Transcriptomic landscape of human primary stromal cells (fibroblasts, endothelial cells and mesenchymal stem cells) upon therapy-induced senescence (genotoxic chemotherapy)

As a prominent hallmark of senescent cells, the senescence-associated secretory phenotype (SASP) accumulates over the course of chronological aging and in diverse age-related diseases, and is a crucial driver of chronic inflammation and aging-associated phenotypes. In humans, senescent cells accumulate in multiple tissues at different rates, from 2- to 20-fold when comparing young (<35 years) to old (>65 years) healthy donors. For decades of years, the identification, characterization and pharmacological elimination of senescent cells have gained attention in the research field of aging and age-related disorders. However, the non-specificity of current senescence markers and the existence of different senescence programs strongly limits these tasks. Despite recent advances in high-throughput technologies, there is still a lack of in-depth comparison of the senescence-associated expression profile among distinct cell lineages in the tissue microenvironment. Here, we chose to profile the genome-wide expression of several primary normal human stromal cell lines including HBF1203, Huc068, HUVEC and IMR90 upon therapy-induced senescence (TIS), with the aim to determine molecular regulators of senescence phenotypes and define the potential contribution of senescent cells to human age-related pathologies. These data may provide a baseline to further explore how senescent cells arising in the local microenvironment can promote tissue dysfunction and organ degeneration in the course of an individual aging. Overall design: High-throughput RNA-seq examination of genome-wide transcriptional alterations of primary normal human stromal cell lines in proliferating versus senescence phase generated by chemotherapeutic agents such as bleomycin. HBF1203, Huc068, HUVEC and IMR90