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Proteome and secretome analysis of human dorsal forebrain organoids reveals a time-dependent shift in the abundance of cell adhesion and extracellular matrix proteins

ABSTRACT: Temporal dynamics of prenatal brain development are influenced by changes in the microenvironment. Particularly, extracellular proteins contribute to the dynamic niche that balances neural stem cell proliferation and differentiation. Here, we present a resource for proteome and secretome analysis of human induced pluripotent stem cell-derived dorsal forebrain organoids over the early developmental period. We used liquid chromatography-mass spectrometry to identify proteins found in whole organoid and secreted proteins at days 20, 35, and 50 of dorsal forebrain organoid differentiation. We show that the whole organoid proteome demonstrates progression in the neurodevelopmental trajectory with reduced proliferation and increased neural differentiation over time. However, secretome analysis revealed a unique signature for developmental progression. Cell adhesion molecules are enriched in the secretome of day 35 organoids, while secretome of day 50 organoids is enriched with extracellular matrix proteins, demonstrating a change in the extracellular interactions over time of organoid differentiation and maturation. We, therefore, show the relevance of secretome analysis for the thorough study of extracellular matrix-related proteins and the importance of time course study of neural organoids to understand the subtle changes that guide human neurodevelopment.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Mohamed Ali Jarboui

PROVIDER: MSV000094878 | MassIVE | Mon May 27 23:53:00 BST 2024

SECONDARY ACCESSION(S): PXD052612

REPOSITORIES: MassIVE

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