Signalling by senescent melanocytes hyperactivates hair growth.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Wang Xiaojie, Ramos Raul, Phan Anne Q, Yamaga Kosuke, Flesher Jessica L, Jiang Shan, Oh Ji Won, Jin Suoqin, Jahid Sohail, Kuan Chen-Hsiang, Nguyen Truman Kt, Liang Heidi Y, Shettigar Nitish Udupi, Hou Renzhi, Tran Kevin H, Nguyen Andrew, Vu Kimberly N, Phung Jennie L, Ingal Jonard P, Levitt Katelyn M, Cao Xiaoling, Liu Yingzi, Deng Zhili, Taguchi Nobuhiko, Scarfone Vanessa M, Wang Guangfang, Paolilli Kara Nicole, Wang Xiaoyang, Guerrero-Juarez Christian F, Davis Ryan T, Greenberg Elyse Noelani, Ruiz-Vega Rolando, Vasudeva Priya, Murad Rabi, Widyastuti Lily Halida Putri, Lee Hye-Lim, McElwee Kevin J, Gadeau Alain-Pierre, Lawson Devon A, Andersen Bogi, Mortazavi Ali, Yu Zhengquan, Nie Qing, Kunisada Takahiro, Karin Michael, Tuckermann Jan, Esko Jeffrey D, Ganesan Anand K, Li Ji, Plikus Maksim V
Аннотация
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 nevi2,3, 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.