小柯机器人

美国麻省理工学院Xiao Wang课题组利用时空分辨的转录物组学揭示亚细胞RNA的动力学景观。这一研究成果于2023年4月10日在线发表在国际学术期刊《自然—方法学》上。

研究人员报道了TEMPOmap——一种在单细胞水平上发现跨时间和空间的亚细胞RNA概况的方法。TEMPOmap整合了脉冲追踪代谢标记和高度复用的三维原位测序，从而同时描述单个RNA分子的年龄和位置。利用TEMPOmap，研究人员构建了各种人类细胞中从转录、转运到降解的亚细胞RNA动力学景观。对单个细胞的RNA动力学参数进行聚类分析，研究人员发现了“动力学基因簇”，其表达模式是由多步骤的动力学雕琢形成的。

重要的是，这些动力学基因簇在功能上是分离的，这表明亚细胞的RNA动力学是以细胞状态和细胞类型依赖的方式受到不同的调节。时空解析的转录组学为揭示新的时空基因调控原理提供了一个途径。

据悉，细胞转录组的时空调节对于蛋白质的正常表达和细胞功能至关重要。然而，由于现有转录组学方法的限制，RNA错综复杂的亚细胞动态仍然被掩盖。

附：英文原文

Title: Spatiotemporally resolved transcriptomics reveals the subcellular RNA kinetic landscape

Author: Ren, Jingyi, Zhou, Haowen, Zeng, Hu, Wang, Connie Kangni, Huang, Jiahao, Qiu, Xiaojie, Sui, Xin, Li, Qiang, Wu, Xunwei, Lin, Zuwan, Lo, Jennifer A., Maher, Kamal, He, Yichun, Tang, Xin, Lam, Judson, Chen, Hongyu, Li, Brian, Fisher, David E., Liu, Jia, Wang, Xiao

Issue&Volume: 2023-04-10

Abstract: Spatiotemporal regulation of the cellular transcriptome is crucial for proper protein expression and cellular function. However, the intricate subcellular dynamics of RNA remain obscured due to the limitations of existing transcriptomics methods. Here, we report TEMPOmap—a method that uncovers subcellular RNA profiles across time and space at the single-cell level. TEMPOmap integrates pulse-chase metabolic labeling with highly multiplexed three-dimensional in situ sequencing to simultaneously profile the age and location of individual RNA molecules. Using TEMPOmap, we constructed the subcellular RNA kinetic landscape in various human cells from transcription and translocation to degradation. Clustering analysis of RNA kinetic parameters across single cells revealed ‘kinetic gene clusters’ whose expression patterns were shaped by multistep kinetic sculpting. Importantly, these kinetic gene clusters are functionally segregated, suggesting that subcellular RNA kinetics are differentially regulated in a cell-state- and cell-type-dependent manner. Spatiotemporally resolved transcriptomics provides a gateway to uncovering new spatiotemporal gene regulation principles.

DOI: 10.1038/s41592-023-01829-8

Source: https://www.nature.com/articles/s41592-023-01829-8

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex