Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
Chem Soc Rev. 2017 Oct 16;46(20):6241-6254. doi: 10.1039/c7cs00330g.
Over the last decade, the development of methods to promote conversion of one type of cell to a specific type of another cell (or change of cell fate) has received great attention in basic biological research and therapeutic applications. A precise, reproducible and safe protocol for inducing this change is a prerequisite for cellular conversion. Although genetic manipulation, which relies on the introduction of specific genes into cells, is a promising approach, the results of initial investigations have highlighted serious safety concerns associated with forced ectopic gene expression with unpredictable side effects. Alternatively, a chemical approach that relies on the use of small molecules to modulate the cell fate has great potential in terms of precise control and clinical safety. In addition, the ease of application, reproducibility and scalability are features that make a small molecule-based approach an extraordinary resource for this purpose. In this review we summarize methods which have been devised to identify small molecules that induce cellular conversion and highlight recent advances made using small molecule modulators to induce changes in the fate of cells.
在过去的十年中，促进一种类型的细胞转化为另一种特定类型的细胞（或改变细胞命运）的方法的发展在基础生物学研究和治疗应用中受到了极大的关注。精确、可重复和安全的诱导这种变化的方案是细胞转化的前提。虽然遗传操作依赖于将特定基因引入细胞，但最初的研究结果突出了与强制异位基因表达相关的严重安全问题，其具有不可预测的副作用。相反，依赖于使用小分子来调节细胞命运的化学方法在精确控制和临床安全性方面具有巨大的潜力。此外，易于应用、可重复性和可扩展性是使基于小分子的方法成为该目的的卓越资源的特征。在这篇综述中，我们总结了鉴定诱导细胞转化的小分子的方法，并强调了使用小分子调节剂诱导细胞命运变化的最新进展。
