Cancer hallmarks in induced pluripotent cells: new insights.
Cancer hallmarks in induced pluripotent cells: new insights.
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DOI：
10.1002/jcp.22280
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发表时间：
2010-11
影响因子：
5.6
通讯作者：
Hendrix, Mary J. C.
中科院分区：
文献类型：
--
作者：
Malchenko, Sergey;Galat, Vasiliy;Seftor, Elisabeth A.;Vanin, Elio F.;Costa, Fabricio F.;Seftor, Richard E. B.;Soares, Marcelo B.;Hendrix, Mary J. C.
研究开始出现，证明人类诱导多能干细胞（hiPSC）和人类胚胎干细胞（hESC）之间有趣的差异。在这里，我们研究了Nodal胚胎信号通路关键成员的表达，这对维持hESCs的多能性至关重要。Western印迹和实时RT-PCR分析显示，与hESC相比，hiPSC中Nodal（TGF-β家族成员）和Cripto-1（Nodal的共受体）的水平略低，Lefty（Nodal的抑制剂和TGF-β家族成员）的水平显著降低。hiPSC的Lefty表达的显著下降与Lefty B CpG岛甲基化的增加相关。基于这些发现，我们解决了与表观遗传学重编程hiPSC的后果相关的更基本的问题，特别是在维持稳定的ESC表型方面。两个hiPSC与四个hESC系中的365个微RNA（miR）的全球比较分析最终鉴定了hiPCS中具有>10倍差异的10个高度表达的miR，其已显示与癌症相关。这些数据证明了hiPSC表达的癌症特征，这将需要进一步评估其对未来治疗的影响。
Studies are beginning to emerge that demonstrate intriguing differences between human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). Here, we investigated the expression of key members of the Nodal embryonic signaling pathway, critical to the maintenance of pluripotency in hESCs. Western blot and Real-time RT-PCR analyses reveal slightly lower levels of Nodal (a TGF-β family member) and Cripto-1 (Nodal’s co-receptor) and a dramatic decrease in Lefty (Nodal’s inhibitor and TGF-β family member) in hiPSCs compared with hESCs. The noteworthy drop in hiPSC’s Lefty expression correlated with an increase in the methylation of Lefty B CpG island. Based on these findings, we addressed a more fundamental question related to the consequences of epigenetically reprogramming hiPSCs, especially with respect to maintaining a stable ESC phenotype. A global comparative analysis of 365 microRNAs (miRs) in two hiPSC vs. four hESC lines ultimately identified 10 highly expressed miRs in hiPCSs with >10-fold difference, which have been shown to be cancer related. These data demonstrate cancer hallmarks expressed by hiPSCs, which will require further assessment for their impact on future therapies.
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影响因子：
11.2
作者：
Mertens-Talcott, Susanne U.;Chintharlapalli, Sudhakar;Safe, Stephen
通讯作者：
Safe, Stephen
DOI：
10.1073/pnas.0806202105
发表时间：
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影响因子：
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作者：
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通讯作者：
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