Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons
Open accessAbstract
Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases.
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Protocols have been published for organoids modeling the hippocampus, midbrain, hypothalamus, cerebellum, anterior pituitary, and retina.
“However, protocols have also been published for the generation of organoids that model the development of other human brain regions, including the hippocampus7, midbrain4,5,8, hypothalamus5, cerebellum5,9, anterior pituitary10 and retina10,11.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [4]
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- Authors
- Jo, J., Xiao, Y., Sun, A. X., Cukuroglu, E., Tran, H.-D., Göke, J., Tan, Z. Y., Saw, T. Y., Tan, C.-P., Lokman, H., Lee, Y., Kim, D., Ko, H. S., Kim, S.-O., Park, J. H., Cho, N.-J., Hyde, T. M., Kleinman, J. E., Shin, J. H., Weinberger, D. R., Tan, E. K., Je, H. S., & Ng, H.-H.
- Affiliations
- Genome Institute of Singapore (SG)
- National University of Singapore (SG)
- National Neuroscience Institute (SG)
- Johns Hopkins University (US)
- Nanyang Technological University (SG)
- Lieber Institute for Brain Development (US)
- Corresponding author
- Je, Hyunsoo Shawn
- Ng, Huck-Hui
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 19
- Issue
- 2
- Pages
- 248-257
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC5510242
- OpenAlex
- W2490424988
- Cited by
- 861
- References
- 32
- Citations by year
- 2026: 71 · 2025: 100 · 2024: 94 · 2023: 70 · 2022: 109 · 2021: 128 · 2020: 101 · 2019: 90 · 2018: 50 · 2017: 38 · 2016: 9
- FWCI
- 32.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- National University of Singapore (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS082205, P50NS038377)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- human pluripotent stem cells, midbrain dopaminergic neurons, neuromelanin, dopamine synthesis, substantia nigra, neuronal differentiation, Parkinson's disease model
- MeSH terms
- Cell Differentiation, Cell Line, Humans, Melanins, Mesencephalon, Organoids, Transcription, Genetic, Pluripotent Stem Cells, Dopaminergic Neurons
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