title: Primitive neural stem cells in the adult mammalian brain give rise to GFAP-expressing neural stem cells.
abstract: Adult forebrain definitive neural stem cells (NSCs) comprise a subpopulation of GFAP-expressing subependymal cells that arise from embryonic fibroblast growth factor (FGF)-dependent NSCs that are first isolated from the developing brain at E8.5. Embryonic FGF-dependent NSCs are derived from leukemia inhibitory factor (LIF)-responsive, Oct4-expressing primitive NSCs (pNSCs) that are first isolated at E5.5. We report the presence of a rare population of pNCSs in the periventricular region of the adult forebrain. Adult-derived pNSCs (AdpNSCs) are GFAP(-), LIF-responsive stem cells that display pNSC properties, including Oct4 expression and the ability to integrate into the inner cell mass of blastocysts. AdpNSCs generate self-renewing, multipotent colonies that give rise to definitive GFAP(+) NSCs in vitro and repopulate the subependyma after the ablation of GFAP(+) NSCs in vivo. These data support the hypothesis that a rare population of pNSCs is present in the adult brain and is upstream of the GFAP(+) NSCs.
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada ; Department of Surgery, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Nadia
authors.initials: N
authors.lastname: Sachewsky
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada ; Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Rachel
authors.initials: R
authors.lastname: Leeder
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada ; Department of Surgery, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xu
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada ; Department of Surgery, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada ; Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Keeley L
authors.initials: KL
authors.lastname: Rose
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada ; Department of Surgery, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Fenggang
authors.initials: F
authors.lastname: Yu
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada ; Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada ; Department of Surgery, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada ; Institute of Biomaterials and Biomedical Engineering, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
authors.forename: Cindi M
authors.initials: CM
authors.lastname: Morshead
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse