State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
The MOE Key Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Cell Prolif. 2022 Mar;55(3):e13201. doi: 10.1111/cpr.13201. Epub 2022 Feb 10.
Human brain organoids can provide not only promising models for physiological and pathological neurogenesis but also potential therapies in neurological diseases. However, technical issues such as surgical lesions due to transplantation still limit their applications.
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.
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.
Our study thus provides a novel method to generate human brain organoids, which is promising in various applications of disease models and therapies.
人类脑类器官不仅为生理和病理神经发生提供了有前景的模型，而且为神经疾病的潜在治疗提供了可能。然而，由于移植导致的手术损伤等技术问题仍然限制了它们的应用。
我们创新性地通过将小的早期脑类器官注入成年 SCID 小鼠的纹状体，在体内开发人类脑类器官，而不是应用成熟的脑类器官。注射后两个月，对来自移植鼠脑的 6131 个 GFP 标记的人类细胞进行单细胞转录组分析。
通过无偏聚类，在这些体内发育的类器官（IVD-类器官）中鉴定出 8 个细胞亚群（包括表达纹状体标记物的神经元细胞）。与体外培养的人类皮质类器官相比，我们发现 IVD-类器官发育出更多的支持细胞，包括周细胞样细胞和脉络丛细胞，这些细胞对于维持类器官的稳态非常重要。此外，IVD-类器官表现出较低的细胞应激和凋亡水平。
因此，我们的研究为生成人类脑类器官提供了一种新方法，在疾病模型和治疗的各种应用中具有广阔的前景。
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