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诱导多能干细胞重编程:表观遗传学及其在再生医学中的应用。

Induced pluripotent stem cells reprogramming: Epigenetics and applications in the regenerative medicine.

作者信息

Gomes Kátia Maria Sampaio, Costa Ismael Cabral, Santos Jeniffer Farias Dos, Dourado Paulo Magno Martins, Forni Maria Fernanda, Ferreira Julio Cesar Batista

机构信息

Department of Anatomy, Institute of Biomedical Sciences III, Universidade de São Paulo (ICB III/USP), São Paulo, SP, Brazil.

Department of Biochemistry, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brazil.

出版信息

Rev Assoc Med Bras (1992). 2017 Feb;63(2):180-189. doi: 10.1590/1806-9282.63.02.180.

Abstract

Induced pluripotent stem cells (iPSCs) are somatic cells reprogrammed into an embryonic-like pluripotent state by the expression of specific transcription factors. iPSC technology is expected to revolutionize regenerative medicine in the near future. Despite the fact that these cells have the capacity to self-renew, they present low efficiency of reprogramming. Recent studies have demonstrated that the previous somatic epigenetic signature is a limiting factor in iPSC performance. Indeed, the process of effective reprogramming involves a complete remodeling of the existing somatic epigenetic memory, followed by the establishment of a "new epigenetic signature" that complies with the new type of cell to be differentiated. Therefore, further investigations of epigenetic modifications associated with iPSC reprogramming are required in an attempt to improve their self-renew capacity and potency, as well as their application in regenerative medicine, with a new strategy to reduce the damage in degenerative diseases. Our review aimed to summarize the most recent findings on epigenetics and iPSC, focusing on DNA methylation, histone modifications and microRNAs, highlighting their potential in translating cell therapy into clinics.

摘要

诱导多能干细胞(iPSC)是通过特定转录因子的表达重编程为胚胎样多能状态的体细胞。iPSC技术有望在不久的将来彻底改变再生医学。尽管这些细胞具有自我更新的能力,但它们的重编程效率较低。最近的研究表明,先前的体细胞表观遗传特征是iPSC性能的限制因素。事实上,有效的重编程过程涉及对现有的体细胞表观遗传记忆进行完全重塑,随后建立一种“新的表观遗传特征”,以符合待分化的新型细胞。因此,需要进一步研究与iPSC重编程相关的表观遗传修饰,以提高其自我更新能力和潜能,以及它们在再生医学中的应用,并采用一种新策略来减少退行性疾病中的损伤。我们的综述旨在总结表观遗传学和iPSC的最新发现,重点关注DNA甲基化、组蛋白修饰和微小RNA,突出它们在将细胞治疗转化为临床应用方面的潜力。

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