Epigenomic programming in early fetal brain development

Epigenomics. 2020 Jun;12(12):1053-1070. doi: 10.2217/epi-2019-0319. Epub 2020 Jul 17.

Abstract

Aim: To provide a comprehensive understanding of gene regulatory networks in the developing human brain and a foundation for interpreting pathogenic deregulation. Materials & methods: We generated reference epigenomes and transcriptomes of dissected brain regions and primary neural progenitor cells (NPCs) derived from cortical and ganglionic eminence tissues of four normal human fetuses. Results: Integration of these data across developmental stages revealed a directional increase in active regulatory states, transcription factor activities and gene transcription with developmental stage. Consistent with differences in their biology, NPCs derived from cortical and ganglionic eminence regions contained common, region specific, and gestational week specific regulatory states. Conclusion: We provide a high-resolution regulatory network for NPCs from different brain regions as a comprehensive reference for future studies.

Keywords: DNA methylation; brain; cortex; enhancer; epigenetics; fetal; ganglionic eminence; gestational week; neural progenitor cells; transcriptional network.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / embryology*
  • Epigenesis, Genetic*
  • Epigenome
  • Female
  • Fetus
  • Gene Expression Regulation, Developmental*
  • Humans
  • Neural Stem Cells
  • Pregnancy
  • Transcriptome
  • Twins