TEN ELEVEN TRANSLOCATION 2 (TET2) Improves the Adipogenic Potential of Dental Pulp Stem Cells

Although mesenchymal stem cells (MSCs) are the major source of adipocytes, adipogenesis is a highly complex process whose mechanisms driving adipocyte origin and development remain poorly understood. Previous findings by our group have shown that different MSCs from the oral cavity displayed differential expression of TET2, a key regulator of DNA methylation, during adipogenic induction. Therefore, we proposed to evaluate the effects of the overexpression of TET2 on the adipogenic response of a cell line with a low natural commitment to this cell fate. We used human dental pulp cells, which were characterized through flow cytometry for mesenchymal markers, analysis of stemness-related genes (OCT4, NANOG, SOX2, KLF4 and c-MYC) and trilineage capacity. The characterized cells were transfected with TET2 and induced to adipogenesis for 21 days. Our results show that TET2-overexpressing cells (pTET2-OE cells) exhibit an earlier adipogenic response. In addition, pTET2-OE cells induced more than 4-, 2.5-, 30-, and 50-fold expression of the adipogenic markers PPAR & gamma;, ADIPOQ, FABP4, and LPL, respectively. Our findings suggest that TET2 overexpression could induce demethylation of the PPAR & gamma; locus, the master regulator of adipogenesis, and of the other adipogenic genes, improving the transition of dental pulp stem cells toward adipogenic commitment.