Abstract
Pluripotent stem cells (PSCs) hold great potential both in studies on developmental biology and clinical practice. Mitochondrial metabolism that encompasses pathways that generate ATP and produce ROS significantly differs between PSCs and somatic cells. Correspondingly, for quite a long time it was believed that the redox homeostasis in PSCs is also highly specific due to the hypoxic niche of their origin—within the pre-implantation blastocyst. However, recent research showed that redox parameters of cultivated PSCs have much in common with that of their differentiated progeny cells. Moreover, it has been proven that, similar to somatic cells, maintaining the physiological ROS level is critical for the regulation of PSC identity, proliferation, differentiation, and de-differentiation. In this review, we aimed to summarize the studies of redox metabolism and signaling in PSCs to compare the redox profiles of pluripotent and differentiated somatic cells. We collected evidence that PSCs possess metabolic plasticity and are able to adapt to both hypoxia and normoxia, that pluripotency is not strictly associated with anaerobic conditions, and that cellular redox homeostasis is similar in PSCs and many other somatic cells under in vitro conditions that may be explained by the high conservatism of the redox regulation system.
Highlights
Oxygen is a critical factor for the existence of all aerobic organisms
This transcription factor was identified as a mediator of the process of cellular pluripotency induction—the peak of its activation preceded the start of the OCT4 gene expression, and knockdown led to a decrease15inofthe number of formed induced pluripotent stem cells (iPSCs) colonies [146]
The activity of both p38α Mitogenic Stimulation vated protein kinases (MAPK) and FOXO1 signaling pathways is known to be dependent on the level of intracellular reactive oxygen species (ROS)
Summary
Oxygen is a critical factor for the existence of all aerobic organisms. Redox reactions, inherent in aerobic metabolism, are among the most abundant chemical interactions in living cells. High oxidizing ability of ROS causes extensive damage to cell macromolecules—proteins, lipids, and nucleic acids [11] In this regard, in the early studies of cellular redox homeostasis, the main attention was paid to the negative impact of oxidative distress induced by external factors or redox metabolism disorders. While the mitochondrial electron transport chain (ETC) is the main energy source in somatic cells, PSCs rely to a greater extent on anaerobic glycolysis even when cultured at atmospheric oxygen levels [23,24,25] Their mitochondria possess morphological and functional differences in comparison to the mitochondrial network of differentiated cells [24]. (1) what is in common between the redox profiles of PSCs and somatic cells; (2) which characteristics of redox homeostasis and signaling can be considered as distinctive features of PSCs, and which ones are highly conservative and similar in pluripotent cells and their differentiated descendants?
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