Sequencing-based Spatial Transcriptomics with scRNA-seq 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 significantly improved from ~100 um to <1 um, well below the size of a mammalian cell. However, their capture efficiency has always been the bottleneck, ~one order of magnitude lower than that of single cell RNA sequencing (scRNA-seq). The low capture efficiency diminishes the effect of high capture resolution and negatively impact subsequent data interpretation. Here, we introduce Salus spatial transcriptomic system (Salus-STS), which provides ~1 um capture resolution and a capture efficiency approaching that of scRNA-seq. A record high of ~13,000 UMIs can be captured from mouse testis sample per 10 x 10 um2 area. The mouse testis data was analyzed at an unprecedented resolution of 2 um, disclosing rare cells organized as single cell layers.