Fan Chunxin, Yuan Xiaoyi, Wang Jian, Pei Wuhong, Zheng Hongfei, Zhang Xinyu, Burgess Shawn M
Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China.
International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China.
bioRxiv. 2025 Apr 19:2025.04.18.649014. doi: 10.1101/2025.04.18.649014.
Regenerative capacity varies significantly among species and across different organs. In mammals, the inner ear exhibits a limited ability to regenerate hair cells, whereas the lateral line sensory organ of zebrafish demonstrates apparently limitless capability to spontaneously regenerate hair cells following injury. However, the specific cell populations representing the stem cells in the neuromast and the mechanism of stem cell self-renewal remain unclear. In this study, we show that a mutation in led to the depletion of neuromast sensory organs and impairment of hair cell regeneration in zebrafish. The decrease of cells peripheral to the neuromasts in mutants indicates that these peripheral cells, particularly cells called "mantle cells", serve as the stem cells within the neuromast. Furthermore, our findings indicate that the ligands Tnfsf10 and Tnfsf10l3 (TRAIL) act through Tnfrsfa activating the NF-κB signaling pathway in the mantle cells in a non-cell-autonomous manner. NF-κB signaling is crucial for maintaining the stem cell identity of the mantle cells through activation or maintenance of expression. These findings demonstrate a critical role for TNF superfamily signaling in stem cell maintenance.
再生能力在不同物种和不同器官之间存在显著差异。在哺乳动物中，内耳毛细胞的再生能力有限，而斑马鱼的侧线感觉器官在受伤后表现出明显的自发再生毛细胞的无限能力。然而，神经丘中代表干细胞的特定细胞群体以及干细胞自我更新的机制仍不清楚。在本研究中，我们表明 中的一个突变导致斑马鱼神经丘感觉器官的耗尽和毛细胞再生的受损。 突变体中神经丘周围细胞的减少表明这些外周细胞，特别是称为“套细胞”的细胞，作为神经丘内的干细胞。此外，我们的研究结果表明，配体Tnfsf10和Tnfsf10l3（TRAIL）通过Tnfrsfa以非细胞自主方式激活套细胞中的NF-κB信号通路。NF-κB信号通路对于通过激活或维持 表达来维持套细胞的干细胞特性至关重要。这些发现证明了TNF超家族信号在干细胞维持中的关键作用。
