Distinct developmental pathways from blood monocytes generate human lung macrophage diversity
Distinct developmental pathways from blood monocytes generate human lung macrophage diversity
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DOI：
10.1016/j.immuni.2020.12.003
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发表时间：
2021-02-09
期刊：
影响因子：
32.4
通讯作者：
Willinger, Tim
中科院分区：
文献类型：
--
作者：
Evren, Elza;Ringqvist, Emma;Willinger, Tim
人类巨噬细胞及其个体发育的研究是一个重要的尚未解决的问题。在这里，我们使用一个人源化的小鼠模型表达人类细胞因子，解剖肺巨噬细胞的发展，从人体造血在体内。人CD34（+）造血干细胞和祖细胞（HSPC）产生三个巨噬细胞群，占据肺中不同的解剖学小生境。血管内细胞标记、细胞移植和命运图谱研究证实，来源于HSPC的经典CD14（+）血液单核细胞迁移到肺组织中，并产生人间质和肺泡巨噬细胞。相比之下，非经典的CD16（+）血液单核细胞优先产生驻留在肺血管系统中的巨噬细胞（肺血管内巨噬细胞）。最后，单细胞RNA测序确定了人肺巨噬细胞从血液单核细胞发育的中间分化阶段。这项研究确定了从循环单核细胞到肺巨噬细胞的不同发育途径，并揭示了细胞起源如何有助于人类巨噬细胞的身份，多样性和体内定位。
The study of human macrophages and their ontogeny is an important unresolved issue. Here, we use a humanized mouse model expressing human cytokines to dissect the development of lung macrophages from human hematopoiesis in vivo. Human CD34(+) hematopoietic stem and progenitor cells (HSPCs) generated three macrophage populations, occupying separate anatomical niches in the lung. Intravascular cell labeling, cell transplantation, and fate-mapping studies established that classical CD14(+) blood monocytes derived from HSPCs migrated into lung tissue and gave rise to human interstitial and alveolar macrophages. In contrast, non-classical CD16(+) blood monocytes preferentially generated macrophages resident in the lung vasculature (pulmonary intravascular macrophages). Finally, single-cell RNA sequencing defined intermediate differentiation stages in human lung macrophage development from blood monocytes. This study identifies distinct developmental pathways from circulating monocytes to lung macrophages and reveals how cellular origin contributes to human macrophage identity, diversity, and localization in vivo.