Epigenomic Programming in Early Fetal Brain Development

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::

• brain
• cortex
• DNA methylation
• enhancer
• epigenetics
• fetal
• ganglionic eminence
• gestational week
• neural progenitor cells
• transcriptional network

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0319

Acknowledgments

The authors thank the production and technical staff at Canada’s Michael Smith Genome Sciences Centre for the generation of the reference epigenomes.

Financial & competing interest disclosure

This work was supported with funding provided by the US National Institutes of Health (NIH) Roadmap Epigenomics Program, NIH grant 5U01ES017154-02 and from Genome British Columbia and the Canadian Institutes of Health Research as part of the Canadian Epigenetics, Environment and Health Research Consortium Network (CIHR-262119). L Li is supported by a Genome Science and Technology Graduate Program Fellowship, University of British Columbia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported with funding provided by the US National Institutes of Health (NIH) Roadmap Epigenomics Program, NIH grant 5U01ES017154-02 and from Genome British Columbia and the Canadian Institutes of Health Research as part of the Canadian Epigenetics, Environment and Health Research Consortium Network (CIHR-262119). L Li is supported by a Genome Science and Technology Graduate Program Fellowship, University of British Columbia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.