A5023401503- Atherosclerosis and Cardiovascular Diseases
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Microtubule and mitosis dynamics
- Bioinformatics and Genomic Networks
- Birth, Development, and Health
- Cerebrovascular and Carotid Artery Diseases
- Advanced Electron Microscopy Techniques and Applications
- Congenital heart defects research
- Hematopoietic Stem Cell Transplantation
- Genetic factors in colorectal cancer
- Coronary Interventions and Diagnostics
- RNA modifications and cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Cardiovascular Health and Disease Prevention
- Caveolin-1 and cellular processes
- Adipokines, Inflammation, and Metabolic Diseases
- Neonatal Respiratory Health Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cellular transport and secretion
Utrecht University
2015-2024
University Medical Center Utrecht
2019-2024
Princess Máxima Center
2024
Heidelberg University
2020-2021
University Hospital Heidelberg
2020-2021
Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within cells of human plaques has not been fully assessed. Using single-cell transcriptomics and chromatin accessibility, we gained a better understanding pathophysiology underlying atherosclerosis. We performed RNA ATAC sequencing on carotid atherosclerotic to define at play determine transcriptomic epigenomic characteristics. identified 14 distinct cell populations including endothelial cells,...
Although sex differences in coronary artery disease are widely accepted with women developing more stable atherosclerosis than men, the underlying pathobiology of such remains largely unknown. In disease, recent integrative systems biological studies have inferred gene regulatory networks (GRNs). Within these GRNs, key driver genes shown great promise but thus far been unidentified women.We generated sex-specific GRNs atherosclerotic arterial wall 160 and age-matched men STARNET study...
BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance human atherosclerosis still evolving. Intraplaque hemorrhage thought to be a major contributor plaque progression part by stimulating influx CD163 + macrophages. Here, we explored hypothesis that macrophages cause through induction proapoptotic endothelial-to-mesenchymal transition (EndMT) within...
Selective cargo transport into axons and dendrites over the microtubule network is essential for neuron polarization. The axon initial segment (AIS) separates from somatodendritic compartment controls microtubule-dependent axon. Interestingly, AIS has a characteristic organization; it contains bundles of closely spaced microtubules with electron dense cross-bridges, referred to as fascicles. binding protein TRIM46 localizes when overexpressed in non-neuronal cells forms arrays that resemble...
Genome-wide association studies (GWASs) have discovered hundreds of common genetic variants for atherosclerotic disease and cardiovascular risk factors. The translation susceptibility loci into biological mechanisms targets drug discovery remains challenging. Intersecting gene expression data has led to the identification candidate genes. However, previously studied tissues are often non-diseased heterogeneous in cell composition, hindering accurate prioritization. Therefore, we analysed...
The atherosclerotic plaque microenvironment is highly complex, and selective agents that modulate stability are not yet available. We sought to develop a scRNA-seq analysis workflow investigate this environment uncover potential therapeutic approaches. designed user-friendly, reproducible will be applicable other disease-specific datasets.Here we incorporated automated cell labeling, pseudotemporal ordering, ligand-receptor evaluation, drug-gene interaction into ready-to-deploy workflow....
Women presenting with coronary artery disease more often present fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically SMCs shape female versus male plaques is unknown.
Epigenetic age estimators (clocks) are predictive of human mortality risk. However, it is not yet known whether the epigenetic atherosclerotic plaques for risk cardiovascular events.
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can hijack the normal bone marrow microenvironment to create a leukemic niche which facilitates blast cell survival and promotes drug resistance. Bone marrow-derived mesenchymal stromal cells (MSCs) mimic this protective environment in ex vivo co-cultures with obtained from children newly diagnosed BCP-ALL. We examined potential mechanisms of protection by RNA sequencing flowsorted MSCs after co-culture BCP-ALL cells. Leukemic induced...
Abstract Rationale Endothelial cells can differentiate into mesenchymal-like via endothelial to mesenchymal transition (EndoMT). In murine models, cell transitions of EndoMT have been assessed with lineage tracing techniques. Knowledge on molecular mechanisms in human vascular lesions is scarce as studies atherosclerosis are limited by observational study designs such histo-pathological studies. Objective We aim identify a gene expression signature combining experimentally induced vitro...
Background Plaque myofibroblasts are critical players in the initiation and advancement of atherosclerotic disease. They involved production extracellular matrix, formation fibrous cap, underlying lipidic core via modulation processes response to different environmental cues. Despite clear phenotypic differences between myofibroblast cells healthy vascular smooth muscle cells, still widely used as a cellular model research. Methods Results Here, we present conditioned outgrowth method...
Abstract Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity lesion types highlight need for improved sub- phenotyping. We hypothesized that unbiased clustering plaques based on gene expression results in an alternative categorization late-stage lesions. analyzed profiles 654 advanced human carotid plaques. The unsupervised, transcriptome-driven five dominant types. These novel phenotypes associated with clinical...
Abstract Women presenting with coronary artery disease (CAD) more often present fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically SMCs shape female versus male plaques is unknown. Here, we show sex-stratified gene regulatory networks (GRNs) from human carotid tissue. Prioritization of identified two main SMC GRNs late-stage atherosclerosis. Single-cell...
Abstract Epigenetic age estimators (clocks) are known to be predictive of human mortality risk. However, it is not yet whether the epigenetic atherosclerotic plaques can used for predicting secondary events. Here we estimated an adjusted measure age, acceleration (EAA), using DNA methylation and blood. EAA plaque, but blood, independently predicted events in a 3-year follow-up (HR=1.3, p= 0.018). Plaque concurred with high metabolic transcriptional state plaques. Patients diabetes body mass...
Abstract Sex differences are evident in the clinical presentation and underlying histology of atherosclerotic disease with women developing more stable lesions than men. It is unknown whether this explained by sex gene regulation cellular compartments plaques. To study we performed genome-wide DNA methylation transcriptomics analysis on plaques 485 carotid endarterectomy patients (31% female). Sex-differential at 4,848 sites autosome was enriched for cell-fate commitment developmental...
Background Genome-wide association studies have discovered hundreds of common genetic variants for atherosclerotic disease and cardiovascular risk factors. The translation susceptibility loci into biological mechanisms targets drug discovery remains challenging. Intersecting gene expression data has led to the identification candidate genes. However, previously studied tissues are often non-diseased heterogeneous in cell composition, hindering accurate prioritization. Therefore, we analyzed...
Abstract Plaque smooth muscle cells are critical players in the initiation and advancement of atherosclerotic disease. They produce extracellular matrix (ECM) components, which play a role lesion progression stabilization. Despite clear phenotypic differences between plaque vascular (VSMCs), VSMCs still widely used as model system research. Here we present conditioned outgrowth method to isolate cells. We obtained from 27 donors (24 carotid 3 femoral endarterectomies). show that these keep...