The lineages of both astrocytes and oligodendrocytes have been popular areas of research in the last decade. The source of these cells in the mature CNS is relevant to the study of the cellular response to CNS injury. A significant amount of evidence exists to suggest that resident precursor cells proliferate and differentiate into mature glial cells that facilitate tissue repair and recovery. Additionally, the re-entry of mature astrocytes into the cell cycle can also contribute to the pool of new astrocytes that are observed following CNS injury. In order to better understand the glial response to injury in the adult CNS we must revisit the astrocyte-oligodendrocyte relationship. Specifically, we argue that there is a common glial precursor cell from which astrocytes and oligodendrocytes differentiate and that the microenvironment surrounding the injury determines the fate of the stimulated precursor cell. Ideally, better understanding the origin of new glial cells in the injured CNS will facilitate the development of therapeutics targeted to alter the glial response in a beneficial way.

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