人前脑发育模型中的染色质可访问性动态
Alexandro E Trevino1,2, Nasa Sinnott-Armstrong3, Jimena Andersen2,4
1Department of Bioengineering, Stanford University, Stanford, CA, USA.
Science (New York, N.Y.)
|January 25, 2020
概括
研究人员在人类前脑器官中绘制了可访问的染色质,以了解发育过程中的基因调节. 这项研究揭示了皮质形成和神经精神疾病的遗传联系.
科学领域:
- 神经科学
- 发育生物学
- 基因组学
背景情况:
- 脑前部的发育涉及复杂的同步细胞过程,
- 这些过程的干扰会导致各种神经和精神疾病.
- 了解控制人类前脑发育的基因调控机制对于疾病研究至关重要.
研究的目的:
- 在人类前脑三维器官中创建可访问的染色质的全面地图.
- 在长期 (20 个月) 的皮质生成过程中研究基因调节的动态变化.
- 确定参与人类前脑发育的调节因素和转录因子及其与疾病的联系.
主要方法:
- 产生人类前脑的三维器官.
- 从背部和腹部前脑器官中取出质和神经元系的纵向采样.
- 染色体可访问性测试 (例如ATAC-seq) 来绘制开放的染色体区域.
- 染色体可访问性数据与转录组学 (例如,RNA-seq) 的整合.
主要成果:
- 在人类前脑器官中生成可访问的染色体区域的详细地图.
- 在不同发育阶段的器官中发现了人脑组织中的活性色素区域.
- 确定了可能的增强剂基因联系和调节人类皮质形成的关键转录因子.
- 该研究在器官模型中确定了与神经精神疾病相关的特征.
结论:
- 开发的器官平台为人类前脑发育过程中的基因调节动态提供了前所未有的洞察力.
- 这种资源有助于绘制疾病的遗传风险和探索进化保护.
- 这些发现为研究神经精神疾病和人类大脑发育的分子基础提供了宝贵的工具.
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