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The Journal of Neuroscience, June 17, 2009, 29(24):7649-7657; doi:10.1523/JNEUROSCI.1027-09.2009

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Development/Plasticity/Repair
β4 Tubulin Identifies a Primitive Cell Source for Oligodendrocytes in the Mammalian Brain

Chuanshen Wu,¹ Ansi Chang,¹ Maria C. Smith,^1,4 Roy Won,¹ Xinghua Yin,¹ Susan M. Staugaitis,^1,2 Dimitri Agamanolis,³ Grahame J. Kidd,¹ Robert H. Miller,⁴ and Bruce D. Trapp¹

Departments of ¹Neurosciences, Lerner Research Institute and ²Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio 44195, ³Department of Pathology, Akron Children's Hospital, Akron, Ohio 44308, and ⁴Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

Correspondence should be addressed to Bruce D. Trapp, Neurosciences Department, NC30, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. Email: trappb{at}ccf.org

We have identified a novel population of cells in the subventricular zone (SVZ) of the mammalian brain that expresses β4 tubulin (βT4) and has properties of primitive neuroectodermal cells. βT4 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, βT4 cell densities peak during the latter stages of gliogenesis, which occurs in the SVZ of the lateral ventricles. βT4 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. βT4 cells produce oligodendrocytes, neurons, and astrocytes in vitro. We compared the myelinating potential of βT4-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 βT4 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 βT4 cells. We propose that βT4 cells are an endogenous cell source that can be recruited to promote neural repair in the adult telencephalon.

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Received Feb. 26, 2009; revised March 25, 2009; accepted May 5, 2009.

Correspondence should be addressed to Bruce D. Trapp, Neurosciences Department, NC30, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. Email: trappb{at}ccf.org

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