Efficient Remyelination Requires DNA Methylation
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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
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2373-2822