1. Single-Cell Analysis Reveals Heterogeneity of High Endothelial Venules and Different Regulation of Genes Controlling Lymphocyte Entry to Lymph Nodes.
- Author
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Veerman K, Tardiveau C, Martins F, Coudert J, and Girard JP
- Subjects
- Animals, Chemokine CCL21 genetics, Chemokine CCL21 metabolism, Endothelium, Vascular cytology, Female, Fucosyltransferases genetics, Fucosyltransferases metabolism, Genetic Heterogeneity, Lymph Nodes cytology, Lymphocytes metabolism, Lymphotoxin beta Receptor genetics, Lymphotoxin beta Receptor metabolism, Mice, Mice, Inbred C57BL, N-Acetylglucosaminyltransferases genetics, N-Acetylglucosaminyltransferases metabolism, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Single-Cell Analysis, Sulfotransferases genetics, Sulfotransferases metabolism, Trans-Activators genetics, Trans-Activators metabolism, Venules cytology, Carbohydrate Sulfotransferases, Cell Movement genetics, Endothelium, Vascular metabolism, Homeostasis, Lymphocytes physiology, Transcriptome, Venules metabolism
- Abstract
High-endothelial venules (HEVs) are specialized blood vessels allowing recirculation of naive lymphocytes through lymphoid organs. Here, using full-length, single-cell RNA sequencing, RNA fluorescence in situ hybridization (FISH), flow cytometry, and immunohistofluorescence, we reveal the heterogeneity of HEVs in adult mouse peripheral lymph nodes (PLNs) under conditions of homeostasis, antigenic stimulation, and after inhibition of lymphotoxin-β receptor (LTβR) signaling. We demonstrate that HEV endothelial cells are in an activated state during homeostasis, and we identify the genes characteristic of the differentiated HEV phenotype. We show that LTβR signaling regulates many HEV genes and pathways in resting PLNs and that immune stimulation induces a global and temporary inflammatory phenotype in HEVs without compromising their ability to recruit naive lymphocytes. Most importantly, we uncover differences in the regulation of genes controlling lymphocyte trafficking, Glycam1, Fut7, Gcnt1, Chst4, B3gnt3, and Ccl21a, that have implications for HEV function and regulation in health and disease., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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