A molecular map of murine lymph node blood vascular endothelium at single cell resolution

A molecular map of murine lymph node blood vascular endothelium at single cell resolution
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DOI:
10.1038/s41467-020-17291-5
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发表时间:
2020-07-30
影响因子:
16.6
通讯作者:
Butcher, Eugene C.
Butcher, Eugene C.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Brulois, Kevin;Rajaraman, Anusha;Butcher, Eugene C.

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血管内皮细胞(BECs)通过调节淋巴组织中的血流和免疫细胞募集来控制免疫反应。然而,BEC在免疫血管生成过程中的多样性及其来源尚不清楚。在这里,我们分析了外周淋巴结中BEC的转录本,并将表型映射到血管系统。我们确定了多个亚群,包括一个髓静脉群体,其基因特征预测了髓系细胞(VS淋巴细胞)招募到髓质中的选择性作用,这一点得到了视频显微镜的证实。我们定义了五个毛细血管亚群,包括显示干细胞和迁移基因特征的毛细血管驻留前体(CRP),并在免疫后有助于动态平衡的BEC周转和高内皮细胞的新生。细胞排列显示发育程序沿从CRP到成熟的静脉和动脉群体的轨迹保持。我们的单细胞图谱提供了淋巴结血管系统的分子路线图,并定义了白细胞募集和血管动态平衡的亚群特化。淋巴组织中血管内皮细胞(BEC)的来源和多样性尚不清楚。在这里,作者通过单细胞分析描述了来自外周淋巴结的小鼠BEC,并确定了专门用于免疫细胞招募和血管动态平衡的细胞亚群。
Blood vascular endothelial cells (BECs) control the immune response by regulating blood flow and immune cell recruitment in lymphoid tissues. However, the diversity of BEC and their origins during immune angiogenesis remain unclear. Here we profile transcriptomes of BEC from peripheral lymph nodes and map phenotypes to the vasculature. We identify multiple subsets, including a medullary venous population whose gene signature predicts a selective role in myeloid cell (vs lymphocyte) recruitment to the medulla, confirmed by videomicroscopy. We define five capillary subsets, including a capillary resident precursor (CRP) that displays stem cell and migratory gene signatures, and contributes to homeostatic BEC turnover and to neogenesis of high endothelium after immunization. Cell alignments show retention of developmental programs along trajectories from CRP to mature venous and arterial populations. Our single cell atlas provides a molecular roadmap of the lymph node blood vasculature and defines subset specialization for leukocyte recruitment and vascular homeostasis. The origin and diversity of blood vascular endothelial cells (BEC) in lymphoid tissues is unclear. Here, the authors profile murine BECs from peripheral lymph nodes by single cell analysis and identify subsets of cells specialised for immune cell recruitment and vascular homeostasis.