IPSC and free radicals

A key factor in reprogramming mature cells into stem cells has been discovered

Oleg Lischuk, N+1

American scientists have discovered one of the key factors responsible for reprogramming mature somatic cells into induced pluripotent stem cells (iPSC). It turned out to be an optimal balance of reactive oxygen species (ROS, ROS) at different stages of cellular transformation. The results of the study are published in the journal Cell Reports (Zhou et al., Optimal ROS Signaling Is Critical for Nuclear Reprogramming).

When somatic cells are reprogrammed, metabolism switches from oxidative phosphorylation to glycolysis. iPSC has fewer mitochondria, they synthesize less ATP and develop better at low oxygen levels. Accordingly, they synthesize fewer ROS (free radical molecules with high reactivity, which are formed during tissue respiration, have a damaging effect on DNA and other macromolecules, but, at the same time, are mediators of some signaling pathways in the cell). iPSCs are also more sensitive to ROS-induced apoptosis (natural death).

The staff of the Methodist Research Institute of Houston obtained iPSC from fibroblasts of mouse embryos and analyzed the metabolism of ROS in them. It turned out that at the early stages of reprogramming (on the second day) in cells under the influence of the universal transcription factor NF-kB, the expression of enzymes of the Nox family (nicotinadenine dinucleotide phosphate oxidases, NADP oxidases), which are responsible for the formation of ROS, increases tenfold. Accordingly, the level of ROS at this time also turned out to be significantly increased.

During the maturation of iPSC (by the sixth day), the level of Nox and ROS gradually returns to normal levels. At the same time, the expression of antioxidant superoxide dismutase (SOD1/2) and glutathione peroxidase (Gpx) genes neutralizing free radicals increases. As a result, in mature iPSCs, the level of ROS is reduced by half compared to the original fibroblasts.

The researchers conducted a series of experiments during which they reduced and increased the levels of ROS in reprogrammed cells by pharmacological and genetic methods. It turned out that both increased and decreased concentrations of ROS led to a significant (up to 50 percent) decrease in the amount of iPSC in culture. Thus, maintaining an optimal balance of ROS and its dynamics in the process of cell transformation plays a key role in obtaining iPSC.

Diagram from an article in Cell Reports – VM.

Induced pluripotent stem cells can develop into different types of cells of the body similarly to embryonic stem cells, which makes them indispensable in the development of different types of cell therapy. John Gurdon and Shinya Yamanaka received the Nobel Prize in 2012 for creating the technology for their production.

Portal "Eternal youth" http://vechnayamolodost.ru  22.04.2016