Senescence induction universally activates transposable element expression

Abstract

Senescent cells constitutively secrete inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP). Previous work has implicated SASP in immune-mediated clearance of senescent cells; however, its regulation remains unknown. Our recent transcriptome profiling study has shown that human senescent human stem and progenitors (s-HSPCs) robustly express genomic transposable elements (TEs) and pathways of inflammation. Furthermore, hypomethylating agents have been previously shown to induce expression of TEs and activate the dsRNA recognition pathway and downstream interferon-stimulated genes, leading to immune mediated cell death. Therefore, to examine whether activation of TEs occurred universally, independent of their modality of senescence induction, we performed transcriptomic analysis in artificially-induced senescent cell-lines and observed a robust activation of TEs. Hence we propose that the expression of TEs might play a role in immune mediated clearance of senescent cells.