Multifaceted regulation of somatic cell reprogramming by mRNA translational control.
|核心内容：
翻译调控在胚胎干细胞的多能性网络调控中起着关键作用，但其对体细胞重新编程为多能性的影响尚未被探讨。
在这里，我们展示了真核翻译起始因子4E(EIF4E)结合蛋白(4E-BPs)，作为翻译抑制因子，对小鼠胚胎成纤维细胞(MEF)重编程为诱导多能干细胞(IPSCs)具有多方面的影响。
4E-BP的表达的失去至少部分地通过增加p21的翻译来减弱IPSCs的诱导，p21是一种已知的体细胞重编程抑制因子。
mTORC1活性的增加也会抑制4E-BPs，也可能增加p21的翻译来减弱IPSCs的诱导。从这个角度看，mTORC1活性对应的分化。
Figure 1. 4E-BPs Are Required for Somatic Cell Reprogramming
然而，缺少p53和4E-bps的MEF表现出极大的重编程能力，这是由于p21转录减少和内源性mRNA(如Sox2和Myc)的翻译增强所致，并且可以仅通过外源Oct4的表达来重编程。
Figure 2. Combined Loss of 4E-BPs and p53 Enhances Efficiency of Somatic Cell Reprogramming
Figure 3. Characterization and Differentiation of Oct4-Induced TKO iPSCs
Figure 4. Oct4-Induced TKO iPSC ClonesAre Pluripotent and Contribute to ChimericMouse Offspring
Figure 5. Increased Translation of Sox2and Myc mRNAs and Downregulated p21Expression Correlate with High Reprogrammability of TKO MEFs.
因此，4E-bps对重新编程既有积极的影响，也有消极的影响，突出了翻译控制在调节这一过程中的关键作用。
Model showing the link between p53/p21pathway and 4E-BP-dependent translationalcontrol in factor-induced reprogramming.
原文摘要：
Translational control plays a pivotal role in the regulation of the pluripotency network in embryonic stem cells, but its effect on reprogramming somatic cells to pluripotency has not been explored.
Here, we show that eukaryotic translation initiation factor 4E (eIF4E) binding proteins (4E-BPs), which are translational repressors, have a multifaceted effect on the reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs).
Loss of 4E-BP expression attenuates the induction of iPSCs at least in part through increased translation of p21, a known inhibitor of somatic cell reprogramming.
However, MEFs lacking both p53 and 4E-BPs show greatly enhanced reprogramming resulting from a combination of reduced p21 transcription and enhanced translation of endogenous mRNAs such as Sox2 and Myc and can be reprogrammed through the expression of only exogenous Oct4.
Thus, 4E-BPs exert both positive and negative effects on reprogramming, highlighting the key role that translational control plays in regulating this process.
参考文献：https://sci-hub.ren/10.1016/j.stem.2014.02.005
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