Spatially resolved single-cell RNA-sequencing reveals expression heterogeneity in tumor microenvironment

To better understand how individual cells function within an anatomical space, we developed XYZeq, a novel scRNA-seq workflow that uses combinatorial indexing in microwells to encode spatial metadata into scRNA-seq libraries. We used XYZeq to profile heterotopic mouse liver and spleen tumor models to capture transcriptomes from tens of thousands of cells across a total of eight tissue slices. Overall design: Spatially resolved single-cell RNA-sequencing from eight tissue sections of MC38-injected liver and spleen organs (samples L30C and L30C8 are from the same slice). Additional experiments using cell lines and comparing to droplet-based single-cell RNA-seq.