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两种适应轴突的细胞剥离平台揭示了对于脊髓和骨再生至关重要的巨细胞依赖过程

Gabriela Johnson, Andrew Hart, Markus Sujansky

bioRxiv : the preprint server for biology

|February 23, 2026

概括

阿克索洛特 (Ambystoma mexicanum) 的再生依赖于巨细胞. 新的诱导性遗传工具,特别是诱导性caspase-9 (iCasp9),可以在再生过程中对巨细胞等细胞类型进行功能研究.

科学领域:

再生生物学再生生物学
发育生物学是发展生物学.
两动物研究研究

背景情况:

(Ambystoma mexicanum) 是无痕修复和再生的关键模型.
在轴突再生过程中对特定细胞类型的功能研究存在有限的工具.
现有的方法缺乏细胞特异性除系统,无法进行全面的功能分析.

研究的目的:

开发和比较可诱导的基因细胞剥离平台在axolotls.
为了验证这些平台在再生过程中对细胞类型的功能研究.
为了研究巨细胞在轴尾部再生中的作用.

主要方法:

开发并比较了两种可诱导的遗传细胞剥离系统:细菌缩酶 (NTR 2.0) 和哺乳动物可诱导的caspase-9 (iCasp9).
评估了平台在不同发育阶段,动物大小和给药途径的疗效.
系统地切除CD68+巨细胞,并在尾巴再生过程中分析后果.

主要成果:

由于药物毒性和溶解性问题,NTR 2.0平台的效用有限,主要用于幼虫阶段.
在所有生命阶段和管理路线上,iCasp9系统被证明是有效的.
巨细胞切除取消了骨再生,导致脊髓轴突退化,并破坏了神经细胞的组织.

结论:

巨细胞的枯竭严重损害了阿克索洛特尾巴的再生,突出了它们的关键作用.
该iCasp9系统是一个经过验证的,多功能工具,用于细胞特异性功能研究在轴突.
巨细胞对于神经系统的再生和骨生成至关重要.

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