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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, Ann Arbor, USA.
Nature communications
|February 10, 2026
概括
Seq-Scope-X通过扩展组织来增强空间转录组学 (sST),实现全转录组和蛋白质组分析的亚微米分辨率. 这一突破揭示了细胞区间的差异和各种组织中的动态代谢作用.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 细胞生物学 细胞生物学
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方法缺乏成像技术 (200-300 nm) 的光学分辨率.
- 分辨率的限制阻碍了对亚细胞结构和基因表达模式的详细研究.
研究的目的:
- 开发一种增强的空间转录学方法,具有亚微米分辨率.
- 为了克服现有的sST技术的分辨率限制.
- 为了使组织中超高分辨率的全转录组和蛋白质组分析成为可能.
主要方法:
- 介绍了Seq-Scope-X (Seq-Scope-eXpanded),一种结合Seq-Scope和组织扩张的技术.
- 组织的物理扩大以最大限度地减少转录扩散并增加空间特征密度.
- 在肝脏,大脑和结肠组织中应用,并适应空间蛋白质组学.
主要成果:
- Seq-Scope-X实现了亚微米分辨率,超过了传统的sST限制.
- 在几乎所有肝脏组织细胞中,核和细胞质区分离.
- 在核与细胞质转录组模式之间发现了广泛的差异,表明肝细胞中的动态代谢切换.
- 在大脑和结肠组织中成功应用,并在脏和桃体中适应空间蛋白质组.
结论:
- Seq-Scope-X是一个强大的平台,用于超高分辨率的全转录组和蛋白质组分析.
- 该方法显著扩大了用于研究细胞架构和功能的空间精度.
- 这些发现为细胞异质性和疾病机制提供了前所未有的新见解.
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