Physical and molecular landscapes of mouse glioma extracellular vesicles define heterogeneity

Extracellular vesicles (EVs) comprise a novel mechanism for cellular communication by transferring protein and nucleic acid cargo between cells. By utilizing a sequential filtration protocol, we were able to effectively separate microvesicles (MVs), exosomes and membrane-unbound ribonuclear protein complexes (RNPs) released from EGFR- (Acquaviva, 2011) and PDGFR-driven (Jun, 2018) genetically engineered mouse glioblastoma (GMB) cell lines. Regardless of the oncogenic driver of the tumor, different species of RNA partition into different extracellular compartments, with the mRNA in MVs most closely representing the cellular transcriptome, while miRNAs and tRNA fragments segregate into exosomes and RNPs, respectively. This EV RNA profile, combined with the cognate proteomics data, also serves as a reference for future GBM biomarker discovery. Examination of small and long RNA libraries from cells, small microvesicles, exosomes and RNPs from an EGFR- and a PDGFR-driven mouse-derived GBM cell line