Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy.
Molecules. 2018 Jan 30;23(2):282. doi: 10.3390/molecules23020282.
In this review, we described different factors that modulate pluripotency in stem cells, in particular we aimed at following the steps of two large families of miRNAs: the miR-200 family and the miR-302 family. We analyzed some factors tuning stem cells behavior as TGF-β, which plays a pivotal role in pluripotency inhibition together with specific miRNAs, reactive oxygen species (ROS), but also hypoxia, and physical stimuli, such as ad hoc conveyed electromagnetic fields. TGF-β plays a crucial role in the suppression of pluripotency thus influencing the achievement of a specific phenotype. ROS concentration can modulate TGF-β activation that in turns down regulates miR-200 and miR-302. These two miRNAs are usually requested to maintain pluripotency, while they are down-regulated during the acquirement of a specific cellular phenotype. Moreover, also physical stimuli, such as extremely-low frequency electromagnetic fields or high-frequency electromagnetic fields conveyed with a radioelectric asymmetric conveyer (REAC), and hypoxia can deeply influence stem cell behavior by inducing the appearance of specific phenotypes, as well as a direct reprogramming of somatic cells. Unraveling the molecular mechanisms underlying the complex interplay between externally applied stimuli and epigenetic events could disclose novel target molecules to commit stem cell fate.
在这篇综述中，我们描述了调节干细胞多能性的不同因素，特别是我们旨在遵循两个大型 miRNA 家族的步骤：miR-200 家族和 miR-302 家族。我们分析了一些调节干细胞行为的因素，如 TGF-β，它与特定的 miRNAs、活性氧 (ROS) 一起在多能性抑制中发挥关键作用，还包括缺氧和物理刺激，如专门传递的电磁场。TGF-β 在抑制多能性方面起着至关重要的作用，从而影响特定表型的获得。ROS 浓度可以调节 TGF-β 的激活，从而下调 miR-200 和 miR-302。这两种 miRNAs 通常被要求维持多能性，而在获得特定的细胞表型时则下调。此外，物理刺激，如极低频电磁场或高频电磁场通过无线电不对称传递器 (REAC) 传递，以及缺氧，都可以通过诱导特定表型的出现以及体细胞的直接重编程，对干细胞行为产生深远影响。揭示外部施加的刺激和表观遗传事件之间复杂相互作用的分子机制，可以揭示新的靶分子来决定干细胞的命运。
