Origin and differentiation trajectories of fibroblastic reticular cells in the splenic white pulp
Origin and differentiation trajectories of fibroblastic reticular cells in the splenic white pulp
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DOI：
10.1038/s41467-019-09728-3
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发表时间：
2019-04-15
影响因子：
16.6
通讯作者：
Ludewig, Burkhard
中科院分区：
文献类型：
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作者：
Cheng, Hung-Wei;Onder, Lucas;Ludewig, Burkhard
脾白色髓由特征不明显的基质细胞支撑，基质细胞划分不同的免疫细胞微环境。在这里，我们建立成纤维网状细胞（FRC）的小鼠特异性命运映射，以确定其胚胎起源和分化轨迹。我们的数据表明，所有网状细胞亚群下降从多能祖细胞出现在胚胎第19.5天动脉周围祖细胞。FRC祖细胞的定型是在出生后第一周通过占据沿着发育中的中央小动脉的小生境完成的。单细胞转录组学分析促进了FRC分化轨迹的去卷积，并表明血管周围网状细胞作为成体淋巴组织细胞和壁细胞祖细胞发挥作用。出生后祖细胞干性的非光敏素-p受体依赖性维持揭示了脾白色髓中的系统性免疫监视是通过来自多能动脉周围祖细胞的网状细胞亚群特化来控制的。总之，血管周围小生境中的离散信号事件决定网状细胞网络的分化轨迹的发现解释了在二级和三级淋巴组织中不同微环境小生境的发展，其对于先天性和适应性免疫过程的诱导和调节至关重要。
The splenic white pulp is underpinned by poorly characterized stromal cells that demarcate distinct immune cell microenvironments. Here we establish fibroblastic reticular cell (FRC)-specific fate-mapping in mice to define their embryonic origin and differentiation trajectories. Our data show that all reticular cell subsets descend from multipotent progenitors emerging at embryonic day 19.5 from periarterial progenitors. Commitment of FRC progenitors is concluded during the first week of postnatal life through occupation of niches along developing central arterioles. Single cell transcriptomic analysis facilitated deconvolution of FRC differentiation trajectories and indicated that perivascular reticular cells function both as adult lymphoid organizer cells and mural cell progenitors. The lymphotoxin-p receptor-independent sustenance of postnatal progenitor stemness unveils that systemic immune surveillance in the splenic white pulp is governed through subset specification of reticular cells from a multipotent periarterial progenitor cell. In sum, the finding that discrete signaling events in perivascular niches determine the differentiation trajectories of reticular cell networks explains the development of distinct microenvironmental niches in secondary and tertiary lymphoid tissues that are crucial for the induction and regulation of innate and adaptive immune processes.