Human Induced Pluripotent Stem Cell-Derived Astrocytes Are Differentially Activated by Multiple Sclerosis-Associated Cytokines
Open accessAbstract
Recent studies highlighted the importance of astrocytes in neuroinflammatory diseases, interacting closely with other CNS cells but also with the immune system. However, due to the difficulty in obtaining human astrocytes, their role in these pathologies is still poorly characterized. Here, we develop a serum-free protocol to differentiate human induced pluripotent stem cells (hiPSCs) into astrocytes. Gene expression and functional assays show that our protocol consistently yields a highly enriched population of resting mature astrocytes across the 13 hiPSC lines differentiated. Using this model, we first highlight the importance of serum-free media for astrocyte culture to generate resting astrocytes. Second, we assess the astrocytic response to IL-1β, TNF-α, and IL-6, all cytokines important in neuroinflammation, such as multiple sclerosis. Our study reveals very specific profiles of reactive astrocytes depending on the triggering stimulus. This model provides ideal conditions for in-depth and unbiased characterization of astrocyte reactivity in neuroinflammatory conditions.
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The serum pervasively used in culture media may render hiPSC-derived astrocytes reactive.
“Importantly, not only are these cells removed from their original milieu, but the serum pervasively used in culture media may render them reactive84.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [84]
hiPSC-derived astrocytes are amenable to study responses to viral infection and to specific stimuli.
“hiPSC-derived astrocytes are also amenable to study responses to viral infection83 and to specific stimuli84.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [84]
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- Authors
- Perriot, S., Mathias, A., Perriard, G., Canales, M., Jonkmans, N., Merienne, N., Meunier, C., El Kassar, L., Perrier, A. L., Laplaud, D.-A., Schluep, M., Déglon, N., & Du Pasquier, R.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Inserm (FR)
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 11
- Issue
- 5
- Pages
- 1199-1210
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC6234919
- OpenAlex
- W2898424850
- Cited by
- 171
- References
- 52
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 26 · 2023: 26 · 2022: 34 · 2021: 21 · 2020: 21 · 2019: 14
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IRIS (submittedVersion, cc-by)
- SERVAL (Université de Lausanne) (submittedVersion, cc-by)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320030_159997)
- AFM-Téléthon
- Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
- Université de Lausanne
- Schweizerische Multiple Sklerose Gesellschaft
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- human induced pluripotent stem cells, astrocyte differentiation, multiple sclerosis, neuroinflammation, reactive astrocytes, IL-1β, TNF-α, interleukin-6, cytokine response, astrocyte activation
- MeSH terms
- Remyelination, Astrocytes, Cell Differentiation, Cells, Cultured, Humans, Multiple Sclerosis, Phenotype, Case-Control Studies, Cytokines, Culture Media, Serum-Free, Inflammation Mediators, Induced Pluripotent Stem Cells, Transcriptome
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