Single-Cell RNA Sequencing of Lymph Node Stromal Cells Reveals Niche-Associated Heterogeneity

Publication date: Available online 8 May 2018
Source:Immunity
Author(s): Lauren B. Rodda, Erick Lu, Mariko L. Bennett, Caroline L. Sokol, Xiaoming Wang, Sanjiv A. Luther, Ben A. Barres, Andrew D. Luster, Chun Jimmie Ye, Jason G. Cyster
Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains undefined. Using droplet-based single-cell RNA sequencing, we identified nine peripheral LN non-endothelial SC clusters. Included are the established subsets, Ccl19^hi T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs), and perivascular cells. We also identified Ccl19^lo TRCs, likely including cholesterol-25-hydroxylase⁺ cells located at the T-zone perimeter, Cxcl9⁺ TRCs in the T-zone and interfollicular region, CD34⁺ SCs in the capsule and medullary vessel adventitia, indolethylamine N-methyltransferase⁺ SCs in the medullary cords, and Nr4a1⁺ SCs in several niches. These data help define how transcriptionally distinct LN SCs support niche-restricted immune functions and provide evidence that many SCs are in an activated state.

Graphical abstract

Teaser

Lymph node stromal cells support diverse processes, but bulk assessments obscure their niche-specific functions. Rodda et al. identify transcriptional profiles for nine lymph node stromal cell clusters using single-cell RNA sequencing, validate subset markers in situ, and suggest niche-restricted functions.


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