ArticleStem cells and development2023
Notch Pathways Regulate Expression of Angiostatic Factor Activin A in Endothelial-Pericyte-Like Mesenchymal Stromal Cell Interactions.
Article in Stem cells and development, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- EZH2 directs HER2+ breast cancer progression through the modulation of epithelial plasticity.EMBO reports · 2026Article
- Role of vascular smooth muscle phenotypic transformation induced by histone modifications in the development of abdominal aortic aneurysms.Clinical epigenetics · 2025Review
- The stem cell within the vessel wall: multipotent pericytes modulating β-cell function and diabetic complications.Stem cell research & therapy · 2025Review
- Activin A Prevents Hyperresponsiveness to Vascular Endothelial Growth Factor in Pathologic Blood Vessels by Perturbing the Trafficking of Activated Vascular Endothelial Growth Factor Receptor 2.The American journal of pathology · 2025Article
- S-Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte-Like Cells by Inhibiting Notch Signalling Pathway.Journal of cellular and molecular medicine · 2024Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Vascularization of ischemic and fabricated tissues is essential for successful tissue repair and replacement therapies. Endothelial cells (ECs) and mesenchymal stem/stromal cells (MSCs) in close proximity spontaneously organize into vessels after coimplantation in semisolid matrices. Thus, local injection of EC mixed with MSC may facilitate tissue (re)vascularization. The organization of these cells into vessels is accompanied by induction of a key regulator of vasculogenesis, activin A, in MSC through juxtacrine pathway. Mechanisms regulating activin A expression are poorly understood; therefore, the contributions of notch signaling pathways were evaluated in EC-adipose mesenchymal stromal cells (ASC) cocultures. Disruption of notch signaling in EC + ASC cocultures with a γ-secretase inhibitor, DAPT, completely abrogated both activin A induction and production, depending on the stage of vasculogenesis. While DAPT stimulated EC proliferation concurrent with increased secretion of vasculogenic factors, it also prevented the crucial transition of ASC from progenitor to smooth muscle cell phenotype, collectively resulting in ineffective tubulogenesis. Silencing Notch2 in ASC abolished activin A production in cocultures, but resulted in normal ASC maturation. In contrast, silencing Notch3 in ASC led to autonomous upregulation of mural cell markers, and intercellular contact with EC further enhanced upregulation of these markers, concurrent with amplified activin A secretion. Strong induction of activin A expression was achieved by exposing ASC to immobilized notch ligand jagged1, whereas jagged1 IgG, added to EC + ASC incubation media, prevented activin A expression. Overall, this study revealed that EC control activin A expression in ASC through
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