High endothelial venules (HEVs) are specialized blood vessels allowing recirculation of naïve lymphocytes through lymphoid organs. Here, using full length single-cell RNA sequencing, RNA-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-b receptor (LTbR) 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 LTbR 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 naïve 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. Overall design: Comparison of High Endothelial Cells and Blood Endothelial Cells from mouse lymph nodes under 4 different conditions with a total of 220 single cells.
Single-Cell Analysis Reveals Heterogeneity of High Endothelial Venules and Different Regulation of Genes Controlling Lymphocyte Entry to Lymph Nodes.
Specimen part, Cell line, Subject
View SamplesCellular drug resistance is associated with an unfavorable prognosis in pediatric acute lymphoblastic leukemia (ALL). To identify genes conferring resistance to antileukemic agents, we analyzed the expression of >12,700 genes in sensitive and resistant ALL cells obtained at diagnosis from 174 patients. This revealed 42, 59, 54 and 22 genes (P0.001) that were differentially expressed in B-lineage ALL that was sensitive versus resistant to prednisolone, vincristine, asparaginase or daunorubicin, respectively, with prediction accuracies of 71-76%. Notably, 149 of the discriminating genes have not been previously associated with resistance to these anticancer agents. These included carbohydrate-metabolism and transcription-associated genes for prednisolone, cytoskeleton and extracellular matrix genes for vincristine, ribosomal protein and translation-associated genes for asparaginase, and RAS signaling and nucleosome remodeling complex genes for daunorubicin. The identification of novel genomic determinants of cellular drug resistance provides new insights for overcoming drug resistance in acute lymphoblastic leukemia.
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B- and T-lineage) sensitive to daunorubicinby the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B- and T-lineage) sensitive to vincristine by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B-lineage) sensitive to daunorubicin by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B- and T-lineage) sensitive to L-asparaginase by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B-lineage) sensitive to vincristine by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B-lineage) sensitive to L-asparaginase by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B- and T-lineage) sensitive to prednisolone by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B- and T-lineage) resistant to L-asparaginase by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samples