Notch1 Signaling Enhances the Differentiation of Mesenchymal Stem Cells to Cardiomyogenic Cells

Notch signaling is a pathway commonly involved in various cells developmental process. However, the precise molecular mechanisms that Notch signaling pathway to control MSCs cardiogenic differentiation are not well known. We investigated the role of Notch for cardiac differentiation in a coculture system with neonatal cardiomyocytes, by adding the ligand and inhibitor of Notch. After coculture, the differentiation of MSCs into cardiomyocytes was quantified as the cardiac marker protein and spontaneous beating activity. The activation and inhibition of Notch and the expression of related Wnt signaling pathway were determined by immunofluorescence, RT-PCR and Western-blot. Differentiation of MSCs into cardiomyocytes was favored by the activation of Notch, although this effect could be inhibited by administration of gamma-secretase inhibitor DAPT. The up-regulation of Jagged1 protein only enhanced the percentage of cardiomyocytes for beating activity derived from MSCs, without the change of spontaneous beating rate. The target genes of Notch signaling pathway and noncanonical Wnt5a protein were un-regulated by the activation of Notch. These findings support that Notch signaling pathway operated in MSCs differentiation into cardiomyocytes. The Jagged1-dependent Notch activation enhances the production of mesenchymal stem cell-derived cardiomyocytes.