1. Dynamic contribution of nestin-expressing stem cells to adult neurogenesis.
- Author
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Lagace DC, Whitman MC, Noonan MA, Ables JL, DeCarolis NA, Arguello AA, Donovan MH, Fischer SJ, Farnbauch LA, Beech RD, DiLeone RJ, Greer CA, Mandyam CD, and Eisch AJ
- Subjects
- Animals, Brain cytology, Cell Differentiation drug effects, Cell Lineage drug effects, Cell Proliferation drug effects, Dentate Gyrus cytology, Dentate Gyrus metabolism, Gene Targeting methods, Luminescent Proteins genetics, Luminescent Proteins metabolism, Mice, Mice, Transgenic, Models, Animal, Nerve Regeneration drug effects, Nerve Regeneration physiology, Nestin, Neuroglia cytology, Neuroglia drug effects, Neuroglia metabolism, Olfactory Bulb cytology, Olfactory Bulb metabolism, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Recombination, Genetic drug effects, Recombination, Genetic genetics, Selective Estrogen Receptor Modulators pharmacology, Stem Cells drug effects, Tamoxifen pharmacology, Brain metabolism, Cell Differentiation physiology, Cell Lineage physiology, Intermediate Filament Proteins metabolism, Nerve Tissue Proteins metabolism, Neurons metabolism, Stem Cells metabolism
- Abstract
Understanding the fate of adult-generated neurons and the mechanisms that influence them requires consistent labeling and tracking of large numbers of stem cells. We generated a nestin-CreER(T2)/R26R-yellow fluorescent protein (YFP) mouse to inducibly label nestin-expressing stem cells and their progeny in the adult subventricular zone (SVZ) and subgranular zone (SGZ). Several findings show that the estrogen ligand tamoxifen (TAM) specifically induced recombination in stem cells and their progeny in nestin-CreER(T2)/R26R-YFP mice: 97% of SGZ stem-like cells (GFAP/Sox2 with radial glial morphology) expressed YFP; YFP+ neurospheres could be generated in vitro after recombination in vivo, and maturing YFP+ progeny were increasingly evident in the olfactory bulb (OB) and dentate gyrus (DG) granule cell layer. Revealing an unexpected regional dissimilarity in adult neurogenesis, YFP+ cells accumulated up to 100 d after TAM in the OB, but in the SGZ, YFP+ cells reached a plateau 30 d after TAM. In addition, most SVZ and SGZ YFP+ cells became neurons, underscoring a link between nestin and neuronal fate. Finally, quantification of YFP+ cells in nestin-CreER(T2)/R26R-YFP mice allowed us to estimate, for example, that stem cells and their progeny contribute to no more than 1% of the adult DG granule cell layer. In addition to revealing the dynamic contribution of nestin-expressing stem cells to adult neurogenesis, this work highlights the utility of the nestin-CreER(T2)/R26R-YFP mouse for inducible gene ablation in stem cells and their progeny in vivo in the two major regions of adult neurogenesis.
- Published
- 2007
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