Comparative Proteomics Reveals Cell-Type-Specific Heterogeneity of Human Neural Cell-Derived Extracellular Vesicles

Neuronal-like SH-SY5Y extracellular vesicles show the highest particle concentration and protein yield among N-EV, AS-EV, and MG-EV, while EV size and zeta potential remain comparable.

• Why it matters: Baseline, cell-type-specific EV cargo differences are unclear, limiting interpretation of disease-linked EV changes and rational selection of EV sources for brain therapeutics.
• What they did: EVs from SH-SY5Y neuronal-like cells, astrocytes, and HMC3 microglia were profiled by TMT-based quantitative proteomics in a single multiplexed batch, with EV identity validated by TEM, nanoparticle tracking analysis, and MISEV2023 markers.
• The result: Proteomic enrichment and consensus clustering linked N-EV, AS-EV, and MG-EV cargo to parental-cell functions, including complement-associated cargo shared by N-EV and MG-EV and a Glial-EV chromatin/epigenetic signature shared by AS-EV and MG-EV.

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