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SCI 5 September 2024 Titration of RAS alters senescent state and influences tumour initiation （Nature; IF:50.5） Chan ASL, Zhu H, Narita M, Cassidy LD, Young ARJ, Bermejo-Rodriguez C, Janowska AT, Chen HC, Gough S, Oshimori N et al: Titration of RAS alters senescent state and influences tumour initiation. Nature 2024. Correspondence to：Masashi.Narita@cruk.cam.ac.uk Oncogenic RAS-induced senescence (OIS) is an autonomous tumour suppressor mechanism associated with premalignancy. Achieving this phenotype typically requires a high level of oncogenic stress, yet the phenotype provoked by lower oncogenic dosage remains unclear. Here we develop oncogenic RAS dose-escalation models in vitro and in vivo, revealing a RAS dose-driven non-linear continuum of downstream phenotypes. In a hepatocyte OIS model in vivo, ectopic expression of NRAS(G12V) does not induce tumours, in part owing to OIS-driven immune clearance. Single-cell RNA sequencing analyses reveal distinct hepatocyte clusters wit
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