共查询到20条相似文献,搜索用时 593 毫秒
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Akira Watanabe Yasuhiro Yamada Shinya Yamanaka 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2013,368(1609)
The differentiation and reprogramming of cells are accompanied by drastic changes in the epigenetic profiles of cells. Waddington''s classical model clearly describes how differentiating cells acquire their cell identity as the developmental potential of an individual cell population declines towards the terminally differentiated state. The recent discovery of induced pluripotent stem cells as well as of somatic cell nuclear transfer provided evidence that the process of differentiation can be reversed. The identity of somatic cells is strictly protected by an epigenetic barrier, and these cells acquire pluripotency by breaking the epigenetic barrier by reprogramming factors such as Oct3/4, Sox2, Klf4, Myc and LIN28. This review covers the current understanding of the spatio-temporal regulation of epigenetics in pluripotent and differentiated cells, and discusses how cells determine their identity and overcome the epigenetic barrier during the reprogramming process. 相似文献
13.
14.
15.
16.
17.
18.
19.
Piccolo FM Pereira CF Cantone I Brown K Tsubouchi T Soza-Ried J Merkenschlager M Fisher AG 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2011,366(1575):2260-2265
Reprogramming differentiated cells towards pluripotency can be achieved by different experimental strategies including the forced expression of specific 'inducers' and nuclear transfer. While these offer unparalleled opportunities to generate stem cells and advance disease modelling, the relatively low levels of successful reprogramming achieved (1-2%) makes a direct analysis of the molecular events associated with productive reprogramming very challenging. The generation of transient heterokaryons between human differentiated cells (such as lymphocytes or fibroblasts) and mouse pluripotent stem cell lines results in a much higher frequency of successful conversion (15% SSEA4 expressing cells) and provides an alternative approach to study early events during reprogramming. Under these conditions, differentiated nuclei undergo a series of remodelling events before initiating human pluripotent gene expression and silencing differentiation-associated genes. When combined with genetic or RNAi-based approaches and high-throughput screens, heterokaryon studies can provide important new insights into the factors and mechanisms required to reprogramme unipotent cells towards pluripotency. 相似文献