MicroRNA-29a promotes smooth muscle cell differentiation from stem cells by targeting YY1

•miR-29a promotes VSMC differentiation from stem cells.•miR-29a suppresses YY1, a negative regulator of VSMC differentiation from stem cells.•YY1 suppression may have implications in the treatment of cardiovascular disease.

MicroRNA-29a (miR-29a) has been extensively studied in tumor biology and fibrotic diseases, but little is known about its functional roles in vascular smooth muscle cell (VSMC) differentiation from embryonic stem cells (ESCs). Using well-established VSMC differentiation models, we have observed that miR-29a induces VSMC differentiation from mouse ESCs by negatively regulating YY1, a transcription factor that inhibits muscle cell differentiation and muscle-specific gene expression. Moreover, gene expression levels of three VSMC specific transcriptional factors were up-regulated by miR-29a over-expression, but down-regulated by miR-29a inhibition or YY1 over-expression. Taken together, our data demonstrate that miR-29a and its target gene, YY1, play a regulatory role in VSMC differentiation from ESCs in vitro and in vivo.