Beta4 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 beta4 tubulin (betaT4) and has properties of primitive neuroectodermal cells. betaT4 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, betaT4 cell densities peak during the latter stages of gliogenesis, which occurs in the SVZ of the lateral ventricles. betaT4 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. betaT4 cells produce oligodendrocytes, neurons, and astrocytes in vitro. We compared the myelinating potential of betaT4-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 betaT4 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 betaT4 cells. We propose that betaT4 cells are an endogenous cell source that can be recruited to promote neural repair in the adult telencephalon.
Wu
Chuanshen
C
Department of Neurosciences, Lerner Research Institute and Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Chang
Ansi
A
Smith
Maria C
MC
Won
Roy
R
Yin
Xinghua
X
Staugaitis
Susan M
SM
Agamanolis
Dimitri
D
Kidd
Grahame J
GJ
Miller
Robert H
RH
Trapp
Bruce D
BD
D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology; D009185:Myelin Proteins / Q000172:deficiency; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D012794:Sialic Acids / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000401:mortality; D013234:Stem Cells / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D005732:Gangliosides; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D011509:Proteoglycans; D012794:Sialic Acids; D014404:Tubulin; D000099216:Chondroitin Sulfate Proteoglycan 4; C472930:PLP1 protein, human; C062875:ganglioside A2B5; C103469:polysialyl neural cell adhesion molecule