International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Embryonic Stem Cells Lacking DNA Methyltransferases Differentiate into Neural Stem Cells that Are Defective in Self-Renewal

  • Bong Jong Seo (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Tae Kyung Hong (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Sang Hoon Yoon (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Jae Hoon Song (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Sang Jun Uhm (Department of Animal Science, Sangji University) ;
  • Hyuk Song (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Kwonho Hong (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Hans Robert Scholer (Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine) ;
  • Jeong Tae Do (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University)
  • Received : 2022.08.04
  • Accepted : 2022.09.30
  • Published : 2023.02.28
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Abstract

Background and Objectives: DNA methyltransferases (Dnmts) play an important role in regulating DNA methylation during early developmental processes and cellular differentiation. In this study, we aimed to investigate the role of Dnmts in neural differentiation of embryonic stem cells (ESCs) and in maintenance of the resulting neural stem cells (NSCs). Methods and Results: We used three types of Dnmt knockout (KO) ESCs, including Dnmt1 KO, Dnmt3a/3b double KO (Dnmt3 DKO), and Dnmt1/3a/3b triple KO (Dnmt TKO), to investigate the role of Dnmts in neural differentiation of ESCs. All three types of Dnmt KO ESCs could form neural rosette and differentiate into NSCs in vitro. Interestingly, however, after passage three, Dnmt KO ESC-derived NSCs could not maintain their self-renewal and differentiated into neurons and glial cells. Conclusions: Taken together, the data suggested that, although deficiency of Dnmts had no effect on the differentiation of ESCs into NSCs, the latter had defective maintenance, thereby indicating that Dnmts are crucial for self-renewal of NSCs.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) of the Republic of Korea (grant no. 2020R1A2C3007562) and Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET), funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (grant no. 322006-05-01-CG000).

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