Factor-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) as a powerful tool for regenerative medicine has gained wide attention in recent years. However, there are certain concerns regarding the efficiency of this reprogramming. Partially reprogrammed iPSCs (piPSCs) are stable cell lines originating from cells that have exited the normal reprogramming route at an early time point. Analysis of the associated global gene expression changes between iPSCs and piPSCs may help understand the barriers to reprogramming. In our study, human fibroblasts were transduced with the four classic transcription factors, OCT4, SOX2, KLF4, and C-MYC. Only a few cells were completely reprogrammed to a fully pluripotent state. Instead, we obtained more number of intermediate standstill clones than human-induced pluripotent stem cells (hiPSCs) during reprogramming. We studied the genome-wide expression profiles of two different fibroblasts, five intermediate standstill clones, and two iPSCs derived from the two fibroblasts. Hierarchical clustering and principal component analysis demonstrated that intermediate standstill clones were on the way to becoming hiPSCs. A remarkable difference in the expression of genes related to cancer and cell adhesion pathway was observed between the intermediate standstill clones and iPSCs. These observations suggest that some cells may become trapped in partially reprogrammed states.

中文翻译：

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中间停顿克隆困在人类成纤维细胞重编程诱导多能干细胞。

因子诱导的体细胞重编程为诱导多能干细胞（iPSC）作为再生医学的强大工具近年来受到了广泛关注。但是，对于这种重新编程的效率存在某些担忧。部分重新编程的iPSC（piPSC）是稳定的细胞系，起源于在早期时间点退出正常重新编程路线的细胞。对iPSC和piPSC之间相关的全局基因表达变化的分析可能有助于理解重编程的障碍。在我们的研究中，人类成纤维细胞被OCT4，SOX2，KLF4和C-MYC四种经典转录因子转导。只有少数细胞被完全重编程为完全多能的状态。相反，在重编程过程中，我们获得了比人类诱导的多能干细胞（hiPSC）多得多的中间停顿克隆。我们研究了两个不同的成纤维细胞，五个中间停顿克隆和两个成纤维细胞衍生的两个iPSC的全基因组表达谱。层次聚类和主成分分析表明，中间停滞克隆正在成为hiPSC。在中间停顿克隆和iPSC之间观察到与癌症和细胞粘附途径相关的基因表达的显着差异。这些观察结果表明某些细胞可能会陷入部分重编程状态。