Differentiation of Human Cardiac Atrial Appendage Stem Cells into Adult Cardiomyocytes: A Role for the Wnt Pathway?
Human cardiac stem cells isolated from atrial appendages based on aldehyde dehydrogenase activity (CASCs) can be expanded in vitro and differentiate into mature cardiomyocytes. In this study, we assess whether Wnt activation stimulates human CASC proliferation, whereas Wnt inhibition induces cardiac maturation. CASCs were cultured as described before. Conventional PCR confirmed the presence of the Frizzled receptors. Small-molecule inhibitors (IWP2, C59, XAV939, and IWR1-endo) and activator (CHIR99021) of the Wnt/β -catenin signaling pathway were applied, and the effect on β-catenin and target genes for proliferation and differentiation was assessed by Western blot and RT-qPCR. CASCs express multiple early cardiac differentiation markers and are committed toward myocardial differentiation. They express several Frizzled receptors, suggesting a role for Wnt signaling in clonogenicity, proliferation, and differentiation. Wnt activation increases total and active β-catenin levels. However, this does not affect CASC proliferation or clonogenicity. Wnt inhibition upregulated early cardiac markers but could not induce mature myocardial differentiation. When CASCs are committed toward myocardial differentiation, the Wnt pathway is active and can be modulated. However, despite its role in cardiogenesis and myocardial differentiation of pluripotent stem-cell populations, our data indicate that Wnt signaling has limited effects on CASC clonogenicity, proliferation, and differentiation.
['Willems|Leen|L|', 'Daniëls|Annick|A|', 'Fanton|Yanick|Y|', 'Linsen|Loes|L|', 'Evens|Lize|L|', 'Bito|Virginie|V|', 'Declercq|Jeroen|J|', 'Rummens|Jean-Luc|JL|', 'Hensen|Karen|K|', 'Hendrikx|Marc|M|']
D000368:Aged D000369:Aged, 80 and over D000818:Animals D020517:Atrial Appendage D002454:Cell Differentiation D049109:Cell Proliferation D002470:Cell Survival D002478:Cells, Cultured D005260:Female D005786:Gene Expression Regulation D006321:Heart D006333:Heart Failure D006801:Humans D008297:Male D008875:Middle Aged D032383:Myocytes, Cardiac D013234:Stem Cells D013552:Swine D060449:Wnt Signaling Pathway
differentiation Wnt pathway proliferation cardiac progenitor cells cardiac regeneration