Identification and mapping of human lymph node stromal cell subsets by combining single-cell RNA sequencing with spatial transcriptomics.

Grasso, C.; Roet, J.; Gago de Graca, C.; Semmelink, J. F.; Remmerswaal, E.; Jongejan, A.; Moerland, P. D.; Mebius, R. E.; van Baarsen, L. G. M.

doi:10.1101/2023.08.18.553530

bioRxiv · 10.1101/2023.08.18.553530

Identification and mapping of human lymph node stromal cell subsets by combining single-cell RNA sequencing with spatial transcriptomics.

Grasso, C.·Roet, J.·Gago de Graca, C.·Semmelink, J. F.·Remmerswaal, E.·Jongejan, A.·Moerland, P. D.·Mebius, R. E.·van Baarsen, L. G. M.

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Abstract

Lymph node stromal cells (LNSCs) have a crucial immunomodulatory function, but their heterogeneity in human is incompletely understood. Here, we report the single cell RNA sequencing (scRNA-seq) of 12000 LNSCs isolated from a human lymph node (LN). This study comprehensively defines the gene signatures of 10 fibroblast subtypes: CCL21+SC, CCL19+SC, CD34+CXCL14+SC, pericytes, DES+SC, LAMP5+SC, NR4A1+BCAM+ SC, HLA-DR+SC, SEPT4+SC and GLDN+SC. To explore the heterogeneous stromal compartment within the complex LN tissue architecture, we integrated the scRNA-seq profiles of the identified LNSC subsets with a publicly available human spatial transcriptomic LN dataset and predicted their location within the complex LN tissue architecture. Each LNSC subtype was spatially restricted to specific LN regions, indicating different LNSC-lymphocyte interactions which was further investigated using NicheNet. The positioning of distinct LNSC subtypes in different LN regions sets the stage for future research on the relationship between LNSC-specific niches and immunomodulatory function during health and disease.

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Grasso, C., Roet, J., Gago de Graca, C., Semmelink, J. F., Remmerswaal, E., Jongejan, A., Moerland, P. D., Mebius, R. E., van Baarsen, L. G. M.. 2023-08-19. Identification and mapping of human lymph node stromal cell subsets by combining single-cell RNA sequencing with spatial transcriptomics.. https://doi.org/10.1101/2023.08.18.553530

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