Abstract:
Exosomes and extracellular vesicles (EV) are increasingly being explored as circulating biomarkers, but their heterogenous composition will likely mandate the development of multiplexed EV technologies. Iteratively multiplexed analyses of near single EVs have been challenging to implement beyond a few colors during spectral sensing. Here we developed a multiplexed analysis of EV technique (MASEV) to interrogate thousands of individual EVs during 5 cycles of multi-channel fluorescence staining for 15 EV biomarkers. Contrary to the common belief, we show that: several markers proposed to be ubiquitous are less prevalent than believed; multiple biomarkers concur in single vesicles but only in small fractions; affinity purification can lead to loss of rare EV subtypes; and deep profiling allows detailed analysis of EV, potentially improving the diagnostic content. These findings establish the potential of MASEV for uncovering fundamental EV biology and heterogeneity and increasing diagnostic specificity.
Notes:
Spitzberg, Joshua D Ferguson, Scott Yang, Katherine S Peterson, Hannah M Carlson, Jonathan C T Weissleder, Ralph eng P01 CA069246/CA/NCI NIH HHS/ T32 CA079443/CA/NCI NIH HHS/ R01 CA237332/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural England 2023/03/05 Nat Commun. 2023 Mar 4;14(1):1239. doi: 10.1038/s41467-023-36932-z.
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