Objective:

To create a detailed protein-level map of the developing human brain and investigate the discrepancies between gene expression and protein abundance, highlighting their significance for neurodevelopmental disorders.

Key Findings:

• Extensive discordance between transcripts and proteins across nearly all cell types, with implications for understanding neurodevelopmental disorders.
• Post-transcriptional regulation plays a central role in defining cellular identity during brain development.
• Protein abundance is more cell-type-specific than mRNA levels, suggesting a need to focus on protein data in developmental studies.
• Distinct protein co-expression modules emerged during the transition from intermediate progenitor cells to excitatory neurons, highlighting critical developmental processes.
• High-risk genes for autism spectrum disorders showed high transcript levels but constrained protein abundance, indicating potential regulatory mechanisms.

Interpretation:

The findings suggest that protein regulation is crucial during early neurogenesis and may contribute to neurodevelopmental disorders, emphasizing the need for further research in this area.

Limitations:

• The study focused on specific gestational weeks and may not represent the entire developmental spectrum, potentially limiting the generalizability of the findings.
• Further research is needed to extend findings to disease tissue and other developmental stages to fully understand the implications.

Conclusion:

Single-cell proteomics can enhance understanding of genetic risk and regulatory control in brain development, potentially informing neurodevelopmental disorder research and guiding future studies.