Physical and Molecular Landscapes of Mouse Glioma Extracellular Vesicles Define Heterogeneity

Citation:

Aron Gyuris, Jose Navarrete-Perea, Ala Jo, Simona Cristea, Shuang Zhou, Kyle Fraser, Zhiyun Wei, Anna M Krichevsky, Ralph Weissleder, Hakho Lee, Steve P Gygi, and Al Charest. 2019. “Physical and Molecular Landscapes of Mouse Glioma Extracellular Vesicles Define Heterogeneity.” Cell Rep, 27, 13, Pp. 3972-3987.e6.

Abstract:

Cancer extracellular vesicles (EVs) are highly heterogeneous, which impedes our understanding of their function as intercellular communication agents and biomarkers. To deconstruct this heterogeneity, we analyzed extracellular RNAs (exRNAs) and extracellular proteins (exPTNs) from size fractionation of large, medium, and small EVs and ribonucleoprotein complexes (RNPs) from mouse glioblastoma cells by RNA sequencing and quantitative proteomics. mRNA from medium-sized EVs most closely reflects the cellular transcriptome, whereas small EV exRNA is enriched in small non-coding RNAs and RNPs contain precisely processed tRNA fragments. The exPTN composition of EVs and RNPs reveals that they are closely related by vesicle type, independent of their cellular origin, and single EV analysis reveals that small EVs are less heterogeneous in their protein content than larger ones. We provide a foundation for better understanding of segregation of macromolecules in glioma EVs through a catalog of diverse exRNAs and exPTNs.