title: Endoglin is a novel endothelial cell specification gene.
abstract: 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.
authors.affiliation: Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Saswati
authors.initials: S
authors.lastname: Banerjee
authors.forename: Sujoy K
authors.initials: SK
authors.lastname: Dhara
authors.forename: Methode
authors.initials: M
authors.lastname: Bacanamwo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism / Q000494:pharmacology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000071063:Endoglin; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005326:Fetal Proteins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051785:Smad Proteins / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D000098908:Brachyury Protein
chemical_list: D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D000071063:Endoglin; D005326:Fetal Proteins; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D051785:Smad Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C502004:Eng protein, mouse; C514061:ihh protein, mouse
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