Translational modelling of human microglia from cultures to chimeras
- 1Department of Neuroscience, Korea University College of Medicine, Seoul, Republic of Korea
- 2BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea
Abstract
Microglia play a crucial role in maintaining homeostasis of the central nervous system, whereas their dysfunction is implicated in the pathogenesis of various neurological diseases. Nevertheless, interspecific genetic differences pose challenges to translating findings from conventional rodent models. Human pluripotent stem cell-derived microglia offer a genetically relevant alternative, but these cells undergo profound transcriptomic changes and lose key homeostatic features when isolated from physiological brain cues. Accordingly, research has increasingly focused on advanced modelling platforms designed to restore the microenvironment required for in vivo microglial identity and functionality. This review examines the evolution of human microglial platforms, encompassing foundational generation protocols and multicellular integration. The discussion extends from two-dimensional co-cultures to three-dimensional brain organoids and includes human microglia chimeric models established via xenotransplantation to provide a physiological niche. In summary, the human pluripotent stem cell-based approach represents a valuable experimental pipeline for microglia research, facilitating the investigation of polygenic structures underlying human neurological diseases, from high-throughput screening to in vivo preclinical validation.
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BibTeX
@article{lee2026translational,
title = {{Translational modelling of human microglia from cultures to chimeras}},
author = {Jina Lee and Yongjin Yoo},
journal = {Experimental \& Molecular Medicine},
year = {2026},
month = oct,
doi = {10.1038/s12276-026-01866-1},
url = {https://doi.org/10.1038/s12276-026-01866-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Translational modelling of human microglia from cultures to chimeras
AU - Jina Lee
AU - Yongjin Yoo
PY - 2026
DA - 2026/10/13
JO - Experimental & Molecular Medicine
DO - 10.1038/s12276-026-01866-1
UR - https://doi.org/10.1038/s12276-026-01866-1
AB - Microglia play a crucial role in maintaining homeostasis of the central nervous system, whereas their dysfunction is implicated in the pathogenesis of various neurological diseases. Nevertheless, interspecific genetic differences pose challenges to translating findings from conventional rodent models. Human pluripotent stem cell-derived microglia offer a genetically relevant alternative, but these cells undergo profound transcriptomic changes and lose key homeostatic features when isolated from physiological brain cues. Accordingly, research has increasingly focused on advanced modelling platforms designed to restore the microenvironment required for in vivo microglial identity and functionality. This review examines the evolution of human microglial platforms, encompassing foundational generation protocols and multicellular integration. The discussion extends from two-dimensional co-cultures to three-dimensional brain organoids and includes human microglia chimeric models established via xenotransplantation to provide a physiological niche. In summary, the human pluripotent stem cell-based approach represents a valuable experimental pipeline for microglia research, facilitating the investigation of polygenic structures underlying human neurological diseases, from high-throughput screening to in vivo preclinical validation.
SN - 1226-3613
SN - 2092-6413
ER -