Epigenomic Landscapes of hESC-Derived Neural Rosettes: Modeling Neural Tube Formation and Diseases.
Epigenomic Landscapes of hESC-Derived Neural Rosettes: Modeling Neural Tube Formation and Diseases.
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DOI：
10.1016/j.celrep.2017.07.036
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发表时间：
2017-08-08
期刊：
影响因子：
8.8
通讯作者：
Hawkins RD
中科院分区：
文献类型：
--
作者：
Valensisi C;Andrus C;Buckberry S;Doni Jayavelu N;Lund RJ;Lister R;Hawkins RD
我们目前缺乏一个全面的了解神经管形成的机制及其对神经管缺陷（NTDs）的贡献。开发一个模型来研究这样一个复杂的形态发生过程是至关重要的，特别是一个模型人类特定的方面。三维，hESC衍生的神经管（NR）提供了一个强大的资源，在体外模拟人类神经管的形成。表观基因组图谱揭示了相对于2D系统，NR特有的增强子元件。一个主要的监管网络表明，关键NR属性与其表观基因组景观。我们发现，叶酸相关的DNA甲基化变化丰富的NR调控元件附近的基因参与神经管的形成和代谢。我们全面的监管地图提供了深入了解叶酸可以预防NTD的机制。最后，我们的远端调控图提供了一个更好的理解神经系统疾病相关的SNP的潜在作用。神经管发育提供了神经管发育的3D模型。Valensisi等人表明，与2D神经干细胞相比，这些细胞具有不同的表观基因组景观。在NR中鉴定的顺式调节元件含有叶酸相关的CpG，其在神经管发育和神经发育障碍相关变体中可能是重要的。
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 is critical, especially one that models 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 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. Neural rosettes offer a 3D model of neural tube development. Valensisi et al. show that these cells have distinct epigenomic landscapes compared to 2D neural stem cells. Cis-regulatory elements identified in NRs harbor folate-associated CpGs, which may be important during neural tube development, and neurodevelopmental disorder associated variants.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
44.1
作者：
Hawkins, R. David;Hon, Gary C.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
5.2
作者：
Esmailpour, Taraneh;Huang, Taosheng
通讯作者：
Huang, Taosheng
影响因子：
14.9
作者：
Burger L;Gaidatzis D;Schübeler D;Stadler MB
通讯作者：
Stadler MB
影响因子：
2.4
作者：
Donovan AP;Basson MA
通讯作者：
Basson MA