Spatial transcriptomics with single cell resolution

Abstract

Abstract CO-Detection by indEXing (CODEX®) is ultra-high plex immunohistochemistry that relies on a DNA-based tagging approach, whereby antibodies are labeled with specific oligonucleotide tags (barcodes), and dye-oligonucleotides (reporters) are iteratively hybridized and dehybridized across multiple cycles. CODEX® can detect dozens of antigens simultaneously, in situ and at single cell resolution. Single-cell RNA sequencing, on the other hand, provides information about hundreds to thousands of mRNA transcripts, but without spatial context. The purpose of our study was to enrich spatially resolved CODEX® data with gene expression data obtained from CITE-seq experiments performed on the same tissues. CITE-Seq concurrently measures single-cell antigen and gene expression data, and it is possible to combine these results with CODEX® data by means of Spatially-resolved Transcriptomics via Epitope Anchoring1. We are testing this approach in intact tissues and cell spreads in order to expand the depth our spatial analysis platform. The combination of CODEX® and single cell gene expression data provides an all-in-one solution for deeply multiplexed spatial analyses of protein and gene expression with single cell resolution.