该课题组提出TimeVault,一个基因编码系统,记录和存储转录组在活的哺乳动物细胞为未来读取。TimeVault利用工程vault颗粒,通过聚(A)结合蛋白捕获mRNA。研究团队证明,TimeVault储存的转录组在活细胞中稳定超过7天。TimeVault能够以最小的细胞扰动进行高保真转录组全范围记录,捕捉瞬时应激反应,揭示逃避EGFR抑制的肺癌细胞中药物初始持续状态下的基因表达变化。通过连接过去和现在的细胞状态,TimeVault提供了一个强大的工具来解码细胞如何应对压力、做出命运决定和抵抗治疗。
据悉,理解细胞如何随着时间的推移做出决定需要将过去的分子状态与未来的表型结果联系起来的能力。
附:英文原文
Title: A genetically encoded device for transcriptome storage in mammalian cells
Author: Yu-Kai Chao, Michelle Wu, Qiyu Gong, Fei Chen
Issue&Volume: 2026-01-15
Abstract: Understanding how cells make decisions over time requires the ability to link past molecular states to future phenotypic outcomes. We present TimeVault, a genetically encoded system that records and stores transcriptomes within living mammalian cells for future readout. TimeVault leverages engineered vault particles that capture mRNA through poly(A) binding protein. We demonstrate that the transcriptome stored by TimeVaults is stable in living cells for over 7 days. TimeVault enables high-fidelity transcriptome-wide recording with minimal cellular perturbation, capturing transient stress responses and revealing gene expression changes underlying drug-naive persister states in lung cancer cells that evade EGFR inhibition. By linking past and present cellular states, TimeVault provides a powerful tool for decoding how cells respond to stress, make fate decisions, and resist therapy.
DOI: adz9353
Source: https://www.science.org/doi/10.1126/science.adz9353
