For the maintenance and repair of CNS myelin, oligodendrocyte progenitor cells (OPCs) continue to proliferate and maturate into myelin-forming oligodendrocytes (OLs) in adult CNS. PDGFR-α is expressed in OPCs and is essential for the development of these cells. The present study was aimed to understand the cell turnover of adult OPCs and the role of PDGFR-α involved. PDGFR-α gene knockout (KO) was induced by giving tamoxifen (TM) to the adult mutant mouse harboring ubiquitous promoter-driven Cre recombinase. Few days after gene KO, the OPCs that show immature immuno-phenotype as positive PDGFR-α/NG2 staining mostly disappeared from entire part of CNS of the mutant. Subsequently, OPCs simultaneously repopulated at multiple sites of brain, and almost restored OPCs populations after 4 weeks. Within this sequence of events, we found that OPCs were transiently depleted because pre-existing OPCs subjected to gene KO quickly differentiated toward myelin-forming OLs. On the other hand, the repopulated OPCs were positive for mesenchymal stem cell (MSC) markers, and were suggested to originate from MSCs that escaped from TM-induced gene KO and were associated with blood vessels and meninges in lineage-tracing studies using GFP-expressing viral infection. Genetic mapping showed few MSCs were recruited from meninges and differentiated into OPCs in PDGFR-α preserving control CNS as well. It was shown that PDGFR-α was essential to maintain the adult OPCs, and that MSCs were potent cellular resources that can be recruited and can transdifferentiate into OPCs.