Closer to fine: fewer steps to endothelial stemness.

Closer to fine: fewer steps to endothelial stemness.
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更接近精细:实现内皮干性的步骤更少。

DOI:
10.1161/atvbaha.110.213959
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发表时间:
2010
期刊:
Arteriosclerosis, thrombosis, and vascular biology
影响因子:
--
通讯作者:
Patterson,Cam
Patterson,Cam
中科院分区:
--
文献类型:
--
作者:
Deb,Arjun;Patterson,Cam

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Yamanaka的开创性工作证明了完全分化的细胞仅用四种因子(c-Myc,Oct 3/4,Sox 2和Klf 4)就能重编程为胚胎干细胞的能力,开创了再生生物学的新时代。1虽然目前认为分化细胞重编程为多能状态涉及多个随机表观遗传事件,但具有一定程度的单能性或多能性的祖细胞可以更容易地用更少的因子重编程。2小鼠神经干细胞可以重编程为多能状态,只需添加一个因子,Oct 4。内源性神经干细胞内源性表达Sox 2、Klf-4和c-Myc以及其他中间重编程基因,可能使Oct 4能够驱动这些细胞进入多能状态。即使在用核转移技术重编程中,从分化程度较低的细胞或祖细胞捐赠的细胞核诱导比来自终末分化细胞的细胞核更高的重编程效率,这表明分化程度较低的细胞的表观遗传景观比终末分化细胞的表观遗传景观更适合重编程。4然而,体细胞中重编程基因的内源性表达不足以用较少的因子诱导重编程。例如,成纤维细胞表达c-Myc以及Klf-4,但仍然需要外源性引入这些基因或添加小分子以增强重编程过程。2,5外源性引入因子的成功重编程取决于多个变量,包括待重编程细胞的表观遗传景观、表达水平、正确平衡和转基因表达的连续性,以及转基因表达的适当时间沉默。2
Yamanaka’s pioneering work demonstrating the ability of fully differentiated cells to reprogram into embryonic stem cells with just four factors (c-Myc, Oct3/4, Sox2, and Klf4) ushered in a new era of regenerative biology. 1 Although it is currently thought that reprogramming of differentiated cells to a pluripotent state involves multiple stochastic epigenetic events, progenitors with some degree of uni-or multipotency can be reprogrammed more easily with fewer factors. 2 Mouse neural stem cells can be reprogrammed to a pluripotent state with the addition of only one factor, Oct4. 3 The endogenous expression of Sox2, Klf-4, and c-Myc, as well as other intermediate reprogramming genes, by endogenous neural stem cells perhaps enables Oct4 to drive these cells to a pluripotent state. Even in reprogramming with nuclear transfer technology, nuclei donated from less differentiated cells or progenitor cells induce a higher efficiency of reprogramming than nuclei from terminally differentiated cells, suggesting that the epigenetic landscape of a less differentiated cell is more amenable to reprogramming than that of a terminally differentiated cell. 4 However, endogenous expression of reprogramming genes in somatic cells is not sufficient for inducing reprogramming with fewer factors. For instance, fibroblasts express c-Myc as well as Klf-4 but still require exogenous introduction of these genes or addition of small molecules to enhance the reprogramming process. 2, 5 Successful reprogramming with exogenous introduction of factors depends on multiple variables, including the epigenetic landscape of the cell to be reprogrammed, expression levels, correct balance, and continuity of transgene expression, as well as appropriate temporal silencing of transgene expression. 2
DOI: 10.1016/j.cell.2006.07.024
发表时间: 2006-08-25
期刊: CELL
影响因子: 64.5
作者:
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者: Yamanaka, Shinya
DOI: 10.1161/atvbaha.110.206540
发表时间: 2010-10-01
影响因子: 8.7
作者:
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