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

Immunity. 2018 May 15;48(5):1014-1028.e6. doi: 10.1016/j.immuni.2018.04.006. Epub 2018 May 8.

Abstract

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, Ccl19hi T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs), and perivascular cells. We also identified Ccl19lo 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.

Keywords: double negative cell; fibroblastic reticular cell; follicular dendritic cell; marginal reticular cell; perivascular cell; single-cell RNA sequencing; stromal cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Chemokine CCL19 / genetics
  • Chemokine CCL19 / immunology
  • Chemokine CCL19 / metabolism
  • Dendritic Cells, Follicular / immunology
  • Dendritic Cells, Follicular / metabolism
  • Female
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Mice, Inbred C57BL
  • Sequence Analysis, RNA / methods*
  • Single-Cell Analysis / methods*
  • Stromal Cells / immunology*
  • Stromal Cells / metabolism
  • Transcriptome / immunology*

Substances

  • Chemokine CCL19