Spatial transcriptomics of fixed tissue micro-regions using Pick-Seq [breast]

Spatial transcriptomics and multiplexed imaging are complementary methods for studying tissue biology. Here we describe a simple method for transcriptional profiling of formalin fixed histology specimens based on mechanical isolation of tissue micro-regions containing 5-20 cells. Sequencing micro-regions from an archival melanoma specimen having multiple distinct histologies reveals significant differences in transcriptional programs associated with tumor invasion, proliferation, and immunoediting and parallel imaging confirms changes in immuno-phenotypes and cancer cell states. mRNA from 40μm regions of interest were collected from three histological sites in human breast cancer sections (Fresh Frozen), sequenced and gene expression profiles were analyzed.