Mandel Center for Heart and Vascular Research, and the Duke Cardiovascular Research Center, Duke University Medical Center, Durham, North Carolina, United States.
Am J Physiol Cell Physiol. 2023 Apr 1;324(4):C843-C855. doi: 10.1152/ajpcell.00402.2022. Epub 2023 Feb 27.
We discovered that innate immunity plays an important role in the reprogramming of fibroblasts into cardiomyocytes. In this report, we define the role of a novel retinoic acid-inducible gene 1 Yin Yang 1 (Rig1:YY1) pathway. We found that fibroblast to cardiomyocyte reprogramming efficacy was enhanced by specific Rig1 activators. To understand the mechanism of action, we performed various transcriptomic, nucleosome occupancy, and epigenomic approaches. Analysis of the datasets indicated that Rig1 agonists had no effect on reprogramming-induced changes in nucleosome occupancy or loss of inhibitory epigenetic motifs. Instead, Rig1 agonists were found to modulate cardiac reprogramming by promoting the binding of YY1 specifically to cardiac genes. To conclude, these results show that the Rig1:YY1 pathway plays a critical role in fibroblast to cardiomyocyte reprogramming.
我们发现先天免疫在成纤维细胞重编程为心肌细胞的过程中起着重要作用。在本报告中，我们定义了一种新的视黄酸诱导基因 1 阴-阳 1（Rig1：YY1）途径的作用。我们发现，特定的 Rig1 激活剂增强了成纤维细胞向心肌细胞的重编程效率。为了了解作用机制，我们进行了各种转录组、核小体占有率和表观基因组学方法的研究。数据集的分析表明，Rig1 激动剂对核小体占有率或抑制性表观遗传模体丢失引起的重编程诱导变化没有影响。相反，发现 Rig1 激动剂通过促进 YY1 特异性结合心脏基因来调节心脏重编程。总之，这些结果表明，Rig1：YY1 途径在成纤维细胞向心肌细胞的重编程中起着关键作用。
