RNA sequencing data of microglia, meningeal macrophages (mMphi) and perivascular macrophages (pvMphi) isolated from brains of Cx3cr1-GFP mice at different age.

All tissue resident macrophages of the central nervous system (CNS), including parenchymal microglia as well as CNS-associated macrophages (CAMs) such as meningeal (mMF) and perivascular macrophages (pvMF) are part of the CNS endogenous innate immune system that acts as the first line of defense during infections or trauma. It has been suggested that microglia and all CAM subsets are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAMs subsets in situ are poorly understood. Using novel fate mapping systems, single-cell profiling and cell-specific mutants, we show that only mMF and microglia share a common prenatal progenitor. In contrast, pvMF originate from perinatal mMF only after birth in an integrin-dependent manner. Furthermore, the establishment of pvMF critically requires the presence of vascular smooth muscle cells. In summary, our data reveal a novel precisely timed process in distinct anatomical niches for the establishment of CNS macrophage subsets. Microglia, mMphi and pvMphi were isolated from brain tissue of 3-5 individual mice per age and used for the generation of bulk transcriptomics data. RNA expression levels between the different groups and ages were compared.中枢神经系统（Central Nervous System，CNS）的所有组织驻留巨噬细胞，包括实质小胶质细胞（parenchymal microglia）以及中枢神经系统相关巨噬细胞（CNS-associated macrophages，CAMs），如脑膜巨噬细胞（meningeal macrophage，mMF）和血管周围巨噬细胞（perivascular macrophage，pvMF），均属于中枢神经系统内源性先天免疫系统的组成部分，在感染或创伤过程中作为第一道防线发挥作用。已有研究表明，小胶质细胞与所有中枢神经系统相关巨噬细胞亚群均起源于卵黄囊中被定义为早期红髓系祖细胞的产前细胞来源。然而，驱动不同中枢神经系统相关巨噬细胞亚群在原位发育的确切发育关系、潜在转录程序及分子信号，目前仍尚不明确。本研究借助新型命运图谱系统、单细胞分析技术及细胞特异性突变体展开研究，结果显示仅脑膜巨噬细胞与小胶质细胞共享共同的产前祖细胞。与之相对，血管周围巨噬细胞仅在出生后以整合素依赖的方式起源于围产期脑膜巨噬细胞。此外，血管周围巨噬细胞群体的建立严格依赖血管平滑肌细胞的存在。综上，本研究数据揭示了在不同解剖微环境中建立中枢神经系统巨噬细胞亚群的全新精准时序调控过程。本研究从每个年龄组的3-5只个体小鼠的脑组织中分离小胶质细胞、脑膜巨噬细胞（mMphi）及血管周围巨噬细胞（pvMphi），用于生成批量转录组学数据，并对不同组别及不同年龄之间的RNA表达水平进行了对比分析。