Mechanical stimuli-induced CCL2 restores adult mouse cells to regenerate hair follicles.
Mechanical stimuli-induced CCL2 restores adult mouse cells to regenerate hair follicles.
复制标题
机械刺激诱导的 CCL2 可恢复成年小鼠细胞的毛囊再生能力。
DOI：
10.1016/j.omtn.2023.03.002
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Mingxing Lei
中科院分区：
文献类型：
--
作者：
Wang Wu;Wei Zhou;Jingwei Jiang;Mengyue Wang;Jinwei Zhang;J. Yang;Qu Tang;Huawen Liu;De;Wei Xu;J. Zhong;Li Yang;Mingxing Lei
老化的细胞在受到环境损伤时再生能力下降。在这里，我们阐明了机制，机械刺激诱导毛发再生的微环境调节水平使用拔毛和类器官培养模型。我们观察到从拔毛后第3天（PPD 3）收获的皮肤细胞在皮肤类器官培养期间具有最好的自组织能力，并且在移植后具有最高的毛发再生。通过批量RNA测序（RNA-seq）和单细胞RNA-seq分析以及原位杂交，我们确定了包括CCL 2在内的趋化因子信号通路基因在PPD 3时的皮肤和皮肤类器官培养物中显著增加。免疫染色显示，PPD 3皮肤上皮细胞具有增加的多能性，这通过在类器官培养期间自组织形成表皮聚集体的能力来验证。通过使用环境重编程方案将CCL 2重组蛋白添加到类器官培养物中，我们观察到失去再生能力的PPD 0成人皮肤细胞可以在类器官培养物中自组织，并在移植后稳健地再生毛囊。我们的研究表明，CCL 2在机械刺激下的毛发再生的免疫调节中起作用，并在类器官培养过程中增强细胞多能性。这为未来的临床应用提供了治疗潜力。
Aged cells have declined regenerative ability when subjected to environmental insult. Here we elucidate the mechanism by which mechanical stimulus induces hair regeneration at the microenvironmental regulation level using the hair plucking and organoid culture models. We observed that the skin cells harvested from post-plucking day 3 (PPD3) have the best self-organizing ability during skin organoid culture and have the highest hair regeneration upon transplantation. By bulk RNA sequencing (RNA-seq) and single-cell RNA-seq analysis andin situhybridization, we identified that the chemokine signaling pathway genes including CCL2 are significantly increased in the skin at PPD3 and in skin organoid cultures. Immunostaining shows that the PPD3 skin epithelial cells have increased multipotency, which is verified by the ability to self-organize to form epidermal aggregates during organoid culture. By adding CCL2 recombinant protein to the organoid culture using an environmental reprogramming protocol, we observed the PPD0 adult skin cells, which lose their regenerative ability can self-organize in organoid culture and regenerate hair follicles robustly upon transplantation. Our study demonstrates that CCL2 functions in immune regulation of hair regeneration under mechanical stimulus, and enhances cell multipotency during organoid culture. This provides a therapeutic potential for future clinical application.