A single-cell transposable element atlas of human cell identity

Single-cell RNA sequencing (scRNA-seq) is revolutionizing the study of complex biological systems. However, most sequencing studies overlook the contribution of transposable element (TE) expression to the transcriptome. The quantification of locus-specific TE expression in scRNA-seq experiments is challenging due to their repetitive sequence content and poorly characterized annotations. Here, we developed a computational tool for single-cell transposable element locus-level analysis of scRNA sequencing (Stellarscope) that reassigns multimapped reads to specific genomic loci using an expectation maximization algorithm. Using Stellarscope, we built an atlas of TE expression in human PBMCs. We found that locus-specific TEs delineate cell types and define cell subsets not identified by standard mRNA expression profiles. Altogether, this study provides comprehensive insights into the influence of TEs in human biology at the single-cell level.