Plate-based long-read single cell gene- and isoform transcriptome profiling using scLIS-seq

Single cell RNA-profiling in tandem with short-read sequencing (SR-scRNA-seq) has revolutionized the field of transcriptomics, permitting a highly granular view on cellular blood and tissue composition and the construction of human cell atlases. However, discrimination between various transcript isoforms remains challenging. Here we propose single cell long-read isoform sequencing (scLIS-seq), a scRNA-seq workflow based on Smart-seq3xpress (SS3X) cDNA generation and Oxford Nanopore Technologies PromethION sequencing. Using scLIS-seq, we profiled the long-read transcriptomes of Jurkat and HEK293T cells and compared its performance to SS3X starting from the identical cDNA.