Sequencing-based Spatial Transcriptomics with High Sensitivity

The advent of spatial transcriptomics has dramatically expanded our ability to study the vast network of cell-cell interactions at the molecular level in tissue. Among current methods, sequencing-based approaches have great potential in discovery because of their unbiased capture of the whole transcriptome. In the last couple of years, the spatial resolution for the capture addresses has been improved from ~100 μm to <1 μm, well below the size of a mammalian cell. However, the capture efficiency of sequencing-based methods is generally low, which diminishes the effect of high capture resolution and negatively impacts subsequent data interpretation. Here, we introduce a new spatial transcriptomic system, which provides ~1 μm capture resolution and a much higher capture efficiency. We demonstrate that as high as ~14,000 UMIs can be captured from mouse testis sample per 10 × 10 μm² area at a sequencing saturation of 0.43. Rare cells organized in single-cell-layers can be recovered when the data was analyzed at an effective resolution of 2 μm.