Single senescent cell sequencing reveals heterogeneity in senescent cells induced by telomere erosion

作者：Huanyin Tang, Anke Geng, Tengjiao Zhang, Chen Wang, Ying Jiang, Zhiyong Mao · 发表于：Protein & Cell · 年份：2018 · DOI：10.1007/s13238-018-0591-y · 被引用次数：50 · 研究领域：Telomeres, Telomerase, and Senescence、Single-cell and spatial transcriptomics、Genetics, Aging, and Longevity in Model Organisms

Dear Editor, Over a half-century ago, Dr. Leonard Hayflick described the phenotype of a finite lifespan for human fibroblasts being passaged in in vitro cell culture (Hayflick et al., 1961), a phenomenon today known as replicative cellular senescence. Cellular senescence has been defined as a state in which cells lose their potential to divide and are permanently arrested in either the G1, or arguably the G2 stage of the cell cycle (Mao et al., 2012). In addition to replicative cellular senescence—which is induced by large amounts of DNA damage at telomeres due to loss of the specialized T-loop structure—exogenous sublethal stresses such as ionizing radiation, genotoxic chemicals or hyper-activated oncogenes may also trigger a similar form of senescence, stress induced premature cellular senescence (SIPS). Cells in the states of replicative senescence and SIPS share a number of common features such as changes in morphology, secretion of inflammatory factors and an increase in β-galactosidase activity. The induction of cellular senescence is mediated by either Rb or p53, two critical tumor suppressors, and represents a potent anti-tumor mechanism (Campisi, 2013). Cellular senescence is also beneficial to injured tissues or organs by secreting inflammatory factors, termed the senescence associated secretory phenotype (SASP), to promote tissue repair and the clearance of senescent cells. Paradoxically, if senescent cells are not promptly removed by NK cells and macrophages (Kriz...