RT Journal Article
SR Electronic
T1 Spatially Resolved Single-cell Translatomics at Molecular Resolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.27.509605
DO 10.1101/2022.09.27.509605
A1 Hu Zeng
A1 Jiahao Huang
A1 Jingyi Ren
A1 Connie Kangni Wang
A1 Zefang Tang
A1 Yiming Zhou
A1 Abhishek Aditham
A1 Hailing Shi
A1 Xin Sui
A1 Xiao Wang
YR 2022
UL http://biorxiv.org/content/early/2022/09/28/2022.09.27.509605.abstract
AB The precise control of mRNA translation is a crucial step in post-transcriptional gene regulation of cellular physiology. However, it remains a major challenge to systematically study mRNA translation at the transcriptomic scale with spatial and single-cell resolutions. Here, we report the development of RIBOmap, a three-dimensional (3D) in situ profiling method to detect mRNA translation for thousands of genes simultaneously in intact cells and tissues. By applying RIBOmap to 981 genes in HeLa cells, we revealed remarkable dependency of translation on cell-cycle stages and subcellular localization. Furthermore, we profiled single-cell translatomes of 5,413 genes in the adult mouse brain tissue with a spatial cell atlas of 62,753 cells. This spatial translatome profiling detected widespread patterns of localized translation in neuronal and glial cells in intact brain tissue networks. Together, RIBOmap presents the first spatially resolved single-cell translatomics technology, accelerating our understanding of protein synthesis in the context of subcellular architecture, cell types, and tissue anatomy.Competing Interest StatementX.W., H.Z., and J.R. are inventors on pending patent applications related to RIBOmap. All methods, protocols, and sequences are freely available to nonprofit institutions and investigators.