Scalable and multiplexed recorders of gene regulation dynamics across weeks

作者：Lirong Zheng, Dongqing Shi, Yixiao Yan, Bingxin Zhou, Jormay Lim, Yongjie Hou, Bobae An, Jason Ken Adhinarta, Michael Lin, Bumjin Ko, William Joesten, Mehul Gautam, Elie D. M. Huez, Eung Chang Kim, Emily Klyder, Boxuan Chang, Sethuramasundaram Pitchiaya, Michael T. Roberts, Denise J. Cai, Edward S. Boyden, Donglai Wei, Pietro Liò, Changyang Linghu · 发表于：Nature · 年份：2026 · DOI：10.1038/s41586-026-10156-9 · 被引用次数：3 · 研究领域：Single-cell and spatial transcriptomics、Gene Regulatory Network Analysis、Cell Image Analysis Techniques

Abstract Gene expression is dynamically controlled by gene regulatory networks comprising multiple regulatory components to mediate cellular functions 1 . An ideal tool for analysing these processes would track multi-component dynamics with both spatiotemporal resolution and scalability within the same cells, a capability not yet achieved. Here we present CytoTape, a genetically encoded, physiologically compatible, modular protein tape recorder for multiplexed and spatiotemporally scalable recording of gene regulation dynamics continuously for up to 3 weeks, with single-cell, up to minutes-scale resolution. CytoTape uses a flexible, thread-like, elongating intracellular protein self-assembly engineered via computationally assisted rational design, built on our earlier XRI technology 2 . We demonstrate 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-dependent and IEG promoter-dependent gene expression histories across up to 14,123 neurons spanning multiple...