Spatially resolved single-cell translatomics at molecular resolution

Author:

Zeng Hu12ORCID,Huang Jiahao12ORCID,Ren Jingyi12ORCID,Wang Connie Kangni2ORCID,Tang Zefang12ORCID,Zhou Haowen2ORCID,Zhou Yiming123ORCID,Shi Hailing12ORCID,Aditham Abhishek24ORCID,Sui Xin12ORCID,Chen Hongyu12ORCID,Lo Jennifer A.2ORCID,Wang Xiao12ORCID

Affiliation:

1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

2. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

3. Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

4. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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