Derivation of induced Pluripotent Stem Cells (iPSCs) by reprogramming somatic cells to a pluripotent state has revolutionized stem cell research. Ensuing this, various groups have used genetic and non-genetic approaches to generate iPSCs from numerous cell types. However, achieving a pluripotent state in most of the reprogramming studies is marred by serious limitations such as low reprogramming efficiency and slow kinetics. These limitations are mainly due to the presence of potent barriers that exist during reprogramming when a mature cell is coaxed to achieve a pluripotent state. Several studies have revealed that intrinsic factors such as non-optimal stoichiometry of reprogramming factors, specific signaling pathways, cellular senescence, pluripotency-inhibiting transcription factors and microRNAs act as a roadblock. In addition, the epigenetic state of somatic cells and specific epigenetic modifications that occur during reprogramming also remarkably impede the generation of iPSCs. In this review, we present a comprehensive overview of the barriers that inhibit reprogramming and the understanding of which will pave the way to develop safe strategies for efficient reprogramming.

中文翻译：

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深入了解iPSC生成的重编程障碍。

通过将体细胞重编程为多能状态来诱导多能干细胞（iPSC），彻底改变了干细胞研究。随之而来的是，各个小组已使用遗传和非遗传方法从多种细胞类型中产生iPSC。但是，在大多数重编程研究中实现多能状态受到严重限制，例如低的重编程效率和缓慢的动力学。这些限制主要是由于当成熟细胞被哄骗达到多能状态时在重编程过程中存在有效屏障。几项研究表明，内在因素（例如重编程因素的非最佳化学计量比，特定的信号传导途径，细胞衰老，多能性抑制转录因子和microRNA）成为障碍。此外，体细胞的表观遗传状态和在重编程期间发生的特定表观遗传修饰也显着阻碍了iPSC的产生。在这篇综述中，我们对抑制重编程的障碍进行了全面的概述，对这些障碍的理解将为开发有效的重编程安全策略铺平道路。