Modulation of microglial metabolism facilitates regeneration in demyelination
Summary: Microglia exhibit diverse phenotypes in various central nervous system disorders and metabolic pathways exert crucial effects on microglial activation and effector functions. Here, we discovered two novel distinct microglial clusters, functionally associated with enhanced phagocytosis (PEMs...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422300665X |
| _version_ | 1797842239922110464 |
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| author | Chuan Qin Sheng Yang Man Chen Ming-Hao Dong Luo-Qi Zhou Yun-Hui Chu Zhu-Xia Shen Dale B. Bosco Long-Jun Wu Dai-Shi Tian Wei Wang |
| author_facet | Chuan Qin Sheng Yang Man Chen Ming-Hao Dong Luo-Qi Zhou Yun-Hui Chu Zhu-Xia Shen Dale B. Bosco Long-Jun Wu Dai-Shi Tian Wei Wang |
| author_sort | Chuan Qin |
| collection | DOAJ |
| description | Summary: Microglia exhibit diverse phenotypes in various central nervous system disorders and metabolic pathways exert crucial effects on microglial activation and effector functions. Here, we discovered two novel distinct microglial clusters, functionally associated with enhanced phagocytosis (PEMs) and myelination (MAMs) respectively, in human patients with multiple sclerosis by integrating public snRNA-seq data. Microglia adopt a PEMs phenotype during the early phase of demyelinated lesions, predominated in pro-inflammatory responses and aggravated glycolysis, while MAMs mainly emerged during the later phase, with regenerative signatures and enhanced oxidative phosphorylation. In addition, microglial triggering receptor expressed on myeloid cells 2 (Trem2) was greatly involved in the phenotype transition in demyelination, but not indispensable for microglia transition toward PEMs. Rosiglitazone could promote microglial phenotype conversion from PEMs to MAMs, thus favoring myelin repair. Taken together, these findings provide insights into therapeutic interventions targeting immunometabolism to switch microglial phenotypes and facilitate regenerative capacity in demyelination. |
| first_indexed | 2024-04-09T16:44:43Z |
| format | Article |
| id | doaj.art-679353d10d6a4ca0a2220caa6d2d9783 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T16:44:43Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-679353d10d6a4ca0a2220caa6d2d97832023-04-23T06:07:32ZengElsevieriScience2589-00422023-05-01265106588Modulation of microglial metabolism facilitates regeneration in demyelinationChuan Qin0Sheng Yang1Man Chen2Ming-Hao Dong3Luo-Qi Zhou4Yun-Hui Chu5Zhu-Xia Shen6Dale B. Bosco7Long-Jun Wu8Dai-Shi Tian9Wei Wang10Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Cardiology, Jing’an District Centre Hospital of Shanghai, Fudan University, Shanghai 200040, ChinaDepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USADepartment of Neurology, Mayo Clinic, Rochester, MN 55905, USADepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Corresponding authorDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Corresponding authorSummary: Microglia exhibit diverse phenotypes in various central nervous system disorders and metabolic pathways exert crucial effects on microglial activation and effector functions. Here, we discovered two novel distinct microglial clusters, functionally associated with enhanced phagocytosis (PEMs) and myelination (MAMs) respectively, in human patients with multiple sclerosis by integrating public snRNA-seq data. Microglia adopt a PEMs phenotype during the early phase of demyelinated lesions, predominated in pro-inflammatory responses and aggravated glycolysis, while MAMs mainly emerged during the later phase, with regenerative signatures and enhanced oxidative phosphorylation. In addition, microglial triggering receptor expressed on myeloid cells 2 (Trem2) was greatly involved in the phenotype transition in demyelination, but not indispensable for microglia transition toward PEMs. Rosiglitazone could promote microglial phenotype conversion from PEMs to MAMs, thus favoring myelin repair. Taken together, these findings provide insights into therapeutic interventions targeting immunometabolism to switch microglial phenotypes and facilitate regenerative capacity in demyelination.http://www.sciencedirect.com/science/article/pii/S258900422300665XNeuroscienceCellular neuroscienceImmunologyCell biology |
| spellingShingle | Chuan Qin Sheng Yang Man Chen Ming-Hao Dong Luo-Qi Zhou Yun-Hui Chu Zhu-Xia Shen Dale B. Bosco Long-Jun Wu Dai-Shi Tian Wei Wang Modulation of microglial metabolism facilitates regeneration in demyelination iScience Neuroscience Cellular neuroscience Immunology Cell biology |
| title | Modulation of microglial metabolism facilitates regeneration in demyelination |
| title_full | Modulation of microglial metabolism facilitates regeneration in demyelination |
| title_fullStr | Modulation of microglial metabolism facilitates regeneration in demyelination |
| title_full_unstemmed | Modulation of microglial metabolism facilitates regeneration in demyelination |
| title_short | Modulation of microglial metabolism facilitates regeneration in demyelination |
| title_sort | modulation of microglial metabolism facilitates regeneration in demyelination |
| topic | Neuroscience Cellular neuroscience Immunology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422300665X |
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