Spatiotemporally resolved transcriptomics reveals the subcellular RNA kinetic landscape.
Spatiotemporally resolved transcriptomics reveals the subcellular RNA kinetic landscape.
复制标题
DOI：
10.1038/s41592-023-01829-8
复制
发表时间：
2023-05
期刊：
影响因子：
48
通讯作者：
Wang, Xiao
中科院分区：
文献类型：
--
作者：
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
细胞转录组的时空调控对蛋白质的正确表达和细胞功能至关重要。然而，由于现有转录学方法的限制，RNA复杂的亚细胞动力学仍然不清楚。在这里，我们报告TEMPOmap-一种在单细胞水平上跨时间和空间揭示亚细胞RNA图谱的方法。TEMPOmap将脉冲追逐代谢标记与高度多元化的三维原位测序相结合，以同时描绘单个RNA分子的年龄和位置。利用TEMPOmap，我们构建了从转录、转位到降解的各种人类细胞中的亚细胞RNA动力学图景。对单个细胞的RNA动力学参数进行的聚类分析揭示了“动力学基因簇”，其表达模式是通过多步动力学雕刻而形成的。重要的是，这些动态基因簇在功能上是分离的，这表明亚细胞RNA动力学是以一种依赖于细胞状态和细胞类型的方式进行差异调控的。时空分辨转录组学为揭示新的时空基因调控原理提供了一种途径。TEMPOmap结合了脉冲追逐代谢标记和多重三维原位测序，同时描绘了来自数千个基因的单个RNA分子的年龄和亚细胞位置，以揭示RNA动力学图景。
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. TEMPOmap combines pulse-chase metabolic labeling with multiplexed three-dimensional in situ sequencing to simultaneously profile the age and subcellular location of individual RNA molecules from thousands of genes to reveal RNA kinetic landscapes.
登录
查看更多内容
影响因子：
23.9
作者：
Joost, Simon;Annusver, Karl;Kasper, Maria
通讯作者：
Kasper, Maria
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
DOI：
10.1038/nrm3918
发表时间：
2015-02
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.6
作者：
Braselmann E;Rathbun C;Richards EM;Palmer AE
通讯作者：
Palmer AE
影响因子：
56.9
作者：
Battich, Nico;Beumer, Joep;van Oudenaarden, Alexander
通讯作者：
van Oudenaarden, Alexander