SUGAR-Seq enables simultaneous detection of glycans, epitopes and the transcriptome in single cells [3'RNA-seq]

Multi-modal single cell RNA sequencing enables the precise mapping of transcriptional and phenotypic features of cellular differentiation states, but does not allow for simultaneous integration of critical post-translational modification data. Here, we describe SUrface-protein Glycan And RNA-seq (SUGAR-seq); a method that enables detection and analysis of N-linked glycosylation, extracellular epitopes and the transcriptome at the single cell level. Integrated SUGAR-seq and glycoproteome analysis identified tumor infiltrating T cells with unique surface glycan properties that report their epigenetic and functional state. Bulk 3' RNA sequencing of TILs from pooled day 14 B16-OVA tumors (CD8+, TCR+) which were FACS sorted on L-Pha low and L-Pha high.