Oligodendrocyte precursor cells (OPCs) are one of the major cell types in cerebral white matter, which are generated from neural progenitor cells (NPCs) and give rise to mature oligodendrocytes. Although past studies have extensively examined how OPCs are generated from NPCs and how OPCs differentiate into mature oligodendrocytes, the underlying mechanisms remain unelucidated. In particular, the roles of DNA methylation and the related enzymes DNA methyltransferases (DNMTs) in oligodendrocyte lineage cells are still mostly unknown, although DNA methylation plays a critical role in cell fate decision in multiple cell types. Recently, OPCs were proposed as a promising source of cell-based therapy for patients with oligodendrocyte/myelin damage. Therefore, understanding the mechanisms underlying the involvement of DNMTs in OPCs would help to develop an approach for the efficient preparation of OPCs for cell-based therapy. As a part of the special issue for \"Stem Cell Therapy\" in Brain Research, this mini-review article first overviews the potential for clinical application of OPCs for cell-based therapy, and then summarizes the key findings of DNMT roles in OPCs, focusing on OPC generation and differentiation.

One of the unsolved problems in the research field of oligodendrocyte (OL) development has been the site(s) of origin of optic nerve OLs and its precursor cells (OPCs). It is generally accepted that OLs in the optic nerve are derived from the brain, and thus optic nerve OLs are immigrant cells. We previously demonstrated the brain origin of optic nerve OPCs in chick embryos. However, the site of optic nerve OPC origin has not been examined experimentally in developing rodents for the past two decades. We have recently reported that optic nerve OPCs in mice arise in the preoptic area by E12.5 and gradually migrate caudally and enter the optic nerve. These OPCs give rise to myelinating OLs in the optic nerve in the postnatal or adult stages. Surprisingly, there are species differences with respect to the origin of optic nerve OPCs between chicks and mice. Here, we summarize the site of OPC origin in the optic nerve based on our own previous and recent results, and discuss possible mechanisms underlying these species differences.