A method for profiling cell surface proteomes by using DNA-barcoded antibodies and droplet-based single cell sequencing (dsc-seq). We developed a new workflow that combines combinatorial indexing and commercially available dsc-seq to enable cost-effective cell surface proteomic profiling of greater than 10x5 cells per microfluidic reaction (SCITO-seq). We demonstrated SCITO-seq's feasibility and scalability by profiling mixed species cell lines and mixed human T and B lymphocytes. We also used SCITO-seq to characterize peripheral blood mononuclear cells from two donors. Our results are reproducible and comparable to those obtained by mass cytometry. SCITO-seq can be extended to include simultaneous profiling of additional modalities such as transcripts and accessible chromatin or tracking of experimental perturbations such as genome edits or extracellular stimuli.
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