Survey of organ‐derived small extracellular vesicles and particles (sEVPs) to identify selective protein markers in mouse serum

Abstract

Extracellular vesicles and particles (EVPs) are secreted by organs across the body into different circulatory systems, including the bloodstream, and reflect pathophysiologic conditions of the organ. However, the heterogeneity of EVPs in the blood makes it challenging to determine their organ of origin. We hypothesized that small (s)EVPs (<100 nm in diameter) in the bloodstream carry distinctive protein signatures associated with each originating organ, and we investigated this possibility by studying the proteomes of sEVPs produced by six major organs (brain, liver, lung, heart, kidney, and fat). We found that each organ contained distinctive sEVP proteins: 68 proteins were preferentially found in brain sEVPs, 194 in liver, 39 in lung, 15 in heart, 29 in kidney, and 33 in fat. Furthermore, we isolated sEVPs from blood and validated the presence of sEVP proteins associated with the brain (DPP6, SYT1, DNM1L), liver (FABPL, ARG1, ASGR1/2), lung (SFPTA), heart (CPT1B), kidney (SLC31), and fat (GDN). We further discovered altered levels of these proteins in serum sEVPs obtained from old mice compared to young mice. In sum, we have cataloged sEVP proteins that can serve as potential biomarkers for organ identification in serum and show differential expression with age.

A beginner's guide to study extracellular vesicles in human blood plasma and serum

“…Examples of such rare populations in blood are EVs originating from cancer cells (Nanou et al., 2023 ; Yang et al., 2018 ), cardiomyocytes (Hegyesi et al., 2022 ) or bacteria (Tulkens et al., 2020 ). Recently, the cellular origin of plasma EVs has also been deduced by measuring the presence of tissue‐specific long RNA sequencing profiles (Li et al., 2020 ) or tissue‐specific protein signatures (Abdelmohsen et al., 2023 ) in plasma or serum. Since EVs are only a small fraction of all particles present in blood, plasma and serum (Johnsen et al., 2019 ; Simonsen, 2017 ), detection of rare EV types is even more challenging.…”