2026年9月5日，美国麻省理工学院Paul C. Blainey等科学家在《Cell》发表研究，开发了一种通过工程化病毒样颗粒实现活细胞“自我报告”转录组的技术，能够对同一细胞样本进行重复采样的时间动态转录组分析。

转录组分析广泛应用于表征细胞基因表达，但现有方法会裂解细胞，无法对同一样本随时间的转录动态进行直接分析。研究人员通过工程化哺乳动物细胞，使其能够通过病毒样颗粒（VLPs）输出mRNA来“自我报告”其转录状态，从而解决了这一局限。对产生VLP的细胞群体培养上清液的重复采样，忠实地捕获了复杂生物学环境中不断演变的转录状态，包括原代细胞球体的急性炎症刺激和多能干细胞的多日分化。研究人员工程化了VLP组分，以实现共培养中不同细胞类型的多重读取，并用于调整自我报告的RNA谱。最后，他们展示了自我报告在微生理共培养系统的封闭结构中选择性纵向追踪内皮细胞动态的独特效用，从而识别出血管生成过程中依赖于血管周围基质的时序基因程序。总之，这项工作确立了细胞自我报告作为一种活细胞全转录组基因表达分析的广泛适用性技术。

附：英文原文

Title: Live-cell transcriptomics with engineered virus-like particles

Author: Mohamad Ali Najia, Anna Le, Jacob Borrajo, Lauren Pruett, FuNien Tsai, Ryan Ogi, Jeremy Y. Huang, Linda G. Griffith, George Q. Daley, Paul C. Blainey

Issue&Volume:

Abstract: Transcriptomic profiling is widely applied to characterize cellular gene expression, yet existing approaches lyse cells and preclude direct analysis of transcriptional dynamics in the same sample over time. We addressed this limitation by engineering mammalian cells to “self-report” their transcriptional states via mRNA export in virus-like particles (VLPs). Repeated sampling of culture media from VLP-producing cell populations faithfully captured evolving transcriptional states in complex biological settings, including acute inflammatory stimulation of primary cell spheroids and multi-day differentiation of pluripotent stem cells. We engineered VLP components for multiplexed readouts from distinct cell types in co-culture and for tuning self-reported RNA profiles. Finally, we demonstrated the unique utility of self-reporting for selective longitudinal tracking of endothelial cell dynamics within the enclosed architecture of a microphysiological co-culture system to identify perivascular stroma-dependent temporal gene programs underlying vasculogenesis. Altogether, this work establishes cellular self-reporting as a broadly enabling technology for live-cell transcriptome-wide gene expression profiling.

DOI: 10.1016/j.cell.2026.08.005

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00932-3