Large field of view-spatially resolved transcriptomics at nanoscale resolution

High-throughput profiling of in situ gene expression represents a major advance towards the systematic understanding of tissue complexity. Yet, current technologies have major bottlenecks that limit widespread application. Here, we have combined DNA nanoball (DNB) patterned array chips and in situ RNA capture to develop DNB stereo-sequencing (Stereo-seq). This approach allowed us to transcriptionally profile histological sections at nanoscale resolution with a captured area expandable to several cm2. As proof of principle, we applied Stereo-seq to the adult mouse brain and longitudinal sections of E11.5 and E16.5 mouse embryos. Thanks to its sensitivity, scalability, and amenability to additional modifications Stereo-seq will pave the way for the systematic spatially resolved-omics characterization of tissues and organisms.