在单细胞分辨率下胚胎发育的 cis 调节动态
Darren A Cusanovich1, James P Reddington2, David A Garfield2
1Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
Nature
|March 15, 2018
概括
这项研究以单细胞分辨率绘制了水果胚胎的染色质可访问性. 它揭示了基因调节网络如何指导胚胎发生过程中的细胞命运,并确定了关键的调节元素.
科学领域:
- 发育生物学
- 基因组学
- 表观遗传学
背景情况:
- 了解控制细胞命运的基因调节网络对于发育生物学至关重要.
- 单细胞基因表达研究提供了对血统承诺的见解,但调节机制仍然不清楚.
- 研究色素可访问性动态可以更深入地了解发育过程.
研究的目的:
- 在单细胞分辨率下研究胚胎形成过程中的染色体调节场景的动态.
- 发现控制甲基动物细菌层和细胞类型规范的Cis调节程序.
- 确定组织特异性的调节元素并验证它们的生殖层特异性.
主要方法:
- 使用单细胞组合索引测定以测序可访问的染色体 (sci-ATAC-seq).
- 在三个关键发育阶段,从固定Drosophila melanogaster胚胎中分析了超过20,000个单核的染色质可访问性.
- 验证了转基因胚胎中生殖层特异性的预测增强剂.
主要成果:
- 在胃化之前观察到调节基因组可访问性的空间异质性,与未来的细胞命运相关.
- 通过胚胎形成中期的染色质可访问性模式来推断单个细胞类型.
- 确定了30 075个具有组织特异性可访问性的远端调节元件,实现了增强剂的90%的验证准确性.
结论:
- 胚胎的单细胞分析有效地解决了发育过程中的动态色素格局变化.
- 在内皮和非肌体内皮之间发现了保存的调节元件使用,这表明共享的内皮程序.
- 提供对甲状动物发育至关重要的监管元素的高分辨率地图.
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