Research Information System
JOURNAL OF CELLULAR BIOCHEMISTRY, vol.123, no.2, pp.406-416, 2022 (SCI-Expanded, Scopus)
Intracellular and extracellular regulatory factors promote the potency and self-renewal property of stem cells. Methionine is fundamental for protein synthesis and regulation of methylation reactions. Specifically, methionine metabolism in embryonic and fetal development processes regulates gene expression profile/epigenetic identity of stem cells to achieve pluripotency and cellular functions. We aimed to reveal the differences in methionine metabolism of bone marrow (BM)-mesenchymal stem cells (MSCs), umbilical cord blood (UCB)-MSCs, and cancer stem cells (CSCs), which reflect different metabolic profiles and developmental stages of stem cells. UCB-MSC, BM-MSCs, and breast CSCs were treated with different doses (0, 10, 25, 50, and 100 mu M) of l-methionine. Cell surface marker and cell cycle assessment were performed by flow cytometry. Changes in gene expressions (OCT3/4, NANOG, DMNT1, DNMT3A, and DNMT3B, MAT2A, and MAT2B) with methionine supplementation were examined by quantitative real-time polymerase chain reaction and the changes in histone methylation (H3K4me3, H3K27me3) levels were demonstrated by western blot analysis. S-adenosylmethionine//S-adenosylhomocysteine (SAM/SAH) levels were evaluated by enzyme-linked immunosorbent assay. Cells that were exposed to different concentrations of l-methionine, were mostly arrested in the G0/G1 phase for each stem cell group. It was evaluated that BM-MSCs increased all gene expressions in the culture medium-containing 100 mu M methionine, in addition to SAM/SAH levels. On the other hand, UCB-MSCs were found to increase OCT3/4, NANOG, and DNMT1 gene expressions and decrease MAT2A and MAT2B expressions in the culture medium containing 10 mu M methionine. Moreover, an increase was observed in the He3K4me3 methylation profile. In addition, OCT3/4, NANOG, DNMT1, and MAT2B gene expressions in CSCs increased starting from the addition of 25 mu M methionine. An increase was determined in H3K4me3 protein expression at 50 and 100 mu M methionine-supplemented culture condition. This study demonstrates that methionine plays a critical role in metabolism and epigenetic regulation in different stem cell groups.