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

OBJECTIVES: 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. MATERIALS AND 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.