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Nature——研究揭示体外“培养微型脑”的细胞异质性和网络动力学
在前几年,在体外培养三维脑组织成为了一种炙手可热的神经科学研究技术,其最大的优势就是保持了神经发育过程中神经网络的自然状态,如轴突投射、网络连接、三维形态等。三维神经培养组织也被用于研究神经系统疾病,记得在前两年的Nature杂志上就报道了在三维神经培养体系中证明了阿尔茨海默病磷酸化的tau是Aβ下游的这样一种假说。然而三维培养的“微型脑”是否能够产生足够多的细胞类型呢?在这个“微型脑”中,神经元之间是否能够建立功能性的脑连接网络呢?最近发表于Nature的一项研究就解答了上述的问题。以下是摘要:
In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (more than 9 months), allowing for the establishment of relatively mature features, including the formation of dendritic spines and spontaneously active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.
1.大规模单细胞测序证明“微型脑”可以产生多种细胞类型
2.“微型脑”包含了前脑和视网膜的多种细胞亚群
3.延长培养时间可以促进神经元进一步成熟,包括发育为视感受器
4.“微型脑”可以产生自发脑网络连接而且光刺激可以诱发神经元反应
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