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Expression profile of human lymphatic endothelial cells under static or oscillatory shear stress conditions in the presence or absence of FOXC2

ABSTRACT: Lymphatic valves are specialized units regularly distributed along collecting vessels that allow unidirectional forward propulsion of the lymph, and its efficient transport from tissues to the bloodstream. Lymphatic endothelial cells that cover lymphatic valve sinuses are subjected to complex flow patterns, due to recirculation of the lymph during the collecting vessel pumping cycle. They also express high levels of FOXC2 transcription factor. We used microarrays to study the transcriptional networks controlled by FOXC2 in human lymphatic endothelial cells subjected to oscillatory shear stress or cultured under static conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE60152 | GEO | 2015/11/09

SECONDARY ACCESSION(S): PRJNA257637

REPOSITORIES: GEO

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Expression profile of human lymphatic endothelial cells under static or oscillatory shear stress conditions in the presence or absence of FOXC2

Project description:Lymphatic valves are specialized units regularly distributed along collecting vessels that allow unidirectional forward propulsion of the lymph, and its efficient transport from tissues to the bloodstream. Lymphatic endothelial cells that cover lymphatic valve sinuses are subjected to complex flow patterns, due to recirculation of the lymph during the collecting vessel pumping cycle. They also express high levels of FOXC2 transcription factor. We used microarrays to study the transcriptional networks controlled by FOXC2 in human lymphatic endothelial cells subjected to oscillatory shear stress or cultured under static conditions. Human lymphatic endothelial cells were transfected with control or FOXC2 siRNAs and subjected to 24-hour oscillatory shear stress (1 dyn/cm2; 1/4 Hz) or kept under static conditions as a control. RNA were amplified and hybridized on Affymetrix Human Gene 1.0 ST Arrays. The experiment was run twice independently, using each time a different siRNA to knockdown FOXC2, as previously described (Sabine et al, 2012, Dev Cell).

2015-11-09 | E-GEOD-60152 | biostudies-arrayexpress

ChIP-chip study aimed at the identification of the repertoire of FOXC2 binding sites affected by the loss of FOXC2 phosphorylation in primary human lymphatic endothelial cells (LECs)

Project description:Chromatin immunoprecipitation microarray (ChIP-chip) study using anti-Myc (9E10) antibodies and primary human lymphatic endothelial cells (LECs) transduced with recombinant adenoviruses expressing wild type or phosphorylation-deficient Myc-tagged FOXC2.

2013-07-13 | E-MTAB-596 | biostudies-arrayexpress

Tissue inflammation reprograms lymphatic collectors to support entry and rapid migration of dendritic cells to draining lymph nodes

Project description:Afferent lymphatic vessels (LVs) connect peripheral tissues with draining lymph nodes (dLNs) and are important for immune-surveillance and tissue drainage. They begin in the tissue as initial lymphatic capillaries, which are highly permeable and branched vessels specialized in the uptake of macromolecules, fluids and immune cells. Conversely, the downstream collecting LVs are impermeable and contractile structures that transport the taken up lymph and immune cells to the dLN. We and others have recently observed that intralymphatic leukocytes actively migrate within lymphatic capillaries but de-adhere and are passively transported by flow once they have reached in the collecting vessels. Besides potential differences in lymph flow we hypothesize that gene expression differences between capillaries and collectors could account for this transition from a crawling to a flowing mode of migration. In this project we aimed to perform a sequencing-based gene expression analysis of lymphatic endothelial cells (LECs) isolated from lymphatic capillaries and collectors, in order to identify new genes involved in leukocyte migration, as well as genes involved in shaping the morphologic phenotype of capillaries and collectors. For this, murine skin was enzymatically digested and LECs from capillaries or collectors were FACS-sorted and their RNA extracted and subjected to sequencing.

2021-05-07 | E-MTAB-9175 | biostudies-arrayexpress

Glycan analysis of promary human lymphatic endothlial cells (LEX) in their resting and activated states, in normal and tumor tissues

2011-06-14 | GSE29933 | GEO

Glycan analysis of promary human lymphatic endothlial cells (LEX) in their resting and activated states, in normal and tumor tissues

Project description:Trafficking of leukocytes (dendritic cells, memory T cells, neutrophils) and tumor cells through the lymphatic network is a key process in inflammation and immunity and an important mechanism in metastatic spread of human cancers (1-3). Such trafficking involves both communication with and passage across lymphatic endothelium, the distinct endothelium that lines lymphatic vessels within the peripheral tissues and forms the lymphatic sinuses within lymph nodes. However, in comparison with blood vascular endothelium, there is only a rudimentary understanding of the molecular phenotype of lymphatic endothelium, and only a basic knowledge of the glycoconjugates that regulate leukocyte-endothelial and tumor cell-endothelial interactions in the lymphatic compartment. We would anticipate that changes in glycosylation of LEC cell surface proteins following activation might affect important functions associated withy LEC including eg. interactions with leukocytes and/or sequestration of GAG-binding chemokines. We already have shown that ligand binding to the lymphatic endothelial hyaluronan receptor LYVE-1 is reversibly masked by terminal sialation in LEC and that functional regulation of LYVE-1 is likely to be important in inflammation. An advantage of our proposal is that we can routinely isolate primary LEC in relatively large numbers, and have the necessary ethical approval to do so from human tissue. Glycan analysis of primary human lymphatic endothelial cells (LEC) in their resting and activated states, in normal and tumour tissues and a comparison of the LEC glycan structures with those from blood vessel endothelial cells

2011-06-14 | E-GEOD-29933 | biostudies-arrayexpress

Apelin-VEGF-C mRNA delivery as therapeutic for the treatment of secondary lymphedema

Project description:Secondary lymphedema (LD) corresponds to a severe lymphatic dysfunction leading to the accumulation of fluid and fibrotic adipose tissue in a limb. Here, we identified apelin (APLN) as a powerful molecule for regenerating lymphatic function in LD. We identified the loss of APLN expression in lymphedematous arm compared to normal arm in patients. The role of APLN in LD was confirmed in APLN-knockout mice, in which LD is increased and associated with fibrosis and dermal backflow. This was reversed by intradermal injection of APLN-lentivectors. Mechanistically, APLN stimulates lymphatic endothelial cell gene expression and induces the binding of E2F8 transcription factor to the promoter of CCBE1 that controls VEGF-C processing. In addition, APLN induces Akt and eNOS pathways to stimulate lymphatic collector pumping. Our results show that APLN represents a novel partner for VEGF-C to restore lymphatic function in both initial and collecting vessels. As LD appears after cancer treatment, we validated the APLN-VEGF-C combination using a novel class of non-integrative RNA-delivery LentiFlash® vector that will be evaluated for phase I/IIa clinical trial.

2023-10-20 | E-MTAB-13381 | biostudies-arrayexpress

FOXC1 and FOXC2 promote endothelial-derived R-spondin 3 and CXCL12 signals in intestinal regeneration after ischemia-reperfusion injury

Project description:Intestinal ischemia induces mucosal damage while simultaneously activating intestinal stem cells (ISCs), which subsequently regenerate the damaged intestinal epithelium. However, whether angiocrine factors secreted from vascular endothelial cells (ECs) - blood and lymphatic ECs (BECs and LECs, respectively) – regulate ISC-mediated regeneration have yet to be elucidated. Here, we identify FOXC1 and FOXC2 as essential regulators of angiocrine signaling in regeneration of the small intestine after ischemia-reperfusion (I/R) injury. EC- and LEC-specific deletions of Foxc1, Foxc2, or both in mice augment I/R-induced intestinal damage by causing defects in vascular regrowth, expression of the chemokine CXCL12 and the Wnt activator R-spondin 3 in BECs and LECs, respectively, and activation of Wnt signaling in ISCs. Treatment with CXCL12 and R-spondin 3 rescues the I/R-induced intestinal damage in EC- and LEC-Foxc mutant mice, respectively. This study provides evidence that FOXC1 and FOXC2 are required for intestinal regeneration by stimulating angiocrine CXCL12 and Wnt signaling.

2021-12-13 | GSE190581 | GEO

FOXC2 controls adult lymphatic endothelial specialization, function and gut lymphatic barrier preventing multi-organ failure

Project description:FOXC2 controls adult lymphatic endothelial specialization, function and gut lymphatic barrier preventing multi-organ failure

| PRJNA657504 | ENA

Expression data from collecting lymphatic vessels

Project description:Lymphogenous metastasis is an important event in the progression of many human cancers, and is associated with expression of vascular endothelial growth factor-D (VEGF-D). Changes to the lymphatic vasculature can occur during metastasis, and may aid metastatic spread. We investigated the effect of tumour derived VEGFD on the endothelium of the collecting lymphatic vessels draining primary tumors. We used microarrays to detail the changes in gene expression in the collecting lymphatic endothelium of mice with 293EBNA xenografts compared to 293EBNA xenografts overexpressing VEGFD. Mice were injected with 293EBNA cells (transfected with either empty APEX vector, or vector containing VEGFD) and tumours were allowed to grow to size. Mice were sacrificed and collecting lymphatic vessels were dissected. The endothelial cell population was isolated and RNA was extracted and hybridized on Affymetrix microarrays.

2012-01-15 | E-GEOD-34135 | biostudies-arrayexpress

Expression analysis of colorectal cancer cell line SW480 expressing FOXC2

Project description:Investigation of whole genome gene expression level changes in a colorectal cancer cell line SW480 expressing FOXC2, compared to the pBabe control cells. Genes associated with metastasis regulated by FOXC2 in colorectal cancer were analysed. The role of FOXC2 in breast cancer metastasis are further described in Mani SA, Yang J et al. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. PNAS 2007; 104: 10069-10074 . A six chip study using total RNA recovered from three separate cultures of SW480/pBabe and three separate cultures of SW480/FOXC2. Each chip measures the expression level of 45033 genes from SW480/pBabe or SW480/FOXC2.

2014-07-02 | E-GEOD-58980 | biostudies-arrayexpress

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