不同的机械力驱动感官上皮形成
Mingyu Xia1,2,3,4, Mingxuan Wu1,2, Yuanrong Li5,6,7
1ENT institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China.
Science advances
|November 3, 2023
概括
细胞外矩阵 (ECM) 刚性指导感官上皮的发育. 适度的度促进了前代细胞的扩张,而较高的度推动了分化到感官毛细胞,为毛细胞再生提供了洞察力.
科学领域:
- 发展生物学 发展生物学
- 生物材料科学 生物材料科学
- 细胞生物学 细胞生物学
背景情况:
- 细胞对微环境的反应对发育至关重要.
- 感官上皮质发育中的细胞内信号已知,但驱动力仍然不清楚.
研究的目的:
- 研究细胞外矩阵 (ECM) 机械性质在感觉上皮形成中的作用.
- 阐明ECM刚性影响耳前祖细胞行为的分子机制.
主要方法:
- 制造一种混合水凝,具有可调节的机械性能,用于耳器官培养.
- 对细胞信号通路 (Integrin α3/F-actin/YAP,Ca2+/PIEZO2/KLF2) 进行分析,以应对不同ECM刚度.
- 耳前祖细胞 (CPC) 扩张和分化的阶段依赖性评估.
主要成果:
- 揭示了ECM感觉上皮质形成的依赖于硬度的调节.
- 中度ECM刚度通过ITGA3/F-actin/YAP信号传递促进了耳前生细胞 (CPC) 衍生的上皮器官体扩张.
- 较高的ECM刚度诱导了CPC通过Ca2+/PIEZO2/KLF2信号传递分化为感官毛细胞 (HCs).
结论:
- ECM机械线索,特别是刚性,被确定为感官上皮质形成的关键驱动因素.
- 在耳发育过程中,阐明了一种将ECM刚性与细胞命运决定 (扩张与分化) 联系起来的分子机制.
- 这些发现为旨在再生感官毛细胞的治疗策略提供了基础.
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