Comprehensive proteomic profiling of plasma and serum phosphatidylserine-positive extracellular vesicles reveals tissue-specific proteins

Extracellular vesicles (EVs) are ubiquitously secreted by almost all tissues and carry many cargoes, including proteins, RNAs, and lipids, which are related to various biological processes. EVs are shed from tissues into the blood and expected to be used as biomarkers for diseases. Here, we isolated EVs from EDTA plasma and serum of six healthy subjects by an affinity capture isolation method, and a total of 4,079 proteins were successfully identified by comprehensive EV proteomics. Our reliable and detailed catalog of the differential expression profiles of EV proteins in plasma and serum between healthy individuals could be useful as a reference for biomarker discovery. Furthermore, tissue-specific protein groups co-regulated between blood EVs from healthy individuals were identified. These EV proteins are expected to be used for more specific and sensitive enrichment of tissue-specific EVs and for screening and monitoring of disease without diagnostic imaging in patient blood in the future.