Grupo Centauro, Universidad de Antioquia, Medellín, Colômbia, Spain.
Theriogenology. 2012 Dec;78(9):1869-86. doi: 10.1016/j.theriogenology.2012.05.030. Epub 2012 Sep 12.
Somatic cell nuclear transfer (SCNT), the technique commonly known as cloning, permits transformation of a somatic cell into an undifferentiated zygote with the potential to develop into a newborn animal (i.e., a clone). In somatic cells, chromatin is programmed to repress most genes and express some, depending on the tissue. It is evident that the enucleated oocyte provides the environment in which embryonic genes in a somatic cell can be expressed. This process is controlled by a series of epigenetic modifications, generally referred to as "nuclear reprogramming," which are thought to involve the removal of reversible epigenetic changes acquired during cell differentiation. A similar process is thought to occur by overexpression of key transcription factors to generate induced pluripotent stem cells (iPSCs), bypassing the need for SCNT. Despite its obvious scientific and medical importance, and the great number of studies addressing the subject, the molecular basis of reprogramming in both reprogramming strategies is largely unknown. The present review focuses on the cellular and molecular events that occur during nuclear reprogramming in the context of SCNT and the various approaches currently being used to improve nuclear reprogramming. A better understanding of the reprogramming mechanism will have a direct impact on the efficiency of current SCNT procedures, as well as iPSC derivation.
体细胞核移植(SCNT),通常称为克隆的技术,允许将体细胞转化为具有发育成新生动物(即克隆)潜能的未分化受精卵。在体细胞中,染色质被编程为抑制大多数基因并表达一些基因,这取决于组织。显然,去核卵母细胞提供了在体细胞中的胚胎基因可以表达的环境。这个过程由一系列表观遗传修饰控制,通常称为“核重编程”,据认为它涉及到在细胞分化过程中获得的可逆表观遗传变化的去除。人们认为,通过过度表达关键转录因子来产生诱导多能干细胞(iPSC)可以绕过 SCNT 的需要,从而发生类似的过程。尽管它具有明显的科学和医学重要性,并且有大量的研究涉及该主题,但在这两种重编程策略中,重编程的分子基础在很大程度上仍然未知。本综述重点介绍了在 SCNT 背景下核重编程过程中发生的细胞和分子事件,以及目前用于改善核重编程的各种方法。对重编程机制的更好理解将直接影响当前 SCNT 程序的效率,以及 iPSC 的衍生。