小柯机器人

美国加州大学尔湾分校Maksim V. Plikus等研究人员合作发现，衰老的黑色素细胞发出的信号过度激活头发的生长。相关论文于2023年6月21日发表在《自然》杂志上。

研究人员使用黑毛痣的遗传小鼠模型，表明真皮层的衰老黑素细胞集群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，从而有力地增强毛发更新。痣黑素细胞激活了一个独特的分泌组，富含信号因子。痣的主要信号因子Osteopontin是诱导毛发生长的必要和充分条件。注射Osteopontin或其基因过表达足以诱导小鼠强大的毛发生长，而Osteopontin或CD44（其在上皮毛发细胞上的同源受体）的种系和条件性缺失，可以拯救由真皮痣黑素细胞诱导的增强的毛发生长。Osteopontin在人类毛痣中过量表达，它能刺激人类毛囊的新生长。虽然衰老细胞的广泛积累，如在老化或基因毒性压力下，对组织的再生能力是有害的，但结果表明，衰老细胞群的信号可以有效地提高邻近完整干细胞的活性，并刺激组织的更新。这一发现确定了衰老细胞及其分泌组是再生障碍中一个有吸引力的治疗靶点。

据了解，微环境信号使干细胞长期处于静止状态，或为适当的再生而短暂地激活它们。改变平衡的生态位信号可导致再生障碍。人类的黑素细胞性皮肤痣经常显示出过度的毛发生长，这表明毛发干细胞的活性过高。

附：英文原文

Title: Signalling by senescent melanocytes hyperactivates hair growth

Author: 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.

Issue&Volume: 2023-06-21

Abstract: 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.

DOI: 10.1038/s41586-023-06172-8

Source: https://www.nature.com/articles/s41586-023-06172-8

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