Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration¹. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi^2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue⁴, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

生态位信号使干细胞长期处于静止状态或短暂激活它们以进行适当的再生¹。改变平衡的生态位信号传导可能导致再生障碍。人类的黑素细胞皮肤痣经常表现出毛发过度生长，表明毛发干细胞过度活跃。^{此处，使用痣2,3}的遗传小鼠模型，我们发现真皮衰老黑素细胞簇驱动上皮毛发干细胞退出静止状态并改变其转录组和组成，有效增强毛发更新。痣黑素细胞激活独特的分泌组，富含信号因子。骨桥蛋白是主要的痣信号因子，对于诱导毛发生长是必要且充分的。注射骨桥蛋白或其基因过度表达足以诱导小鼠毛发生长旺盛，而骨桥蛋白或上皮毛细胞上的同源受体CD44的种系和条件性缺失则可挽救真皮痣黑素细胞诱导的毛发生长增强。骨桥蛋白在人类毛痣中过度表达，它刺激人类毛囊的新生长。尽管衰老细胞广泛积累，^如图4所示，我们表明衰老细胞簇的信号传导可以有效增强邻近完整干细胞的活性并刺激组织更新。这一发现将衰老细胞及其分泌蛋白组确定为再生性疾病中有吸引力的治疗靶点。