定义的人类三系血统大脑微组织
Takeshi Uenaka1,2, Sascha Jung3, Ishan Kumar1,2
1Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
bioRxiv : the preprint server for biology
|August 13, 2025
概括
人类iPSC衍生的微质细胞与神经元和星体细胞在新型大脑微组织中共同培养. 这些微组织促进恒常的微细胞表型,并模拟神经退行性疾病.
科学领域:
- 神经科学是一个神经科学.
- 干细胞生物学 干细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 微质细胞是中枢神经系统免疫细胞,对大脑健康和疾病至关重要.
- 人类和小鼠的微质细胞有很大的差异,需要人类特异的模型.
- 现有的模型很难复制人类微质体的体内环境和相互作用.
研究的目的:
- 开发一种基于人类iPSC的强大的脑微组织模型,用于研究微质神经与星细胞的相互作用.
- 建立一个系统,支持静态微质表型在体外.
- 研究细胞细胞通信网络和模型神经退行过程.
主要方法:
- 在2D和3D微组织中共同培养人类诱导多能干细胞 (iPSC) 衍生的神经元,星体和微质细胞.
- 在完全定义的介质中培养,没有外源性细胞因子.
- 通过scRNA-seq和snRNA-seq分析细胞形态,功能,生存,成熟和基因表达.
- 对α-synuclein播种和聚合的建模.
主要成果:
- 开发出稳定,自给自足的脑微组织,具有特征性的细胞形态和功能.
- 共同培养的微质细胞表现出恒常的表型,与外源性细胞因子不同.
- 星细胞,而不是神经元,足以维持微质的生存和成熟,M-CSF是必不可少的.
- 通过多原子分析确定了互惠的细胞通信网络.
- 在微组织中成功地回顾了α-synuclein病理.
结论:
- 人类iPSC衍生的大脑微组织为研究微质在恒常性和疾病背景下提供了一个强大的平台.
- 天星细胞在支持微质细胞的发育和功能方面发挥着至关重要的作用.
- 这些微组织作为神经退行性疾病研究的有价值的人类细胞模型.
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