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Nat Commun. 2019 May 20;10(1):2226. doi: 10.1038/s41467-019-10197-x.

Methylation and PTEN activation in dental pulp mesenchymal stem cells promotes osteogenesis and reduces oncogenesis.

Author information

1
Drug Development Center, Institute of New Drug Development, Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan.
2
Integrative Stem Cell Center, Department of Orthopaedics, China Medical University Hospital, Taichung, 404, Taiwan.
3
Institute of Biomedical Sciences, Academia Sinica, Taipei, 105, Taiwan.
4
Department of Stomatology, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
5
Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, 112, Taiwan.
6
Department of Pathology, China Medical University Hospital, Taichung, 404, Taiwan.
7
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
8
Drug Development Center, Institute of New Drug Development, Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan. hung3340@gmail.com.
9
Integrative Stem Cell Center, Department of Orthopaedics, China Medical University Hospital, Taichung, 404, Taiwan. hung3340@gmail.com.
10
Institute of Biomedical Sciences, Academia Sinica, Taipei, 105, Taiwan. hung3340@gmail.com.

Abstract

Lineage commitment and tumorigenesis, traits distinguishing stem cells, have not been well characterized and compared in mesenchymal stem cells derived from human dental pulp (DP-MSCs) and bone marrow (BM-MSCs). Here, we report DP-MSCs exhibit increased osteogenic potential, possess decreased adipogenic potential, form dentin pulp-like complexes, and are resistant to oncogenic transformation when compared to BM-MSCs. Genome-wide RNA-seq and differential expression analysis reveal differences in adipocyte and osteoblast differentiation pathways, bone marrow neoplasm pathway, and PTEN/PI3K/AKT pathway. Higher PTEN expression in DP-MSCs than in BM-MSCs is responsible for the lineage commitment and tumorigenesis differences in both cells. Additionally, the PTEN promoter in BM-MSCs exhibits higher DNA methylation levels and repressive mark H3K9Me2 enrichment when compared to DP-MSCs, which is mediated by increased DNMT3B and G9a expression, respectively. The study demonstrates how several epigenetic factors broadly affect lineage commitment and tumorigenesis, which should be considered when developing therapeutic uses of stem cells.

PMID:
31110221
PMCID:
PMC6527698
DOI:
10.1038/s41467-019-10197-x
[Indexed for MEDLINE]
Free PMC Article

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