title: MicroRNA-199a induces differentiation of induced pluripotent stem cells into endothelial cells by targeting sirtuin 1.
abstract: The ability to reprogram induced pluripotent stem (iPS) cells from somatic cells may facilitate significant advances in regenerative medicine. MicroRNAs (miRNAs) are involved in a number of core biological processes, including cardiogenesis, hematopoietic lineage differentiation and oncogenesis. An improved understanding of the complex molecular signals that are required for the differentiation of iPS cells into endothelial cells (ECs) may allow specific targeting of their activity in order to enhance cell differentiation and promote tissue regeneration. The present study reports that miR‑199a is involved in EC differentiation from iPS cells. Augmented expression of miR‑199a was detected during EC differentiation, and reached higher levels during the later stages of this process. Furthermore, miR‑199a inhibited the differentiation of iPS cells into smooth muscle cells. Notably, sirtuin 1 was identified as a target of miR‑199a . Finally, the ability of miR‑199a to induce angiogenesis was evaluated in vitro, using Matrigel plugs assays. This may indicate a novel function for miR‑199a as a regulator of the phenotypic switch during vascular cell differentiation. The present study provides support to the notion that with an understanding of the molecular mechanisms underlying vascular cell differentiation, stem cell regenerative therapy may ultimately be developed as an effective treatment for cardiovascular disease.
authors.affiliation: Department of Cardiothoracic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Zhoubin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT12 6BA, UK.
authors.forename: Andriana
authors.initials: A
authors.lastname: Margariti
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Cardiothoracic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D018919:Neovascularization, Physiologic; D056564:Sirtuin 1 / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C534780:Mirn199 microRNA, mouse; D056564:Sirtuin 1