Dental Pulp Stem Cells Model Early Life and Imprinted DNA Methylation Patterns

Area of Science:

• Epigenetics
• Stem Cell Biology
• Genomics

Background:

• Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are commonly used to model early embryonic epigenomic stages.
• However, ESCs and iPSCs do not accurately represent DNA methylation levels found in preimplantation embryos, particularly regarding partially methylated domains (PMDs).
• Abnormally high DNA methylation in ESCs and iPSCs contrasts with levels in the inner cell mass (ICM) and placenta.

Purpose of the Study:

• To investigate dental pulp stem cells (DPSCs) as an alternative model for epigenomic studies.
• To compare the DNA methylation patterns of DPSCs with those of ESCs, iPSCs, and other human cell lines.
• To assess the utility of DPSCs in modeling epigenetic alterations in neurodevelopmental disorders, specifically chromosome 15q11.2-q13.3 maternal duplication syndrome (Dup15q).

Main Methods:

• Whole genome bisulfite sequencing (WGBS) was employed to analyze DNA methylation patterns.
• Principal component analysis (PCA) was used to compare methylation profiles across different cell types.
• Differential methylation region (DMR) analysis was performed on DPSC samples from Dup15q patients and controls.

Main Results:

• DPSCs exhibit PMDs and their methylome more closely resembles the ICM and placenta compared to iPSCs and ESCs.
• DPSC methylation patterns clustered more closely with neural stem cell types and placenta than with iPSCs, ESCs, or other human cell lines.
• DMR analysis in Dup15q-derived DPSCs identified expected hypermethylation at the imprinting control region, hypomethylation over SNORD116, and novel DMRs in 147 genes, including autism candidate genes.

Conclusions:

• DPSCs provide a more accurate model for studying DNA methylation in early human development than ESCs and iPSCs.
• DPSCs are suitable for modeling epigenetic differences associated with neurodevelopmental disorders.
• These findings support the use of DPSCs for epigenomic and functional studies of human neurodevelopmental disorders.