In situ visualization of endothelial cell-derived extracellular vesicle formation in steady state and malignant conditions
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.
Authors
- Andrew H. Wei (ORCID: https://orcid.org/0000-0002-7514-3298)
- Amanda Light (ORCID: https://orcid.org/0000-0003-3970-3654)
- Catherine Chang (ORCID: https://orcid.org/0009-0002-9679-6615)
- Darryl N. Johnson (ORCID: https://orcid.org/0000-0003-3205-0371)
- Michele D. Binder (ORCID: https://orcid.org/0000-0002-4494-6717)
- Ivan K. H. Poon (ORCID: https://orcid.org/0000-0002-9119-7173)
- Erinna F. Lee (ORCID: https://orcid.org/0000-0003-1255-9808)
- Edwin D. Hawkins (ORCID: https://orcid.org/0000-0002-3686-8261)
- Niall D. Geoghegan (ORCID: https://orcid.org/0000-0001-9884-0769)
- Sharon Tran (ORCID: https://orcid.org/0000-0003-1321-5556)
- Dilara C. Ozkocak (ORCID: https://orcid.org/0000-0003-4614-5638)
- Vanessa L. Bryant (ORCID: https://orcid.org/0000-0002-4697-7410)
- Pradeep Rajasekhar (ORCID: https://orcid.org/0000-0002-1983-7244)
- Kelly L. Rogers (ORCID: https://orcid.org/0000-0002-6755-0221)
- Georgia K. Atkin‐Smith (ORCID: https://orcid.org/0000-0001-8577-6171)
- Jascinta P. Santavanond (ORCID: https://orcid.org/0000-0002-7950-6316)
- Mai B. Margetts (ORCID: https://orcid.org/0000-0003-0615-1515)
- Raymond K. H. Yip (ORCID: https://orcid.org/0000-0003-2698-7686)
- Maria-Cristina Keightley (ORCID: https://orcid.org/0000-0001-8141-4069)
- Joy Liu (ORCID: https://orcid.org/0000-0002-2531-8387)
- W. Douglas Fairlie (ORCID: https://orcid.org/0000-0002-2498-1160)
- Trevor J. Kilpatrick (ORCID: https://orcid.org/0000-0003-3999-085X)
- André L. Samson (ORCID: https://orcid.org/0000-0002-0637-2716)
- Joel S. Rimes (ORCID: https://orcid.org/0000-0001-6488-2784)
- Jeremy Er
- Matthew Page
Institutions
- The Royal Melbourne Hospital (AU)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- La Trobe University (AU)
- Florey Institute of Neuroscience and Mental Health (AU)
- Peter MacCallum Cancer Centre (AU)
- Monash Alfred Psychiatry Research centre (AU)
- Bendigo Health (AU)
- Olivia Newton-John Cancer Wellness & Research Centre (AU)
- Monash University (AU)
- RMIT University (AU)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-22
- DOI
- https://doi.org/10.1038/s41467-024-52867-5
- Citations
- 12
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 2.81
Funders
- Cancer Research Institute
- Victorian Cancer Agency
- Marshfield Clinic Research Foundation
- Jack Brockhoff Foundation
- Cass Foundation
- La Trobe University
- Monash University
- University of Melbourne
- Peter MacCallum Cancer Centre
- Medical Research Council
- National Health and Medical Research Council