Phosphatidylserine-deficient small extracellular vesicle is a major somatic cell-derived sEV subpopulation in blood

Description

Summary Small extracellular vesicles (sEVs) are important mediators of intercellular communication with respect to diverse pathophysiological processes. Here, we determined novel phosphatidylserine (PS)-deficient sEV subpopulations as a major somatic cell-derived sEV subpopulation in blood because of long blood circulation half-life through escape from macrophage uptake. PS(−)-sEVs were identified in various cultured cells as a minor population. However, as a result of rapid uptake of PS(+)-sEVs by macrophages, circulating somatic cell-derived sEVs in the blood were found to be mainly PS(−)-sEVs. These results suggest that endogenous PS(−)-sEVs could indeed be the key player in sEV-mediated intercellular communication, a good target for sEV-based diagnosis, and a potent candidate for sEV-based drug delivery. Our findings bring a paradigm shift in the understanding of the biology and translational applications of sEVs.

Highlights • PS(−)-sEV was found in various cell line and in plasma • PS(−)-sEV showed extremely long blood retention time • PS(−)-sEVs could indeed be important in sEV-mediated intercellular communication

Molecular physiology; Cell biology; Proteomics

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Journal

  • iScience

    iScience 24 (8), 102839-, 2021-08

    Elsevier BV

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