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Upregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cells

Research output: Contribution to journalArticle

X. Yu, L. Zhang, G. Wen, H. Zhao, L. A. Luong, Q. Chen, Y. Huang, J. Zhu, S. Ye, Q. Xu, W. Wang, Q. Xiao

Original languageEnglish
Pages (from-to)1170-1180
Number of pages11
Issue number7
Publication statusPublished - 1 Jul 2015

King's Authors


microRNA-34a (miR-34a) and sirtuin 1 (SirT1) have been extensively studied in tumour biology and longevityaging, but little is known about their functional roles in smooth muscle cell (SMC) differentiation from pluripotent stem cells. Using well-established SMC differentiation models, we have demonstrated that miR-34a has an important role in SMC differentiation from murine and human embryonic stem cells. Surprisingly, deacetylase sirtuin 1 (SirT1), one of the top predicted targets, was positively regulated by miR-34a during SMC differentiation. Mechanistically, we demonstrated that miR-34a promoted differentiating stem cells' arrest at G0G1 phase and observed a significantly decreased incorporation of miR-34a and SirT1 RNA into Ago2-RISC complex upon SMC differentiation. Importantly, we have identified SirT1 as a transcriptional activator in the regulation of SMC gene programme. Finally, our data showed that SirT1 modulated the enrichment of H3K9 tri-methylation around the SMC gene-promoter regions. Taken together, our data reveal a specific regulatory pathway that miR-34a positively regulates its target gene SirT1 in a cellular context-dependent and sequence-specific manner and suggest a functional role for this pathway in SMC differentiation from stem cells in vitro and in vivo.

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