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Abstract
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.
Original language | English |
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Pages (from-to) | 1448-1462 |
Number of pages | 15 |
Journal | Cell Reports |
Volume | 20 |
Issue number | 6 |
DOIs | |
Publication status | Published - 8 Aug 2017 |
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Dive into the research topics of 'Epigenomic Landscapes of hESC-Derived Neural Rosettes: Modeling Neural Tube Formation and Diseases'. Together they form a unique fingerprint.Projects
- 1 Finished
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The role of the neuronal epigenome in natural brain ageing and the progression of Alzheimer’s disease
Buckberry, S. (Investigator 01)
NHMRC-ARC Dementia Research Development Fellowships
1/01/16 → 31/12/19
Project: Research