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).
-
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.
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.
Metrics
-
- 16,928
- views
-
- 3,335
- downloads
-
- 189
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Generation of vascularized brain organoids to study neurovascular interactions
eLife 11:e76707.
https://doi.org/10.7554/eLife.76707
Further reading
-
- Neuroscience
When navigating environments with changing rules, human brain circuits flexibly adapt how and where we retain information to help us achieve our immediate goals.
-
- Neuroscience
When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.
