心脏特异的转录因子在胚胎干细胞分化为心肌细胞中的作用

Effects of Cardiac Transcription Factors on the Differentiation of Embryonic Stem Cells into Cardiomyocytes

胚胎干细胞在没有白血病抑制因子(leukemia inhibitory factor,LIF)的条件下培养时可以分化成心肌细胞,这些细胞表达一些收缩蛋白,如肌浆球蛋白重链(myosin heavy chain,MHC)和肌球蛋白轻链-2V(ventricular myosin light chain,MLC2V)。很多研究者进一步从转录因子的角度研究了控制心脏发育的转录因子在胚胎干细胞向心肌细胞分化过程中的表达,结果表明心脏转录因子GATA4、肌细胞增强因子2C(myocyte-specific enhancer factor 2C,MEF2C)和NKx2.5控制着心脏相关基因的表达,它们在心脏发生进程中发挥重要的转录调控作用。研究同时发现多条信号通路参与了心肌细胞分化的调节。此外,纯化胚胎干细胞源性心肌细胞用于治疗心肌梗塞亦是一个关键问题。然而,胚胎细胞向心肌细胞分化的分子机理还有待进一步研究。

The experimental technique for obtaining murine embryonic stem （ES） cell-derived cardiomyocytes were established and the cells were eletrophysiologically studied at single cell level. When mouse ES cells were cultured in vitro in the absence of leukemia inhibitory factor （ LIF）, some of them differentiated into cardiomyocytes, which expressed characteristic contractile proteins, such as myosin heavy chain （MHC） and ventricular myosin light chain （MLC2v）. Furthermore, cardiac transcription factors GATA4, myocyte-specific enhancer factor 2C （MEF2C） and NKx2. 5 have been reported to control a cardiac gene program and thus play a crucial role in transcriptional regulation during cardiogenesis. Meanwhile, several signaling pathways are involved in the activation of MEF2C. In addition, the purity of differentiated ES-derived cardiomyocyte cultures is a key issue. However, the molecular mechanisms of cardiomyocyte differentiation from ES cells remain largely unexplored.