Self-organized cerebral organoids with human specific features predict effective drugs to combat Zika virus infection
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The human cerebral cortex possesses distinct structural and functional features that are not found in the lower species traditionally used to model brain development and disease. Accordingly, considerable attention has been placed on the development of methods to direct pluripotent stem cells to form human brain-like structures termed organoids. However, many organoid differentiation protocols are inefficient and display marked variability in their ability to recapitulate the three-dimensional architecture and course of neurogenesis in the developing human brain. Here, we describe optimized organoid culture methods that efficiently and reliably produce cortical and basal ganglia structures similar to those in the human fetal brain in vivo. Neurons within the organoids are functional and exhibit network-like activities. We further demonstrate the utility of this organoid system for modeling the teratogenic effects of Zika virus on the developing brain and identifying more susceptibility receptors and therapeutic compounds that can mitigate its destructive actions.
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Organoid development followed the expected temporal changes.
“Organoid development followed the expected temporal changes (Lancaster et al., 2013; Velasco et al., 2019; Watanabe et al., 2017; Yoon et al., 2019; Figures 1B–1D; Figure S1A).”
From ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids (2021) · cites this paper as Watanabe et al., 2017
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- Authors
- Watanabe, M., Buth, J. E., Vishlaghi, N., de la Torre-Ubieta, L., Taxidis, J., Khakh, B. S., Coppola, G., Pearson, C. A., Yamauchi, K., Gong, D., Dai, X., Damoiseaux, R., Aliyari, R., Liebscher, S., Schenke-Layland, K., Caneda, C., Huang, E. J., Zhang, Y., Cheng, G., Geschwind, D. H., Golshani, P., Sun, R., & Novitch, B. G.
- Affiliations
- University of California, Los Angeles (US)
- California NanoSystems Institute (US)
- University of Tübingen (DE)
- University of California, San Francisco (US)
- Corresponding author
- Novitch, Bennett G.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 21
- Issue
- 2
- Pages
- 517-532
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5637483
- OpenAlex
- W2761945803
- Cited by
- 401
- References
- 55
- Citations by year
- 2026: 26 · 2025: 45 · 2024: 45 · 2023: 39 · 2022: 51 · 2021: 65 · 2020: 53 · 2019: 47 · 2018: 27 · 2017: 2
- FWCI
- 14.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion, other-oa)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Funders
- UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research
- Rose Hills Foundation
- Binder Family Foundation
- UCLA Clinical and Translational Science Institute
- California Institute for Regenerative Medicine (CIRM) (DISC1-08819)
- NIH (R01NS089817, R01NS085227, R01MH060233, R01MH100027, U01MH103339, R01MH110927, R01MH094714, R01AI069120, R01AI056154, R01AI078389, R00NS089780, P01NS083513)
- UCLA Broad Stem Cell Research Center
- Uehara Memorial Foundation
- UCLA-California State University Northridge CIRM-Bridges (TB1-00183)
- California Institute for Regenerative Medicine (CIRM)-BSCRC (TG2-01169)
- Ministry of Science, Research and Arts of Baden-Württemberg (33-729.55-3/214)
- NINDS Informatics Center for Neurogenetics and Neurogenomics (P30NS062691)
- NICHD (U54HD087101)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- brain organoids, Zika virus, teratogenicity, human brain development, basal ganglia, cortical organoids, neurogenesis, pluripotent stem cells, drug screening, therapeutic compounds, neuronal network activity
- MeSH terms
- Zika Virus, c-Mer Tyrosine Kinase, Cell Line, Cerebral Cortex, Drug Evaluation, Preclinical, Humans, Neurons, Organoids, Receptor Protein-Tyrosine Kinases, Anti-Retroviral Agents, STAT3 Transcription Factor, Embryonic Stem Cells, Primary Cell Culture
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