Structural variation in senescent IMR-90 cells

Cellular senescence is characterized by replication arrest in response to stress stimuli and is marked by several hallmarks linked to aging tissues. Beyond epigenetic changes such as the loss of heterochromatin, potential structural variants triggered by increased mobility of TEs and mtDNA - causing numts - are both linked to aging genomes. We therefore compared proliferating and senescent IMR-90 cells in terms of somatic de novo numts and integrations of non-autonomous composite retrotransposons - so-called SVA elements. We applied a subtractive and kinetic enrichment technique called RDA coupled with deep sequencing and obtained a genomic readout for SVA retrotransposition occurring during cellular senescence in IMR-90 cells. With a total of 1695 de novo integrations of which 333 were unique, we managed to localize senescence-associated SVA retrotranspositions in IMR-90 genomes. Furthermore, by comparing the genomes of proliferative and senescent IMR-90 cells by deep sequencing, we identified a total of 81 de novo numts with perfect identity to both mtDNA and nuclear hg38 flanks, adding previously unidentified senescence-associated numts. In summary, we present evidence for age-dependent structural genomic changes that go beyond epigenetic modifications. We hypothesize that the structural variants we observe potentially impact processes associated with replicative aging of IMR-90 cells.