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Specificities of Living Human Microglial Cells
Giampaolo Milior1, Mariagiovanna Di Chiano2, Melanie Morin-Brureau3
1Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Paris, France. giampaolo.milior@college-de-france.fr.
Abstract:
Microglia are macrophages residing in the central nervous system, where they perform immune surveillance, synaptic remodeling, neurogenesis, and monitor signals arising from brain injuries or potential pathogens.Commonly, rodent models are used for studying microglia because of the available transgenic mouse lines in which specific genetic manipulations are successfully accomplished. However, human and rodents microglia showed significant differences, which are reflected in different morphological and functional properties. These differences are in genetic and transcriptomic, but also in the expression of signaling molecules and age-associated changes.Several strategies are available to study human microglia, as using surgical brain resections from epileptic and tumoral tissues and from post mortem brain samples. In addition, the generation of human-induced pluripotent stem cells (hPSCs) and the possibility to differentiate them in microglia-like cells provide unique opportunities to compare microglia functions between rodents' and human brain.The use of human ex vivo and in vitro brain models allows the study of human microglia, mimicking in vivo conditions. This will be useful for a better understanding of the real live behavior and functions of microglia in the human brain. This chapter aims to highlight significant similarities and differences between human and rodent microglia in order to re-evaluate mouse models of different human brain disorders, proposing the use of in vitro and ex vivo human brain models.Studies on living human microglia in the brain may help to define divergences from animal models and to improve clinical interventions to treat brain pathologies, using alternatives targets.
Insights
Rodent models show significant differences from human microglia, impacting brain disorder research. Human ex vivo and in vitro models offer better insights into human microglia function for improved therapies.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's resident macrophages, are crucial for immune surveillance, synaptic remodeling, and neurogenesis.
- Rodent models, particularly mice, are widely used for microglia research due to genetic manipulation accessibility.
- Significant morphological, functional, genetic, and transcriptomic differences exist between human and rodent microglia.
Purpose of the Study:
- To highlight key similarities and differences between human and rodent microglia.
- To re-evaluate the utility of rodent models for human brain disorders.
- To advocate for the use of human ex vivo and in vitro models for studying microglia.
Main Methods:
- Utilizing surgical brain resections (epileptic, tumoral) and post-mortem samples for human microglia studies.
- Generating human-induced pluripotent stem cells (hPSCs) and differentiating them into microglia-like cells.
- Employing human ex vivo and in vitro brain models to mimic in vivo conditions for microglia research.
Main Results:
- Identified significant genetic, transcriptomic, and functional disparities between human and rodent microglia.
- Demonstrated the potential of hPSC-derived microglia for comparative functional studies.
- Highlighted the value of human ex vivo and in vitro models in replicating in vivo human microglia behavior.
Conclusions:
- Rodent microglia models do not fully recapitulate human microglia characteristics, necessitating caution in interpreting results for human brain disorders.
- Human ex vivo and in vitro models provide a more accurate platform for studying human microglia functions.
- Further research using human microglia models can lead to improved understanding and novel therapeutic targets for human brain pathologies.
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