Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute , Houston, Texas.
Antioxid Redox Signal. 2018 Jul 10;29(2):205-218. doi: 10.1089/ars.2017.7364. Epub 2018 Apr 26.
Yamanaka and colleagues galvanized the field of stem cell biology and regenerative medicine by their generation of induced pluripotent stem cells. Evidence is emerging that activation of innate immune signaling is critical for efficient reprogramming to pluripotency and for the nuclear reprogramming occurring in transdifferentiation. Recent Advances: We have shown that innate immune signaling triggers a global change in the expression of epigenetic modifiers to enhance DNA accessibility. In this state of epigenetic plasticity, overexpression of lineage determination factors, and/or environmental cues and paracrine factors, can induce pluripotency, or can direct transdifferentiation to another somatic cell lineage. Accumulating evidence reveals that innate immune activation triggers the generation of reactive oxygen species and reactive nitrogen species, and that these free radicals are required for nuclear reprogramming to pluripotency or for transdifferentiation.
We have discovered a limb of innate immune signaling that regulates DNA accessibility, in part, by the action of free radicals to induce post-translational modification of epigenetic modifiers.
It is of scientific interest and clinical relevance to understand the mechanisms by which free radicals influence epigenetic plasticity, and how these mechanisms may be therapeutically modulated. Antioxid. Redox Signal. 00, 000-000.
山中伸弥和同事们通过生成诱导多能干细胞，推动了干细胞生物学和再生医学领域的发展。有证据表明，先天免疫信号的激活对于高效重编程为多能性以及在转分化过程中发生的核重编程至关重要。最新进展：我们已经表明，先天免疫信号会触发表观遗传修饰物表达的全局变化，以增强 DNA 可及性。在这种表观遗传可塑性状态下，谱系决定因子的过表达，以及/或环境线索和旁分泌因子，可以诱导多能性，或可以指导向另一个体体细胞谱系的转分化。越来越多的证据表明，先天免疫激活会触发活性氧和活性氮的产生，而这些自由基对于核重编程为多能性或转分化是必需的。
我们发现了先天免疫信号的一个分支，它通过自由基的作用部分调节 DNA 可及性，从而诱导表观遗传修饰物的翻译后修饰。
了解自由基如何影响表观遗传可塑性，以及这些机制如何在治疗上得到调节，这在科学上具有重要意义和临床相关性。抗氧化。氧化还原信号。00，000-000。
