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多能状态转变中的代谢-表观遗传轴

Metabolic-Epigenetic Axis in Pluripotent State Transitions.

作者信息

D'Aniello Cristina, Cermola Federica, Patriarca Eduardo J, Minchiotti Gabriella

机构信息

Stem Cell Fate Laboratory, Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", CNR, 80131 Naples, Italy.

出版信息

Epigenomes. 2019 Jul 31;3(3):13. doi: 10.3390/epigenomes3030013.

Abstract

Cell state transition (CST) occurs during embryo development and in adult life in response to different stimuli and is associated with extensive epigenetic remodeling. Beyond growth factors and signaling pathways, increasing evidence point to a crucial role of metabolic signals in this process. Indeed, since several epigenetic enzymes are sensitive to availability of specific metabolites, fluctuations in their levels may induce the epigenetic changes associated with CST. Here we analyze how fluctuations in metabolites availability influence DNA/chromatin modifications associated with pluripotent stem cell (PSC) transitions. We discuss current studies and focus on the effects of metabolites in the context of naïve to primed transition, PSC differentiation and reprogramming of somatic cells to induced pluripotent stem cells (iPSCs), analyzing their mechanism of action and the causal correlation between metabolites availability and epigenetic alteration.

摘要

细胞状态转变(CST)发生在胚胎发育过程中以及成年期,以响应不同刺激,并且与广泛的表观遗传重塑相关。除了生长因子和信号通路外,越来越多的证据表明代谢信号在这一过程中起着关键作用。事实上,由于几种表观遗传酶对特定代谢物的可用性敏感,它们水平的波动可能会诱导与CST相关的表观遗传变化。在这里,我们分析代谢物可用性的波动如何影响与多能干细胞(PSC)转变相关的DNA/染色质修饰。我们讨论当前的研究,并重点关注代谢物在从原始态到启动态转变、PSC分化以及体细胞重编程为诱导多能干细胞(iPSC)的背景下的作用,分析它们的作用机制以及代谢物可用性与表观遗传改变之间的因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc89/8594706/d5224c54bdcc/epigenomes-03-00013-g001.jpg

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