Generation of vascularized brain organoids to study neurovascular interactions

  1. Xin-Yao Sun
  2. Xiang-Chun Ju  Is a corresponding author
  3. Yang Li
  4. Peng-Ming Zeng
  5. Jian Wu
  6. Ying-Ying Zhou
  7. Li-Bing Shen
  8. Jian Dong
  9. Yuejun Chen
  10. Zhen-Ge Luo  Is a corresponding author
  1. ShanghaiTech University, China
  2. Chinese Academy of Sciences, China

Abstract

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures, and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain-barrier (BBB)-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, in particular the vasculature and microglia niche.

Data availability

Single cell RNA sequencing transcriptome data supporting this study have been deposited in NCBI Sequence Read Archive (SRA) repository (https://www.ncbi.nlm.nih.gov/sra) with accession number SRP338043 (VOR: SRR15992286; VOR2:SRR15992285).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Xin-Yao Sun

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiang-Chun Ju

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    For correspondence
    xiangchun.ju@oist.jp
    Competing interests
    The authors declare that no competing interests exist.
  3. Yang Li

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Peng-Ming Zeng

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Jian Wu

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Ying-Ying Zhou

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Li-Bing Shen

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Jian Dong

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yuejun Chen

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Zhen-Ge Luo

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    For correspondence
    luozhg@shanghaitech.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5037-0542

Funding

National Key Research and Development Program of China (PI,2021ZD0202500)

  • Zhen-Ge Luo

National Natural Science Foundation of China (PI,32130035)

  • Zhen-Ge Luo

National Natural Science Foundation of China (PI,92168107)

  • Zhen-Ge Luo

National Natural Science Foundation of China (PI,31871034)

  • Xiang-Chun Ju

Chinese Academy of Sciences Key Project (PI,QYZDJ-SSW-SMC025)

  • Zhen-Ge Luo

Shanghai Municipal People's Government (Co-I,2018SHZDZX05)

  • Zhen-Ge Luo

Shanghai Municipal People's Government (PI,201409001700)

  • Zhen-Ge Luo

National Key Research and Development Program of China (Co-I,2017YFA0700500)

  • Xiang-Chun Ju

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States

Publication history

  1. Received: December 30, 2021
  2. Accepted: May 1, 2022
  3. Accepted Manuscript published: May 4, 2022 (version 1)

Copyright

© 2022, Sun et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xin-Yao Sun
  2. Xiang-Chun Ju
  3. Yang Li
  4. Peng-Ming Zeng
  5. Jian Wu
  6. Ying-Ying Zhou
  7. Li-Bing Shen
  8. Jian Dong
  9. Yuejun Chen
  10. Zhen-Ge Luo
(2022)
Generation of vascularized brain organoids to study neurovascular interactions
eLife 11:e76707.
https://doi.org/10.7554/eLife.76707
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