Cells derived from the epicardium are required for coronary vessel development. Transforming growth factor beta (TGFbeta) induces loss of epithelial character and smooth muscle differentiation in chick epicardial cells. Here, we show that epicardial explants from embryonic day (E) 11.5 mouse embryos incubated with TGFbeta1 or TGFbeta2 lose epithelial character and undergo smooth muscle differentiation. To further study TGFbeta Signaling, we generated immortalized mouse epicardial cells. Cells from E10.5, 11.5, and 13.5 formed tightly packed epithelium and expressed the epicardial marker Wilm's tumor 1 (WT1). TGFbeta induced the loss of zonula occludens-1 (ZO-1) and the appearance of SM22alpha and calponin consistent with smooth muscle differentiation. Inhibition of activin receptor-like kinase (ALK) 5 or p160 rho kinase activity prevented the effects of TGFbeta while inhibition of p38 mitogen activated protein (MAP) kinase did not. These data demonstrate that TGFbeta induces epicardial cell differentiation and that immortalized epicardial cells provide a suitable model for differentiation.
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http://dx.doi.org/10.1002/dvdy.21421 | DOI Listing |
Cell Biosci
January 2025
Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, China.
Epicardium, the most outer mesothelium, exerts crucial functions in fetal heart development and adult heart regeneration. Here we use a three-step manipulation of WNT signalling entwined with BMP and RA signalling for generating a self-organized epicardial organoid that highly express with epicardium makers WT1 and TCF21 from human embryonic stem cells. After 8-days treatment of TGF-beta following by bFGF, cells enter into epithelium-mesenchymal transition and give rise to smooth muscle cells.
View Article and Find Full Text PDFCells
December 2024
Université Côte d'Azur, CNRS, INSERM, iBV, 06107 Nice, France.
The Wilms' tumor suppressor WT1 is essential for the development of the heart, among other organs such as the kidneys and gonads. The Wt1 gene encodes a zinc finger transcription factor that regulates proliferation, cellular differentiation processes, and apoptosis. WT1 is also involved in cardiac homeostasis and repair.
View Article and Find Full Text PDFBull Exp Biol Med
December 2024
Cardiology Research Institute, Tomsk National Research Medical Center, Russian academy of Sciences, Tomsk, Russia.
FoxP3 T-regulatory (Treg) lymphocytes and cytokine production by cells from the stromal vascular fraction (SVF) of epicardial (EAT) and thymus (TAT) adipose tissue of 42 patients with chronic coronary heart disease (CHD) were studied. In the SVF of TAT in patients with Gensini Score (GS)≥74 (the most severe atherosclerosis), the production of IL-1β, TNF, IL-4, and IFNγ was higher, while FoxP3 translocation into the nucleus was lower than in patients with GS<74. The GS index directly correlated with the production of IL-4, IL-1β, and TNF by cells of the SVF of TAT, and inversely - with the production of TNF, IL-17, and IL-10 by cells of the SVF of EAT.
View Article and Find Full Text PDFTheranostics
January 2025
Department of Molecular Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Cardiac fibroblasts are activated following myocardial infarction (MI) and cardiac fibrosis is a major driver of the growing burden of heart failure. A non-invasive targeting method for activated cardiac fibroblasts would be advantageous because of their importance for imaging and therapy. Targeting was achieved by linking a 7-amino acid peptide (EP9) to a perfluorocarbon-containing nanoemulsion (PFC-NE) for visualization by F-combined with H-MRI.
View Article and Find Full Text PDFStem Cell Res
February 2025
Cardiology Section, Medical Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Radiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
Coronary artery vasospasm (CAV) is characterized by transient constriction of epicardial coronary arteries leading to angina. Its disease mechanisms are multifactorial but has centered mostly on endothelial dysfunction and smooth muscle hyperreactivity. To facilitate the investigation of these mechanisms in cell culture, we generated and characterized three induced pluripotent stem cell (iPSC) lines from patients with CAV.
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