Scalable and Multiplexed Recorders of Gene Regulation Dynamics Across Weeks

On March 22, 2026, from 9:00 to 10:30 AM Beijing Time, Biolà hosted the twenty-first issue of the Bioneer First-Author Forum, featuring Yixiao Yan, a PhD candidate at the University of Michigan. The session was delivered in English. Under the talk theme “Cellular Tape Recorders for Long-Term Gene Regulation Dynamics,” Yan introduced the study “Scalable and Multiplexed Recorders of Gene Regulation Dynamics Across Weeks,” for which she is a co-first author, published in Nature in 2026.

Gene expression is dynamically controlled by interacting regulatory networks, yet conventional approaches often capture only snapshots of these processes. Yan and colleagues developed CytoTape, a genetically encoded and modular intracellular protein “tape recorder” designed to continuously record multiple gene-regulatory activities within the same cells for up to three weeks, while maintaining single-cell and minutes-scale resolution.

Built on a flexible, thread-like protein assembly engineered through computationally assisted rational design, CytoTape was demonstrated across multiple mammalian cell types and enabled simultaneous recording of several transcription-factor and gene-expression activities. These recordings revealed how distinct transcriptional trajectories relate to prior cellular states and signal integration, as well as complex temporal relationships among immediate-early genes within individual cells.

The authors further extended the platform to CytoTape-vivo, enabling long-term recording of gene-expression histories directly in the living brain. In mice, the system captured doxycycline- and immediate-early-gene promoter-dependent activity across as many as 14,123 neurons spanning multiple brain regions, providing a scalable way to reconstruct weeks-long molecular histories in vivo. Together, the CytoTape toolkit offers a new framework for studying dynamic cellular processes that are difficult to resolve with conventional endpoint measurements.

We sincerely thank Yixiao Yan for sharing the development and scientific ideas behind CytoTape with the Biolà community, and for discussing how engineered intracellular recording systems can make long-timescale gene-regulatory dynamics experimentally accessible.

Citation: Zheng, L., Shi, D., Yan, Y.*, Zhou, B., Lim, J., Hou, Y., An, B., Adhinarta, J. K., Lin, M., Ko, B., Joesten, W. C., Gautam, M., Huez, E. D. M., Kim, E. C., Klyder, E. G., Chang, B., Pitchiaya, S., Roberts, M. T., Cai, D. J., … Linghu, C. (2026). Scalable and multiplexed recorders of gene regulation dynamics across weeks. Nature. https://doi.org/10.1038/s41586-026-10156-9