Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain

Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin+ immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine. [Display omitted] •Oligodendrocyte progenitor cells (OPCs) disappeared and then repopulated in CAGG-iKO mice•Repopulated OPCs are partly derived from pericyte and/or mesenchymal cell population (PC/MC)•PC/MC-derived OPCs differentiate into MBP-expressing mature oligodendrocytes Đặng et al. show that oligodendrocyte progenitor cells (OPCs) are repopulated from pericyte and/or mesenchymal cell population (PC/MC) and from OPCs that escape Pdgfra inactivation. PC/MC-derived OPCs can differentiate into MBP-expressing mature oligodendrocytes. Our findings reveal a mechanism of homeostatic control of adult OPCs engaging dual cellular sources of adult OPC formation.