Bidirectional Communication Between Astrocytes and Neurons via Extracellular Vesicles: A Multi‐Omics Approach

Cells modulate their physiology through multiple mechanisms-cell-cell contacts and autocrine/paracrine signaling, including via extracellular vesicles (EVs). In this study, we exposed mouse hippocampal astrocyte and neuron monocultures to EVs from the opposing cell type and subsequently performed RNA sequencing to examine transcriptomic changes. Mass spectrometry was used to analyze the proteomes of EVs from astrocyte and neuron monocultures, as well as from astrocyte-neuron co-cultures, to investigate the molecular basis of EVs-induced transcriptomic alterations and to determine the extent to which cells adjust EV cargo in response to feedback signals. EVs secreted by both cell types induced cell-specific transcriptomic changes in target cells, related to migration, proliferation, differentiation, and energy production. Unique changes in the proteome of EVs from astrocytic-neuronal co-cultures highlighted the dynamic regulation of signaling molecule secretion via cell interactions.