In situ visualization of endothelial cell-derived extracellular vesicle formation in steady state and malignant conditions

Georgia K. Atkin-Smith (), Jascinta P. Santavanond, Amanda Light, Joel S. Rimes, Andre L. Samson, Jeremy Er, Joy Liu, Darryl N. Johnson, Mélanie Le Page, Pradeep Rajasekhar, Raymond K. H. Yip, Niall D. Geoghegan, Kelly L. Rogers, Catherine Chang, Vanessa L. Bryant, Mai Margetts, M. Cristina Keightley, Trevor J. Kilpatrick, Michele D. Binder, Sharon Tran, Erinna F. Lee, Walter D. Fairlie, Dilara C. Ozkocak, Andrew H. Wei, Edwin D. Hawkins () and Ivan K. H. Poon ()
Additional contact information
Georgia K. Atkin-Smith: Walter and Eliza Hall Institute of Medical Research
Jascinta P. Santavanond: La Trobe University
Amanda Light: Walter and Eliza Hall Institute of Medical Research
Joel S. Rimes: Walter and Eliza Hall Institute of Medical Research
Andre L. Samson: Walter and Eliza Hall Institute of Medical Research
Jeremy Er: Walter and Eliza Hall Institute of Medical Research
Joy Liu: Walter and Eliza Hall Institute of Medical Research
Darryl N. Johnson: University of Melbourne
Mélanie Le Page: Monash University
Pradeep Rajasekhar: Walter and Eliza Hall Institute of Medical Research
Raymond K. H. Yip: Walter and Eliza Hall Institute of Medical Research
Niall D. Geoghegan: Walter and Eliza Hall Institute of Medical Research
Kelly L. Rogers: Walter and Eliza Hall Institute of Medical Research
Catherine Chang: Walter and Eliza Hall Institute of Medical Research
Vanessa L. Bryant: Walter and Eliza Hall Institute of Medical Research
Mai Margetts: Walter and Eliza Hall Institute of Medical Research
M. Cristina Keightley: La Trobe University
Trevor J. Kilpatrick: Florey Institute of Neuroscience and Mental Health
Michele D. Binder: Florey Institute of Neuroscience and Mental Health
Sharon Tran: Olivia Newton-John Cancer Research Institute
Erinna F. Lee: La Trobe University
Walter D. Fairlie: La Trobe University
Dilara C. Ozkocak: La Trobe University
Andrew H. Wei: Walter and Eliza Hall Institute of Medical Research
Edwin D. Hawkins: Walter and Eliza Hall Institute of Medical Research
Ivan K. H. Poon: La Trobe University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial cells are constantly exposed to a variety of molecular factors and shear force that can induce cellular damage and stress. However, how endothelial cells are removed or eliminate unwanted cellular contents, remains unclear. The generation of large extracellular vesicles (EVs) has emerged as a key mechanism for the removal of cellular waste from cells that are dying or stressed. Here, we used intravital microscopy of the bone marrow to directly measure the kinetics of EV formation from endothelial cells in vivo under homoeostatic and malignant conditions. These large EVs are mitochondria-rich, expose the ‘eat me’ signal phosphatidylserine, and can interact with immune cell populations as a potential clearance mechanism. Elevated levels of circulating EVs correlates with degradation of the bone marrow vasculature caused by acute myeloid leukaemia. Together, our study provides in vivo spatio-temporal characterization of EV formation in the murine vasculature and suggests that circulating, large endothelial cell-derived EVs can provide a snapshot of vascular damage at distal sites.

Date: 2024
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DOI: 10.1038/s41467-024-52867-5

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