Deciphering the Epigenetic Code of Stem Cells Derived From Dental Tissues

Abstract

Stem cells derived from dental tissues (DSCs) exhibit multipotent regenerative potential in pioneering tissue engineering regimens. The multipotency of DSCs is critically regulated by an intricate range of factors, of which the epigenetic influence is considered vital. To gain a better understanding of how epigenetic alterations are involved in the DSC fate determination, the present review overviews the current knowledge relating to DSC epigenetic modifications, paying special attention to the landscape of epigenetic modifying agents as well as the related signaling pathways in DSC regulation. In addition, insights into the future opportunities of epigenetic targeted therapies mediated by DSCs are discussed to hold promise for the novel therapeutic interventions in future translational medicine.

The Role of Epigenetic in Dental and Oral Regenerative Medicine by Different Types of Dental Stem Cells: A Comprehensive Overview

“…Also, DNA methylation modulates the DSCs' odontogenic differentiation by regulating osteogenic differentiation. TET1 inhibited DPSC proliferation and odontogenic differentiation, indicating that demethylation of DNA affects dental tissue regeneration [ 3 ]. Epigenetic mechanisms such as methylation of cytosine remain in DNA, changing the posttranslational histone cores, and intercepting transcriptional information and translation can activate epigenetic mechanisms at different levels ( Figure 1 ).…”

“…Lysine demethylase 3B (KDM3B) increases osteogenic differentiation of SCAPs. Lysine demethylase 4B (KDM4B) removes H3K9 trimethylation via attaching to DLX stimulators, contributing to aim gene expression [ 3 ]. It was reported by Yang et al that DLX5 and KDM4B are modulated by SCAP-positive feedback loop.…”

“…DSCs positively expressed markers related to MSCs in vitro containing cluster of differentiation (CD)146, 105, 90, 73, 59, 44, 29, 13, and STRO-1. Contrarily, some hematopoietic markers (CD45, 34, 31, and 14) were negatively expressed [ 3 ]. In many tissues, including the dental pulp, the renewal of stem cells depends on epigenetic mechanisms to histone proteins.…”

“…As a result of DNMTs, the 5-methylcytosine existing in CpG islands can be methylated into DNMTs. It is also possible to reverse DNA methylation using enzymes from the ten-eleven translocation (TET) family [ 3 ]. DNA methylation regulates the expression of phosphatase and tensin homolog (PTEN), which contributes to tumor progression and resistance to chemotherapy.…”

“…A variety of internal modifications of messenger RNA (mRNA), such as N 6 -methyladenosine (m6A), N 1 -methyladenosine (m1A), 5-methylcytosine, and 5-hydroxymethylcytosine, are crucial to mRNA stability. Methyltransferases catalyze the transformation of m6A from one state to another, while demethylases reverse it [ 3 ]. DNA methylation and posttranslational modifications are the most studied epigenetic modifications, particularly acetylation, methylation, and phosphorylation of histone proteins.…”