Locus-specific expression of transposable elements in single cells with CELLO-seq

Transposable Elements (TEs) regulate diverse biological processes, from early development to cancer. Expression of young TEs is difficult to measure with next generation single-cell sequencing technologies as their highly repetitive nature means that short cDNA reads cannot be unambiguously mapped to a specific locus. CELLO-seq combines long-read scRNA sequencing with computational analyses to measure TE expression at unique loci. We use CELLO-seq to assess the widespread expression of TEs in 2-cell mouse blastomeres as well as human induced pluripotent stem cells (hiPSCs). Across both species, old and young TEs showed evidence of locus-specific expression, with simulations demonstrating that only a small number of very young elements in the mouse could not be mapped back to the reference with high confidence. Exploring the relationship between the expression of individual elements and putative regulators revealed large heterogeneity, with TEs within a class showing different patterns of correlation, suggesting distinct regulatory mechanisms.