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 |
|---|---|
| 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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Epigenomic Landscapes of hESC-Derived Neural Rosettes : Modeling Neural Tube Formation and Diseases. / Valensisi, Cristina; Andrus, Colin; Buckberry, Sam; Doni Jayavelu, Naresh; Lund, Riikka J.; Lister, Ryan; Hawkins, R. David.
In: Cell Reports, Vol. 20, No. 6, 08.08.2017, p. 1448-1462.Research output: Contribution to journal › Article
TY - JOUR
T1 - Epigenomic Landscapes of hESC-Derived Neural Rosettes
T2 - Modeling Neural Tube Formation and Diseases
AU - Valensisi, Cristina
AU - Andrus, Colin
AU - Buckberry, Sam
AU - Doni Jayavelu, Naresh
AU - Lund, Riikka J.
AU - Lister, Ryan
AU - Hawkins, R. David
PY - 2017/8/8
Y1 - 2017/8/8
N2 - 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.
AB - 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.
KW - DNA methylation
KW - enhancers
KW - epigenetics
KW - epigenomics
KW - neural tube defects
UR - http://www.scopus.com/inward/record.url?scp=85026890640&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2017.07.036
DO - 10.1016/j.celrep.2017.07.036
M3 - Article
VL - 20
SP - 1448
EP - 1462
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 6
ER -