Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE58056 | GEO | 2014/08/31
SECONDARY ACCESSION(S): PRJNA248768
REPOSITORIES: GEO
Similar Datasets
Project description:This file contains gene microarray data from FACS purified mouse high endothelial cells and capillary endothelial cells from peripheral lymph nodes, mesenteric lymph nodes, and Peyer’s patches. The data will allow for better understanding of the specialization of high endothelial venules (HEV) and their role in lymphocyte recruitment from the blood; the tissue-specific differentiation of lymphoid tissue vasculature; and the specialized features of capillary vs. post-capillary endothelium, including differences in signaling pathways, adhesive properties and mechanisms of hemostasis. We analyzed transcript expression data from vascular endothelial subsets from BALB/c mouse lymphoid tissue.
2014-08-31 | E-GEOD-58056 | biostudies-arrayexpress
Project description:High endothelial venules (HEVs) are specialized postcapillary venules that mediate lymphocyte trafficking from the blood into lymph nodes. HEV-like blood vessels are found in solid tumors in association with CD8+ T cell infiltration.This study uses single cell RNA-sequencing using the Fluidigm C1 system as a method to evaluate the transcriptome in lymph node and tumor-associated HEV endothelial cells (LN-HECs and TA-HECs). We isolated MECA-79+ TA-HECs and CD31+MECA-79- tumor-associated endothelial cells (TA-ECs) by cell sorting and we compared their transcriptome to those of their counterparts in homeostatic (LN-HECs and LN-ECs) or inflamed (iLN-HECs) lymph nodes. TA-HECs express high levels of endothelial cell markers Cdh5 and Pecam1 (CD31), post-capillary venule marker Ackr1 (DARC) and venous transcription factor Nr2f2, indicating that they correspond to post-capillary venule endothelium, like their lymph node counterparts. The genes encoding HEV sialomucins decorated by the sulfated MECA-79 epitope (CD34 and Emcn, endomucin) and the core 1 branching enzyme B3gnt3 that is essential for its biosynthesis, are equally expressed in all HEC populations, whereas sulfotransferases Chst2 and Chst4 are expressed at lower levels in TA-HECs. Although TA-HECs are molecularly distinct from lymph node HECs, they share several important characteristics with iLN-HECs, including the upregulation of endothelial selectins (Selp, Sele) and inflammatory chemokines CXCL9 and CXCL10, the ligands for chemokine receptor CXCR3 on effector T cells. Finally, endothelial cell adhesion molecules ICAM1, ICAM2 and VCAM1 that are important for lymphocyte sticking to HEVs, are expressed at similar levels in all HECs. Together, these findings indicated that MECA-79+ TA-HECs, similar to HECs in immune-stimulated lymph nodes, exhibit an inflamed phenotype characterized by co-expression of MECA-79+ antigens with endothelial selectins and inflammatory chemokines.
2021-12-14 | GSE154898 | GEO
Project description: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.
2019-03-12 | GSE106514 | GEO
Project description:High endothelial venules (HEVs) are specialized post-capillary venules that recruit naïve lymphocytes to the lymph nodes and are essential for the development of adaptive immunity. HEVs can also develop in tumors. These specialized tumor vessels are thought to be important for recruiting naïve T cells and B cells into tumors and locally enhancing anti-tumor immunity by supporting the formation of tertiary lymphoid structures. By a comparative transcriptome analysis in human breast cancer, we investigated differentially expressed genes between tumor-associated HEVs and the rest of the tumor vasculature. Tumor vessels highly expressing HEV-upregulated genes, such as the homeobox gene MEOX2 and the tetraspanin gene TSPAN7, were associated with extensive infiltration of T and B lymphocytes and the occurrence of tertiary lymphoid structures, which is known to predict therapeutic responses to immune checkpoint inhibitors. Moreover, high transcript counts of these genes in clinical tumor specimens were associated with a significant survival benefit in advanced breast cancer. The molecular signature of HEVs identified here may be useful for guiding immunotherapies and provide a new direction for investigating tumor-associated HEVs and their clinical significance.
2022-03-31 | GSE196703 | GEO
Project description:Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules (HEV), providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3+ capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define an NKX-COUP-TFII morphogenetic code that targets expression of mucosal vascular addressins.
2022-11-14 | GSE217886 | GEO
Project description:Lymphoma growth is facilitated by the well-balanced infrastructure of the microenvironment in lymph nodes (LN). LNs undergo rapid expansion during lymphoma progression, often accompanied by excessive blood vessel growth. Here we report that aggressive lymphoma cause severe high endothelial venule (HEV) regression which impairs lymphocyte recirculation. In this study, we used transferred (i.v.) Eµ-Myc tumor cells as a mouse model of aggressive lymphoma. Blood endothelial cells from tumor bearing and control LNs were isolated by FACS and processed for single-cell RNA sequencing. The results revealed a detrimental mechanisms causing HEV-dedifferentiation during lymphoma growth with potential implications on tumor-targeting immune surveillance and strategies of immune therapy in LNs
2021-10-14 | E-MTAB-10389 | biostudies-arrayexpress
Project description:Endothelial cells in the blood vessels in the kidney exert different functions depending on the (micro)vascular bed they are located in. These functional differences are likely a result of differential microRNA and mRNA transcription patterns, yet the identity of these molecules is not well known. We zoomed in on the endothelial cells of microvascular compartments in mouse renal cortex by laser microdissecting the microvessels prior to (small) RNA sequencing analyses. By these means, we characterised microRNA and mRNA transcription profiles of arterioles, glomeruli, peritubular capillaries, and post-capillary venules. RT-qPCR, in situ hybridisation, and immunohistochemistry were used to validate sequencing results. Unique microRNA and mRNA transcription profiles were found in all microvascular compartments, with dedicated marker microRNAs and mRNAs showing enriched transcription in a single microvascular compartment. In situ hybridisation validated localisation of microRNAs mmu-miR-140-3p in arterioles, of mmu-miR-322-3p in glomeruli, and of mmu-miR-451a in post-capillary venules. Immunohistochemical staining showed that von Willebrand Factor protein was mainly expressed in arterioles and post-capillary venules, while GABRB1 expression was enriched in glomeruli and IGF1 in post-capillary venules. Our study shows that microvascular endothelial heterogeneity in mouse kidney is a result of a combination of differentially expressed microRNAs and mRNAs. The identified profiles provide important molecular information to take into account for future studies into microvascular engagement in health and disease.
2023-06-30 | GSE220985 | GEO
Project description:Endothelial cells in the blood vessels in the kidney exert different functions depending on the (micro)vascular bed they are located in. These functional differences are likely a result of differential microRNA and mRNA transcription patterns, yet the identity of these molecules is not well known. We zoomed in on the endothelial cells of microvascular compartments in mouse renal cortex by laser microdissecting the microvessels prior to (small) RNA sequencing analyses. By these means, we characterised microRNA and mRNA transcription profiles of arterioles, glomeruli, peritubular capillaries, and post-capillary venules. RT-qPCR, in situ hybridisation, and immunohistochemistry were used to validate sequencing results. Unique microRNA and mRNA transcription profiles were found in all microvascular compartments, with dedicated marker microRNAs and mRNAs showing enriched transcription in a single microvascular compartment. In situ hybridisation validated localisation of microRNAs mmu-miR-140-3p in arterioles, of mmu-miR-322-3p in glomeruli, and of mmu-miR-451a in post-capillary venules. Immunohistochemical staining showed that von Willebrand Factor protein was mainly expressed in arterioles and post-capillary venules, while GABRB1 expression was enriched in glomeruli and IGF1 in post-capillary venules. Our study shows that microvascular endothelial heterogeneity in mouse kidney is a result of a combination of differentially expressed microRNAs and mRNAs. The identified profiles provide important molecular information to take into account for future studies into microvascular engagement in health and disease.
2023-06-30 | GSE220986 | GEO
Project description:Patterns of chemotactic receptors regulate the homing of leukocytes to tissues. Here we report that the CCRL2/chemerin/CMKLR1 axis represent a selective pathway for the homing of NK cells to the lung. CCRL2 is a non-signaling seven-transmembrane domain receptor able to control lung tumor growth. Total or endothelial cell targeted CCRL2 deletion or the deletion of its ligand chemerin were found to promote tumor progression in a KrasG12D/+;p53LoxP lung cancer model. This phenotype was dependent on the reduced recruitment of CD27-CD11b+ mature NK cells. Mining scRNA-seq databases identified CCRL2 expression as the hallmark of general alveolar lung capillary endothelial cells (gCaps). CCRL2 expression is epigenetically regulated in lung endothelium. In vivo administration of low doses of the demethylating agent 5-Aza induced CCRL2 upregulation, increased recruitment of NK cells and lung protection in a tumor model. These results identify CCRL2 as a NK cell lung homing molecule that might be exploited to promote NK cell-mediated lung immune surveillance.
2023-08-04 | GSE212088 | GEO
Project description:Impaired angiogenesis characterized by the reduced proliferation of pulmonary endothelial cells leads to reduced capillary density in patients with bronchopulmonary dysplasia (BPD). In a mouse model of BPD, perinatal hyperoxic injury decreases the number of the recently identified lung capillary stem cells termed as general capillary (gCap) cells, along with the specific reduction of Ntrk2, which encodes for Tropomyosin receptor kinase B (TRKB) within this subpopulation. Herein, we determine whether TRKB signaling is required for perinatal gCap cell proliferation and further promoting pulmonary angiogenesis using the hyperoxia mouse BPD model. TRKB activation by BDNF treatment led to enhanced tube-forming ability of endothelial cells in vitro. In vivo treatment of mice with BDNF increased the proliferation of gCap cells and alleviated capillary loss caused by hyperoxic injury. Conversely, inhibition of TRKB signaling disrupted the tube formation of endothelial cells and exaggerated the vascular endothelial damage caused by hyperoxia. We further show that MAPK/ERK signaling might act downstream of TRKB to modulate pulmonary angiogenesis. These data indicate that TRKB signaling play a critical role in pulmonary angiogenesis upon perinatal lung injury, supporting the concept that TRKB activation might be a potential therapeutic for preserving endothelial cells for lung diseases associated with prematurity.
2024-09-15 | GSE276575 | GEO