The paper introduces novel imaging platforms, Deep-STARmap and Deep-RIBOmap, designed for scalable, single-cell spatial transcriptomics and translatomics within thick, three-dimensional (3D) tissue blocks, overcoming limitations of traditional thin-sectioning methods. The researchers detail the technological advancements, including scalable probe synthesis and robust complementary DNA crosslinking, which enable the quantification of thousands of gene transcripts and their corresponding translation activities. The utility of these methods is demonstrated through comprehensive studies in mouse brain tissue, combining molecular profiling with neuronal morphology tracing, and in human cutaneous squamous cell carcinoma (cSCC) to analyze tumor–immune cell interactions in 3D. Ultimately, the new platforms provide a more accurate and quantitative understanding of gene expression and cellular organization within complex biological structures, offering significant potential for advancing neuroscience and oncology research.

References:

• Sui X, Lo J A, Luo S, et al. Scalable spatial single-cell transcriptomics and translatomics in 3D thick tissue blocks[J]. Nature Methods, 2025: 1-11.