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

Wen-Ching Shen, Yung-Chih Lai, Ling-Hui Li, Kolin Liao, Hung-Chang Lai, Shou-Yen Kao, John Wang, Cheng-Ming Chuong and Shih-Chieh Hung ()
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Wen-Ching Shen: China Medical University
Yung-Chih Lai: China Medical University Hospital
Ling-Hui Li: Academia Sinica
Kolin Liao: China Medical University
Hung-Chang Lai: Taipei Veterans General Hospital
Shou-Yen Kao: Taipei Veterans General Hospital
John Wang: China Medical University Hospital
Cheng-Ming Chuong: China Medical University Hospital
Shih-Chieh Hung: China Medical University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10197-x

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