Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells
© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd 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 an...
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| Format: | Article |
| Language: | English |
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Wiley
2021
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| Online Access: | https://hdl.handle.net/1721.1/134009 |
| _version_ | 1811086142765793280 |
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| author | Murai, Nobuhito Mitalipova, Maisam Jaenisch, Rudolf |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Murai, Nobuhito Mitalipova, Maisam Jaenisch, Rudolf |
| author_sort | Murai, Nobuhito |
| collection | MIT |
| description | © 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd 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. |
| first_indexed | 2024-09-23T13:21:32Z |
| format | Article |
| id | mit-1721.1/134009 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:21:32Z |
| publishDate | 2021 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1340092023-02-23T20:47:36Z Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells Murai, Nobuhito Mitalipova, Maisam Jaenisch, Rudolf Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Department of Biology © 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd 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. 2021-10-27T19:57:37Z 2021-10-27T19:57:37Z 2020 2021-07-19T17:31:50Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134009 en 10.1111/EJN.14879 European Journal of Neuroscience Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley PMC |
| spellingShingle | Murai, Nobuhito Mitalipova, Maisam Jaenisch, Rudolf Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells |
| title | Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells |
| title_full | Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells |
| title_fullStr | Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells |
| title_full_unstemmed | Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells |
| title_short | Functional analysis of CX3CR1 in human induced pluripotent stem (iPS) cell‐derived microglia‐like cells |
| title_sort | functional analysis of cx3cr1 in human induced pluripotent stem ips cell derived microglia like cells |
| url | https://hdl.handle.net/1721.1/134009 |
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