2. Academic Validation
  3. In vivo development and single-cell transcriptome profiling of human brain organoids

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

  • Cell Prolif. 2022 Mar;55(3):e13201. doi: 10.1111/cpr.13201.
Shichao Huang 1,  Fei Huang 2,  Huiying Zhang 2,  Yongfeng Yang 1,  Juan Lu 1,  Jiadong Chen 3,  Li Shen 2 4 5,  Gang Pei 1 6 7
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 NHC and CAMS Key Laboratory of Medical Neurobiology, Center for Neuroscience and Department of Neurology of Second Affiliated Hospital, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Department of Orthopedics Surgery, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.
  • 5 Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University (HIC-ZJU), Hangzhou, China.
  • 6 Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Biomedicine, The Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 7 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
PMID: 35141969 DOI: 10.1111/cpr.13201
Abstract

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.

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