title: Origin of oligodendrocytes in the subventricular zone of the adult brain.
abstract: Glial fibrillary acidic protein (GFAP)-positive astrocytes (type B cells) in the subventricular zone (SVZ) generate large numbers of new neurons in the adult brain. SVZ stem cells can also generate oligodendrocytes in vitro, but it is not known whether these adult primary progenitors generate oligodendrocytes in vivo. Myelin repair and oligodendrocyte formation in the adult brain is instead associated with glial-restricted progenitors cells, known as oligodendrocyte progenitor cells (OPCs). Here we show that type B cells also generate a small number of nonmyelinating NG2-positive OPCs and mature myelinating oligodendrocytes. Some type B cells and a small subpopulation of actively dividing type C (transit-amplifying) cells expressed oligodendrocyte lineage transcription factor 2 (Olig2), suggesting that oligodendrocyte differentiation in the SVZ begins early in the lineage. Olig2-positive, polysialylated neural cell adhesion molecule-positive, PDGF receptor alpha-positive, and beta-tubulin-negative cells originating in the SVZ migrated into corpus callosum, striatum, and fimbria fornix to differentiate into the NG2-positive nonmyelinating and mature myelinating oligodendrocytes. Furthermore, primary clonal cultures of type B cells gave rise to oligodendrocytes alone or oligodendrocytes and neurons. Importantly, the number of oligodendrocytes derived from type B cells in vivo increased fourfold after a demyelinating lesion in corpus callosum, indicating that SVZ astrocytes participate in myelin repair in the adult brain. Our work identifies SVZ type B cells as progenitors of oligodendrocytes in normal and injured adult brain.
authors.affiliation: Department of Neurosurgery and Developmental and Stem Cell Biology Program, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Menn
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.forename: Cynthia
authors.initials: C
authors.lastname: Yaschine
authors.forename: Oscar
authors.initials: O
authors.lastname: Gonzalez-Perez
authors.forename: David
authors.initials: D
authors.lastname: Rowitch
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001921:Brain; D002454:Cell Differentiation / Q000502:physiology; D002552:Cerebral Ventricles / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C512773:Olig2 protein, mouse