Georgia’s most recent study has harnessed 4D intravital microscopy of the bone marrow calvarium to track
the cellular dynamics of endothelial cells under steady state and malignant conditions. This study identified
a population of large EVs generated by endothelial cells that contained polarized mitochondria, active
caspase 3/7 and exposed the ‘eat me’ signal, phosphatidylserine (PtdSer). Notably, these EVs were also
identified in zebrafish and human samples. Through extensive immune cell panelling and Image Flow
Cytometry, this study identified a number of immune cell populations including monocytes and neutrophils
that could interact with and engulf these EVs. EV clearance was in part driven through a PtdSer dependent
mechanism as EVs accumulated in the spleen of mice lacking the engulfment machinery, MerTK.
This study adopted multiple blood cancer models including acute myeloid leukemia (AML), T cell acute
lymphoblastic leukemia (T-ALL) and EμMyc-driven B cell lymphoma to explore EV formation during
malignant haematopoiesis. Strikingly, live intravital imaging of the bone marrow calvarium and dual
confocal/multiphoton microscopy of cleared long bones revealed that both AML and T-ALL resulted in the
degradation of the bone marrow vasculature at late-stage of disease. Excitingly, this correlated with elevated
numbers of endothelial cell-derived EVs found in circulation. In comparison to the extensive vasculature
damage observed during AML and T-ALL, expansion of EμMyc lymphoma resulted in drastic vascular
remodelling in the bone marrow microenvironment but not endothelial cell loss. As such, circulating EV
levels remained unchanged.
Together, this study identified a new EV population that is generated and cleared under steady state and
malignant conditions. Moreover, EV numbers correlate with endothelial cell degradation, providing a
snapshot into the health status of the endothelium at distal sites during disease.
From 07 Oct 2024 14:00
Until 07 Oct 2024 15:00
Location W122, FSVM I building
Speaker Georgia Atkin Smith
Affiliation WEHI, Melbourne, Australia
Host Peter Vandenabeele
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About the speaker Dr Georgia Atkin-Smith is a Senior Postdoctoral Researcher and NHMRC Investigator Grant Fellow at the Walter and Eliza Hall Institute (WEHI) in Melbourne, Australia, working under the mentorship of A/Prof Edwin Hawkins, A/Prof Gemma Kelly and Prof Andreas Strasser. Georgia completed her PhD in 2019 at the La Trobe Institute for Molecular Science in the laboratory of Prof Ivan Poon. Her research combines a variety of imaging techniques to study cell death, efferocytosis, extracellular vesicles (EVs) and cancer biology, including confocal, lattice light sheet and multiphoton/intravital microscopy (https://someblondescientist.com/)
