Mouse Neural Organoids Model the Mature In Vivo Synaptic Proteome

Giandomenico, S. L.; van Oostrum, M.; Waselenchuk, Q.; Dalla Costa, I.; Langer, J. D.; Schuman, E. M.

doi:10.64898/2026.09.24.753785

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bioRxiv · 10.64898/2026.09.24.753785

Mouse Neural Organoids Model the Mature In Vivo Synaptic Proteome

Giandomenico, S. L.·van Oostrum, M.·Waselenchuk, Q.·Dalla Costa, I.·Langer, J. D.·Schuman, E. M.

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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.

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Giandomenico, S. L., van Oostrum, M., Waselenchuk, Q., Dalla Costa, I., Langer, J. D., Schuman, E. M.. 2026-09-25. Mouse Neural Organoids Model the Mature In Vivo Synaptic Proteome. https://doi.org/10.64898/2026.09.24.753785

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