Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Immunity. 2022 Apr 12;55(4):606-622.e6. doi: 10.1016/j.immuni.2022.03.002. Epub 2022 Mar 30.
Lymph node (LN) stromal cells play a crucial role in LN development and in supporting adaptive immune responses. However, their origin, differentiation pathways, and transcriptional programs are still elusive. Here, we used lineage-tracing approaches and single-cell transcriptome analyses to determine origin, transcriptional profile, and composition of LN stromal and endothelial progenitors. Our results showed that all major stromal cell subsets and a large proportion of blood endothelial cells originate from embryonic Hoxb6 progenitors of the lateral plate mesoderm (LPM), whereas lymphatic endothelial cells arise from Pax3 progenitors of the paraxial mesoderm (PXM). Single-cell RNA sequencing revealed the existence of different Cd34 and Cxcl13 stromal cell subsets and showed that embryonic LNs contain proliferating progenitors possibly representing the amplifying populations for terminally differentiated cells. Taken together, our work identifies the earliest embryonic sources of LN stromal and endothelial cells and demonstrates that stromal diversity begins already during LN development.
淋巴结（LN）基质细胞在 LN 发育和支持适应性免疫反应中起着至关重要的作用。然而，它们的起源、分化途径和转录程序仍然难以捉摸。在这里，我们使用谱系追踪方法和单细胞转录组分析来确定 LN 基质和血管内皮祖细胞的起源、转录谱和组成。我们的结果表明，所有主要的基质细胞亚群和很大一部分血液内皮细胞都起源于侧板中胚层（LPM）的胚胎 Hoxb6 祖细胞，而淋巴管内皮细胞则起源于轴旁中胚层（PXM）的 Pax3 祖细胞。单细胞 RNA 测序揭示了不同的 Cd34 和 Cxcl13 基质细胞亚群的存在，并表明胚胎 LN 中存在增殖祖细胞，这些祖细胞可能代表终末分化细胞的扩增群体。总之，我们的工作确定了 LN 基质和血管内皮细胞的最早胚胎来源，并证明了基质的多样性在 LN 发育过程中就已经开始了。
