A5047669998- Atherosclerosis and Cardiovascular Diseases
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Nuclear Receptors and Signaling
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- RNA regulation and disease
- RNA Research and Splicing
- Infrared Target Detection Methodologies
- TGF-β signaling in diseases
- Cardiovascular Health and Risk Factors
- Pulmonary Hypertension Research and Treatments
- Cardiac Fibrosis and Remodeling
- Genomic variations and chromosomal abnormalities
- Cancer-related gene regulation
- Cardiovascular Disease and Adiposity
- Coronary Interventions and Diagnostics
- Viral Infections and Immunology Research
- Pluripotent Stem Cells Research
- Hippo pathway signaling and YAP/TAZ
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
Chongqing University of Technology
2024
Stanford University
2018-2024
Cardiovascular Institute of the South
2019-2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2019-2024
Palo Alto University
2021-2024
Fu Wai Hospital
2022-2024
Academia Sinica
2023
Peking Union Medical College Hospital
2020
Wuhan University
2012-2019
Host pathogen-recognition receptors detect nucleic acid from invading viruses and initiate a series of signaling pathways that lead to the production type I interferons (IFNs) proinflammatory cytokines. Here, we found viral infection-induced deubiquitinase (DUB), ubiquitin-specific protease 25 (USP25) was required for host defense against RNA DNA viruses. The activation transcription factors IRF3 NF-κB impaired IFNs cytokines inhibited in Usp25-/- cells compared with wild-type counterparts...
Rationale: The gene encoding TCF21 (transcription factor 21) has been linked to coronary artery disease risk by human genome-wide association studies in multiple racial ethnic groups. In murine models, Tcf21 is required for phenotypic modulation of smooth muscle cells (SMCs) atherosclerotic tissues and promotes a fibroblast phenotype these cells. humans, expression inhibits disease. molecular mechanism which regulates SMC not known. Objective: To better understand how affects the phenotype,...
Smooth muscle cells (SMC) play a critical role in atherosclerosis. The Aryl hydrocarbon receptor (AHR) is an environment-sensing transcription factor that contributes to vascular development, and has been implicated coronary artery disease risk. We hypothesized AHR can affect atherosclerosis by regulating phenotypic modulation of SMC.We combined RNA-sequencing, chromatin immunoprecipitation followed sequencing, assay for transposase-accessible using vitro assays human SMCs, with single-cell...
Smooth muscle cells (SMCs) transition into a number of different phenotypes during atherosclerosis, including those that resemble fibroblasts and chondrocytes, make up the majority in atherosclerotic plaque. To better understand epigenetic transcriptional mechanisms mediate these cell state changes, how they relate to risk for coronary artery disease (CAD), we have investigated causality function transcription factors at genome-wide associated loci.
Epigenetic regulation has emerged to be the critical steps for tumorigenesis and metastasis. Multiple histone methyltransferase demethylase have been implicated as tumor suppressors or oncogenes recently. But key epigenomic events in cancer cell transformation still remain poorly understood. A breast model was established via stably expressing three primary epithelial cells. Chromatin immunoprecipitation followed by next-generation sequencing of methylations performed determine epigenetic...
Hippo pathway is involved in tumorigenesis, and its regulation cytosol has been extensively studied, but regulatory mechanisms the nuclear are not clear. In current study, using a FBS-inducing model following serum starvation, we identified KDM3A, demethylase of histone H3K9me1/2, as positive regulator for hippo target genes. KDM3A promotes gene expression through two mechanisms, one to upregulate YAP1 expression, other facilitate H3K27ac on enhancers upregulation more relevant with...
Reperfusion therapy is critical to myocardial salvage in the event of a infarction but complicated by ischemia-reperfusion injury (IRI). Limited understanding spatial organization cardiac cells, which governs cellular interaction and function, has hindered search for targeted interventions minimizing deleterious effects IRI.We used imaging mass cytometry characterize distribution dynamics cell phenotypes communities mouse left ventricle following IRI. Heart sections were collected from 12...
Fulminant myocarditis (FM) is a life-threatening inflammatory disease. However, the mechanisms underlying its acute onset are unknown. By dynamic cardiac function measurement, we discovered that initiation of sudden hemodynamic collapse was on day 4 in mouse model FM. Single-cell RNA-sequencing study revealed healthy cardiomyocytes (CMs) lost their contractile and metabolic differentiated into pro-angiogenic pro-inflammatory CMs. Meanwhile, neutrophils, most expanded immune cells, exhibited...
Genome-wide association studies have identified over 160 loci that are associated with coronary artery disease. As other complex human diseases, risk in disease is determined primarily by altered expression of the causal gene, due to variation binding transcription factors and chromatin-modifying proteins directly regulate transcriptional apparatus. We previously a network downstream disease-associated factor TCF21, work reported here extends these investigate mechanisms which it interacts...
Although numerous genetic loci have been associated with coronary artery disease (CAD) genome wide association studies, efforts are needed to identify the causal genes in these and link them into fundamental signaling pathways. Recent studies investigated mechanism of CAD gene SMAD3, a central transcription factor (TF) TGFβ pathway, investigating its role smooth muscle biology. In vitro human cells (HCASMC) revealed that SMAD3 modulates cellular phenotype, promoting expression...
Abstract Cardiovascular diseases are the most common cause of death globally. Accurately modeling cardiac homeostasis, dysfunction, and drug response lies at heart research. Adult human primary cardiomyocytes (hPCMs) a promising cellular model, but unstable isolation efficiency quality, rapid cell in culture, unknown to cryopreservation prevent them from becoming reliable flexible vitro model. Combing use reversible inhibitor myosin II ATPase, (-)-blebbistatin (Bleb), multiple optimization...
ABSTRACT Unlike other members of the polycomb group protein family, EZH1 has been shown to positively associate with active transcription on a genome-wide scale. However, underlying mechanism for this behavior still remains elusive. Here, we report that physically interacts UXT, small chaperon-like co-activator. UXT specifically and SUZ12, but not EED. Similar upon knockdown or SUZ12 through RNA interference in cell impairs transcriptional activation nuclear factor (NF)-κB target genes...
Understanding the processes behind carotid plaque instability is necessary to develop methods for identification of patients and lesions with stroke risk. Here, we investigated molecular signatures in human plaques stratified by echogenicity as assessed duplex ultrasound.Lesion was correlated microarray gene expression profiles from endarterectomies (n=96). The findings were extended into studies mouse atherosclerotic situ, followed functional investigations vitro smooth muscle cells...
Abstract The Drosophila tracheal system is a favorable model for investigating the program of tubular morphogenesis. This established in embryo by post-mitotic cells, but also undergoes remodeling adult stem cells. Here, we provide comprehensive cell atlas trachea using single-cell RNA-sequencing (scRNA-seq) technique. documents transcriptional profiles tracheoblasts within airway, delineating 9 major subtypes. Further evidence gained from silico as well genetic investigations highlight set...
Abstract Background To investigate the epigenetic and transcriptional mechanisms of coronary artery disease (CAD) risk, as well functional regulation chromatin structure function, we create a catalog genetic variants associated with three stages cis -regulation in primary human vascular smooth muscle cells (HCASMCs). Results We use pooling approach HCASMC lines to map regulatory that mediate binding CAD-associated transcription factor TCF21 ChIPseq studies (bQTLs), regulate accessibility...
Abstract Adult progenitor cells in the trachea of Drosophila larvae are activated and migrate out niches when metamorphosis induces tracheal remodeling. Here we show that response to metabolic deficiency decaying branches, signaling by insulin pathway controls regulating Yorkie (Yki)-dependent proliferation migration. Yki, a transcription coactivator is regulated Hippo signaling, promotes transcriptional activation cell cycle regulators components extracellular matrix cells. These findings...
Vascular beds show different propensities for vascular pathologies, yet mechanisms explaining these fundamental differences remain unknown. We sought to build a transcriptomic, cellular, and spatial atlas of human arterial cells across multiple segments understand this phenomenon. found significant cell type-specific segmental heterogeneity. Determinants identity are predominantly encoded in fibroblasts smooth muscle cells, their differentially expressed genes particularly enriched...
Abstract Multiple epigenetic changes, including alterations in DNA methylation occur during tumorigenesis. Various inhibitors of have been developed to prevent proliferation cancer cells. 5-fluoro-2 ′ -deoxycytidine (FCdR) is one such inhibitor, which currently phase II clinical trial. To investigate the molecular mechanism/s by FCdR might mediate repression tumor cell proliferation, we analyzed toxicity various lines established from different sarcomas. We found HCT116, a colon line, much...
Smooth muscle cells (SMC), the major cell type in atherosclerotic plaques, are vital coronary artery diseases (CADs). SMC phenotypic transition, which leads to formation of various types is regulated by a network genetic and epigenetic mechanisms governs risk disease. The involvement long noncoding RNAs (lncRNAs) has been increasingly identified cardiovascular However, lncRNAs have not comprehensively characterized, their regulatory role state transition remains unknown.
Progressive remodeling of cardiac gene expression underlies decline in function, eventually leading to heart failure. However, the major determinants transcriptional network switching from normal failed hearts remain be determined.
Abstract Background RAP1 interacting factor 1 ( Rif1 ) is highly expressed in mice embryos and mouse embryonic stem cells (mESCs). It plays critical roles telomere length homeostasis, DNA damage, replication timing ERV silencing. However, whether regulates early differentiation of mESC still unclear. Methods In this study, we generated a conditional knockout (ES) cell line based on Cre-loxP system. Western blot, flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), RNA...
Aim: Epigenetic marks are critical regulators of chromatin and gene activity. Their roles in normal physiology disease states, including cancer development, still remain elusive. Herein, the epigenomic change H3K9me3, as well its potential impacts on activity genome stability, was investigated an vitro breast transformation model. Methods: The global H3K9me3 level studied with western blotting. distribution expression ChIP-Seq RNA-Seq, respectively. Results: decreases during is reprogrammed....
Aortic dissection is a devastating cardiovascular disease with high lethality. Histone variants maintain the genomic integrity and play important roles in development diseases. However, role of histone aortic has not been well identified. In present study, H3f3b knockdown reduced synthetic genes expression VSMCs, while overexpressing exacerbated cellular immune response VSMCs induced by inflammatory cytokines. Combined RNA-seq ChIP-seq analyses revealed that variant H3.3B directly bound to...
Environmental exposure to dioxin has been linked increased myocardial infarction. Smooth muscle cells (SMC) in the coronary vasculature play a critical role atherosclerotic plaque remodeling due their phenotypic plasticity, however, detailed mechanism linking adverse SMC modulation is not well understood.