Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.
Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.
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DOI：
10.1371/journal.pone.0008975
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发表时间：
2010-02-01
期刊：
影响因子：
3.7
通讯作者：
Wu JC
中科院分区：
文献类型：
--
作者：
Ghosh Z;Wilson KD;Wu Y;Hu S;Quertermous T;Wu JC
通过成体细胞去分化产生的人诱导多能干细胞（hiPSC）为围绕人胚胎干细胞（hESC）的伦理问题以及细胞移植后的免疫排斥提供了潜在的解决方案。然而，尽管hiPSC已被描述为“胚胎干细胞样”，但与hESC相比，这些细胞具有独特的基因表达模式，使得不完全重编程成为潜在的陷阱。目前还不清楚在何种程度上的差异组织的起源可能有助于这些基因表达差异。为了回答这些重要的问题，有必要进行仔细的转录谱分析，以研究hiPSC的确切重编程状态，以及分析所得hiPSC上来源组织的印记（如果有的话）。在这项研究中，我们比较了来自胎儿成纤维细胞、新生儿成纤维细胞、脂肪干细胞和角质形成细胞的hiPSC与其相应的供体细胞和hESC的基因谱。我们的分析阐明了每个hiPSC系内重编程的总体程度，以及每个hiPSC系与其供体细胞之间的“距离”。我们进一步鉴定了与hESC相比在hiPSC及其相应供体细胞中具有相似调控模式的基因，从而使我们能够指定在每个hiPSC系中继续表达的供体基因的核心组。我们报告说，供体细胞类型的残余基因表达显著影响了hiPSCs和hESC之间的差异，并增加了重编程的不完整性。具体而言，我们的分析揭示了胎儿成纤维细胞来源的hiPSC更接近hESC，其次是脂肪、新生儿成纤维细胞和角质形成细胞来源的hiPSC。
Human induced pluripotent stem cells (hiPSCs) generated by de-differentiation of adult somatic cells offer potential solutions for the ethical issues surrounding human embryonic stem cells (hESCs), as well as their immunologic rejection after cellular transplantation. However, although hiPSCs have been described as “embryonic stem cell-like”, these cells have a distinct gene expression pattern compared to hESCs, making incomplete reprogramming a potential pitfall. It is unclear to what degree the difference in tissue of origin may contribute to these gene expression differences. To answer these important questions, a careful transcriptional profiling analysis is necessary to investigate the exact reprogramming state of hiPSCs, as well as analysis of the impression, if any, of the tissue of origin on the resulting hiPSCs. In this study, we compare the gene profiles of hiPSCs derived from fetal fibroblasts, neonatal fibroblasts, adipose stem cells, and keratinocytes to their corresponding donor cells and hESCs. Our analysis elucidates the overall degree of reprogramming within each hiPSC line, as well as the “distance” between each hiPSC line and its donor cell. We further identify genes that have a similar mode of regulation in hiPSCs and their corresponding donor cells compared to hESCs, allowing us to specify core sets of donor genes that continue to be expressed in each hiPSC line. We report that residual gene expression of the donor cell type contributes significantly to the differences among hiPSCs and hESCs, and adds to the incompleteness in reprogramming. Specifically, our analysis reveals that fetal fibroblast-derived hiPSCs are closer to hESCs, followed by adipose, neonatal fibroblast, and keratinocyte-derived hiPSCs.
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影响因子：
3.7
作者：
Marchetto MC;Yeo GW;Kainohana O;Marsala M;Gage FH;Muotri AR
通讯作者：
Muotri AR
影响因子：
7
作者：
Gibbons, FD;Roth, FP
通讯作者：
Roth, FP
影响因子：
23.9
作者：
Kim D;Kim CH;Moon JI;Chung YG;Chang MY;Han BS;Ko S;Yang E;Cha KY;Lanza R;Kim KS
通讯作者：
Kim KS
影响因子：
20.3
作者：
Loh, Yuin-Han;Agarwal, Suneet;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
14.8
作者：
Park, In-Hyun;Lerou, Paul H.;Daley, George Q.
通讯作者：
Daley, George Q.