Scalable full-transcript coverage single cell RNA sequencing with Smart-seq3xpress

Abstract Plate-based single-cell RNA-sequencing methods with full-transcript coverage typically excel at sensitivity but are more costly and time-consuming. Here, we miniaturized and streamlined the Smart-seq3 protocol for drastically reduced cost and increased throughput. Applying Smart-seq3xpress to 16,349 human peripheral blood mononuclear cells revealed a highly granular atlas complete with both common and rare cell types whose identification previously relied on additional protein measurements or the integration with a reference atlas.