Epigenomic Landscapes of hESC-Derived Neural Rosettes: Modeling Neural Tube Formation and Diseases
Cristina Valensisi,
Colin Andrus,
Sam Buckberry,
Naresh Doni Jayavelu,
Riikka J. Lund,
Ryan Lister,
R. David Hawkins
Affiliations
Cristina Valensisi
Division of Medical Genetics, Department of Medicine and Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Colin Andrus
Division of Medical Genetics, Department of Medicine and Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Sam Buckberry
Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia
Naresh Doni Jayavelu
Division of Medical Genetics, Department of Medicine and Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Riikka J. Lund
Turku Centre for Biotechnology, University of Turku, Turku, Finland
Ryan Lister
Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia
R. David Hawkins
Division of Medical Genetics, Department of Medicine and Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
We currently lack a comprehensive understanding of the mechanisms underlying neural tube formation and their contributions to neural tube defects (NTDs). Developing a model to study such a complex morphogenetic process, especially one that models human-specific aspects, is critical. Three-dimensional, human embryonic stem cell (hESC)-derived neural rosettes (NRs) provide a powerful resource for in vitro modeling of human neural tube formation. Epigenomic maps reveal enhancer elements unique to NRs relative to 2D systems. A master regulatory network illustrates that key NR properties are related to their epigenomic landscapes. We found that folate-associated DNA methylation changes were enriched within NR regulatory elements near genes involved in neural tube formation and metabolism. Our comprehensive regulatory maps offer insights into the mechanisms by which folate may prevent NTDs. Lastly, our distal regulatory maps provide a better understanding of the potential role of neurological-disorder-associated SNPs.
