title: miR-1-mediated induction of cardiogenesis in mesenchymal stem cells via downregulation of Hes-1.
abstract: 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.
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital of Central South University, Hunan, Changsha 410011, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Zhen-fei
authors.initials: ZF
authors.lastname: Fang
authors.forename: Xin-qun
authors.initials: XQ
authors.lastname: Hu
authors.forename: Jia-yi
authors.initials: JY
authors.lastname: Pan
authors.forename: Sheng-hua
authors.initials: SH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D005786:Gene Expression Regulation; D006321:Heart / Q000254:growth & development / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D016086:Lentivirus / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010641:Phenotype; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C517731:Mirn1 microRNA, mouse