医学院课题信息表-同济大学医学院.docVIP

彭鲁英课题组 课题组研究方向 干细胞定向心肌细胞分化的表观遗传调控及基因修饰大鼠心脏疾病模型的研究 课题组简介 胚胎干细胞是建立转基因或基因敲出小鼠或大鼠的独特遗传操作系统。通过体外培养拟胚体，胚胎干细胞可以分化成心肌细胞等所有原始胚层源的特异细胞。在分化过程中，心肌细胞的特异基因如离子通道随发育而表达，密切吻合心脏发育的模式。我们课题组主要利用胚胎干细胞分化心肌细胞系统来探讨离子通道在心脏早期发育时期的表观遗传调节，从遗传角度理解心律失常以及心衰的分子机制。此外，我们还通过基因打靶策略进行大鼠房颤或心衰模型构建研究，并以此为体内平台，筛选潜在的靶向药物，同时探索可能的再生细胞治疗策略。 Embryonic stem (ES) cells provide a unique system for the genetic manipulation and the creation of knockout strains of mice or rat as diseases models through gene modification. By cultivation in vitro embryoid bodies, ES cells can differentiate into derivatives of all primary germ layers, including cardiomyocytes. During differentiation, cardiac-specific genes such as ion channels are expressed in a developmental continuum, which closely recapitulates the developmental pattern of early cardiogenesis. Our group research focuses on exploitation of the system of ES cell–derived cardiomyocytes for epigenetic analysis of ion channel regulation in early cardiac development and understanding in vitro “gain-of-function” or “loss-of-function” genetics which involved the molecular mechanisms underlying arrhythmia and heart failure. In addition, more recent efforts have also focused on creation of rat models for the diseases by gene targeting in rat ES cell in order to set up an in vivo platform for screening potential drugs for antiarrhythmic or heart failure treatment and determining the basic strategies of regenerative cell therapy for the diseases.