窦房结
连环素
细胞生物学
钙粘蛋白
诱导多能干细胞
生物
干细胞
Wnt信号通路
胚胎干细胞
细胞
信号转导
内分泌学
遗传学
心率
基因
血压
作者
Wei Zhang,Fengyuan Wang,Lu Yin,Yanhong Tang,Xi Wang,Mingxin Liu
摘要
Our study was conducted to investigate whether cadherin-5 (CDH5), a vascular endothelial cell adhesion glycoprotein, could facilitate the differentiation of human induced pluripotent stem cells (hiPSCs) into sinoatrial node-like pacemaker cells (SANLPCs), following previous findings of silk-fibroin hydrogel-induced direct conversion of quiescent cardiomyocytes into pacemaker cells in rats through the activation of CDH5. In this study, the differentiating hiPSCs were treated with CDH5 (40 ng/mL) between Day 5 and 7 during cardiomyocytes differentiation. The findings in the present study demonstrated that CDH5 stimulated the expression of pacemaker-specific markers while suppressing markers associated with working cardiomyocytes, resulting in an increased proportion of SANLPCs among hiPSCs-derived cardiomyocytes (hiPSC-CMs) population. Moreover, CDH5 induced typical electrophysiological characteristics resembling cardiac pacemaker cells in hiPSC-CMs. Further mechanistic investigations revealed that the enriched differentiation of hiPSCs into SANLPCs induced by CDH5 was partially reversed by iCRT14, an inhibitor of β-catenin. Therefore, based on the aforementioned findings, it could be inferred that the regulation of β-catenin by CDH5 played a crucial role in promoting the enriched differentiation of hiPSCs into SANLPCs, which presents a novel avenue for the construction of biological pacemakers in forthcoming research.
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