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Stem Cell Reports. 2014 May 22;2(6):810-24. doi: 10.1016/j.stemcr.2014.04.008. eCollection 2014 Jun 3.

Primitive neural stem cells in the adult mammalian brain give rise to GFAP-expressing neural stem cells.

Author information

1
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.
2
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.
3
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.
4
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.

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.

PMID:
24936468
PMCID:
PMC4050350
DOI:
10.1016/j.stemcr.2014.04.008
[Indexed for MEDLINE]
Free PMC Article

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