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Temporal proteomic profiling of postnatal human cortical development.

Michael S Breen1,2,3, Sureyya Ozcan4, Jordan M Ramsey4

  • 1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. michael.breen@mssm.edu.

Translational Psychiatry
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Summary
This summary is machine-generated.

This study maps protein changes during human brain development, revealing key shifts in gene expression related to cell growth and metabolism. These findings offer insights into neurodevelopment and intellectual disability.

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Area of Science:

  • Neuroscience
  • Proteomics
  • Genomics

Background:

  • Precise regulation of protein expression is crucial for healthy brain development.
  • The dynamic changes in protein expression, function, and interaction during postnatal human cortical development are not well understood.

Purpose of the Study:

  • To comprehensively map the proteomic landscape of the human prefrontal cortex across postnatal development.
  • To integrate proteomic data with transcriptomic data to understand gene and protein co-regulation.
  • To investigate the impact of genetic risk factors for intellectual disability on developmental pathways.

Main Methods:

  • Proteomic analysis of 69 dorsolateral prefrontal cortex samples using liquid chromatography-mass spectrometry.
  • Integration of proteomic data with paired transcriptome data.
  • Network analysis to identify modules of co-regulated proteins associated with age.

Main Results:

  • 911 proteins were detected, with 83 significantly associated with postnatal age.
  • Identified three age-correlated protein modules: increasing gliogenesis/NADH metabolism, decreasing neurogenesis.
  • RNA and protein expression showed tighter correlation for dynamically regulated genes, decreasing with age, particularly for myelination and cytoskeleton genes.

Conclusions:

  • Protein expression dynamics significantly change throughout postnatal cortical development.
  • Age-related protein modules align with RNA modules, indicating coordinated regulation.
  • The proteomic and transcriptomic data provide insights into intellectual disability, highlighting pathways in gliogenesis, myelination, and ATP metabolism.