2026年3月3日，约翰霍普金斯大学林鼎昌团队在《自然》杂志发表论文，宣布他们开发出遗传编码的组装记录器实现细胞历史的时序解析。

研究团队介绍了细胞内叙事整合的颗粒扩展记忆（GEMINI），这是一种细胞内记录平台，利用计算设计的蛋白质组装作为细胞内记忆设备来记录单个细胞的历史。GEMINI在活细胞中可预测地生长，以树轮状荧光模式捕捉细胞事件，用于基于成像的回顾性读数。活动历史的绝对时间信息具有更高级别的准确性。GEMINI有效地绘制了不同的NFκB介导的转录变化，解决了15分钟的快速动态，并提供了可量化的信号幅度。

在异种移植物模型中，GEMINI记录了炎症诱导的跨组织信号动力学，揭示了与血管密度相关的空间异质性。当在单母脑中表达时，GEMINI对神经元功能的影响最小，可以解决神经元的转录变化和活动模式。总之，GEMINI为培养和完整组织中潜在的生理和病理过程的细胞动力学的时空映射提供了一个机器人和通用的方法。

研究人员表示，细胞不断地改变分子状态，以响应内部和外部的信号。在组织中绘制具有时空精度的细胞活动对于理解器官生理、病理和再生过程至关重要。当前的细胞传感模式主要依赖于静态快照的端点分析，或监测一小部分细胞的实时传感。

附：英文原文

Title: Genetically encoded assembly recorder temporally resolves cellular history

Author: Yan, Yuqing, Lu, Jiaxi, Li, Zhe, Zhao, Zuohan, Shay, Timothy F., Wang, Shunzhi, Lei, Yaping, Wang, Yimei, Chen, Wei, Parker, Patrick, Yang, Hongru, Qi, Aileen, Sun, Yongzhi, Bergles, Dwight E., Baker, David, Lin, Dingchang

Issue&Volume: 2026-03-03

Abstract: Cells constantly change their molecular state in response to internal and external cues1. Mapping cellular activity in tissues with spatiotemporal precision is essential for understanding organ physiology, pathology, and regenerative processes. Current cell-sensing modalities primarily rely on either endpoint analysis that takes static snapshots, or real-time sensing that monitors a small subset of cells3,4. Here, we introduce Granularly Expanding Memory for Intracellular Narrative Integration (GEMINI), an in cellulo recording platform that leverages a computationally designed protein assembly as an intracellular memory device to record the history of individual cells. GEMINI grows predictably within live cells, capturing cellular events as tree-ring-like fluorescent patterns for imaging-based retrospective readout. Absolute chronological information of activity histories is attainable with hour-level accuracy. GEMINI effectively maps differential NFκB-mediated transcriptional changes, resolving fast dynamics of 15 minutes and providing quantifiable signal amplitudes. In a xenograft model, GEMINI records inflammation-induced signaling dynamics across tissue, revealing spatial heterogeneity linked to vascular density. When expressed in the mouse brain, GEMINI minimally impacts neuronal functions and can resolve both transcriptional changes and activity patterns of neurons. Together, GEMINI provides a robust and generalizable means for spatiotemporal mapping of cell dynamics underlying physiological and pathological processes in both culture and intact tissues.

DOI: 10.1038/s41586-026-10323-y

Source: https://www.nature.com/articles/s41586-026-10323-y