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在iPSC衍生模型中保存了人类大脑边界相关的巨细胞的表型和功能

Helena J Barr^1,2,3, Constanze Depp^2,3, Maximilian Hingerl^2,3

¹Harvard Division of Medical Sciences, Program in Neuroscience, Boston, MA.

bioRxiv : the preprint server for biology

|December 22, 2025

概括

人类边界相关的巨细胞 (BAMs) 对大脑健康至关重要. 研究人员开发了新的模型来研究人类BAMs,揭示了它们提高清除粉样β的能力,并为未来的研究提供了工具.

科学领域:

神经免疫学神经免疫学
干细胞生物学干细胞生物学
巨细胞生物学巨细胞生物学

背景情况:

边界相关的巨细胞 (BAMs) 在脑免疫中起着至关重要的作用,包括清除粉样β (Aβ).
现有的人类BAM模型是有限的,阻碍了全面的研究.
了解BAM功能对于神经退行性疾病研究至关重要.

研究的目的:

开发和描述人类BAM模型用于功能研究.
研究跨物种BAMs保存的转录和功能性质.
建立用于研究人类BAMs的体外和体内工具.

主要方法:

人类诱导的多能干细胞 (iPS) 细胞衍生的造血原始体的产后移植到小鼠大脑中.
单细胞RNA测序用于分析异种移植BAMs (xBAMs) 和小鼠BAMs的转录特征.
在实验室中,iPS细胞的分化产生了类似BAM细胞 (iBAMs) 和类似微质细胞 (iMGLs).

主要成果:

人类iPS细胞衍生的原始细胞成功地植入并分化为xBAMs,填充大脑边界.
在xBAM和小鼠BAM中都发现了保存的超内细胞表型和增强的Aβ清理能力.
在体外,iBAM与iMGL相比,表现出优越的细胞能力.
通过BAMs观察到对帕伦基马物质的分区限制采样.

结论:

一个保存的超内细胞表型定义了跨物种的BAM,突出了它们在脑免疫监测中的专门功能.
该研究提供了新的体内和体外模型来研究人类BAMs.
这些模型为了解BAM在神经健康和疾病中的作用提供了有价值的工具,特别是Aβ清除.

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