Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions

ABSTRACT: CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions

PROVIDER: PRJNA698579 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions [RNA-seq]

Project description:CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions [RNA-seq]

| PRJNA698583 | ENA

CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions [pooled CRISPR screen]

Project description:CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions [pooled CRISPR screen]

| PRJNA698581 | ENA

CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions [RNA-seq]

Project description:Genome-wide association studies have identified 161 genetic variants associated with coronary artery disease (CAD), but the causal genes and biological pathways remain unknown at most loci. This knowledge is critical to optimize precision medicine strategies and develop new drugs for CAD. Here, we performed multiple pooled CRISPR screens to test the impact of CAD-associated genetic variants on vascular endothelial cell functions. Using CRISPR knockout, inhibition and activation, we targeted 1998 variants at 83 CAD loci to assess their effect by flow cytometry on three adhesion proteins (E-selectin, ICAM1, VCAM1) and three key endothelial functions (nitric oxide and reactive oxygen species production, calcium signaling). At a false discovery rate ≤10%, we identified 42 significant variants located within 26 CAD loci. Although a few of these loci include genes previously characterized in endothelial cells (e.g. MIA3/AIDA, FURIN, ARHGEF26, ADAMTS7), most are implicated in endothelial dysfunction for the first time. Detailed cellular and molecular characterization of the RNA helicase DHX38, as well as CRISPR-mediated over-expression experiments at the FURIN/FES, CCDC92/ZNF664 and CNNM2 loci, revealed a strong effect on vascular endothelial cell senescence. Our findings implicate many CAD-associated loci in the regulation of atherosclerosis-related endothelial functions and offer new insights into how modulating these functions could help prevent or treat CAD.

2021-02-11 | GSE165924 | GEO

CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions [pooled CRISPR screen]

2021-02-11 | GSE165923 | GEO

CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-02-10 | GSE165925 | GEO

Multi-ancestry genetic analysis of gene regulation in coronary artery prioritizes disease risk loci

Project description:Genome-wide association studies (GWAS) have identified hundreds of genetic risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in coronary artery disease (CAD). However, non-European populations are underrepresented in GWAS and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotype information to identify quantitative trait loci (QTL) for gene expression and splicing in coronary arteries obtained from 138 ancestrally diverse Americans.

2023-11-14 | GSE225650 | GEO

Quantitative trait loci mapped for TCF21 binding, chromatin accessibility and chromosomal looping in coronary artery smooth muscle cells reveal molecular mechanisms of coronary disease loci

Project description:To better understand the fundamental molecular mechanisms that contribute to complex human diseases such as coronary artery disease (CAD), we have created a catalog of genetic variants associated with three stages of transcriptional cis-regulation in primary human coronary artery vascular smooth muscle cells. To this end, we used a pooling approach to map quantitative trait locus associations (QTLs) for TCF21 binding (ChIPseq), chromatin accessibility (ATACseq), and chromosomal looping (HiC). We find significant overlap of these QTLs, and several analyses indicate their relationship to smooth muscle specific genes, the binding of smooth muscle transcription factors, and enrichment in CAD-associated loci. These QTLs are extensively validated and allele-specific chromatin looping at the FN1 disease locus is shown to be mediated by activation of the CAD-associated TGFb1 pathway. In sum, these results uncover thousands of loci affecting cis-regulation in a key cell type for CAD, including many that may contribute to CAD risk.

2020-05-07 | GSE141752 | GEO

Quantitative trait loci mapped for TCF21 binding, chromatin accessibility and chromosomal looping in coronary artery smooth muscle cells reveal molecular mechanisms of coronary disease loci [array]

2020-05-12 | GSE150403 | GEO

Quantitative trait loci mapped for TCF21 binding, chromatin accessibility and chromosomal looping in coronary artery smooth muscle cells reveal molecular mechanisms of coronary disease loci (ChIP-Seq)

2020-05-07 | GSE141751 | GEO

Quantitative trait loci mapped for TCF21 binding, chromatin accessibility and chromosomal looping in coronary artery smooth muscle cells reveal molecular mechanisms of coronary disease loci (Hi-C)

2020-05-07 | GSE141749 | GEO