title: Liver protects neuron viability and electrocortical activity in post-cardiac arrest brain injury

city: Guangzhou

first: Meixian

last: Yin

address: No. 58 Zhongshan Er Road

department: Organ Transplant Centre

institute: The First Affiliated Hospital, Sun Yat-sen University

summary: Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury.

overall_design: To investigate how the liver might affect post-CA brain injury, we performed gene expression profiling analysis using data obtained from RNA-seq of the frontal (F) and temporal (T) lobes at the experimental endpoint.We compared the differences between groups with and without simultaneous hepatic ischemia.

first: Zhiyong

last: Guo

first: Tielong

first: Zehua

last: Jia

first: Liqiang

last: Zhan

first: Jin

last: Xu

first: Qiang

last: Zhao

first: Xiaoshun

last: He


title: Integrative identification of non-coding regulatory regions driving metastatic prostate cancer [MPRA]

status: Public on Oct 01 2025

city: San Francisco

first: Hani

last: Goodarzi

state: CA

department: Biochemistry and Biophysics

country: USA

institute: UCSF

summary: Large-scale sequencing efforts have been undertaken to understand the mutational landscape of the coding genome. However, the vast majority of variants occur within non-coding genomic regions. We designed an integrative computational and experimental framework to identify recurrently mutated non-coding regulatory regions that drive tumor progression. Applying this framework to sequencing data from a large prostate cancer patient cohort revealed a large set of candidate drivers. We used (i) in silico analyses, (ii) massively parallel reporter assays, and (iii) in vivo CRISPR interference screens to systematically validate mCRPC drivers. One found enhancer region, GH22I030351, acts on a bidirectional promoter to simultaneously modulate expression of U2-associated splicing factor SF3A1 and chromosomal protein CCDC157. SF3A1 and CCDC157 promote tumor growth in vivo. We nominated a number of transcription factors, notably SOX6, to regulate expression of SF3A1 and CCDC157. Our integrative approach enables the systematic detection of non-coding regulatory regions that drive human cancers.

overall_design: For the MPRA dataset, which we conducted in C4-2B cell lines, we generated whole genome DNA-sequencing data, as well as RNA-seq transcriptomic data from screen endpoint. This data contains the initial CRS-barcode association sequencing for our lentiMPRA library, the gDNA fraction (used for normalizing counts), and the corresponding RNA fraction.

first: Brian

middle: J

last: Woo

first: Ruhollah

last: Moussavi-Baygi

first: Heather

last: Karner

first: Mehran

last: Karimzadeh


city: Chengdu

first: Xinyi

last: Fang

address: Guoxue alley

country: China

institute: Lab for Aging Research and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University

type: Expression profiling by high throughput sequencing

summary: A polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber (PEDOT-PSF) network and a H2S sustained-release system utilizing bovine serum albumin nanoparticles (BNP) is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and promote functional tissue regeneration in periodontitis in diabetes. The RNA sequencing of THP-1 on Polyphenol-Mediated Redox-Active Hydrogel with H2S Gaseous-Bioelectric Coupling was conducted to explore the underlying mechanism.

overall_design: To investigate the effect of the BNP-PEDOT-PSF-AG hydrogel,  we conducted RNA seq of THP-1 cultured on various hydrogels.


title: Transcriptome analysis of leptin on OVCAR8 cells

city: Wuhan

first: jingtao

last: wang

address: No. 299, Bayi Road, Wuchang District, Wuhan City, Hubei Province

institute: Wuhan University

summary: Elevated levels of leptin in the blood, the increased expression of leptin receptor (LEPR) in tumor cells, and a high leptin to adiponectin ratio in patients with ovarian cancer are linked to a poorer prognosis. Recent research has investigated the connection between leptin and ovarian cancer, revealing the role of leptin in promoting proliferation, invasion, metastasis, and chemotherapy resistance in ovarian cancer cells. Moreover, leptin was shown to contribute to maintaining the stemness phenotype of ovarian cancer stem cells (OCSCs) and enhancing tumor metastasis potential. However, the specific downstream targets that is responsible for the regulation that potentiates leptin-induced stemness maintenance in OCSCs has not been conclusively identified.

overall_design: To identify the key downstream markers of leptin- driven stemness maintenance in human ovarian cancer, we analyzed genes that showed altered gene expression at the transcription level before and after leptin treatment. OVCAR8 cells were serum starved overnight and then treated with 100 ng/ml leptin for 24 h, after which transcriptome sequencing was performed to obtain differently expressed genes (DEGs) after leptin treatment.

first: J

middle: T

last: Wang

first: F

last: Yang

last: Li

first: W

last: Zhang


title: PHF6 regulates stress susceptibility in the pituitary intermediate lobe [RNA-seq]

city: Shanghai

first: Bing

last: Liu

address: No. 280, South Chongqing Road

institute: Shanghai Jiao Tong University School of Medicine

summary: We revealed that stress triggers PHF6 to bind to the promoters of various stress-regulated genes in IL-melanotrophic cells and regulate their expression levels.

overall_design: We performed SMART-RNA sequencing on pituitary intermediate lobe tissues meticulously dissected and captured by laser-capture microdissection (LCM) from both Phf6cKO and control mice under control and RS-stress conditions

first: Jingjie

first: Xiaohua

last: Wu

first: Linhua

last: Gan

first: Jingjing

last: Sun

first: Guangzhong

first: Qian

first: Ju

last: Huang


title: HMGA2 overexpression drives a leiomyoma-like phenotype by modulating the epigenomic environment in primary myometrial cells [ChIP-Seq]

city: Chicago

first: Debabrata

last: Chakravarti

state: IL

address: 303 E Superior St.

department: Obstetrics and Gynecology

institute: Northwestern University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: With the utilization of advanced tools for genome-wide studies, the role of the epigenome in regulating gene expression is becoming more evident in both normal tissue development and disease states. Uterine fibroids, also known as leiomyomas, are a major reproductive disease that manifests as benign tumors and altered extracellular matrix composition leading to severe pathological symptoms. Several genomic alterations have been associated with leiomyoma. HMGA2 overexpression has been noted in approximately 10% of all patients with leiomyoma. HMGA2 is a chromatin-targeted protein and is therefore an important contributor to altered transcriptomic outcomes. However, due to a lack of specific antibodies against HMGA2 and appropriate in vitro cellular models, there is a lack in understanding of HMGA2 interaction with and regulation of chromatin in the context of leiomyoma. To address this gap, we engineered primary myometrial cells that express V5-tagged HMGA2 at levels comparable to those observed in leiomyoma. We observed transcriptomic and H3K27 acetylation changes that appeared to drive a leiomyoma-like phenotype in the engineered HMGA2v5 cells. HMGA2 was found to be diffusedly bound to chromatin, with most of the binding occurring at promoter- distal regions. Moreover, altered chromatin accessibility was observed in HMGA2v5 cells, with enrichment of AP-1 family transcription factor binding motifs at various sites. Thus, our study suggests that overexpression of HMGA2 modulates the genomic architecture of myometrial cells to cause leiomyoma-like gene expression and epigenomic changes.

overall_design: Primary myometrial cells were obtained from three patients and treated with empty or V5-tagged HMGA2 vector using lentiviral transduction. ChIP-sequencing was performed for histone modification -H3K27ac and V5-tagged HMGA2 using antibody against V5 epitope.

first: Priyanka

last: Saini

first: Austin

middle: G

last: Holmes

first: Jian-Jun

last: Wei

first: James

middle: B

last: Parker


title: Interferon Mediated Bronchial Epithelium Cellular Senescence in Chronic Obstructive Pulmonary Disease

city: Belfast

first: Clifford

last: Taggart

state: Northern Ireland

address: 97 Lisburn Rd

department: Wellcome-Wolfson Institute for Experimental Medicine

country: United Kingdom

institute: Queen's University Belfast

summary: Cellular senescence has been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis.  We used single cell RNA sequencing (scRNA-seq) to analyze gene expressions in bronchial epthelium, finding increased expression of cellular senescence signature in COPD samples.

overall_design: Bronchial epithelial cells from COPD and healthy controls were cultured in an air-liquid interface (ALI) model, at 28 days ALI culture, cells were trypsinized and anylized using scRNA-Seq.

first: Hong

last: Guo-Parke

first: Oisín

last: Cappa

first: Dermot

last: Linden

first: Jeremy

last: Domis

first: Lee

middle: A

last: Borthwick

first: Andrew

last: Fisher

first: Sinéad

last: Weldon

first: David

last: Simpson

middle: C

first: Joseph

last: Kidney


title: HMGA2 overexpression drives a leiomyoma-like phenotype by modulating the epigenomic environment in primary myometrial cells [ATAC-seq]

overall_design: Primary myometrial cells were obtained from three patients and treated with empty or V5-tagged HMGA2 vector using lentiviral transduction. ATAC libraries were generated from these samples and used for next generation sequencing.


title: Circulating miRNA profile and atherogenic Lp(a) levels in asymptomatic patients with familial hypercholesterolemia.

city: Barcelona

first: Lina

last: Badimon

state: BARCELONA

address: Carrer de Sant Antoni Maria Claret, 167

department: ICCC-Cardiovascular Program

country: Spain

institute: Research Institut- HSCSP

summary:
Affymetrix microarray (GeneChip microRNA 4.0) profilling of circulating miRNAs.
We used miRNA arrays to profile miRNAs isolated from plasma of familial hypercholesterolemia patients with [FH-Lp(a)_High_50 mg/dL] or without [FH-Lp(a)_Low_50 mg/dL] atherogenic Lp(a) concentration.

overall_design: We isolated circulating miRNAs from plasma samples of familial hypercholesterolemia patients and profiled them to determine miRNA signature.

first: Rafael

last: Escate

first: Sandra

last: Camino

first: Teresa

last: Padró


title: CRISPRi Screening of Enhancers in Human Primary Astrocytes Identifies Regulatory Circuitry Disrupted in Alzheimer’s Disease [NanoString]

city: Kensington

first: Irina

last: Voineagu

state: NSW

address: High St

department: Biotechnology and Biomolecular Sciences

country: Australia

institute: The University of New South Wales

summary: We used CROP-seq to perform a high-throughput, parallel screen of 979 candidate enhancer perturbations in normal human astrocytes (NHAs), a primary cell-line. We identified the target gene(s) for 145 of these candidates, which were enriched for transcription with eRNA, transcription factor footprinting, and superenhancer annotation. Most regulatory interactions were <50kb, targeting the nearest gene in ~50% of cases, but were not typically captured by eQTL or in silico predictions. These data elucidate the regulatory network of an understudied-but-crucial brain cell-type.

overall_design: To validate results from our CRISPRi scRNA-seq screen, we selected 19 enhancers linked to 14 genes to validate in singleton experiments. The top performing sgRNA for each enhancer was cloned in CROP-seq-opti-GFP and transduced into NHA cells that stably express dCas9-KRAB at an MOI of 1. We also generated 4 pooled lines, where sgRNA for 2-3 enhancers linked to the same gene were transduced into the NHA-dCas9-KRAB cells at an MOI of 1 for each sgRNA. After 4 days, cells were selected with 3 µg/mL of puromycin and 10 µg/mL blasticidine S hydrochloride, and RNA was extracted after 7 days. Gene expression was then measured using a Nanostring nCounter Elements TagSets.

first: Nicole

middle: F

last: Green

first: Gavin

last: Sutton

first: Hannah

last: Danon


title: Effect of obesity on the neurovascular unit transcriptome in the female mice hippocampus using single nuclei RNA seq

city: Davis

first: Saivageethi

last: Nuthikattu

address: 550 Hutchison Dr

department: Internal Medicine, Cardiovascular division

institute: University of California Davis

summary: Obesity is a global pandemic and a key risk factor for several neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease, or dementia. The neurovascular unit (NVU), essential for blood-brain barrier (BBB) integrity and comprised of endothelial cells, glial cells (microglia and astrocytes), and neurons, plays an important role in the pathogenesis of neurodegenerative diseases. However, molecular mechanisms underlying the effects of obesity on endothelial and other cells of and its contribution to neurodegeneration remains largely unknown, especially in females. In this study we aimed to decipher in-dept molecular modifications induced by obesity in cells of neurovascular unit by integrative multiomics analysis of endothelial cells, neurons, microglial cells, and astrocytes from the hippocampus of ob/ob female mice. Hippocampus were isolated from ob/ob and C57BL/6J female mice at 17-18 weeks of age. Gene expression profiles of cells of hippocampus were obtained using single nuclei RNA sequencing (snRNAseq) and data analyzed using in-depth bioinformatic analyses.

overall_design: Wild type (C57BL/6J) and ob/ob female mice were fed a standard purified diet AIN-93M, for 8 wks. Mice were sacrificed at 18 weeks of age and hippocampus was dissected from left hemisphere and then stored at -80 degree celcius. Hippocampal nuclei was isolated and single nuclei RNA sequencing was performed. Brain hippocampal endothelial cells, microglial cells, astrocytes, and neuronal cells gene expression was analyzed using a multiomic approach for differential expression of protein and non-protein coding genes, gene networks, functional pathways, and transcription factors.

first: Jennifer

last: Norman

first: Dragan

last: Milenkovic

first: Amparo

last: Villablanca


title: Castration Model Illuminates Sex Differences in Healthy Aging: Insights from Metabolome and Transcriptome Analyses

city: Seattle

first: Jianjun

last: Jiang

address: 401 Terry Ave N

institute: Institute for Systems Biology

summary: Females typically outlive males, a disparity mitigated by castration, yet the molecular underpinnings remain elusive. Our study leverages untargeted metabolomics and RNA sequencing to uncover the pivotal compounds and genes influencing healthy aging post-castration, examining serum, kidney, and liver biospecimens from 12-week and 18-month old castrated male mice and their unaltered counterparts. Behavioral tests and LC-MS/MS metabolomics reveal that castrated males exhibit altered steroid hormones, superior cognitive performance, and higher levels of anti-oxidative compounds like taurine, despite identical diets. Integrated metabolome-transcriptome analysis confirms reduced lipid peroxidation and oxidative stress in female and castrated male mice, suggesting a protective mechanism against aging. Histological examinations post-cisplatin treatment highlight the model’s applicability in studying drug toxicity and reveal varying susceptibility in organ-specific toxicities, underlining the crucial role of sex hormones in physiological defenses. In essence, our castration model unveils a feminized metabolic and transcriptomic intermediary, serving as a robust tool for studying gender-specific aspects of healthy aging and exploring sex hormone-induced differences in diverse biomedical domains.

overall_design: RNA-seq and untargeted-metabolomics were performed on kidney, liver and/or serum samples of shamM, shamF and casM at 12week and 18month old to explore the underlying mechanisms of castration related healthy aging.

last: Ge

first: Yuzhi

last: Wang

first: Juntao

last: Qi

first: Guibiao

last: Wen

first: Xiufen

last: Gu

first: Xuewen

last: Yu

first: Muming

last: Shao

first: Yueming

last: Luo

first: Kangshuyun

first: Feng

last: Lin

first: Shudong

last: Yang

first: Wei

last: Wei


city: Beijing

first: Junjie

last: Du

state: Beijing

address: Dongdajie Street 8

institute: The Fifth Medical Center of Chinese PLA General Hospital

summary: Hematopoietic stem cells (HSCs), with the capability of self-renewal and all blood lineages reconstruction, serve a crucial role in maintaining steady-state hematopoiesis within bone marrow during adulthood. The adaptor protein receptor for activated C kinase 1 (RACK1) has been implicated in the regulation of various transcription factors and signaling pathways by modulating their activation and/or stability. However, the specific role of RACK1 in the transcriptional control of HSC fates has not been previously elucidated. Here, we reported that RACK1 is enriched in hematopoietic progenitors. And its absence leads to BM failure with rapid loss of HSCs and downstream progenitors. Such phenotypes result from cell-intrinsic defects with enhanced proliferation and apoptosis of HSCs. scRNA-seq indicates Rack1 deletion leads to aberrant lineage molecular character of transcriptional HSCs and the emergence of HSK-like cells. At the molecular level, RACK1 directly binds to TAL1 core complex components and facilitates the assembly of the complex. Thus, RACK1 maintains mouse hematopoietic stem cell quiescence through, at least partially, promoting the assembly of TAL1 core complex.

overall_design: Single cell profiling from bone marrow Lin-cKit+ hematopoietic cells derived from RACK1 knockdown mice or control mice at 8 ~ 12-week-age respectively.

first: Lijiao

last: Deng

first: Zhe

last: Xu

first: Lu

last: Guo

first: Qingyang

first: Guang

first: Yuchen

last: Lu

first: Yu

last: Lan

first: Bingshui

last: Xiu

first: Jiannan

last: Feng

first: Jiyan

last: Zhang


title: Pseudogenes contribute to the evolution of topological domains across species via forming three-dimensional genome [Hi-C]

first: Liu

last: He

address: No. 5, Dongdan Sanjo, Dongcheng District

institute: Peking Union Medical College

summary: The human genome harbors 15,000 pseudogenes, except very few can transcribe non-coding RNAs or encode truncated proteins, a large number of which without transcriptional capacity are functional unknown. Here, we found that DNA sequence of pseudogenes can form chromatin contacts, acting as anchors of chromatin loops and boundaries of topological associated domains (TADs), many of them are proved to be structural important and essential for human embryonic stem cells (hESCs) survival. Incorporating genetic data, we defined a hominoidea-specific pseudogene, TUBBP2, which acted as a TAD boundary by enriching CTCF, to maintain the 3D genome and self-renewal of hESCs. Evolutionally, TUBBP2 was generated in 18.8 million years ago through retroposition and inherited the CTCF binding motif from its parent gene-TUBB, thus enhance the strength of TADs at the insertion site in great apes genome. More amazing, by inheritance from parent genes or sequence variation, a part of pseudogenes can introduce additional CTCF binding sequence at their insertion sites to generate species-specific topological domains, which may contribute to species evolution. Overall, we not only demonstrate the essentiality of pseudogenes in the formation and maintenance of 3D chromatin structure, but provide insights on their functions of driving species evolution.

overall_design: We performed Hi-C, ChIP-seq for CTCF in WT/TUBBP2 KO human embryonic stem cells (hESC),each with two replicates. To find out how pseudogenes influence gene expression in hESC, we also performed RNA-seq in WT/KRT18P37 KO hESC, and in WT/TUBBP2 KO/ALOX KO hESC, each with two replicates.

first: Mengyao

last: Sun


title: SARS-CoV-2 infection of human lung ALI cultures reveals basal cells as relevant targets

city: Berlin

first: Benedikt

last: Obermayer

address: Chariteplatz 1

department: Core Unit Bioinformatics

country: Germany

institute: Berlin Institute of Health

summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets ciliated cells during the initial infection of the upper respiratory tract, although uncertainties persist regarding other involved epithelial cell types. Herein, we utilized viral replication analysis, single-cell RNA sequencing, and spectral microscopy on infected air-liquid interface cultures of human primary nasal and bronchial epithelial cells to discern cell type proportions in relation to SARS-CoV-2 tropism and immune activation. We revealed that, alongside ciliated and secretory cells, SARS-CoV-2 (wildtype and lineage B1.1.7 [Alpha variant]) strongly infects basal cells, significantly contributing to the epithelial immune response in a donor-specific manner. Moreover, local Camostat mesylate treatment was effective on both the basal and apical cell compartment, resulting in a notable reduction in viral load and reduced immune activation. Collectively, our data emphasize the critical role of basal cells in facilitating SARS-CoV-2 dissemination within the upper respiratory tract and their substantial contribution to the epithelial immune response. Furthermore, our results highlight the potential of local application of Camostat mesylate as an effective strategy for early inhibiting SARS-CoV-2 infection and mitigating associated immune activation.

overall_design:
We used primary human nasal and bronchial epithelial cells cultured at air-liquid interface (ALI) for infection with SARS-CoV-2 wild type and variant B1.1.7 to investigate viral replication, cellular tropism and related transcriptomic response as well as therapeutic-like treatment using Camostat mesylate.
***Submitters state that raw data unavailable due to patient privacy restrictions***

first: Morris

last: Baumgardt

first: Anita

last: Balázs

first: Anna

last: Löwa

first: Emanuel

last: Wyler

first: Luiz

last: Alves

first: Katharina

last: Hellwig

first: Dieter

last: Beule

first: Markus

last: Landthaler

first: Christian

last: Drosten

first: Marcus

last: Mall

first: Stefan

last: Hippenstiel

first: Katja

last: Hönzke

first: Andreas

last: Hocke


title: Pseudogenes contribute to the evolution of topological domains across species via forming three-dimensional genome

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

overall_design: Refer to individual Series


title: Pseudogenes contribute to the evolution of topological domains across species via forming three-dimensional genome [ChIP-seq]


title: p53 activation in mouse culture neurons

city: Cambridge

first: Ping-Cheih

last: Pao

state: MA

address: 43 Vassar St

department: Brain and Cognitive Sciences

institute: MIT

summary: To investigate the effects of p53 activation in mouse culture neurons

overall_design: 15 DIV culture neurons were treated with p53 activator (Nutlin-3) for 2 days

first: Ping-Chieh

first: Li-Huei

last: Tsai


title: Transcriptional and epigenetic targets of MEF2C in human microglia contribute to cellular functions related to autism risk and age-related disease

city: Austin

last: Warden

state: TX

address: 2500 Speedway

institute: University of Texas at Austin

summary: MEF2C encodes a transcription factor that is critical in nervous system development. To examine disease-associated functions of MEF2C in human microglia, we profiled microglia differentiated from isogenic MEF2C-haploinsufficient and -knockout induced pluripotent stem cell lines. Complementary transcriptomic and functional analyses revealed that loss of MEF2C lead to a hyperinflammatory phenotype with broad phagocytic impairment, lipid accumulation, lysosomal dysfunction, and elevated basal inflammatory cytokine secretion. Genome-wide profiling of MEF2C-bound sites coupled with the active regulatory landscape enabled inference of its transcriptional functions and potential mechanisms for MEF2C-associated cellular functions. Transcriptomic and epigenetic approaches identified substantial overlap with idiopathic autism datasets, suggesting a broader role of human microglial MEF2C dysregulation in idiopathic autism. In a murine xenotransplantation model, loss of MEF2C led to morphological, lysosomal and lipid abnormalities in human microglia in vivo. Altogether, these studies reveal mechanisms by which reduced microglial MEF2C could contribute to the development of neurological diseases.

overall_design:
To investigate the effect of the in MEF2C genotype, we generated a cohort of we profile microglia differentiated from isogenic, CRISPR-modified MEF2C haploinsufficient and knockout induced-pluripotent stem cell (iPSC) lines
We then performed gene expression profiling of iPSC-derived microglia from lines with Control, haploinsufficiency (MHS) and knockout genotypes. We used comparative gene expression methods (DESeq2) to determine differential expression, gene patterns (DEGreport) and co-expression networks (WGCNA).

first: Celina

last: Nguyen

first: Emily

last: Hansen

middle: S

first: Cristina

last: Mora

first: Claudia

last: Han

first: Zahara

last: Keulen

first: Nathan

last: Spann

first: Jing

last: Wang

first: Gabriela

last: Ramirez

first: Samantha

last: Mak

last: Trescott

first: Mohammadparsa

last: Khakpour

first: Avalon

last: Johnson

first: Fatir

last: Qureshi

first: Michael

middle: R

last: La Frano

first: Kiana

last: Mohajeri

middle: E

last: Talkowski

first: Olivia

last: Corradin

first: Marie-Eve

last: Tremblay

first: Christopher

middle: K

last: Glass

first: Nicole

last: Coufal


title: Genetic and pharmaceutical targeting of Suv39h1 ameliorates renal fibrosis by unlocking CXCL10 transcription [I]

city: nanjing

first: kong

last: ming

address: 南京市江宁区龙眠大道639号

department: college of pharmacy

institute: China Pharmaceutical University

summary: Renal fibrosis is present in all forms of chronic kidney disease (CKD) and when dysregulated contributes to renal failure. Renal fibroblast is the major precursor to myofibroblast, the effector cell type of renal fibrosis. In the present study we investigated the role of Suv39h1, a lysine methyltransferase, in fibroblast-myofibroblast transition (FMyT) and renal fibrosis. We report that Su39h1 is up-regulated during FMyT both in vitro and in vivo. Suv39h1 deletion in fibroblasts partially blocked FMyT in vitro and attenuated renal fibrosis in three different animal models. Additionally, conditional Suv39h1 knockout in Postn+ mature myofibroblasts mitigated renal fibrosis in mice. Importantly, Suv39h1 inhibition with a small-molecule compound chaetocin suppressed FMyT in cell culture and ameliorated renal fibrosis in mice. Transcriptomic analysis uncovered CXCL10 as a downstream target for Suv39h1. CXCL10 knockdown nullified the protective effect of Suv39h1 insufficiency on renal fibrosis. Mechanistically, CXCL10 regulated FMyT by suppressing the Hippo/YAP pathway. In conclusion, our data illustrate a previously unrecognized role for Suv39h1 in regulating renal fibrosis.

overall_design: Comparative gene expression profiling analysis using data for RFB cells and its KD derivatives(SUV39H1-KD)

first: Ming

last: Kong

first: Xiaoyan

last: Wu

first: Aoqi

last: Kang

first: Yajun

last: Luo


title: Genetic and pharmaceutical targeting of Suv39h1 ameliorates renal fibrosis by unlocking CXCL10 transcription

address: 南京市江宁区龙眠大道639号


title: Pseudogenes contribute to the evolution of topological domains across species via forming three-dimensional genome [RNA-Seq]

first: Liu

last: He

first: Mengyao

last: Sun


title: Genetic and pharmaceutical targeting of Suv39h1 ameliorates renal fibrosis by unlocking CXCL10 transcription [III]

address: 南京市江宁区龙眠大道639号


title: WWOX promotes osteosarcoma development via upregulation of Myc

city: Jerusalem

first: Rami

last: Aqeilan

address: Ein Kerem

country: Israel

institute: Hebrew University of Jerusalem


title: WWOX promotes osteosarcoma development via upregulation of Myc [RNA-Seq]

summary: Osteosarcoma (OS) is an aggressive bone tumor that primarily affects children and adolescents. This malignant tumor is highly aggressive, associated with poor clinical outcomes, and metastasizes mainly to the lungs. Due to its rarity and biological heterogeneity, limited studies of its molecular basis exist, thus hindering the development of effective therapies. WW domain-containing oxidoreductase (WWOX) spans one of the most active and common fragile sites that is frequently altered in human OS. The combined deletion of Wwox and Trp53 using Osterix1-Cre transgenic mice has been shown to accelerate OS development. In this study, we generated a traceable OS mouse model, SKO-Trp53 or DKO-Wwox/Trp53, expressing a tdTomato reporter. By tracking tomato expression at different time points, we detected the early presence of tdTomato-positive cells in the bone marrow (BM) mesenchymal stem cells (MSCs) of non-OS bearing mice, young BM (yBM). We found that DKO yBM cells, but not SKO yBM cells, exhibited tumorigenic traits both in vitro and in vivo. Molecular and cellular characterization of these DKO yBM cells revealed their resemblance to OS tumor cells. Interestingly, one of the observed significant transcriptomic changes in DKO yBM was the upregulation of Myc and its target genes, as compared to SKO yBM cells. Intriguingly, Myc-chromatin immunoprecipitation sequencing (ChIP-Seq) revealed increased enrichment on Myc targets, which were upregulated in DKO yBM cells. Restoration of WWOX in DKO-yBM cells reduced Myc protein levels. As a prototype target, we demonstrated upregulation of MCM7, a known Myc target, in DKO yBM relative to SKO yBM.  Inhibition of MCM7 expression using Simvastatin resulted in reduced proliferation and tumor cell growth of DKO yBM cells. Our findings revealed BM-MSCs as a platform to study OS and Myc and its targets as WWOX effectors and early molecular events during osteosarcomagenesis.

overall_design: collect yBM from non tumor bearing mice at different time points in addition to the collection of BMT and tumors at the time of tumor detection to validate the genetic makeup in all these gropups compared to the control BM cells (Cre negative mice)

first: Rania

last: Akkawi

first: Osama

last: Hidmi

first: Ameen

last: Haj Yehia

first: Judith

last: Diment

first: Yotam

last: Drier

middle: I

first: Gary

last: S Stein


title: Mutual regulation of novel transcription factors POX_c03583 and POX_a00954 positively modulates the biosynthesis of raw-starch-degrading enzymes in Penicillium oxalicum

city: Nanning

first: Hao

last: Guo

state: Guangxi

address: No. 100 East University Road, Nanning

department: College of Life Science and Technology

institute: Guangxi University

summary: In order to investigate the regulatory function of POX_a00954 on Raw Starch Digesting Glucoamylase production in Penicillium oxalicum,we deleted POX_a00954 in Penicillium oxalicum Δku70 ,and we want to investigating the function of deletion of POX_a00954 at transcriptional level.

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of  at 24h after tansfer to the enzyme production medium with starch (the only carbon source).

first: Shuai

last: Zhao


title: Precise hourly personalized embryo transfer significantly improves clinical outcomes in patients with repeated implantation failure

city: GuangZhou

first: Yameng

last: Xu

address: 6 Chenggui Road, East District

institute: Boai Hospital of Zhongshan Affiliated to Southern Medical University

summary: This was a retrospective study enrolling patients with a history of RIF who received at least one autologous high-quality blastocyst during the subsequent FET cycle. Patients were divided into two groups: Group rsERT, comprising patients who underwent rsERT-guided pET (n=115), and Group FET, comprising patients who underwent standard FET without rsERT (n=272). Of the patients who underwent rsERT, 39.1% (45/115) were receptive, and 60.9% (70/115) were non-receptive. Group rsERT patients showed a significantly higher probability of achieving both a positive human chorionic gonadotropin rate (63.5% vs. 51.5%, P=0.03) and clinical pregnancy rate (54.8% vs. 38.6%, P=0.003). In the subgroup analysis, Group rsERT patients with non-receptive results showed a significantly higher clinical pregnancy rate than patients in Group FET (58.6% vs. 38.6%, P=0.003). Furthermore, Group rsERT patients with receptive results guided by rsERT with a precise window-of-implantation time showed a higher clinical pregnancy rate (48.9% vs. 38.6%, P=0.192) compared with patients who underwent standard-time FET, although the difference was not significant. Hourly precise rsERT can significantly improve the probability of achieving clinical pregnancy in patients with RIF, especially in those with non-receptive rsERT results.

overall_design:
Patients were divided into two groups: Group rsERT, comprising patients who underwent rsERT-guided pET (n=115), and Group FET, comprising patients who underwent standard FET without rsERT (n=272).
This dataset includes the samples from the Group rsERT patients.

first: Jing

last: Du

first: Yangyun

last: Zou

first: Xiufeng

last: Lin


title: Genome-wide binding sites of Mss11 in  Candida glabrata

first: Lu Ling

last: Wang

address: 170 Danshui Road

institute: Ruijin hospital,school of medicine,shanghai jiaotong university

summary: We found Mss11 as a transcription factor is vital for the adhesion and biofilm formation abilities of C. glabrata, and it consequently impacts its virulence. This modulation is achieved by regulating C. glabrata Epa1 and Epa6 expression. To analyze Mss11 regulation of EPA1 and EPA6 expression further, we constructed the FLAG-tagged Mss11 and conducted ChIP-seq. The results revealed that Mss11 exhibited extensive binding across all chromosomes of C. glabrata, with enriched peaks predominantly concentrated within specific genomic features. In particular, most Mss11 binding sites were located within promoter regions of the genes (89.01%), with a smaller fraction in the upstream regions (4.95%) and the remainder distributed among the exon (3.30%) and intergenic (2.75%) regions. This binding pattern aligned with the expected behavior of Mss11 as a transcription factor. Notably, our investigation revealed that Mss11 binds to approximately 2829 bp upstream of EPA1 and 2576 bp upstream of EPA6, as well as to the promoter regions of the subtelomeric silencing-related genes SIR4, RIP1, and RAP1.

overall_design: Chromatin immunoprecipitation DNA-sequencing(ChIP-seq) for the FLAG-tagged and the untagged Mss11 protein in Candida glabrata

first: Luling

first: Sijia

last: Huang

first: Juntao

first: Jinyan

last: Liu

first: Mingjie

last: Xiang


title: Carbon/nitrogen metabolism in responses to phosphate deficiency as revealed by comparative transcriptome profiling in nodules of the model cultivar Williams 82 (soybean)

city: Lubbock

first: chien

middle: Van

last: ha

address: 1006 Carton Avenue, Box 43135

department: IGCAST

institute: texas tech university

summary:
To understand the responses of plants to environmental stresses will help mitigate the problems via creating stress-tolerant crop.Whole genome DNA  microarrays were used to compare the nodule transcriptome profiling of soybean ‘Williams 82’ grown in vermiculite and subjected to low (0.1 mM; LP) or adequate (2.0 mM; HP) Pi levels. Plants were inoculated with two Bradyrhizobium diazoefficiens strains (USDA110 vs. CB1809), which exhibited contrasting growth and nodulation patterns under LP conditions, with the former model strain displaying a lower Pi-stress acclimatization in combination with the model Williams 82. Affymetrix’s whole Soybean Gene Expression Microarray (66K) was used.
Microarrays were used to compare the nodule transcriptomes of the model soybean ‘Williams 82’ plants grown in vermiculite and subjected to low (0.1 mM) or sufficient (2.0 mM) inorganic phosphate levels

overall_design: Plants were inoculated with two Bradyrhizobium diazoefficiens strains (USDA110 vs. CB1809) and exposed and to low (0.1 mM) or sufficient (2.0 mM) Pi levels. Nodule samples were collected at 35 day after sowing for RNA extraction and hybridization on Affymetrix microarrays.

first: C

middle: V

last: Ha

first: S

last: Suliemans

first: M

last: Tanaka

last: Seki

first: L

last: Tran

first: D

last: Le

middle: D

first: Y

last: Watanabe


title: RNA-seq data for T-47D ER.WT and ER.D538G cells treated with investigational endocrine therapies [NGS4917_RNA]

city: South San Francisco

first: Marc

last: Hafner

address: Building 45-1, 1 DNA Way

department: Oncology Bioinformatics

institute: Genentech

summary: T-47D cells expressing either wildtype (parental) or mutant ER (D538G) were treated with ER antagonist/degraders for 24 hours and then subject to gene expression analysis

overall_design: Bulk RNA-Seq

first: Ciara

last: Metcalfe

first: Jane

last: Guan

first: Jinchu

last: Vijay


title: Gene expression profile at single-cell level of Rspo3-overexpressing xenograft from C57BL/6 mice

city: Shanghai

first: Cong

last: Zhou

state: None Selected

address: 160 Pujian Road, Pudong New Area, Shanghai, China,200127.

institute: Renji hospital

summary: R-Spondin 3 (Rspo3) has been reported to exert either oncogenic or tumor suppressive functions in tumorigenesis. However, the exact roles and the molecular mechanisms of RSPO3 in colon cancer development are not explored. Here, single-cell RNA-seq was performed to deeply dissect the underlying mechanism by which Rspo3 inhibits colorectal tumorigenesis and growth.

overall_design: Murine MC38-RSPO3-OE and MC38-Ctrl xenograft tissues from C57BL/6 mice were harvested to perform scRNA-seq.


title: FACT-mediated depletion of macroH2A-nucleosome regulates the cell response of macrophage

first: ji

last: yiliang

address: No. 10 right outside the Western headlines

department: Department of Immunology

institute: Capital Medical University

summary: The histone variant macroH2A has been shown to generally associate with transcriptionally silent chromatin states. However, how macroH2A regulates the chromatin structure and functions in transcriptional process still remains elusive at the molecular level. In this study, we demonstrate that the incorporation of macroH2A does not affect the stability and the folding dynamics of nucleosome, but greatly impairs the FACT’s maintenance function at the nucleosome level. FACT can greatly impair the stability of macroH2A nucleosome, and quickly deplete the macroH2A nucleosome after the first unfolding process. Furthermore, we identify the key residue S139 of macroH2A, whose mutation can rescue the FACT’s function to maintain nucleosome integrity. Genome-wide analyses show that S139 mutation in macroH2A reshapes the position of macroH2A and regulates the stimulation-induced transcription in macrophage. Our findings provide mechanistic insights of how histone variant macroH2A coregulates with FACT at the nucleosome level and functions in cell response of macrophage in immunity.

overall_design: RNA-seq for vector,overexpress macroH2A and macroH2AS139A in RAW264.7 cells

first: Ping

last: Chen


title: Gene expression data from DLPFC of schizophrenia patients

first: Sergi

last: Mas

address: Casanova 143, Unidad Farmacologia, Facultad de Medicina, Barcelona

department: Pharmacology Unit

institute: University of Barcelona

summary: We analyzed gene co-expression modules (clusters of genes with highly correlated expression) in the dorsolateral prefrontal cortex (DLPFC) of postmortem brains from patients with schizophrenia and healthy controls. We aimed to identify the co-expressed modules that reflect the genetic differences between clozapine-treated and non-clozapine-treated patients with schizophrenia as a proxy of TRS.


title: HUMAN POLD3 COORDINATES LEADING AND LAGGING STRAND IN MITOTIC DNA SYNTHESIS

city: Geneva

first: Vasilis

last: Dionellis

address: 30, quai Ernest-Ansermet

country: Switzerland

institute: University of Geneva

summary: Deregulation of origin firing and licensing, shortage of deoxyribonucleotides in the cell and interference between transcription and replication are among the causes of DNA replication stress in cancer cells. This leads in various ways (notably, through common fragile sites expression and uncomplete replication of late-replicating regions of the genome during S phase) to the necessity of finishing DNA replication in mitosis by a mechanisms called Mitotic DNA synthesis (MiDAS), which is related to Break-Induced Replication (BIR). Even if it is of primary importance for cancer cells, the molecular mechanism of MiDAS, and generally of BIR, is not yet well understood. Recently, the third subunit of the eukaryotic DNA polymerase delta (POLD3) has been recognized as a key player of BIR, though its role is not yet clear. In this work, using a protocol established in our group to map at high resolution newly replicated DNA at MiDAS sites, we provide new insights into the molecular role of POLD3 in this repair mechanism. In particular, by analyzing MiDAS in mutant HeLa clones lacking the PCNA-interacting domain of POLD3, we demonstrate that the interaction between POLD3 and PCNA is required for coordinating leading and lagging strand synthesis in MiDAS. This work represents an important step forward towards the comprehension of the molecular mechansisms of Mitotic DNA synthesis, the full understanding of which is of primary importance for the possible development of novel cancer therapies targeting BIR-related pathways.

overall_design: EdU-seq from HeLa cells in S phase and upon induction of Mitotic DNA Synthesis

first: Demetrio

last: Turati

first: Laurence

last: Tropia

first: Thanos

last: Halazonetis


title: Targeting FAM3D improves renal fibrosis via inhibiting tubular cell inflammation and pyroptosis

city: Guangzhou

first: Xiaolong

last: Li

address: 1838 North Guangzhou Ave

department: Nanfang Hospital

institute: Southern Medical University

summary: Renal fibrosis is the common pathological feature of CKD and plays a key role in the progression of CKD to ESRD. However, the underlying mechanisms of renal fibrosis initiation and progression remains unclear. FAM3D belongs to FAM3 gene family and is associate with nutrient regulation and inflammation. In this study, we found that FAM3D was de novo expressed in tubules during CKD and positively correlated with fibrogenesis. Knockout of tubular FAM3D effectively improved UIRI- or UUO-induced renal fibrosis. Mechanistically, FAM3D depletion suppressed NF-κB activation in epithelial cells via FPRs/MAPK pathway and then alleviated cell pyroptosis. Furthermore, blockade of FPR1/2 prevented renal inflammation, tubular cell pyroptosis, and fibrosis development. Our findings provided the first evidence for the critical role of FAM3D in renal fibrosis progression.

overall_design: To verify the potential mechanism by which FAM3D protects CKD, we established UUO models and performed RNA-seq in WT and FAM3DCKO mice. We compared the gene expression differences between the two groups and performed KEGG and GSEA enrichment analysis


title: A critical role of the mitochondrial permeability transition pore (mPTP) in the survival of senescent cells

city: Barcelona

first: Oscar

last: Reina Garcia

state: Barcelona

address: C/Baldiri Reixac 10

department: Biostatistics and Bioinformatics

institute: IRB Barcelona

summary: Senescent cells are present in many pathological contexts and their elimination by pharmacological agents, known as senolytics, is a promising therapeutic strategy. Senescent cells exhibit distinctive mitochondrial adaptations, including an abnormally high influx of calcium from the endoplasmic reticulum. Here, through a genome-wide CRISPR/Cas9 screen, we identify the gene PPIF, encoding the mitochondrial protein cyclophilin D (CypD), as a senolytic target. CypD promotes the opening of the mitochondrial permeability transition pore (mPTP) and we show that senescent cells undergo frequent events of transient mPTP opening, known as mPTP flickering. Inhibition of CypD using genetic or pharmacologic tools, including cyclosporin A, impairs mPTP flickering, leading to toxic accumulation of mitochondrial calcium and cell death specifically in senescent cells. Pharmacological inhibition of NCLX, another mitochondrial Ca2+ efflux channel, also leads to senolysis. Our study links mPTP flickering to the survival of senescent cells and identifies novel targets for aging-associated diseases.

overall_design: Mouse embryonic stem cells (mESC) were induced to differentiate by the removal of leukimia inhibitory factor (LIF) and addition of retinoic acid for 5 days. Differentiated cells (diff) were induced to senesce via irradiation (IR), CDK4/6 inhibition (palbociclib, PD) or doxorubicin (doxo). 7 days after the senescence inducers were adminstered, Cas9 was activated in senescent cells by the addition of doxycycline to the media for 10 days. Doxycyline was also adminstered to non-senescent differentiated cells (doxy), and to the untreated mESCs (ESC). Screen was conducted in biological triplicate (R1, R2, R3)

first: Marta

last: Kovatcheva


title: Genetic and pharmaceutical targeting of Suv39h1 ameliorates renal fibrosis by unlocking CXCL10 transcription [II]

first: kong

last: ming

address: 南京市江宁区龙眠大道639号

first: Ming

last: Kong

first: Xiaoyan

last: Wu

first: Aoqi

last: Kang

first: Yajun

last: Luo


title: Simulating cell-free chromatin using preclinical cancer models for liquid biopsy applications [RNA-Seq]

city: Toronto

first: Scott

middle: Victor

last: Bratman

state: ON

address: 101 College Ave.

department: Medical Biophysics

country: Canada

institute: Princess Margaret Cancer Centre

summary: Cell-free DNA circulates in blood bound to nucleosomes, forming cell-free chromatin (cfChromatin) that retains epigenetic features, including nucleosome positioning and histone modifications. cfChromatin provides a rich source of cancer biomarkers; however, low abundance of tumor-derived cfChromatin and limited availability of clinical samples pose challenges for liquid biopsy research. To address this, we developed a framework to simulate cfChromatin nucleosomal distributions using nuclease-treated conditioned media from tissue cultures. Whole-genome sequencing confirmed that inferred nucleosome positioning reflected cell-type-specific gene expression and chromatin accessibility patterns, and comparisons with plasma cfChromatin from xenografted mice revealed concordant nucleosome profiles. Notably, simulated cfChromatin displayed stronger tumor-specific nucleosome profiles than patient plasma, where hematopoietic-derived cfChromatin dilutes signal. We further leveraged simulated cfChromatin to advance cell-free chromatin immunoprecipitation and sequencing methods, identifying repressive and bivalent chromatin domains predictive of transcriptional activity. Altogether, our results demonstrate utility of simulated cfChromatin as a scalable preclinical tool for liquid biopsy research.

overall_design: We performed gene expression profiling analysis by RNA-Seq using CAMA-1 and MCF7 cells.

first: Sasha

last: Main

first: Steven

last: De Michino

first: Lucas

last: Penny

first: Aleem

last: Aamir

first: Tina

last: Keshavarzian

first: Benjamin

middle: H

last: Lok

first: Robert

last: Kridel

first: David

middle: W

last: Cescon

first: Michael

middle: M

last: Hoffman

first: Mathieu

last: Lupien


title: Simulating cell-free chromatin using preclinical cancer models for liquid biopsy applications [cfChIPseq]

overall_design: Chromatin Immunoprecipitation DNA sequencing (ChIP-Seq) of media cell-free chromatin (cf-chromatin) from SU-DHL-6 cells, at varying input concentrations (H3K4me3, 30ng and 300ng; H3K27me3, 10ng, 30ng, and 300ng) after 30 minutes of micrococcal nuclease (MNase) digestion. Biological replicates were generated per condition.


title: Accurate quantification of CRISPR effects in pooled FACS screens using Waterbear

city: San Francisco

first: Alexander

last: Marson

address: 1650 Owens St

institute: Gladstone-UCSF Institute of Genomic Immunology

summary: CRISPR screens are powerful tools to identify key genes that underlie biological processes. One important type of screen uses fluorescence activated cell sorting (FACS) to sort perturbed cells into bins based on the expression level of a marker gene, followed by guide RNA (gRNA) sequencing. Analysis of these data presents multiple statistical challenges due to multiple factors including the discrete nature of the bins and typically small numbers of replicate experiments. To address these challenges, we developed a robust and powerful Bayesian random effects model and software package called Waterbear. Furthermore, we used Waterbear to explore how various experimental design parameters affect statistical power to establish principled guidelines for future screens. Finally, we experimentally validated our model findings that, when using Waterbear for analysis, high power is maintained even at low coverage and a high multiplicity of infection. We anticipate that Waterbear will be of broad utility for analyzing FACS-based CRISPR screens.

sample_organism:
Homo sapiens
synthetic construct

platform_organism:
Homo sapiens
synthetic construct

overall_design: Pooled CRISPR screen followed by FACS to sort CD25 (IL2RA) high or low expressing cells.

first: Harold

last: Pimentel

first: Jacob

last: Freimer

first: Maya

last: Arce

first: Christian

last: Garrido

first: Jonathan

last: Pritchard


title: WWOX promotes osteosarcoma development via upregulation of Myc [ChIP-Seq]

first: Rami

last: Aqeilan

overall_design: ChIP-Seq c-Myc DKO WWOX and p53 deletion

first: Rania

last: Akkawi

first: Osama

last: Hidmi

first: Ameen

last: Haj Yehia

first: Judith

last: Diment

first: Yotam

last: Drier

first: Gary

last: S Stein


title: Efferct of Vista deficiency on mucosal damage in DSS-induced colitis

first: Binfeng

last: Chen

address: 58 Zhongshan Second Road

institute: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University

summary: To investigate the effect of Vista, a novel immune checkpoint, on intestinal damage of DSS(dextran sulfate sodium)-induced colitis mice.

overall_design: Vista-/- and WT mice were orally administrated with 2% DSS in drinking water for the induction of colitis and subsequently the colons were collected respectively. Three biological replicates were performed for RNA-sequencing in each group.

first: Hui

last: Zhang


title: A bone regenerative strategy based on extracellular vesicles transporting citrate for promoting biomineralization [QH]

city: Wuhan

first: yiqian

last: yu

state: Hubei

address: Luoyu Road 237#, 430079, Wuhan, Hubei

institute: wuhan university

summary: The mineralization of extracellular matrix (ECM) rich in collagen is a biological process in many bones. It is well known that organic molecules from the extracellular matrix of mineralized tissues are crucial for constructing apatite minerals. Here we found that differences in cellular metabolic status significantly affect the degree of mineralization. The metabolite citrate, as a component of apatite nanocomposites, is crucial to the biomineralization of bones. Citrate is transported to the ECM through extracellular vesicles (EVs) and amorphous calcium phosphate (ACPs). Functionally, citrate can bridge more Ca2+ in EVs, contributing to higher intra-fiber mineralization. EVs produced by cells with active metabolic levels can improve the mineralization of poorly mineralized cells. The results indicate that the content of EVs can reflect the metabolic state of cells, thereby regulating the function of ECM. In general, this work reveals the complex metabolic process as a way to regulate biomineralization and proposes a new form of molecular transport, which provides a new bio-inspired strategy for bone regeneration.

overall_design: The mRNA profiles of mouse E14.5 frontal bone of the calvaria and parietal and inerparietal bone of the calvaria

first: Wenjin

last: Cai

first: Jinglun

first: Yufen


title: A bone regenerative strategy based on extracellular vesicles transporting citrate for promoting biomineralization

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

overall_design: Refer to individual Series


title: Transcriptome-wide RNA structure probing with temporal resolution

city: PRINCETON

first: Danyang

last: Wang

state: NJ

address: 307 Frick Chemistry Laboratory, Washington Road

institute: Princeton University

summary: Reactive small-molecule probes are widely used for RNA structure probing, however current approaches largely measure average RNA transcript dynamics and do not resolve structural differences that occur during folding or transcript maturation. Here, we present SNIPER-seq, an RNA structure probing method relying upon metabolic labeling with 2’-aminodeoxycytidine, structure-dependent 2’-amino reaction with an aromatic isothiocyanate, and high-throughput RNA sequencing. Our method maps cellular RNA structure transcriptome-wide with temporal resolution enabling determination of transcript age-dependent RNA structural dynamics. We benchmark our approach against known RNA structures and investigate the dynamics of human 5S rRNA during ribosome biogenesis, revealing specific structural changes in 5S rRNA loops that occur over the course of several hours. Taken together, our work sheds light on the maturation and coordinated conformational changes that take place during ribosome biogenesis and provides a general strategy for surveying evolving RNA structural dynamics across the transcriptome.

overall_design: SNIPER-Seq of six samples from HEK293T cells, including two treated with DMSO as control, two treated with 2’-aminodeoxycytidine and isoS-N3 in living cells, and two treated with2’-aminodeoxycytidine after RNA extraction and reacted with isoS-N3 in vitro

first: Yongkang

last: Tang

first: Ang

last: Li

first: Lei

last: Sun

first: Ralph

last: Kleiner


title: Primate-specific ZNF808 is essential for pancreatic development in humans [RNA-seq]_NEW

city: Exeter

first: Nick

last: Owens

state: Exeter

address: Barrack Road

institute: University of Exeter Medical School

summary: Functional investigation of the role primate-specific gene ZNF808 over pancreas differentiation. Loss of function of ZNF808 is a cause of pancreatic agenesis, which is a failure of pancreas development.

overall_design: Gene expression measured by RNA-seq over timecourse of pancreatic differentiation later stages in WT and ZNF808 KO conditions.

first: Michael

last: Imbeault

first: Jouni

last: Kvist

first: Hossam

last: Montaser

first: Timo

last: Otonkoski


title: Primate-specific ZNF808 is essential for pancreatic development in humans [ChIP-seq]_NEW

overall_design: ChIP-seq for H3K27me3 and H3K27ac over timecourse of pancreatic differentiation later stages in WT and ZNF808 KO conditions.


title: scRNA-seq analysis revealed the molecular characteristics of HSPCs and erythroid cells in bone marrow upon HAPC

city: Tianjin

first: Peng

last: Wu

address: 288 Nanjing Road

institute: IHCAMS

summary: High-altitude polycythemia (HAPC) is a most common chronic mountain sickness, characterized by excessive erythrocytosis caused primarily by persistent arterial hypoxia and ventilatory impairment. It has been a serious public health problem in high-altitude regions. Despite numerous studies on HAPC via genomics, transcriptomics or metabolome approaches, the pathogenesis of HAPC remains largely unclear. Here, we performed single-cell RNA sequencing to reveal the change of transcriptomics profiles of stem progenitor cells and erythrocytes in bone marrow of mice between HAPC subjects and healthy controls.

overall_design: Single-cell RNA sequencing for stem progenitor cells and erythrocytes in spleen of mice between HAPC models and healthy controls.

first: Weili

last: Liu

first: Xiaoru

first: Lingling

last: Pu

first: Jinhua

first: Lihong

last: Shi


title: scRNA-seq analysis revealed the molecular characteristics of erythroid cells in spleen upon HAPC

summary: High-altitude polycythemia (HAPC) is a most common chronic mountain sickness, characterized by excessive erythrocytosis caused primarily by persistent arterial hypoxia and ventilatory impairment. It has been a serious public health problem in high-altitude regions. Despite numerous studies on HAPC via genomics, transcriptomics or metabolome approaches, the pathogenesis of HAPC remains largely unclear. Here, we performed single-cell RNA sequencing to reveal the change of transcriptomics profiles of MNC in spleen of mice between HAPC subjects and healthy controls.

overall_design: Single-cell RNA sequencing for MNC in spleen of mice between HAPC models and healthy controls.

last: Zhang


title: Oncogenic fatty acid oxidation senses sleep deficiency-induced circadian disruption to promote tumorigenesis

city: Dalian

first: jinxin

last: lu

state: Liaoning

address: lvshunkou district lvshun south goad west sector No.9

institute: Dalian Medical University


title: Oncogenic fatty acid oxidation senses sleep deficiency-induced circadian disruption to promote tumorigenesis [circadian]

summary: Insufficient sleep and circadian disruption are associated with poor prognosis in cancer patients, yet how sleep deficiency (SD) disrupts circadian cellular biological process that promote tumor growth and development remains elusive. To investigate the effects of sleep deficiency on tumorigenesis, we evaluated the gene expression in the lung from KRASG12D/WT mice after sleep deficient treatment (7 weeks). Analyzing Gene Ontology (GO) Enrichment of significantly up-regulated genes from lung tumors of SD mice, we found that lipid metabolism processes were enriched in the top 20 GO terms. Lipid metabolomics results showed that SD dramatically stimulates fatty acid oxidation process during lung tumorigenesis. Moreover, genetic ablation of ACSL1, a key regulatory factor in FAO, marked reversed SD-promoted lung tumor development. In addition, SD triggered fatty acid oxidation to enhance cancer stem-like properties.

overall_design: RNA-seq circadian profiles genetated  for the lung taken every 4 hours for 24 hours in Ctrl and SD group in C57BL/6J mice.

first: Fei

last: Peng

first: Jinxin

last: Lu

first: Bai

last: Cui

first: Quentin


title: RNA Sequencing  Analysis of HPMVECs with 80% oxygen exposure or shCXCR1 treatment, and Control Cells

city: shanghai

first: Xiucheng

address: zhengmin road 557

institute: Shanghai pulmonary hospital

summary: Purpose: To study the effect of hyperoxia on HPMVECs. HPMVECs with or without shCXCR1 were cultured in 21% or 80% O2 for 3 days, and RNA-seq was performed.

overall_design: Total RNAs from the H1299 cells treated with hyperoxia treatment (24 h) and control cells were isolated and quantified. The high-throughput RNA sequencing analysis was performed by Shanghai Aksomics Biotech Company Ltd. (Shanghai, China). Briefly, The ribosomal RNA (rRNA) was removed from the total RNA using the NEBNext® rRNA Depletion Kit (New England Biolabs, Inc., Ipswich, MA, USA) following the manufacturer's instructions. RNA libraries were constructed by using NEBNext® Ultra™ II Directional RNA Library Prep Kit (New England Biolabs, Inc., Massachusetts, USA) according to the manufacturer’s instructions. Then, HTSeq software (v0.9.1) was used to obtain the transcript level (lncRNA) raw count as the expression profiling, and edgeR (v3.16.5) was used to perform normalization, and differentially expressed mRNAs were identified by p-value and fold change.

first: Wei

last: Zhuang


title: Lovastatin Promotes Phagocytosis of Glaucomatous Trabecular Meshwork Cells Through Up-Regulation of Low Density Lipoprotein Receptor

city: Qingdao

first: xuejiao

last: Yang

address: #16 Jiangsu Rd.

institute: the affiliated hospital of Qingdao University

summary:
Purpose: Primary open-angle glaucoma (POAG) is the most common glaucoma with elevated intraocular pressure (IOP). Dysfunction of trabecular meshwork (TM) cells affects the outflow facility of aqueous humor, resulting in high IOP. Phagocytosis is an important function for TM cells, this study aims to identify phagocytosis related genes/proteins and the effect of lovastatin in glaucomatous TM cells.
Methods: The phagocytic ability of immortal normal human TM cells (iHTM) and glaucomatous TM cells (GTM3) was detected by fluorescent beads and flow cytometry. RNA sequencing and proteomic analysis were used to identify different genes and proteins that potentially involved in regulating the phagocytic function of TM cells. The expression of low density lipoprotein receptor (LDLR) in iHTM and GTM3 was validated by immunofluorescence staining and Western blot. Lovastatin was used to test the effect of LDLR on the phagocytosis of TM cells. The expression of LDLR and the phagocytic ability was measured by western blot and fluorescent beads respectively.
Results: The Phagocytosis of GTM3 was significantly weaker than that of iHTM. The integrated analysis upon the transcriptome and proteome identified 3 differentially expressed genes/proteins closely related to phagocytosis of cells, including DAB2: NM_001244871.1, DNAJC6: NM_001256864.1 and LDLR: NM_000527.4. Their expression in GTM3 was obviously lower than that in iHTM. In addition, we have further illustrated the decreased expression of LDLR in GTM3 by immunofluorescence staining and Western blot. However, Lovastatin was found to increase its expression and the phagocytosis ability of GTM3.
Conclusions: Three phagocytosis-related genes/proteins were obviously decreased in GTM3 compared to iHTM, they might be responsible for the decreased phagocytic function of TM cells in glaucoma. The up-regulation of LDLR by Lovastatin can enhanced the phagocytosis of GTM3, suggesting Lovastatin might be a new potential medicine to promote the phagocytosis of TM cells in glaucoma.

overall_design: To compare the different gene expression between iHTM and GTM4. Three iHTM and three GTM3 samples were used.

first: Xuejiao

first: Wenshi

last: Chen

first: Junwei

last: Yan

first: Lu

first: Yao

last: Zong

first: Xian


title: Single nucleus RNAseq of VHL hemangioblastomas

city: Bethesda

first: Prashant

last: Chittiboina

state: MD

address: 3D20, 10 Center Drive

department: NINDS

institute: NIH

summary: Hemangioblastomas are frequently associated with Von-Hippel Lindau (VHL) disease, but underlying transcriptional and epigenetic alterations are poorly understood. We performed single nucleus RNAseq on VHL cerebellar hemangioblastomas

overall_design: VHL hemangioblastomas from two patients were dissociated into single nuclei and RNAseq was performed comparing transcriptomic profiles before and after Vorinostat treatment

first: David

last: Asuzu


title: Simulating cell-free chromatin using preclinical cancer models for liquid biopsy applications [cfMNase]

first: Scott

last: Bratman

overall_design: We subjected HCT116 and CAMA-1 conditioned media to a nuclease digestion with MNase (variable digestion time, including no digestion and one to 30-minutes).  We also subjected A549, MCF7, and SUD-HL-6 conditioned media to a nuclease digestion with MNase (30-minutes). Following MNase treatment, we purified cell-free DNA from all samples and conducted low-pass WGS, a technique which we called cell-free MNase-Seq (cfMNase-Seq).

first: Sasha

last: Main

first: Steven

last: De Michino

first: Lucas

last: Penny

first: Aleem

last: Aamir

first: Tina

last: Keshavarzian

first: Benjamin

last: Lok

first: Robert

last: Kridel

last: Cescon

first: Michael

last: Hoffman

first: Mathieu

last: Lupien


title: Simulating cell-free chromatin using preclinical cancer models for liquid biopsy applications [ATAC-Seq]

overall_design: We performed open chromatin profiling by the assay for transposase-accessible chromatin with sequencing (ATAC-Seq) of cellular chromatin from CAMA-1 cells. ATAC-seq from CAMA-1 cells was performed with biological replicates.


title: Soluble VE-cadherin disrupts endothelial barrier function via VE-PTP/RhoA signalling

city: Wuerzburg

first: Natalie

last: Burkard

address: Oberduerrbacherstr. 6

department: Experimentelle Viszeralchirurgie

institute: Universitätsklinikum Würzburg

summary: We generated recombinant human sVE-cadherin (extracellular domains EC1-5) which was applied to human dermal microvascular endothelial cells (HDMEC) to investigate it`s role in endothelial barrier function. In other experiments we observed that sVE-cadherin disrupted endothelial barrier function by dismantling the VE-cadherin complex at cell borders via VE-PTP-dependent RhoA activation. The sequencing project compares untreated HDMEC vs treated cells.

overall_design: Comparative gene expression profiling analysis of Soluble VE-cadherin treated and control human primary endothelial (HDMEC) cells

first: Juna-Lisa

last: Knop

first: Mugdha

last: Srivastava

first: Nicolas

last: Schlegel


title: Investigation of anti-cancer effects of 6-shogaol on glioma through analysis of transcriptome and experimental verification

city: wenzhou

first: xiandong

last: zhu

address: The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai

department: Department of Hepatobiliary Surgery

institute: The First Affiliated Hospital, Wenzhou Medical University,

summary: Glioma is one of the most fatal and complex cancer types. Patients have poor prognosis due to aggressive disease progression or tumor recurrence, resulting in poor survival. Ginger (Zingiber officinale Roscoe) is extensively regarded as a traditional Chinese herbal medicine or condiment in cooking in Asia. 6-shogaol, the most abundant ingredient in ginger, has antiviral, anti-inflammatory, and anticancer properties. However, there are no data on 6-shogaol against glioma, and its potential mechanism has not been thoroughly elucidated. Our study demonstrated that 6-shogaol significantly inhibited glioma cell growth, migration and invasion, and induced cell apoptosis in vitro and in vivo. Transcriptomic analysis and western blot data indicated that 6-shogaol significantly upregulated the p38-MAPK pathway, which plays a key factor in its powerful antitumor effect. These findings demonstrated that 6-shogaol has a strong anti-tumor activity in glioma, which through regulating the p38-MAPK signaling pathway.

overall_design: The U251 cancer cells were treated with or without 6-shogaol (60μm) for 24 h

first: Xiandong

last: Zhu

first: Yan

last: Zhang

first: Xiaowu

last: Wang

first: Yongqiang

first: Mengmeng

last: Ji

first: Linxiao

last: Sun

first: Qichuan

last: Zhuge

first: Shengwei

last: Huang


title: A bone regenerative strategy based on extracellular vesicles transporting citrate for promoting biomineralization [timepoint]

first: yiqian

last: yu

overall_design: The mRNA profiles of mouse frontal bone of the calvaria at E8.5, E9, E9.5, E10, E10.5, E11, E11.5, E12, E12.5, E13.5 and E14.5

first: Wenjin

last: Cai

first: Jinglun

first: Yufen


title: DYNAMIC INTERPLAY BETWEEN TUMOR AND MICRO-ENVIRONMENT DURING MULTIPLE MYELOMA DISEASE PROGRESSION

city: Liège

first: Jo

last: Caers

address: Avenue de l'Hôpital

country: Belgium

institute: CHU de Liège

summary: Characterizing the changes between normal, pre-malignant and active disease states increases our understanding of multiple myeloma (MM) pathogenesis and helps further the identification of novel preventive/therapeutic strategies. Here, using single cell multi-modal processing of whole bone marrow (BM) samples, we generated a single cell atlas of the BM from 123 individuals, including healthy volunteers, patients with monoclonal gammopathy of unknown significance (MGUS), smoldering MM (SMM) and active MM. We observed plasma cells alterations and MGUS/SMM early immune dysregulation, which increases as the disease progresses. We show evidence of population shifts in CD8+ T-cells, macrophages and classical dendritic cells. Shifts in CD8+ T-cells and macrophages were further associated with poor overall survival outcomes. We identified ligand-receptor interactions correlated to the downstream changes observed between pre-malignant and MM cells. Our findings show that myeloma tumorigenesis is associated with pathway dysregulation driven by gradual immunophenotypic changes in the tumor and tumor micro-environment.

overall_design:
Using single cell RNA sequencing, surface proteome profiling, and B lymphocyte antigen receptor profiling of unsorted, whole bone marrow aspirates, mononuclear fractions, we generated a cell atlas of the BM micro-environments from 123 individuals to explore tumor micro-environment during MM progression. These subjects included healthy volunteers (HV), and patients with monoclonal gammopathy of unknown significance (MGUS), smoldering MM (SMM) and active MM.
>>>Raw data for human samples not available due to patient privacy concerns<<<

first: Murat

last: Köse

first: Isabelle

last: Bergiers

first: Tine

last: Casneuf


title: Clinically relevant metabolic subtypes of lung cancer for immunotherapy

status: Public on Sep 30 2025

city: Seoul

first: Seo

middle: Young

last: Lee

state: Goyang-si,Gyeonggi-do

address: Ilsan-ro, Ilsandong-gu

country: South Korea

institute: National Cancer Center

summary: The metabolic pathway subtypes (MPSs) showed distinct differences in outcomes from anti-PD-(L)1 treatment. Using metabolic pathway–based clustering, we identified clinically relevant metabolic signatures that may be used to determine the efficacy of immuno-oncology drugs in non-small cell lung cancer (NSCLC). These findings suggest that metabolic features play a critical role in shaping the response to immuno-oncology therapies. To establish these relationships, we integrated individual clinical data, including clinicopathologic and genomic variables, as well as survival information, into the transcriptional analysis.

overall_design: This study was designed as a post hoc analysis of a prospective observational cohort conducted at the National Cancer Center Hospital in Korea between November 2017 and February 2021. Patients with stage IV non-small cell lung cancer (NSCLC) who had measurable lesions and were scheduled to receive anti–PD-(L)1 therapy were prospectively enrolled. Whole blood samples and archival tumor tissues were collected prior to treatment, and tumor responses were assessed by computed tomography or other imaging every 6 to 9 weeks until disease progression. Transcriptomic profiling of tumor tissues was performed using the NanoString Metabolic Pathways Panel, which measures the expression of 768 metabolism-related genes, to investigate metabolic heterogeneity. Unsupervised clustering with non-negative matrix factorization (NMF) was applied to identify distinct metabolic subtypes, followed by differential gene expression and pathway enrichment analyses, including GSVA and GSEA. The reproducibility and robustness of the identified subtypes were validated using an independent cohort from the GSE161537 dataset. Clinical, pathological, and genomic characteristics were integrated with transcriptomic data. Survival analyses using Kaplan–Meier curves and log-rank tests were conducted to compare progression-free survival and overall survival across subtypes, while Chi-squared and Fisher’s exact tests were applied to assess associations with categorical variables. Collectively, this experimental design enabled the identification and validation of clinically relevant metabolic pathway subtypes of NSCLC with potential implications for immunotherapy response.

first: Young-Joo

first: Seo-Young


title: Maternal plasma micro-RNAs in fetal congenital diaphragmatic hernia: A potential non-invasive tool for prenatal diagnosis and risk stratification

city: Chicago

first: Amir

middle: M.

last: Alhajjat

state: Illinois

address: 225 E Chicago Ave

institute: Ann & Robert H. Lurie Children's Hospital of Chicago

type: Non-coding RNA profiling by high throughput sequencing

summary: Congenital diaphragmatic hernia (CDH) is characterized by a wide range of morbidity. Although imaging studies are used for CDH risk stratification, these modalities remain limited in their predictive and informational capacity. Distinct miRNA profiles have been found in other prenatally diagnosed conditions including Twin–Twin Transfusion Syndrome. Furthermore, it is differentially expressed in amniotic fluid from pregnancies with severe CDH suggesting utility in risk stratification. We hypothesized that patients carrying fetuses with CDH would display a unique miRNA profile detectable within maternal plasma that will be associated with both disease and severity. There were 17 differentially expressed miRNAs including several previously implicated in CDH and pulmonary hypertension. Subgroup analysis revealed further differential expression in high-risk CDH patients with distinct clustering of patients with severe and mild disease. 10 miRNAs were associated with clinical severity including let-7c, miR-30 d, and miR-98, miRNAs associated with pulmonary hypertension in the literature. Gene target prediction identified interactions with VEGF and other genes relevant to CDH pathogenesis.These results support the hypothesis that maternal plasma miRNA can differentiate pregnancies with CDH from those carrying healthy fetuses. Furthermore, our findings indicate that maternal plasma miRNA can potentially predict severity of disease prenatally. A larger sample size and validation cohort is now prudent.

overall_design: Patients carrying fetuses with CDH (n = 20) and healthy singleton pregnancies (n = 8) were consented for peripheral blood collection. Small RNA sequencing was performed. Subgroup analysis included clinical factors associated with disease severity.

first: Daniel

last: Liesman

first: Cassandra

middle: B

last: Huerta

first: Steven

middle: T

last: Papastefan

first: Morgan

last: Langereis

first: Catherine

last: Redden

first: Hee Kap

last: Kang

first: Katherine

last: Ott

first: Lucas

last: Turner

first: Manmeet

last: Singh

first: Joyceline

last: Ito

first: Aimen

last: Shaaban


title: GAS41 controls nuclear morphology by targeting multiple genes encoding nuclear envelope proteins

city: 长春市

last: Liu

state: 吉林省

address: 东民主大街519转化医学院

institute: 1st hospital

summary: Nuclear morphology is normally maintained in a defined manner within a given cell type, and aberrant nuclear morphology correlates with a wide range of human diseases. However, the underlying mechanisms that define nuclear morphology are largely unknown. Here we show that depletion of YEATS family protein-GAS41 exhibits striking nuclear shape abnormalities.The misshapen nuclei can be rescued by GAS41 wild type, but not by GAS41 Y74A W93A mutant deficient in histone H3 lysine 27 acetylation (H3K27ac) binding. GAS41 depletion significantly decreased the expression of multiple genes encoding nuclear envelope (NE) architecture components including LMNB1, LMNB2, SYNE4 and LEMD2, and dysregulation of these genes directly leads to nuclear shape abnormalities. Using mass spectrometry and ChIP sequencing, we found GAS41 interacts with BRD2 and mediator components MED14 /MED23, and co-localizes with H3K27ac and BRD2 at target gene loci. The occupancy of BRD2 and MED14/MED23 at LMNB1, LMNB2, SYNE4 and LEMD2 is dependent on the presence of GAS41. Depletion of GAS41 or disruption of GAS41-H3K27ac recognition abrogated GAS41 binding at these gene loci, which further prevents the enrichment of BRD2, mediator complex as well as RNA polymerase II, thus consequently deactivated target gene expression and leading to nuclear morphology abnormalities. Overall, our study identified GAS41 as a novel nuclear shape regulator that works in concert with BRD2/mediator complex to control nuclear morphology

overall_design:
ChIP-seq of Flag-GAS41 was applied in HCT116 GAS41 KO cells transiently or stably expressing Flag-GAS41. ChIP-seq of H3K27ac was performed in HCT116 cells.
Flag ChIP-seq was applied in HCT116 GAS41 KO cells  stably expressing Flag-GAS41 Y74A W93A.

first: Deyu

last: Wang

last: Zhao

first: Lingling

last: Cao

first: Siwei

last: Zhang


title: Single-Cell Multi-Omics Sequencing Reveals the Dynamic Epigenome Landscape of Human Adult Spermatogenesis

city: Guangzhou

first: Lin

last: Li

address: Shatai South Road

department: Pathophysiology

institute: Southern Medical University

type: Methylation profiling by high throughput sequencing

summary: Stepwise and sequential cell fate transition accomplished by global transcriptional changes occurs across human spermatogenesis, but the epigenome roadmap and regulatory networks underlying this process have not been established. Here, we explore a single-cell multi-omics landscape of human adult testicular cells using the single-cell chromatin overall omic-scale landscape sequencing (scCOOL-seq) technique, deriving an unbiased multi-omics reference map of human adult spermatogenesis. The initial commitment to meiosis coincides with a novel dramatic DNA demethylation process in non-coding regions that highly overlapped with crossover and double strand break (DSB) hotspots. Chromatin accessibility mainly accounts for the global expression dynamics in human spermatogenesis. Further studies identify the cis- regulatory elements of several key regulators such as STRA8, ID3, HMGA1 and TEX29 in human spermatogenesis. Thus, our data characterize the regulatory networks orchestrating gene expression and chromatin configuration under the state of normal human spermatogenesis and its perturbation imposed by disease lesion, providing novel insights into the association of epigenome with germ cell development and male infertility.

overall_design:
In total, we analyzed 1097 scCOOL-seq data of normal human adult testicular cells and 176 scCOOL-seq data of testicular cells from one nonobstructive azoospermia (NOA) donor.
Samples 1-29 are RNA-seq data (UMI barcode RNA part), samples 30-1302 are scCOOL-seq data (DNA part).
*** All the raw fastq data have been uploaded to GSA for Human as access controlled data under accession HRA000148 (https://bigd.big.ac.cn/gsa-human/browse/HRA000148).

first: Xiaoyang


title: Impaired IL-10 Receptor Signaling Leads to Inflammation Induced Exhaustion in Hematopoietic Stem Cells

city: Irvine

first: William Lucas

middle: Paredes

last: Wadley

email: wwadley@uci.edu, Lucas.wadley@gmail.com

state: CA

address: 845 Health Sciences Road

department: Biological Chemistry

institute: University of California Irvine

summary: Chronic-inflammation compromises normal hematopoiesis, and interleukin-10 (IL-10) signaling is essential for restraining inflammatory responses. When inflammation persists, hematopoietic stem cells (HSCs) undergo proliferative exhaustion with loss of fitness and regenerative capacity. We previously showed that in JAK2V617F myeloproliferative neoplasm (MPN) primary monocytes exhibit impaired IL-10 signaling. Because clonal hematopoiesis is a hallmark of exhaustion, we hypothesize that impaired IL-10 signaling confers a selective advantage to clonal hematopoiesis by promoting inflammation-induced exhaustion in nonmalignant cells. We used an IL-10R blocking antibody in murine models with repeated exposure to lipopolysaccharide (LPS), an inflammatory stimulus, this showed IL-10R blockade exacerbated exhaustion phenotypes, increasing proliferation, myeloid skewing, and reduced HSC fitness relative to controls. In JAK2V617F murine models, JAK2V617F-expressing cells were not impaired by inflammatory exposure in the presence of IL-10R blockade, which in turn aggravated MPN-like phenotypes and clonal expansion. Taken together, these findings indicate that defective IL-10 receptor signaling prolongs inflammatory responses, accelerates exhaustion phenotypes, and reduces the competitiveness of normal hematopoietic clones in the context of hematologic malignancy.

overall_design: Wild-type C57BL/6J mice were intraperitoneally injected with 5ug LPS (L2880; Sigma-Aldrich) with or without 100ug IL-10R blocking antibody (112702; BioLegend), or phosphate buffered saline (DPBS; 14200075; ThermoFisher Scientific) for 72 or 24 hours prior to BM harvest for cell sorting using BD FACSAria Fusion sorter at the UCI Institute of Immunology Flow Cytometry Facility.

first: William

middle: L

first: Helen

last: Huang

first: Hew

middle: Y

last: Lai

first: Jane

last: Chen

first: Jianhong

last: Heidmann

first: Eli

last: Soyfer

first: Kalei

last: Guillermo

first: Eshika

last: Arora

first: Lauren

first: Brianna

last: Hoover

first: Angela

last: Fleischman


title: Oncogenic fatty acid oxidation senses sleep deficiency-induced circadian disruption to promote tumorigenesis [Ctrl vs SD]

first: jinxin

last: lu

overall_design: RNA-seq data of the lung tumor in Ctrl and  SD group in the KrasLSL-G12D/WT lung tumor model.

first: Fei

last: Peng

first: Jinxin

last: Lu

first: Bai

last: Cui

first: Quentin


title: Integrative Epigenomic and Genomic Profiling of HCC Patients to Identify Key Driver Signaling Pathways of HCC Progression and Poor Outcome

first: Xin

middle: Wei

last: Wang

address: 37 Convent Drive

department: Laboratory of Human Carcinogenesis

institute: National Cancer Institute

summary: Globally, hepatocellular carcinoma (HCC) accounts for 70-85% of primary liver cancers and is the second leading cause of male cancer death. Among patients with HCC there is widespread heterogeneity, yet just a single standard therapeutic, Sorafenib, which is only effective in patients with overactive MAP kinase signaling. Identifying homogeneous subgroups of HCC patients will improve our ability to develop more effective targeted treatment modalities derived from specific signaling pathways that lead to poor survival. Recently, many 'omics based studies have further described the current problem of cancer heterogeneity. Genomics is the application of high-throughput methods to analyze the expression of genes at a global level, while epigenomics focuses on epigenetic modifications, such as DNA methylation changes, across the genome. Though genome-wide analysis by various 'omics methods is popular, the integration of the data is uncommon. We hypothesize that the integration of patient expression data will reveal distinct epigenetic and genomic modifications in subsets of HCC patients that lead to poor outcome. In this study, we employed Illumina or Affymetrix array platforms to analyze paired tumor and non-tumor tissue specimens from 82 HCC patients in an integrative approach incorporating DNA methylation, somatic DNA copy number alteration (SCNA) and expression of mRNA and microRNA genes. First we performed a class comparison analysis between tumor and non-tumor patients to identify 2,173 differentially methylated genes (Illumina 27k BeadChip). Of those genes, only 621 overlapped with tumor-specific genes differentially expressed in the same patients (Affymetrix array). We further narrowed that tumor-specific gene list by removing only a subset of genes that correlated with methylation data. An epigenetic-driven gene signature of 46 genes was established using a correlation coefficient of -0.185 corresponding to the 95th percentile of the 1000-fold random distribution. In a similar manner, an SCNA-related gene signature made up of 2,722 tumor-specific genes was established using a correlation coefficient of 0.3 corresponding to the 99th percentile of the 1000-fold random distribution. The gene signatures do not significantly overlap and each has the ability to cluster HCC patients with poor outcome apart from patients with better prognosis. Moving forward, we plan to focus on key signaling pathways derived from integrated gene and miRNA expression data that are responsible for poor prognosis in patients. Upon identification, driver pathways will be validated in vitro and in vivo to elucidate the mechanisms of HCC progression and poor outcome.

overall_design: Illumina Human BeadChip Methylation microarrays were completed on 40 tumor HCC tissues and 88 non-tumor HCC tissues.


title: Cytokine–ontogeny interaction shapes macrophage transcriptional states (combined GM-CSF– and M-CSF–derived macrophages)

city: Schlieren

first: Florence

last: Vallelian

address: Wagistrasse 12

department: Department of Internal Medicine

institute: University Hospital and University of Zurich

summary: We generated eight macrophage states using a cytokine–ontogeny matrix, combining two macrophage ontogenies (M-CSF and GM-CSF) with four cytokines (IL‑4, IFN‑γ, IL‑10, TGF‑β). Bulk RNA‑seq on five biological replicates per condition revealed that PC1 (54% variance) segregated ontogeny: GM‑CSF states loaded negatively, M‑CSF states positively.  Gene‑set enrichment analysis of negative PC1 loadings highlighted NfkB programs, confirming the intrinsic inflammatory bias of GM‑CSF macrophages (Hamilton 2008; Hamilton et al. 2016)

overall_design: M-CSF–derived and GM-CSF–derived macrophages were stimulated with IL‑4, IFN‑γ, IL‑10, TGF‑β, or left untreated (control). Bulk RNA-seq was performed on five biological replicates per condition.

first: Dominik

last: Schaer

first: Livio

last: Baselgia

first: Elena

last: Duerst

first: Matthias

last: Peterhans


title: Hippocampus RNA-sequencing of aging rats with cognitive decline

city: Beijing

first: Shi

last: Cuige

address: 12 Dahuisi road

institute: National Research Institute for Family Planning

summary: Aging is an inevitable process for everyone. Aging is mostly characterized by decline of cognitive function. Themechanisms are still not clear. Hippocampus has been shown to participate in cognition process,the basic mechanism of which are involved in molecularalterations in genes expression. Objective of the present research was to find the transcriptomic changes influenced by aging in hippocampus using RNA-sequencing. The 22-monthrats with cognition decline were used as a model system to analyze the changes in transcriptional networks. There were121 differentially expressed genes identified in the hippocampus of aged rats, including 54 genes upregulated and67 genes downregulated. After GO analysis,differentially expressed genes were found to be enriched inprotein hetorotrimerization, positive regulation of kinase activity, multivesicular body,mitochondrial membrane, oxygen binding and protease binding. KEGG analysesshowed thatDEGs were mainly observed at biochemical signaling pathways, containing Neuroactive ligand-receptor interaction (likeAplnr,Htr2a,Nmur2,Rxfp3), Apelin signaling pathway(likeAplnr,Cdh1,Serpine1),Serotonergic synapse（like Htr2a,Tph2）,Tryptophan metabolism（Tph2）,and so on. These DEGsin the hippocampusmay be involved in the formation of learning and memory. At last, quantitative reverse transcription-polymerase chain reaction was applied to verify the RNAsequencing data.Altogether, the above analysis help to identify specific genes in the aging hippocampus, which might be used as potential molecular targets for the prevention and treatment of aging-related cognition disorders.

overall_design: Male,adult (4 months; n = 10) and aged (22 months; n =10) Sprague Dawley rats were used.Cognitive function in both rat groups were evaluated by Morris water maze. After the MWM test, three male rats from each group were randomly selected and the ventral hippocampus was harvested and processed for transcriptome sequencing.

first: Li

last: Hou

first: Cuige

last: Shi


title: Cytokine–ontogeny interaction shapes macrophage transcriptional states (M-CSF–derived macrophages)

summary: In M-CSF–derived macrophages, bulk RNA-seq was performed on five biological replicates per cytokine condition (IL‑4, IFN‑γ, IL‑10, TGF‑β). IL‑4 dominated PC1 (54% variance) driving a reparative module with EMT, UPR, and mTORC1 signatures, while IFN‑stimulated genes (Gbp4, Ifi44) were repressed.  PC2 (26% variance) spanned an inflammatory‑to‑remodeling continuum: IFN‑γ anchored the chemokine‑rich, IFN‑responsive pole (Ccl7, Ccl2, Ccl12), whereas TGF‑β anchored a matrix‑remodeling/angiogenic pole (Mmp14, Cav1, Cspg4); IL‑10 shifted modestly toward the IFN‑low quadrant.

overall_design: M-CSF–derived macrophages were stimulated with IL‑4, IFN‑γ, IL‑10, TGF‑β, or left untreated (control). Bulk RNA-seq was performed on five biological replicates per condition.


title: Single-cell RNA-sequencing resolves IL-4 and IFN-γ into distinct inflammatory trajectories within GM-CSF macrophages

summary: To account for the within-state heterogeneity of GM-CSF compared to M-CSF macrophages (Helft et al. 2015), we performed multiplexed scRNA-seq on 49,441 GM-CSF–derived macrophages stimulated with IL‑4, IFN‑γ, IL‑10, or TGF‑β. Cells were visualized by principal component analysis (PC1 = 13.21%, PC2 = 4.65%), which recapitulated patterns previously observed in bulk RNA-seq. IL‑4 displaced cells farthest along PC1 towards a cell cluster enriched for NfkB controlled gene expression with high Ccl22 and Ccr7, consistent with a dendritic‑cell‑like, T‑cell‑activating phenotype. IFN‑γ dominated PC2, retaining high MHC-II expression while adding a complement/interferon module (C1qb, C1qc, Gbp2, Irf1), and showed enrichment for IRF1/8 and STAT1 transcription factor signatures. TGF‑β and IL‑10 co-clustered in the PC1/PC2 low quadrant and shared expression of reparative markers including Chil3 and Cd24, forming an immunosuppressive, trophic branch distinct from either inflammatory pole. Together, these data show that within the GM-CSF lineage, IL‑4 and IFN‑γ drive orthogonal inflammatory trajectories, whereas IL‑10 and TGF‑β consolidate a shared remodeling program.

overall_design: GM-CSF–derived macrophages stimulated with IL‑4, IFN‑γ, IL‑10, TGF‑β, TNF‑α or left untreated were harvested on days 5 and 7 for multiplexed scRNA‑seq; only day 7 cells without TNF‑α (n = 49,441) were retained for analysis.


title: Cytokine–ontogeny interaction shapes macrophage transcriptional states

summary:
Macrophage ontogeny and local cytokines jointly govern tumor-associated macrophage behaviour, yet how these signals integrate to generate pro- or antitumor outputs is unknown. Here, we apply a reductionist, multi-scale pipeline to systematically map eight reference macrophage states generated by ex vivo differentiation of mouse bone marrow cells with macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF) and subsequent cytokine polarization (IFN-gamma, IL-4, IL-10, TGF-beta). We integrated transcriptomic, 3D spheroid, and in vivo metastatic analyses to discover a lineage dependent polarity switch: IL-4 drives an ARG1+, tumor-supportive programme in M-CSF macrophages but, via NfkB, induces a CCR7+ inflammatory phenotype in GM-CSF macrophages. IFN-gamma uniformly activates STAT1/IRF pathways, maintaining antitumor profiles, whereas IL-10 and TGF-beta maximally evoke SPP1+ immunosuppressive signatures after GM-CSF priming. Functional assays confirmed these transcriptional states dictate opposite effects on tumor growth, invasion, and pulmonary metastasis. Integration of all parameters yielded an "ontogeny cytokine code" that predicts macrophage function based on developmental history and cytokine milieu. Identifying CSF-defined lineage as a master regulator of macrophage heterogeneity provides a blueprint for precision immunotherapies that reprogram macrophages in solid tumors.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Targeting dendritic cells with a PD-L1 based bispecific antibody rejuvenates specific anti-tumor T cells

city: Dallas

first: Longchao

last: Liu

state: Texas

address: 6001 Forest Park Rd.

institute: UTSW

summary: Bispecific T-cell engagers (BiTEs) that preferentially target tumor-associated antigens to engage CD3 signaling have been approved to treat acute B-cell lymphoblastic leukemia. However, their applications in solid tumors have been hampered by short half-life and severe toxicity at therapeutic doses. Whether antigen-specific T cells would be rejuvenated by directing to tumor cells remains unclear. To address this, we designed a bispecific antibody (BsAb) which simultaneously targets CD3 and immune checkpoint PD-L1. Compared with conventional tumor cell targeting BsAb, PD-L1xCD3 generates superior anti-tumor immune responses in vivo. By single-cell sequencing of tumor-infiltrated T cells in different BiTE treatment, we found that PD-L1xCD3 treatment generate unique T cell subsets in the tumor microenvironment which contribute to the increased antitumor efficacy and reduced side effect.

overall_design: Tumor infiltrated T cells in different bispecific antibody treatment

first: Jiahui

last: Chen


title: Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation [hmC-seq (CRISPR)]

city: Miami

first: Luisa

last: Cimmino

state: Florida

address: 1501 NW 10th Ave, BRB 711

institute: University of Miami

summary: Enhancing TET2 activity through genetic or pharmacologic approaches, such as ascorbate supplementation, can slow myeloid malignancy progression. However, ascorbate alone may be insufficient to fully activate TET2 in malignant cells due to pharmacokinetic constraints and the need for chromatin remodeling to enable effective epigenetic reprogramming. Here, we identify a novel mechanism to enhance TET2 activity via all-trans retinoic acid (ATRA), which induces RARA-mediated TET2 transcription in myeloid leukemia cells and synergizes with ascorbate to promote DNA hydroxymethylation and chromatin remodeling at key myeloid differentiation loci. Using Tet1/2/3-deficient mice and primary human AML models, we show that ATRA plus ascorbate more effectively induces differentiation, inhibits leukemia stem cell self-renewal in a TET2-dependent manner, and sensitizes AML cells to targeted therapies in vivo leading to improved survival. These findings support the combined use of ATRA and ascorbate as a strategy to enhance TET2 activity for the treatment of myeloid malignancies.

overall_design: Non-target guide (NTG) or single guide RARA (sgRARA) CRISPR-knockout U-937 cells were treated 72hr with LAA (250µM) + ATRA (1µM) or vehicle control and then assayed for changes in hydroxymethylation by reduced representation enzymatic base-resolution 5hmC-seq

first: Tiffany

last: Leesang

first: Yoon-Sing

last: Yap

first: John

middle: P

last: Brabson

first: Panagiotis

last: Vlantis

first: Aristeidis

middle: G

last: Telonis


title: Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation [MV4-11 RNA-Seq]

overall_design: MV4-11 AML cells were treated 72hr with LAA (250µM) + ATRA (1µM) and then assayed for changes in gene expression by RNA-seq

first: Felipe

last: Beckedorff


title: Immune Profiling-Based Treatment for ANCA-Associated Glomerulonephritis with Ustekinumab

city: Hamburg

first: Yu

last: Zhao

address: Falkenried 94

department: Institute of Medical Systems Biology

institute: University Medical Center Hamburg-Eppendorf

summary: Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a life-threatening systemic autoimmune disease that frequently presents as crescentic glomerulonephritis (GN) leading to kidney failure1. Despite recent advances2, treatment for most patients with ANCA-associated GN relies on unspecific immunosuppressive agents that are hazardous and only partially efficacious. To develop an anti-T-cell cytokine treatment strategy based on the immunopathogenesis of the individual patient, we established the combination of rapid single-cell immune profiling with standard histopathological analyses of renal biopsies. We report two patients with biopsy-proven ANCA-associated GN who presented with renal failure and active urinary sediment despite immunosuppressive therapy. Our data suggest that the integration of single-cell immune profiling with clinical and histopathological information facilitates personalized anti-cytokine therapies, such as ustekinumab in ANCA-GN, and warrants further investigation.

overall_design: Single cell sequencing of kidney and blood T cells from ANCA-GN patients. We combined scRNA-seq with CITE-seq and also used hasttag to distinguish blood and kidney T cells.

first: Christian

middle: F

last: Krebs