In vivo development and single-cell transcriptome profiling of human brain organoids

人类脑类器官的体内发育和单细胞转录组分析

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作者:Shichao Huang, Fei Huang, Huiying Zhang, Yongfeng Yang, Juan Lu, Jiadong Chen, Li Shen, Gang Pei

Conclusions

Our study thus provides a novel method to generate human brain organoids, which is promising in various applications of disease models and therapies.

Methods

Instead of applying mature organoids, we innovatively developed human brain organoids in vivo by injecting small premature organoids into corpus striatum of adult SCID mice. Two months after injection, single-cell transcriptome analysis was performed on 6131 GFP-labeled human cells from transplanted mouse brains.

Results

Eight subsets of cells (including neuronal cells expressing striatal markers) were identified in these in vivo developed organoids (IVD-organoids) by unbiased clustering. Compared with in vitro cultured human cortical organoids, we found that IVD-organoids developed more supporting cells including pericyte-like and choroid plexus cells, which are important for maintaining organoid homeostasis. Furthermore, IVD-organoids showed lower levels of cellular stress and apoptosis. Conclusions: Our study thus provides a novel method to generate human brain organoids, which is promising in various applications of disease models and therapies.

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