Microglia, the brain’s resident macrophages, shape neural development and are key neuroimmune hubs in the pathological signatures of neurodevelopmental disorders. Despite the importance of microglia, their development has not been carefully examined in the human brain, and most of our knowledge derives from rodents. We aimed to address this gap in knowledge by establishing an extensive collection of 97 post-mortem tissues in order to enable quantitative, sex-matched, detailed analysis of microglia across the human lifespan. We identify the dynamics of these cells in the human telencephalon, describing waves in microglial density across gestation, infancy, and childhood, controlled by a balance of proliferation and apoptosis, which track key neurodevelopmental milestones. These profound changes in microglia are also observed in bulk RNA-seq and single-cell RNA-seq datasets. This study provides a detailed insight into the spatiotemporal dynamics of microglia across the human lifespan and serves as a foundation for elucidating how microglia contribute to shaping neurodevelopment in humans.

小胶质细胞是大脑中常驻的巨噬细胞，它塑造神经发育，并且是神经发育障碍病理特征中的关键神经免疫中枢。尽管小胶质细胞很重要，但它们的发育尚未在人脑中得到仔细研究，而且我们的大部分知识都来自啮齿类动物。我们旨在通过建立 97 个死后组织的广泛收集来弥补这一知识差距，以便能够对整个人类生命周期的小胶质细胞进行定量、性别匹配、详细的分析。我们确定了人类端脑中这些细胞的动态，描述了妊娠期、婴儿期和儿童期的小胶质细胞密度波，由增殖和凋亡的平衡控制，跟踪关键的神经发育里程碑。小胶质细胞的这些深刻变化也在批量 RNA-seq 和单细胞 RNA-seq 数据集中观察到。这项研究提供了对小胶质细胞在人类一生中的时空动态的详细了解，并为阐明小胶质细胞如何促进人类神经发育奠定了基础。