Abstract:

First impressions can have a lasting impact. In science, this can be especially problematic, because our lack of understanding often causes us to mislabel and thus ignore important biological processes. In this vein, extracellular vesicles (EVs) were once considered to be “cellular dust”. Similar to the previous concept of “junk DNA” to describe protein non-coding regions, EVs are far more than just cellular dust. In fact, EVs are emerging as key mediators of intracellular communication across nearly all biological systems. This includes peripheral immune responses (e.g., arthropathies and sepsis), intra-organ communication (Seim et al., 2023), and a host of other physiological and pathological states (Figure 1A and B). EV signaling is multi-faceted due to the diverse assortment of cargo (protein, lipid, nucleic acids) and surface molecules (bioactive lipids, cell surface markers, proteins) (Tricarico et al., 2017). This allows for the communication of complex biological signals that are needed to regulate complex biological processes. Unfortunately, EVs are still often overlooked. EV surface proteins play critical roles as do content within EVs. The encapsulation of internal EV cargo by their lipid membranes can preclude the identification of EV contents if EVs are not specifically isolated or lysed prior to assessment. Thus, it is easy to miss key mediators in EVs. Ignoring the role of EVs across biological processes can lead to missed discoveries, and slow the advancement of research and therapeutics.