- Dimethyl sulfoxide (DMSO), beyond its well-known applications as a solvent and cryoprotectant, has significant effects on the epigenetic landscape of cells, including stem cells. Its influence on epigenetic regulation is of growing interest, particularly because epigenetic mechanisms—such as DNA methylation, histone modifications, and chromatin remodeling—are crucial in controlling gene expression, cell identity, and lineage specification.
- One of the key ways DMSO impacts epigenetic regulation is through its ability to alter DNA methylation patterns. DNA methylation, especially at cytosine residues in CpG dinucleotides, is a major epigenetic mechanism that silences gene expression. Studies have shown that DMSO exposure can lead to global hypomethylation or, in some cases, hypermethylation at specific loci, thereby altering the expression of key regulatory genes. These changes can disrupt normal cell function or trigger differentiation in stem cells by modifying transcriptional programs.
- DMSO also affects histone modification states. Histones are subject to various post-translational modifications, such as acetylation, methylation, and phosphorylation, which collectively determine chromatin accessibility and gene expression. DMSO has been reported to influence histone acetylation and methylation levels, potentially by modulating the activity or expression of histone-modifying enzymes such as histone deacetylases (HDACs) and methyltransferases. These changes can impact the open or closed state of chromatin, influencing whether specific genes are actively transcribed or silenced.
- Furthermore, DMSO has been implicated in modulating the expression of non-coding RNAs, including microRNAs (miRNAs), which play regulatory roles in epigenetic control. Alterations in miRNA expression profiles upon DMSO treatment may have downstream effects on the stability and translation of mRNA targets, further contributing to changes in gene expression and cellular behavior.
- In stem cell research, these epigenetic effects are particularly important. Since stem cells rely heavily on tightly controlled epigenetic states to maintain pluripotency or commit to specific lineages, DMSO-induced epigenetic changes can inadvertently shift their developmental potential. While this property can be harnessed to induce differentiation under certain conditions, it can also introduce variability and unpredictability in experimental outcomes, especially in high-throughput screens or regenerative medicine applications.
- Given these impacts, the use of DMSO in experiments involving epigenetic readouts requires careful consideration. Researchers must be aware of DMSO’s potential to act as an epigenetic modifier and include proper controls to distinguish its effects from those of the compounds under investigation. In therapeutic contexts, such as stem cell transplantation, minimizing residual DMSO is critical to avoid unintended epigenetic reprogramming that could affect cell safety or efficacy.
