Systematic analyses of transposable element expression dynamics using long read RNA-seq in pluripotent stem cells and germ lineage cells

Transposable elements (TEs) are genomic elements that are found in multiple copies in mammalian genomes. Previously thought to have little functional relevance, recent studies have reported roles for TEs in multiple biological processes, and particularly in embryonic development. However, due to their repetitive nature it has been hard to fully account for the contributions of TEs to the transcriptome. To study the expression dynamics of TEs in human early development (hED), we performed in vitro differentiation of human pluripotent stem cells (hPSCs) to endoderm, mesoderm and ectoderm lineages, and constructed lineage-specific transcriptome assemblies using long-read sequence data to accurately place TE sequences in their transcript context. The analyses of specific TE types and genomic loci revealed lineage-specific expression patterns reflecting dynamic expression trajectories with an expression outburst of multiple TEs, including multiple LINEs and LRTs in the ectoderm lineage. We found several LTRs, including HERVH and LTRY7, to be highly expressed in hPSC and the endoderm, including endoderm-specific LTR6A. Indeed, a common feature of germ lineage-specific expression is the lineage-specific regulation of TE-containing transcripts with highly dynamic stability and subcellular localization. Chromatin association with TEs increased with differentiation. This study suggests that TEs contribute to hED via the regulation of chromatin structure.