Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide analysis of gene expression in endothelial colony forming cells and mature endothelial cells

ABSTRACT: Autologous endothelial cells are promising alternative angiogenic cell sources in trials of therapeutic vasculogenesis; in the treatment of vascular diseases and in the field of tissue engineering. A population of endothelial cells (ECs) with long-term proliferative capability can be isolated from human peripheral blood. They are called endothelial colony forming cells (ECFCs), and are considered to be an endothelial precursor population. They can be expanded in cell factories to sufficient numbers for clinical applications, but as the number of isolated primary ECs is low, the culture period required may be quite long. Another EC population that is easily available in the autologous setting and may be expanded in vitro through several population doublings are the ECs from adipose tissue (AT-ECs). Through extensive comparisons using whole-genome microarray analysis, morphology, phenotype and functional assays, we wanted to evaluate the potential of these EC populations for use in clinical neovascularization. Global gene expression profiling of ECFCs, AT-ECs and the classical EC population, human umbilical vein ECs showed that the EC populations clustered as unique populations, but very close to each other. By cell surface phenotype and vasculogenic potential in vitro and in vivo we also found the ECFCs to be extremely similar to AT-ECs. These properties, and easy access in the autologous setting, suggest that both AT-ECs and ECFCs may be useful in trials of therapeutic neovascularization. However, AT-ECs may be a more practical alternative for obtaining large quantities of autologous ECs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE55695 | GEO | 2015/09/30

SECONDARY ACCESSION(S): PRJNA240584

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

Project description:Endothelial cell (EC) metabolism is an emerging target for anti-angiogenic therapy in tumor and choroidal neovascularization (CNV), but little is known about individual EC metabolic transcrip-tomes. Here, by scRNA-sequencing 28,337 murine choroidal ECs (CECs) and sprouting CNV-ECs, we constructed a taxonomy to characterize their heterogeneity. Comparison with murine lung tumor ECs (TECs) revealed congruent marker gene expression by distinct EC phenotypes across tissues and diseases, suggesting similar angiogenic mechanisms. Trajectory inference of CNV-ECs revealed that differentiation of venous to angiogenic ECs was accompanied by metabolic transcriptome plasticity. EC phenotypes displayed metabolic transcriptome heterogeneity. Hypothesizing that conserved genes are more important, we used an integrated analysis, based on congruent transcriptome analysis, CEC-tailored genome scale metabolic modeling, and gene expression me-ta-analysis in multiple cross-species datasets, followed by functional validation, to identify the top-ranking metabolic targets SQLE and ALDH18A1, involved in EC proliferation and collagen production, respectively, as novel angiogenic targets.

2020-03-31 | E-MTAB-8604 | biostudies-arrayexpress

Endothelial metabolic transcriptome plasticity in pathological angiogenesis

Project description:Endothelial cell (EC) metabolism is an emerging target for anti-angiogenic therapy in tumor and choroidal neovascularization (CNV), but little is known about individual EC metabolic transcriptomes. Here, by scRNA-sequencing 28,337 murine choroidal ECs (CECs) and sprouting CNV-ECs, we constructed a taxonomy to characterize their heterogeneity. Comparison with murine lung tumor ECs (TECs) revealed congruent marker gene expression by distinct EC phenotypes across tissues and diseases, suggesting similar angiogenic mechanisms. Trajectory inference of CNV-ECs revealed that differentiation of venous to angiogenic ECs was accompanied by metabolic transcriptome plasticity. EC phenotypes displayed metabolic transcriptome heterogeneity. Hypothesizing that conserved genes are more important, we used an integrated analysis, based on congruent transcriptome analysis, CEC-tailored genome scale metabolic modeling, and gene expression meta-analysis in multiple cross-species datasets, followed by functional validation, to identify the top-ranking metabolic targets SQLE and ALDH18A1, involved in EC proliferation and collagen production, respectively, as novel angiogenic targets. The effect of SQLE and ALDH18A1 silencing in ECs was investigated by transcriptomics and proteomics analysis.

2020-04-14 | PXD016678 | Pride

Suppression of ANGPTL4 Reprograms Endothelial Cell Metabolism and Inhibits Angiogenesis

Project description:Angiopoietin-like 4 (ANGPTL4) is known to regulate various cellular and systemic functions. However, its cell-specific role in endothelial cells (ECs) function and metabolic homeostasis remains to be elucidated. Here, using endothelial-specific Angptl4 knock-out mice (Angptl4iEC), and transcriptomics and metabolic flux analysis, we demonstrate that ANGPTL4 is required for maintaining EC metabolic function vital for vascular permeability and angiogenesis. Knockdown of ANGPTL4 in ECs promotes lipase-mediated lipoprotein lipolysis, which results in increased fatty acid (FA) uptake and oxidation. This is also paralleled by a decrease in proper glucose utilization for angiogenic activation of ECs. Mice with endothelial-specific deletion of Angptl4 showed decreased pathological neovascularization with stable vessel structures characterized by increased pericyte coverage and reduced permeability. Together, our study denotes the role of endothelial-ANGPTL4 in regulating cellular metabolism and angiogenic functions of EC.

2023-11-22 | GSE211128 | GEO

Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

Project description:Endothelial cell (EC) metabolism regulates angiogenesis and is an emerging target for anti-angiogenic therapy in tumor and choroidal neovascularization (CNV). In contrast to tumor ECs (TECs), CNV-ECs cannot be isolated for unbiased metabolic target discovery. Here we used scRNA-sequencing to profile 28,337 choroidal ECs (CECs) from mice to in silico distinguish healthy CECs from CNV-ECs. Trajectory inference suggested that CNV-ECs plastically upregulate genes in central carbon metabolism and collagen biosynthesis during differentiation from quiescent postcapillary venous ECs. CEC-tailored genome scale metabolic modeling predicted essentiality of SQLE and ALDH18A1 for proliferation and collagen production, respectively. Comparative analysis in TECs revealed more outspoken metabolic transcriptome heterogeneity in subtypes and consistent upregulation of SQLE and ALDH18A1 across tumor types. Inhibition of SQLE and ALDH18A1 reduced sprouting angiogenesis in vitro. These findings demonstrate the potential of integrated scRNA-seq analysis to identify angiogenic metabolic targets in disease ECs.

2020-06-25 | E-MTAB-8119 | biostudies-arrayexpress

Bulk RNA-sequencing of FACS isolated human fetal lung, intestine, and kidney endothelial cells

Project description:Adult endothelial cells (ECs) are known to possess organ-specific gene expression, morphology and function, but whether organ-specific EC gene expression is present during human development is not known. Here, we used bulk RNA-sequencing (RNA-seq) to interrogate the developing human intestine, lung, and kidney in order to identify organ-enriched EC-gene signatures. FACS was used to isolate EC (CD31+CD144+, n=13) and non-EC (CD31-CD144-, n=16) populations from these three organs, profiling at least 4 biological replicates for each organ system. The biological specimens profiled were between 11-20 gestational weeks. We also sequenced cultured human umbilical vein endothelial cells (HUVECs) via bulk RNAseq. Computational approaches were used to identify organ-specific EC-enriched gene signatures across human fetal lung, intestine, and kidney ECs.

2020-12-20 | E-MTAB-9372 | biostudies-arrayexpress

NOVEL ROLE OF FATTY ACID SYNTHASE IN ANGIOGENESIS THROUGH MODULATION OF LYSINE MALONYLATION OF MTOR

Project description:The role of fatty acid synthesis (FAS) in endothelial cells (ECs) remains incompletely characterized. In this project, we found that silencing of fatty acid synthase (FASN) impedes vessel sprouting by reducing EC proliferation. Moreover, loss of FASN in ECs impaired angiogenesis in vivo, and FASN blockade reduced pathological ocular neovascularization. FASN silencing increased malonyl-CoA levels and immunoblotting of EC lysates for malonylated lysine residues (Kmal) revealed that this led to increased levels of protein malonylation. To identify the nature of some of the malonylated proteins we performed a proteomics screen using an anti-Kmal antibody to enrich Kmal peptides from a tryptic digest of EC lysates, and then analyzed Kmal peptides by LC-MS/MS. In proteomics analysis, we identified malonylation of mTOR at lysine 1218, a poorly characterized post-translational modification. Malonylation of mTOR did not compromise the mTORC1 complex stability or lysosomal membrane localization, but reduced the kinase activity of the complex.

2019-07-08 | PXD006503 | Pride

Krüppel-like factor 2 in VCAM1+ endothelial cells is a critical regulator of vascular inflammation

Project description:Endothelial cells (ECs) act as an internal barrier to the vessel wall, hindering the development of inflammation, and only when activated will promote the development of vascular inflammation. However, the heterogeneity of the aortic ECs in the setting of vascular inflammation have not been fully assessed. Here, we defined 4 EC subpopulations, including Cd36+ EC, Notch3+ EC, Vcam1+ EC and Lyve1+ EC. Based on the enrichment analysis, Vcam1+ EC were considered to be a subpopulation of ECs susceptible to activation. After high-fat diet (HFD) intake, decreased expression of Krüppel-like factor 2 (Klf2) occurred only in Vcam1+ EC. Moreover, S1pr1 was validated as a downstream target protein of klf2. Upregulation of Klf2 expression ameliorated vascular ECs inflammation under HFD condition. Our study elucidates the Klf2 in Vcam1+ EC is a critical regulator of vascular inflammation and increases understanding of development and progression of aortic inflammatory disease.

2024-01-01 | GSE214014 | GEO

Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth

Project description:<p>The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer. </p>

2020-06-29 | MTBLS1764 | MetaboLights

Distinct phenotype and proteomic signature of peripheral blood-endothelial colony-forming cells of subjects with varied cardiovascular disease risks

Project description:Endothelial progenitor cells (EPCs) are circulating endothelial precursors shown to incorporate into foci of neovascularisation. Herein, we describe phenotypic characteristics of an EPC sub-type called endothelial colony-forming cells (ECFCs). Peripheral blood-isolated ECFCs expressed endothelial and progenitor surface antigens and displayed cobblestone-patterned colonies with clonal proliferative and angiogenic capacities in vitro. ECFCs demonstrated endothelial cell-like shear stress responses including cell alignment and PECAM-1 expression. Proteomic comparison with an endothelial reference population (human umbilical vein endothelial cells) confirmed a similar proteomic profile. Hierarchical clustering revealed two distinct ECFC clusters with differences in cell growth, proliferation and angiogenesis capacities. The cluster with compromised functionality was also associated with elevated blood pressure and impaired lipid profile. Our findings described an endothelial-like phenotype of blood-derived ECFCs with distinctive proteomic signatures based on cellular and clinical characteristics. ECFCs may aid in identifying novel mechanisms associated with cardiovascular disease risk and new targets to enhance angiogenesis.

2022-02-15 | PXD020677 | Pride

A single cell transcriptome atlas of murine endothelial cells

Project description:The heterogeneity of endothelial cells (ECs), lining blood vessels, across tissues remains incompletely inventoried. We constructed an atlas of >32,000 single-EC transcriptomic data from 11 tissues of the model organism Mus musculus. We propose a new classification of EC phenotypes based on transcriptome signatures and inferred putative biological features. We identified top-ranking markers for ECs from each tissue. ECs from different vascular beds (arteries, capillaries, veins, lymphatics) resembled each other across tissues, but only arterial, venous and lymphatic (not capillary) ECs shared markers, illustrating a greater heterogeneity of capillary ECs. We identified high-endothelial-venule and lacteal-like ECs in the intestines, and angiogenic ECs in healthy tissues. Metabolic transcriptomes of ECs differed amongst spleen, lung, liver, brain and testis, while being similar for kidney, heart, muscle and intestines. Within tissues, metabolic gene expression was heterogeneous amongst ECs from different vascular beds, altogether highlighting large EC heterogeneity.

2020-02-13 | E-MTAB-8077 | 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