This study investigates the heterogeneity of oligodendrocytes in the mouse juvenile and adult central nervous system (CNS) using single-cell RNA sequencing. Researchers analyzed 5072 cells from ten regions of the CNS and identified twelve distinct populations, ranging from Pdgfra+ oligodendrocyte precursors (OPCs) to mature oligodendrocytes. The differentiation process was found to be continuous, with initial stages similar across the juvenile CNS, while mature oligodendrocyte subsets were enriched in specific regions in the adult brain. Newly-formed oligodendrocytes were found to be resident in the adult CNS and responsive to complex motor learning. A second Pdgfra+ population, distinct from OPCs, was found along vessels, indicating a vascular and leptomeningeal cell population (VLMCs). The study reveals the dynamics of oligodendrocyte differentiation and maturation, highlighting their transcriptional heterogeneity. Oligodendrocytes ensheath axons, enabling rapid saltatory conduction and providing metabolic support to neurons. The study identified distinct cell populations, including differentiation-committed oligodendrocyte precursors (COPs), newly-formed oligodendrocytes (NFOL1-2), and myelin-forming oligodendrocytes (MFOL1-2). These populations exhibited unique gene expression patterns, with some enriched in lipid biosynthesis and myelination genes, while others were enriched in synapse-related genes. The study also identified ITPR2+ oligodendrocytes, which are involved in rapid myelination during complex motor learning. These cells were found to be progeny of OPCs and were present in regions of active differentiation. The study provides a high-resolution view of the transcriptional landscape of oligodendrocytes across multiple regions of the CNS, indicating a transcriptional continuum between oligodendrocyte populations. The findings suggest that oligodendrocyte heterogeneity is intrinsic and that different regions of the CNS optimize their circuitry by representing unique proportions and combinations of mature oligodendrocytes. The study also highlights the potential role of ITPR2+ oligodendrocytes in remyelination processes in disease/lesion paradigms. The results contribute to a better understanding of oligodendrocyte development and function in the CNS.This study investigates the heterogeneity of oligodendrocytes in the mouse juvenile and adult central nervous system (CNS) using single-cell RNA sequencing. Researchers analyzed 5072 cells from ten regions of the CNS and identified twelve distinct populations, ranging from Pdgfra+ oligodendrocyte precursors (OPCs) to mature oligodendrocytes. The differentiation process was found to be continuous, with initial stages similar across the juvenile CNS, while mature oligodendrocyte subsets were enriched in specific regions in the adult brain. Newly-formed oligodendrocytes were found to be resident in the adult CNS and responsive to complex motor learning. A second Pdgfra+ population, distinct from OPCs, was found along vessels, indicating a vascular and leptomeningeal cell population (VLMCs). The study reveals the dynamics of oligodendrocyte differentiation and maturation, highlighting their transcriptional heterogeneity. Oligodendrocytes ensheath axons, enabling rapid saltatory conduction and providing metabolic support to neurons. The study identified distinct cell populations, including differentiation-committed oligodendrocyte precursors (COPs), newly-formed oligodendrocytes (NFOL1-2), and myelin-forming oligodendrocytes (MFOL1-2). These populations exhibited unique gene expression patterns, with some enriched in lipid biosynthesis and myelination genes, while others were enriched in synapse-related genes. The study also identified ITPR2+ oligodendrocytes, which are involved in rapid myelination during complex motor learning. These cells were found to be progeny of OPCs and were present in regions of active differentiation. The study provides a high-resolution view of the transcriptional landscape of oligodendrocytes across multiple regions of the CNS, indicating a transcriptional continuum between oligodendrocyte populations. The findings suggest that oligodendrocyte heterogeneity is intrinsic and that different regions of the CNS optimize their circuitry by representing unique proportions and combinations of mature oligodendrocytes. The study also highlights the potential role of ITPR2+ oligodendrocytes in remyelination processes in disease/lesion paradigms. The results contribute to a better understanding of oligodendrocyte development and function in the CNS.