Epigenomic landscapes of hESC-derived neural rosettes

We currently lack a comprehensive understanding of epigenetic mechanisms for neural tube formation and its implication in neural tube defects (NTDs). Developing a model to study such a complex morphogenetic process is critical, especially for its human-specific aspects. Three-dimensional, hESCs-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 investigated epigenetic mechanisms that may play a role in NTDs and found that folate-associated DNA methylation change were enriched within NR regulatory elements near genes involved in neural tube formation and metabolism. Our comprehensive regulatory maps offer new insights into epigenetic mechanisms by which folate may prevent NTDs. Lastly, our distal regulatory maps provide a better understanding on the potential role of neurological disorder-associated SNPs.