Head of the Research Laboratory University Hospital of Tübingen, Dept. of Oral and Maxillofacial Surgery, Baden-Wurttemberg, Germany
Abstract: Our present study reports on epigenetic changes identified after the differentiation of induced pluripotent stem cells (iPSCs) into mesenchymal stem cells (MSCs), referred to as iMSCs. A genome-wide DNA methylation analysis revealed that the methylation patterns of iMSCs closely resemble those of jaw periosteal cells (JPCs) but differ significantly from iPSCs. This was confirmed through heatmap analyses and principal component analysis (PCA), which showed that iMSCs are positioned between JPCs and iPSCs, with distinct methylation patterns specific to iMSCs. The functional implications of these epigenetic differences were investigated using gene enrichment analyses. The results indicated processes related to extracellular matrix organization and cell adhesion, explaining the distinct adhesion behavior of iMSCs compared to JPCs. Genes with specific methylation patterns for iMSCs, JPCs, or iPSCs were identified, including for instance COL4A2 for iMSCs, COL1A1 for JPCs and the tumor suppressor gene DLC1 for iPSCs. Furthermore, we could confirm that biological aging can be assessed using DNA methylation clocks (DNAm clocks). Reprogrammed iPSCs showed epigenetic rejuvenation with an age close to zero, which was maintained after differentiation into iMSCs. This result highlights the rejuvenating effects of cell reprogramming. In summary, the findings of our study demonstrate that iMSCs exhibit functional and epigenetic similarities to JPCs while also possessing specific differences. These insights could influence future applications in regenerative medicine, particularly in the development of rejuvenated cell therapies.
Funding Source: This study was partially funded by German Research Foundation, grant number AL 1486/6-1/AV 133/7-1.
