An Adeno-Associated Virus-Based Toolkit for Preferential Targeting and Manipulating Quiescent Neural Stem Cells in the Adult Hippocampus
| Autor: | Domenic H. Cerri, Yen-Yu Ian Shih, Chia-Yu Yeh, Josh Wooten, Szu Aun Lim, Brent Asrican, Blake H. Albright, Hechen Bao, Jessica Hu, Andrew J. Crowther, Aravind Asokan, Juan Song |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Resource adult hippocampal neural stem cells Transgene Genetic enhancement Neurogenesis Genetic Vectors Hippocampus toolkit Hippocampal formation Biology medicine.disease_cause Biochemistry radial law.invention Viral vector Rats Sprague-Dawley 03 medical and health sciences Mice Neural Stem Cells law rAAV4 Genetics medicine Animals quiescence Transgenes Adeno-associated virus lcsh:QH301-705.5 Cells Cultured lcsh:R5-920 Cell Biology Dependovirus Neural stem cell Cell biology Rats Mice Inbred C57BL Adult Stem Cells 030104 developmental biology lcsh:Biology (General) Recombinant DNA lcsh:Medicine (General) Developmental Biology |
| Zdroj: | Stem Cell Reports Stem Cell Reports, Vol 10, Iss 3, Pp 1146-1159 (2018) |
| ISSN: | 2213-6711 |
| Popis: | Summary 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. Highlights • rAAV4 vectors preferentially target quiescent NSCs in the adult hippocampus • rAAV4 vectors with distinct promoters reveal differential selectivity for radial NSCs • rAAV4 allows for genetic manipulation and lineage tracing of quiescent NSCs • rAAV4 allows for calcium imaging and activity manipulation of quiescent NSCs In this article, Song and colleagues report a recombinant adeno-associated virus serotype 4-based toolkit comprising several distinct rAAV4 vectors that preferentially target qNSCs within the hippocampus. They demonstrate that rAAV4-mediated transgene expression is robust in qNSCs and allows for lineage tracing, genetic manipulation using the Cre-Lox system, functional analyses using electrophysiology and calcium imaging, and activity manipulation using chemogenetics. |
| Databáze: | OpenAIRE |
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