Myocardial Notch signaling reprograms cardiomyocytes to a conduction-like phenotype.
Myocardial Notch signaling reprograms cardiomyocytes to a conduction-like phenotype.
复制标题
DOI：
10.1161/circulationaha.112.103390
复制
发表时间：
2012-08-28
期刊：
影响因子：
37.8
通讯作者：
Epstein JA
中科院分区：
文献类型：
--
作者：
Rentschler S;Yen AH;Lu J;Petrenko NB;Lu MM;Manderfield LJ;Patel VV;Fishman GI;Epstein JA
Notch信号转导在包括果蝇、爪蟾和哺乳动物在内的许多系统的心脏发生过程中，在调节细胞命运决定和分化中发挥重要作用。我们假设Notch也可能参与指导心肌细胞向特化传导细胞的进行性谱系限制。在从早期发育开始在心肌内激活Notch信号传导的心脏中，Notch促进基于传导系统特异性基因的异位表达和电生理学中的细胞自主变化的传导样表型。使用体外试验来激活新生心肌细胞中的Notch，我们观察到转录组以及动作电位特征的整体变化与重编程为传导样表型一致。Notch可以指导室性心脏祖细胞分化为特化的传导样细胞。可塑性仍然存在于晚期心肌细胞中，这对专门的心血管组织的工程具有潜在的意义。
Notch signaling has previously been shown to play an essential role in regulating cell fate decisions and differentiation during cardiogenesis in many systems including Drosophila, Xenopus and mammals. We hypothesized that Notch may also be involved in directing the progressive lineage restriction of cardiomyocytes into specialized conduction cells. In hearts where Notch signaling is activated within the myocardium from early development onwards, Notch promotes a conduction-like phenotype based on ectopic expression of conduction system-specific genes and cell autonomous changes in electrophysiology. Using an in vitro assay to activate Notch in newborn cardiomyocytes, we observed global changes in the transcriptome as well as in action potential characteristics consistent with reprogramming to a conduction-like phenotype. Notch can instruct the differentiation of chamber cardiac progenitors into specialized conduction-like cells. Plasticity remains in late-stage cardiomyocytes, which has potential implications for engineering of specialized cardiovascular tissues.