Signalling by senescent melanocytes hyperactivates hair growth.
Signalling by senescent melanocytes hyperactivates hair growth.
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DOI：
10.1038/s41586-023-06172-8
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发表时间：
2023-06
期刊：
影响因子：
64.8
通讯作者：
Plikus, Maksim V.
中科院分区：
文献类型：
--
作者：
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.
小生境信号使干细胞保持长时间的静止或短暂激活它们进行适当的再生。改变平衡的生态位信号可能导致再生障碍。人类皮肤黑素细胞痣通常表现为毛发过度生长，提示毛发干细胞过度活跃。在这里，使用痣的遗传小鼠模型，我们表明衰老黑素细胞的真皮簇驱动上皮毛干细胞退出静止，改变它们的转录组和组成，有力地促进毛发更新。痣黑素细胞激活一个独特的分泌组，富含信号因子。骨桥蛋白是痣的主要信号传导因子，对诱导毛发生长是必要的和充分的。注射骨桥蛋白或其基因过表达足以诱导小鼠的毛发生长，而骨桥蛋白或其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由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，并刺激人类毛囊的新生长。虽然衰老细胞的广泛积累，如老化或遗传毒性应激，对组织的再生能力是有害的，但我们表明衰老细胞簇的信号传导可以有效地增强相邻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组确定为再生障碍中有吸引力的治疗靶点。皮肤痣的衰老黑素细胞通过信号因子SPP1驱动毛发生长的过度激活。
Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration. 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, 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 tissue, 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. Senescent melanocytes of skin nevi drive hyperactivation of hair growth through the signalling factor SPP1.
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影响因子：
11.2
作者：
Pazolli, Ermira;Luo, Xianmin;Brehm, Sarah;Carbery, Kelly;Chung, Jun Jae;Prior, Julie L.;Doherty, Jason;Demehri, Shadmehr;Salavaggione, Lorena;Piwnica-Worms, David;Stewart, Sheila A.
通讯作者：
Stewart, Sheila A.
影响因子：
23.9
作者：
Pietras, Alexander;Katz, Amanda M.;Ekstroem, Elin J.;Wee, Boyoung;Halliday, John J.;Pitter, Kenneth L.;Werbeck, Jillian L.;Amankulor, Nduka M.;Huse, Jason T.;Holland, Eric C.
通讯作者：
Holland, Eric C.
影响因子：
8.8
作者：
Dikovskaya, Dina;Cole, John J.;Adams, Peter D.
通讯作者：
Adams, Peter D.
DOI：
10.1126/science.1201647
发表时间：
2011-04-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Plikus MV;Baker RE;Chen CC;Fare C;de la Cruz D;Andl T;Maini PK;Millar SE;Widelitz R;Chuong CM
通讯作者：
Chuong CM
影响因子：
18.2
作者：
Campisi J
通讯作者：
Campisi J