Endogenous Brain Repair: Overriding intrinsic lineage determinates through injury-induced micro-environmental signals

Adult human neurogenesis has generated excitement over the last 2 decades with the idea that endogenous adult stem cells could act as a potential cell source for brain repair after injury. Indeed, many forms of experimentally induced brain injury including stroke and excitotoxic lesioning can promote proliferation from the subventricular zone and mobilise neuroblasts and oligodendrocyte progenitor cells to migrate through brain parenchyma to damaged regions. However the failure of neuroblasts to mature into appropriate neuronal subtypes for cell replacement has been an issue. Recent work by our group and others has indicated that micro-environmental signals released from areas of cell loss may be able to override intrinsic gene expression lineages and covert neuroblasts into oligodendrocyte progenitor cells. This commentary will discuss the enhanced fate plasticity of both adult neural progenitors and parenchymal NG2 cells after injury, and the importance of understanding brain-injury induced micro-environmental signals in the quest toward promoting endogenous regeneration after injury.