Generation of vascularized brain organoids to study neurovascular interactions
- ShanghaiTech University, China
- 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).
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Generation of vascularized brain organoids to study neurovascular interactionsNCBI Sequence Read Archive, SRP338043.
Article and author information
Author details
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
- Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States
Version history
- Received: December 30, 2021
- Preprint posted: January 4, 2022 (view preprint)
- Accepted: May 1, 2022
- Accepted Manuscript published: May 4, 2022 (version 1)
- Version of Record published: June 30, 2022 (version 2)
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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Generation of vascularized brain organoids to study neurovascular interactions
eLife 11:e76707.
https://doi.org/10.7554/eLife.76707
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