIP-sequencing for dimeric p53 (p53AD) and PPAR-alpha in p53AD basal thymus tissues


title: p53 dimers elicit unique tumor suppressive activities through an altered metabolic program [WES]

overall_design: Comparison of genomic alterations in thymic lymphomas and sarcomas derived from dimeric vs. monomeric p53-bearing mice


title: Analysis of gene expression of the lungs of mice challenged intratracheally with methicillin-resistant Staphylococcus aureus（MRSA） USA300 clone

city: Beijing

first: Yue

last: Zhao

address: FengTai street

institute: Beijing Institute of Microbiology and Epidemiology

summary:
In order to explore the mechanism of host immune response after infection with MRSA (USA300 clone) pneumonia, we established a mouse animal infection model and took lung tissue for RNA sequencing.
Then We performed gene expression profiling using RNA-seq data obtained from lung tissues at five time points.

overall_design: Analysis and comparison of gene expression profiles of non-infected lung tissues (0h) and infected lung tissues (12h, 24h, 48h, 96h).

first: Lina

last: Zhai

first: Tongtong

last: Qin


title: p53 dimers elicit unique tumor suppressive activities through an altered metabolic program


title: Selective Vulnerability of hiPSCs to DHODH Inhibition during Mesenchymal Stem/Stromal Cell Purification

city: Kyoto

first: Makoto

last: Ikeya

address: 53 kawahara-cho, shogoin

department: Center for iPS Cell Research and Application(CiRA)

country: Japan

institute: Kyoto University

summary: To demonstrate the transcriptional changes after BRQ treatment on hiPSCs and MSCs induced from the hiPSCs

overall_design:
We investigated the differentially gene expression and preformed gene set enrichment analysis
Differential gene expression analysis for BRQ treat iPSCs/iMSCs against DMSO treated control

first: Ziadoon

last: Al-Akashi


title: Human SMARCA5 Is Continuously Required to Maintain Nucleosome Spacing [MNAse-Seq]

city: Nashville

first: Scott

last: Hiebert

state: TN

address: 512 B Preston Research Building

department: Biochemistry

institute: Vanderbilt University

summary: Genetic models suggested that SMARCA5 was required for DNA templated events including transcription, DNA replication and DNA repair.  We engineered a degron tag into the endogenous alleles of SMARCA5, a catalytic component of the imitation switch (ISWI) complexes, in three different human cell lines to define the effects of rapid degradation of this key regulator.  Degradation of SMARCA5 was associated with a rapid increase in global nucleosome repeat length, which may allow greater chromatin compaction. However, there were few changes in nascent transcription within the first 6hr of degradation. Nevertheless, we demonstrated a requirement for SMARCA5 to control nucleosome repeat length at G1/S and during the S phase. SMARCA5 co-localized with CTCF and H2A.Z, and we found a rapid loss of CTCF DNA binding and disruption of nucleosomal phasing around CTCF binding sites. This spatiotemporal analysis indicates that SMARCA5 is continuously required for maintaining nucleosomal spacing.

overall_design: MNase-seq was performed on biological replicates.Untreated Kasumi-1 cells expressing endogenous expressed SMARCA5-FKBP12F36V on both alleles as negative controls. Kasumi-1 SMARCA5- FKBP12F36V cells were harvested after 2hr, 6hr, and 24hr with 500nM dTAG-47 treatment. Nuclei were isolated to miccrococal nuclease incubation. Libraries were made with gel extracted mononucleosomes.

first: Monica

last: Bomber


title: New insights from transcriptome profiling of rat quadriceps muscle response to catgut embedding acupoint

city: Huhhot

last: Song

address: No. 306, Zhaowuda Road

department: College of Veterinary

institute: Inner Mongolia Agricultural University

summary:
purpose:The goals of this study is to investigate rat quadriceps muscle responses treated with different catgut embedding acupoint in various molecular pahtways by RNA-seq and real-time quantitative PCR methods and evaluaate protocols for optimal high-throughput data analysis.
Methods:mRNA profiles of rat quadriceps muscle responses treated with catgut embedding acupoint 1 and 2 group,treadmill group and control were generated by sequencing, in sextuplicate, utilizing Illumina HiSeq 4000 platform. The raw RNA-seq data was filtered to remove adaptor contamination, low quality bases, and undetermined beses utilizing Cutadapt software. The filtered reads were aligned and mapped to the reference genome using Hisat 2.0. RT-qPCR validation was performed using SYBR green assays.
Results:The transcription profiling results showed that there were 346 differentially expressed genes (DEGs) between the A and B groups. These included 221 up-regulated DEGs and 125 down-regulated DEGs. There were 363 DEGs between the B group and the C, which included 144 up-regulated DEGs and 219 down-regulated DEGs. There were 458 DEGs between the B group and D which included 248 up-regulated DEGs and 210 down-regulated DEGs. Through GO functional annotation, the DEGs were divided into three categories: cellular components, biological processes, and molecular functions. The above three functions were further divided into positive regulation of transcription by RNA polymerase II, and RNA polymerase II on transcription. Negative regulation, participation in nuclear synthesis, synthesis with cytoplasm, participation in extracellular exosome synthesis, participation in protein binding, and participation in metal ion binding, etc.  After enrichment analysis, 16 metabolic pathways were found to be significantly enriched (p<0.05), which included chemical carcinogenesis, metabolism of cytochrome P450 to exogenous substances, circadian entrainment, circadian rhythm, protein digestion and absorption, PPAR Signaling pathways, drug metabolism - cytochrome P450, parathyroid hormone synthesis, secretion and action, steroid hormone biosynthesis, leishmaniasis, arachidonic acid metabolism, bile secretion, measles, linoleic acid metabolism, fat digestion and absorption, and fluid shear stress and atherosclerosis. By inspecting the bubble enrichment plot, we decided that the following would be important targets of our future studies: protein digestion and absorption; PPAR signaling pathway; synthesis, secretion and action of parathyroid hormone and other metabolic pathways.DEGs that enriche into pathways were verified by RT-qPCR.
Conclusions: Our study provides new insights on the interaction between catgut embedding acupoint and rat quadriceps muscle responses.

overall_design: mRNA profiles of rat quadriceps muscle treat with catgut embedding acupoint 1and 2 group, treadmill group and control group were generated by sequencing, in sextuplicate, utilizing Illumina HiSeq 4000 platform.


title: ENRICHMENT IN C-KIT IMPROVES STEM CELL POTENTIAL OF FOETAL HUMAN AMNIOTIC FLUID CELLS: CHARACTERIZATION FROM SINGLE CELL ANALYSIS TO THE SECRETOME EFFECT [Bulk RNA-Seq]

city: PADOVA

first: GIUSEPPE

last: PERSICO

state: PD

address: VIA UGO BASSI 58/B

country: Italy

institute: UNIVERSITA' DI PADOVA

summary:
Human amniotic fluid cells (hAFSCs) are a fascinating foetal cell-type that have important stem cell characteristics, since described as broadly multipotent immature cells with high self-renewal and no tumorigenic properties. However, amniotic fluid contains a heterogeneous population of amniocytes, from totally differentiated or progenitor cells to highly multipotent stem cells. There is no single approach to isolating the stem cell component, but the selection of a subpopulation of hAFSCs expressing c-Kit (or CD117) is widely employed, while a deep characterization of the two populations is still lacking.
Here we performed single-cell and bulk RNAseq analysis to compare the gene expression profiles of adherent amniotic fluid cells and their subpopulation c-Kit+. Information deriving from this high throughput technology on the transcriptome was then confirmed for specific targets with protein expression experiments and functional analysis.

overall_design: Comparative gene expression profiling analysis of bulk and single cell RNA-seq data for total and ckit selected amniotic fluid stem cells (AFSCs)

first: Francesca

last: Casciaro

last: Beretti

first: Maartina

last: Gatti

first: Giuseppe

last: Persico

first: Emma

last: Bertucci

first: Marco

last: Giorgio

first: Tullia

last: Maraldi


title: ENRICHMENT IN C-KIT IMPROVES STEM CELL POTENTIAL OF FOETAL HUMAN AMNIOTIC FLUID CELLS: CHARACTERIZATION FROM SINGLE CELL ANALYSIS TO THE SECRETOME EFFECT [scRNA-Seq]


title: ENRICHMENT IN C-KIT IMPROVES STEM CELL POTENTIAL OF FOETAL HUMAN AMNIOTIC FLUID CELLS: CHARACTERIZATION FROM SINGLE CELL ANALYSIS TO THE SECRETOME EFFECT

overall_design: Refer to individual Series


title: Effect of a high fat diet on gene expression in enteroendocrine cells of the mouse jejunum

city: Illkirch

first: Gérard

last: Gradwohl

address: 1 rue Laurent Fries

institute: IGBMC

summary: To identify the genes differentially expressed in jejunal enteroendocrine cells (EECs) under a high fat diet we purified EEC (eYFP+) and non-EEC(eYFP-) using FACS from jejunal villi of Neurog3eYFP/+ mice (Mellitzer et al, Mol. Endo 2004) fed with a normal chow or high fat diet (HFD). In Neurog3eYFP/+ mice enteroendocrine progenitors and their descendants are labeled with eYFP. We then purified the RNA and perfomed gene exspression profiling using RNAseq.

overall_design: All samples are from jejunal villi: Normal diet (ND), EEC (eYFP-plus)  (n=3); non-EEC (eYFP-minus)  (n=3); High fat diet (HFD) EEC (eYFP-plus) (n=3), non-EEC (eYFP-minus)  (n=3).

first: Miriam

last: Ejarque

first: Céline

last: Keime


title: Molecular Dissection of Polycomb Group Protein-mediated Fetal Hemoglobin Repression [CUT&RUN]

city: Philadelphia

first: KUNHUA

last: QIN

email: qink@chop.edu, kunhua.qin@gmail.com

state: PA

address: 3615 Civic Center Blvd, 315H

institute: Children's Hospital of Philadelphia

summary: The fetal (HbF)-to-adult (HbA) hemoglobin switch is a paradigm for developmental gene expression control with relevance to sickle cell disease and beta-thalassemia. Polycomb repressive complex (PRC) proteins regulate this switch, and an inhibitor of the EED subunit of PRC2 entered clinical trials for fetal hemoglobin activation. Yet, how PcG complexes function in this process, their target genes and relevant subunit composition are unknown. Here, we identified the PRC1 subunit BMI1 as a novel HbF repressor. We uncovered LIN28B, IGF2BP1, and IGF2BP3 as direct BMI1 targets and demonstrate that they account for the BMI1 effects. BMI1 functions as part of the canonical PRC1 (cPRC1) subcomplex as revealed by the physical and functional dissection of BMI1 protein partners. Lastly, we demonstrate that BMI1/cPRC1 acts in concert with the PRC2 to repress HbF through the same target genes. Our study illuminates how PRC silences HbF, highlighting an epigenetic mechanism involved in hemoglobin switching.

overall_design: Chromatin occupancies of BMI1, EZH2, RING1B, CBX2, CBX4, CBX7, CBX7, and CBX8 and genomic enrichment of H3K27me3, H3K4me3, H3K27Ac, and H2AK119ub1 in HUDEP2 and primary erythroblasts were analyzed by CUT&RUN or ChIP-seq

first: Kunhua

last: Qin

first: Gerd

middle: A

last: Blobel


title: Molecular Dissection of Polycomb Group Protein-mediated Fetal Hemoglobin Repression

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


title: Genetics of tolerance in honey bees to the neonicotinoid clothianidin.

city: Toronto

first: Amro

last: Zayed

state: Ontario

address: 4700 Keele Street

department: Biology

country: Canada

institute: York University

summary: The effects of neonicotinoid insecticides (NNIs) on honey bee health is intensely debated, with numerous studies showing negative effects of exposure, while others report no such effects. Understanding the cause of these differences is critical for developing evidence-based policy on the use of NNIs. We carried out experiments to study the genetic and molecular basis of NNI tolerance in honey bees, which may underlie the discrepancies observed in the literature. We discovered that worker survival post-exposure to an acute oral dose of clothianidin is heritable (H2=37.8%).

overall_design:
Tolerance to clothianidin was not associated with differences in expression of detoxification enzymes in our experiments. Instead, mutations in the primary neonicotinoid detoxification genes CYP9Q1 and CYP9Q3 were strongly associated with worker survival post clothianidin exposure. In some instances, the strong association between CYP9Q haplotypes and worker survival was associated with the protein’s predicted binding affinity for clothianidin. Our findings have implications regarding future toxicological studies utilizing honey bees as a model pollinator.
Eight day old bees were exposed to 4.27ppb of clothianidin individually through a sugar solution. 24 Hours post exposure, the bees were frozen on dry ice.  The patriline of each bee was determined using DNA microsatalites. 'suseptible' and tolorant' patrilines were determined based on a previous experiment described in the manuscript. We performed dissections of the brain, Malpighian tubules, and ventriculus and kept them at -80oC until RNA could be extracted.  RNA extractions were completed using the miRNeasy Mini kit (Qiagen).  The ventriculus, brains, and Malpighian tubules of 5 individual bees from each patriline were pooled separately based on their organ (e,g., all the brains of a patriline were pooled together). We had a total of 3 tolerant patrilines, and 3 susceptible patrilines and 18 pools in total.  To ensure equal representation for each bee, we added 300 ng of RNA to each pool (1500 ng/5 bees). Library preparation and 100 bp pair-end sequencing using the Illumina NovaSeq 6000 S4 were carried out by Genome Quebec’s sequencing facility (Montreal, QC).

first: Nadejda

last: Tsvetkov

first: Simran

last: Bahia

first: Bernarda

last: Calla

first: May

last: Berenbaum


title: The menin inhibitor SNDX-5613 for KMT2A rearranged or NPM1 mutant leukemia

city: Hannover

first: Florian

last: Perner

address: Carl-Neuberg-Str. 1

department: Hematology, Hemostasis, Oncology and Stem Cell Transplantation

institute: Hannover Medical School

summary:
Targeting critical epigenetic regulators reverses aberrant transcription in cancer,
thereby restoring normal tissue function. The interaction of menin with lysine
methyltransferase 2A (KMT2A), an epigenetic regulator, is a dependency in acute
leukaemia caused by either rearrangement of KMT2A or mutation in Nucleophosmin 1(NPM1). KMT2A rearrangements occur in up to 10% of acute leukaemias and have an adverse prognosis whereas NPM1 mutations occur in up to 30%, forming the most common genetic alteration in acute myeloid leukaemia7,8. Here, we describe the results of the first-in-human phase 1 clinical trial investigating revumenib (SNDX-5613), a potent and selective oral inhibitor of the menin–KMT2A interaction, in patients with relapsed or refractory acute leukaemia (ClinicalTrials.gov, NCT04065399). We show that therapy with revumenib was associated with a low frequency of grade 3 or higher treatment-related adverse events and a 30% rate of complete remission or complete remission with partial haematologic recovery (CR/CRh) in the efficacy analysis population. Asymptomatic prolongation of the QT interval on electrocardiography was identified as the only dose-limiting toxicity. Remissions occurred in leukaemias refractory to multiple previous lines of therapy. We demonstrate clearance of residual disease using sensitive clinical assays and identify hallmarks of differentiation into normal haematopoietic cells, including differentiation syndrome. These data establish menin inhibition as a therapeutic strategy for susceptible acute leukaemia subtypes.

overall_design: RNA-sequencing of human leukemia cells from bone marrow on patient derived xenografts (PDX) treated with SNDX-5613 for 1 week.

first: Charlie

last: Hatton


title: Single-cell RNA sequencing reveals transcriptional changes in the cartilage of subchondral insufficiency fracture of the knee

city: Shenyang

first: Lutian

last: Yao

address: 155 Nanjing st

department: Department of Orthopedic

institute: the First Affiliated Hospital of China Medical University

summary: Subchondral insufficiency fracture of the knee (SIFK) is a common cause of knee joint pain that mainly afflicts the elderly. Yet its transcriptional profiles of cartilage in SIFK and OA patients are largely unknown. We performed single-cell RNA sequencing (scRNA-seq) on the cartilage of a SIFK patient, then compared with the processed scRNA-seq files of normal and OA cartilage tissues which were acquired from GSE169454. Cartilage samples from SIFK and OA patients  were used to confirm some of the transcriptional expression.

overall_design: Articular chondrocytes from Subchondral insufficiency fracture of the knee (SIFK) patient were harvested and analyzed by scRNA-seq

first: Huan-Tian

last: Zhang


title: Decoupling of mRNA and protein expression in aging brains reveals the age-dependent adaptation of specific gene subsets

city: Sherbrooke

first: Benoit

last: Laurent

address: 3201 Jean Mignault

institute: University of Sherbrooke

summary:
To investigate the connection between changes of mRNA and protein expression in the brain during aging, we compared the transcriptome and proteome of the mouse cortex.
We profiled gene expression in the mouse cortex using data obtained from RNA-seq of three individuals at 6-months old and three individuals at 24-months old.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for the cortex of mice at 6 and 24-months old

first: Marie

last: Brunet


title: Microglial gene expression in Bmal1 cKO and WT mice

city: Stanford

first: Sur

last: Herrera Paredes

address: 371 Serra Mall,  Gilbert Building Room 109

institute: Stanford University

summary: To investigate the interaction between aging and microglial circadian rhythmicity, we examined mice deficient in the core clock transcription factor, BMAL1, in microglia.

overall_design: Comparison of gene expression profiles in WT and mutant mice, at two ages in a 2x2 full factorial design.

first: Chinyere

last: Agbaegbu Iweka

first: Katrin

last: Andreasson


title: First characterization of the transcriptome of lung fibroblasts of SSc patients and healthy donors of African ancestry.

city: Charleston

first: Carol

last: Feghali-Bostwick

state: SC

address: 96 Jonathan Lucas St room 822

department: Medicine

institute: Medical University of South Carolina

summary: Systemic sclerosis (SSc) is a rare and devastating connective tissue disorder that results in fibrosis and vascular abnormalities that affect the skin and visceral organs, and SSc-associated pulmonary fibrosis (SSc-PF) is the leading cause of death amongst SSc patients. Racial disparity is noticeable in SSc as African Americans (AA) have a higher frequency and severity of diseases than European Americans (EA). Using RNAseq, we determined differentially expressed genes (DEGs) in primary pulmonary fibroblasts (pFBs) outgrown from SSc-PF lungs (SScL) and normal lungs (NL) of AA and EA patients to characterize the unique transcriptomic signatures of AA-NL and AA-SScL pFBs by performing a systems level analysis. We identified 69 DEGs in “AA-NL vs. EA-NL” and 384 DEGs in “AA-SScL vs. EA-SScL” comparisons, and only 7.5% DEGs were commonly deregulated in the “SScL vs. NL in AA and EA” disease mechanisms comparison. Surprisingly, we also identified a disease-like signature in AA-NL pFBs. Our data highlight that the transcriptome of AA pFBs is unique and may hold the key to understanding racial disparity in SSc-PF, the first step in developing efficacious therapeutic strategies.

overall_design: differential expression analysis between (1) normal lung (NL) pulmonary fibroblasts (pFBs) of African American (AA) and European Americans (EA) donors "AA-NL vs. EA-NL"; (2) SSc-PF pFBs (SScL) and NL pFBs in AA and EA: "AA-SScL vs. AA-NL" and "EA-SScL vs. EA-NL" followed by venn comparison; (3) "AA-SScL vs. EA-SScL"

first: Ludivine

last: Renaud

first: Kristy

last: Waldrep


title: Cancer-Associated Fibroblasts are the Main Source of Epithelial-to-Mesenchymal Signaling in the Tumor Microenvironment

city: Boston

first: Michael

last: Tolstorukov

address: 450 Brookline Ave

institute: Dana-Farber Cancer Institute

summary: Epithelial-to-mesenchymal transition (EMT) is associated with tumor initiation, metastasis, and drug resistance. However, the mechanisms underlying these associations are largely unknown. We studied several tumor types to identify the source of EMT gene expression signals and to illuminate mechanisms of resistance to immuno-oncology treatment. Across tumor types, EMT-related gene expression was strongly associated with expression of stroma-related genes. Based on RNA sequencing of multiple patient-derived xenograft models, EMT-related gene expression was enriched in the stroma versus parenchyma. EMT-related markers were predominantly expressed by cancer-associated fibroblasts (CAFs), cells of mesenchymal origin which produce a variety of matrix proteins and growth factors. Scores derived from a 3-gene CAF transcriptional signature (COL1A1, COL1A2, COL3A1) were sufficient to reproduce association between EMT-related markers and disease prognosis. Our results suggest that CAFs are the primary source of EMT signaling and have potential roles as biomarkers and targets for immuno-oncology therapies.

overall_design:
Comparative gene expression profiling of patient-derived xenografts for multi-cancer cohort using RNA-seq assay
*** Submitter declares that the patients from which these files have been derived have not consented to the raw data public release but processed data is allowed. ***

first: Peter

last: Szabo

first: Kin-Hoe

last: Chow

first: Keith

last: Ligon