Senescence induction universally activates transposable element expression

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.

衰老细胞可持续性分泌炎性细胞因子，该现象被称为衰老相关分泌表型（senescence-associated secretory phenotype，SASP）。既往研究已证实SASP参与衰老细胞的免疫清除过程，但其具体调控机制仍未明确。我们近期开展的转录组谱分析研究显示，人类衰老干祖细胞（senescent human stem and progenitors，s-HSPCs）会显著表达基因组转座元件（transposable elements，TEs）及炎症相关通路。此外，已有研究表明，去甲基化试剂可诱导转座元件表达，并激活双链RNA识别通路与下游干扰素刺激基因，最终引发免疫介导的细胞死亡。据此，为探究转座元件的激活是否普遍存在于不同衰老诱导方式中，我们对人工诱导衰老的细胞系进行了转录组学分析，观察到转座元件的显著激活。因此我们提出，转座元件的表达可能在衰老细胞的免疫清除过程中发挥作用。