Extracellular vesicles underlie cell-type-specific crosstalk during human cortical development and disease

Cellular crosstalk is an essential process influenced by numerous factors including secreted vesicles that transfer nucleic acids, lipids, and proteins between cells. Extracellular vesicles (EVs) have been the center of many studies focusing on neuron-to-neuron communication but whether EVs display cell-type-specific features for cellular crosstalk during neurogenesis is unknown. Using human-derived cerebral organoids, neural progenitors, neurons and astrocytes, we characterized the protein content of EVs and showed their cell-type-specific dynamics and function during brain development. Moreover, as many proteins coded by genes associated with neurodevelopmental disorders were detected in EVs, we examined EVs from patients with myoclonic epilepsy and found alterations in size, composition and function. This study sheds new light on the biology of EVs during brain development.