Efficient Remyelination Requires DNA Methylation

Moyon, Sarah, Ma, Dan, Huynh, Jimmy L., Coutts, David J.c., Zhao, Chao, Casaccia, Patrizia and Franklin, Robin J.m. (2017). Efficient Remyelination Requires DNA Methylation. eNeuro, 4 (2),

Abstract

Oligodendrocyte progenitor cells (OPCs) are the principal source of new myelin in the central nervous system. A better understanding of how they mature into myelin-forming cells is of high relevance for remyelination. It has recently been demonstrated that during developmental myelination, the DNA methyltransferase 1 (DNMT1), but not DNMT3A, is critical for regulating proliferation and differentiation of OPCs into myelinating oligodendrocytes (OLs). However, it remains to be determined whether DNA methylation is also critical for the differentiation of adult OPCs during remyelination. After lysolecithin-induced demyelination in the ventrolateral spinal cord white matter of adult mice of either sex, we detected increased levels of DNA methylation and higher expression levels of the DNA methyltransferase DNMT3A and lower levels of DNMT1 in differentiating adult OLs. To functionally assess the role of DNMT1 and DNMT3 in adult OPCs, we used mice with inducible and lineage-specific ablation of Dnmt3a and/or Dnmt1 (i.e., Plp-creER(t);Dnmt3a-flox, Plp-creER(t);Dnmt1-flox, Plp-creER(t);Dnmt1-flox;Dnmt3a-flox). Upon lysolecithin injection in the spinal cord of these transgenic mice, we detected defective OPC differentiation and inefficient remyelination in the Dnmt3a null and Dnmt1/Dnmt3a null mice, but not in the Dnmt1 null mice. Taken together with previous results in the developing spinal cord, these data suggest an age-dependent role of distinct DNA methyltransferases in the oligodendrocyte lineage, with a dominant role for DNMT1 in neonatal OPCs and for DNMT3A in adult OPCs.

Publication DOI: https://doi.org/10.1523/ENEURO.0336-16.2017
Divisions: Aston Medical School
Additional Information: Copyright © 2017 Moyon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed
Uncontrolled Keywords: Adult oligodendrocyte progenitor cells; DNA methylation; remyelination
Full Text Link: http://eneuro.s ... RO.0336-16.2017
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Published Date: 2017-03-20
Authors: Moyon, Sarah
Ma, Dan ( 0000-0001-8628-8954)
Huynh, Jimmy L.
Coutts, David J.c.
Zhao, Chao
Casaccia, Patrizia
Franklin, Robin J.m.

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