miR-1-mediated induction of cardiogenesis in mesenchymal stem cells via downregulation of Hes-1.
miR-1-mediated induction of cardiogenesis in mesenchymal stem cells via downregulation of Hes-1.
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DOI：
10.1155/2013/216286
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发表时间：
2013
影响因子：
--
通讯作者：
Zhou SH
中科院分区：
文献类型：
--
作者：
Huang F;Tang L;Fang ZF;Hu XQ;Pan JY;Zhou SH
microRNAs（miRNAs，miRs）具有控制干细胞命运决定的潜力。心肌和平滑肌特异性miRNA miR-1可通过抑制替代谱系的基因表达来调控胚胎干细胞向心肌谱系的分化。因此，我们假设miR-1的过表达也可能促进间充质干细胞中心脏基因的表达。由于Notch信号可以抑制肌肉分化，这一过程与miR-1的作用相反，miR-1介导的Notch信号抑制可能有助于观察到的miR-1在间充质干细胞中的作用。因此，用携带miR-1的慢病毒载体感染间充质干细胞，并选择表达miR-1的细胞。在第1、7和14天，通过蛋白质印迹法在感染的细胞中鉴定Notch信号传导和心肌细胞标志物Nkx 2.5、加塔-4、cTnT和CX 43的改变。我们的研究表明，在miR-1修饰的间充质干细胞中，Notch通路下游靶分子Hes-1的表达明显降低，miR-1的过表达促进了感染细胞中特异性心脏基因的表达。Hes-1的敲低导致对细胞谱系决定的相同影响。我们的研究结果表明，miR-1促进MSCs向心脏谱系分化的部分原因是Hes-1的负调控。
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.
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影响因子：
9.8
作者：
Lowell, Sally;Benchoua, Alexandra;Heavey, Barry;Smith, Austin G
通讯作者：
Smith, Austin G
影响因子：
5.2
作者：
Kern, Susanne;Eichler, Hermann;Bieback, Karen
通讯作者：
Bieback, Karen
影响因子：
64.8
作者：
Hatfield, SD;Shcherbata, HR;Ruohola-Baker, H
通讯作者：
Ruohola-Baker, H
DOI：
10.1073/pnas.0509535102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Kwon, C;Han, Z;Srivastava, D
通讯作者：
Srivastava, D
DOI：
10.1073/pnas.0808357105
发表时间：
2008-10-07
影响因子：
11.1
作者：
Boni, Alessandro;Urbanek, Konrad;Leri, Annarosa
通讯作者：
Leri, Annarosa