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In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics |
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| Authors: | Bonaguidi Michael A Wheeler Michael A Shapiro Jason S Stadel Ryan P Sun Gerald J Ming Guo-li Song Hongjun |
| Affiliation: | 1 Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 3 The Human Genetics Predoctoral Training Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 4 The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA |
| Abstract: | Neurogenesis and gliogenesis continue in discrete regions of the adult mammalian brain. A fundamental question remains whether cell genesis occurs from distinct lineage-restricted progenitors or from self-renewing and multipotent neural stem cells in the adult brain. Here, we developed a genetic marking strategy for lineage tracing of individual, quiescent, and nestin-expressing radial glia-like (RGL) precursors in the adult mouse dentate gyrus. Clonal analysis identified multiple modes of RGL activation, including asymmetric and symmetric self-renewal. Long-term lineage tracing in?vivo revealed a significant percentage of clones that contained RGL(s), neurons, and astrocytes, indicating capacity of individual RGLs for both self-renewal and multilineage differentiation. Furthermore, conditional Pten deletion in RGLs initially promotes their activation and symmetric self-renewal but ultimately leads to terminal astrocytic differentiation and RGL depletion in the adult hippocampus. Our study identifies RGLs as self-renewing and multipotent neural stem cells and provides novel insights into in?vivo properties of adult neural stem cells. |
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