Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome analysis of human embryonic stem cell differentiation to endothelial cells

ABSTRACT: Deep RNA sequencing was performed during human embryonic stem cell (hESC) differentiation to endothelial cells (ECs), via mesodermal precursors. Our work focused on long non-coding RNAs (lncRNAs) regulated during EC differentiation as lncRNA are known regulators of cell differentiation, physiology and disease. EC-enriched lncRNAs were screened for binding sites for the transcription factor ERG, important for endothelial cell identity and function. The LINC00961 gene, first annotated as a lncRNA but now reassigned as a protein coding gene for the SPAAR micropeptide, was potently activated during differentiation. Using primary ECs, we studied the role of LINC00961 locus after depletion and gain of function experiments and showed its effect on EC adhesion, tube formation, migration and proliferation. We showed that LINC00961 functions as a bona fide non-coding RNA in ECs, at least in part, through binding to TMSB4X.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118106 | GEO | 2020/03/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNAAngiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA

Project description:Endothelial cell (EC)-enriched protein coding genes, such as endothelial nitric oxide synthase (eNOS), define quintessential EC-specific physiologic functions. It is not clear whether long noncoding RNAs (lncRNAs) also define cardiovascular cell-type specific phenotypes, especially in the vascular endothelium. Here, we report the existence of a set of EC-enriched lncRNAs and define a role for STEEL (spliced transcript – endothelial enriched lncRNA) in angiogenic potential, macrovascular/microvascular identity and shear stress responsiveness. STEEL is expressed from the terminus of the HOXD locus and is transcribed antisense to HOXD transcription factors. STEEL RNA increases the number and integrity of de novo perfused microvessels in an in vivo model and augments angiogenesis in vitro. The STEEL RNA is polyadenylated, nuclear-enriched and has microvascular predominance. Functionally, STEEL regulates a number of genes in diverse endothelial cells. Of interest, STEEL upregulates both eNOS and the transcription factor Kruppel-like factor 2 (KLF2), and is subject to feedback inhibition by both eNOS and shear-augmented KLF2. Mechanistically, STEEL upregulation of eNOS and KLF2 is transcriptionally mediated, in part, via interaction of chromatin-associated STEEL with the poly-ADP ribosylase, PARP1. For instance, STEEL recruits PARP1 to the KLF2 promoter. This work identifies a role for EC-enriched lncRNAs in the phenotypic adaptation of ECs to both body position and hemodynamic forces, and establishes a newer role for lncRNAs in the transcriptional regulation of EC identity.

2018-02-28 | PXD008581 | Pride

RAMP2-AS1 Regulates Endothelial Homeostasis and Aging

Project description:The homeostasis of vascular endothelium is crucial for cardiovascular health and endothelial cell (EC) aging and dysfunction could negatively impact vascular function. Leveraging time-series transcriptomic data obtained from endothelial cells (ECs) subjected to physiological pulsatile flow versus pathophysiological oscillatory flow, we performed principal component analysis (PCA) to identify key genes contributing to divergent transcriptional states of ECs under distinct flow patterns. Through bioinformatics analysis, we identified that a long non-coding RNA (lncRNA) RAMP2- AS1 encoded on the antisense of RAMP2, a determinant of endothelial homeostasis and vascular integrity, is a novel regulator essential for EC homeostasis and function. Knockdown of RAMP2-AS1 inhibited EC angiogenesis and promoted EC senescence, as a result of extensive changes of EC transcriptome. Our study demonstrates an integrative approach to quantifying EC aging based on transcriptome changes, which also identified a number of novel regulators, including protein-coding genes and many lncRNAs involved EC functional modulation.

2021-04-20 | GSE163433 | GEO

Comparative study of mRNAs and lncRNAs in endothelial and non-endothelial cells

Project description:To identify lncRNAs enriched in ECs, a microarray was performed to profile ~30,000 lncRNAs and ~26,000 coding transcripts using an Arraystar human LncRNA microarray v3.0 system (Arraystar, Rockville, MD). Three primary human EC lines and two non-EC lines at low passages, namely, human umbilical vein EC (HUVEC), human retinal EC (HREC), human choroidal EC, human dermal fibroblast cell (HDF) and human retinal pigment epithelial (RPE) cell lines, were used in the array. Purity of EC lines was confirmed by acetyl-LDL uptake and EC marker staining

2018-10-08 | GSE105107 | 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

Long non-coding RNA profiling in 6 cell types

Project description:To identify endothelial cell (EC)-enriched long noncoding RNAs (lncRNAs), gene expression analysis was conducted on two EC cell types and 4 non-EC cell types. Specifically, the EC cell types were human umbilical vein endothelial cells (HUVEC) and human dermal microvascular endothelial cells (HMVEC). The 4 non-EC cell types were human aortic smooth muscle cells (HASMC), Fibroblasts, Hepatocytes, and keratinocytes. Of the 23 155 putative lncRNAs represented in the custom lncRNA microarrays, 18 524 lncRNAs were found to be expressed above the 20% percentile in at least one cell type. Importantly, 28 EC-enriched lncRNAs were identified in common between HUVEC and HMVEC with 28 and 59 enriched uniquely in either HUVEC or HMVEC, respectively. Of interest, STEEL, an EC-enriched lncRNA was identified and its role in EC biology was further characterized.

2018-03-30 | GSE108318 | GEO

Translation and Natural Selection of long non-canonical RNA micropeptides

Project description:Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but lacking canonical coding sequences. Apparently unable to produce peptides, lncRNA function seems to only involve RNA sequence and structure. Here, we exhaustively detect in-vivo translation of small open reading frames (small ORFs) within lncRNAs using Ribosomal profiling during Drosophila melanogaster embryogenesis. We show that around 30% of lncRNAs contain small ORFs engaged by ribosomes, leading to regulated translation of 100 to 300 micropeptides. We identify lncRNA features that favour translation, such as cistronicity, Kozak sequences, and conservation. For this latter, we develop a bioinformatics pipeline to detect small ORF homologues, and we reveal evidence of natural selection favouring the conservation of micropeptide sequence and function across evolution. Our results expand the repertoire of lncRNA functions, and suggest that lncRNAs give rise to novel coding genes throughout evolution. Since most lncRNAs contain small ORFs with as yet unknown translation potential, we propose to rename them “long non-canonical RNAs”.

2022-11-02 | GSE204739 | GEO

Comparison of human embroynic stem cell derived vascular cells to mature human vascular and hematopoietic cells

Project description:The pathways involved in hierarchical differentiation of human embryonic stem cells (hESC) into abundant and durable endothelial cells (EC) are unknown. We employed an EC-specific VE-cadherin promoter driving GFP (hVPr-GFP) to screen for factors that augmented yields of vascular-committed ECs from hESCs. In phase 1 of our approach, inhibition of TGFb, precisely at day 7 of hESC differentiation, enhanced emergence of hVPr-GFP+ ECs by 10-fold. In the second phase, TGFb-inhibition preserved proliferation and vascular identity of purified ECs, resulting in net 36-fold expansion of homogenous EC-monolayers, and allowing transcriptional profiling that revealed a unique angiogenic signature defined by the VEGFR2highId1highVE-cadherin+EphrinB2+CD133+HoxA9- phenotype. Using an Id1-YFP hESC reporter line, we showed that TGFb-inhibition sustained Id1 expression in hESC-derived ECs, which was required for increased proliferation and preservation of EC commitment. These data provide a multiphasic method for serum-free differentiation and long-term maintenance of authentic hESC-derived ECs, establishing clinical-scale generation of transplantable human ECs. The experiment compared 6 sets of biological duplicates which included human embryonic stem cell derived and mature vascular cell types.

2010-01-05 | E-GEOD-19735 | biostudies-arrayexpress

MiRNA expression profile in the aortas of Apoe-/- mice with an specific knock-out of Dicer in endothelial cells compared to control mice after 4 weeks of a high-fat diet

Project description:Increased monocyte adhesion to dysfunctional endothelial cells (ECs) orchestrated by chemokines plays an important role in arterial inflammation during atherosclerosis. Endothelial microRNAs (miRNAs) processed by the RNase Dicer1 determine the phenotype of ECs by posttranscriptional regulation of gene expression. However, the impact of endothelial miRNAs on endothelial inflammation and atherosclerosis is currently unclear. To study the effect of Dicer-dependent miRNAs in ECs during the development of atherosclerosis, Apoe-/- mice with an inducible, EC-specific knock-out of Dicer (EC-Dicerflox) and control mice (EC-DicerWT) mice were treated with tamoxifen to induce Cre-recombinase activity and fed with a high fat-diet (HFD) for 4 weeks. The comparison of the miRNA expression profile in the aortas of EC-Dicerflox and EC-DicerWT mice after 4 weeks of a HFD was performed to identify EC-specific miRNAs that may play a role in the EC function during atherogenesis.

2015-05-31 | GSE53435 | GEO

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

MiRNA profiling in aortas of Apoe-/- mice with an specific knock-out of Dicer in endothelial cells compared to control mice after 12 weeks of a high-fat diet

Project description:Increased monocyte adhesion to dysfunctional endothelial cells (ECs) orchestrated by chemokines plays an important role in arterial inflammation during atherosclerosis. Endothelial microRNAs (miRNAs) processed by the RNase Dicer1 determine the phenotype of ECs by posttranscriptional regulation of gene expression. However, the impact of endothelial miRNAs on endothelial inflammation and atherosclerosis is currently unclear. To study the effect of Dicer-dependent miRNAs in ECs on atherosclerosis, Apoe-/- mice with an inducible, EC-specific knock-out of Dicer (EC-Dicerflox) and control mice (EC-DicerWT) mice were treated with tamoxifen to induce Cre-recombinase activity and fed with a high fat-diet (HFD) for 12 weeks. The comparison of the miRNA expression profile in the aortas of EC-Dicerflox and EC-DicerWT mice after 12 weeks of a HFD was performed to identify EC-specific miRNAs that may play a role in the EC function during atherogenesis.

2015-05-31 | GSE53433 | GEO

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