Single-Cell Analysis Reveals Heterogeneity of High Endothelial Venules and Different Regulation of Genes Controlling Lymphocyte Entry to Lymph Nodes
Cell Reports. 2019-03-01; 26(11): 3116-3131.e5
DOI: 10.1016/j.celrep.2019.02.042
1. Cell Rep. 2019 Mar 12;26(11):3116-3131.e5. doi: 10.1016/j.celrep.2019.02.042.
Single-Cell Analysis Reveals Heterogeneity of High Endothelial Venules and
Different Regulation of Genes Controlling Lymphocyte Entry to Lymph Nodes.
Veerman K(1), Tardiveau C(1), Martins F(2), Coudert J(1), Girard JP(3).
Author information:
(1)Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de
Toulouse, CNRS, UPS, Toulouse, France.
(2)Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), UMR1048,
INSERM, UPS, Toulouse, France; Plateforme Genome et Transcriptome (GeT),
Genopole Toulouse, Toulouse, France.
(3)Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de
Toulouse, CNRS, UPS, Toulouse, France. Electronic address:
.
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.
DOI: 10.1016/j.celrep.2019.02.042
PMID: 30865898 [Indexed for MEDLINE]