Epigenomic programming in early fetal brain development

Author:

Li Luolan1,Maire Cecile L2,Bilenky Misha3,Carles Annaïck1,Heravi-Moussavi Alireza3,Hong Chibo4,Tam Angela3,Kamoh Baljit3,Cho Stephanie3,Cheung Dorothy3,Li Irene3,Wong Tina3,Nagarajan Raman P4,Mungall Andrew J3,Moore Richard3,Wang Ting5,Kleinman Claudia L6,Jabado Nada6,Jones Steven JM3,Marra Marco A37,Ligon Keith L2,Costello Joseph F4,Hirst Martin13ORCID

Affiliation:

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

2. Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA

3. Canada's Michael Smith Genome Science Center, BC Cancer, Vancouver, BC, V5Z 4S6, Canada

4. Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94158, USA

5. Department of Genetics, Washington University, St Louis, MO 63108, USA

6. Department of Human Genetics, McGill University, Montreal, QC, H3T 1E2, Canada

7. Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6H 3N1, Canada

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.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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