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Reprogramming mammalian somatic cells

机译:重编程哺乳动物体细胞

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摘要

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.
机译:体细胞核移植(SCNT),通常称为克隆,可将体细胞转化为未分化的合子,并有可能发育为新生动物(即克隆)。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,具体取决于组织。显然,去核卵母细胞提供了可以在体细胞中表达胚胎基因的环境。该过程由一系列表观遗传修饰(通常称为“核重编程”)控制,这些修饰被认为涉及去除细胞分化过程中获得的可逆表观遗传变化。人们认为,通过关键转录因子的过表达来产生诱导性多能干细胞(iPSC),从而绕过了SCNT的发生,发生了类似的过程。尽管其具有明显的科学和医学重要性,并且针对该主题进行了大量研究,但在两种重编程策略中重编程的分子基础仍是未知的。本综述着眼于在SCNT的背景下在核重编程期间发生的细胞和分子事件以及当前用于改善核重编程的各种方法。对重新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推导。

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