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Front Mol Neurosci. 2018 Nov 15;11:415. doi: 10.3389/fnmol.2018.00415. eCollection 2018.

Long-Term Labeling of Hippocampal Neural Stem Cells by a Lentiviral Vector.

Author information

1
Department of Neurosciences, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, United States.
2
Department of Pathology and Experimental Therapeutics, Institut d'Investigació Biomédica de Bellvitge, Bellvitge University Hospital, Barcelona, Spain.
3
Institute of Biomedicine of the University of Barcelona, Barcelona, Spain.
4
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, United States.
5
Center of Regenerative Medicine in Barcelona, Hospital Duran i Reynals, Barcelona, Spain.
6
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Madrid, Spain.
7
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
8
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Abstract

Using a lentivirus-mediated labeling method, we investigated whether the adult hippocampus retains long-lasting, self-renewing neural stem cells (NSCs). We first showed that a single injection of a lentiviral vector expressing a green fluorescent protein (LV PGK-GFP) into the subgranular zone (SGZ) of the adult hippocampus enabled an efficient, robust, and long-term marking of self-renewing NSCs and their progeny. Interestingly, a subset of labeled cells showed the ability to proliferate multiple times and give rise to Sox2+ cells, clearly suggesting the ability of NSCs to self-renew for an extensive period of time (up to 6 months). In addition, using GFP+ cells isolated from the SGZ of mice that received a LV PGK-GFP injection 3 months earlier, we demonstrated that some GFP+ cells displayed the essential properties of NSCs, such as self-renewal and multipotency. Furthermore, we investigated the plasticity of NSCs in a perforant path transection, which has been shown to induce astrocyte formation in the molecular layer of the hippocampus. Our lentivirus (LV)-mediated labeling study revealed that hippocampal NSCs are not responsible for the burst of astrocyte formation, suggesting that signals released from the injured perforant path did not influence NSC fate determination. Therefore, our studies showed that a gene delivery system using LVs is a unique method to be used for understanding the complex nature of NSCs and may have translational impact in gene therapy by efficiently targeting NSCs.

KEYWORDS:

hippocampal neurogenesis; lentiviral vectors; lesion; neural stem cells; targeting

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