Pladevall-Morera David, Zylicz Jan J
Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, Denmark.
Front Cell Dev Biol. 2022 Oct 10;10:1014498. doi: 10.3389/fcell.2022.1014498. eCollection 2022.
Cellular metabolism is a complex network of biochemical reactions fueling development with energy and biomass; however, it can also shape the cellular epigenome. Indeed, some intermediates of metabolic reactions exert a non-canonical function by acting as co-factors, substrates or inhibitors of chromatin modifying enzymes. Therefore, fluctuating availability of such molecules has the potential to regulate the epigenetic landscape. Thanks to this functional coupling, chromatin can act as a sensor of metabolic changes and thus impact cell fate. Growing evidence suggest that both metabolic and epigenetic reprogramming are crucial for ensuring a successful embryo development from the zygote until gastrulation. In this review, we provide an overview of the complex relationship between metabolism and epigenetics in regulating the early stages of mammalian embryo development. We report on recent breakthroughs in uncovering the non-canonical functions of metabolism especially when re-localized to the nucleus. In addition, we identify the challenges and outline future perspectives to advance the novel field of epi-metabolomics especially in the context of early development.
细胞代谢是一个由生物化学反应构成的复杂网络，为发育提供能量和生物质；然而，它也能够塑造细胞表观基因组。实际上，一些代谢反应的中间产物通过作为染色质修饰酶的辅助因子、底物或抑制剂发挥非经典功能。因此，此类分子可用性的波动有可能调节表观遗传格局。得益于这种功能耦合，染色质可作为代谢变化的传感器，从而影响细胞命运。越来越多的证据表明，代谢重编程和表观遗传重编程对于确保从受精卵到原肠胚形成的胚胎成功发育都至关重要。在这篇综述中，我们概述了代谢与表观遗传学在调节哺乳动物胚胎发育早期阶段的复杂关系。我们报道了在揭示代谢的非经典功能方面的最新突破，尤其是当代谢重新定位到细胞核时。此外，我们确定了挑战并概述了未来前景，以推动表观代谢组学这一新兴领域的发展，特别是在早期发育的背景下。
