Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia.
Int J Mol Sci. 2022 Aug 26;23(17):9691. doi: 10.3390/ijms23179691.
Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; and pathologies, including cardiovascular diseases, neurodegeneration, and cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying ploidy-related adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs of embryonality. Chromatin opening switches on genes with bivalent chromatin domains that promote adaptation via rapid induction in response to signals of stress or morphogenesis. Therefore, stress-associated polyploidy can activate Myc proto-oncogenes, which further promote chromatin opening. Moreover, Myc proto-oncogenes can trigger polyploidization de novo and accelerate genome accumulation in already polyploid cells. As a result of these cooperative effects, polyploidy can increase the ability of cells to search for adaptive states of cellular programs through gene regulatory network rewiring. This ability is manifested in epigenetic plasticity associated with traits of stemness, unicellularity, flexible energy metabolism, and a complex system of DNA damage protection, combining primitive error-prone unicellular repair pathways, advanced error-free multicellular repair pathways, and DNA damage-buffering ability. These three features can be considered important components of the increased adaptability of polyploid cells. The evidence presented here contribute to the understanding of the nature of stress resistance associated with ploidy and may be useful in the development of new methods for the prevention and treatment of cardiovascular and oncological diseases.
多倍体细胞在进化、发育和病理学（包括心血管疾病、神经退行性疾病和癌症）中表现出生物可塑性和应激适应能力。多倍体相关优势的性质尚不完全清楚。在这里，我们总结了与多倍体相关适应特征相关的分子机制的文献。多倍体可以通过染色质开放来调节基因表达，重新激活胚胎发生的古老进化程序。染色质开放会开启具有双价染色质结构域的基因，通过快速诱导来应对应激或形态发生的信号，从而促进适应。因此，与应激相关的多倍体可以激活 Myc 原癌基因，这进一步促进了染色质的开放。此外，Myc 原癌基因可以引发多倍体的从头发生，并加速已经多倍体化的细胞中的基因组积累。由于这些协同效应，多倍体可以通过基因调控网络重连增加细胞搜索适应性细胞程序状态的能力。这种能力表现在与干性、单细胞性、灵活的能量代谢和复杂的 DNA 损伤保护系统相关的表观遗传可塑性中，结合了原始易错的单细胞修复途径、先进的无差错多细胞修复途径和 DNA 损伤缓冲能力。这三个特征可以被认为是多倍体细胞适应能力增强的重要组成部分。本文提供的证据有助于理解与多倍体相关的应激抗性的本质，并可能有助于开发预防和治疗心血管和肿瘤疾病的新方法。
