miR-1-Mediated Induction of Cardiogenesis in Mesenchymal Stem Cells via Downregulation of Hes-1

• Main Authors: Feng Huang, Liang Tang, Zhen-fei Fang, Xin-qun Hu, Jia-yi Pan, Sheng-hua Zhou
• Format: Article
• Language: English
• Published: Hindawi Limited 2013-01-01
• Series: BioMed Research International
• Online Access: http://dx.doi.org/10.1155/2013/216286
• ISSN: 2314-6133; 2314-6141

MicroRNAs (miRNAs, miRs) have the potential to control stem cells fate decisions. The cardiac- and skeletal-muscle-specific miRNA, miR-1, can regulate embryonic stem cells differentiation to cardiac lineage by suppressing gene expression of alternative lineages. Accordingly, we hypothesized that overexpression of miR-1 may also promote cardiac gene expression in mesenchymal stem cells. Since Notch signaling could inhibit muscle differentiation, a process in contrast with the effect of miR-1, miR-1-mediated repression of Notch signaling may contribute to the observed effects of miR-1 in mesenchymal stem cells. Thus, mesenchymal stem cells were infected by lentiviral vectors carrying miR-1, and cells expressing miR-1 were selected. Alterations in Notch signaling and cardiomyocyte markers, Nkx2.5, GATA-4, cTnT, and CX43, were identified by Western blot in the infected cells on days 1, 7, and 14. Our study showed that the downstream target molecule of Notch pathway, Hes-1, was obviously decreased in mesenchymal stem cells modified with miR-1, and overexpression of miR-1 promotes the specific cardiac gene expression in the infected cells. Knockdown of Hes-1 leads to the same effects on cell lineage decisions. Our results indicated that miR-1 promotes the differentiation of MSCs into cardiac lineage in part due to negative regulation of Hes-1.