Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction
Abstract Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS) to glycolysis or alterations in other metabolic pathways. However, most of the experimental findings have been acqu...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42096-7 |
| _version_ | 1797558239093587968 |
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| author | Angélica María Sabogal-Guáqueta Alejandro Marmolejo-Garza Marina Trombetta-Lima Asmaa Oun Jasmijn Hunneman Tingting Chen Jari Koistinaho Sarka Lehtonen Arjan Kortholt Justina C. Wolters Barbara M. Bakker Bart J. L. Eggen Erik Boddeke Amalia Dolga |
| author_facet | Angélica María Sabogal-Guáqueta Alejandro Marmolejo-Garza Marina Trombetta-Lima Asmaa Oun Jasmijn Hunneman Tingting Chen Jari Koistinaho Sarka Lehtonen Arjan Kortholt Justina C. Wolters Barbara M. Bakker Bart J. L. Eggen Erik Boddeke Amalia Dolga |
| author_sort | Angélica María Sabogal-Guáqueta |
| collection | DOAJ |
| description | Abstract Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS) to glycolysis or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells, and little is known about the metabolic reprogramming of human microglia. In this study, we investigate the transcriptomic, proteomic, and metabolic profiles of mouse and iPSC-derived human microglia challenged with the TLR4 agonist LPS. We demonstrate that both species display a metabolic shift and an overall increased glycolytic gene signature in response to LPS treatment. The metabolic reprogramming is characterized by the upregulation of hexokinases in mouse microglia and phosphofructokinases in human microglia. This study provides a direct comparison of metabolism between mouse and human microglia, highlighting the species-specific pathways involved in immunometabolism and the importance of considering these differences in translational research. |
| first_indexed | 2024-03-10T17:28:33Z |
| format | Article |
| id | doaj.art-84b22256347c40f5852d44e2ee2ceacc |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:28:33Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-84b22256347c40f5852d44e2ee2ceacc2023-11-20T10:06:07ZengNature PortfolioNature Communications2041-17232023-10-0114112410.1038/s41467-023-42096-7Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway inductionAngélica María Sabogal-Guáqueta0Alejandro Marmolejo-Garza1Marina Trombetta-Lima2Asmaa Oun3Jasmijn Hunneman4Tingting Chen5Jari Koistinaho6Sarka Lehtonen7Arjan Kortholt8Justina C. Wolters9Barbara M. Bakker10Bart J. L. Eggen11Erik Boddeke12Amalia Dolga13Department of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of GroningenDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of GroningenDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of GroningenDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of GroningenDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of GroningenDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of GroningenA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandDepartment of Cell Biochemistry, University of GroningenLaboratory of Pediatrics, Section Systems Medicine of Metabolism and Signaling, Faculty of Medical Sciences, University of Groningen, University Medical Center GroningenLaboratory of Pediatrics, Section Systems Medicine of Metabolism and Signaling, Faculty of Medical Sciences, University of Groningen, University Medical Center GroningenDepartment of Biomedical Sciences of Cells & Systems, section Molecular Neurobiology, Faculty of Medical Sciences, University of Groningen, University Medical Center GroningenDepartment of Biomedical Sciences of Cells & Systems, section Molecular Neurobiology, Faculty of Medical Sciences, University of Groningen, University Medical Center GroningenDepartment of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of GroningenAbstract Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS) to glycolysis or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells, and little is known about the metabolic reprogramming of human microglia. In this study, we investigate the transcriptomic, proteomic, and metabolic profiles of mouse and iPSC-derived human microglia challenged with the TLR4 agonist LPS. We demonstrate that both species display a metabolic shift and an overall increased glycolytic gene signature in response to LPS treatment. The metabolic reprogramming is characterized by the upregulation of hexokinases in mouse microglia and phosphofructokinases in human microglia. This study provides a direct comparison of metabolism between mouse and human microglia, highlighting the species-specific pathways involved in immunometabolism and the importance of considering these differences in translational research.https://doi.org/10.1038/s41467-023-42096-7 |
| spellingShingle | Angélica María Sabogal-Guáqueta Alejandro Marmolejo-Garza Marina Trombetta-Lima Asmaa Oun Jasmijn Hunneman Tingting Chen Jari Koistinaho Sarka Lehtonen Arjan Kortholt Justina C. Wolters Barbara M. Bakker Bart J. L. Eggen Erik Boddeke Amalia Dolga Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction Nature Communications |
| title | Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction |
| title_full | Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction |
| title_fullStr | Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction |
| title_full_unstemmed | Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction |
| title_short | Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction |
| title_sort | species specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction |
| url | https://doi.org/10.1038/s41467-023-42096-7 |
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