Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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. 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).

ORGANISM(S): Homo sapiens

SUBMITTER: Nadine Zangger

PROVIDER: E-GEOD-60152 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature.

Sabine Amélie A Bovay Esther E Demir Cansaran Saygili CS Kimura Wataru W Jaquet Muriel M Agalarov Yan Y Zangger Nadine N Scallan Joshua P JP Graber Werner W Gulpinar Elgin E Kwak Brenda R BR Mäkinen Taija T Martinez-Corral Inés I Ortega Sagrario S Delorenzi Mauro M Kiefer Friedemann F Davis Michael J MJ Djonov Valentin V Miura Naoyuki N Petrova Tatiana V TV

The Journal of clinical investigation 20150921 10

Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC ...[more]

PMID: 26389677

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Project description:The lymphatic vascular system plays important roles in the maintenance of interstitial fluid pressure, the afferent immune response and the absorption of dietary lipids. However, the molecular mechanisms that control lymphatic vessel network maturation and function remain largely unknown. To identify novel players in lymphatic vessel function, we isolated pure populations of lymphatic and blood vascular endothelial cells from mouse intestine using fluorescence-activated high-speed cell sorting and performed transcriptional profiling. We found that the axonal guidance molecules semaphorin 3A (Sema3A) and Sema3D were specifically expressed by lymphatic vessels. Quantitative PCR of ex vivo isolated cells and immunohistochemical analysis confirmed these results. Importantly, we found that the semaphorin receptor neuropilin-1 (Nrp-1) is expressed on the valves of collecting lymphatic vessels. Treatment of mice in utero (E12.5-E16.5) with an antibody that blocks Sema3A binding to Nrp-1, but not with an antibody that blocks VEGFA binding to Nrp-1, resulted in abnormal development of collecting lymphatic vessels and valves, and aberrant smooth muscle cell coverage. Conversely, Sema3A-deficient mice displayed branching defects of collecting lymphatic vessels as well as impaired valve development. Together, these results reveal an unanticipated role of Sema3A/Nrp-1 signaling in the maturation of the lymphatic vascular network. Colon single-cell suspensions were prepared by a fast protocol that minimizes the RNA degradation. Fluorescence-activated cell sorting (FACS) was used to sort blood vascular endothelial cells (BEC) and lymphatic endothelial cells (LEC). 4 animal-matched pairs of LEC and BEC were chosen based on the quality of extracted and amplified material to provide homogenous groups of biological replicates. This gave 8 samples to analyze. Samples present LEC and BEC isolated from 4 healthy normal mice. The 4 mice used present the 4 biological replicates.

Dataset Information

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

Publications

FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature.

Similar Datasets

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