Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada.
Cell Stem Cell. 2012 Dec 7;11(6):769-82. doi: 10.1016/j.stem.2012.11.008.
Reprogramming of somatic cells to a pluripotent state via expression of Oct4, Klf4, Myc, and Sox2 is a multistep process involving phased changes in gene expression. Here, we focus on the later stages of reprogramming, termed maturation and stabilization. We show that the stabilization phase and the acquisition of pluripotency are dependent on the removal of transgene expression late in the maturation phase. Clonal analysis of cells undergoing reprogramming revealed subsets of stabilization-competent (SC) and stabilization-incompetent (SI) cells. SC clones acquire a competency gene-expression signature late in the maturation phase. Functional analysis of SC signature genes identified enhancers of the transition to the stabilization phase and a distinct subset of genes required for the maintenance of pluripotency. Thus, the acquisition and maintenance of pluripotency are regulated by distinct molecular networks, and a specific regulatory program not previously implicated in reprogramming is required for the transition to transgene independence.
通过表达 Oct4、Klf4、Myc 和 Sox2 将体细胞重编程为多能状态是一个多步骤的过程，涉及基因表达的分阶段变化。在这里，我们关注重编程的后期阶段，称为成熟和稳定。我们表明，稳定阶段和获得多能性依赖于成熟阶段后期去除转基因表达。经历重编程的细胞的克隆分析揭示了稳定能力（SC）和稳定能力丧失（SI）细胞的亚群。SC 克隆在成熟阶段后期获得了一个竞争力的基因表达特征。SC 特征基因的功能分析确定了向稳定阶段过渡的增强子，以及一组独特的基因，这些基因对于维持多能性是必需的。因此，多能性的获得和维持受不同的分子网络调控，并且需要一个以前未涉及重编程的特定调控程序来过渡到对转基因的独立性。
