Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells
Open accessAbstract
Microglia are the primary immune cells of the central nervous system and crucial to proper development and maintenance of the brain. Microglia have been recognized to be associated with neurodegenerative diseases and neuroinflammatory disorders. CX3C chemokine receptor 1 (CX3CR1), which is specifically expressed in microglia, regulates microglia homeostatic functions such as microglial activation and is downregulated in aged brain and disease‐associated microglia in rodents, yet its role in human microglia is not fully understood. In this study, we investigated the function of CX3CR1 in human microglia using human induced pluripotent stem (iPS) cell‐derived microglia‐like cells. Human iPS cell‐derived microglia‐like cells expressed microglial markers and showed an activated state and phagocytic activity. Using CRISPR/Cas9 genome editing, we deleted CX3CR1 in human iPS cells and found increased inflammatory responses and phagocytic activity in mutant as compared to wild‐type microglia‐like cells. In addition, the CX3C chemokine ligand 1 (CX3CL1, a ligand for CX3CR1) significantly decreased the upregulation of IL‐6 by lipopolysaccharide stimulation in human iPS cell‐derived microglia‐like cells. These results suggest that CX3CR1 in human microglia may contribute to microglial homeostasis by regulating inflammatory response and phagocytosis.
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Deletion of CX3CR1 results in an increased inflammatory response and phagocytic activity.
“while deletion results in an increased inflammatory response and phagocytic activity [45].”
From Heterozygous expression of the Alzheimer’s disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses (2022) · cites this paper as [45]
M7 shows high expression of activation marker Tyrobp.
“whereas M7 shows high expression of activation marker Tyrobp. 36 , 37 , 38”
From Loss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes (2024) · cites this paper as [36]
The Results section on activation markers identifies TNFα, IL-6, IL-1β, CD206, IL-4 and ARG1, but does not discuss Tyrobp or M7. Searches for the quoted phrase and for Tyrobp with M7 found no passage addressing the claimed expression pattern; page numbers were unavailable in our copy. (LLM, conf=0.75)
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Sorted by citations
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Stöberl, N., Maguire, E., Salis, E., Shaw, B., & Hall-Roberts, H. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02919-2 · Cited by 71 · see citing works
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“Certainly increased expression of CX3CR1 attenuates microglial inflammatory responses to LPS (liposaccharide) [44], while deletion results in an increased inflammatory response and phagocytic activity [45].”
BackgroundLoss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes
Dabin, L. C., Kersey, H., Kim, B., Acri, D. J., Sharify, D., Lee‐Gosselin, A., Lasagna‐Reeves, C. A., Oblak, A. L., Lamb, B. T., & Kim, J. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13901 · Cited by 10 · see citing works
“Two 36–38 M8 shows high expression of Lpl , a gene recently implicated in myelin-scavenging activated microlia.”
- Authors
- Murai, N., Mitalipova, M., & Jaenisch, R.
- Affiliations
- Astellas Pharma (Japan) (JP)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Jaenisch, Rudolf
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2020-09-14
- Volume
- 52
- Issue
- 7
- Pages
- 3667-3678
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC8168698
- OpenAlex
- W3037767942
- Cited by
- 33
- References
- 9
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 11 · 2020: 1
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institutes of Health (1R01‐NS088538, 5R01‐MH104610, R37HD045022)
- Cure Alzheimer's Fund
- Novo Nordisk
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- CX3CR1, fractalkine, microglia, microglial homeostasis, microglial activation, phagocytosis, neuroinflammation, interleukin-6, lipopolysaccharide, CRISPR/Cas9 knockout, human microglia
- MeSH terms
- CX3C Chemokine Receptor 1, Aged, Brain, Humans, Phagocytosis, Microglia, Induced Pluripotent Stem Cells
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