美国密歇根大学Changyang Linghu小组提出了可扩展与多重化的基因调控动态跨周记录器。这一研究成果于2026年1月26日发表在国际顶尖学术期刊《自然》上。

课题组人员展示了CytoTape，一种基因编码的模块化蛋白质磁带记录器，用于连续记录基因调控动态长达三周的多路和时空可扩展记录，生理上兼容，具有单细胞，分钟级分辨率。CytoTape采用了一种灵活的、线状的、细长的细胞内蛋白质自组装，通过计算辅助理性设计，建立在早期XRI技术的基础上。该研究组证明了它在多种哺乳动物细胞类型中的实用性，实现了五种转录因子活性和基因转录活性的同时记录。CytoTape揭示了不同的转录轨迹与转录历史和信号整合相关，并且不同的即时早期基因（IEGs）在单个细胞中表现出复杂的时间相关性。

该团队进一步将CytoTape扩展到CytoTape-vivo，以便在活脑中进行可扩展的、时空分辨率的单细胞记录，从而能够同时记录长达数周的多西环素和IEG启动子依赖的基因表达历史，这些基因表达历史跨越每个主题的多个大脑区域，多达14123个神经元。总之，CytoTape工具包建立了一个多功能平台，可扩展和多路分析体外和体内的细胞生理过程。

研究人员表示，基因表达受多种调控组分组成的基因调控网络动态调控，介导细胞功能。分析这些过程的理想工具是在同一单元内跟踪具有时空分辨率和可扩展性的多组分动态，这是目前尚未实现的能力。

附：英文原文

Title: Scalable and multiplexed recorders of gene regulation dynamics across weeks

Author: Zheng, Lirong, Shi, Dongqing, Yan, Yixiao, Zhou, Bingxin, Lim, Jormay, Hou, Yongjie, An, Bobae, Adhinarta, Jason K., Lin, Michael, Ko, BumJin, Joesten, William C., Gautam, Mehul, Huez, Elie D. M., Kim, Eung Chang, Klyder, Emily G., Chang, Boxuan, Pitchiaya, Sethuramasundaram, Roberts, Michael T., Cai, Denise J., Boyden, Edward S., Wei, Donglai, Li, Pietro, Linghu, Changyang

Issue&Volume: 2026-01-26

Abstract: Gene expression is dynamically regulated by gene regulatory networks comprising multiple regulatory components to mediate cellular functions1. An ideal tool for analyzing these processes would track multiple-component dynamics with both spatiotemporal resolution and scalability within the same cells, a capability not yet achieved. Here, we present CytoTape, a genetically encoded, modular protein tape recorder for multiplexed and spatiotemporally scalable recording of gene regulation dynamics continuously for up to three weeks, physiologically compatible, with single-cell, minutes-scale resolution. CytoTape employs a flexible, thread-like, elongating intracellular protein self-assembly engineered via computationally assisted rational design, built on earlier XRI technology2. We demonstrated its utility across multiple mammalian cell types, achieving simultaneous recording of five transcription factor activities and gene transcriptional activities. CytoTape reveals that divergent transcriptional trajectories correlate with transcriptional history and signal integration, and that distinct immediate early genes (IEGs) exhibit complex temporal correlations within single cells. We further extended CytoTape into CytoTape-vivo for scalable, spatiotemporally resolved single-cell recording in the living brain, enabling simultaneous weeks-long recording of doxycycline- and IEG promoter-dependent gene expression histories across up to 14,123 neurons spanning multiple brain regions per mouse. Together, the CytoTape toolkit establishes a versatile platform for scalable and multiplexed analysis of cell physiological processes in vitro and in vivo.

DOI: 10.1038/s41586-026-10156-9

Source: https://www.nature.com/articles/s41586-026-10156-9