Centre of Perinatal Medicine and Health, Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden.
Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg 413 90, Sweden.
Genes Dev. 2021 Aug 1;35(15-16):1190-1207. doi: 10.1101/gad.348190.120. Epub 2021 Jul 22.
The meninges are important for brain development and pathology. Using single-cell RNA sequencing, we have generated the first comprehensive transcriptional atlas of neonatal mouse meningeal leukocytes under normal conditions and after perinatal brain injury. We identified almost all known leukocyte subtypes and found differences between neonatal and adult border-associated macrophages, thus highlighting that neonatal border-associated macrophages are functionally immature with regards to immune responses compared with their adult counterparts. We also identified novel meningeal microglia-like cell populations that may participate in white matter development. Early after the hypoxic-ischemic insult, neutrophil numbers increased and they exhibited increased granulopoiesis, suggesting that the meninges are an important site of immune cell expansion with implications for the initiation of inflammatory cascades after neonatal brain injury. Our study provides a single-cell resolution view of the importance of meningeal leukocytes at the early stage of development in health and disease.
脑膜对于大脑发育和病理学都很重要。我们通过单细胞 RNA 测序，生成了第一个关于正常情况下和围产期脑损伤后新生小鼠脑膜白细胞的全面转录图谱。我们鉴定出了几乎所有已知的白细胞亚型，并发现了新生期和成年期边缘相关巨噬细胞之间的差异，这突出表明，与成年期边缘相关巨噬细胞相比，新生期边缘相关巨噬细胞在免疫反应方面功能不成熟。我们还鉴定出了可能参与白质发育的新型脑膜类小胶质细胞群体。在缺氧缺血损伤后早期，中性粒细胞数量增加，表现出更强的粒细胞生成能力，这表明脑膜是免疫细胞扩增的重要部位，对新生儿脑损伤后炎症级联反应的启动有重要影响。我们的研究提供了一个单细胞分辨率的视角，展示了脑膜白细胞在健康和疾病的早期发育阶段的重要性。
