Mouse Neural Organoids Model the Mature In Vivo Synaptic Proteome

Abstract

Neural organoids represent a promising approach for modelling neural circuits and neurological disease, yet their utility depends on whether they can recapitulate the molecular complexity of mature brain synapses. Here, we optimized a protocol to generate mature forebrain organoids from mouse embryonic stem cells and used time-resolved proteomics to define the emergence of synaptic proteins during maturation. Using fluorescence-activated synaptosome sorting coupled with mass spectrometry, we quantified the synapse-enriched proteome and found a high correlation with matched in vivo synaptic proteomes. These findings demonstrate that complex mature synaptic molecular architecture is present within an in vitro organoid environment.