皮质器官中的细胞应力损害了分子亚型的规范
Aparna Bhaduri1,2, Madeline G Andrews1,2, Walter Mancia Leon2
1Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Nature
|January 31, 2020
概括
人类大脑有机体模仿发育中的大脑皮质,但缺乏细胞多样性和适当的细胞成熟. 将器官移植到小鼠身上可以提高它们对人类大脑发育的准确性.
科学领域:
- 神经科学
- 发育生物学
- 干细胞生物学
背景情况:
- 皮质器官是模拟人类大脑皮层发育的3D培养.
- 这些器官模型对人类大脑发育的准确性仍然不确定.
研究的目的:
- 分析和比较个人原发性皮质细胞和皮质器官的转录组.
- 评估皮质器官在人类大脑发育模型中的忠实性.
主要方法:
- 人类皮质细胞在不同发育阶段和区域的单细胞转录组分析.
- 人类皮质器官的转录组分析.
- 在体内皮层细胞和器官之间基因表达特征的比较.
- 在移植到小鼠皮层后评估器官缺陷.
主要成果:
- 人类皮层发育显示了前代细胞的成熟,多样化的细胞亚型和区域神经元的特异性.
- 皮质有机体表现出广泛的细胞类,但缺乏明显的亚型和适当的祖先成熟.
- 皮层区域的分子特征出现在有机神经元中,但没有空间组织.
- 器官激活应激通路, 损害细胞类型的特异性, 但移植减轻这些缺陷.
结论:
- 皮质器官部分模拟人类大脑发育,但在细胞多样性和成熟方面存在局限性.
- 移植到小鼠的大脑可以改善器官的忠实性,并减轻与压力相关的缺陷.
- 开发的数据集和工具为评估和提高皮质器官精度提供了一个框架.
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