RNAseq of oncogene-induced senescent murine macrophages

Aging organisms accumulate senescent cells, which are the result of exposure to important stress such as telomere attrition, irradiation, oncogene activation, oxidative stress or cytotoxic drugs. These senescent cells are characterized by a stable cell cycle arrest and an important secretion of pro-inflammatory factors. This senescence-associated secretory phenotype (SASP) has been shown to promote chronic inflammation leading to age-associated diseases. While a lot of in vitro models of senescence focus on senescent fibroblasts, it has been shown that a major portion of the burden of senescent cells in old mice are macrophages. Senescent macrophages have been shown to contribute to atherosclerosis, neurodegenerative diseases and macular degeneration. Yet little is known about senescent macrophages. Considering their potential role in age-associated diseases, we think these senescent macrophages and their secretions need to be investigated. Here we aimed to establish and characterize an in vitro model for oncogene-induced senescence in macrophages, to characterize secretions of these senescent macrophages and to assess impacts of these secretions on recipient cells. Overall design: RNA profiles of 3 days post-induction of control (vehicle treated) and oncogene-induced senescent (4-hydroxytamoxifen treated) murine RAW264.7 macrophages in triplicate. RAW 264.7 macrophages were retrovirally infected to express a ?Raf-1:ER construction which allows conditional activation of Raf-1 oncoprotein upon 4-hydroxytamoxifen treatment.