The effects of epigenetic modifiers on the differentiation of human dental pulp stem cells into neural progenitor-like cells

Abstract

Background: Human dental pulp stem cells (HDPSCs) may be differentiated into neural lineages. The main aim of the study was to assess the DNA demethylation and histone deacetylation inhibition on the differentiation of HDPSCs into neural progenitor-like cells (NPCs). Methods: HDPSCs were treated with 5-aza2′-deoxycytidine (AZA), DNA methylation inhibitor, and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) for 3 and 5 days followed by their differentiation into NPCs. The efficiency of the differentiation was evaluated by apoptosis, cellular proliferation, and relative expression of Nestin among the NPCs derived with the different treatments. Results: Five-day treatment of AZA was crucial for the more efficient demethylation of the HDPSCs. Analysis of the proliferation, apoptosis, and relative expression of the Nestin indicated that the AZA and SAHA neither enhance nor inhibit the differentiation of the HDPSCs into NPCs. Howevere, the expression of Nestin decreased at day 7 in NPCs derived with SAHAH treatment compared with NPCs derived with AZA treatmement. However, there was no difference in Nestin expression in any treatment-derived NPCs compared with control NPCs. All of the NPCs derived from all of the groups were able to differentiate into terminal neurons. Conclusion: Neither DNA demethylation nor the histone deacetylation has any main effects on proliferation and apoptosis during the differentiation of HDPSCs into NPCs. The only significant effect of the treatments was on the size of the NPCs at day 7; the SAHAH treatment had the smallest NPCs.