Glutathione - a'barometer' in the differentiation process of stem cells

In recent years, the role of glutathione in regulating stem cell differentiation by participating in the energy metabolism of stem cells has become increasingly clear.

Hypoxic environment can protect stem cells from the production and accumulation of harmful reactive oxygen species. Stem cells can effectively maintain their self-renewal ability and cell stemness in a microenvironment with low levels of reactive oxygen species, while high levels of reactive oxygen species will not only hinder stem cell growth. Self-renewal and promotes stem cell differentiation.

In fact, in order to meet energy demands and mitigate the risk of ROS-dependent DNA damage, pluripotent stem cells mainly rely on the glycolytic metabolic pathway for energy compared to their differentiated cells. Pluripotent stem cells enhance NADPH production through the glycolysis and pentose phosphate pathways. As a key factor in maintaining thioredoxin and reduced glutathione, NADPH ensures the ability of stem cells to scavenge reactive oxygen species by the antioxidant system represented by reduced glutathione, and protects the integrity of stem cell genomes.

With the progress of differentiation, glycolysis is gradually replaced by oxidative metabolism, the expression of glycolysis-related genes is inhibited, the level of reduced glutathione is down-regulated, and reactive oxygen species generated during mitochondrial respiration become the main source of DNA damage. . The damage generated by the accumulation of reactive oxygen species then further affects the self-renewal and differentiation capacity of stem cells. During the differentiation process, reduced glutathione is continuously inhibited, making it difficult to maintain the redox state of stem cells, thereby aggravating stem cell differentiation.

In conclusion, whether through reduced glutathione-related enzymes and transcription factors involved in the regulation of stem cell differentiation, or through cellular energy metabolism mechanisms, it is indicated that the level of reduced glutathione changes before and after stem cell differentiation. And the impact, predictably, is that glutathione acts as a "barometer" during stem cell differentiation.

Article source: Huang Chenwei, Fei Yankang, Zhu Mengmei, Li Penghao, Yu Bing. The important role of glutathione in stem cell "stemness" and regulation [J]. Chinese Tissue Engineering Research, 2022, 26(07): 1119-1124.

Tag: Glutathione

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