Forced expression of lineage-specific transcription factors in somatic cells can result in the generation of different cell types in a process named direct reprogramming, bypassing the pluripotent state. However, the introduction of transgenes limits the therapeutic applications of the produced cells. Numerous small-molecules have been introduced in the field of stem cell biology capable of governing self-renewal, reprogramming, transdifferentiation and regeneration. These chemical compounds are versatile tools for cell fate conversion toward desired outcomes. Cell fate conversion using small-molecules alone (chemical reprogramming) has superiority over arduous traditional genetic techniques in several aspects. For instance, rapid, transient, and reversible effects in activation and inhibition of functions of specific proteins are of the profits of small-molecules. They are cost-effective, have a long half-life, diversity on structure and function, and allow for temporal and flexible regulation of signaling pathways. Additionally, their effects could be adjusted by fine-tuning concentrations and combinations of different small-molecules. Therefore, chemicals are powerful tools in cell fate conversion and study of stem cell and chemical biology in vitro and in vivo. Moreover, transgene-free and chemical-only transdifferentiation approaches provide alternative strategies for the generation of various cell types, disease modeling, drug screening, and regenerative medicine. The current review gives an overview of the recent findings concerning transdifferentiation by only small-molecules without the use of transgenes.

中文翻译：

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化学物质作为细胞命运的唯一变形金刚。

在体细胞中谱系特异性转录因子的强制表达可导致绕过多能状态的过程称为直接重编程，从而导致生成不同类型的细胞。然而，转基因的引入限制了产生的细胞的治疗应用。在干细胞生物学领域中已经引入了许多小分子，它们能够控制自我更新，重编程，转分化和再生。这些化合物是将细胞命运转化为所需结果的通用工具。仅在几个方面，仅使用小分子的细胞命运转化（化学重编程）就比艰苦的传统遗传技术优越。例如，快速，短暂，激活和抑制特定蛋白质功能的可逆作用是小分子的收益。它们具有成本效益，半衰期长，结构和功能多样，并且可以及时灵活地调节信号传导途径。此外，可以通过微调浓度和不同小分子的组合来调节其作用。因此，化学物质是细胞命运转化以及体外和体内干细胞和化学生物学研究的有力工具。此外，无转基因且仅化学的转分化方法为多种细胞类型的产生，疾病建模，药物筛选和再生医学提供了替代策略。