Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

54 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Blood flow diverts extracellular vesicles from endothelial degradative compartments to promote angiogenesis

ABSTRACT: Extracellular vesicles released by tumors (tEVs) disseminate via circulatory networks and promote microenvironmental changes in distant organs favoring metastatic seeding. Despite their abundance in the bloodstream, how hemodynamics affect the function of circulating tEVs remains unsolved. We experimentally tuned flow profiles in vitro (microfluidics) and in vivo (zebrafish) and demonstrated that efficient uptake of tEVs occurs in endothelial cells subjected to capillary-like hemodynamics. Such flow profiles partially reroute internalized tEVs towards non-acidic and non-degradative Rab14-positive endosomes, at the expense of lysosomes, suggesting that endothelial mechanosensing diverts tEVs from degradation. Subsequently, tEVs promote the expression of pro-angiogenic transcription factors in flow-stimulated endothelial cells and favor vessel sprouting in zebrafish. Altogether, we demonstrate that capillary-like flow profiles potentiate the pro-tumoral function of circulating tEVs by promoting their uptake and rerouting their trafficking. We propose that tEVs contribute to pre-metastatic niche formation by exploiting endothelial mechanosensing in specific vascular regions with permissive hemodynamics. This set of experiments represents RNAseq of HUVEC cells subjected to 400 µm/s flow versus no flow (static conditon).

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Raphael Carapito

PROVIDER: E-MTAB-13156 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Transcription profiling of pig aortic endothelial cells to investigate the impact of gender, high fat/high cholesterol diet and regional hemodynamics on gene expression

Project description:Atherosclerosis preferentially develops in susceptible regions of the arterial system that are defined by the regional vascular hemodynamics. Previous work in adult castrate male pigs revealed the coexistence of pro- and anti-atherosclerotic profiles in endothelial cell gene expression in disturbed flow regions of arteries in the absence of risk factors for atherogenesis. This study investigates the impact of gender, high fat/high cholesterol diet and regional hemodynamics on arterial endothelial cell gene expression profiles in sexually mature intact pigs.

2007-12-15 | E-CBIL-41 | biostudies-arrayexpress

Effect of autophagy deficiency in endothelial cells

Project description:Dysregulated autophagy is associated with cardiovascular and metabolic diseases, where impaired flow-mediated endothelial cell responses promote cardiovascular risk. The mechanism by which the autophagy machinery regulates endothelial functions is complex. We applied multi-omics approaches and in vitro and in vivo functional assays to decipher the diverse roles of autophagy in endothelial cells. We demonstrate that autophagy regulates VEGF-dependent VEGFR signaling and VEGFR-mediated and flow-mediated eNOS activation. Endothelial ATG5 deficiency in vivo results in selective loss of flow-induced vasodilation in mesenteric arteries and kidneys, along with increased cerebral and renal vascular resistance. We found a crucial pathophysiological role for autophagy in endothelial cells in flow-mediated outward arterial remodeling, prevention of neointima formation following wire injury, and recovery after myocardial infarction. Together, these findings unravel a fundamental role for autophagy in endothelial function, linking cell proteostasis to mechanosensing.

2023-07-01 | GSE235785 | GEO

Transcription profiling of pig aortic endothelium taken from regions of disturbed and undisturbed flow

Project description:This study investigates the role of endothelial cell (EC) gene expression in the focal origin of atherosclerosis, particularly in response to local hemodynamics. Differential gene expression was profiled in EC isolated from athero-susceptible and athero-protected regions of the normal pig aorta. Specifically, a region of disturbed flow (DF, the inner aortic arch) was compared to a region of undisturbed flow (UF, descending thoracic aorta). Linearly amplified RNA was used to screen nylon filter arrays of 13,824 human cDNAs.

2006-07-21 | E-CBIL-17 | biostudies-arrayexpress

3D vascularized proximal tubule model improves cell phenotype

Project description:Cultured proximal tubule epithelial cells (PTECs) under physiological flow in a 3D channel embedded within an engineered extracellular matrix (ECM) that is colocalized with an adjacent channel lined with human glomerular endothelial cells (HGECs) to mimic a peritubular capillary. After a period of maturation under continuous flow, both cell types were harvested for RNAseq analyses. Our results revealed that PTECs’ transcriptional profile is highly dependent on both the matrix on which these cells are cultured and the flow conditions. By contrast, endothelial cells exhibit greater phenotypic plasticity and are affected by matrix, flow, and co-culture conditions.

2022-03-20 | GSE198822 | GEO

Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics

Project description:Objective The vessel wall is continuously exposed to hemodynamic forces generated by blood flow. Endothelial mechanosensors perceive and translate mechanical signals via cellular signaling pathways into biological processes that control endothelial development, phenotype and function. Here, we aim to unravel the molecular mechanisms underlying endothelial mechanosensing. Approach and results We applied a quantitative mass spectrometry approach combined with cell surface chemical footprinting to assess the hemodynamic effects on the endothelium on a system-wide level. These studies revealed that of the >5000 quantified proteins 104 were altered, which were highly enriched for extracellular matrix proteins and proteins involved in cell-matrix adhesion. Cell surface proteomics furthermore indicated that LAMA4 was proteolytically processed upon flow-exposure, which corresponded to the decreased LAMA4 mass observed on immunoblot. Immunofluorescence microscopy studies highlighted that the endothelial basement membrane was drastically remodeled upon flow exposure. We observed a network-like pattern of LAMA4 and LAMA5, which corresponded to the localization of laminin-adhesion molecules ITGA6 and ITGB4. Furthermore, the adaptation to flow-exposure did not affect the inflammatory response to tumor necrosis factor α, indicating that inflammation and flow trigger fundamentally distinct endothelial signaling pathways with limited reciprocity and synergy. Conclusions Taken together, this study uncovers the blood flow-induced remodeling of the basement membrane and stresses the importance of the subendothelial basement membrane in vascular homeostasis.

2020-04-29 | PXD014526 | Pride

Global gene expression differences between blood- and lymphatic-specific endothelial colony forming cells

Project description:The identification of circulating endothelial progenitor cells has led to speculation regarding their origin as well as their contribution to neovascular development. Two distinct types of endothelium make up the blood and lymphatic vessel system. However, it has yet to be determined whether there are distinct lymphatic-specific circulating endothelial progenitor cells. We isolated circulating endothelial colony forming cells (ECFCs) from whole peripheral blood. These cells are endothelial in nature, as defined by their expression of endothelial markers and their ability to undergo capillary morphogenesis in three-dimensional culture. A subset of isolated colonies express markers of lymphatic endothelium, including VEGFR-3 and Prox-1, with low levels of VEGFR-1, a blood endothelial marker, while the bulk of the isolated cells express high VEGFR-1 levels with low VEGFR-3 and Prox-1 expression. The different isolates have differential responses to VEGF-C, a lymphatic endothelial specific cytokine, strongly suggesting that there are lymphatic specific and blood specific ECFCs. Global analysis of gene expression revealed key differences in the regulation of pathways involved in cellular differentiation between blood and lymphatic-specific ECFCs. These data indicate that there are two distinguishable circulating ECFC types, blood and lymphatic, which are likely to have discrete functions during neovascularization. RNA was isolated from 2 blood-specific ECFC cell lines and 2 lymphatic-specific ECFC cell lines 3 separate times each

2014-06-23 | E-GEOD-54416 | biostudies-arrayexpress

Effect of mechanical constriction forces on breast cell lines transcripts

Project description:During metastatic dissemination, circulating tumour cells (CTCs) enter capillary beds, where they experience mechanical constriction forces. A high-throughput microfluidic platform mimicking human capillaries to investigate the impact of mechanical constriction forces on malignant and normal breast cell lines was developed. Cells were collected after transiting the constrictions, followed by RNA extraction and sequencing. The non-malignant cell line experienced transcriptional changes, particularly downregulation of epithelial markers, while the metastatic cell lines showed minimal alterations.

2024-02-16 | GSE246824 | GEO

Shear stress switches the association of endothelial enhancers from ETV/ETS to KLF transcription factor binding sites

Project description:The study shows transcriptional and chromatin changes in human umbilical cord endothelial cells (HUVEC) exposed to shear stress. In addition transcriptional changes in zebrafish endothelial cells in response to blood flow block are shown

2022-03-14 | GSE198221 | GEO

Global gene expression differences between blood- and lymphatic-specific endothelial colony forming cells

2014-06-23 | GSE54416 | GEO

Tumor exosome integrins determine organotropic metastasis

Project description:Stephen Paget first proposed, in 1889, that organ distribution of metastases is a non-random event, yet metastatic organotropism remains one of the greatest mysteries in cancer biology. Here, we demonstrate that exosomes released by lung-, liver- and brain-tropic tumor cells fuse preferentially with resident cells at their predicted destination, such as fibroblasts and epithelial cells in the lung, Kupffer cells in the liver, and endothelial cells in the brain. We found that exosome homing to organ-specific cell types prepares the pre-metastatic niche and that treatment with exosomes derived from lung tropic models can redirect metastasis to the lung. Proteomic profiling of exosomes revealed distinct integrin expression patterns associated with each organ-specific metastasis. Whereas exosomal integrins α6β4 and α6β1 were associated with lung metastasis, exosomal integrins αvβ5 and αvβ3 were linked with liver and brain metastases, respectively. Targeting α6β4 and αvβ5 integrins decreased exosome uptake and metastasis in the lung and liver, respectively. Importantly, we demonstrate that exosome uptake activates a cell-specific subset of S100 family genes, known to support cell migration and niche formation. Finally, our clinical data indicate that integrin-expression profiles in circulating plasma exosomes from cancer patients could be used to predict organ-specific metastasis. Education of human von Kupffer cells in vitro with human pancreatic cancer exosomes

2015-06-17 | E-GEOD-68919 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data