Department of Biological Chemistry, David Geffen School of Medicine , University of California Los Angeles, Los Angeles, CA 90095, USA.
Cell Stem Cell. 2010 Aug 6;7(2):263-9. doi: 10.1016/j.stem.2010.06.019.
Recent work from our group and others has argued that human induced pluripotent stem cells (hiPSCs) generated by the introduction of four viruses bearing reprogramming factors differ from human embryonic stem cells (hESCs) at the level of gene expression (Chin et al., 2009). Many of the differences seen were common across independent labs and, at least to some extent, are thought to be a result of residual expression of donor cell-specific genes (Chin et al., 2009; Ghosh et al., 2010; Marchetto et al., 2009). Two new reports reanalyze similar expression data sets as those used in Chin et al. (2009) and come to different conclusions (Newman and Cooper, 2010; Guenther et al., 2010). We compare various approaches to perform gene expression meta-analysis that all support our original conclusions and present new data to demonstrate that polycistronic delivery of the reprogramming factors and extended culture brings hiPSCs transcriptionally closer to hESCs.
我们小组和其他小组的最近研究表明,通过引入携带重编程因子的四种病毒产生的人类诱导多能干细胞(hiPSC)在基因表达水平上与人类胚胎干细胞(hESC)不同(Chin 等人,2009 年)。许多观察到的差异在独立实验室中是共同的,至少在某种程度上,被认为是供体细胞特异性基因残留表达的结果(Chin 等人,2009 年;Ghosh 等人,2010 年;Marchetto 等人,2009 年)。两项新的报告重新分析了类似于 Chin 等人使用的表达数据集(2009 年),得出了不同的结论(Newman 和 Cooper,2010 年;Guenther 等人,2010 年)。我们比较了执行基因表达荟萃分析的各种方法,所有方法都支持我们的原始结论,并提出了新的数据来证明重编程因子的多顺反子传递和延长培养使 hiPSC 在转录上更接近 hESC。