Microglia are the main innate immune cells of the central nervous system (CNS). Unlike neurons and glial cells, which derive from ectoderm, microglia migrate early during embryo development from the yolk-sac, a mesodermal-derived structure. Microglia regulate synaptic pruning during development and induce or modulate inflammation during aging and chronic diseases. Microglia are sensitive to brain injuries and threats, altering their phenotype and function to adopt a so-called immune-activated state in response to any perceived threat to the CNS integrity. Here, we present a short overview on the role of microglia in human neurodegenerative diseases and provide an update on the current model systems to study microglia, including cell lines, iPSC-derived microglia with an emphasis in their transcriptomic profile and integration into 3D brain organoids. We present various strategies to model and study their role in neurodegeneration providing a relevant platform for the development of novel and more effective therapies.

小胶质细胞是中枢神经系统（CNS）的主要先天免疫细胞。与源自外胚层的神经元和神经胶质细胞不同，小胶质细胞在胚发育过程中从卵黄囊（中胚层衍生的结构）早期迁移。小胶质细胞在发育过程中调节突触修剪，并在衰老和慢性疾病过程中诱导或调节炎症。小胶质细胞对脑损伤和威胁敏感，会改变其表型和功能，以响应对CNS完整性的任何感知威胁而采取所谓的免疫激活状态。在这里，我们简要介绍了小胶质细胞在人类神经退行性疾病中的作用，并提供了有关研究小胶质细胞（包括细胞系，iPSC衍生的小胶质细胞，其转录组特征和与3D脑器官的整合非常重要。我们提出了各种策略来建模和研究其在神经退行性病变中的作用，为开发新型更有效的疗法提供了相关平台。