Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Protein Cell. 2012 May;3(5):329-45. doi: 10.1007/s13238-012-2920-x. Epub 2012 Mar 31.
Nuclear reprogramming is described as a molecular switch, triggered by the conversion of one cell type to another. Several key experiments in the past century have provided insight into the field of nuclear reprogramming. Previously deemed impossible, this research area is now brimming with new findings and developments. In this review, we aim to give a historical perspective on how the notion of nuclear reprogramming was established, describing main experiments that were performed, including (1) somatic cell nuclear transfer, (2) exposure to cell extracts and cell fusion, and (3) transcription factor induced lineage switch. Ultimately, we focus on (4) transcription factor induced pluripotency, as initiated by a landmark discovery in 2006, where the process of converting somatic cells to a pluripotent state was narrowed down to four transcription factors. The conception that somatic cells possess the capacity to revert to an immature status brings about huge clinical implications including personalized therapy, drug screening and disease modeling. Although this technology has potential to revolutionize the medical field, it is still impeded by technical and biological obstacles. This review describes the effervescent changes in this field, addresses bottlenecks hindering its advancement and in conclusion, applies the latest findings to overcome these issues.
核重编程被描述为一种分子开关，由一种细胞类型向另一种细胞类型的转化触发。过去一个世纪的几项关键实验为核重编程领域提供了深入的了解。以前被认为不可能的事情，这个研究领域现在充满了新的发现和发展。在这篇综述中，我们旨在从历史角度介绍核重编程概念是如何确立的，描述了所进行的主要实验，包括 (1) 体细胞核转移，(2) 细胞提取物和细胞融合暴露，以及 (3) 转录因子诱导谱系转换。最终，我们将重点介绍 (4) 转录因子诱导多能性，这是 2006 年的一项里程碑式发现引发的，该发现将体细胞转化为多能状态的过程缩小到四个转录因子。体细胞具有恢复到不成熟状态的能力的概念带来了巨大的临床意义，包括个性化治疗、药物筛选和疾病建模。尽管这项技术有可能彻底改变医学领域，但它仍然受到技术和生物学障碍的阻碍。本综述描述了该领域的蓬勃发展，探讨了阻碍其发展的瓶颈，并在结论中应用最新发现来克服这些问题。
