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Multiomic profiling of in vitro models of endothelial-to-mesenchymal transition reveals endothelial cell subtype is a major determinant of fidelity to observed states in atherosclerosis

ABSTRACT: Endothelial-to-mesenchymal transition (EndMT) is an example of endothelial cell (EC) heterogeneity which is commonly modeled in vitro to better understand driving mechanisms of disease proceses, including atherosclerosis. We used multi-modal single nucleus RNA sequencing (snRNA-seq) and ATAC sequencing (snATAC-seq) to analyze the diversity of ECs in vitro, divergent EC responses to known EndMT perturbations, and the ability of in vitro EC known EndMT models to recapitulate the in vivo 'omic profiles of cells observed in atherosclerosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228428 | GEO | 2023/05/03

REPOSITORIES: GEO

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Long non-coding RNA MIR503HG controls endothelial-to-mesenchymal transition

Project description:Endothelial-to-mesenchymal transition (EndMT) is a dynamic transformation process that has a functional impact upon pathological vascular remodelling. The molecular mechanisms that govern EndMT remain largely unknown. By induction of EndMT in human primary endothelial cells (EC), using a combination of transforming growth factor-β2 (TGF-b2) and interleukin-1b (IL-1β), we identified the dramatic loss of the lncRNA MIR503HG, as a common signature across multiple primary EC types. Targeted depletion of MIR503HG spontaneously induced EndMT. Overexpression of MIR503HG repressed EndMT despite TGF-β2 and IL-1β co-stimulation. RNA-seq was carried out to identify the changes in gene expression induced by MIR503HG overexpression. We showed that over 25% of the EndMT-transcriptome signature was inhibited upon MIR503HG overexpression. Crucially, phenotypic changes induced by MIR503HG were independent of the functional regulation of miR-503 and miR-424, both harbored within the MIR503HG locus. Collectively, we identify the lncRNA MIR503HG as an essential regulator of EndMT.

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ARPCs Can Revert Lps-Induced Endothelial-to-Mesenchymal Transition of Endothelial Cells

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Multiomic profiling of in vitro models of endothelial-to-mesenchymal transition reveals endothelial cell subtype is a major determinant of fidelity to observed states in atherosclerosis

Project description:Multiomic profiling of in vitro models of endothelial-to-mesenchymal transition reveals endothelial cell subtype is a major determinant of fidelity to observed states in atherosclerosis

| PRJNA949674 | ENA

Endothelial Cells from different anatomical origin have distinct responses during Snail/TGF-β2-mediated Endothelial-Mesenchymal Transition

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