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

Summary

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.

Highlights

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  Rare, multipotent, self-renewing, Oct4 ⁺ AdpNSCs in the adult brain

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  AdpNSCs lie upstream of definitive, GFAP-expressing adult NSCs

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  AdpNSCs repopulate the SE after ablation of GFAP-expressing NSCs

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  The AdpNSC pool is activated and expands after injury or LIF infusion in vivo

Abstract

The identification of primitive NSCs that persist in the adult brain redefines the adult NSC lineage. Morshead and colleagues show that these adult-derived primitive NSCs, similar to primitive NSCs found in the developing embryo, express the pluripotency marker Oct4 in vitro and in vivo and give rise to GFAP ⁺ definitive NSCs.