β4 Tubulin Identifies a Primitive Cell Source for Oligodendrocytes in the Mammalian Brain

We have identified a novel population of cells in the subventricular zone (SVZ) of the mammalian brain that expresses beta 4 tubulin (beta T4) and has properties of primitive neuroectodermal cells. beta T4 cells are scattered throughout the SVZ of the lateral ventricles in adult human brain and are significantly increased in the SVZs bordering demyelinated white matter in multiple sclerosis brains. In human fetal brain, beta T4 cell densities peak during the latter stages of gliogenesis, which occurs in the SVZ of the lateral ventricles. beta T4 cells represent <2% of the cells present in neurospheres generated from postnatal rat brain but >95% of cells in neurospheres treated with the anti-mitotic agent Ara C. beta T4 cells produce oligodendrocytes, neurons, and astrocytes in vitro. We compared the myelinating potential of beta T4-positive cells with A2B5-positive oligodendrocyte progenitor cells after transplantation (25,000 cells) into postnatal day 3 (P3) myelin-deficient rat brains. At P20, the progeny of beta T4 cells myelinated up to 4 mm of the external capsule, which significantly exceeded that of transplanted A2B5-positive progenitor cells. Such extensive and rapid mature CNS cell generation by a relatively small number of transplanted cells provides in vivo support for the therapeutic potential of beta T4 cells. We propose that beta T4 cells are an endogenous cell source that can be recruited to promote neural repair in the adult telencephalon.