School of Biological Sciences, University of Southampton, Southampton, United Kingdom; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
School of Biological Sciences, University of Southampton, Southampton, United Kingdom.
Dev Cell. 2022 Sep 12;57(17):2127-2139.e6. doi: 10.1016/j.devcel.2022.07.015. Epub 2022 Aug 16.
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的常驻巨噬细胞，它们塑造着神经发育，并在神经发育障碍的病理特征中充当关键的神经免疫中枢。尽管小胶质细胞非常重要，但它们在人类大脑中的发育尚未得到仔细研究，我们的大部分知识都来自于啮齿动物。我们旨在通过建立一个广泛的 97 个人体组织库来填补这一知识空白，以便能够对人类整个生命周期的小胶质细胞进行定量的、性别匹配的、详细的分析。我们确定了这些细胞在人类端脑中的动态，描述了在妊娠、婴儿期和儿童期小胶质细胞密度的波动，由增殖和凋亡的平衡控制，这些波动与关键的神经发育里程碑相吻合。这些小胶质细胞的深刻变化也在批量 RNA-seq 和单细胞 RNA-seq 数据集中被观察到。这项研究深入了解了人类整个生命周期中小胶质细胞的时空动态，为阐明小胶质细胞如何在人类中塑造神经发育提供了基础。
