Clonal Proliferation and Stochastic Pruning Orchestrate Lymph Node Vasculature Remodeling
Clonal Proliferation and Stochastic Pruning Orchestrate Lymph Node Vasculature Remodeling
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DOI：
10.1016/j.immuni.2016.09.017
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发表时间：
2016-10-18
期刊：
影响因子：
32.4
通讯作者：
Bajenoff, Marc
中科院分区：
文献类型：
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作者：
Mondor, Isabelle;Jorquera, Audrey;Bajenoff, Marc
免疫反应期间淋巴结（LN）的扩张依赖于其脉管系统的瞬时重塑。尽管人们开始了解驱动 LN 内皮细胞分裂的机制，但缺乏对单细胞水平的 LN 内皮细胞动力学的全面了解。在这里，我们使用彩色荧光命运图谱模型来追踪炎症时 LN 扩张以及随后恢复稳态期间血液内皮细胞的行为。我们发现淋巴结脉管系统的扩张依赖于内皮细胞增殖单位的顺序组装。这种分段生长是通过高内皮微静脉 (HEV) 细胞的克隆增殖来维持的，这些细胞充当局部祖细胞，在淋巴结周围形成毛细血管和 HEVneo 血管。恢复稳态伴随着预先存在的和新合成的 LN 内皮细胞的随机死亡。因此，我们的命运图谱研究在单细胞水平上揭示了淋巴结扩张和收缩过程中血管树重塑的复杂动态。
Lymph node (LN) expansion during an immune response relies on the transient remodeling of its vasculature. Although the mechanisms driving LN endothelial cell division are beginning to be understood, a comprehensive view of LN endothelial cell dynamics at the single-cell level is lacking. Here, we used multicolored fluorescent fate-mapping models to track the behavior of blood endothelial cells during LN expansion upon inflammation and subsequent return to homeostasis. We found that expansion of the LN vasculature relied on the sequential assembly of endothelial cell proliferative units. This segmented growth was sustained by the clonal proliferation of high endothelial venule (HEV) cells, which act as local progenitors to create capillaries andHEVneo-vessels at the periphery of the LN. Return to homeostasis was accompanied by the stochastic death of pre-existing and neo-synthesized LN endothelial cells. Thus, our fate-mapping studies unravel-at a single-cell level-the complex dynamics of vascular-tree remodeling during LN expansion and contraction.