Primitive Neural Stem Cells in the Adult Mammalian Brain Give Rise to GFAP-Expressing Neural Stem Cells

•Rare, multipotent, self-renewing, Oct4+ AdpNSCs in the adult brain•AdpNSCs lie upstream of definitive, GFAP-expressing adult NSCs•AdpNSCs repopulate the SE after ablation of GFAP-expressing NSCs•The AdpNSC pool is activated and expands after injury or LIF infusion in vivo

SummaryAdult 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.