Highly multiplexed single-cell RNA-seq by DNA oligonucleotide tagging of cellular proteins.

Single-cell RNA sequencing is readily multiplexed by labeling cells with ClickTags. We describe a universal sample multiplexing method for single-cell RNA sequencing in which fixed cells are chemically labeled by attaching identifying DNA oligonucleotides to cellular proteins. Analysis of a 96-plex perturbation experiment revealed changes in cell population structure and transcriptional states that cannot be discerned from bulk measurements, establishing an efficient method for surveying cell populations from large experiments or clinical samples with the depth and resolution of single-cell RNA sequencing.