Vesicle-mediated information transfer in cardiovascular cell differentiation.

Extracellular vesicles (EVs)-including exosomes, microvesicles, and apoptotic bodies-are membrane-bound carriers of diverse molecular cargo such as nucleic acids, proteins, and lipids. They are increasingly recognized as critical mediators of information transfer during cardiovascular cell differentiation, development, diseases, and regeneration. Emerging evidence highlights the capacity of EV-encapsulated microRNAs (miRNAs) to drive cardiomyocyte differentiation and support angiogenesis. We recently discovered a novel EV-mediated mechanism termed "phenotypic synchronization of cells" (PSyC). When protein kinase A (PKA) is activated in pluripotent stem cells, the speed of mesodermal differentiation increases, partly through elevated EV-encapsulated miR-132. miR-132, transferred to neighboring cells with EVs, reactivates PKA signaling in recipient cells, synchronizing differentiation stages. Additionally, ex vivo assays reveal that EVs derived from PKA-activated cells can induce cardiomyocyte differentiation in early-stage embryos, underscoring the potency of EV-based signaling in shaping cardiovascular phenotypes. We recently uncovered a novel modality of vesicle-mediated intercellular communication, named direct intercellular vesicle exchange (DIVE), a distinct pathway enabling rapid and direct vesicle transfer between adjacent cells. By facilitating the direct traverse of nucleic acid-laden vesicles across the plasma membrane, DIVE may reinforce conventional EV-based signaling in cardiovascular differentiation. Together, these findings underscore the fundamental role of vesicle-mediated information exchange in orchestrating cardiac and vascular cell fates. Exploiting vesicle-mediated communication may open new avenues in regenerative medicine, disease modeling, and therapeutic interventions aimed at modulating cardiovascular cell function.