University of North Carolina McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, UNC-Chapel Hill, Chapel Hill, NC 27599 USA.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Cell Rep. 2018 Feb 13;22(7):1913-1922. doi: 10.1016/j.celrep.2018.01.047.
Direct reprogramming of fibroblasts into cardiomyocyte-like cells (iCM) holds great potential for heart regeneration and disease modeling and may lead to future therapeutic applications. Currently, application of this technology is limited by our lack of understanding of the molecular mechanisms that drive direct iCM reprogramming. Using a quantitative mass spectrometry-based proteomic approach, we identified the temporal global changes in protein abundance that occur during initial phases of iCM reprogramming. Collectively, our results show systematic and temporally distinct alterations in levels of specific functional classes of proteins during the initiating steps of reprogramming including extracellular matrix proteins, translation factors, and chromatin-binding proteins. We have constructed protein relational networks associated with the initial transition of a fibroblast into an iCM. These findings demonstrate the presence of an orchestrated series of temporal steps associated with dynamic changes in protein abundance in a defined group of protein pathways during the initiating events of direct reprogramming.
成纤维细胞直接重编程为心肌细胞样细胞（iCM）在心脏再生和疾病建模方面具有巨大的潜力，并可能为未来的治疗应用铺平道路。目前，这项技术的应用受到我们对驱动直接 iCM 重编程的分子机制缺乏了解的限制。本研究采用基于定量质谱的蛋白质组学方法，鉴定了 iCM 重编程初始阶段发生的蛋白质丰度的全局变化。总的来说，我们的研究结果表明，在重编程的起始步骤中，特定功能类别的蛋白质水平会发生系统的、时间上的不同改变，包括细胞外基质蛋白、翻译因子和染色质结合蛋白。我们构建了与成纤维细胞向 iCM 初始转变相关的蛋白质关系网络。这些发现表明，在直接重编程的起始事件中，在一组特定的蛋白质通路中，存在一系列与蛋白质丰度动态变化相关的协调时间步骤。
