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

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Listed:
  • 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
    National Yang-Ming University)

  • John Wang

    (China Medical University Hospital)

  • Cheng-Ming Chuong

    (China Medical University Hospital
    University of Southern California)

  • Shih-Chieh Hung

    (China Medical University
    China Medical University Hospital
    Academia Sinica)

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.

Suggested Citation

  • Wen-Ching Shen & Yung-Chih Lai & Ling-Hui Li & Kolin Liao & Hung-Chang Lai & Shou-Yen Kao & John Wang & Cheng-Ming Chuong & Shih-Chieh Hung, 2019. "Methylation and PTEN activation in dental pulp mesenchymal stem cells promotes osteogenesis and reduces oncogenesis," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10197-x
    DOI: 10.1038/s41467-019-10197-x
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    Cited by:

    1. Gonggong Lu & Yang Xu & Quanying Liu & Manyu Chen & Huan Sun & Peilei Wang & Xing Li & Yuxiang Wang & Xiang Li & Xuhui Hui & En Luo & Jun Liu & Qing Jiang & Jie Liang & Yujiang Fan & Yong Sun & Xingdo, 2022. "An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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