Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Brain Behav Immun. 2023 Jan;107:369-382. doi: 10.1016/j.bbi.2022.10.008. Epub 2022 Nov 3.
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.
小胶质细胞可能仅占中枢神经系统 (CNS) 细胞的 10%，但它们在发育、稳态和神经疾病中发挥着关键作用。小胶质细胞也受到环境的调节，一旦离开 CNS，它们的转录组和表观遗传特征就会迅速丢失。小胶质细胞生物学的这一方面既迷人又具有技术挑战性，以一种再现 CNS 环境的方式影响了人类小胶质细胞的遗传学和功能研究。在这篇综述中，我们提供了对体外和体内研究人类小胶质细胞的现有方法的全面概述，例如永生化细胞系、干细胞衍生的小胶质细胞、脑类器官和异种移植。由于目前没有一种方法可以完全再现体外成年稳态人类小胶质细胞的所有特征，因此我们还讨论了每种现有模型的优缺点，作为研究人员的实用指南。
