Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells
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There is significant need to develop physiologically relevant models for investigating human astrocytes in health and disease. Here, we present an approach for generating astrocyte lineage cells in a three-dimensional (3D) cytoarchitecture using human cerebral cortical spheroids (hCSs) derived from pluripotent stem cells. We acutely purified astrocyte-lineage cells from hCSs at varying stages up to 20 months in vitro using immunopanning and cell sorting and performed high-depth bulk and single-cell RNA sequencing to directly compare them to purified primary human brain cells. We found that hCS-derived glia closely resemble primary human fetal astrocytes and that, over time in vitro, they transition from a predominantly fetal to an increasingly mature astrocyte state. Transcriptional changes in astrocytes are accompanied by alterations in phagocytic capacity and effects on neuronal calcium signaling. These findings suggest that hCS-derived astrocytes closely resemble primary human astrocytes and can be used for studying development and modeling disease.
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hiPSC-derived astrocytes can be generated with a fast protocol in 2D layers or integrated in 3D systems such as spheroids and organoids.
“hiPSC-derived astrocytes, which can be generated with a fast protocol in 2D layers104 or integrated in 3D systems such as spheroids and organoids105–108”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [105]
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- Authors
- Sloan, S. A., Darmanis, S., Huber, N., Khan, T. A., Birey, F., Caneda, C., Reimer, R., Quake, S. R., Barres, B. A., & Paşca, S. P.
- Affiliations
- Stanford Medicine (US)
- Stanford University (US)
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 95
- Issue
- 4
- Pages
- 779-790.e6
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5890820
- OpenAlex
- W2747850876
- Cited by
- 593
- References
- 55
- Citations by year
- 2026: 46 · 2025: 65 · 2024: 68 · 2023: 69 · 2022: 60 · 2021: 89 · 2020: 80 · 2019: 70 · 2018: 39 · 2017: 5
- FWCI
- 21.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01 MH099555, NS081703, MH107800)
- California Institute of Regenerative Medicine
- the MQ Fellow Award
- Donald E. and Delia B. Baxter Foundation
- Stanford Neurosciences Institute’s Brain Rejuvenation Project
- Kwan Research Fund
- Stanford Start-up Funds
- NIMH (T32GM007365, F30MH106261)
- Bio-X Predoctoral Fellowship
- Dean’s Postdoctoral Fellowship
- Child Health Research Institute Postdoctoral Fellowship (UL1-TR001085)
- NSF Graduate Research Fellowship
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- human astrocytes, astrocyte maturation, pluripotent stem cells, 3D brain models, astrocyte lineage, fetal astrocytes, phagocytosis, neuronal calcium signaling, single-cell RNA sequencing, immunopanning, disease modeling
- MeSH terms
- Astrocytes, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Fetus, Humans, Models, Biological, Transcription Factors, Imaging, Three-Dimensional, Pluripotent Stem Cells
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