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要构建心脏起搏细胞首先需要理解起搏自动节律性,“膜钟”和“Ca2+钟”两种特征性现象负责起搏活性的调控。在过去几十年,生物起搏器取得了极大的发展,窦房结发育的关键调控因子Tbx18能直接将心肌细胞重编程为起搏样细胞。另一个关键转录因子Tbx3,具体表达在包括窦房结在内的心脏传导系统,其足以诱导心脏起搏基因表达。为了成功实现细胞治疗,生成的细胞应该具有心脏起搏细胞的所有调节机制。否则,生成的起搏细胞仅能作为基础研究的调查模型或新型抗心律失常药物的测试模型。
To construct cardiac pacemaker cells, we must first understand the pacemaker automatic pacemaker, and two characteristic phenomena, “membrane clock” and “Ca2 + clock”, are responsible for the regulation of pacemaker activity. In the past few decades, biological pacemaker has made tremendous progress. Tbx18, a key regulator of sinus node development, can reprogram cardiomyocytes directly into pacemaker-like cells. Another key transcription factor, Tbx3, is specifically expressed in cardiac conduction systems, including the sinoatrial node, which is sufficient to induce cardiac pacing gene expression. For successful cell therapy, the resulting cells should have all the regulatory mechanisms of cardiac pacemaker cells. Otherwise, the resulting paced cells can only serve as a model for investigating underlying studies or as a test model for novel antiarrhythmic drugs.