Center for iPS Cell Research and Application, Kyoto University 53, Sakyo-ku, Kyoto, Japan.
J Cell Sci. 2012 Jun 1;125(Pt 11):2553-60. doi: 10.1242/jcs.084822. Epub 2012 Jun 26.
During development, cell fate is specified precisely through programming by multiple complex elements and processes, including chromatin modifications that result in epigenetic marks. Once determined, cell fate is specified further only through maturation processes, which include differentiation and senescence. However, recent studies have shown that it is possible to influence cell fate through artificial manipulation. For example, the exogenous expression of a set of transcription factors can result in the reprogramming of differentiated skin fibroblasts to a pluripotent state. In addition, recent reports have demonstrated the directed reprogramming of one type of differentiated somatic cell to another type of differentiated somatic cell, without rejuvenation to a pluripotent state. Reprogramming factors blur the boundaries between different cell fates, which can never meet, as if the hierarchy were flattened by 'lowering gravity'. Although attempts to use direct reprogramming to generate certain cell types, such as those found in the kidneys and the lungs, have remained unsuccessful, recent advances suggest that we are nearing the identification of determinants that allow cells to be directly reprogrammed into cell types from all organs in the not too distant future. This Commentary summarises our current knowledge on cellular reprogramming, and more specifically, recent advances in direct reprogramming to generate a variety of cell types.
在发育过程中，细胞命运是通过多种复杂的元素和过程来精确编程的，包括导致表观遗传标记的染色质修饰。一旦确定，细胞命运只能通过成熟过程进一步指定，包括分化和衰老。然而，最近的研究表明，通过人工操作可以影响细胞命运。例如，一组转录因子的外源表达可以使分化的皮肤成纤维细胞重新编程为多能状态。此外，最近的报道表明，可以将一种分化的体细胞定向重编程为另一种分化的体细胞，而无需恢复到多能状态。重编程因子模糊了不同细胞命运之间永远不会相遇的界限，就好像层次结构被“降低重力”所扁平化一样。尽管尝试使用直接重编程来产生某些细胞类型，如肾脏和肺部中的细胞类型，仍然没有成功，但最近的进展表明，我们即将确定允许细胞直接重编程为所有器官中细胞类型的决定因素。这篇评论总结了我们目前对细胞重编程的认识，特别是最近在直接重编程方面的进展，以产生各种细胞类型。
