Seq-Scope-eXpanded:超越光学分辨率的空间奥米克
Angelo Anacleto1, Weiqiu Cheng2, Qianlu Feng3,4
1Department of Molecular & Integrative Physiology, University of Michigan.
bioRxiv : the preprint server for biology
|February 20, 2025
概括
Seq-Scope-X通过扩展组织来增强空间转录学 (sST),实现亚微米分辨率. 这一突破揭示了细胞区的基因表达差异,并使空间蛋白质组分析成为可能.
科学领域:
- 空间生物学 空间生物学
- 基因组学就是基因组学.
- 分子成像学分子成像学
背景情况:
- 基于测序的空间转录组学 (sST) 提供了全转录组的基因表达映射.
- 目前的sST方法缺乏基于成像技术 (200-300 nm) 的光学分辨率.
- 转录扩散限制了现有的sST方法中的空间精度.
研究的目的:
- 通过组织扩张来提高Seq-Scope的亚微米分辨率.
- 为了克服当前sST方法的分辨率限制.
- 为了实现超高分辨率的全转录组和蛋白质组分析.
主要方法:
- 开发使用物理组织扩张的Seq-Scope-X (Seq-Scope-eXpanded).
- 通过组织扩张最大限度地减少转录扩散效应.
- 将Seq-Scope-X应用于肝脏,大脑和结肠组织进行转录组分析.
- 修改Seq-Scope-X用于使用条形码标记抗体进行空间蛋白质组分析.
主要成果:
- Seq-Scope-X实现了亚微米分辨率,超过了之前的sST限制.
- 组织扩张增加了空间特征密度的数量级.
- 在几乎所有肝细胞中解决了核和细胞质区间,揭示了明显的转录组模式.
- 证明了肝细胞的动态代谢作用切换,通过成像方法证实.
- 已成功应用于非肝脏组织,并适用于空间蛋白质基因分析.
结论:
- Seq-Scope-X是超高分辨率空间转录组学和蛋白质组学的一个变革性工具.
- 该技术为细胞分析提供了无与伦比的空间精度.
- 这些发现提升了对细胞结构,功能和疾病机制的理解.
- 揭示了显著的核-细胞质转录组差异影响细胞功能.
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