Differential requirement of cyclin-dependent kinase 2 for oligodendrocyte progenitor cell proliferation and differentiation

During development, the majority of oligodendrocyte progenitor cells (OPCs) undergo a limited period of proliferation, before cell cycle exit and terminal differentiation into postmitotic myelinating oligodendrocytes [1]. However, a population of slowly dividing OPCs persists throughout the adult CNS [2-4] and there is growing interest concerning the signals influencing proliferation and differentiation of these progenitors [5]. Adult OPCs share common features with perinatal OPCs such as the expression of NG2 and PDGFRα and the ability to differentiate into oligodendrocytes but also astrocytes and neurons [4,6-11]. However, their cell cycle length and rate of differentiation are slower comparing with perinatal OPCs. They exhibit precise proliferative capacity defined as intrinsic timer concept with each cell dividing invariably 8 times in culture before exiting the cell cycle and differentiating [1,12]. Moreover, despite their low oligodendrogenic potential under physiological conditions, adult OPCs can be reactivated in terms of proliferation, migration and differentiation leading to remyelination after CNS white matter insults [4,13-15]. Therefore they are considered as major targets for therapeutical strategies. OPCs can also be generated from the subventricular zone (SVZ) in the adult forebrain both under physiological conditions [16,17] and after demyelination in rodents and human brain [18-21]. After demyelination of the adult brain, SVZ-derived OPCs are recruited to the lesions and contribute to periventricular remyelination [22,23]. All these specificities make the study of the cell cycle regulation in this cell type of great interest.Cell proliferation is a key phenomenon during development and repair. It is regulated by complex extrinsic and intrinsic mechanisms involving cyclin-dependent kinases (Cdks), a family of serine/threonine kinases that represents the core of the cell cycle machinery. Successive waves of Cdk activity control initiation and progre