Quantification of transcript isoforms at the single-cell level using SCALPEL

3' based single-cell RNA sequencing (scRNA-seq) has enabled the study of gene expression at the individual cell level and the development of few methods to quantify transcriptomic variability at the single-cell level. Yet, most of these methods have low sensitivity and specificity. Here, we present SCALPEL, a new tool to quantify and characterize transcript isoforms at the single-cell level using standard 3' based single-cell transcriptomics data. SCALPEL predictions have higher sensitivity than that of other tools and can be validated experimentally. We have used SCALPEL to study the changes in isoform usage during mouse spermatogenesis and in the differentiation of induced pluripotent stem cells (iPSCs) to neural progenitors (NPCs). These analyses confirmed known changes in the 3' UTR length during cell differentiation and allowed the identification of new cell populations and cell type specific microRNA signatures controlling isoform expression in individual cells. Together, our results highlight the importance of isoform quantification to gain insight on the gene regulatory mechanisms at the single-cell level. Human induced pluripotent stem cells (iPSCs) and neural progenitor cells (NPCs) derived from the same iPSc were dissociated to performe single-cell RNAseq analysis