Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression
Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression
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DOI：
10.1172/jci.insight.124574
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发表时间：
2019-02-21
期刊：
影响因子：
8
通讯作者：
Loke, P'ng
中科院分区：
文献类型：
--
作者：
Lin, Jian-Da;Nishi, Hitoo;Loke, P'ng
在工业化国家，动脉粥样硬化是世界范围内主要的死亡原因。疾病的进展和消退与炎性单核细胞进入斑块的巨噬细胞的不同激活状态有关。然而，斑块进展或消退过程中单核细胞向巨噬细胞转变的特征和巨噬细胞激活状态的全谱尚未完全确定。在这里，我们使用单细胞RNA测序和遗传命运图谱的组合来描述我们所知的来自CX3CR1(+)前体的斑块细胞在小鼠动脉粥样硬化的进展和消退过程中的情况。分析揭示了巨噬细胞激活状态的频谱比传统的M1和M2极化状态更复杂，与CXC3R1(+)单核细胞分化为比退化过程中更明显的状态相关的进展。我们还发现了一群意想不到的具有干细胞样特征的增殖单核细胞，这表明单核细胞可能在炎症组织中保持增殖自我更新状态，而不是在进入组织后立即分化为巨噬细胞。
Atherosclerosis is a leading cause of death worldwide in industrialized countries. Disease progression and regression are associated with different activation states of macrophages derived from inflammatory monocytes entering the plaques. The features of monocyte-to-macrophage transition and the full spectrum of macrophage activation states during either plaque progression or regression, however, are incompletely established. Here, we use a combination of single-cell RNA sequencing and genetic fate mapping to profile, for the first time to our knowledge, plaque cells derived from CX3CR1(+) precursors in mice during both progression and regression of atherosclerosis. The analyses revealed a spectrum of macrophage activation states with greater complexity than the traditional M1 and M2 polarization states, with progression associated with differentiation of CXC3R1(+) monocytes into more distinct states than during regression. We also identified an unexpected cluster of proliferating monocytes with a stem cell-like signature, suggesting that monocytes may persist in a proliferating self-renewal state in inflamed tissue, rather than differentiating immediately into macrophages after entering the tissue.