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dc.contributor.authorYu, Xen_US
dc.contributor.authorZhang, Len_US
dc.contributor.authorWen, Gen_US
dc.contributor.authorZhao, Hen_US
dc.contributor.authorLuong, LAen_US
dc.contributor.authorChen, Qen_US
dc.contributor.authorHuang, Yen_US
dc.contributor.authorZhu, Jen_US
dc.contributor.authorYe, Sen_US
dc.contributor.authorXu, Qen_US
dc.contributor.authorWang, Wen_US
dc.contributor.authorXiao, Qen_US
dc.date.accessioned2016-02-03T16:39:05Z
dc.date.issued2015-07-01en_US
dc.identifier.issn1350-9047en_US
dc.identifier.other10.1038/cdd.2014.206
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/11031
dc.description.abstract© 2015 Macmillan Publishers Limited. All rights reserved. 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.en_US
dc.format.extent1170 - 1180en_US
dc.relation.ispartofCell Death and Differentiationen_US
dc.titleUpregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cellsen_US
dc.typeArticle
dc.rights.holder© 2016 ADMC Associazione Differenziamento e Morte Cellulare
dc.identifier.doi10.1038/cdd.2014.206en_US
pubs.issue7en_US
pubs.notesNo embargoen_US
pubs.notesSix months embargo has been passeden_US
pubs.publication-statusPublisheden_US
pubs.volume22en_US


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