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Embryonic Stem Cells Lacking DNA Methyltransferases Differentiate into Neural Stem Cells that Are Defective in Self-Renewal
International Journal of Stem Cells
Published online October 31, 2022;  
© 2022 Korean Society for Stem Cell Research.

Bong Jong Seo1,*, Tae Kyung Hong1,2,*, Sang Hoon Yoon1,2, Jae Hoon Song1, Sang Jun Uhm3, Hyuk Song1, Kwonho Hong1, Hans Robert Schöler4, Jeong Tae Do1,2

1Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul, Korea
23D Tissue Culture Research Center, Konkuk University, Seoul, Korea
3Department of Animal Science, Sangji University, Wonju, Korea
4Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany
Correspondence to: Jeong Tae Do
Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea
Tel: +82-2-450-3673, Fax: +82-2-455-1044
E-mail: dojt@konkuk.ac.kr
*These authors contributed equally to this work.
Received August 4, 2022; Revised September 27, 2022; Accepted September 30, 2022.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 : Neural stem cells, DNA methyltransferases, Neuronal and glial differentiation