Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing

Abstract

While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile. We find that clearing p21 highly expressing cells expedites wound closure and is partially mediated by NF-κB inhibition, thus enhancing our understanding of the multifaceted functions of senescence in tissue remodeling. Senescent cells can exert detrimental effects, yet beneficial roles of p16 highly expressing cells have been reported in contexts such as wound healing. Enhancing our understanding of the heterogeneity of senescence in vivo, Gasek et al. identify a distinct and detrimental p21 highly expressing cell population induced upon wound healing.