Functional Modules Distinguish Human Induced Pluripotent Stem Cells from Embryonic Stem Cells
Functional Modules Distinguish Human Induced Pluripotent Stem Cells from Embryonic Stem Cells
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DOI：
10.1089/scd.2010.0574
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发表时间：
2011-11-01
影响因子：
4
通讯作者：
Fan, Guoping
中科院分区：
文献类型：
--
作者：
Wang, Anyou;Huang, Kevin;Fan, Guoping
人类诱导多能干细胞（iPSC）和胚胎干细胞（ESC）是否表达不同的转录组一直存在争议。通过使用加权基因共表达网络分析的方法，我们在这里表明，iPSCs表现出改变的功能模块相比，胚胎干细胞。值得注意的是，iPSC和ESC差异表达17个模块，主要在转录，代谢，发育和免疫应答中发挥作用。这些模块激活（上调和下调）在各种iPSC中高度保守，并且每个模块中的基因都是一致共表达的。此外，这些模块化基因的激活水平可以用作定量变量，以高准确度（96%）区分iPSC和ESC。因此，这些功能模块的差异激活是区分iPSC和ESC的保守特征。引人注目的是，这些模块的整体激活水平与DNA甲基化水平呈负相关，这表明DNA甲基化可能是调节模块差异的一种机制。总的来说，我们得出结论，人类iPSC和ESC表现出不同的基因表达网络，这可能与iPSC和ESC衍生过程中不同的表观遗传重编程事件有关。
It has been debated whether human induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) express distinctive transcriptomes. By using the method of weighted gene co-expression network analysis, we showed here that iPSCs exhibit altered functional modules compared with ESCs. Notably, iPSCs and ESCs differentially express 17 modules that primarily function in transcription, metabolism, development, and immune response. These module activations (up- and downregulation) are highly conserved in a variety of iPSCs, and genes in each module are coherently co-expressed. Furthermore, the activation levels of these modular genes can be used as quantitative variables to discriminate iPSCs and ESCs with high accuracy (96%). Thus, differential activations of these functional modules are the conserved features distinguishing iPSCs from ESCs. Strikingly, the overall activation level of these modules is inversely correlated with the DNA methylation level, suggesting that DNA methylation may be one mechanism regulating the module differences. Overall, we conclude that human iPSCs and ESCs exhibit distinct gene expression networks, which are likely associated with different epigenetic reprogramming events during the derivation of iPSCs and ESCs.