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PreprintCC BY-NC-NDbioRxiv

Mouse Neural Organoids Model the Mature In Vivo Synaptic Proteome

  • S. L. Giandomenico
  • M. van Oostrum
  • Q. Waselenchuk
  • I. Dalla Costa
  • J. D. Langer
  • E. M. Schuman1
  1. 1MPI for Brain Research
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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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Cite

BibTeXRIS
BibTeX
@misc{giandomenico2026mouse,
  title = {{Mouse Neural Organoids Model the Mature In Vivo Synaptic Proteome}},
  author = {S. L. Giandomenico and M. van Oostrum and Q. Waselenchuk and I. Dalla Costa and J. D. Langer and E. M. Schuman},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.24.753785},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.24.753785v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Mouse Neural Organoids Model the Mature In Vivo Synaptic Proteome
AU  - S. L. Giandomenico
AU  - M. van Oostrum
AU  - Q. Waselenchuk
AU  - I. Dalla Costa
AU  - J. D. Langer
AU  - E. M. Schuman
PY  - 2026
DA  - 2026/09/24
PB  - bioRxiv
DO  - 10.64898/2026.09.24.753785
UR  - https://www.biorxiv.org/content/10.64898/2026.09.24.753785v1
AB  - 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.
ER  -