Endoglin is a Novel Endothelial Cell Specification Gene
Overview
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Endothelial cells (EC) are important in vasculogenesis and organogenesis during development and in the pathogenesis of cancer and cardiovascular diseases. However, few EC specification factors are known and primary EC production remains inefficient. Based on recent studies implicating endoglin (Eng) in early vascular development and angiogenesis, we hypothesized that Eng may be an EC specification gene. Mouse embryonic stem cells (ESC) were treated with recombinant Eng or a plasmid expressing the Eng ORF, and differentiated in the presence or absence of bone morphogenic protein 4 (BMP4). Expression of the mesoderm and EC marker genes, the known mediators of EC specification and their downstream targets was monitored by quantitative PCR, western blot, immunocytochemistry, and flow cytometry. Functionality of the differentiated EC was assessed by in vitro angiogenesis assay and the induction of Icam1 expression in response to TNF-α treatment. Both recombinant Eng and forced Eng expression increased the number of functional EC expressing the EC marker genes VE-cadherin, vWF, and Tie2, and enhanced the effect of BMP4. The Eng-induced EC differentiation was independent of known mediators of EC specification such as Indian Hedgehog (IHH) and BMP4 or of BMP4/Smad1/5/8 signaling. These studies suggest that Eng is a novel EC specification gene.
Derivation and Characterization of Endothelial Cells from Porcine Induced Pluripotent Stem Cells.
Yu Y, Li X, Li Y, Wei R, Li H, Liu Z Int J Mol Sci. 2022; 23(13).
PMID: 35806048 PMC: 9266935. DOI: 10.3390/ijms23137029.
Mitroi D, Tian M, Kawaguchi R, Lowry W, Carmichael S J Cell Mol Med. 2022; 26(11):3183-3195.
PMID: 35543222 PMC: 9170821. DOI: 10.1111/jcmm.17315.
Cho J, Kim S, Lee H, Rah W, Cho H, Kim N Nat Biomed Eng. 2021; 5(8):880-896.
PMID: 34426676 PMC: 8809198. DOI: 10.1038/s41551-021-00783-0.
Understanding the Adult Mammalian Heart at Single-Cell RNA-Seq Resolution.
Marin-Sedeno E, Martinez de Morentin X, Perez-Pomares J, Gomez-Cabrero D, Ruiz-Villalba A Front Cell Dev Biol. 2021; 9:645276.
PMID: 34055776 PMC: 8149764. DOI: 10.3389/fcell.2021.645276.
Zhou F, Zhao X, Liu X, Liu Y, Ma F, Liu B Pulm Circ. 2020; 10(4):2045894019885357.
PMID: 33282178 PMC: 7691931. DOI: 10.1177/2045894019885357.