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Epigenomic programming in early fetal brain development.

Luolan Li1, Cecile L Maire2, Misha Bilenky3

  • 1Department of Microbiology & Immunology, Michael Smith Laboratories, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.

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|July 18, 2020
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Summary
This summary is machine-generated.

This study maps gene regulatory networks in the developing human brain, revealing dynamic changes in neural progenitor cells (NPCs) across development and brain regions. This provides a foundational reference for understanding brain development and disease.

Keywords:
DNA methylationbraincortexenhancerepigeneticsfetalganglionic eminencegestational weekneural progenitor cellstranscriptional network

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Area of Science:

  • Developmental Neuroscience
  • Epigenetics
  • Genomics

Background:

  • Gene regulatory networks are crucial for human brain development.
  • Understanding these networks is essential for interpreting pathogenic deregulation.
  • Neural progenitor cells (NPCs) play a key role in brain formation.

Purpose of the Study:

  • To comprehensively understand gene regulatory networks in the developing human brain.
  • To establish a foundation for interpreting pathogenic deregulation in brain development.
  • To create a high-resolution regulatory network reference for NPCs.

Main Methods:

  • Generated reference epigenomes and transcriptomes from dissected human fetal brain regions.
  • Isolated and analyzed primary neural progenitor cells (NPCs) from cortical and ganglionic eminence tissues.
  • Integrated multi-omics data across developmental stages and brain regions.

Main Results:

  • Identified a directional increase in active regulatory states, transcription factor activities, and gene transcription with developmental stage.
  • Characterized common, region-specific, and gestational week-specific regulatory states in NPCs.
  • Revealed distinct regulatory landscapes between cortical and ganglionic eminence-derived NPCs.

Conclusions:

  • A high-resolution regulatory network for human fetal NPCs from different brain regions was established.
  • This network serves as a comprehensive reference for future studies on brain development and disease.
  • The findings highlight the dynamic and region-specific nature of gene regulation during human brain development.