Tools for studying human microglia: In vitro and in vivo strategies

• Published in: Brain, behavior, and immunity behavior, and immunity, 2023-01, Vol.107, p.369-382
• Main Authors: Warden, Anna S., Han, Claudia, Hansen, Emily, Trescott, Samantha, Nguyen, Celina, Kim, Roy, Schafer, Danielle, Johnson, Avalon, Wright, Madison, Ramirez, Gabriela, Lopez-Sanchez, Mark, Coufal, Nicole G.
• Format: Article
• Language: English
• Subjects: Epigenomics; Humans
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2022.10.008

[Display omitted] •Microglia are dependent on their environment for aspects of their cellular identity.•Stem cell derived microglia offer strategic advantages over other culture methods.•Genetic editing and patient-derived lines permit exploration of disease states.•Coculture methods can dissect microglia interactions with other CNS cell types.•Xenotransplantation can restore environment-dependent microglia identity. Microglia may only represent 10% of central nervous system (CNS) cells but they perform critical roles in development, homeostasis and neurological disease. Microglia are also environmentally regulated, quickly losing their transcriptomic and epigenetic signature after leaving the CNS. This facet of microglia biology is both fascinating and technically challenging influencing the study of the genetics and function of human microglia in a manner that recapitulates the CNS environment. In this review we provide a comprehensive overview of existing in vitro and in vivo methodology to study human microglia, such as immortalized cells lines, stem cell-derived microglia, cerebral organoids and xenotransplantation. Since there is currently no single method that completely recapitulates all hallmarks of human ex vivo adult homeostatic microglia, we also discuss the advantages and limitations of each existing model as a practical guide for researchers.