microRNAs在多能干细胞向心肌细胞分化中的作用

microRNAs Play Roles in Differentiation of Pluripotent Stem Cells into Myocardial Cells

microRNAs(miRNAs)是长约22 nt的非编码RNAs,广泛参与细胞的增殖、分化、病变、修复和凋亡等多种生命活动.多能干细胞(pluripotent stem cells)是指体外具有自我更新和多向分化潜能的细胞,在一定条件下可被定向诱导分化为多种细胞类型.miRNAs在多能干细胞中表达丰富,并通过调控基因表达影响其自我更新及分化.由多能干细胞向心肌细胞分化的方法主要有3种,即拟胚体形成法、与内胚层细胞共培养法和特定诱导物添加法.虽然这3种方法均可成功诱导多能干细胞向心肌细胞分化,但重复率很低.所以,人们把研究的视野逐渐转向miRNAs——这个广泛参与细胞生命活动的小分子物质.大量研究表明,在多能干细胞中,不同的miRNAs可通过打靶不同基因影响其向心肌细胞分化.在间充质干细胞中,miR-1、miR-133和miR-499可分别打靶Hes-1、SRF和Pdcd4;而在胚胎干细胞中,miR-1和miR-499分别打靶Hand2和Pacs2促进其向心肌细胞分化.miRNAs在多能干细胞向心肌分化作用机制的研究必将促进再生医学在心脏疾病治疗上的应用.

microRNAs （miRNAs） are long about 22 nt non-coding RNAs, involving in various life activities, such as proliferation, differentiation, pathological changes, repair, apoptosis, etc. Pluripotent stem cells are a class of self-renewal and differentiation potential ceils. More and more experimental results showed that these pluripotent stem cells could be directionally induced to multiple cell types. Mature miRNAs are expressed abundantly in pluripotent stem cells. They can control the self-renewal and differentiation of pluripotent ceils by regulating gene expression. Myocardial cells can be induced from pluripotent stem cells by three main methods. There are three methods to induce differentiation of myocardial cells in pluripotent stem ceils, which comprises： embryoid body formation, co-culturing with endoderm cell and specific inducer addition. Although these methods are feasible, the repetition rate is very low. People turn the perspective of the research field to miRNAs. A large study showed that different miRNAs could affect the differentiation of the pluripotent stem cell to cardiomyocytes by targeting different gene. miR-1, miR-133 and miR-499 can target Hes-1, SRF and Pdcd4 ,respectively in mesenchymal stem cells, while miR-1 and miR-499 can target Hand2 and Pacs2, resoectively in embryonic stem cells, both of which can make these cells differentiate into cardiomyocytes. The mechanism research on roles of miRNAs during pluripotent stem cell differentiation into myocardial cell will promote the application of regenerative medicine in the treatment of heart disease.