Spatially resolved single-cell translatomics at molecular resolution

The precise control of messenger RNA (mRNA) translation is a crucial step in posttranscriptional gene regulation of cellular physiology. However, it remains a challenge to systematically study mRNA translation at the transcriptomic scale with spatial and single-cell resolution. Here, we report the development of ribosome-bound mRNA mapping (RIBOmap), a highly multiplexed three-dimensional in situ profiling method to detect cellular translatome. RIBOmap profiling of 981 genes in HeLa cells revealed cell cycle-dependent translational control and colocalized translation of functional gene modules. We mapped 5413 genes in mouse brain tissues, yielding spatially resolved single-cell translatomic profiles for 119,173 cells and revealing cell type-specific and brain region-specific translational regulation, including translation remodeling during oligodendrocyte maturation. Our method detected widespread patterns of localized translation in neuronal and glial cells in intact brain tissue networks.

Automated summary

The precise control of mRNA translation is crucial in posttranscriptional gene regulation, but it is challenging to study it systematically at the transcriptomic scale with spatial and single-cell resolution. The researchers developed a method called RIBOmap to detect cellular translatome. The study revealed cell cycle-dependent translational control and colocalized translation of functional gene modules.