美国麻省总医院的Konrad Hochedlinger和加州大学旧金山分校的Gene W. Yeo等研究人员合作发现，RNA解旋酶DDX6通过调节P小体稳态来控制细胞可塑性。这一研究成果2019年10月3日在线发表在国际学术期刊《细胞—干细胞》上。

研究人员发现对RNA解旋酶DDX6的抑制使得人类和小鼠活化的胚胎干细胞（ESC）具有分化抗性，即“高多能”状态，该状态很容易重新编程为类似于植入前胚胎的初始状态。研究人员进一步证明，DDX6在成年祖细胞中起关键作用，它以背景相关的方式控制自我更新与分化之间的平衡。从机理上讲，DDX6介导了P小体内靶mRNA的翻译抑制。在DDX6活性丧失后，P小体溶解并释放编码命运指示性转录和染色质因子的mRNA，从而重新进入核糖体。这些靶基因翻译的增加通过重连未分化细胞类型的增强子、异染色质和DNA甲基化状态而影响细胞命运。总的来说，这些数据在P小体稳态、染色质组织和干细胞潜能之间建立了联系。

据悉，转录后机制有可能影响基因表达的复杂变化，但是它们在细胞命运转变中的作用仍未得到充分探索。

附：英文原文

Title: The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis

Author: Bruno Di Stefano, En-Ching Luo, Chuck Haggerty, Stefan Aigner, Jocelyn Charlton, Justin Brumbaugh, Fei Ji, Inés Rabano Jiménez, Katie J. Clowers, Aaron J. Huebner, Kendell Clement, Inna Lipchina, Marit A.C. de Kort, Anthony Anselmo, John Pulice, Mattia F.M. Gerli, Hongcang Gu, Steven P. Gygi, Ruslan I. Sadreyev, Alexander Meissner, Gene W. Yeo, Konrad Hochedlinger

Issue&Volume: 3 October 2019

Abstract: Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells (ESCs) with a differentiation-resistant, "hyper-pluripotent" state, which readily reprograms to a naive state resembling the preimplantation embryo. We further demonstrate that DDX6 plays a key role in adult progenitors where it controls the balance between self-renewal and differentiation in a context-dependent manner. Mechanistically, DDX6 mediates the translational suppression of target mRNAs in P-bodies. Upon loss of DDX6 activity, P-bodies dissolve and release mRNAs encoding fate-instructive transcription and chromatin factors that re-enter the ribosome pool. Increased translation of these targets impacts cell fate by rewiring the enhancer, heterochromatin, and DNA methylation landscapes of undifferentiated cell types. Collectively, our data establish a link between P-body homeostasis, chromatin organization, and stem cell potency.

DOI: 10.1016/j.stem.2019.08.018

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30385-6