title: In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics.
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.
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bonaguidi
authors.forename: Michael A
authors.initials: MA
authors.lastname: Wheeler
authors.forename: Jason S
authors.initials: JS
authors.lastname: Shapiro
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Stadel
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Sun
authors.forename: Guo-li
authors.initials: GL
authors.lastname: Ming
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology; D006624:Hippocampus / Q000166:cytology*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis
chemical_list: D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin