Emergent properties of extracellular vesicles: arnholistic approach to decode the complexity ofrnintercellular communication networks

摘要

Shedding of nano-sized bilayered extracellular vesicles and extracellular vesicle-mediated intercellularrncommunication are evolutionarily conserved biological processes. Communication between cells andrnthe environment is an essential process in living organisms and dysregulation of intercellularrncommunication leads to various diseases. Thus, systematic studies on extracellular vesicles, also knownrnas exosomes, microvesicles, and outer membrane vesicles, are critical for a deeper understandingrnof intercellular communication networks that are crucial for decoding the exact causes of variousrndifficult-to-cure diseases. Recent progress in this emerging field reveals that extracellular vesicles arernendogenous carriers of specific subsets of proteins, mRNAs, miRNAs, and other bioactive materials, asrnwell as play diverse pathophysiological roles. However, certain issues regarding diverse subtypes and therncomplex pathophysiological roles of extracellular vesicles are not yet clearly elucidated. In this review,rnwe first briefly introduce the complexity of extracellular vesicles in terms of their vesicular cargosrnand protein–protein interaction networks, their diverse subtypes, and multifaceted pathophysiologicalrnfunctions. Then, we introduce the limitation of reductionist approaches in understanding the complexityrnof extracellular vesicles. We finally suggest that molecular systems biology approaches based on thernconcept of emergent properties are essential for a comprehensive understanding of the complex pathophysiologicalrnfunctions of heterogeneous extracellular vesicles, either at the single vesicle level or at arnsystems level as a whole.