Directed differentiation of human pluripotent stem cells to microglia
Open accessAbstract
Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers. Analyses of gene expression and cytokine release showed close similarities between iPSC-derived (iPSC-MG) and human primary microglia as well as clear distinctions from macrophages. iPSC-MG were able to phagocytose and responded to ADP by producing intracellular Ca 2+ transients, whereas macrophages lacked such response. The differentiation protocol was highly reproducible across several pluripotent stem cell lines.
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Protocols have been developed to produce human iPSC-derived microglial-like cells (iMG).
“Recently, protocols for induce human iPSC-derived microglial-like cells (iMG) have been developed [67-71].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [69]
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References 32 · Cited by 381
- Authors
- Douvaras, P., Sun, B., Wang, M., Kruglikov, I., Lallos, G., Zimmer, M., Terrenoire, C., Zhang, B., Gandy, S., Schadt, E., Freytes, D. O., Noggle, S., & Fossati, V.
- Affiliations
- New York Stem Cell Foundation (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Douvaras, Panagiotis
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 8
- Issue
- 6
- Pages
- 1516-1524
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC5470097
- OpenAlex
- W2614953780
- Cited by
- 381
- References
- 32
- Citations by year
- 2026: 26 · 2025: 39 · 2024: 56 · 2023: 37 · 2022: 46 · 2021: 56 · 2020: 44 · 2019: 36 · 2018: 31 · 2017: 10
- FWCI
- 13.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNC Libraries
- Funders
- New York Stem Cell Foundation
- NIH (U01AG046170)
- Oak Foundation (ORIO-13-051)
- Conrad N. Hilton Foundation (20140243)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microglia differentiation, human pluripotent stem cells, induced pluripotent stem cells, embryonic stem cells, myeloid progenitor cells, ramified microglia, phagocytosis, calcium transients, macrophage differentiation, neuroinflammation
- MeSH terms
- Human Embryonic Stem Cells, CX3C Chemokine Receptor 1, Adenosine Diphosphate, Calcium, Cell Differentiation, Cell Line, Humans, Macrophages, Gene Expression, Cytokines, Microglia, Lipopolysaccharide Receptors, Pluripotent Stem Cells
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