PMID- 30865898 OWN - NLM STAT- MEDLINE DCOM- 20200415 LR - 20231213 IS - 2211-1247 (Electronic) VI - 26 IP - 11 DP - 2019 Mar 12 TI - Single-Cell Analysis Reveals Heterogeneity of High Endothelial Venules and Different Regulation of Genes Controlling Lymphocyte Entry to Lymph Nodes. PG - 3116-3131.e5 LID - S2211-1247(19)30213-X [pii] LID - 10.1016/j.celrep.2019.02.042 [doi] AB - 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-beta receptor (LTbetaR) 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 LTbetaR 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. CI - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Veerman, Krystle AU - Veerman K AD - Institut de Pharmacologie et de Biologie Structurale (IPBS), Universite de Toulouse, CNRS, UPS, Toulouse, France. FAU - Tardiveau, Claire AU - Tardiveau C AD - Institut de Pharmacologie et de Biologie Structurale (IPBS), Universite de Toulouse, CNRS, UPS, Toulouse, France. FAU - Martins, Frederic AU - Martins F AD - Institut des Maladies Metaboliques et Cardiovasculaires (I2MC), UMR1048, INSERM, UPS, Toulouse, France; Plateforme Genome et Transcriptome (GeT), Genopole Toulouse, Toulouse, France. FAU - Coudert, Juliette AU - Coudert J AD - Institut de Pharmacologie et de Biologie Structurale (IPBS), Universite de Toulouse, CNRS, UPS, Toulouse, France. FAU - Girard, Jean-Philippe AU - Girard JP AD - Institut de Pharmacologie et de Biologie Structurale (IPBS), Universite de Toulouse, CNRS, UPS, Toulouse, France. Electronic address: jean-philippe.girard@ipbs.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 RN - 0 (Ccl21a protein, mouse) RN - 0 (Chemokine CCL21) RN - 0 (GCN1 protein, mouse) RN - 0 (Ltbr protein, mouse) RN - 0 (Lymphotoxin beta Receptor) RN - 0 (RNA-Binding Proteins) RN - 0 (Trans-Activators) RN - EC 2.4.1.- (Fucosyltransferases) RN - EC 2.4.1.- (N-Acetylglucosaminyltransferases) RN - EC 2.4.1.- (fucosyltransferase VII, mouse) RN - EC 2.8.2.- (Sulfotransferases) SB - IM MH - Animals MH - Cell Movement/*genetics MH - Chemokine CCL21/genetics/metabolism MH - Endothelium, Vascular/cytology/*metabolism MH - Female MH - Fucosyltransferases/genetics/metabolism MH - Genetic Heterogeneity MH - *Homeostasis MH - Lymph Nodes/cytology MH - Lymphocytes/metabolism/*physiology MH - Lymphotoxin beta Receptor/genetics/metabolism MH - Mice MH - Mice, Inbred C57BL MH - N-Acetylglucosaminyltransferases/genetics/metabolism MH - RNA-Binding Proteins/genetics/metabolism MH - Single-Cell Analysis MH - Sulfotransferases/genetics/metabolism MH - Trans-Activators/genetics/metabolism MH - *Transcriptome MH - Venules/cytology/*metabolism MH - Carbohydrate Sulfotransferases OTO - NOTNLM OT - endothelial cell OT - high-endothelial venule OT - homeostasis OT - inflammation OT - lymphocyte homing OT - lymphocyte trafficking OT - lymphotoxin-beta receptor OT - peripheral lymph node OT - scRNA-seq OT - single-cell RNA sequencing EDAT- 2019/03/14 06:00 MHDA- 2020/04/16 06:00 CRDT- 2019/03/14 06:00 PHST- 2018/12/05 00:00 [received] PHST- 2019/01/25 00:00 [revised] PHST- 2019/02/11 00:00 [accepted] PHST- 2019/03/14 06:00 [entrez] PHST- 2019/03/14 06:00 [pubmed] PHST- 2020/04/16 06:00 [medline] AID - S2211-1247(19)30213-X [pii] AID - 10.1016/j.celrep.2019.02.042 [doi] PST - ppublish SO - Cell Rep. 2019 Mar 12;26(11):3116-3131.e5. doi: 10.1016/j.celrep.2019.02.042.