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Stem Cell Reports. 2018 Mar 13;10(3):1146-1159. doi: 10.1016/j.stemcr.2018.01.018. Epub 2018 Mar 1.

An Adeno-Associated Virus-Based Toolkit for Preferential Targeting and Manipulating Quiescent Neural Stem Cells in the Adult Hippocampus.

Author information

1
Department of Pharmacology and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA.
2
Department of Pharmacology and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
3
Department of Genetics and Gene Therapy Center, University of North Carolina, Chapel Hill, NC 27599, USA; Genetics and Molecular Biology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA.
4
Department of Pharmacology and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Genetics and Molecular Biology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA.
5
Department of Neurology and Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC 27599, USA.
6
Department of Pharmacology and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA; Genetics and Molecular Biology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: juansong@email.unc.edu.

Abstract

Quiescent neural stem cells (qNSCs) with radial morphology are the only proven source of new neurons in the adult mammalian brain. Our understanding of the roles of newly generated neurons depends on the ability to target and manipulate adult qNSCs. Although various strategies have been developed to target and manipulate adult hippocampal qNSCs, they often suffer from prolonged breeding, low recombination efficiency, and non-specific labeling. Therefore, developing a readily manufactured viral vector that allows flexible packaging and robust expression of various transgenes in qNSCs is a pressing need. Here, we report a recombinant adeno-associated virus serotype 4 (rAAV4)-based toolkit that preferentially targets hippocampal qNSCs and allows for lineage tracing, functional analyses, and activity manipulation of adult qNSCs. Importantly, targeting qNSCs in a non-Cre-dependent fashion opens the possibility for studying qNSCs in less genetically tractable animal species and may have translational impact in gene therapy by preferentially targeting qNSCs.

KEYWORDS:

adult hippocampal neural stem cells; quiescence; rAAV4; radial; toolkit

PMID:
29478897
PMCID:
PMC5918266
DOI:
10.1016/j.stemcr.2018.01.018
[Indexed for MEDLINE]
Free PMC Article

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