Epigenetic Signatures of Dental Stem Cells: Insights into DNA Methylation and Noncoding RNAs
Source abstract
Abstract
Tooth development (odontogenesis) is regulated by interactions between epithelial and mesenchymal tissues through signaling pathways such as Bone Morphogenetic Protein (BMP), Wingless-related integration site (Wnt), Sonic Hedgehog (SHH), and Fibroblast Growth Factor (FGF). Mesenchymal stem cells (MSCs) derived from dental tissues—including dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs)—show promise for regenerative dentistry due to their multilineage differentiation potential. Epigenetic regulation, particularly DNA methylation, is hypothesized to underpin their distinct regenerative capacities. This study reanalyzed publicly available DNA methylation data generated with Illumina Infinium HumanMethylation450 BeadChip arrays (450K arrays) from DPSCs, PDLSCs, and DFPCs. High-confidence CpG sites were selected based on detection p-values, probe variance, and genomic annotation. Principal Component Analysis (PCA) and hierarchical clustering identified distinct methylation profiles. Functional enrichment analyses highlighted biological processes and pathways associated with specific methylation clusters. Noncoding RNA analysis was integrated to construct regulatory networks linking DNA methylation patterns with key developmental genes. Distinct epigenetic signatures were identified for DPSCs, PDLSCs, and DFPCs, characterized by differential methylation across specific genomic contexts. Functional enrichment revealed pathways involved in odontogenesis, osteogenesis, and neurodevelopment. Network analysis identified central regulatory nodes—including genes, such as PAX6, FOXC2, NR2F2, SALL1, BMP7, and JAG1—highlighting their roles in tooth development. Several noncoding RNAs were also identified, sharing promoter methylation patterns with developmental genes and being implicated in regulatory networks associated with stem cell differentiation and tissue-specific function. Altogether, DNA methylation profiling revealed that distinct epigenetic landscapes underlie the developmental identity and differentiation potential of dental-derived mesenchymal stem cells. This integrative analysis highlights the relevance of noncoding RNAs and regulatory networks, suggesting novel biomarkers and potential therapeutic targets in regenerative dentistry and orthodontics.
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Research context
OpenAlex topics: Epigenetics and DNA Methylation · Cancer-related gene regulation · dental development and anomalies
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Odontostomatological and Maxillofacial Sciences, Sapienza University of Rome, 00161 Rome, Italy
Computational Biology and Bioinformatics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Laboratory of Bioinformatics, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy
Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, 00185 Rome, Italy
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
Funding
Sapienza University of Rome
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