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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-023-02673-1

摘要内容如下：

人类中枢神经系统（CNS）的先天免疫区室是高度多样化的，包括几种免疫细胞群，如在脑实质中常见的巨噬细胞（小胶质细胞）和在脑界面数量较少的CNS相关巨噬细胞（CAMs）。由于它们的稀少和特殊位置，在发育、健康和扰动过程中，对时间和空间受限的CAM亚类的存在知之甚少。在这里，我们将单细胞RNA测序、飞行时间质量细胞术和单细胞空间转录组学与命运图谱和先进的免疫组织化学相结合，以全面表征人类CNS界面的免疫系统，分析了来自102个个体的超过356，000个转录组。我们还对15名接受外周血干细胞移植的患者脑内的固有和移植的骨髓细胞进行了全面分析，揭示了不同CNS界面的区室特异性植入率。解剖解剖的胶质母细胞瘤样本的整合多组学和高分辨率空间转录组分析显示，由缺氧驱动的区域不同的髓系细胞类型分布。值得注意的是，胶质母细胞瘤相关的缺氧反应不同于胎儿小胶质细胞和CAMs的生理性缺氧反应。我们的研究结果突出了人类中枢神经系统与外周界面的骨髓多样性，并为人类大脑免疫系统的复杂性提供了见解。

英文原文如下：

Abstracts

The innate immune compartment of the human central nervous system (CNS) is highly diverse and includes several immune-cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs). Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here we combined single-cell RNA sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces with over 356,000 analyzed transcriptomes from 102 individuals. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces. Integrated multiomic and high-resolution spatial transcriptome analysis of anatomically dissected glioblastoma samples shows regionally distinct myeloid cell-type distributions driven by hypoxia. Notably, the glioblastoma-associated hypoxia response was distinct from the physiological hypoxia response in fetal microglia and CAMs. Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain's immune system.

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