A5060610707- Extracellular vesicles in disease
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Liver physiology and pathology
- Cytomegalovirus and herpesvirus research
- Circular RNAs in diseases
- Herpesvirus Infections and Treatments
- Immune cells in cancer
- Hippo pathway signaling and YAP/TAZ
- Pediatric Hepatobiliary Diseases and Treatments
- Cell Adhesion Molecules Research
- Phagocytosis and Immune Regulation
- Neuropeptides and Animal Physiology
- Immunotherapy and Immune Responses
- Adenosine and Purinergic Signaling
- Alzheimer's disease research and treatments
- Axon Guidance and Neuronal Signaling
- Viral-associated cancers and disorders
- Cellular Mechanics and Interactions
- Systemic Lupus Erythematosus Research
- Receptor Mechanisms and Signaling
- Cellular transport and secretion
- Pancreatic function and diabetes
- Monoclonal and Polyclonal Antibodies Research
- Sphingolipid Metabolism and Signaling
Amsterdam University Medical Centers
2019-2024
Amsterdam UMC Location Vrije Universiteit Amsterdam
2018-2024
Vrije Universiteit Amsterdam
2018-2024
Max Planck Institute of Molecular Cell Biology and Genetics
2023-2024
Institut de Psychiatrie et Neurosciences de Paris
2022
Université Paris Cité
2022
Institute of Medicinal Plant Development
2018
Exosomes are small endosome-derived extracellular vesicles implicated in cell–cell communication and secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology based on isolation procedures after secretion, precluding direct dynamic insight into mechanics of biogenesis regulation their release. In this study, we propose real-time visualization MVB–PM fusion overcome these limitations. We designed...
Exosomes are endosome-derived extracellular vesicles involved in intercellular communication. They generated as intraluminal within endosomal compartments that fuse with the plasma membrane (PM). The molecular events generate secretory endosomes and lead to release of exosomes not well understood. We identified a subclass non-proteolytic at prelysosomal stage compartment origin CD63 positive exosomes. These undergo Rab7a/Arl8b/Rab27a GTPase cascade PM. Dynamic endoplasmic reticulum (ER)-late...
Glioblastoma (GBM) is the most aggressive and an incurable type of brain cancer. Human cytomegalovirus (HCMV) DNA encoded proteins, including chemokine receptor US28, have been detected in GBM tumors. US28 displays constitutive activity able to bind several human chemokines, leading activation various proliferative inflammatory signaling pathways. Here we show that HCMV, through expression significantly enhanced growth 3D spheroids U251- neurospheres primary glioblastoma cells. Moreover,...
Abstract While various GPCRs, including US28, display constitutive, ligand-independent activity, it remains to be established whether ligand-dependent and -independent active conformations differ can selectively modulated. Previously, the agonist-bound conformation of US28 was stabilized its structure solved using anti-US28 nanobody Nb7. Here we report recognition constitutively active, apo-conformation by another VUN103. Nb7 intrabody inhibits ligand-induced signaling, VUN103 blocks...
The G protein–coupled receptor (GPCR) US28 encoded by the human cytomegalovirus (HCMV) is associated with accelerated progression of glioblastomas, aggressive brain tumors a generally poor prognosis. Here, we showed that increased malignancy U251 glioblastoma cells enhancing signaling mediated sphingosine-1-phosphate (S1P), bioactive lipid stimulates oncogenic pathways in glioblastoma. expression abundance key components S1P axis, including an enzyme generates [sphingosine kinase 1 (SK1)],...
Hepatocytes grow their apical surfaces anisotropically to generate a 3D network of bile canaliculi (BC). BC elongation is ensured by bulkheads, membrane extensions that traverse the lumen and connect juxtaposed hepatocytes. We hypothesize bulkheads are mechanical elements shape in liver development but also counteract elevated biliary pressure. Here, resolving structure using STED microscopy, we found they sealed tight junction loops, connected adherens junctions, contain contractile...
Hepatocytes have a unique multiaxial polarity with several apical and basal surfaces. The prevailing model for the emergence of this multipolarity coordination lumen formation between adjacent hepatocytes is based on asymmetric cell division. Here, investigating generation in liver progenitors, hepatoblasts, during development vivo vitro, we found that cannot explain observed dynamics embryonic liver. Instead, identified new mechanism multi-axial polarization: We polarization can be...
Abstract Purpose: Therapy resistance is a major clinical hurdle in bone cancer treatment and seems to be largely driven by poorly understood microenvironmental factors. Recent evidence suggests critical role for unique subpopulation of mesenchymal stem cells with inflammatory features (iMSC), though their origin function remained unexplored. We demonstrate that cancer-secreted extracellular vesicles (EV) trigger the development iMSCs, which hinder therapy response vivo, set out identify...
Abstract Dysregulated extracellular vesicle (EV) release has been implicated in various pathologies, including cancer, neurodegenerative disease and osteoarthritis. Despite clear therapeutic potential, drug screening for EV modulators yielded limited success due to the lack of a sensitive scalable read-out system. Here, we employed CRISPR-Cas9 engineer HEK293 cells expressing HA-NanoLuciferase-(NL)-tagged endogenous CD63. We found that under basal culture conditions, CD63-containing EVs are...
The human cytomegalovirus (HCMV)-encoded chemokine receptor US28 contributes to various aspects of the viral life cycle and promotes immune evasion by scavenging chemokines from microenvironment HCMV-infected cells. In contrast plasma membrane localization most receptors, has a predominant intracellular localization. this study, we used immunofluorescence electron microscopy determine upon exogenous expression, as well in We observed that localizes late endosomal compartments called...
Human cytomegalovirus (HCMV) encodes four G protein-coupled receptor (GPCR) homologs. Three of these receptors, UL78, US27 and US28, are known for their roles in HCMV dissemination latency. Despite importance its rodent orthologs viral replication pathogenesis, such a function is not reported the HCMV-encoded GPCR UL33. Using clinical strain Merlin, we show that UL33 facilitates both cell-associated cell-free virus transmission. A UL33-deficient derivative revealed retarded spread, formation...
Summary Hepatocytes have a unique multiaxial polarity with several apical and basal surfaces. The prevailing model for the emergence of this multipolarity coordination lumen formation between adjacent hepatocytes is based on asymmetric cell division. Here, investigating generation in liver progenitors, hepatoblasts, during development vivo vitro , we found that cannot explain observed dynamics embryonic liver. Instead, identified new mechanism multi-axial polarization: We polarization can be...
ABSTRACT During liver development, bipotential progenitor cells called hepatoblasts differentiate into hepatocytes or cholangiocytes. Hepatocyte differentiation is uniquely associated with multi-axial polarity, enabling the anisotropic expansion of apical lumina between adjacent and formation a three-dimensional network bile canaliculi. Cholangiocytes, forming ducts, exhibit vectorial polarity characteristic epithelial cells. Whether cell polarization feeds back on gene regulatory pathways...
Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such myocardial infarction (MI). However, basic mechanisms driving cardiomyocyte-derived EV (CM-EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express NanoLuc-tetraspanin reporters. These modified hiPSC-CMs allow for...
Abstract Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such myocardial infarction (MI). However, basic mechanisms driving cardiomyocyte-derived EV (CM-EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express NanoLuc-tetraspanin reporters. These modified hiPSC-CMs allow for...
Abstract During liver development, bipotential progenitor cells called hepatoblasts differentiate into hepatocytes or cholangiocytes. Hepatocyte differentiation is uniquely associated with multi-axial polarity, enabling the anisotropic expansion of apical lumina between adjacent and formation a three-dimensional network bile canaliculi (BC). Cholangiocytes, forming ducts, exhibit vectorial polarity common to epithelial cells. Whether how cell polarization feeds back on gene regulatory...
<p>Suppl. Figure 4. a-b) scRNA-seq mapping of human osteosarcoma tumors. MSC and other indicated clusters were identified through the UMAP (a) marker gene expression analysis (b).</p>
<p>Suppl. Figure 3. a-e) Relative expression levels of IL6, IL8, CXCL2, CXCL3 and CXCL6 in MSCs from an independent donor (MSC#2) exposed to plasma-derived EVs healthy #1 (H#1) MM patient (MM#1).</p>
<p>Suppl. Figure 6. a-b) Expression of the most upregulated TGFβ-dependent (a) and independent/partially dependent (b) genes in bone marrow MSCs based on RNA-seq normalized counts. c-f) Relative expression levels CXCL1, CXCL2, CXCL5, CXCL6 mRNAs (donor #1) exposed to 143B EVs presence or absence TGFBR1 inhibitor SB-431542 as assessed by RT-qPCR. g-m) IL6, IL8, CXCL3, #2) EW-7197. n-o) IL6 IL8 adipose-derived #3) EW-7197.</p>