Transcriptomic landscape of human primary stromal cells upon therapy-induced senescence (genotoxic chemotherapy and ionizing radiation)

Cellular senescence is a permanent state of cell cycle arrest that promotes tissue remodeling during embryonic development and after trauma or injury, but can also contribute to the decline of organ regenerative potential and tissue normal function, to local and systemic inflammation, and to tumorigenesis in aged organisms. For years, the identification, characterization, and pharmacological elimination of senescent cells have gained attention in the research field of aging and age-related diseases. However, the non-specificity of current senescence markers and the existence of different senescence programs strongly limit these tasks. Here, we profiled the genome-wide expression of primary normal human prostate stromal cells (PSC27) upon therapy-induced senescence (TIS), with the aim to determine molecular regulators of senescence phenotypes and define the inherent correlation of gene expression pattern with the extensive senescence-associated 3D genome reorganization. This TIS-specific configuration of chromosome architecture brings active genes located in genomic regions adjacent to senescence-associated heterochromatin domains (SAHDs) in close spatial proximity and favors their expression. These data may provide a baseline to further explore show how multi-omics and 3D mapping can identify critical features of cellular senescence and discover key determinants of senescence and SAHF formation in the genome-wide landscape.